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Herndon II, James Emmett

Overview:

Current research interests have application to the design and analysis of cancer clinical trials. Specifically, interests include the use of time-dependent covariables within survival models, the design of phase II cancer clinical trials which minimize some of the logistical problems associated with their conduct, and the analysis of longitudinal studies with informative censoring (in particular, quality of life studies of patients with advanced cancer).

Positions:

Professor of Biostatistics and Bioinformatics

Biostatistics & Bioinformatics
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 1988

Ph.D. — University of North Carolina at Chapel Hill

Grants:

CCL3 as a Developmental Therapeutic to Enhance Brain Tumor Therapy

Administered By
Neurosurgery
AwardedBy
National Institutes of Health
Role
Statistician
Start Date
December 01, 2016
End Date
November 30, 2021

Regional Oncolytic Poliovirus Immunotherapy for Breast Cancer

Administered By
Surgery, Surgical Sciences
AwardedBy
Department of Defense
Role
Investigator
Start Date
August 01, 2016
End Date
July 31, 2021

Human EGFRvIII-specific BiTE for the treatment of Glioblastoma

Administered By
Neurosurgery
AwardedBy
National Institutes of Health
Role
Investigator
Start Date
July 01, 2015
End Date
June 30, 2020

Lost and Found: The Bone Marrow as Counterproductive Site of T cell Sequestration in GBM

Administered By
Neurosurgery
AwardedBy
Sontag Foundation
Role
Statistician
Start Date
October 01, 2015
End Date
September 30, 2019

Systemic EGFRvIII-targeted bispecific antibody as immunotherapy for glioblastoma

Administered By
Neurosurgery
AwardedBy
National Institutes of Health
Role
Collaborator
Start Date
March 01, 2015
End Date
February 28, 2019

Brain Tumor Targeting Using Tumor-Specific Neuroimmunology

Administered By
Neurosurgery
AwardedBy
National Institutes of Health
Role
Biostatistician
Start Date
September 15, 2014
End Date
May 31, 2018

EGFRvIII-targeted Bispecific T cell Engagers for brain tumors

Administered By
Neurosurgery
AwardedBy
National Institutes of Health
Role
Investigator
Start Date
September 30, 2013
End Date
May 31, 2018

Brain tumors with regulatory T-cells treated with EGFRvIII-specific T-cells

Administered By
Neurosurgery
AwardedBy
National Institutes of Health
Role
Investigator
Start Date
April 05, 2013
End Date
March 31, 2018

Ph 1/2 trial BMX-001

Administered By
Neurosurgery, Neuro-Oncology
AwardedBy
BioMimetix JV LLC
Role
Biostatistician Investigator
Start Date
September 18, 2015
End Date
August 31, 2017

A clinically-relevant anti-CD27 agonist antibody as a vaccine adjuvant for brain tumor immunotherapy

Administered By
Neurosurgery
AwardedBy
National Institutes of Health
Role
Collaborator
Start Date
August 01, 2016
End Date
July 31, 2017

Therapeutic Vaccine Targeting CMV Antigens in Glioblastoma

Administered By
Neurosurgery
AwardedBy
Annias Immunotherapeutics, Inc.
Role
Investigator
Start Date
August 10, 2015
End Date
July 31, 2017

Randomized Trial of Optimal Type of Aerobic Training in Breast Cancer

Administered By
Biostatistics & Bioinformatics
AwardedBy
Memorial Sloan Kettering Cancer Center
Role
Principal Investigator
Start Date
August 01, 2015
End Date
July 31, 2017

Improving Adherence to Recommended Surveillance in Breast Cancer Survivors

Administered By
Psychiatry & Behavioral Sciences, Behavioral Medicine
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
September 01, 2010
End Date
August 31, 2015

Adoptive Immunotherapy for GBM During Hematopoietic Recovery from Temozolomide

Administered By
Neurosurgery
AwardedBy
National Institutes of Health
Role
Statistician
Start Date
September 23, 2009
End Date
July 31, 2014

Targeting EGFRvIII in Brain Tumors with Bispecific Antibodies

Administered By
School of Medicine
AwardedBy
National Institutes of Health
Role
Collaborator
Start Date
May 01, 2013
End Date
April 30, 2014

(PQA5) 'Dose and Mechanisms of Exercise in Breast Cancer Prevention'

Administered By
Radiation Oncology
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 23, 2013
End Date
February 14, 2014

Aerobic Training During or After Adjuvant Therapy: A Randomized Trial

Administered By
Radiation Oncology
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 20, 2012
End Date
February 14, 2014

Phase II Trial of Aerobic Training in Metastatic Breast Cancer

Administered By
Radiation Oncology
AwardedBy
National Institutes of Health
Role
Biostatistician Investigator
Start Date
September 17, 2010
End Date
February 14, 2014

Randomized Trial of Optimal Type of Aerobic Training in Breast Cancer

Administered By
Radiation Oncology
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
April 01, 2010
End Date
February 14, 2014

Modulation of the blood-tumor barrier through targeted suppression of claudin 5

Administered By
Neurosurgery
AwardedBy
National Institutes of Health
Role
Collaborator
Start Date
August 16, 2011
End Date
August 02, 2013

Reversal of CMV-specific immune deficits in patients with glioblastoma

Administered By
Neurosurgery
AwardedBy
National Institutes of Health
Role
Biostatistician
Start Date
September 15, 2009
End Date
June 30, 2013

Brain Tumors - Immunological and Biological Studies

Administered By
Pathology
AwardedBy
National Institutes of Health
Role
Investigator
Start Date
April 20, 2001
End Date
March 31, 2013

Neuroimmunology of Vaccines in Adoptive T-cell Therapy for Brain Tumor

Administered By
Neurosurgery
AwardedBy
National Institutes of Health
Role
Biostatistician
Start Date
July 01, 2010
End Date
June 30, 2012

Pre-clinical Translation of Regulatory T-cell Inhibition in Brain Tumors

Administered By
Neurosurgery
AwardedBy
National Institutes of Health
Role
Biostatistician
Start Date
July 01, 2010
End Date
June 30, 2012

The Role of OTX2 in Molecular Pathogenesis of Medulloblastoma

Administered By
Pathology
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
July 01, 2006
End Date
May 31, 2012

Gene Targeted Therapy of Brain Tumors

Administered By
Neurosurgery
AwardedBy
National Institutes of Health
Role
Biostatistician
Start Date
September 30, 2009
End Date
February 29, 2012

Prospective Validation of Genomic Signatures of Chemosensitivity in NSCLC

Administered By
Institutes and Centers
AwardedBy
National Institutes of Health
Role
Investigator
Start Date
January 01, 2009
End Date
November 30, 2010

Discovery of Biomarkers for Lung Cancer Metastasis

Administered By
Radiology, Cardiothoracic Imaging
AwardedBy
National Institutes of Health
Role
Statistician
Start Date
April 01, 2005
End Date
March 30, 2010

Effect on IL-2R Antibody on Regulatory T-cells in Patients with Malignant Gliomas

Administered By
Neurosurgery
AwardedBy
National Institutes of Health
Role
Statistician
Start Date
January 04, 2008
End Date
December 31, 2009

Palliative Oxygen for the Relief of Breathlessness

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Senior Statistician
Start Date
September 15, 2006
End Date
May 31, 2009

Serum Biomarkers for Early Diagnosis of NSCLC

Administered By
Radiology, Cardiothoracic Imaging
AwardedBy
Johns Hopkins University
Role
Statistician
Start Date
July 01, 2007
End Date
February 28, 2009

Stem Cell-Like Glioma Cells in Angiogenesis

Administered By
Neurology, General & Community Neurology
AwardedBy
National Institutes of Health
Role
Consultant
Start Date
April 07, 2008
End Date
January 31, 2009

DNA Methylation and GSTP1 Gene Regulation in Gliomas

Administered By
Surgery, Surgical Sciences
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 01, 2002
End Date
June 30, 2008

Phase I/II Trial of ZD1839 and Celecoxib in Ex-Smokers

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 26, 2002
End Date
August 31, 2007

Measurement of Hypoxia in Non-Small Cell Lung Carcinoma

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Statistician
Start Date
April 01, 2002
End Date
March 31, 2006

ACOSOG-Statistics and Data Coordinating Center

Administered By
Surgery
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
June 01, 2000
End Date
May 31, 2005

ZD1839 Therapy of Glioblastoma Multiforme

Administered By
Pediatrics
AwardedBy
National Institutes of Health
Role
Collaborator
Start Date
April 01, 2001
End Date
March 31, 2003

Using Plasma TGFB1 Levels to Escalate Radiotherapy Doses

Administered By
Radiation Oncology
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
February 15, 2000
End Date
January 31, 2003

Src On Primary And Matastatic Tumors Of The Cns

Administered By
Pathology
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
May 01, 1994
End Date
March 31, 1999

Src On Primary And Metastatic Tumors Of The Cns

Administered By
Pathology
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
March 01, 1997
End Date
February 28, 1999

Cancer Center Core Support Grant

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
September 01, 1976
End Date
December 31, 1998

Comprehensive Cancer Center Core Support Grant

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
September 01, 1976
End Date
December 31, 1998

Cancer And Leukemia Group B - Statistical Center

Administered By
Duke Cancer Institute
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
April 01, 1994
End Date
March 31, 1998

Cancer And Leukemia Group B Statistical Center

Administered By
Duke Cancer Institute
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
December 01, 1982
End Date
March 31, 1998

Src On Malignant Human Gliomas And Medulloblastomas

Administered By
Pathology
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
April 01, 1992
End Date
March 31, 1994

Comprehensive Cancer Center Core Support Grant

Administered By
Medicine, Cardiology
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
May 01, 1992
End Date
December 31, 1993

Cancer And Leukemia Group B Statistical Center

Administered By
Duke Cancer Institute
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
April 01, 1992
End Date
March 31, 1993
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Publications:

Rethinking Autoantibody Signature Panels for Cancer Diagnosis: A Brief Report.

Most pulmonary nodules found on imaging studies are indeterminate, but because of the concern for lung cancer, all patients require further evaluation with resultant radiation risk, significant cost, and delays in diagnosis. We hypothesized that a diagnostic blood test based on detection of autoantibodies against cancer antigens would be able to distinguish a benign nodule from lung cancer.We identified a panel of 25 serum autoantibodies associated with NSCLC and constructed a protein microarray containing the autoantigens. We tested the microarray with human sera (from 125 patients with NSCLC and 125 matched controls with a benign nodule) and attempted to develop a classification algorithm that would separate the two groups.In the training data set the logistic regression c-index statistic was 0.691; in the validation data set, the model predicting the score generated from the training set model had a c-index of 0.490. The relationship between the score and outcome (final diagnosis) was not statistically significant (p = 0.460).When the current panel of antigens and assay format was used, classification algorithms based on levels of autoantibodies to cancer antigens did not prove to have statistically significant value for predicting the presence of cancer. We suggest that there are inherent biological limitations to this approach.

Authors
Campa, MJ; Gottlin, EB; Herndon, JE; Patz, EF
MLA Citation
Campa, MJ, Gottlin, EB, Herndon, JE, and Patz, EF. "Rethinking Autoantibody Signature Panels for Cancer Diagnosis: A Brief Report." Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (January 23, 2017).
PMID
28126538
Source
epmc
Published In
Journal of Thoracic Oncology
Publish Date
2017
DOI
10.1016/j.jtho.2017.01.017

Phase II Study of Dasatinib in Previously Treated Patients with Advanced Non-Small Cell Lung Cancer.

The Src pathway in activated in about one-third of non-small cell lung cancer (NSCLC) tumors. Dasatinib has Src-inhibitor activity. We examined the activity of dasatinib in 37 patients with advanced, previously treated NSCLC. Among the 29 patients who underwent pre-treatment biopsy for RNA biomarker analysis, 25 were treated with dasatinib 70 mg twice daily. There were no responses. Five patients discontinued treatment due to toxicity. Three patients had minor biopsy-related pneumothoraces. Given the lack of responses, no biomarkers were analyzed. Dasatinib 70 mg twice daily does not have activity nor is it well tolerated in unselected patients with advanced stage, previously treated NSCLC.

Authors
Kelley, MJ; Jha, G; Shoemaker, D; Herndon, JE; Gu, L; Barry, WT; Crawford, J; Ready, N
MLA Citation
Kelley, MJ, Jha, G, Shoemaker, D, Herndon, JE, Gu, L, Barry, WT, Crawford, J, and Ready, N. "Phase II Study of Dasatinib in Previously Treated Patients with Advanced Non-Small Cell Lung Cancer." Cancer investigation 35.1 (January 2017): 32-35.
PMID
27911119
Source
epmc
Published In
Cancer Investigation (Informa)
Volume
35
Issue
1
Publish Date
2017
Start Page
32
End Page
35
DOI
10.1080/07357907.2016.1253710

A Phase II single-arm trial of palonosetron for the prevention of acute and delayed chemotherapy-induced nausea and vomiting in malignant glioma patients receiving multidose irinotecan in combination with bevacizumab.

Given that the prognosis of recurrent malignant glioma (MG) remains poor, improving quality of life (QoL) through symptom management is important. Meta-analyses establishing antiemetic guidelines have demonstrated the superiority of palonosetron (PAL) over older 5-hydroxytryptamine 3-receptor antagonists in chemotherapy-induced nausea and vomiting (CINV) prevention, but excluded patients with gliomas. Irinotecan plus bevacizumab is a treatment frequently used in MG, but is associated with low (55%) CINV complete response (CR; no emesis or use of rescue antiemetic) with commonly prescribed ondansetron. A single-arm Phase II trial was conducted in MG patients to determine the efficacy of intravenous PAL (0.25 mg) and dexamethasone (DEX; 10 mg) received in conjunction with biweekly irinotecan-bevacizumab treatment. The primary end point was the proportion of subjects achieving acute CINV CR (no emesis or antiemetic ≤24 hours postchemotherapy). Secondary end points included delayed CINV CR (days 2-5), overall CINV CR (days 1-5), and QoL, fatigue, and toxicity.A two-stage design of 160 patients was planned to differentiate between CINV CR of 55% and 65% after each dose of PAL-DEX. Validated surveys assessed fatigue and QoL.A total of 63 patients were enrolled, after which enrollment was terminated due to slow accrual; 52 patients were evaluable for the primary outcome of acute CINV CR. Following PAL-DEX dose administrations 1-3, acute CINV CR rates were 62%, 68%, and 70%; delayed CINV CR rates were 62%, 66%, and 70%, and overall CINV CR rates were 47%, 57%, and 62%, respectively. Compared to baseline, there was a clinically meaningful increase in fatigue during acute and overall phases, but not in the delayed phase. There were no grade ≥3 PAL-DEX treatment-related toxicities.Data suggest that PAL-DEX is effective in preventing CINV in MG patients, which ultimately maintains the QoL of patients with glioma.

Authors
Affronti, ML; Woodring, S; Peters, KB; Herndon, JE; McSherry, F; Healy, PN; Desjardins, A; Vredenburgh, JJ; Friedman, HS
MLA Citation
Affronti, ML, Woodring, S, Peters, KB, Herndon, JE, McSherry, F, Healy, PN, Desjardins, A, Vredenburgh, JJ, and Friedman, HS. "A Phase II single-arm trial of palonosetron for the prevention of acute and delayed chemotherapy-induced nausea and vomiting in malignant glioma patients receiving multidose irinotecan in combination with bevacizumab." Therapeutics and clinical risk management 13 (January 2017): 33-40.
PMID
28096679
Source
epmc
Published In
Therapeutics and clinical risk management
Volume
13
Publish Date
2017
Start Page
33
End Page
40
DOI
10.2147/tcrm.s122480

Psychosocial distress and its effects on the health-related quality of life of primary brain tumor patients.

All cancer patients experience distress from the diagnosis, the effects of the disease or the treatment. Clinically significant distress decreases overall quality of life and the recognition of distress with prompt intervention is essential. The National Comprehensive Cancer Network distress thermometer (NCCN-DT) is a validated measuring tool that has been utilized in the primary brain tumor population to detect psychologic distress thereby provoking a referral process to the appropriate support system. Brain tumor patients commonly reported emotional and physical distress encompassing: fatigue, fears, memory and concentration and worry. More research is needed to identify the stressors of all primary brain tumor patients and their caretakers and integrate appropriate interventions to improve health-related quality of life in both groups.

Authors
Randazzo, D; Peters, KB
MLA Citation
Randazzo, D, and Peters, KB. "Psychosocial distress and its effects on the health-related quality of life of primary brain tumor patients." October 2016.
PMID
27397796
Source
epmc
Published In
CNS Oncology
Volume
5
Issue
4
Publish Date
2016
Start Page
241
End Page
249
DOI
10.2217/cns-2016-0010

Phase II study to evaluate the safety and efficacy of intravenous palonosetron (PAL) in primary malignant glioma (MG) patients receiving standard radiotherapy (RT) and concomitant temozolomide (TMZ)

Authors
Affronti, ML; Woodring, S; Allen, K; Kirkpatrick, J; Peters, KB; II, HJE; McSherry, F; Healy, PN; Desjardins, A; Vredenburgh, JJ; Friedman, HS
MLA Citation
Affronti, ML, Woodring, S, Allen, K, Kirkpatrick, J, Peters, KB, II, HJE, McSherry, F, Healy, PN, Desjardins, A, Vredenburgh, JJ, and Friedman, HS. "Phase II study to evaluate the safety and efficacy of intravenous palonosetron (PAL) in primary malignant glioma (MG) patients receiving standard radiotherapy (RT) and concomitant temozolomide (TMZ)." SUPPORTIVE CARE IN CANCER 24.10 (October 2016): 4365-4375.
Source
wos-lite
Published In
Supportive Care in Cancer
Volume
24
Issue
10
Publish Date
2016
Start Page
4365
End Page
4375
DOI
10.1007/s00520-016-3276-1

Neurobehavioral radiation mitigation to standard brain cancer therapy regimens by Mn(III) n-butoxyethylpyridylporphyrin-based redox modifier.

Combinations of radiotherapy (RT) and chemotherapy have shown efficacy toward brain tumors. However, therapy-induced oxidative stress can damage normal brain tissue, resulting in both progressive neurocognitive loss and diminished quality of life. We have recently shown that MnTnBuOE-2-PyP(5+) (Mn(III)meso-tetrakis(N-n-butoxyethylpyridinium -2-yl)porphyrin) rescued RT-induced white matter damage in cranially-irradiated mice. Radiotherapy is not used in isolation for treatment of brain tumors; temozolomide is the standard-of-care for adult glioblastoma, whereas cisplatin is often used for treatment of pediatric brain tumors. Therefore, we evaluated the brain radiation mitigation ability of MnTnBuOE-2-PyP(5+) after either temozolomide or cisplatin was used singly or in combination with 10 Gy RT. MnTnBuOE-2-PyP(5+) accumulated in brains at low nanomolar levels. Histological and neurobehavioral testing showed a drastic decrease (1) of axon density in the corpus callosum and (2) rotorod and running wheel performance in the RT only treatment group, respectively. MnTnBuOE-2-PyP(5+) completely rescued this phenotype in irradiated animals. In the temozolomide groups, temozolomide/ RT treatment resulted in further decreased rotorod responses over RT alone. Again, MnTnBuOE-2-PyP(5+) treatment rescued the negative effects of both temozolomide ± RT on rotorod performance. While the cisplatin-treated groups did not give similar results as the temozolomide groups, inclusion of MnTnBuOE-2-PyP(5+) did not negatively affect rotorod performance. Additionally, MnTnBuOE-2-PyP(5+) sensitized glioblastomas to either RT ± temozolomide in flank tumor models. Mice treated with both MnTnBuOE-2-PyP(5+) and radio-/chemo-therapy herein demonstrated brain radiation mitigation. MnTnBuOE-2-PyP(5+) may well serve as a normal tissue radio-/chemo-mitigator adjuvant therapy to standard brain cancer treatment regimens. Environ. Mol. Mutagen. 57:372-381, 2016. © 2016 Wiley Periodicals, Inc.

Authors
Weitzel, DH; Tovmasyan, A; Ashcraft, KA; Boico, A; Birer, SR; Roy Choudhury, K; Herndon, J; Rodriguiz, RM; Wetsel, WC; Peters, KB; Spasojevic, I; Batinic-Haberle, I; Dewhirst, MW
MLA Citation
Weitzel, DH, Tovmasyan, A, Ashcraft, KA, Boico, A, Birer, SR, Roy Choudhury, K, Herndon, J, Rodriguiz, RM, Wetsel, WC, Peters, KB, Spasojevic, I, Batinic-Haberle, I, and Dewhirst, MW. "Neurobehavioral radiation mitigation to standard brain cancer therapy regimens by Mn(III) n-butoxyethylpyridylporphyrin-based redox modifier." Environmental and molecular mutagenesis 57.5 (June 2016): 372-381.
PMID
27224425
Source
epmc
Published In
Environmental and Molecular Mutagenesis
Volume
57
Issue
5
Publish Date
2016
Start Page
372
End Page
381
DOI
10.1002/em.22021

Serum elevation of B lymphocyte stimulator does not increase regulatory B cells in glioblastoma patients undergoing immunotherapy.

Regulatory B cells that secrete IL-10 (IL-10(+) Bregs) represent a suppressive subset of the B cell compartment with prominent anti-inflammatory capacity, capable of suppressing cellular and humoral responses to cancer and vaccines. B lymphocyte stimulator (BLyS) is a key regulatory molecule in IL-10(+) Breg biology with tightly controlled serum levels. However, BLyS levels can be drastically altered upon chemotherapeutic intervention. We have previously shown that serum BLyS levels are elevated, and directly associated, with increased antigen-specific antibody titers in patients with glioblastoma (GBM) undergoing lymphodepletive temozolomide chemotherapy and vaccination. In this study, we examined corresponding IL-10(+) Breg responses within this patient population and demonstrate that the IL-10(+) Breg compartment remains constant before and after administration of the vaccine, despite elevated BLyS levels in circulation. IL-10(+) Breg frequencies were not associated with serum BLyS levels, and ex vivo stimulation with a physiologically relevant concentration of BLyS did not increase IL-10(+) Breg frequency. However, BLyS stimulation did increase the frequency of the overall B cell compartment and promoted B cell proliferation upon B cell receptor engagement. Therefore, using BLyS as an adjuvant with therapeutic peptide vaccination could promote humoral immunity with no increase in immunosuppressive IL-10(+) Bregs. These results have implications for modulating humoral responses in human peptide vaccine trials in patients with GBM.

Authors
Saraswathula, A; Reap, EA; Choi, BD; Schmittling, RJ; Norberg, PK; Sayour, EJ; Herndon, JE; Healy, P; Congdon, KL; Archer, GE; Sanchez-Perez, L; Sampson, JH
MLA Citation
Saraswathula, A, Reap, EA, Choi, BD, Schmittling, RJ, Norberg, PK, Sayour, EJ, Herndon, JE, Healy, P, Congdon, KL, Archer, GE, Sanchez-Perez, L, and Sampson, JH. "Serum elevation of B lymphocyte stimulator does not increase regulatory B cells in glioblastoma patients undergoing immunotherapy." Cancer immunology, immunotherapy : CII 65.2 (February 2016): 205-211.
PMID
26759007
Source
epmc
Published In
Cancer Immunology, Immunotherapy
Volume
65
Issue
2
Publish Date
2016
Start Page
205
End Page
211
DOI
10.1007/s00262-015-1784-3

Insomnia and its associations in patients with recurrent glial neoplasms.

Patient with neurological disorders and cancer can develop sleep disturbance, in particular insomnia. Etiology of insomnia is multi-factorial in primary brain tumour patients with possible causes including corticosteroids, psychoactive medications, co-morbid psychiatric/medical conditions, and damage to neuronal tissue.To understand better insomnia in recurrent glioma patients, a single-center retrospective analysis was performed looking at recurrent glioma patients from January 2004 to May 2009. Data was extracted and included demographics, clinical factors, psychoactive medications, and co-morbid symptoms. Presence and absence of insomnia complaints was evaluated with other co-morbidities using Chi square and Wilcoxon analyses. Records from 340 recurrent glioma patients were evaluated and 46.8 % (n = 159) indicated presence of insomnia with 20 % (n = 66) actively using medications for sleep. Use of corticosteroids were significantly associated with insomnia (p = 0.0003). Age, gender, tumour location, use of stimulants, antipsychotics, and antidepressants were not significantly associated with insomnia in recurrent glioma patients. There was a trend towards a possible significant association with insomnia to fatigue complaints and use of anti-epileptics, p-values of 0.0501 and 0.0725 respectively.In conclusion, insomnia is commonly encountered in patients with recurrent glial tumors. Corticosteroid use is associated with insomnia in this population. In light of the frequency of insomnia and its associations, future analysis is warranted into sleep complaints in recurrent glioma patients and its impact on quality of life.

Authors
Robertson, ME; McSherry, F; Herndon, JE; Peters, KB
MLA Citation
Robertson, ME, McSherry, F, Herndon, JE, and Peters, KB. "Insomnia and its associations in patients with recurrent glial neoplasms." SpringerPlus 5.1 (January 2016): 823-.
Website
http://hdl.handle.net/10161/13036
PMID
27390663
Source
epmc
Published In
SpringerPlus
Volume
5
Issue
1
Publish Date
2016
Start Page
823
DOI
10.1186/s40064-016-2578-6

X-Ray Psoralen Activated Cancer Therapy (X-PACT).

This work investigates X-PACT (X-ray Psoralen Activated Cancer Therapy): a new approach for the treatment of solid cancer. X-PACT utilizes psoralen, a potent anti-cancer therapeutic with current application to proliferative disease and extracorporeal photopheresis (ECP) of cutaneous T Cell Lymphoma. An immunogenic role for light-activated psoralen has been reported, contributing to long-term clinical responses. Psoralen therapies have to-date been limited to superficial or extracorporeal scenarios due to the requirement for psoralen activation by UVA light, which has limited penetration in tissue. X-PACT solves this challenge by activating psoralen with UV light emitted from novel non-tethered phosphors (co-incubated with psoralen) that absorb x-rays and re-radiate (phosphoresce) at UV wavelengths. The efficacy of X-PACT was evaluated in both in-vitro and in-vivo settings. In-vitro studies utilized breast (4T1), glioma (CT2A) and sarcoma (KP-B) cell lines. Cells were exposed to X-PACT treatments where the concentrations of drug (psoralen and phosphor) and radiation parameters (energy, dose, and dose rate) were varied. Efficacy was evaluated primarily using flow cell cytometry in combination with complimentary assays, and the in-vivo mouse study. In an in-vitro study, we show that X-PACT induces significant tumor cell apoptosis and cytotoxicity, unlike psoralen or phosphor alone (p<0.0001). We also show that apoptosis increases as doses of phosphor, psoralen, or radiation increase. Finally, in an in-vivo pilot study of BALBc mice with syngeneic 4T1 tumors, we show that the rate of tumor growth is slower with X-PACT than with saline or AMT + X-ray (p<0.0001). Overall these studies demonstrate a potential therapeutic effect for X-PACT, and provide a foundation and rationale for future studies. In summary, X-PACT represents a novel treatment approach in which well-tolerated low doses of x-ray radiation are delivered to a specific tumor site to generate UVA light which in-turn unleashes both short- and potentially long-term antitumor activity of photo-active therapeutics like psoralen.

Authors
Oldham, M; Yoon, P; Fathi, Z; Beyer, WF; Adamson, J; Liu, L; Alcorta, D; Xia, W; Osada, T; Liu, C; Yang, XY; Dodd, RD; Herndon, JE; Meng, B; Kirsch, DG; Lyerly, HK; Dewhirst, MW; Fecci, P; Walder, H; Spector, NL
MLA Citation
Oldham, M, Yoon, P, Fathi, Z, Beyer, WF, Adamson, J, Liu, L, Alcorta, D, Xia, W, Osada, T, Liu, C, Yang, XY, Dodd, RD, Herndon, JE, Meng, B, Kirsch, DG, Lyerly, HK, Dewhirst, MW, Fecci, P, Walder, H, and Spector, NL. "X-Ray Psoralen Activated Cancer Therapy (X-PACT)." PloS one 11.9 (January 2016): e0162078-.
Website
http://hdl.handle.net/10161/13034
PMID
27583569
Source
epmc
Published In
PloS one
Volume
11
Issue
9
Publish Date
2016
Start Page
e0162078
DOI
10.1371/journal.pone.0162078

Practical Dyspnea Assessment: Relationship Between the 0-10 Numerical Rating Scale and the Four-Level Categorical Verbal Descriptor Scale of Dyspnea Intensity.

Measurement of dyspnea is important for clinical care and research.To characterize the relationship between the 0-10 Numerical Rating Scale (NRS) and four-level categorical Verbal Descriptor Scale (VDS) for dyspnea assessment.This was a substudy of a double-blind randomized controlled trial comparing palliative oxygen to room air for relief of refractory breathlessness in patients with life-limiting illness. Dyspnea was assessed with both a 0-10 NRS and a four-level categorical VDS over the one-week trial. NRS and VDS responses were analyzed in cross section and longitudinally. Relationships between NRS and VDS responses were portrayed using descriptive statistics and visual representations.Two hundred twenty-six participants contributed responses. At baseline, mild and moderate levels of breathlessness were reported by 41.9% and 44.6% of participants, respectively. NRS scores demonstrated increasing mean and median levels for increasing VDS intensity, from a mean (SD) of 0.6 (±1.04) for VDS none category to 8.2 (1.4) for VDS severe category. The Spearman correlation coefficient was strong at 0.78 (P < 0.0001). Based on the distribution of NRS scores within VDS categories, we calculated test characteristics of two different cutpoint models. Both models yielded 75% correct translations from NRS to VDS; however, Model A was more sensitive for moderate or greater dyspnea, with fewer misses downcoded.There is strong correlation between VDS and NRS measures for dyspnea. Proposed practical cutpoints for the relationship between the dyspnea VDS and NRS are 0 for none, 1-4 for mild, 5-8 for moderate, and 9-10 for severe.

Authors
Wysham, NG; Miriovsky, BJ; Currow, DC; Herndon, JE; Samsa, GP; Wilcock, A; Abernethy, AP
MLA Citation
Wysham, NG, Miriovsky, BJ, Currow, DC, Herndon, JE, Samsa, GP, Wilcock, A, and Abernethy, AP. "Practical Dyspnea Assessment: Relationship Between the 0-10 Numerical Rating Scale and the Four-Level Categorical Verbal Descriptor Scale of Dyspnea Intensity." Journal of pain and symptom management 50.4 (October 2015): 480-487.
PMID
26004401
Source
epmc
Published In
Journal of Pain and Symptom Management
Volume
50
Issue
4
Publish Date
2015
Start Page
480
End Page
487
DOI
10.1016/j.jpainsymman.2015.04.015

Reply to "Prognostic Value of Fluorodeoxyglucose-Positron Emission Tomography".

Authors
Kwon, W; Howard, BA; Herndon, JE; Patz, EF
MLA Citation
Kwon, W, Howard, BA, Herndon, JE, and Patz, EF. "Reply to "Prognostic Value of Fluorodeoxyglucose-Positron Emission Tomography"." Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 10.10 (October 2015): e102-.
Website
http://hdl.handle.net/10161/11156
PMID
26398827
Source
epmc
Published In
Journal of Thoracic Oncology
Volume
10
Issue
10
Publish Date
2015
Start Page
e102
DOI
10.1097/jto.0000000000000637

Phase II Trial of Upfront Bevacizumab, Irinotecan, and Temozolomide for Unresectable Glioblastoma.

Trials focusing on unresectable multifocal glioblastoma are needed because of the extremely poor prognosis and challenges in receiving standard therapy, such as concurrent radiation and chemotherapy.Developing a strategy to chemically debulk tumors before radiation and/or surgery is warranted.Extent of resection remains a key prognostic factor in glioblastoma (GBM), with gross total resection providing a better prognosis than biopsy or subtotal resection. We conducted a phase II trial of upfront therapy with bevacizumab (BV), irinotecan (CPT-11), and temozolomide (TMZ) prior to chemoradiation in patients with unresectable, subtotally resected, and/or multifocal GBM.Patients received up to 4 cycles of TMZ at 200 mg/m(2) per day on days 1-5 (standard dosing) and BV at 10 mg/kg every 2 weeks on a 28-day cycle. CPT-11 was given every 2 weeks on a 28-day cycle at 125 mg/m(2) or 340 mg/m(2) depending on antiepileptic drugs. Magnetic resonance imaging of the brain was done every 4 weeks, and treatment continued as long as there was no tumor progression or unmanageable toxicity. The primary endpoint was tumor response rate, with a goal of 26% or greater.Forty-one patients were enrolled from December 2009 to November 2010. Radiographic responses were as follows: 9 patients (22.0%) had partial response, 25 (61.0%) had stable disease, and 2 (4.9%) had progression; 5 patients were not assessed. Cumulative response rate was 22%. Median overall survival was 12 months (95% confidence interval: 7.2-13.5 months).Upfront treatment with BV, TMZ, and CPT-11 is tolerable and can lead to radiographic response in unresectable and/or subtotally resected GBM.

Authors
Peters, KB; Lou, E; Desjardins, A; Reardon, DA; Lipp, ES; Miller, E; Herndon, JE; McSherry, F; Friedman, HS; Vredenburgh, JJ
MLA Citation
Peters, KB, Lou, E, Desjardins, A, Reardon, DA, Lipp, ES, Miller, E, Herndon, JE, McSherry, F, Friedman, HS, and Vredenburgh, JJ. "Phase II Trial of Upfront Bevacizumab, Irinotecan, and Temozolomide for Unresectable Glioblastoma." The oncologist 20.7 (July 2015): 727-728.
PMID
26025933
Source
epmc
Published In
The oncologist
Volume
20
Issue
7
Publish Date
2015
Start Page
727
End Page
728
DOI
10.1634/theoncologist.2015-0135

FDG Uptake on Positron Emission Tomography Correlates with Survival and Time to Recurrence in Patients with Stage I Non-Small-Cell Lung Cancer.

Patients with stage I non-small-cell lung cancer (NSCLC) have a wide variation in outcomes, most likely because there are undetected metastases at presentation. We retrospectively reviewed patients with early stage lung cancer to determine if FDG uptake of the primary tumor as measured on positron emission tomography (PET) at the time of diagnosis was associated with overall survival (OS) or time to recurrence (TTR).We reviewed the Tumor Registry at our institution and identified 336 consecutive patients diagnosed with stage I NSCLC over a 5-year period who underwent an FDG-PET/computed tomography within 90 days before surgery. Kaplan-Meier curves were used to describe the survival and TTR experience within subgroups defined by PET maximum standardized uptake value (SUVmax). Cox proportional hazards model was used to assess the impact of PET SUVmax as a continuous variable on OS and TTR. Logistic regression was used to analyze the effect of SUVmax on dichotomized outcomes.Three hundred thirty-six consecutive patients (176 women and 160 men) with stage I NSCLC were retrospectively reviewed. Mean SUVmax was 9.2 ± 6.9 (range 0.6-30.3). The hazard or risk of dying and recurrence increased significantly as SUVmax increased (p = 0.0008 and 0.024, respectively).Preoperative FDG uptake in the primary tumor in patients with stage I disease is associated with OS and TTR. This may be useful in identifying early stage patients who may benefit from more aggressive therapy after surgical resection.

Authors
Kwon, W; Howard, BA; Herndon, JE; Patz, EF
MLA Citation
Kwon, W, Howard, BA, Herndon, JE, and Patz, EF. "FDG Uptake on Positron Emission Tomography Correlates with Survival and Time to Recurrence in Patients with Stage I Non-Small-Cell Lung Cancer." Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 10.6 (June 2015): 897-902.
PMID
25811445
Source
epmc
Published In
Journal of Thoracic Oncology
Volume
10
Issue
6
Publish Date
2015
Start Page
897
End Page
902
DOI
10.1097/jto.0000000000000534

Secondary cancers in long-term survivors of primary glioblastoma.

Authors
Kim, J-Y; Woodring, S; Affronti, ML; Randazzo, D; McSherry, F; Herndon, JE; Lipp, ES; Desjardins, A; Vlahovic, G; Friedman, HS; Peters, KB
MLA Citation
Kim, J-Y, Woodring, S, Affronti, ML, Randazzo, D, McSherry, F, Herndon, JE, Lipp, ES, Desjardins, A, Vlahovic, G, Friedman, HS, and Peters, KB. "Secondary cancers in long-term survivors of primary glioblastoma." May 20, 2015.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
33
Issue
15
Publish Date
2015

Phase II study of bevacizumab and vorinostat for recurrent glioblastoma.

Authors
Ghiaseddin, A; Reardon, DA; Massey, W; Mannerino, A; Lipp, ES; Herndon, JE; McSherry, F; Desjardins, A; Randazzo, DM; Vlahovic, G; Friedman, HS; Peters, KB
MLA Citation
Ghiaseddin, A, Reardon, DA, Massey, W, Mannerino, A, Lipp, ES, Herndon, JE, McSherry, F, Desjardins, A, Randazzo, DM, Vlahovic, G, Friedman, HS, and Peters, KB. "Phase II study of bevacizumab and vorinostat for recurrent glioblastoma." May 20, 2015.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
33
Issue
15
Publish Date
2015

Phase I study of combination of antitumor immunotherapy targeted against cytomegalovirus (CMV) plus regulatory T-cell inhibition in patients with newly diagnosed glioblastoma multiforme (GBM).

Authors
Vlahovic, G; Archer, GE; Lally-Goss, D; Reap, E; Desjardins, A; Peters, KB; Randazzo, D; Healy, P; Herndon, JE; Friedman, AH; Friedman, HS; Bigner, DD; Sampson, JH
MLA Citation
Vlahovic, G, Archer, GE, Lally-Goss, D, Reap, E, Desjardins, A, Peters, KB, Randazzo, D, Healy, P, Herndon, JE, Friedman, AH, Friedman, HS, Bigner, DD, and Sampson, JH. "Phase I study of combination of antitumor immunotherapy targeted against cytomegalovirus (CMV) plus regulatory T-cell inhibition in patients with newly diagnosed glioblastoma multiforme (GBM)." May 20, 2015.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
33
Issue
15
Publish Date
2015

Oncolytic polio/rhinovirus recombinant (PVSRIPO) against recurrent glioblastoma (GBM): Optimal dose determination.

Authors
Desjardins, A; Sampson, JH; Peters, KB; Vlahovic, G; Randazzo, D; Threatt, S; Herndon, JE; Boulton, S; Lally-Goss, D; McSherry, F; Lipp, ES; Friedman, AH; Friedman, HS; Bigner, DD; Gromeier, M
MLA Citation
Desjardins, A, Sampson, JH, Peters, KB, Vlahovic, G, Randazzo, D, Threatt, S, Herndon, JE, Boulton, S, Lally-Goss, D, McSherry, F, Lipp, ES, Friedman, AH, Friedman, HS, Bigner, DD, and Gromeier, M. "Oncolytic polio/rhinovirus recombinant (PVSRIPO) against recurrent glioblastoma (GBM): Optimal dose determination." May 20, 2015.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
33
Issue
15
Publish Date
2015

Carboxyamidotriazole orotate (CTO) in combination with bevacizumab (BEV) for adult patients with recurrent malignant glioma post-BEV failure: Phase 1.

Authors
Desjardins, A; Peters, KB; Vlahovic, G; Randazzo, D; Boulton, S; Massey, WC; Lipp, ES; Herndon, JE; Healy, P; Miller, E; Karmali, RA; Friedman, HS
MLA Citation
Desjardins, A, Peters, KB, Vlahovic, G, Randazzo, D, Boulton, S, Massey, WC, Lipp, ES, Herndon, JE, Healy, P, Miller, E, Karmali, RA, and Friedman, HS. "Carboxyamidotriazole orotate (CTO) in combination with bevacizumab (BEV) for adult patients with recurrent malignant glioma post-BEV failure: Phase 1." May 20, 2015.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
33
Issue
15
Publish Date
2015

Phase 1 clinical trial of carboxyamidotriazole orotate (CTO) in combination with lomustine (CCNU) for adult patients with recurrent malignant glioma (MG).

Authors
Friedman, HS; Peters, KB; Vlahovic, G; Randazzo, D; Boulton, S; Woodring, S; Lipp, ES; Herndon, JE; Healy, P; Miller, E; Karmali, RA; Desjardins, A
MLA Citation
Friedman, HS, Peters, KB, Vlahovic, G, Randazzo, D, Boulton, S, Woodring, S, Lipp, ES, Herndon, JE, Healy, P, Miller, E, Karmali, RA, and Desjardins, A. "Phase 1 clinical trial of carboxyamidotriazole orotate (CTO) in combination with lomustine (CCNU) for adult patients with recurrent malignant glioma (MG)." May 20, 2015.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
33
Issue
15
Publish Date
2015

Prognostic marker analysis in pediatric intracranial ependymomas.

Histologic grading methods dependent upon H&E staining review have not been shown to reliably predict survival in children with intracranial ependymomas due to the subjectivity of the analytical methods. We hypothesized that the immunohistochemical detection of MIB-1, Tenascin C, CD34, VEGF, and CA IX may represent objective markers of post-operative survival (Progression Free and Overall Survival; PFS, OS) in these patients. Intracranial ependymomas from patients aged 22 years or less were studied. The original histologic grade was recorded, H&E sections were reviewed for vascular proliferation status, and immunohistochemistry was used to determine MIB-1, Tenascin C, CD34, VEGF, and CA IX status. Based upon the World Health Organization (WHO) grading system, 3 Grade I, 18 Grade II and 9 Grade III ependymomas were studied. Median follow-up time was 9.0 years; median PFS was, 6.1 years. Original WHO grade did not correlate with PFS or OS. Peri-necrotic CA IX localization correlated with PFS (Log rank = 0.0181) and OS (Log rank p = 0.0015). All patients with a CA IX ≤ 5 % total area localization were alive at last follow-up. Perinecrotic CA IX staining was also associated with vascular proliferation (p = 0.006), though not with VEGF expression score. MIB-1 labeling index (LI) correlated with OS (HR 1.06, 95 % CI 1.01, 1.12) and PFS (HR 1.08, 95 % CI 1.02, 1.14). MIB-1 LI and perinecrotic CA IX individually correlated with PFS. The effect of perinecrotic CA IX remained when grade was added to a Cox model predicting PFS. Immunodetection of CA IX and MIB-1 expression are predictive biomarkers for survival in children with posterior fossa ependymomas. These markers represent objective indicators of survival that supplement H&E grading alone.

Authors
McLendon, RE; Lipp, E; Satterfield, D; Ehinger, M; Austin, A; Fleming, D; Perkinson, K; Lefaivre, M; Zagzag, D; Wiener, B; Gururangan, S; Fuchs, H; Friedman, HS; Herndon, JE; Healy, P
MLA Citation
McLendon, RE, Lipp, E, Satterfield, D, Ehinger, M, Austin, A, Fleming, D, Perkinson, K, Lefaivre, M, Zagzag, D, Wiener, B, Gururangan, S, Fuchs, H, Friedman, HS, Herndon, JE, and Healy, P. "Prognostic marker analysis in pediatric intracranial ependymomas." Journal of neuro-oncology 122.2 (April 2015): 255-261.
PMID
25563815
Source
epmc
Published In
Journal of Neuro-Oncology
Volume
122
Issue
2
Publish Date
2015
Start Page
255
End Page
261
DOI
10.1007/s11060-014-1711-z

Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients.

After stimulation, dendritic cells (DCs) mature and migrate to draining lymph nodes to induce immune responses. As such, autologous DCs generated ex vivo have been pulsed with tumour antigens and injected back into patients as immunotherapy. While DC vaccines have shown limited promise in the treatment of patients with advanced cancers including glioblastoma, the factors dictating DC vaccine efficacy remain poorly understood. Here we show that pre-conditioning the vaccine site with a potent recall antigen such as tetanus/diphtheria (Td) toxoid can significantly improve the lymph node homing and efficacy of tumour-antigen-specific DCs. To assess the effect of vaccine site pre-conditioning in humans, we randomized patients with glioblastoma to pre-conditioning with either mature DCs or Td unilaterally before bilateral vaccination with DCs pulsed with Cytomegalovirus phosphoprotein 65 (pp65) RNA. We and other laboratories have shown that pp65 is expressed in more than 90% of glioblastoma specimens but not in surrounding normal brain, providing an unparalleled opportunity to subvert this viral protein as a tumour-specific target. Patients given Td had enhanced DC migration bilaterally and significantly improved survival. In mice, Td pre-conditioning also enhanced bilateral DC migration and suppressed tumour growth in a manner dependent on the chemokine CCL3. Our clinical studies and corroborating investigations in mice suggest that pre-conditioning with a potent recall antigen may represent a viable strategy to improve anti-tumour immunotherapy.

Authors
Mitchell, DA; Batich, KA; Gunn, MD; Huang, M-N; Sanchez-Perez, L; Nair, SK; Congdon, KL; Reap, EA; Archer, GE; Desjardins, A; Friedman, AH; Friedman, HS; Herndon, JE; Coan, A; McLendon, RE; Reardon, DA; Vredenburgh, JJ; Bigner, DD; Sampson, JH
MLA Citation
Mitchell, DA, Batich, KA, Gunn, MD, Huang, M-N, Sanchez-Perez, L, Nair, SK, Congdon, KL, Reap, EA, Archer, GE, Desjardins, A, Friedman, AH, Friedman, HS, Herndon, JE, Coan, A, McLendon, RE, Reardon, DA, Vredenburgh, JJ, Bigner, DD, and Sampson, JH. "Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients." Nature 519.7543 (March 11, 2015): 366-369.
PMID
25762141
Source
epmc
Published In
Nature
Volume
519
Issue
7543
Publish Date
2015
Start Page
366
End Page
369
DOI
10.1038/nature14320

Quantitative measures of physical functioning after autologous hematopoietic stem cell transplantation in multiple myeloma: a feasibility study.

BACKGROUND: The safety and feasibility of the symptom-limited cardiopulmonary exercise test (CPET) and the 6-minute walk test (6MWT) has not been rigorously tested in patients with multiple myeloma (MM) after high-dose chemotherapy with autologous stem cell transplantation (ASCT), nor have correlations with patient-reported outcomes (PROs) been explored. PATIENTS AND METHODS: We undertook CPET, 6MWT, and PRO assessments using standardized measurements and questionnaires in patients with MM in remission after ASCT. RESULTS: A total of 22 patients who were a median of 17 months after ASCT underwent assessment. No severe adverse events were observed. Exercise capacity, measured during CPET as the peak oxygen consumption, was 17.5 ± 5.9 mL/kg/min, the equivalent of 38% ± 18% less than that for age- and sex-predicted sedentary normative values. During the 6MWT, the mean 6-minute walk distance was 500 m, or 25% ± 13% less than the predicted values. Additional analysis using Pearson's correlation revealed no significant univariate associations between exercise or functional capacity and any PROs. CONCLUSION: Patients with MM have marked and significant reductions in quantitative measures of physical function for years after the initial therapy, although that did not correlate with PROs in the present pilot study. Larger prospective studies are required to determine the clinical ramifications of these findings and to mechanistically dissect them, as well to test interventions aimed at mitigating them.

Authors
Tuchman, SA; Lane, A; Hornsby, WE; Bishop, C; Thomas, S; Herndon, JE; Long, G; Gasparetto, C; Jones, LW
MLA Citation
Tuchman, SA, Lane, A, Hornsby, WE, Bishop, C, Thomas, S, Herndon, JE, Long, G, Gasparetto, C, and Jones, LW. "Quantitative measures of physical functioning after autologous hematopoietic stem cell transplantation in multiple myeloma: a feasibility study." Clinical lymphoma, myeloma & leukemia 15.2 (February 2015): 103-109.
PMID
25445473
Source
epmc
Published In
Clinical Lymphoma, Myeloma and Leukemia
Volume
15
Issue
2
Publish Date
2015
Start Page
103
End Page
109
DOI
10.1016/j.clml.2014.09.002

Radioprotection of the brain white matter by Mn(III) n-Butoxyethylpyridylporphyrin-based superoxide dismutase mimic MnTnBuOE-2-PyP5+.

Cranial irradiation is a standard therapy for primary and metastatic brain tumors. A major drawback of radiotherapy (RT), however, is long-term cognitive loss that affects quality of life. Radiation-induced oxidative stress in normal brain tissue is thought to contribute to cognitive decline. We evaluated the effectiveness of a novel mimic of superoxide dismutase enzyme (SOD), MnTnBuOE-2-PyP(5+)(Mn(III) meso-tetrakis(N-n-butoxyethylpyridinium-2-yl)porphyrin), to provide long-term neuroprotection following 8 Gy of whole brain irradiation. Long-term RT damage can only be assessed by brain imaging and neurocognitive studies. C57BL/6J mice were treated with MnTnBuOE-2-PyP(5+) before and after RT and evaluated three months later. At this time point, drug concentration in the brain was 25 nmol/L. Mice treated with MnTnBuOE-2-PyP(5+)/RT exhibited MRI evidence for myelin preservation in the corpus callosum compared with saline/RT treatment. Corpus callosum histology demonstrated a significant loss of axons in the saline/RT group that was rescued in the MnTnBuOE-2-PyP(5+)/RT group. In addition, the saline/RT groups exhibited deficits in motor proficiency as assessed by the rotorod test and running wheel tests. These deficits were ameliorated in groups treated with MnTnBuOE-2-PyP(5+)/RT. Our data demonstrate that MnTnBuOE-2-PyP(5+) is neuroprotective for oxidative stress damage caused by radiation exposure. In addition, glioblastoma cells were not protected by MnTnBuOE-2-PyP(5+) combination with radiation in vitro. Likewise, the combination of MnTnBuOE-2-PyP(5+) with radiation inhibited tumor growth more than RT alone in flank tumors. In summary, MnTnBuOE-2-PyP(5+) has dual activity as a neuroprotector and a tumor radiosensitizer. Thus, it is an attractive candidate for adjuvant therapy with RT in future studies with patients with brain cancer.

Authors
Weitzel, DH; Tovmasyan, A; Ashcraft, KA; Rajic, Z; Weitner, T; Liu, C; Li, W; Buckley, AF; Prasad, MR; Young, KH; Rodriguiz, RM; Wetsel, WC; Peters, KB; Spasojevic, I; Herndon, JE; Batinic-Haberle, I; Dewhirst, MW
MLA Citation
Weitzel, DH, Tovmasyan, A, Ashcraft, KA, Rajic, Z, Weitner, T, Liu, C, Li, W, Buckley, AF, Prasad, MR, Young, KH, Rodriguiz, RM, Wetsel, WC, Peters, KB, Spasojevic, I, Herndon, JE, Batinic-Haberle, I, and Dewhirst, MW. "Radioprotection of the brain white matter by Mn(III) n-Butoxyethylpyridylporphyrin-based superoxide dismutase mimic MnTnBuOE-2-PyP5+." Molecular cancer therapeutics 14.1 (January 2015): 70-79.
PMID
25319393
Source
epmc
Published In
Molecular cancer therapeutics
Volume
14
Issue
1
Publish Date
2015
Start Page
70
End Page
79
DOI
10.1158/1535-7163.mct-14-0343

Defining the optimal planning target volume in image-guided stereotactic radiosurgery of brain metastases: results of a randomized trial.

PURPOSE: To identify an optimal margin about the gross target volume (GTV) for stereotactic radiosurgery (SRS) of brain metastases, minimizing toxicity and local recurrence. METHODS AND MATERIALS: Adult patients with 1 to 3 brain metastases less than 4 cm in greatest dimension, no previous brain radiation therapy, and Karnofsky performance status (KPS) above 70 were eligible for this institutional review board-approved trial. Individual lesions were randomized to 1- or 3- mm uniform expansion of the GTV defined on contrast-enhanced magnetic resonance imaging (MRI). The resulting planning target volume (PTV) was treated to 24, 18, or 15 Gy marginal dose for maximum PTV diameters less than 2, 2 to 2.9, and 3 to 3.9 cm, respectively, using a linear accelerator-based image-guided system. The primary endpoint was local recurrence (LR). Secondary endpoints included neurocognition Mini-Mental State Examination, Trail Making Test Parts A and B, quality of life (Functional Assessment of Cancer Therapy-Brain), radionecrosis (RN), need for salvage radiation therapy, distant failure (DF) in the brain, and overall survival (OS). RESULTS: Between February 2010 and November 2012, 49 patients with 80 brain metastases were treated. The median age was 61 years, the median KPS was 90, and the predominant histologies were non-small cell lung cancer (25 patients) and melanoma (8). Fifty-five, 19, and 6 lesions were treated to 24, 18, and 15 Gy, respectively. The PTV/GTV ratio, volume receiving 12 Gy or more, and minimum dose to PTV were significantly higher in the 3-mm group (all P<.01), and GTV was similar (P=.76). At a median follow-up time of 32.2 months, 11 patients were alive, with median OS 10.6 months. LR was observed in only 3 lesions (2 in the 1 mm group, P=.51), with 6.7% LR 12 months after SRS. Biopsy-proven RN alone was observed in 6 lesions (5 in the 3-mm group, P=.10). The 12-month DF rate was 45.7%. Three months after SRS, no significant change in neurocognition or quality of life was observed. CONCLUSIONS: SRS was well tolerated, with low rates of LR and RN in both cohorts. However, given the higher potential risk of RN with a 3-mm margin, a 1-mm GTV expansion is more appropriate.

Authors
Kirkpatrick, JP; Wang, Z; Sampson, JH; McSherry, F; Herndon, JE; Allen, KJ; Duffy, E; Hoang, JK; Chang, Z; Yoo, DS; Kelsey, CR; Yin, F-F
MLA Citation
Kirkpatrick, JP, Wang, Z, Sampson, JH, McSherry, F, Herndon, JE, Allen, KJ, Duffy, E, Hoang, JK, Chang, Z, Yoo, DS, Kelsey, CR, and Yin, F-F. "Defining the optimal planning target volume in image-guided stereotactic radiosurgery of brain metastases: results of a randomized trial." International journal of radiation oncology, biology, physics 91.1 (January 2015): 100-108.
PMID
25442342
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
91
Issue
1
Publish Date
2015
Start Page
100
End Page
108
DOI
10.1016/j.ijrobp.2014.09.004

Impact of health-related quality of life and fatigue on survival of recurrent high-grade glioma patients.

Quality of life (QoL) impairment and fatigue are frequently experienced during treatment for recurrent high-grade glioma (HGG). Fatigue and QoL impairments can be due to primary neurological dysfunction, cytotoxic treatments, mood disturbances, and supportive medications. We now seek to understand how QoL and fatigue impacts survival in recurrent HGG. Using a prospective observational design, 237 patients with recurrent HGG and KPS ≥70 completed a self-administered questionnaire that evaluated QoL and fatigue. QoL was assessed with Functional Assessment of Cancer Therapy-General (FACT-G) and FACT-Brain (FACT-Br) scales while fatigue was assessed using Functional Assessment of Chronic Illness Therapy (FACIT-F) scale. Cox proportional hazard models were utilized to evaluate the association between QoL and fatigue and survival. Seventy-three (31 %) subjects had recurrent WHO grade III gliomas and 164 (69 %) had recurrent WHO grade IV gliomas. Median follow-up analysis was 27.60 months. In univariate Cox analyses, the FACT-Br specific subscale (HR 0.88; CI 95 %, 0.77-1; p = 0.048) and FACIT-F (HR 0.82; CI 95 %, 0.68-0.99; p = 0.045) were both significant predictors of survival. Fatigue added prognostic information beyond that provided by KPS, age, sex, tumor grade, and number of prior progressions (HR 0.80; CI 95 %, 0.68-0.9; p = 0.031). A greater degree of fatigue was associated with poorer survival in recurrent HGG patients. In multivariable analyses, FACT-G and FACT-Br are not independent predictors of prognosis. Fatigue is a strong independent predictor of survival that provides incremental prognostic value to the traditional markers of prognosis in recurrent HGG. Pharmacological or non-pharmacological strategies to treat fatigue warrant investigation.

Authors
Peters, KB; West, MJ; Hornsby, WE; Waner, E; Coan, AD; McSherry, F; Herndon, JE; Friedman, HS; Desjardins, A; Jones, LW
MLA Citation
Peters, KB, West, MJ, Hornsby, WE, Waner, E, Coan, AD, McSherry, F, Herndon, JE, Friedman, HS, Desjardins, A, and Jones, LW. "Impact of health-related quality of life and fatigue on survival of recurrent high-grade glioma patients." Journal of neuro-oncology 120.3 (December 2014): 499-506.
PMID
25115739
Source
epmc
Published In
Journal of Neuro-Oncology
Volume
120
Issue
3
Publish Date
2014
Start Page
499
End Page
506
DOI
10.1007/s11060-014-1574-3

Abstract CT416: Intratumoral administration of an Oncolytic Polio/Rhinovirus Recombinant (PVSRIPO) in recurrent glioblastoma (GBM): Preliminary results of the Phase I clinical trial

Authors
Desjardins, A; Sampson, JH; Peters, KB; Ranjan, T; Vlahovic, G; Threatt, S; Herndon, JE; Boulton, S; Lally-Goss, D; McSherry, F; Friedman, A; Friedman, HS; Bigner, DD; Gromeier, M
MLA Citation
Desjardins, A, Sampson, JH, Peters, KB, Ranjan, T, Vlahovic, G, Threatt, S, Herndon, JE, Boulton, S, Lally-Goss, D, McSherry, F, Friedman, A, Friedman, HS, Bigner, DD, and Gromeier, M. "Abstract CT416: Intratumoral administration of an Oncolytic Polio/Rhinovirus Recombinant (PVSRIPO) in recurrent glioblastoma (GBM): Preliminary results of the Phase I clinical trial." October 1, 2014.
Source
crossref
Published In
Cancer Research
Volume
74
Issue
19 Supplement
Publish Date
2014
Start Page
CT416
End Page
CT416
DOI
10.1158/1538-7445.AM2014-CT416

Cardiopulmonary exercise testing prior to myeloablative allo-SCT: a feasibility study.

The feasibility of symptom-limited cardiopulmonary exercise testing (CPET) prior to allo-SCT was assessed in addition to the prognostic value of CPET-derived measures. CPET was performed prospectively on 21 patients with hematologic malignancies, with assessments of peak (for example, peak oxygen consumption, VO2peak) and submaximal (for example, ventilatory threshold (VT)) measures of cardiopulmonary function. No serious adverse events were observed during CPET procedures, with 95% of patients achieving criteria for a peak test. Mean VO2peak was 24.7±6.4 mL kg(-1 )min(-1) (range: 10.9-35.5), equivalent to 29%±17% below that of age-matched healthy controls. All patients proceeded with the conditioning regimen followed by allo-SCT. Median follow-up was 25 months. During this period, 11 (52.4%) patients died (n=6, relapsed disease; n=5, non-relapse mortality (NRM)); 9 patients (43%) developed pulmonary toxicity. In univariate analyses, both peak and submaximal markers of cardiopulmonary function were predictors of OS, pulmonary toxicity and NRM. For OS, the HR for VO2peak and VT were 0.89 (95% CI, 0.8-0.99, P=0.04) and 0.84 (95% CI, 0.71-0.98, P=0.03), respectively. In conclusion, CPET is safe and feasible prior to allo-SCT. Patients have marked impairments in cardiopulmonary function prior to allo-SCT. CPET-derived metrics may complement conventional measures to improve risk stratification.

Authors
Kelsey, CR; Scott, JM; Lane, A; Schwitzer, E; West, MJ; Thomas, S; Herndon, JE; Michalski, MG; Horwitz, ME; Hennig, T; Jones, LW
MLA Citation
Kelsey, CR, Scott, JM, Lane, A, Schwitzer, E, West, MJ, Thomas, S, Herndon, JE, Michalski, MG, Horwitz, ME, Hennig, T, and Jones, LW. "Cardiopulmonary exercise testing prior to myeloablative allo-SCT: a feasibility study." Bone marrow transplantation 49.10 (October 2014): 1330-1336.
PMID
25068429
Source
epmc
Published In
Bone Marrow Transplantation
Volume
49
Issue
10
Publish Date
2014
Start Page
1330
End Page
1336
DOI
10.1038/bmt.2014.159

Pre-exercise participation cardiovascular screening in a heterogeneous cohort of adult cancer patients.

The purpose of this study was to investigate the extent of pre-exercise participation ("preparticipation") health screening in a heterogeneous cohort of adult cancer patients.Patients (n = 413) with histologically confirmed solid or hematologic malignancy were categorized into preparticipation health screening risk stratification based on American College Sports Medicine (ACSM) recommendations. Risk of an exercise-related event was evaluated during a symptom-limited cardiopulmonary exercise test (CPET) with 12-lead electrocardiography (ECG).Participant risk was categorized as low risk (n = 59, 14%), moderate risk (n = 217, 53%), and high risk (n = 137, 33%). Mean peak oxygen consumption was 21.7 ± 6.7 mL/kg(-1) per minute(-1) or 19.5 ± 21.7% below age- and sex-predicted sedentary values. No major serious adverse events or fatal events were observed during CPET procedures. A total of 31 positive ECG tests were observed, for an event rate of 8%. ACSM risk stratification did not predict the risk of a positive test. Age, statin use, antiplatelet therapy use, cardiovascular disease, prior treatment with anthracycline or radiation therapy, and being sedentary were predictors of a positive test (all p < .10).The patient risk-stratification profile strongly suggests that the use of formalized preparticipation health screening is required in all oncology scenarios; however, risk of an exercise-induced event is low, suggesting that the use of exercise testing is not required for pre-exercise clearance in the majority of patients.

Authors
Kenjale, AA; Hornsby, WE; Crowgey, T; Thomas, S; Herndon, JE; Khouri, MG; Lane, AR; Bishop, CE; Eves, ND; Peppercorn, J; Douglas, PS; Jones, LW
MLA Citation
Kenjale, AA, Hornsby, WE, Crowgey, T, Thomas, S, Herndon, JE, Khouri, MG, Lane, AR, Bishop, CE, Eves, ND, Peppercorn, J, Douglas, PS, and Jones, LW. "Pre-exercise participation cardiovascular screening in a heterogeneous cohort of adult cancer patients." The oncologist 19.9 (September 2014): 999-1005.
PMID
25061091
Source
epmc
Published In
The oncologist
Volume
19
Issue
9
Publish Date
2014
Start Page
999
End Page
1005
DOI
10.1634/theoncologist.2014-0078

A novel, reproducible, and objective method for volumetric magnetic resonance imaging assessment of enhancing glioblastoma.

Robust methodology that allows objective, automated, and observer-independent measurements of brain tumor volume, especially after resection, is lacking. Thus, determination of tumor response and progression in neurooncology is unreliable. The objective of this study was to determine if a semi-automated volumetric method for quantifying enhancing tissue would perform with high reproducibility and low interobserver variability.Fifty-seven MR images from 13 patients with glioblastoma were assessed using our method, by 2 neuroradiologists, 1 neurosurgeon, 1 neurosurgical resident, 1 nurse practitioner, and 1 medical student. The 2 neuroradiologists also performed traditional 1-dimensional (1D) and 2-dimensional (2D) measurements. Intraclass correlation coefficients (ICCs) assessed interobserver variability between measurements. Radiological response was determined using Response Evaluation Criteria In Solid Tumors (RECIST) guidelines and Macdonald criteria. Kappa statistics described interobserver variability of volumetric radiological response determinations.There was strong agreement for 1D (RECIST) and 2D (Macdonald) measurements between neuroradiologists (ICC = 0.42 and 0.61, respectively), but the agreement using the authors' novel automated approach was significantly stronger (ICC = 0.97). The volumetric method had the strongest agreement with regard to radiological response (κ = 0.96) when compared with 2D (κ = 0.54) or 1D (κ = 0.46) methods. Despite diverse levels of experience of the users of the volumetric method, measurements using the volumetric program remained remarkably consistent in all users (0.94).Interobserver variability using this new semi-automated method is less than the variability with traditional methods of tumor measurement. This new method is objective, quick, and highly reproducible among operators with varying levels of expertise. This approach should be further evaluated as a potential standard for response assessment based on contrast enhancement in brain tumors.

Authors
Kanaly, CW; Mehta, AI; Ding, D; Hoang, JK; Kranz, PG; Herndon, JE; Coan, A; Crocker, I; Waller, AF; Friedman, AH; Reardon, DA; Sampson, JH
MLA Citation
Kanaly, CW, Mehta, AI, Ding, D, Hoang, JK, Kranz, PG, Herndon, JE, Coan, A, Crocker, I, Waller, AF, Friedman, AH, Reardon, DA, and Sampson, JH. "A novel, reproducible, and objective method for volumetric magnetic resonance imaging assessment of enhancing glioblastoma." Journal of neurosurgery 121.3 (September 2014): 536-542.
PMID
25036205
Source
epmc
Published In
Journal of neurosurgery
Volume
121
Issue
3
Publish Date
2014
Start Page
536
End Page
542
DOI
10.3171/2014.4.jns121952

Adherence to antiemetic guidelines in patients with malignant glioma: a quality improvement project to translate evidence into practice.

A quality improvement project was implemented to improve adherence to evidence-based antiemetic guidelines for malignant glioma patients treated with moderately emetic chemotherapy (MEC). Poorly controlled chemotherapy-induced nausea and vomiting (CINV) reduce cancer treatment efficacy and significantly impair cancer patients' quality of life (QOL). A review of Duke University Preston Robert Tisch Brain Tumor Center (PRTBTC)'s usual practice demonstrates a high incidence (45%) of CINV, despite premedication with short-acting 5-HT3-serotonin-receptor antagonists (5-HT3-RAs). National Comprehensive Cancer Network (NCCN)'s evidence-based guidelines recommend the combination of the long-acting 5-HT3-RA palonosetron (PAL) and dexamethasone (DEX) for the prevention of acute and delayed CINV with MEC. Low adherence (58%) to antiemetic guidelines may have explained our high CINV incidence.One-sample binomial test, quasi-experimental design, evaluated a combination intervention that included a provider education session; implementation of risk-assessment tool with computerized, standardized antiemetic guideline order sets; and a monthly audit-feedback strategy. Post-implementation adherence to evidence-based antiemetic order sets and patient outcomes were measured and compared to baseline and historical data. Primary outcome was the guideline order set adherence rate. Secondary outcomes included nausea/vomiting rates and QOL.Adherence to ordering MEC guideline antiemetics increased significantly, from 58% to a sustained 90%, with associated improvement in nausea/vomiting. In acute and delayed phases, 75 and 84% of patients, respectively, did not experience CINV. There was no significant change in QOL.Combination intervention and audit-feedback strategy to translate evidence into oncology practice improved and sustained adherence to antiemetic guidelines. Adherence corresponded with effective nausea/vomiting control and preserved QOL in patients with malignant gliomas.

Authors
Affronti, ML; Schneider, SM; Herndon, JE; Schlundt, S; Friedman, HS
MLA Citation
Affronti, ML, Schneider, SM, Herndon, JE, Schlundt, S, and Friedman, HS. "Adherence to antiemetic guidelines in patients with malignant glioma: a quality improvement project to translate evidence into practice." Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 22.7 (July 2014): 1897-1905.
PMID
24570103
Source
epmc
Published In
Supportive Care in Cancer
Volume
22
Issue
7
Publish Date
2014
Start Page
1897
End Page
1905
DOI
10.1007/s00520-014-2136-0

Oncolytic polio/rhinovirus recombinant (pvsripo) in recurrent glioblastoma (gbm): first phase I clinical trial evaluating the intratumoral administration.

PVSRIPO is the live attenuated, oral (SABIN) serotype 1 poliovirus vaccine containing a heterologous internal ribosomal entry site stemming from human rhinovirus type 2. PVSRIPO recognizes nectin-like molecule-5, an oncofetal cell adhesion molecule and tumor antigen widely expressed ectopically in malignancy. Within, we report on the ongoing phase I study evaluating the intratumoral convection-enhanced delivery (CED) of PVSRIPO.

Authors
Desjardins, A; Sampson, JH; Peters, KB; Ranjan, T; Vlahovic, G; Threatt, S; Herndon, JE; Boulton, S; Lally-Goss, D; McSherry, F; Friedman, AH; Friedman, HS; Bigner, DD; Gromeier, M
MLA Citation
Desjardins, A, Sampson, JH, Peters, KB, Ranjan, T, Vlahovic, G, Threatt, S, Herndon, JE, Boulton, S, Lally-Goss, D, McSherry, F, Friedman, AH, Friedman, HS, Bigner, DD, and Gromeier, M. "Oncolytic polio/rhinovirus recombinant (pvsripo) in recurrent glioblastoma (gbm): first phase I clinical trial evaluating the intratumoral administration." Neuro Oncol 16 Suppl 3 (July 2014): iii43-.
PMID
25165331
Source
pubmed
Published In
Neuro-Oncology
Volume
16 Suppl 3
Publish Date
2014
Start Page
iii43
DOI
10.1093/neuonc/nou209.5

Tert promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal.

Malignant cells must maintain their telomeres, but genetic mechanisms responsible for telomere maintenance in tumors have only recently been discovered. In particular, mutations of the telomere binding proteins alpha thalassemia/mental retardation syndrome X-linked (ATRX) or death-domain associated protein (DAXX) have been shown to underlie a telomere maintenance mechanism not involving telomerase (alternative lengthening of telomeres), and point mutations in the promoter of the telomerase reverse transcriptase (TERT) gene increase telomerase expression and have been shown to occur in melanomas.

Authors
Yan, H; Killela, PJ; Reitman, ZJ; Jiao, Y; Bettegowda, C; Agrawal, N; Diaz, LA; Friedman, AH; Friedman, H; Gallia, GL; Giovanella, BC; Grollman, AP; He, TC; He, Y; Hruban, RH; Jallo, GI; Mandahl, N; Meeker, AK; Mertens, F; Netto, GJ; Rasheed, BA; Riggins, GJ; Rosenquist, TA; Schiffman, M; Shih, I; Theodorescu, D; Torbenson, MS; Velculescu, VE; Wang, TL; Wentzensen, N; Wood, LD; Zhang, M; Healy, P; Yang, R; Diplas, B; Wang, ZH; Greer, P; Zhu, HS; Wang, C; Carpenter, A; Herndon, JE; McLendon, RE et al.
MLA Citation
Yan, H, Killela, PJ, Reitman, ZJ, Jiao, Y, Bettegowda, C, Agrawal, N, Diaz, LA, Friedman, AH, Friedman, H, Gallia, GL, Giovanella, BC, Grollman, AP, He, TC, He, Y, Hruban, RH, Jallo, GI, Mandahl, N, Meeker, AK, Mertens, F, Netto, GJ, Rasheed, BA, Riggins, GJ, Rosenquist, TA, Schiffman, M, Shih, I, Theodorescu, D, Torbenson, MS, Velculescu, VE, Wang, TL, Wentzensen, N, Wood, LD, Zhang, M, Healy, P, Yang, R, Diplas, B, Wang, ZH, Greer, P, Zhu, HS, Wang, C, Carpenter, A, Herndon, JE, and McLendon, RE et al. "Tert promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal." Neuro Oncol 16 Suppl 3 (July 2014): iii5-iii6.
PMID
25165359
Source
pubmed
Published In
Neuro-Oncology
Volume
16 Suppl 3
Publish Date
2014
Start Page
iii5
End Page
iii6
DOI
10.1093/neuonc/nou206.18

Relationship between exercise behavior, cardiorespiratory fitness, and cognitive function in early breast cancer patients treated with doxorubicin-containing chemotherapy: a pilot study.

The purpose of this study was to examine the relationship between self-reported exercise behavior, cardiorespiratory fitness (CRF), and cognitive function in early breast cancer patients. Thirty-seven breast cancer patients following completion of chemotherapy (median 16 months) and 14 controls were studied. Cognitive function was assessed using the Central Nervous System (CNS) Vital Signs software (CNS Vital Signs, LLC, Morrisville, N.C., USA), a computerized test battery consisting of 9 cognitive subtests. Exercise behavior was evaluated using the Godin Leisure Time Exercise Questionnaire, and CRF was assessed via a cardiopulmonary exercise test to assess peak oxygen consumption. Patients' mean total exercise was 184 ± 141 min·week(-1) compared with 442 ± 315 min·week(-1) in controls (p < 0.001). Significantly fewer patients (32%) were meeting exercise guidelines (i.e., ≥150 min of moderate-intensity or vigorous exercise per week) compared with 57% of controls (p = 0.014). Patients' peak oxygen consumption averaged 23.5 ± 6.3 mL·kg(-1)·min(-1) compared with 30.6 ± 7.0 mL·kg(-1)·min(-1) in controls (p < 0.01). Scores on the cognitive subdomains were generally lower in patients compared with controls, although only the difference in verbal memory was significant (unadjusted p = 0.041). In patients, weak to moderate correlations were indicated between exercise, peak oxygen consumption, and the majority of cognitive subdomain scores; however, there was a significant positive correlation between exercise and visual memory (r = 0.47, p = 0.004). In conclusion, breast cancer patients following the completion of primary adjuvant chemotherapy exhibit, in general, worse cognitive performance than healthy women from the general population, and such performance may be related to their level of exercise behavior.

Authors
Crowgey, T; Peters, KB; Hornsby, WE; Lane, A; McSherry, F; Herndon, JE; West, MJ; Williams, CL; Jones, LW
MLA Citation
Crowgey, T, Peters, KB, Hornsby, WE, Lane, A, McSherry, F, Herndon, JE, West, MJ, Williams, CL, and Jones, LW. "Relationship between exercise behavior, cardiorespiratory fitness, and cognitive function in early breast cancer patients treated with doxorubicin-containing chemotherapy: a pilot study." Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme 39.6 (June 2014): 724-729.
PMID
24869976
Source
epmc
Published In
Applied Physiology, Nutrition and Metabolism
Volume
39
Issue
6
Publish Date
2014
Start Page
724
End Page
729
DOI
10.1139/apnm-2013-0380

Phase I study of the intratumoral administration of an oncolytic polio/rhinovirus recombinant (PVSRIPO) in recurrent glioblastoma (GBM)

Authors
Desjardins, A; Sampson, JH; Peters, KB; Ranjan, T; Vlahovic, G; Watts, J; Threatt, S; Herndon, JE; Boulton, S; Lally-Goss, D; McSherry, F; Friedman, AH; Friedman, HS; Bigner, DD; Gromeier, M
MLA Citation
Desjardins, A, Sampson, JH, Peters, KB, Ranjan, T, Vlahovic, G, Watts, J, Threatt, S, Herndon, JE, Boulton, S, Lally-Goss, D, McSherry, F, Friedman, AH, Friedman, HS, Bigner, DD, and Gromeier, M. "Phase I study of the intratumoral administration of an oncolytic polio/rhinovirus recombinant (PVSRIPO) in recurrent glioblastoma (GBM)." May 20, 2014.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
32
Issue
15
Publish Date
2014

Long-term survivorship in adult primary glioblastoma: Clinical and neurological outcomes of a large, single-center study.

Authors
Peters, KB; Woodring, S; Affronti, ML; McSherry, F; Herndon, JE; Desjardins, A; Ranjan, T; Vlahovic, G; Friedman, AH; Friedman, HS
MLA Citation
Peters, KB, Woodring, S, Affronti, ML, McSherry, F, Herndon, JE, Desjardins, A, Ranjan, T, Vlahovic, G, Friedman, AH, and Friedman, HS. "Long-term survivorship in adult primary glioblastoma: Clinical and neurological outcomes of a large, single-center study." May 20, 2014.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
32
Issue
15
Publish Date
2014

Regulatory T-cell inhibition plus antitumor immunotherapy targeted against cytomegalovirus (CMV) in patients with newly diagnosed glioblastoma multiforme (GBM).

Authors
Vlahovic, G; Archer, GE; Lally-Goss, D; Norman, S; Desjardins, A; Peters, KB; Ranjan, T; Watts, J; Healy, P; Herndon, JE; Friedman, HS; Friedman, AH; Bigner, DD; Sampson, JH
MLA Citation
Vlahovic, G, Archer, GE, Lally-Goss, D, Norman, S, Desjardins, A, Peters, KB, Ranjan, T, Watts, J, Healy, P, Herndon, JE, Friedman, HS, Friedman, AH, Bigner, DD, and Sampson, JH. "Regulatory T-cell inhibition plus antitumor immunotherapy targeted against cytomegalovirus (CMV) in patients with newly diagnosed glioblastoma multiforme (GBM)." May 20, 2014.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
32
Issue
15
Publish Date
2014

Single-institution retrospective review of newly diagnosed glioblastoma (GBM) patients (pis) treated on bevacizumab (BEV) in clinical practice

Authors
Friedman, HS; Herndon, JE; McSherry, F; Ravelo, A; Lipp, ES; Healy, P; Peters, KB; Ranjan, T; Viahovic, G; Watts, J; Sampson, JH; Friedman, AH; Desjardins, A
MLA Citation
Friedman, HS, Herndon, JE, McSherry, F, Ravelo, A, Lipp, ES, Healy, P, Peters, KB, Ranjan, T, Viahovic, G, Watts, J, Sampson, JH, Friedman, AH, and Desjardins, A. "Single-institution retrospective review of newly diagnosed glioblastoma (GBM) patients (pis) treated on bevacizumab (BEV) in clinical practice." May 20, 2014.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
32
Issue
15
Publish Date
2014

Mutations in IDH1, IDH2, and in the TERT promoter define clinically distinct subgroups of adult malignant gliomas.

Frequent mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) and the promoter of telomerase reverse transcriptase (TERT) represent two significant discoveries in glioma genomics. Understanding the degree to which these two mutations co-occur or occur exclusively of one another in glioma subtypes presents a unique opportunity to guide glioma classification and prognosis. We analyzed the relationship between overall survival (OS) and the presence of IDH1/2 and TERT promoter mutations in a panel of 473 adult gliomas. We hypothesized and show that genetic signatures capable of distinguishing among several types of gliomas could be established providing clinically relevant information that can serve as an adjunct to histopathological diagnosis. We found that mutations in the TERT promoter occurred in 74.2% of glioblastomas (GBM), but occurred in a minority of Grade II-III astrocytomas (18.2%). In contrast, IDH1/2 mutations were observed in 78.4% of Grade II-III astrocytomas, but were uncommon in primary GBM. In oligodendrogliomas, TERT promoter and IDH1/2 mutations co-occurred in 79% of cases. Patients whose Grade III-IV gliomas exhibit TERT promoter mutations alone predominately have primary GBMs associated with poor median OS (11.5 months). Patients whose Grade III-IV gliomas exhibit IDH1/2 mutations alone predominately have astrocytic morphologies and exhibit a median OS of 57 months while patients whose tumors exhibit both TERT promoter and IDH1/2 mutations predominately exhibit oligodendroglial morphologies and exhibit median OS of 125 months. Analyzing gliomas based on their genetic signatures allows for the stratification of these patients into distinct cohorts, with unique prognosis and survival.

Authors
Killela, PJ; Pirozzi, CJ; Healy, P; Reitman, ZJ; Lipp, E; Rasheed, BA; Yang, R; Diplas, BH; Wang, Z; Greer, PK; Zhu, H; Wang, CY; Carpenter, AB; Friedman, H; Friedman, AH; Keir, ST; He, J; He, Y; McLendon, RE; Herndon, JE; Yan, H; Bigner, DD
MLA Citation
Killela, PJ, Pirozzi, CJ, Healy, P, Reitman, ZJ, Lipp, E, Rasheed, BA, Yang, R, Diplas, BH, Wang, Z, Greer, PK, Zhu, H, Wang, CY, Carpenter, AB, Friedman, H, Friedman, AH, Keir, ST, He, J, He, Y, McLendon, RE, Herndon, JE, Yan, H, and Bigner, DD. "Mutations in IDH1, IDH2, and in the TERT promoter define clinically distinct subgroups of adult malignant gliomas." Oncotarget 5.6 (March 2014): 1515-1525.
PMID
24722048
Source
epmc
Published In
Oncotarget
Volume
5
Issue
6
Publish Date
2014
Start Page
1515
End Page
1525

EGFRvIII mCAR-modified T-cell therapy cures mice with established intracerebral glioma and generates host immunity against tumor-antigen loss

Purpose: Chimeric antigen receptor (CAR) transduced T cells represent a promising immune therapy that has been shown to successfully treat cancers in mice and humans. However, CARs targeting antigens expressed in both tumors and normal tissues have led to significant toxicity. Preclinical studies have been limited by the use of xenograft models that do not adequately recapitulate the immune system of a clinically relevant host. A constitutively activated mutant of the naturally occurring epidermal growth factor receptor (EGFRvIII) is antigenically identical in both human and mouse glioma, but is also completely absent from any normal tissues. Experimental Design: We developed a third-generation, EGFRvIII-specific murine CAR (mCAR), and performed tests to determine its efficacy in a fully immunocompetent mouse model of malignant glioma. Results: At elevated doses, infusion with EGFRvIIImCART cells led to cures in all mice with brain tumors. In addition, antitumor efficacy was found to be dependent on lymphodepletive host conditioning. Selective blockade with EGFRvIII soluble peptide significantly abrogated the activity of EGFRvIII mCAR T cells in vitro and in vivo, and may offer a novel strategy to enhance the safety profile for CAR-based therapy. Finally, mCAR-treated, cured mice were resistant to rechallenge with EGFRvIIINEG tumors, suggesting generation of host immunity against additional tumor antigens. Conclusion: All together, these data support that third-generation, EGFRvIII-specific mCARs are effective against gliomas in the brain and highlight the importance of syngeneic, immunocompetent models in the preclinical evaluation of tumor immunotherapies. © 2014 American Association for Cancer Research.

Authors
Sampson, JH; Choi, BD; Sanchez-Perez, L; Suryadevara, CM; Snyder, DJ; Flores, CT; Schmittling, RJ; Nair, SK; Reap, EA; Norberg, PK; Herndon, JE; Kuan, CT; Morgan, RA; Rosenberg, SA; Johnson, LA
MLA Citation
Sampson, JH, Choi, BD, Sanchez-Perez, L, Suryadevara, CM, Snyder, DJ, Flores, CT, Schmittling, RJ, Nair, SK, Reap, EA, Norberg, PK, Herndon, JE, Kuan, CT, Morgan, RA, Rosenberg, SA, and Johnson, LA. "EGFRvIII mCAR-modified T-cell therapy cures mice with established intracerebral glioma and generates host immunity against tumor-antigen loss." Clinical Cancer Research 20.4 (February 26, 2014): 972-984.
Source
scopus
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
20
Issue
4
Publish Date
2014
Start Page
972
End Page
984
DOI
10.1158/1078-0432.CCR-13-0709

EGFRvIII mCAR-modified T-cell therapy cures mice with established intracerebral glioma and generates host immunity against tumor-antigen loss.

PURPOSE: Chimeric antigen receptor (CAR) transduced T cells represent a promising immune therapy that has been shown to successfully treat cancers in mice and humans. However, CARs targeting antigens expressed in both tumors and normal tissues have led to significant toxicity. Preclinical studies have been limited by the use of xenograft models that do not adequately recapitulate the immune system of a clinically relevant host. A constitutively activated mutant of the naturally occurring epidermal growth factor receptor (EGFRvIII) is antigenically identical in both human and mouse glioma, but is also completely absent from any normal tissues. EXPERIMENTAL DESIGN: We developed a third-generation, EGFRvIII-specific murine CAR (mCAR), and performed tests to determine its efficacy in a fully immunocompetent mouse model of malignant glioma. RESULTS: At elevated doses, infusion with EGFRvIII mCAR T cells led to cures in all mice with brain tumors. In addition, antitumor efficacy was found to be dependent on lymphodepletive host conditioning. Selective blockade with EGFRvIII soluble peptide significantly abrogated the activity of EGFRvIII mCAR T cells in vitro and in vivo, and may offer a novel strategy to enhance the safety profile for CAR-based therapy. Finally, mCAR-treated, cured mice were resistant to rechallenge with EGFRvIII(NEG) tumors, suggesting generation of host immunity against additional tumor antigens. CONCLUSION: All together, these data support that third-generation, EGFRvIII-specific mCARs are effective against gliomas in the brain and highlight the importance of syngeneic, immunocompetent models in the preclinical evaluation of tumor immunotherapies.

Authors
Sampson, JH; Choi, BD; Sanchez-Perez, L; Suryadevara, CM; Snyder, DJ; Flores, CT; Schmittling, RJ; Nair, SK; Reap, EA; Norberg, PK; Herndon, JE; Kuan, C-T; Morgan, RA; Rosenberg, SA; Johnson, LA
MLA Citation
Sampson, JH, Choi, BD, Sanchez-Perez, L, Suryadevara, CM, Snyder, DJ, Flores, CT, Schmittling, RJ, Nair, SK, Reap, EA, Norberg, PK, Herndon, JE, Kuan, C-T, Morgan, RA, Rosenberg, SA, and Johnson, LA. "EGFRvIII mCAR-modified T-cell therapy cures mice with established intracerebral glioma and generates host immunity against tumor-antigen loss." Clin Cancer Res 20.4 (February 15, 2014): 972-984.
PMID
24352643
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
20
Issue
4
Publish Date
2014
Start Page
972
End Page
984
DOI
10.1158/1078-0432.CCR-13-0709

Utility of 3-dimensional echocardiography, global longitudinal strain, and exercise stress echocardiography to detect cardiac dysfunction in breast cancer patients treated with doxorubicin-containing adjuvant therapy

Conventional resting left ventricular ejection fraction (LVEF) assessments have limitations for detecting doxorubicin (DOX)-related cardiac dysfunction. Novel resting echocardiographic parameters, including 3-dimensional echocardiography (3DE) and global longitudinal strain (GLS), have potential for early identification of chemotherapy-related myocardial injury. Exercise "stress" is an established method to uncover impairments in cardiac function but has received limited attention in the adult oncology setting. We evaluated the utility of an integrated approach using 3DE, GLS, and exercise stress echocardiography for detecting subclinical cardiac dysfunction in early breast cancer patients treated with DOX-containing chemotherapy. Fifty-seven asymptomatic women with early breast cancer (mean 26 ± 22 months post-chemotherapy) and 20 sex-matched controls were studied. Resting left ventricular (LV) function was assessed by LVEF using 2-dimensional echocardiography (2DE) and 3DE and by GLS using 2-dimensional speckle-tracking echocardiography (2D-STE). After resting assessments, subjects completed cardiopulmonary exercise testing with stress 2DE. Resting LVEF was lower in patients than controls by 3DE (55 ± 4 vs. 59 ± 5 %; p = 0.005) but not 2DE (56 ± 4 vs. 58 ± 3 %; p = 0.169). 10 of 51 (20 %) patients had GLS greater than or equal to -17 %, which was below the calculated lower limit of normal (control mean 2SD); this patient subgroup had a mean 20 % impairment in GLS (-16.1 ± 0.9 vs. -20.1 ± 1.5 %; p < 0.001), despite similar LVEF by 2DE and 3DE compared to controls (p > 0.05). Cardiopulmonary function (VO2peak) was 20 % lower in patients than controls (p < 0.001). Exercise stress 2DE assessments of stroke volume (61 ± 11 vs. 69 ± 15 ml; p = 0.018) and cardiac index (2.3 ± 0.9 vs. 3.1 ± 0.8 l min-1 m-2 mean increase; p = 0.003) were lower in patients than controls. Post-exercise increase in cardiac index predicted VO2peak (r = 0.429, p = 0.001). Resting 3DE, GLS, and exercise stress 2DE detect subclinical cardiac dysfunction not apparent with resting 2DE in post-DOX breast cancer patients. © 2014 Springer Science+Business Media New York.

Authors
Khouri, MG; Hornsby, WE; Risum, N; Velazquez, EJ; Thomas, S; Lane, A; Scott, JM; Koelwyn, GJ; Herndon, JE; Mackey, JR; Douglas, PS; Jones, LW
MLA Citation
Khouri, MG, Hornsby, WE, Risum, N, Velazquez, EJ, Thomas, S, Lane, A, Scott, JM, Koelwyn, GJ, Herndon, JE, Mackey, JR, Douglas, PS, and Jones, LW. "Utility of 3-dimensional echocardiography, global longitudinal strain, and exercise stress echocardiography to detect cardiac dysfunction in breast cancer patients treated with doxorubicin-containing adjuvant therapy." Breast Cancer Research and Treatment 143.3 (February 1, 2014): 531-539.
Source
scopus
Published In
Breast Cancer Research and Treatment
Volume
143
Issue
3
Publish Date
2014
Start Page
531
End Page
539
DOI
10.1007/s10549-013-2818-1

SEER insights

Authors
Sampson, JH; Lad, SP; Herndon, JE; Starke, RM; Kondziolka, D
MLA Citation
Sampson, JH, Lad, SP, Herndon, JE, Starke, RM, and Kondziolka, D. "SEER insights." Journal of Neurosurgery 120.2 (February 1, 2014): 297-298.
Source
scopus
Published In
Journal of neurosurgery
Volume
120
Issue
2
Publish Date
2014
Start Page
297
End Page
298
DOI
10.3171/2013.6.JNS13993

SEER insights.

Authors
Sampson, JH; Lad, SP; Herndon, JE; Starke, RM; Kondziolka, D
MLA Citation
Sampson, JH, Lad, SP, Herndon, JE, Starke, RM, and Kondziolka, D. "SEER insights." J Neurosurg 120.2 (February 2014): 297-298.
PMID
24286150
Source
pubmed
Published In
Journal of neurosurgery
Volume
120
Issue
2
Publish Date
2014
Start Page
297
End Page
298
DOI
10.3171/2013.6.JNS13993

Utility of 3-dimensional echocardiography, global longitudinal strain, and exercise stress echocardiography to detect cardiac dysfunction in breast cancer patients treated with doxorubicin-containing adjuvant therapy.

Conventional resting left ventricular ejection fraction (LVEF) assessments have limitations for detecting doxorubicin (DOX)-related cardiac dysfunction. Novel resting echocardiographic parameters, including 3-dimensional echocardiography (3DE) and global longitudinal strain (GLS), have potential for early identification of chemotherapy-related myocardial injury. Exercise "stress" is an established method to uncover impairments in cardiac function but has received limited attention in the adult oncology setting. We evaluated the utility of an integrated approach using 3DE, GLS, and exercise stress echocardiography for detecting subclinical cardiac dysfunction in early breast cancer patients treated with DOX-containing chemotherapy. Fifty-seven asymptomatic women with early breast cancer (mean 26 ± 22 months post-chemotherapy) and 20 sex-matched controls were studied. Resting left ventricular (LV) function was assessed by LVEF using 2-dimensional echocardiography (2DE) and 3DE and by GLS using 2-dimensional speckle-tracking echocardiography (2D-STE). After resting assessments, subjects completed cardiopulmonary exercise testing with stress 2DE. Resting LVEF was lower in patients than controls by 3DE (55 ± 4 vs. 59 ± 5 %; p = 0.005) but not 2DE (56 ± 4 vs. 58 ± 3 %; p = 0.169). 10 of 51 (20 %) patients had GLS greater than or equal to -17 %, which was below the calculated lower limit of normal (control mean 2SD); this patient subgroup had a mean 20 % impairment in GLS (-16.1 ± 0.9 vs. -20.1 ± 1.5 %; p < 0.001), despite similar LVEF by 2DE and 3DE compared to controls (p > 0.05). Cardiopulmonary function (VO2peak) was 20 % lower in patients than controls (p < 0.001). Exercise stress 2DE assessments of stroke volume (61 ± 11 vs. 69 ± 15 ml; p = 0.018) and cardiac index (2.3 ± 0.9 vs. 3.1 ± 0.8 l min(-1) m(-2) mean increase; p = 0.003) were lower in patients than controls. Post-exercise increase in cardiac index predicted VO2peak (r = 0.429, p = 0.001). Resting 3DE, GLS, and exercise stress 2DE detect subclinical cardiac dysfunction not apparent with resting 2DE in post-DOX breast cancer patients.

Authors
Khouri, MG; Hornsby, WE; Risum, N; Velazquez, EJ; Thomas, S; Lane, A; Scott, JM; Koelwyn, GJ; Herndon, JE; Mackey, JR; Douglas, PS; Jones, LW
MLA Citation
Khouri, MG, Hornsby, WE, Risum, N, Velazquez, EJ, Thomas, S, Lane, A, Scott, JM, Koelwyn, GJ, Herndon, JE, Mackey, JR, Douglas, PS, and Jones, LW. "Utility of 3-dimensional echocardiography, global longitudinal strain, and exercise stress echocardiography to detect cardiac dysfunction in breast cancer patients treated with doxorubicin-containing adjuvant therapy." Breast Cancer Res Treat 143.3 (February 2014): 531-539.
PMID
24390149
Source
pubmed
Published In
Breast Cancer Research and Treatment
Volume
143
Issue
3
Publish Date
2014
Start Page
531
End Page
539
DOI
10.1007/s10549-013-2818-1

Intracerebral delivery of a third generation EGFRvIII-specific chimeric antigen receptor is efficacious against human glioma

Chimeric antigen receptors (CAR)-transduced T cells hold great promise in the treatment of malignant disease. Here, we demonstrate that intracerebral injection with a human, epidermal growth factor receptor variant III (EGFRvIII)-specific, third generation CAR successfully treats glioma in mice. Importantly, these results endorse clinical translation of this CAR in patients with EGFRvIII-expressing brain tumors. © 2013 Elsevier Ltd. All rights reserved.

Authors
Choi, BD; Suryadevara, CM; Gedeon, PC; Herndon, JE; Sanchez-Perez, L; Bigner, DD; Sampson, JH
MLA Citation
Choi, BD, Suryadevara, CM, Gedeon, PC, Herndon, JE, Sanchez-Perez, L, Bigner, DD, and Sampson, JH. "Intracerebral delivery of a third generation EGFRvIII-specific chimeric antigen receptor is efficacious against human glioma." Journal of Clinical Neuroscience 21.1 (January 1, 2014): 189-190.
Source
scopus
Published In
Journal of Clinical Neuroscience
Volume
21
Issue
1
Publish Date
2014
Start Page
189
End Page
190
DOI
10.1016/j.jocn.2013.03.012

Effects of nonlinear aerobic training on erectile dysfunction and cardiovascular function following radical prostatectomy for clinically localized prostate cancer

Erectile dysfunction (ED) is a major adverse effect of radical prostatectomy (RP). We conducted a randomized controlled trial to examine the efficacy of aerobic training (AT) compared with usual care (UC) on ED prevalence in 50 men (n = 25 per group) after RP. AT consisted of five walking sessions per week at 55-100% of peak oxygen uptake (VO2peak) for 30-60 min per session following a nonlinear prescription. The primary outcome was change in the prevalence of ED, as measured by the International Index of Erectile Function (IIEF), from baseline to 6 mo. Secondary outcomes were brachial artery flow-mediated dilation (FMD), VO2peak, cardiovascular (CV) risk profile (eg, lipid profile, body composition), and patient-reported outcomes (PROs). The prevalence of ED (IIEF score ≤21) decreased by 20% in the AT group and by 24% in the UC group (difference: p = 0.406). There were no significant between-group differences in any erectile function subscale (p > 0.05). Significant between-group differences were observed for changes in FMD and VO2peak, favoring AT. There were no group differences in other markers of CV risk profile or PROs. In summary, nonlinear AT does not improve ED in men with localized prostate cancer in the acute period following RP. Trial registration Clinicaltrials.gov identifier NCT00620932. © 2013 European Association of Urology.

Authors
Jones, LW; Hornsby, WE; Freedland, SJ; Lane, A; West, MJ; Moul, JW; Ferrandino, MN; Allen, JD; Kenjale, AA; Thomas, SM; Herndon, JE; Koontz, BF; Chan, JM; Khouri, MG; Douglas, PS; Eves, ND
MLA Citation
Jones, LW, Hornsby, WE, Freedland, SJ, Lane, A, West, MJ, Moul, JW, Ferrandino, MN, Allen, JD, Kenjale, AA, Thomas, SM, Herndon, JE, Koontz, BF, Chan, JM, Khouri, MG, Douglas, PS, and Eves, ND. "Effects of nonlinear aerobic training on erectile dysfunction and cardiovascular function following radical prostatectomy for clinically localized prostate cancer." European Urology 65.5 (January 1, 2014): 852-855.
Source
scopus
Published In
European Urology
Volume
65
Issue
5
Publish Date
2014
Start Page
852
End Page
855
DOI
10.1016/j.eururo.2013.11.009

Adherence to antiemetic guidelines in patients with malignant glioma: A quality improvement project to translate evidence into practice

Purpose: A quality improvement project was implemented to improve adherence to evidence-based antiemetic guidelines for malignant glioma patients treated with moderately emetic chemotherapy (MEC). Poorly controlled chemotherapy-induced nausea and vomiting (CINV) reduce cancer treatment efficacy and significantly impair cancer patients' quality of life (QOL). A review of Duke University Preston Robert Tisch Brain Tumor Center (PRTBTC)'s usual practice demonstrates a high incidence (45 %) of CINV, despite premedication with short-acting 5-HT3-serotonin-receptor antagonists (5-HT 3-RAs). National Comprehensive Cancer Network (NCCN)'s evidence-based guidelines recommend the combination of the long-acting 5-HT3-RA palonosetron (PAL) and dexamethasone (DEX) for the prevention of acute and delayed CINV with MEC. Low adherence (58 %) to antiemetic guidelines may have explained our high CINV incidence. Methods: One-sample binomial test, quasi-experimental design, evaluated a combination intervention that included a provider education session; implementation of risk-assessment tool with computerized, standardized antiemetic guideline order sets; and a monthly audit-feedback strategy. Post-implementation adherence to evidence-based antiemetic order sets and patient outcomes were measured and compared to baseline and historical data. Primary outcome was the guideline order set adherence rate. Secondary outcomes included nausea/vomiting rates and QOL. Results: Adherence to ordering MEC guideline antiemetics increased significantly, from 58 % to a sustained 90 %, with associated improvement in nausea/vomiting. In acute and delayed phases, 75 and 84 % of patients, respectively, did not experience CINV. There was no significant change in QOL. Conclusion: Combination intervention and audit-feedback strategy to translate evidence into oncology practice improved and sustained adherence to antiemetic guidelines. Adherence corresponded with effective nausea/vomiting control and preserved QOL in patients with malignant gliomas. © 2014 Springer-Verlag.

Authors
Affronti, ML; Schneider, SM; Herndon, JE; Schlundt, S; Friedman, HS
MLA Citation
Affronti, ML, Schneider, SM, Herndon, JE, Schlundt, S, and Friedman, HS. "Adherence to antiemetic guidelines in patients with malignant glioma: A quality improvement project to translate evidence into practice." Supportive Care in Cancer 22.7 (January 1, 2014): 1897-1905.
Source
scopus
Published In
Supportive Care in Cancer
Volume
22
Issue
7
Publish Date
2014
Start Page
1897
End Page
1905
DOI
10.1007/s00520-014-2136-0

Cardiopulmonary exercise testing prior to myeloablative allo-SCT: A feasibility study

© 2014 Macmillan Publishers Limited All rights reserved.The feasibility of symptom-limited cardiopulmonary exercise testing (CPET) prior to allo-SCT was assessed in addition to the prognostic value of CPET-derived measures. CPET was performed prospectively on 21 patients with hematologic malignancies, with assessments of peak (for example, peak oxygen consumption, VO2peak) and submaximal (for example, ventilatory threshold (VT)) measures of cardiopulmonary function. No serious adverse events were observed during CPET procedures, with 95% of patients achieving criteria for a peak test. Mean VO2peak was 24.7 ± 6.4 mL kg-1 min-1 (range: 10.9-35.5), equivalent to 29% ± 17% below that of age-matched healthy controls. All patients proceeded with the conditioning regimen followed by allo-SCT. Median follow-up was 25 months. During this period, 11 (52.4%) patients died (n = 6, relapsed disease; n = 5, non-relapse mortality (NRM)); 9 patients (43%) developed pulmonary toxicity. In univariate analyses, both peak and submaximal markers of cardiopulmonary function were predictors of OS, pulmonary toxicity and NRM. For OS, the HR for VO2peak and VT were 0.89 (95% CI, 0.8-0.99, P = 0.04) and 0.84 (95% CI, 0.71-0.98, P = 0.03), respectively. In conclusion, CPET is safe and feasible prior to allo-SCT. Patients have marked impairments in cardiopulmonary function prior to allo-SCT. CPET-derived metrics may complement conventional measures to improve risk stratification.

Authors
Kelsey, CR; Scott, JM; Lane, A; Schwitzer, E; West, MJ; Thomas, S; Herndon, JE; Michalski, MG; Horwitz, ME; Hennig, T; Jones, LW
MLA Citation
Kelsey, CR, Scott, JM, Lane, A, Schwitzer, E, West, MJ, Thomas, S, Herndon, JE, Michalski, MG, Horwitz, ME, Hennig, T, and Jones, LW. "Cardiopulmonary exercise testing prior to myeloablative allo-SCT: A feasibility study." Bone Marrow Transplantation 49.10 (January 1, 2014): 1330-1336.
Source
scopus
Published In
Bone Marrow Transplantation
Volume
49
Issue
10
Publish Date
2014
Start Page
1330
End Page
1336
DOI
10.1038/bmt.2014.159

Comparison of performance status with peak oxygen consumption in operable patients with non-small-cell lung cancer.

In this era of increasing options for treatment of 'surgical' lung cancer patients, preoperative physiologic assessment of accurate patient selection is becoming more important. The variability in an objective measure of cardiorespiratory fitness (peak oxygen consumption (VO2peak )) across performance in operable non-small-cell lung cancer (NSCLC) patients enrolled in the Cancer and Leukemia Group B trial was compared.Using a cross-sectional design, 392 NSCLC patients underwent an incremental cardiopulmonary cycling exercise test to symptom limitation with expired gas analysis to determine VO2peak . Performance status (PS) was assessed using the Eastern Cooperative Oncology Group (ECOG) tool.There was a significant decrease in VO2peak across increasing ECOG categories (P < 0.0001). However, there was a large range in VO2peak for any given ECOG category with overlap between categories (ECOG 0: 5.0-31.5 mL/kg/min; ECOG 1: 4.3-24.8 mL/kg/min; ECOG 2: 8.9-21.9 mL/kg/min; ECOG 3; 3.3-11.7 mL/kg/min).PS scoring systems do not provide a sensitive measure of functional status. Objective measures such as VO2peak may be a useful in the clinical management of oncology patients.

Authors
Roman, MA; Koelwyn, GJ; Eves, ND; Hornsby, WE; Watson, D; Herndon Ii, JE; Kohman, L; Loewen, G; Jones, LW
MLA Citation
Roman, MA, Koelwyn, GJ, Eves, ND, Hornsby, WE, Watson, D, Herndon Ii, JE, Kohman, L, Loewen, G, and Jones, LW. "Comparison of performance status with peak oxygen consumption in operable patients with non-small-cell lung cancer." Respirology (Carlton, Vic.) 19.1 (January 2014): 105-108.
PMID
23890224
Source
epmc
Published In
Respirology
Volume
19
Issue
1
Publish Date
2014
Start Page
105
End Page
108
DOI
10.1111/resp.12162

EGFRvIII-specific chimeric antigen receptor T cells migrate to and kill tumor deposits infiltrating the brain parenchyma in an invasive xenograft model of glioblastoma.

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults and is uniformly lethal. T-cell-based immunotherapy offers a promising platform for treatment given its potential to specifically target tumor tissue while sparing the normal brain. However, the diffuse and infiltrative nature of these tumors in the brain parenchyma may pose an exceptional hurdle to successful immunotherapy in patients. Areas of invasive tumor are thought to reside behind an intact blood brain barrier, isolating them from effective immunosurveillance and thereby predisposing the development of "immunologically silent" tumor peninsulas. Therefore, it remains unclear if adoptively transferred T cells can migrate to and mediate regression in areas of invasive GBM. One barrier has been the lack of a preclinical mouse model that accurately recapitulates the growth patterns of human GBM in vivo. Here, we demonstrate that D-270 MG xenografts exhibit the classical features of GBM and produce the diffuse and invasive tumors seen in patients. Using this model, we designed experiments to assess whether T cells expressing third-generation chimeric antigen receptors (CARs) targeting the tumor-specific mutation of the epidermal growth factor receptor, EGFRvIII, would localize to and treat invasive intracerebral GBM. EGFRvIII-targeted CAR (EGFRvIII+ CAR) T cells demonstrated in vitro EGFRvIII antigen-specific recognition and reactivity to the D-270 MG cell line, which naturally expresses EGFRvIII. Moreover, when administered systemically, EGFRvIII+ CAR T cells localized to areas of invasive tumor, suppressed tumor growth, and enhanced survival of mice with established intracranial D-270 MG tumors. Together, these data demonstrate that systemically administered T cells are capable of migrating to the invasive edges of GBM to mediate antitumor efficacy and tumor regression.

Authors
Miao, H; Choi, BD; Suryadevara, CM; Sanchez-Perez, L; Yang, S; De Leon, G; Sayour, EJ; McLendon, R; Herndon, JE; Healy, P; Archer, GE; Bigner, DD; Johnson, LA; Sampson, JH
MLA Citation
Miao, H, Choi, BD, Suryadevara, CM, Sanchez-Perez, L, Yang, S, De Leon, G, Sayour, EJ, McLendon, R, Herndon, JE, Healy, P, Archer, GE, Bigner, DD, Johnson, LA, and Sampson, JH. "EGFRvIII-specific chimeric antigen receptor T cells migrate to and kill tumor deposits infiltrating the brain parenchyma in an invasive xenograft model of glioblastoma." PloS one 9.4 (January 2014): e94281-.
PMID
24722266
Source
epmc
Published In
PloS one
Volume
9
Issue
4
Publish Date
2014
Start Page
e94281
DOI
10.1371/journal.pone.0094281

Safety and efficacy of aerobic training in operable breast cancer patients receiving neoadjuvant chemotherapy: a phase II randomized trial.

BACKGROUND: To evaluate the safety and efficacy of moderate-to-high intensity aerobic training in breast cancer patients receiving neoadjuvant chemotherapy. METHODS: Twenty patients with stage IIB-IIIC operable breast cancer were randomly assigned to receive doxorubicin plus cyclophosphamide (AC) or AC in combination with aerobic training (AC + AET) (n = 10/group) for 12 weeks. The AC+ AET group performed three supervised aerobic cycle ergometry sessions per week at 60%-100% of exercise capacity (VO2peak). Safety outcomes included exercise testing as well as treatment- and exercise training-related adverse events (AEs), whereas efficacy outcomes included cardiopulmonary function and patient-reported outcomes (PROs) as measured by a cardiopulmonary exercise test (CPET) and Functional Assessment of Cancer Therapy-Breast (FACT-B) scale. RESULTS: Twelve non-significant ECG abnormalities and three non-life threatening events occurred during CPET procedures. One AE was reported during aerobic training. There were no significant between group differences for clinician-documented events (e.g. pain, nausea) or hematological parameters (p's > 0.05). Attendance and adherence rates to aerobic training were 82% and 66%, respectively. Intention-to-treat analysis indicated that VO2peak increased by 2.6 ± 3.5 ml/kg/min (+ 13.3%) in the AC + AET group and decreased by 1.5 ± 2.2 ml/kg/min (-8.6%) in the AC group (between group difference, p = 0.001). FACT-B increased 11.1 points in the AC + AET group compared to a 1.5 point decrease in the AC group (between group difference, p = 0.685). CONCLUSION: Moderate-to-high intensity aerobic training when conducted with one-on-one supervision is a safe adjunct therapy associated with improvements in cardiopulmonary function and select PROs during neoadjuvant chemotherapy.

Authors
Hornsby, WE; Douglas, PS; West, MJ; Kenjale, AA; Lane, AR; Schwitzer, ER; Ray, KA; Herndon, JE; Coan, A; Gutierrez, A; Hornsby, KP; Hamilton, E; Wilke, LG; Kimmick, GG; Peppercorn, JM; Jones, LW
MLA Citation
Hornsby, WE, Douglas, PS, West, MJ, Kenjale, AA, Lane, AR, Schwitzer, ER, Ray, KA, Herndon, JE, Coan, A, Gutierrez, A, Hornsby, KP, Hamilton, E, Wilke, LG, Kimmick, GG, Peppercorn, JM, and Jones, LW. "Safety and efficacy of aerobic training in operable breast cancer patients receiving neoadjuvant chemotherapy: a phase II randomized trial." Acta Oncol 53.1 (January 2014): 65-74.
PMID
23957716
Source
pubmed
Published In
Acta Oncologica (Informa)
Volume
53
Issue
1
Publish Date
2014
Start Page
65
End Page
74
DOI
10.3109/0284186X.2013.781673

Intracerebral delivery of a third generation EGFRvIII-specific chimeric antigen receptor is efficacious against human glioma.

Chimeric antigen receptors (CAR)-transduced T cells hold great promise in the treatment of malignant disease. Here, we demonstrate that intracerebral injection with a human, epidermal growth factor receptor variant III (EGFRvIII)-specific, third generation CAR successfully treats glioma in mice. Importantly, these results endorse clinical translation of this CAR in patients with EGFRvIII-expressing brain tumors.

Authors
Choi, BD; Suryadevara, CM; Gedeon, PC; Herndon, JE; Sanchez-Perez, L; Bigner, DD; Sampson, JH
MLA Citation
Choi, BD, Suryadevara, CM, Gedeon, PC, Herndon, JE, Sanchez-Perez, L, Bigner, DD, and Sampson, JH. "Intracerebral delivery of a third generation EGFRvIII-specific chimeric antigen receptor is efficacious against human glioma." J Clin Neurosci 21.1 (January 2014): 189-190.
PMID
24054399
Source
pubmed
Published In
Journal of Clinical Neuroscience
Volume
21
Issue
1
Publish Date
2014
Start Page
189
End Page
190
DOI
10.1016/j.jocn.2013.03.012

Prognostic Validation of the Body Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity (BODE) Index in Inoperable Non-Small-Cell Lung Cancer

Authors
Denehy, L; Hornsby, WE; Herndon, JE; Thomas, S; Ready, NE; Granger, CL; Valera, L; Kenjale, AA; Eves, ND; Jones, LW
MLA Citation
Denehy, L, Hornsby, WE, Herndon, JE, Thomas, S, Ready, NE, Granger, CL, Valera, L, Kenjale, AA, Eves, ND, and Jones, LW. "Prognostic Validation of the Body Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity (BODE) Index in Inoperable Non-Small-Cell Lung Cancer." JOURNAL OF THORACIC ONCOLOGY 8.12 (December 2013): 1545-1550.
PMID
24389436
Source
wos-lite
Published In
Journal of Thoracic Oncology
Volume
8
Issue
12
Publish Date
2013
Start Page
1545
End Page
1550
DOI
10.1097/JTO.0000000000000032

ADOPTIVE LYMPHOCYTE THERAPY (ALT) PLUS DENDRITIC CELL VACCINATION (DCV) AFTER MYELOABLATIVE (MA) OR NON-MYELOABLATIVE (NMA) CONDITIONING IN PATIENTS WITH RECURRENT CENTRAL PNET (C-PNET)

Authors
Gururangan, S; Grant, GA; Driscoll, T; Archer, G; Sayour, EJ; II, HJE; Friedman, HS; Kurtzberg, J; Bigner, DD; Sampson, JH; Mitchell, DA
MLA Citation
Gururangan, S, Grant, GA, Driscoll, T, Archer, G, Sayour, EJ, II, HJE, Friedman, HS, Kurtzberg, J, Bigner, DD, Sampson, JH, and Mitchell, DA. "ADOPTIVE LYMPHOCYTE THERAPY (ALT) PLUS DENDRITIC CELL VACCINATION (DCV) AFTER MYELOABLATIVE (MA) OR NON-MYELOABLATIVE (NMA) CONDITIONING IN PATIENTS WITH RECURRENT CENTRAL PNET (C-PNET)." PEDIATRIC BLOOD & CANCER 60 (September 2013): 13-13.
Source
wos-lite
Published In
Pediatric Blood & Cancer
Volume
60
Publish Date
2013
Start Page
13
End Page
13

Human regulatory T cells kill tumor cells through granzyme-dependent cytotoxicity upon retargeting with a bispecific antibody.

A major mechanism by which human regulatory T cells (T(regs)) have been shown to suppress and kill autologous immune cells is through the granzyme-perforin pathway. However, it is unknown whether T(regs) also possess the capacity to kill tumor cells using similar mechanisms. Bispecific antibodies (bscAbs) have emerged as a promising class of therapeutics that activate T cells against tumor antigens without the need for classical MHC-restricted TCR recognition. Here, we show that a bscAb targeting the tumor-specific mutation of the epidermal growth factor receptor, EGFRvIII, redirects human CD4(+)CD25(+)FoxP3(+) T(regs) to kill glioblastoma (GBM) cells. This activity was significantly abrogated by inhibitors of the granzyme-perforin pathway. Notably, analyses of human primary GBM also displayed diffuse infiltration of granzyme-expressing FoxP3(+) T cells. Together, these data suggest that despite their known suppressive functions, tumor-infiltrating T(regs) possess potent cytotoxic mechanisms that can be co-opted for efficient tumor cell lysis.

Authors
Choi, BD; Gedeon, PC; Herndon, JE; Archer, GE; Reap, EA; Sanchez-Perez, L; Mitchell, DA; Bigner, DD; Sampson, JH
MLA Citation
Choi, BD, Gedeon, PC, Herndon, JE, Archer, GE, Reap, EA, Sanchez-Perez, L, Mitchell, DA, Bigner, DD, and Sampson, JH. "Human regulatory T cells kill tumor cells through granzyme-dependent cytotoxicity upon retargeting with a bispecific antibody." Cancer immunology research 1.3 (September 2013): 163-.
PMID
24570975
Source
epmc
Published In
Cancer Immunology Research
Volume
1
Issue
3
Publish Date
2013
Start Page
163
DOI
10.1158/2326-6066.cir-13-0049

Biomarkers to help guide management of patients with pulmonary nodules.

RATIONALE: Indeterminate pulmonary nodules are a common radiographic finding and require further evaluation because of the concern for lung cancer. OBJECTIVES: We developed an algorithm to assign patients to a low- or high-risk category for lung cancer, based on a combination of serum biomarker levels and nodule size. METHODS: For the serum biomarker assay, we determined levels of carcinoembryonic antigen, α1-antitrypsin, and squamous cell carcinoma antigen. Serum data and nodule size from a training set of 509 patients with (n = 298) and without (n = 211) lung cancer were subjected to classification and regression tree and logistic regression analyses. Multiple models were developed and tested in an independent, masked validation set for their ability to categorize patients with (n = 203) or without (n = 196) lung cancer as being low- or high-risk for lung cancer. MEASUREMENTS AND MAIN RESULTS: In all models, a large percentage of individuals in the validation study with small nodules (<1 cm) were assigned to the low-risk group, and a large percentage of individuals with large nodules (≥3 cm) were assigned to the high-risk group. In the validation study, the classification and regression tree algorithm had overall sensitivity, specificity, and positive and negative predictive values for determining lung cancer of 88%, 82%, 84%, and 87%, respectively. The logistic regression model had overall sensitivity, specificity, and positive and negative predictive values of 80%, 89%, 89%, and 81%, respectively. CONCLUSION: Integration of biomarkers with lung nodule size has the potential to help guide the management of patients with indeterminate pulmonary nodules.

Authors
Patz, EF; Campa, MJ; Gottlin, EB; Trotter, PR; Herndon, JE; Kafader, D; Grant, RP; Eisenberg, M
MLA Citation
Patz, EF, Campa, MJ, Gottlin, EB, Trotter, PR, Herndon, JE, Kafader, D, Grant, RP, and Eisenberg, M. "Biomarkers to help guide management of patients with pulmonary nodules." Am J Respir Crit Care Med 188.4 (August 15, 2013): 461-465.
Website
http://hdl.handle.net/10161/11579
PMID
23306547
Source
pubmed
Published In
American journal of respiratory and critical care medicine
Volume
188
Issue
4
Publish Date
2013
Start Page
461
End Page
465
DOI
10.1164/rccm.201210-1760OC

Concurrent stereotactic radiosurgery and bevacizumab in recurrent malignant gliomas: a prospective trial.

PURPOSE: Virtually all patients with malignant glioma (MG) eventually recur. This study evaluates the safety of concurrent stereotactic radiosurgery (SRS) and bevacizumab (BVZ), an antiangiogenic agent, in treatment of recurrent MG. METHODS AND MATERIALS: Fifteen patients with recurrent MG, treated at initial diagnosis with surgery and adjuvant radiation therapy/temozolomide and then at least 1 salvage chemotherapy regimen, were enrolled in this prospective trial. Lesions <3 cm in diameter were treated in a single fraction, whereas those 3 to 5 cm in diameter received 5 5-Gy fractions. BVZ was administered immediately before SRS and 2 weeks later. Neurocognitive testing (Mini-Mental Status Exam, Trail Making Test A/B), Functional Assessment of Cancer Therapy-Brain (FACT-Br) quality-of-life assessment, physical exam, and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) were performed immediately before SRS and 1 week and 2 months following completion of SRS. The primary endpoint was central nervous system (CNS) toxicity. Secondary endpoints included survival, quality of life, microvascular properties as measured by DCE-MRI, steroid usage, and performance status. RESULTS: One grade 3 (severe headache) and 2 grade 2 CNS toxicities were observed. No patients experienced grade 4 to 5 toxicity or intracranial hemorrhage. Neurocognition, quality of life, and Karnofsky performance status did not change significantly with treatment. DCE-MRI results suggest a significant decline in tumor perfusion and permeability 1 week after SRS and further decline by 2 months. CONCLUSIONS: Treatment of recurrent MG with concurrent SRS and BVZ was not associated with excessive toxicity in this prospective trial. A randomized trial of concurrent SRS/BVZ versus conventional salvage therapy is needed to establish the efficacy of this approach.

Authors
Cabrera, AR; Cuneo, KC; Desjardins, A; Sampson, JH; McSherry, F; Herndon, JE; Peters, KB; Allen, K; Hoang, JK; Chang, Z; Craciunescu, O; Vredenburgh, JJ; Friedman, HS; Kirkpatrick, JP
MLA Citation
Cabrera, AR, Cuneo, KC, Desjardins, A, Sampson, JH, McSherry, F, Herndon, JE, Peters, KB, Allen, K, Hoang, JK, Chang, Z, Craciunescu, O, Vredenburgh, JJ, Friedman, HS, and Kirkpatrick, JP. "Concurrent stereotactic radiosurgery and bevacizumab in recurrent malignant gliomas: a prospective trial." Int J Radiat Oncol Biol Phys 86.5 (August 1, 2013): 873-879.
PMID
23725997
Source
pubmed
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
86
Issue
5
Publish Date
2013
Start Page
873
End Page
879
DOI
10.1016/j.ijrobp.2013.04.029

BLyS levels correlate with vaccine-induced antibody titers in patients with glioblastoma lymphodepleted by therapeutic temozolomide.

B lymphocyte stimulator (BLyS) is a cytokine involved in differentiation and survival of follicular B cells along with humoral response potentiation. Lymphopenia is known to precipitate dramatic elevation in serum BLyS; however, the use of this effect to enhance humoral responses following vaccination has not been evaluated. We evaluated BLyS serum levels and antigen-specific antibody titers in 8 patients undergoing therapeutic temozolomide (TMZ)-induced lymphopenia, with concomitant vaccine against a tumor-specific mutation in the epidermal growth factor receptor (EGFRvIII). Our studies demonstrate that TMZ-induced lymphopenia corresponded with spikes in serum BLyS that directly preceded the induction of anti-EGFRvIII antigen-specific antibody titers, in some cases as high as 1:2,000,000. Our data are the first clinical observation of BLyS serum elevation and greatly enhanced humoral immune responses as a consequence of chemotherapy-induced lymphopenia. These observations should be considered for the development of future vaccination strategies in the setting of malignancy.

Authors
Sanchez-Perez, L; Choi, BD; Reap, EA; Sayour, EJ; Norberg, P; Schmittling, RJ; Archer, GE; Herndon, JE; Mitchell, DA; Heimberger, AB; Bigner, DD; Sampson, JH
MLA Citation
Sanchez-Perez, L, Choi, BD, Reap, EA, Sayour, EJ, Norberg, P, Schmittling, RJ, Archer, GE, Herndon, JE, Mitchell, DA, Heimberger, AB, Bigner, DD, and Sampson, JH. "BLyS levels correlate with vaccine-induced antibody titers in patients with glioblastoma lymphodepleted by therapeutic temozolomide." Cancer Immunol Immunother 62.6 (June 2013): 983-987.
PMID
23591978
Source
pubmed
Published In
Cancer Immunology, Immunotherapy
Volume
62
Issue
6
Publish Date
2013
Start Page
983
End Page
987
DOI
10.1007/s00262-013-1405-y

Phase II trial for patients with newly diagnosed glioblastoma (GBM) treated with carmustine wafers followed by concurrent radiation therapy (RT), temozolomide (TMZ), and bevacizumab (BV), then followed by TMZ and BV post-RT.

Authors
Ranjan, T; Peters, KB; Vlahovic, G; Alderson, LM; Herndon, JE; McSherry, F; Threatt, S; Sampson, JH; Friedman, AH; Bigner, DD; Friedman, HS; Vredenburgh, JJ; Desjardins, A
MLA Citation
Ranjan, T, Peters, KB, Vlahovic, G, Alderson, LM, Herndon, JE, McSherry, F, Threatt, S, Sampson, JH, Friedman, AH, Bigner, DD, Friedman, HS, Vredenburgh, JJ, and Desjardins, A. "Phase II trial for patients with newly diagnosed glioblastoma (GBM) treated with carmustine wafers followed by concurrent radiation therapy (RT), temozolomide (TMZ), and bevacizumab (BV), then followed by TMZ and BV post-RT." May 20, 2013.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
31
Issue
15
Publish Date
2013

Dose-finding and safety study of an oncolytic polio/rhinovirus recombinant against recurrent glioblastoma.

Authors
Desjardins, A; Sampson, JH; Peters, KB; Ranjan, T; Vlahovic, G; Threatt, S; Herndon, JE; Friedman, AH; Friedman, HS; Bigner, DD; Gromeier, M
MLA Citation
Desjardins, A, Sampson, JH, Peters, KB, Ranjan, T, Vlahovic, G, Threatt, S, Herndon, JE, Friedman, AH, Friedman, HS, Bigner, DD, and Gromeier, M. "Dose-finding and safety study of an oncolytic polio/rhinovirus recombinant against recurrent glioblastoma." May 20, 2013.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
31
Issue
15
Publish Date
2013

Phase II trial of upfront bevacizumab and temozolomide for unresectable or multifocal glioblastoma.

Patients with unresectable glioblastomas have a poor prognosis, with median survival of 6-10 months. We conducted a phase II trial of upfront 5-day temozolomide (TMZ) and bevacizumab (BV) in patients with newly diagnosed unresectable or multifocal glioblastoma. Patients received up to four cycles of TMZ at 200 mg/m(2) on days 1-5, and BV at 10 mg/kg on days 1 and 15 of a 28-day cycle. Brain magnetic resonance imaging (MRI) was performed monthly. Therapy was continued as long as there was no tumor progression, grade 4 nonhematologic toxicity, or recurrent grade 4 hematologic toxicity after dose reduction. The primary end point was best tumor response as measured on MRI. Forty-one patients were accrued over 12 months; 39 had a full set of MRI scans available for evaluation. Assessment for best radiographic responses was as follows: partial responses in 24.4%, stable disease in 68.3%, and progressive disease in 2.4%. Treatment-related toxicities included seven grade 4 toxicities and one grade 5 toxicity (myocardial infarction). From this study, it was concluded that an upfront regimen of TMZ and BV for unresectable glioblastoma was well tolerated and provided a significant level of disease stabilization. Therapeutic toxicities were consistent with those seen in the adjuvant setting using these agents. The upfront approach to treatment of glioblastoma in the unresectable population warrants further investigation in randomized controlled phase III trials.

Authors
Lou, E; Peters, KB; Sumrall, AL; Desjardins, A; Reardon, DA; Lipp, ES; Herndon, JE; Coan, A; Bailey, L; Turner, S; Friedman, HS; Vredenburgh, JJ
MLA Citation
Lou, E, Peters, KB, Sumrall, AL, Desjardins, A, Reardon, DA, Lipp, ES, Herndon, JE, Coan, A, Bailey, L, Turner, S, Friedman, HS, and Vredenburgh, JJ. "Phase II trial of upfront bevacizumab and temozolomide for unresectable or multifocal glioblastoma." Cancer Med 2.2 (April 2013): 185-195.
PMID
23634286
Source
pubmed
Published In
Cancer Med
Volume
2
Issue
2
Publish Date
2013
Start Page
185
End Page
195
DOI
10.1002/cam4.58

ONCOLYTIC POLIOVIRUS IMMUNOTHERAPY OF PRIMARY CNS TUMORS

Authors
Gromeier, M; Desjardins, A; Sampson, JH; Threatt, SJE; Herndon, JE; Friedman, A; Friedman, HS; Bigner, DD
MLA Citation
Gromeier, M, Desjardins, A, Sampson, JH, Threatt, SJE, Herndon, JE, Friedman, A, Friedman, HS, and Bigner, DD. "ONCOLYTIC POLIOVIRUS IMMUNOTHERAPY OF PRIMARY CNS TUMORS." April 2013.
Source
wos-lite
Published In
Neuro-Oncology
Volume
15
Publish Date
2013
Start Page
20
End Page
20

Effect of socioeconomic status as measured by education level on survival in breast cancer clinical trials.

OBJECTIVES: This paper aims to investigate the effect of socioeconomic status, as measured by education, on the survival of breast cancer patients treated on 10 studies conducted by the Cancer and Leukemia Group B. METHODS: Sociodemographic data, including education, were reported by the patient at trial enrollment. Cox proportional hazards model stratified by treatment arm/study was used to examine the effect of education on survival among patients with early stage and metastatic breast cancer, after adjustment for known prognostic factors. RESULTS: The patient population included 1020 patients with metastatic disease and 5146 patients with early stage disease. Among metastatic patients, factors associated with poorer survival in the final multivariable model included African American race, never married, negative estrogen receptor status, prior hormonal therapy, visceral involvement, and bone involvement. Among early stage patients, significant factors associated with poorer survival included African American race, separated/widowed, post/perimenopausal, negative/unknown estrogen receptor status, negative progesterone receptor status, >4 positive nodes, tumor diameter >2 cm, and education. Having not completed high school was associated with poorer survival among early stage patients. Among metastatic patients, non-African American women who lacked a high school degree had poorer survival than other non-African American women, and African American women who lacked a high school education had better survival than educated African American women. CONCLUSIONS: Having less than a high school education is a risk factor for death among patients with early stage breast cancer who participated in a clinical trial, with its impact among metastatic patients being less clear. Post-trial survivorship plans need to focus on women with low social status, as measured by education.

Authors
Herndon, JE; Kornblith, AB; Holland, JC; Paskett, ED
MLA Citation
Herndon, JE, Kornblith, AB, Holland, JC, and Paskett, ED. "Effect of socioeconomic status as measured by education level on survival in breast cancer clinical trials." Psychooncology 22.2 (February 2013): 315-323.
PMID
22021121
Source
pubmed
Published In
Psycho-Oncology
Volume
22
Issue
2
Publish Date
2013
Start Page
315
End Page
323
DOI
10.1002/pon.2094

Subarachnoid hemorrhage trials

Authors
Zomorodi, A; II, HJE; Sampson, JH
MLA Citation
Zomorodi, A, II, HJE, and Sampson, JH. "Subarachnoid hemorrhage trials." NEUROSURGICAL FOCUS 34.1 (January 2013): 1-2.
Source
wos-lite
Published In
Neurosurgical focus
Volume
34
Issue
1
Publish Date
2013
Start Page
1
End Page
2
DOI
10.3171/2012.5.JNS12730

Subarachnoid hemorrhage trials

Authors
Zomorodi, A; II, HJE; Sampson, JH
MLA Citation
Zomorodi, A, II, HJE, and Sampson, JH. "Subarachnoid hemorrhage trials." JOURNAL OF NEUROSURGERY 118.1 (January 2013): 1-2.
PMID
23039153
Source
wos-lite
Published In
Journal of neurosurgery
Volume
118
Issue
1
Publish Date
2013
Start Page
1
End Page
2
DOI
10.3171/2012.5.JNS12730

Effects of Nonlinear Aerobic Training on Erectile Dysfunction and Cardiovascular Function Following Radical Prostatectomy for Clinically Localized Prostate Cancer

Authors
Jones, LW; Hornsby, WE; Freedland, SJ; Lane, A; West, MJ; Moul, JW; Ferrandino, MN; Allen, JD; Kenjale, AA; Thomas, SM; Herndon II, JE; Koontz, BF; Chan, JM; Khouri, MG; Douglas, PS; Eves, ND
MLA Citation
Jones, LW, Hornsby, WE, Freedland, SJ, Lane, A, West, MJ, Moul, JW, Ferrandino, MN, Allen, JD, Kenjale, AA, Thomas, SM, Herndon II, JE, Koontz, BF, Chan, JM, Khouri, MG, Douglas, PS, and Eves, ND. "Effects of Nonlinear Aerobic Training on Erectile Dysfunction and Cardiovascular Function Following Radical Prostatectomy for Clinically Localized Prostate Cancer." European Urology (2013).
PMID
24315706
Source
scopus
Published In
European Urology
Publish Date
2013

Hazard-rate analysis and patterns of recurrence in early stage melanoma: moving towards a rationally designed surveillance strategy.

BACKGROUND: While curable at early stages, few treatment options exist for advanced melanoma. Currently, no consensus exists regarding the optimal surveillance strategy for patients after resection. The objectives of this study were to identify patterns of metastatic recurrence, to determine the influence of metastatic site on survival, and to identify high-risk periods for recurrence. METHODS: A retrospective review of the Duke Melanoma Database from 1970 to 2004 was conducted that focused on patients who were initially diagnosed without metastatic disease. The time to first recurrence was computed from the date of diagnosis, and the associated hazard function was examined to determine the peak risk period of recurrence. Metastatic sites were coded by the American Joint Committee on Cancer (AJCC) system including local skin, distant skin and nodes (M1a), lung (M1b), and other distant (M1c). RESULTS: Of 11,615 patients initially diagnosed without metastatic disease, 4616 (40%) had at least one recurrence. Overall the risk of initial recurrence peaked at 12 months. The risk of initial recurrence at the local skin, distant skin, and nodes peaked at 8 months, and the risk at lung and other distant sites peaked at 24 months. Patients with a cutaneous or nodal recurrence had improved survival compared to other recurrence types. CONCLUSIONS: The risk of developing recurrent melanoma peaked at one year, and the site of first recurrence had a significant impact on survival. Defining the timing and expected patterns of recurrence will be important in creating an optimized surveillance strategy for this patient population.

Authors
Salama, AKS; de Rosa, N; Scheri, RP; Pruitt, SK; Herndon, JE; Marcello, J; Tyler, DS; Abernethy, AP
MLA Citation
Salama, AKS, de Rosa, N, Scheri, RP, Pruitt, SK, Herndon, JE, Marcello, J, Tyler, DS, and Abernethy, AP. "Hazard-rate analysis and patterns of recurrence in early stage melanoma: moving towards a rationally designed surveillance strategy." PLoS One 8.3 (2013): e57665-.
PMID
23516415
Source
pubmed
Published In
PloS one
Volume
8
Issue
3
Publish Date
2013
Start Page
e57665
DOI
10.1371/journal.pone.0057665

Myeloablative temozolomide enhances CD8⁺ T-cell responses to vaccine and is required for efficacy against brain tumors in mice.

Temozolomide (TMZ) is an alkylating agent shown to prolong survival in patients with high grade glioma and is routinely used to treat melanoma brain metastases. A prominent side effect of TMZ is induction of profound lymphopenia, which some suggest may be incompatible with immunotherapy. Conversely, it has been proposed that recovery from chemotherapy-induced lymphopenia may actually be exploited to potentiate T-cell responses. Here, we report the first demonstration of TMZ as an immune host-conditioning regimen in an experimental model of brain tumor and examine its impact on antitumor efficacy of a well-characterized peptide vaccine. Our results show that high-dose, myeloablative (MA) TMZ resulted in markedly reduced CD4(+), CD8(+) T-cell and CD4(+)Foxp3(+) TReg counts. Adoptive transfer of naïve CD8(+) T cells and vaccination in this setting led to an approximately 70-fold expansion of antigen-specific CD8(+) T cells over controls. Ex vivo analysis of effector functions revealed significantly enhanced levels of pro-inflammatory cytokine secretion from mice receiving MA TMZ when compared to those treated with a lower lymphodepletive, non-myeloablative (NMA) dose. Importantly, MA TMZ, but not NMA TMZ was uniquely associated with an elevation of endogenous IL-2 serum levels, which we also show was required for optimal T-cell expansion. Accordingly, in a murine model of established intracerebral tumor, vaccination-induced immunity in the setting of MA TMZ-but not lymphodepletive, NMA TMZ-led to significantly prolonged survival. Overall, these results may be used to leverage the side-effects of a clinically-approved chemotherapy and should be considered in future study design of immune-based treatments for brain tumors.

Authors
Sanchez-Perez, LA; Choi, BD; Archer, GE; Cui, X; Flores, C; Johnson, LA; Schmittling, RJ; Snyder, D; Herndon, JE; Bigner, DD; Mitchell, DA; Sampson, JH
MLA Citation
Sanchez-Perez, LA, Choi, BD, Archer, GE, Cui, X, Flores, C, Johnson, LA, Schmittling, RJ, Snyder, D, Herndon, JE, Bigner, DD, Mitchell, DA, and Sampson, JH. "Myeloablative temozolomide enhances CD8⁺ T-cell responses to vaccine and is required for efficacy against brain tumors in mice." PLoS One 8.3 (2013): e59082-.
PMID
23527092
Source
pubmed
Published In
PloS one
Volume
8
Issue
3
Publish Date
2013
Start Page
e59082
DOI
10.1371/journal.pone.0059082

The influence of adjuvant therapy on cardiorespiratory fitness in early-stage breast cancer seven years after diagnosis: the Cooper Center Longitudinal Study

We examined cardiorespiratory fitness (CRF) levels in early stage breast cancer patients and determined whether CRF differs as a function of adjuvant therapy regimen. A total of 180 early breast cancer patients representing three treatment groups (surgery only, single-, and multi-modality adjuvant therapy) in the Cooper Center Longitudinal Study (CCLS) were studied. A non-cancer control group (n = 180) matched by sex, age, and date of the CCLS visit was included. All subjects underwent an incremental exercise tolerance test to symptom limitation to assess CRF (i.e., peak metabolic equivalents [METs] and time to exhaustion). The mean time from breast cancer diagnosis to exercise tolerance testing was 7.4 ± 6.2 years. In adjusted analyses, time to exhaustion and peak METs were incrementally impaired with the addition of surgery, single-, and multi-modality adjuvant therapy compared to those of matched controls (p = 0.006 and 0.028, respectively). CRF was lowest in the multi-modality group compared to all other groups (all p's < 0.05). Despite being 7 years post-diagnosis, asymptomatic early breast cancer survivors have marked reductions in CRF. Patients treated with multi-modal adjuvant therapy have the greatest impairment in CRF. © 2013 Springer Science+Business Media New York.

Authors
Lakoski, SG; Barlow, CE; Koelwyn, GJ; Hornsby, WE; Hernandez, J; DeFina, LF; Radford, NB; Thomas, SM; II, JEH; Peppercorn, J; al, E
MLA Citation
Lakoski, SG, Barlow, CE, Koelwyn, GJ, Hornsby, WE, Hernandez, J, DeFina, LF, Radford, NB, Thomas, SM, II, JEH, Peppercorn, J, and al, E. "The influence of adjuvant therapy on cardiorespiratory fitness in early-stage breast cancer seven years after diagnosis: the Cooper Center Longitudinal Study." Breast Cancer Research and Treatment (2013): 1-8.
PMID
23504137
Source
scival
Published In
Breast Cancer Research and Treatment
Publish Date
2013
Start Page
1
End Page
8
DOI
10.1007/s10549-013-2478-1

Effect of socioeconomic status as measured by education level on survival in breast cancer clinical trials

Objectives This paper aims to investigate the effect of socioeconomic status, as measured by education, on the survival of breast cancer patients treated on 10 studies conducted by the Cancer and Leukemia Group B. Methods Sociodemographic data, including education, were reported by the patient at trial enrollment. Cox proportional hazards model stratified by treatment arm/study was used to examine the effect of education on survival among patients with early stage and metastatic breast cancer, after adjustment for known prognostic factors. Results The patient population included 1020 patients with metastatic disease and 5146 patients with early stage disease. Among metastatic patients, factors associated with poorer survival in the final multivariable model included African American race, never married, negative estrogen receptor status, prior hormonal therapy, visceral involvement, and bone involvement. Among early stage patients, significant factors associated with poorer survival included African American race, separated/widowed, post/perimenopausal, negative/unknown estrogen receptor status, negative progesterone receptor status, >4 positive nodes, tumor diameter >2 cm, and education. Having not completed high school was associated with poorer survival among early stage patients. Among metastatic patients, non-African American women who lacked a high school degree had poorer survival than other non-African American women, and African American women who lacked a high school education had better survival than educated African American women. Conclusions Having less than a high school education is a risk factor for death among patients with early stage breast cancer who participated in a clinical trial, with its impact among metastatic patients being less clear. Post-trial survivorship plans need to focus on women with low social status, as measured by education. Copyright © 2011 John Wiley & Sons, Ltd.

Authors
Herndon, JE; Kornblith, AB; Holland, JC; Paskett, ED
MLA Citation
Herndon, JE, Kornblith, AB, Holland, JC, and Paskett, ED. "Effect of socioeconomic status as measured by education level on survival in breast cancer clinical trials." Psycho-Oncology 22.2 (2013): 315-323.
Source
scival
Published In
Psycho-Oncology
Volume
22
Issue
2
Publish Date
2013
Start Page
315
End Page
323
DOI
10.1002/pon.2094

The influence of adjuvant therapy on cardiorespiratory fitness in early-stage breast cancer seven years after diagnosis: The Cooper Center Longitudinal Study

We examined cardiorespiratory fitness (CRF) levels in early stage breast cancer patients and determined whether CRF differs as a function of adjuvant therapy regimen. A total of 180 early breast cancer patients representing three treatment groups (surgery only, single-, and multi-modality adjuvant therapy) in the Cooper Center Longitudinal Study (CCLS) were studied. A non-cancer control group (n = 180) matched by sex, age, and date of the CCLS visit was included. All subjects underwent an incremental exercise tolerance test to symptom limitation to assess CRF (i.e., peak metabolic equivalents [METs] and time to exhaustion). The mean time from breast cancer diagnosis to exercise tolerance testing was 7.4 ± 6.2 years. In adjusted analyses, time to exhaustion and peak METs were incrementally impaired with the addition of surgery, single-, and multi-modality adjuvant therapy compared to those of matched controls (p = 0.006 and 0.028, respectively). CRF was lowest in the multi-modality group compared to all other groups (all p's < 0.05). Despite being 7 years post-diagnosis, asymptomatic early breast cancer survivors have marked reductions in CRF. Patients treated with multi-modal adjuvant therapy have the greatest impairment in CRF. © 2013 Springer Science+Business Media New York.

Authors
Lakoski, SG; Barlow, CE; Koelwyn, GJ; Hornsby, WE; Hernandez, J; Defina, LF; Radford, NB; Thomas, SM; II, JEH; Peppercorn, J; Douglas, PS; Jones, LW
MLA Citation
Lakoski, SG, Barlow, CE, Koelwyn, GJ, Hornsby, WE, Hernandez, J, Defina, LF, Radford, NB, Thomas, SM, II, JEH, Peppercorn, J, Douglas, PS, and Jones, LW. "The influence of adjuvant therapy on cardiorespiratory fitness in early-stage breast cancer seven years after diagnosis: The Cooper Center Longitudinal Study." Breast Cancer Research and Treatment 138.3 (2013): 909-916.
Source
scival
Published In
Breast Cancer Research and Treatment
Volume
138
Issue
3
Publish Date
2013
Start Page
909
End Page
916
DOI
10.1007/s10549-013-2478-1

BLyS levels correlate with vaccine-induced antibody titers in patients with glioblastoma lymphodepleted by therapeutic temozolomide

B lymphocyte stimulator (BLyS) is a cytokine involved in differentiation and survival of follicular B cells along with humoral response potentiation. Lymphopenia is known to precipitate dramatic elevation in serum BLyS; however, the use of this effect to enhance humoral responses following vaccination has not been evaluated. We evaluated BLyS serum levels and antigen-specific antibody titers in 8 patients undergoing therapeutic temozolomide (TMZ)-induced lymphopenia, with concomitant vaccine against a tumor-specific mutation in the epidermal growth factor receptor (EGFRvIII). Our studies demonstrate that TMZ-induced lymphopenia corresponded with spikes in serum BLyS that directly preceded the induction of anti-EGFRvIII antigen-specific antibody titers, in some cases as high as 1:2,000,000. Our data are the first clinical observation of BLyS serum elevation and greatly enhanced humoral immune responses as a consequence of chemotherapy-induced lymphopenia. These observations should be considered for the development of future vaccination strategies in the setting of malignancy. © 2013 Springer-Verlag Berlin Heidelberg.

Authors
Sanchez-Perez, L; Choi, BD; Reap, EA; Sayour, EJ; Norberg, P; Schmittling, RJ; Archer, GE; II, JEH; Mitchell, DA; Heimberger, AB; Bigner, DD; Sampson, JH
MLA Citation
Sanchez-Perez, L, Choi, BD, Reap, EA, Sayour, EJ, Norberg, P, Schmittling, RJ, Archer, GE, II, JEH, Mitchell, DA, Heimberger, AB, Bigner, DD, and Sampson, JH. "BLyS levels correlate with vaccine-induced antibody titers in patients with glioblastoma lymphodepleted by therapeutic temozolomide." Cancer Immunology, Immunotherapy 62.6 (2013): 983-987.
Source
scival
Published In
Cancer Immunology, Immunotherapy
Volume
62
Issue
6
Publish Date
2013
Start Page
983
End Page
987
DOI
10.1007/s00262-013-1405-y

Concurrent stereotactic radiosurgery and bevacizumab in recurrent malignant gliomas: A prospective trial

Purpose: Virtually all patients with malignant glioma (MG) eventually recur. This study evaluates the safety of concurrent stereotactic radiosurgery (SRS) and bevacizumab (BVZ), an antiangiogenic agent, in treatment of recurrent MG. Methods and Materials: Fifteen patients with recurrent MG, treated at initial diagnosis with surgery and adjuvant radiation therapy/temozolomide and then at least 1 salvage chemotherapy regimen, were enrolled in this prospective trial. Lesions <3 cm in diameter were treated in a single fraction, whereas those 3 to 5 cm in diameter received 5 5-Gy fractions. BVZ was administered immediately before SRS and 2 weeks later. Neurocognitive testing (Mini-Mental Status Exam, Trail Making Test A/B), Functional Assessment of Cancer Therapy-Brain (FACT-Br) quality-of-life assessment, physical exam, and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) were performed immediately before SRS and 1 week and 2 months following completion of SRS. The primary endpoint was central nervous system (CNS) toxicity. Secondary endpoints included survival, quality of life, microvascular properties as measured by DCE-MRI, steroid usage, and performance status. Results: One grade 3 (severe headache) and 2 grade 2 CNS toxicities were observed. No patients experienced grade 4 to 5 toxicity or intracranial hemorrhage. Neurocognition, quality of life, and Karnofsky performance status did not change significantly with treatment. DCE-MRI results suggest a significant decline in tumor perfusion and permeability 1 week after SRS and further decline by 2 months. Conclusions: Treatment of recurrent MG with concurrent SRS and BVZ was not associated with excessive toxicity in this prospective trial. A randomized trial of concurrent SRS/BVZ versus conventional salvage therapy is needed to establish the efficacy of this approach. © 2013 Elsevier Inc.

Authors
Cabrera, AR; Cuneo, KC; Desjardins, A; Sampson, JH; McSherry, F; II, JEH; Peters, KB; Allen, K; Hoang, JK; Chang, Z; Craciunescu, O; Vredenburgh, JJ; Friedman, HS; Kirkpatrick, JP
MLA Citation
Cabrera, AR, Cuneo, KC, Desjardins, A, Sampson, JH, McSherry, F, II, JEH, Peters, KB, Allen, K, Hoang, JK, Chang, Z, Craciunescu, O, Vredenburgh, JJ, Friedman, HS, and Kirkpatrick, JP. "Concurrent stereotactic radiosurgery and bevacizumab in recurrent malignant gliomas: A prospective trial." International Journal of Radiation Oncology Biology Physics 86.5 (2013): 873-879.
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
86
Issue
5
Publish Date
2013
Start Page
873
End Page
879
DOI
10.1016/j.ijrobp.2013.04.029

O6-methylguanine-DNA methyltransferase (MGMT) immunohistochemistry as a predictor of resistance to temozolomide in primary CNS lymphoma

Temozolomide, an alkylating agent, has shown promise in treating primary central nervous system lymphoma (PCNSL). The enzyme O6-methylguanine- DNA methyltransferase (MGMT) repairs alkylating damage, such as that induced by temozolomide. We hypothesized that MGMT immunohistochemistry would predict resistance to temozolomide in PCNSL. A retrospective study of newly-diagnosed and recurrent PCNSL patients treated at our institution was conducted to study the predictive value of MGMT immunohistochemistry for response to temozolomide. 20 patients who were treated with temozolomide as a single agent were identified during the study time period. 6/20 patients demonstrated a response, corresponding to an objective response rate of 30 % (95 % CI 8-52). Five patients with low MGMT level (<30 %) showed a response to temozolomide. Only one of 10 patients (10 %) with high MGMT level (≥30 %) exhibited a response to temozolomide. Small sample numbers precluded formal statistical comparisons. Two patients with complete response remain alive without progressive disease 6.7 and 7.2 years after temozolomide initiation. Immunohistochemistry can be performed on small biopsies to selectively assess MGMT status in tumor versus surrounding inflammation. MGMT analysis by immunohistochemistry may predict response to temozolomide in PCNSL and should be prospectively investigated. © 2013 Springer Science+Business Media New York.

Authors
Jiang, X; Reardon, DA; Desjardins, A; Vredenburgh, JJ; Quinn, JA; Austin, AD; II, JEH; McLendon, RE; Friedman, HS
MLA Citation
Jiang, X, Reardon, DA, Desjardins, A, Vredenburgh, JJ, Quinn, JA, Austin, AD, II, JEH, McLendon, RE, and Friedman, HS. "O6-methylguanine-DNA methyltransferase (MGMT) immunohistochemistry as a predictor of resistance to temozolomide in primary CNS lymphoma." Journal of Neuro-Oncology 114.1 (2013): 135-140.
Source
scival
Published In
Journal of Neuro-Oncology
Volume
114
Issue
1
Publish Date
2013
Start Page
135
End Page
140
DOI
10.1007/s11060-013-1162-y

The effect of metastatic site and decade of diagnosis on the individual burden of metastatic melanoma: contemporary estimates of average years of life lost.

OBJECTIVES: Metastatic melanoma (MM) is a leading cause of years of life lost due to malignancy. This study aimed to identify the average years of life lost (AYLL) in MM patients. METHODS: MM patients were identified from a prospectively maintained database, and a linear model predicting AYLL was developed. RESULTS: Between 1970 and 1999, 4,774 patients diagnosed with MM died. The AYLL was 23.2 years. AYLL remained stable across three decades. CONCLUSIONS: AYLL for MM is greater than 20 years, and has not improved. This burden underscores the need for continued research and access to funding for this disease.

Authors
Salama, AKS; Rosa, ND; Scheri, RP; Herndon, JE; Tyler, DS; Marcello, J; Pruitt, SK; Abernethy, AP
MLA Citation
Salama, AKS, Rosa, ND, Scheri, RP, Herndon, JE, Tyler, DS, Marcello, J, Pruitt, SK, and Abernethy, AP. "The effect of metastatic site and decade of diagnosis on the individual burden of metastatic melanoma: contemporary estimates of average years of life lost." Cancer Invest 30.9 (November 2012): 637-641.
PMID
23020583
Source
pubmed
Published In
Cancer Investigation (Informa)
Volume
30
Issue
9
Publish Date
2012
Start Page
637
End Page
641
DOI
10.3109/07357907.2012.726387

Bevacizumab continuation beyond initial bevacizumab progression among recurrent glioblastoma patients.

BACKGROUND: Bevacizumab improves outcome for most recurrent glioblastoma patients, but the duration of benefit is limited and survival after initial bevacizumab progression is poor. We evaluated bevacizumab continuation beyond initial progression among recurrent glioblastoma patients as it is a common, yet unsupported practice in some countries. METHODS: We analysed outcome among all patients (n=99) who received subsequent therapy after progression on one of five consecutive, single-arm, phase II clinical trials evaluating bevacizumab regimens for recurrent glioblastoma. Of note, the five trials contained similar eligibility, treatment and assessment criteria, and achieved comparable outcome. RESULTS: The median overall survival (OS) and OS at 6 months for patients who continued bevacizumab therapy (n=55) were 5.9 months (95% confidence interval (CI): 4.4, 7.6) and 49.2% (95% CI: 35.2, 61.8), compared with 4.0 months (95% CI: 2.1, 5.4) and 29.5% (95% CI: 17.0, 43.2) for patients treated with a non-bevacizumab regimen (n=44; P=0.014). Bevacizumab continuation was an independent predictor of improved OS (hazard ratio=0.64; P=0.04). CONCLUSION: The results of our retrospective pooled analysis suggest that bevacizumab continuation beyond initial progression modestly improves survival compared with available non-bevacizumab therapy for recurrent glioblastoma patients require evaluation in an appropriately randomised, prospective trial.

Authors
Reardon, DA; Herndon, JE; Peters, KB; Desjardins, A; Coan, A; Lou, E; Sumrall, AL; Turner, S; Lipp, ES; Sathornsumetee, S; Rich, JN; Sampson, JH; Friedman, AH; Boulton, ST; Bigner, DD; Friedman, HS; Vredenburgh, JJ
MLA Citation
Reardon, DA, Herndon, JE, Peters, KB, Desjardins, A, Coan, A, Lou, E, Sumrall, AL, Turner, S, Lipp, ES, Sathornsumetee, S, Rich, JN, Sampson, JH, Friedman, AH, Boulton, ST, Bigner, DD, Friedman, HS, and Vredenburgh, JJ. "Bevacizumab continuation beyond initial bevacizumab progression among recurrent glioblastoma patients." Br J Cancer 107.9 (October 23, 2012): 1481-1487.
PMID
23037712
Source
pubmed
Published In
British Journal of Cancer
Volume
107
Issue
9
Publish Date
2012
Start Page
1481
End Page
1487
DOI
10.1038/bjc.2012.415

Phase II study of Gleevec plus hydroxyurea in adults with progressive or recurrent low-grade glioma.

BACKGROUND: We evaluated the efficacy of imatinib plus hydroxyurea in patients with progressive/recurrent low-grade glioma. METHODS: A total of 64 patients with recurrent/progressive low-grade glioma were enrolled in this single-center study that stratified patients into astrocytoma and oligodendroglioma cohorts. All patients received 500 mg of hydroxyurea twice a day. Imatinib was administered at 400 mg per day for patients not on enzyme-inducing antiepileptic drugs (EIAEDs) and at 500 mg twice a day if on EIAEDs. The primary endpoint was progression-free survival at 12 months (PFS-12) and secondary endpoints were safety, median progression-free survival, and radiographic response rate. RESULTS: Thirty-two patients were enrolled into each cohort. Eleven patients (17%) had before radiotherapy and 24 (38%) had received before chemotherapy. The median PFS and PFS-12 were 11 months and 39%, respectively. Outcome did not differ between the histologic cohorts. No patient achieved a radiographic response. The most common grade 3 or greater adverse events were neutropenia (11%), thrombocytopenia (3%), and diarrhea (3%). CONCLUSIONS: Imatinib plus hydroxyurea was well tolerated among recurrent/progressive LGG patients but this regimen demonstrated negligible antitumor activity.

Authors
Reardon, DA; Desjardins, A; Vredenburgh, JJ; Herndon, JE; Coan, A; Gururangan, S; Peters, KB; McLendon, R; Sathornsumetee, S; Rich, JN; Lipp, ES; Janney, D; Friedman, HS
MLA Citation
Reardon, DA, Desjardins, A, Vredenburgh, JJ, Herndon, JE, Coan, A, Gururangan, S, Peters, KB, McLendon, R, Sathornsumetee, S, Rich, JN, Lipp, ES, Janney, D, and Friedman, HS. "Phase II study of Gleevec plus hydroxyurea in adults with progressive or recurrent low-grade glioma." Cancer 118.19 (October 1, 2012): 4759-4767.
PMID
22371319
Source
pubmed
Published In
Cancer
Volume
118
Issue
19
Publish Date
2012
Start Page
4759
End Page
4767
DOI
10.1002/cncr.26541

Clinicopathologic study of 85 cases of melanoma of the female genitalia.

BACKGROUND: Melanoma of the female genitalia has poor overall prognosis. OBJECTIVE AND METHODS: To examine prognostic factors influencing survival, the Duke Melanoma and Tumor Registry Databases were queried for patients who had received their clinical care at Duke University Medical Center, with a diagnosis of melanoma of the female genitalia, including vulva, vagina, and cervix, between 1970 and 2009. From this group, any available histopathologic specimens were procured for further review. RESULTS: Eighty-five patients were identified. The median follow-up time was 8.8 years with 60% of the patients experiencing melanoma-related mortality at last follow-up. Survival rates at 1, 5, and 10 years were 85%, 51%, and 30%, respectively. The available histopathologic specimens from 36 cases were reviewed by a dermatopathologist (M.A.S.). Fifteen of 36 cases were notable for the presence of atypical melanocytic hyperplasia adjacent to the primary melanoma. Breslow depth, lymph node status, systemic therapy, and surgery were also examined for differences in survival distributions using the log-rank test. In general, survival was inversely correlated with Breslow depth, extent of nodal involvement, and provision of systemic therapy. A higher survival rate was observed among those who received wide local excision. Log-rank test demonstrated that survival between different decades of diagnosis was not significantly different. LIMITATIONS: Because of its small sample size, this study may be underpowered. CONCLUSION: Despite new treatments developed and attempted, there is no evidence that survival has improved over the past 40 years. In summary, patients with thinner melanomas amenable to surgical resection had a better prognosis than those with more extensive, metastatic disease at presentation.

Authors
Tcheung, WJ; Selim, MA; Herndon, JE; Abernethy, AP; Nelson, KC
MLA Citation
Tcheung, WJ, Selim, MA, Herndon, JE, Abernethy, AP, and Nelson, KC. "Clinicopathologic study of 85 cases of melanoma of the female genitalia." J Am Acad Dermatol 67.4 (October 2012): 598-605.
PMID
22243767
Source
pubmed
Published In
Journal of The American Academy of Dermatology
Volume
67
Issue
4
Publish Date
2012
Start Page
598
End Page
605
DOI
10.1016/j.jaad.2011.11.921

Unmet spiritual care needs impact emotional and spiritual well-being in advanced cancer patients.

PURPOSE: Spiritual care is an important part of healthcare, especially when facing the crisis of advanced cancer. Do oncology inpatients receive spiritual care consistent with their needs? When inconsistent, are there deleterious effects on patient outcomes? METHODS: Patients with advanced cancer (N = 150) were surveyed during their inpatient stay at a southeastern medical center using validated instruments documenting spirituality, quality of life, mood, and satisfaction with care. Relationships between the receipt of less spiritual care than desired and patient outcomes were examined. RESULTS: Almost all patients had spiritual needs (91%) and the majority desired and received spiritual care from their healthcare providers (67%; 68%), religious community (78%; 73%), and hospital chaplain (45%; 36%). However, a significant subset received less spiritual care than desired from their healthcare providers (17%), religious community (11%), and chaplain (40%); in absolute terms, the number who received less care than desired from one or more sources was substantial (42 of 150). Attention to spiritual care would improve satisfaction with care while hospitalized for 35% of patients. Patients who received less spiritual care than desired reported more depressive symptoms [adjusted β (SE) = 1.2 (0.47), p = 0.013] and less meaning and peace [adjusted β (SE) = -2.37 (1.15), p = 0.042]. CONCLUSIONS: A substantial minority of patients did not receive the spiritual care they desired while hospitalized. When spiritual needs are not met, patients are at risk of depression and reduced sense of spiritual meaning and peace. Spiritual care should be matched to cancer patients' needs.

Authors
Pearce, MJ; Coan, AD; Herndon, JE; Koenig, HG; Abernethy, AP
MLA Citation
Pearce, MJ, Coan, AD, Herndon, JE, Koenig, HG, and Abernethy, AP. "Unmet spiritual care needs impact emotional and spiritual well-being in advanced cancer patients." Support Care Cancer 20.10 (October 2012): 2269-2276.
PMID
22124529
Source
pubmed
Published In
Supportive Care in Cancer
Volume
20
Issue
10
Publish Date
2012
Start Page
2269
End Page
2276
DOI
10.1007/s00520-011-1335-1

PHASE II STUDY TO EVALUATE THE EFFICACY AND SAFETY OF INTRAVENOUS PALONOSETRON IN PRIMARY MALIGNANT GLIOMA PATIENTS RECEIVING STANDARD RADIOTHERAPY AND CONCOMITANT TEMOZOLOMIDE

Authors
Affronti, ML; Woodring, S; Allen, K; II, HJE; McSherry, F; Peters, KB; Friedman, HS; Desjardins, A; Freeman, W; Cheshire, S; Cone, C; Kalinowski, KH; Kim, J-Y; III, LHH; Poillucci, V; Southerland, C; Tetterton, J; Kirkpatrick, J; Vredenburgh, JJ
MLA Citation
Affronti, ML, Woodring, S, Allen, K, II, HJE, McSherry, F, Peters, KB, Friedman, HS, Desjardins, A, Freeman, W, Cheshire, S, Cone, C, Kalinowski, KH, Kim, J-Y, III, LHH, Poillucci, V, Southerland, C, Tetterton, J, Kirkpatrick, J, and Vredenburgh, JJ. "PHASE II STUDY TO EVALUATE THE EFFICACY AND SAFETY OF INTRAVENOUS PALONOSETRON IN PRIMARY MALIGNANT GLIOMA PATIENTS RECEIVING STANDARD RADIOTHERAPY AND CONCOMITANT TEMOZOLOMIDE." October 2012.
PMID
27271867
Source
wos-lite
Published In
Neuro-Oncology
Volume
14
Publish Date
2012
Start Page
156
End Page
156

A PHASE II SINGLE-ARM TRIAL OF PALONOSETRON FOR THE PREVENTION OF ACUTE AND DELAYED CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING IN MALIGNANT GLIOMA PATIENTS RECEIVING IRINOTECAN IN COMBINATION WITH BEVACIZUMAB

Authors
Affronti, ML; Woodring, S; II, HJE; McSherry, F; Peters, KB; Friedman, HS; Desjardins, A; Freeman, W; Cheshire, S; Cone, C; Kalinowski, KH; Kim, J-Y; III, LHH; Poillucci, V; Southerland, C; Tetterton, J; Vredenburgh, JJ
MLA Citation
Affronti, ML, Woodring, S, II, HJE, McSherry, F, Peters, KB, Friedman, HS, Desjardins, A, Freeman, W, Cheshire, S, Cone, C, Kalinowski, KH, Kim, J-Y, III, LHH, Poillucci, V, Southerland, C, Tetterton, J, and Vredenburgh, JJ. "A PHASE II SINGLE-ARM TRIAL OF PALONOSETRON FOR THE PREVENTION OF ACUTE AND DELAYED CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING IN MALIGNANT GLIOMA PATIENTS RECEIVING IRINOTECAN IN COMBINATION WITH BEVACIZUMAB." October 2012.
Source
wos-lite
Published In
Neuro-Oncology
Volume
14
Publish Date
2012
Start Page
156
End Page
156

NEWLY DIAGNOSED GLIOBLASTOMA TREATED WITH GLIADEL (R) FOLLOWED BY RADIATION THERAPY (RT), TEMOZOLOMIDE AND BEVACIZUMAB, AND POST-RT BEVACIZUMAB AND TEMOZOLOMIDE: A PHASE II STUDY

Authors
Desjardins, A; Peters, KB; II, HJE; Bailey, LA; Alderson, LM; Ranjan, T; Sampson, JH; Friedman, AH; Bigner, DD; Friedman, HS; Vredenburgh, JJ
MLA Citation
Desjardins, A, Peters, KB, II, HJE, Bailey, LA, Alderson, LM, Ranjan, T, Sampson, JH, Friedman, AH, Bigner, DD, Friedman, HS, and Vredenburgh, JJ. "NEWLY DIAGNOSED GLIOBLASTOMA TREATED WITH GLIADEL (R) FOLLOWED BY RADIATION THERAPY (RT), TEMOZOLOMIDE AND BEVACIZUMAB, AND POST-RT BEVACIZUMAB AND TEMOZOLOMIDE: A PHASE II STUDY." October 2012.
Source
wos-lite
Published In
Neuro-Oncology
Volume
14
Publish Date
2012
Start Page
104
End Page
104

LONG-TERM SURVIVORSHIP IN PRIMARY GLIOBLASTOMA: A FOCUS ON NEUROCOGNITION

Authors
Peters, KB; Woodring, S; II, HJE; McSherry, F; Vredenburgh, JJ; Desjardins, A; Friedman, HS
MLA Citation
Peters, KB, Woodring, S, II, HJE, McSherry, F, Vredenburgh, JJ, Desjardins, A, and Friedman, HS. "LONG-TERM SURVIVORSHIP IN PRIMARY GLIOBLASTOMA: A FOCUS ON NEUROCOGNITION." October 2012.
Source
wos-lite
Published In
Neuro-Oncology
Volume
14
Publish Date
2012
Start Page
62
End Page
62

VORINOSTAT, BEVACIZUMAB, AND METRONOMIC TEMOZOLOMIDE FOR RECURRENT HIGH-GRADE GLIOMA: A PHASE I/II CLINICAL TRIAL

Authors
Peters, KB; Reardon, DA; Vredenburgh, JJ; Desjardins, A; II, HJE; Coan, A; McSherry, F; Lipp, E; Brickhouse, A; Massey, W; Friedman, HS
MLA Citation
Peters, KB, Reardon, DA, Vredenburgh, JJ, Desjardins, A, II, HJE, Coan, A, McSherry, F, Lipp, E, Brickhouse, A, Massey, W, and Friedman, HS. "VORINOSTAT, BEVACIZUMAB, AND METRONOMIC TEMOZOLOMIDE FOR RECURRENT HIGH-GRADE GLIOMA: A PHASE I/II CLINICAL TRIAL." October 2012.
Source
wos-lite
Published In
Neuro-Oncology
Volume
14
Publish Date
2012
Start Page
81
End Page
81

LONG-TERM SURVIVORSHIP IN PRIMARY GLIOBLASTOMA: A FOCUS ON QUALITY OF LIFE

Authors
Peters, KB; Woodring, S; Herndon, JE; McSherry, F; Vredenburgh, JJ; Desjardins, A; Friedman, HS
MLA Citation
Peters, KB, Woodring, S, Herndon, JE, McSherry, F, Vredenburgh, JJ, Desjardins, A, and Friedman, HS. "LONG-TERM SURVIVORSHIP IN PRIMARY GLIOBLASTOMA: A FOCUS ON QUALITY OF LIFE." October 2012.
Source
wos-lite
Published In
Neuro-Oncology
Volume
14
Publish Date
2012
Start Page
158
End Page
158

Bevacizumab therapy for adults with recurrent/progressive meningioma: a retrospective series.

Intracranial meningiomas are often indolent tumors which typically grow over years to decades. Nonetheless, meningiomas that progress after maximum safe resection and radiation therapy pose a significant therapeutic challenge and effective therapies have yet to be identified. Preclinical studies implicate angiogenesis in the pathophysiology of more aggressive meningiomas, suggesting that anti-angiogenic therapies may be of utility in this setting. We performed a retrospective review of fourteen patients with recurrent meningioma treated at Duke University Medical Center with bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor, administered either alone or in combination with chemotherapy. Most patients were heavily pre-treated. Progression-free survival at 6 months was 86 % and was comparable regardless of meningioma grade and whether bevacizumab was administered as monotherapy or in combination with chemotherapy. Most toxicities were mild however single patients developed CNS hemorrhage (grade 1) and intestinal perforation (grade 4), respectively. Bevacizumab can be administered safely to patients with meningioma and appears to be associated with encouraging anti-tumor effect when administered as either a single agent or in combination with chemotherapy. Phase II trials investigating bevacizumab in patients with progressive/recurrent meningioma are warranted.

Authors
Lou, E; Sumrall, AL; Turner, S; Peters, KB; Desjardins, A; Vredenburgh, JJ; McLendon, RE; Herndon, JE; McSherry, F; Norfleet, J; Friedman, HS; Reardon, DA
MLA Citation
Lou, E, Sumrall, AL, Turner, S, Peters, KB, Desjardins, A, Vredenburgh, JJ, McLendon, RE, Herndon, JE, McSherry, F, Norfleet, J, Friedman, HS, and Reardon, DA. "Bevacizumab therapy for adults with recurrent/progressive meningioma: a retrospective series." J Neurooncol 109.1 (August 2012): 63-70.
PMID
22535433
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
109
Issue
1
Publish Date
2012
Start Page
63
End Page
70
DOI
10.1007/s11060-012-0861-0

Cardiopulmonary function and age-related decline across the breast cancer survivorship continuum.

PURPOSE: To evaluate cardiopulmonary function (as measured by peak oxygen consumption [VO(2peak)]) across the breast cancer continuum and its prognostic significance in women with metastatic disease. PATIENTS AND METHODS: Patients with breast cancer representing four cross-sectional cohorts--that is, (1) before, (2) during, and (3) after adjuvant therapy for nonmetastatic disease, and (4) during therapy in metastatic disease--were studied. A cardiopulmonary exercise test (CPET) with expired gas analysis was used to assess VO(2peak). A Cox proportional hazards model was used to estimate the risk of death according to VO(2peak) category (< 15.4 v ≥ 15.4 mL · kg(-1) · min(-1)) with adjustment for clinical factors. RESULTS: A total of 248 women (age, 55 ± 8 years) completed a CPET. Mean VO(2peak) was 17.8 ± a standard deviation of 4.3 mL · kg(-1) · min(-1), the equivalent of 27% ± 17% below age-matched healthy sedentary women. For the entire cohort, 32% had a VO(2peak) less than 15.4 mL · kg(-1) · min(-1)--the VO(2peak) required for functional independence. VO(2peak) was significantly different across breast cancer cohorts for relative (mL · kg(-1) · min(-1)) and absolute (L · min(-1)) VO(2peak) (P = .017 and P < .001, respectively); VO(2peak) was lowest in women with metastatic disease. In patients with metastatic disease (n = 52), compared with patients achieving a VO(2peak) ≤ 1.09 L · min(-1), the adjusted hazard ratio for death was 0.32 (95% CI, 0.16 to 0.67, P = .002) for a VO(2peak) more than 1.09 L · min(-1). CONCLUSION: Patients with breast cancer have marked impairment in VO(2peak) across the entire survivorship continuum. VO(2peak) may be an independent predictor of survival in metastatic disease.

Authors
Jones, LW; Courneya, KS; Mackey, JR; Muss, HB; Pituskin, EN; Scott, JM; Hornsby, WE; Coan, AD; Herndon, JE; Douglas, PS; Haykowsky, M
MLA Citation
Jones, LW, Courneya, KS, Mackey, JR, Muss, HB, Pituskin, EN, Scott, JM, Hornsby, WE, Coan, AD, Herndon, JE, Douglas, PS, and Haykowsky, M. "Cardiopulmonary function and age-related decline across the breast cancer survivorship continuum." J Clin Oncol 30.20 (July 10, 2012): 2530-2537.
PMID
22614980
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
30
Issue
20
Publish Date
2012
Start Page
2530
End Page
2537
DOI
10.1200/JCO.2011.39.9014

Phase 1 trial of dasatinib plus erlotinib in adults with recurrent malignant glioma.

To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of dasatinib, an inhibitor of the Src family kinase proteins, with erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor, among recurrent malignant glioma patients. Once daily dasatinib was escalated in successive cohorts while erlotinib was administered daily at established doses based on concurrent CYP3A-inducing anticonvulsant (EIAEDS) use. Dasatinib pharmacokinetic analyzes were performed. Forty-seven patients enrolled including 37 (79 %) with grade IV and 10 (21 %) with grade III malignant glioma. Thirty patients (64 %) were at ≥second recurrence, while 27 (57 %) had received prior bevacizumab. The dasatinib MTD was 180 mg when combined with either 150 mg of erlotinib for patients not on EIAEDs, or 450 mg of erlotinib for patients on EIAEDs. The most common DLTs were diarrhea and fatigue, while most adverse events were grade 2. Pharmacokinetic data suggests that dasatinib exposure increased with increased dasatinib dose and concurrent erlotinib administration, while concurrent EIAED use diminished dasatinib exposure. No radiographic responses were observed, and only one patient (2 %) remained progression-free at 6 months. We demonstrate that dasatinib plus erlotinib can be safely co-administered on a continuous, daily dosing schedule with erlotinib, and established the recommended dose level of this combination.

Authors
Reardon, DA; Vredenburgh, JJ; Desjardins, A; Peters, KB; Sathornsumetee, S; Threatt, S; Sampson, JH; Herndon, JE; Coan, A; McSherry, F; Rich, JN; McLendon, RE; Zhang, S; Friedman, HS
MLA Citation
Reardon, DA, Vredenburgh, JJ, Desjardins, A, Peters, KB, Sathornsumetee, S, Threatt, S, Sampson, JH, Herndon, JE, Coan, A, McSherry, F, Rich, JN, McLendon, RE, Zhang, S, and Friedman, HS. "Phase 1 trial of dasatinib plus erlotinib in adults with recurrent malignant glioma." J Neurooncol 108.3 (July 2012): 499-506.
PMID
22407177
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
108
Issue
3
Publish Date
2012
Start Page
499
End Page
506
DOI
10.1007/s11060-012-0848-x

Phase II study of bevacizumab plus irinotecan and carboplatin for recurrent WHO grade 3 malignant gliomas with no prior bevacizumab failure.

Authors
Desjardins, A; Vredenburgh, JJ; Peters, KB; Threatt, S; Herndon, JE; Sampson, JH; Friedman, AH; Friedman, HS; Reardon, DA
MLA Citation
Desjardins, A, Vredenburgh, JJ, Peters, KB, Threatt, S, Herndon, JE, Sampson, JH, Friedman, AH, Friedman, HS, and Reardon, DA. "Phase II study of bevacizumab plus irinotecan and carboplatin for recurrent WHO grade 3 malignant gliomas with no prior bevacizumab failure." May 20, 2012.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
30
Issue
15
Publish Date
2012

The addition of bevacizumab to temozolomide and radiation therapy followed by bevacizumab, temozolomide, and oral topotecan for newly diagnosed glioblastoma multiforme (GBM).

Authors
Friedman, HS; Desjardins, A; Peters, KB; Reardon, DA; Kirkpatrick, J; Herndon, JE; Coan, AD; Bailey, L; Sampson, JH; Friedman, AH; Vredenburgh, JJ
MLA Citation
Friedman, HS, Desjardins, A, Peters, KB, Reardon, DA, Kirkpatrick, J, Herndon, JE, Coan, AD, Bailey, L, Sampson, JH, Friedman, AH, and Vredenburgh, JJ. "The addition of bevacizumab to temozolomide and radiation therapy followed by bevacizumab, temozolomide, and oral topotecan for newly diagnosed glioblastoma multiforme (GBM)." May 20, 2012.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
30
Issue
15
Publish Date
2012

Vorinostat, temozolomide, and bevacizumab for patients with recurrent glioblastoma: A phase I/II trial

Authors
Peters, KB; Vredenburgh, JJ; Desjardins, A; Friedman, HS; Herndon, JE; Coan, AD; McSherry, F; Lipp, ES; Brickhouse, A; Massey, WC; Reardon, DA
MLA Citation
Peters, KB, Vredenburgh, JJ, Desjardins, A, Friedman, HS, Herndon, JE, Coan, AD, McSherry, F, Lipp, ES, Brickhouse, A, Massey, WC, and Reardon, DA. "Vorinostat, temozolomide, and bevacizumab for patients with recurrent glioblastoma: A phase I/II trial." May 20, 2012.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
30
Issue
15
Publish Date
2012

Safety and efficacy of the addition of bevacizumab to temozolomide and radiation therapy followed by bevacizumab, temozolomide, and irinotecan for newly diagnosed glioblastoma multiforme

Authors
Vredenburgh, JJ; Desjardins, A; Peters, KB; Reardon, DA; Herndon, JE; Coan, AD; Kirkpatrick, J; Bailey, L; Threatt, S; Sampson, JH; Friedman, AH; Friedman, HS
MLA Citation
Vredenburgh, JJ, Desjardins, A, Peters, KB, Reardon, DA, Herndon, JE, Coan, AD, Kirkpatrick, J, Bailey, L, Threatt, S, Sampson, JH, Friedman, AH, and Friedman, HS. "Safety and efficacy of the addition of bevacizumab to temozolomide and radiation therapy followed by bevacizumab, temozolomide, and irinotecan for newly diagnosed glioblastoma multiforme." May 20, 2012.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
30
Issue
15
Publish Date
2012

Prognostic significance of functional capacity and exercise behavior in patients with metastatic non-small cell lung cancer.

BACKGROUND: To investigate the prognostic importance of functional capacity and exercise behavior in patients with metastatic non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Using a prospective design, 118 consecutive participants with histologically confirmed metastatic (inoperable) NSCLC and Eastern Cooperative Oncology group (ECOG) 0-3 completed a six-minute walk test to assess functional capacity and questionnaire that assessed self-reported exercise behavior. Cox proportional models were used to estimate the risk of all-cause mortality according to six-minute walk distance (6MWD) (<358.5m, 358.5-450 m, ≥450 m) and exercise behavior (MET-hrswk(-1)) categories with adjustment for important covariates. RESULTS: Median follow-up was 26.6 months; 77 deaths were reported during this period. Functional capacity was an independent predictor of survival (P(trend)=0.003) and added incremental prognostic value beyond that provided by PS plus other traditional markers of prognosis (P(trend)=0.025). Compared with patients achieving a 6MWD <358.5m, the adjusted hazard ratio (HR) for all-cause mortality was 0.61 (95% CI, 0.34-1.07) for a 6MWD of 358.5-450 m, and 0.48 (95% CI, 0.24-0.93) for a 6MWD >450 m. In unadjusted analysis, there was a borderline significant effect of exercise behavior on survival (p=0.052). Median survival was 12.89 months (95% CI, 9.11-21.05 months) for those reporting <9MET-hrswk(-1) compared with 25.63 months (95% CI, 11.28 to ∞ months) for those reporting ≥9MET-hrswk(-1). CONCLUSIONS: Functional capacity is a strong independent predictor of survival in advanced NSCLC that adds to the prediction of survival beyond traditional risk factors. This parameter may improve risk stratification and prognostication in NSCLC.

Authors
Jones, LW; Hornsby, WE; Goetzinger, A; Forbes, LM; Sherrard, EL; Quist, M; Lane, AT; West, M; Eves, ND; Gradison, M; Coan, A; Herndon, JE; Abernethy, AP
MLA Citation
Jones, LW, Hornsby, WE, Goetzinger, A, Forbes, LM, Sherrard, EL, Quist, M, Lane, AT, West, M, Eves, ND, Gradison, M, Coan, A, Herndon, JE, and Abernethy, AP. "Prognostic significance of functional capacity and exercise behavior in patients with metastatic non-small cell lung cancer." Lung Cancer 76.2 (May 2012): 248-252.
PMID
22112290
Source
pubmed
Published In
Lung Cancer
Volume
76
Issue
2
Publish Date
2012
Start Page
248
End Page
252
DOI
10.1016/j.lungcan.2011.10.009

Bevacizumab and daily temozolomide for recurrent glioblastoma.

BACKGROUND: The authors performed a phase 2 trial of combined protracted daily temozolomide and biweekly bevacizumab for patients with recurrent glioblastoma who had previously received radiation therapy and temozolomide. METHODS: There was no limit on the number of previous disease progressions or previous regimens allowed. Thirty-two adult patients were enrolled. Patients received temozolomide 50 mg/m(2) daily and bevacizumab 10 mg/kg intravenously every 14 days. Patients underwent physical examination and brain magnetic resonance imaging every 8 weeks. RESULTS: The authors observed a 6-month progression-free survival (PFS) rate of 18.8% (95% confidence interval [CI], 7.6%-33.7%) and a median PFS of 15.8 weeks. The median overall survival (OS) was 37 weeks, the 6-month OS rate was 62.5% (95% CI, 43.5%-76.7%), and the 12-month OS rate was 31.3% (95% CI, 16.4%-47.3%). Nine patients (28%) had a radiographic response, and 7 patients (22%) had disease progression within the first 8 weeks of treatment. Patterns of progression were available for 21 patients. The authors observed that 52% of patients (n = 11) progressed locally, 38% (n = 8) progressed with a diffuse pattern, and 10% (n = 2) progressed at a distant site. Two patients discontinued therapy secondary to toxicity (prolonged thrombocytopenia and grade 4 pancreatitis). One patient experienced grade 5 pneumonia. CONCLUSIONS: The current study demonstrated that a regimen of combined daily temozolomide and biweekly bevacizumab had some activity and was well tolerated. However, the results obtained in this study were inferior to those observed in studies of bevacizumab monotherapy and of combined irinotecan and bevacizumab therapy. The current patient population was more heterogeneous and was pretreated more heavily than patients in previous studies.

Authors
Desjardins, A; Reardon, DA; Coan, A; Marcello, J; Herndon, JE; Bailey, L; Peters, KB; Friedman, HS; Vredenburgh, JJ
MLA Citation
Desjardins, A, Reardon, DA, Coan, A, Marcello, J, Herndon, JE, Bailey, L, Peters, KB, Friedman, HS, and Vredenburgh, JJ. "Bevacizumab and daily temozolomide for recurrent glioblastoma." Cancer 118.5 (March 1, 2012): 1302-1312.
PMID
21792866
Source
pubmed
Published In
Cancer
Volume
118
Issue
5
Publish Date
2012
Start Page
1302
End Page
1312
DOI
10.1002/cncr.26381

Phase II study of carboplatin, irinotecan, and bevacizumab for bevacizumab naïve, recurrent glioblastoma.

We evaluated the efficacy of carboplatin, irinotecan, and bevacizumab among bevacizumab-naïve, recurrent glioblastoma (GBM) patients in a phase 2, open-label, single arm trial. Forty eligible patients received carboplatin (area under the plasma curve [AUC] 4 mg/ml-min) on day one, while bevacizumab (10 mg/kg) and irinotecan (340 mg/m(2) for patients on CYP3A-enzyme-inducing anti-epileptics [EIAEDs] and 125 mg/m(2) for patients not on EIAEDs) were administered on days 1 and 14 of every 28-day cycle. Patients were evaluated after each of the first two cycles and then after every other cycle. Treatment continued until progressive disease, unacceptable toxicity, non-compliance, or voluntary withdrawal. The primary endpoint was progression-free survival at 6 months (PFS-6) and secondary endpoints included safety and median overall survival (OS). All patients had progression after standard therapy. The median age was 51 years. Sixteen patients (40%) had a KPS of 90-100, while 27 (68%) were at first progression. The median time from original diagnosis was 11.4 months. The PFS-6 rate was 46.5% (95% CI: 30.4, 61.0%) and the median OS was 8.3 months [95% confidence interval (CI): 5.9, and 10.7 months]. Grade 4 events were primarily hematologic and included neutropenia and thrombocytopenia in 20 and 10%, respectively. The most common grade 3 events were neutropenia, thrombocytopenia, fatigue, and infection in 25, 20, 13, and 10%, respectively. Eleven patients (28%) discontinued study therapy due to toxicity and 17 patients (43%) required dose modification. One patient died due to treatment-related intestinal perforation. The addition of carboplatin and irinotecan to bevacizumab significantly increases toxicity but does not improve anti-tumor activity to that achieved historically with single-agent bevacizumab among bevacizumab-naïve, recurrent GBM patients. (ClinicalTrials.gov number NCT00953121).

Authors
Reardon, DA; Desjardins, A; Peters, KB; Gururangan, S; Sampson, JH; McLendon, RE; Herndon, JE; Bulusu, A; Threatt, S; Friedman, AH; Vredenburgh, JJ; Friedman, HS
MLA Citation
Reardon, DA, Desjardins, A, Peters, KB, Gururangan, S, Sampson, JH, McLendon, RE, Herndon, JE, Bulusu, A, Threatt, S, Friedman, AH, Vredenburgh, JJ, and Friedman, HS. "Phase II study of carboplatin, irinotecan, and bevacizumab for bevacizumab naïve, recurrent glioblastoma." J Neurooncol 107.1 (March 2012): 155-164.
PMID
21986722
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
107
Issue
1
Publish Date
2012
Start Page
155
End Page
164
DOI
10.1007/s11060-011-0722-2

Clinical data simplified.

Authors
Sampson, JH; Herndon, JE; McLendon, RE; Hasselblad, V; Asher, AL; McGirt, MJ; Peterson, ED
MLA Citation
Sampson, JH, Herndon, JE, McLendon, RE, Hasselblad, V, Asher, AL, McGirt, MJ, and Peterson, ED. "Clinical data simplified." J Neurosurg 116.2 (February 2012): 346-348.
PMID
22054209
Source
pubmed
Published In
Journal of neurosurgery
Volume
116
Issue
2
Publish Date
2012
Start Page
346
End Page
348
DOI
10.3171/2011.5.JNS11279

Addition of bevacizumab to standard radiation therapy and daily temozolomide is associated with minimal toxicity in newly diagnosed glioblastoma multiforme.

PURPOSE: To determine the safety of the addition of bevacizumab to standard radiation therapy and daily temozolomide for newly diagnosed glioblastoma multiforme (GBM). METHODS AND MATERIALS: A total of 125 patients with newly diagnosed GBM were enrolled in the study, and received standard radiation therapy and daily temozolomide. All patients underwent a craniotomy and were at least 2 weeks postoperative. Radiation therapy was administered in 1.8-Gy fractions, with the clinical target volume for the primary course treated to a dose of 45 to 50.4 Gy, followed by a boost of 9 to 14.4 Gy, to a total dose of 59.4 Gy. Patients received temozolomide at 75 mg/m(2) daily throughout the course of radiation therapy. Bevacizumab was given at 10 mg/kg intravenously every 14 days, beginning a minimum of 4 weeks postoperatively. RESULTS: Of the 125 patients, 120 (96%) completed the protocol-specified radiation therapy. Five patients had to stop the protocol therapy, 2 patients with pulmonary emboli, and 1 patient each with a Grade 2 central nervous system hemorrhage, Grade 4 pancytopenia, and wound dehiscence requiring surgical intervention. All 5 patients ultimately finished the radiation therapy. After radiation therapy, 3 patients had progressive disease, 2 had severe fatigue and decreased performance status, 1 patient had a colonic perforation, and 1 had a rectal fissure; these 7 patients therefore did not proceed with the protocol-specified adjuvant temozolomide, bevacizumab, and irinotecan. However, 113 patients (90%) were able to continue on study. CONCLUSIONS: The addition of bevacizumab to standard radiation therapy and daily temozolomide was found to be associated with minimal toxicity in patients newly diagnosed with GBM.

Authors
Vredenburgh, JJ; Desjardins, A; Kirkpatrick, JP; Reardon, DA; Peters, KB; Herndon, JE; Marcello, J; Bailey, L; Threatt, S; Sampson, J; Friedman, A; Friedman, HS
MLA Citation
Vredenburgh, JJ, Desjardins, A, Kirkpatrick, JP, Reardon, DA, Peters, KB, Herndon, JE, Marcello, J, Bailey, L, Threatt, S, Sampson, J, Friedman, A, and Friedman, HS. "Addition of bevacizumab to standard radiation therapy and daily temozolomide is associated with minimal toxicity in newly diagnosed glioblastoma multiforme." Int J Radiat Oncol Biol Phys 82.1 (January 1, 2012): 58-66.
PMID
21036490
Source
pubmed
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
82
Issue
1
Publish Date
2012
Start Page
58
End Page
66
DOI
10.1016/j.ijrobp.2010.08.058

Radioimmunotargeting of malignant glioma by monoclonal antibody D2C7 reactive against both wild-type and variant III mutant epidermal growth factor receptors.

INTRODUCTION: Malignant glioma remains a significant therapeutic challenge, and immunotherapeutics might be a beneficial approach for these patients. A monoclonal antibody (MAb) specific for multiple molecular targets could expand the treatable patient population and the fraction of tumor cells targeted, with potentially increased efficacy. This motivated the generation of MAb D2C7, which recognizes both wild-type epidermal growth factor receptor (EGFRwt) and a tumor-specific mutant, EGFRvIII. METHODS: D2C7 binding affinity was determined by surface plasmon resonance and its specificity characterized through comparison to EGFRwt-specific EGFR.1 and EGFRvIII-specific L8A4 MAbs by flow cytometry and immunohistochemical analysis. The three MAbs were labeled with (125)I or (131)I using Iodogen, and paired-label internalization assays and biodistribution experiments in athymic mice with human tumor xenografts were performed. RESULTS: The affinity of D2C7 for EGFRwt and EGFRvIII was 5.2×10(9) M(-1) and 3.6×10(9) M(-1), and cell-surface reactivity with both receptors was documented by flow cytometry. Immunohistochemical analyses revealed D2C7 reactivity with malignant glioma tissue from 90 of 101 patients. Internalization assays performed on EGFRwt-expressing WTT cells and EGFRvIII-expressing NR6M cells indicated a threefold lower degradation of (125)I-labeled D2C7 compared with (131)I-labeled EGFR.1. Uptake of (125)I-labeled D2C7 in NR6M xenografts (52.45±13.97 %ID g(-1) on Day 3) was more than twice that of (131)I-labeled L8A4; a threefold to fivefold tumor delivery advantage was seen when compared to (131)I-labeled EGFR.1 in mice with WTT xenografts. CONCLUSIONS: These results suggest that D2C7 warrants further evaluation for the development of MAb-based therapeutics against cancers expressing EGFRwt and EGFRvIII.

Authors
Zalutsky, MR; Boskovitz, A; Kuan, C-T; Pegram, CN; Ayriss, J; Wikstrand, CJ; Buckley, AF; Lipp, ES; Herndon, JE; McLendon, RE; Bigner, DD
MLA Citation
Zalutsky, MR, Boskovitz, A, Kuan, C-T, Pegram, CN, Ayriss, J, Wikstrand, CJ, Buckley, AF, Lipp, ES, Herndon, JE, McLendon, RE, and Bigner, DD. "Radioimmunotargeting of malignant glioma by monoclonal antibody D2C7 reactive against both wild-type and variant III mutant epidermal growth factor receptors." Nucl Med Biol 39.1 (January 2012): 23-34.
PMID
21958852
Source
pubmed
Published In
Nuclear Medicine and Biology
Volume
39
Issue
1
Publish Date
2012
Start Page
23
End Page
34
DOI
10.1016/j.nucmedbio.2011.06.005

Phase II study of Gleevec® plus hydroxyurea (HU) in adults with progressive or recurrent meningioma.

We prospectively evaluated the efficacy and safety of imatinib plus hydroxyurea in patients with progressive/recurrent meningioma. A total of 21 patients with progressive/recurrent meningioma were enrolled in this dual center, single-arm, phase II trial. All patients received 500 mg of hydroxyurea twice a day. Imatinib was administered at 400 mg/day for patients not on CYP3A enzyme inducing anti-epileptic drugs (EIAEDs) and at 500 mg twice a day for patients on EIAEDs. The primary endpoint was progression-free survival at 6 months (PFS-6) and secondary endpoints were safety, radiographic response rate, and overall survival (OS). Best radiographic response was stable disease and was observed in 14 patients (67%). PFS-6 for all patients, those with grade I tumors (n = 8) and those with grade II or III tumors (n = 13) was 61.9, 87.5 and 46.2%, respectively. Patients with grade II or III tumors had poorer PFS and OS than those with grade I tumors, (P = 0.025 and P = 0.018) respectively. The only grade 3 or greater adverse event occurring in ≥ 10% of patients was anemia (10%). Imatinib plus hydroxyurea is well tolerated among patients with meningioma but has modest anti-tumor activity for this indication.

Authors
Reardon, DA; Norden, AD; Desjardins, A; Vredenburgh, JJ; Herndon, JE; Coan, A; Sampson, JH; Gururangan, S; Peters, KB; McLendon, RE; Norfleet, JA; Lipp, ES; Drappatz, J; Wen, PY; Friedman, HS
MLA Citation
Reardon, DA, Norden, AD, Desjardins, A, Vredenburgh, JJ, Herndon, JE, Coan, A, Sampson, JH, Gururangan, S, Peters, KB, McLendon, RE, Norfleet, JA, Lipp, ES, Drappatz, J, Wen, PY, and Friedman, HS. "Phase II study of Gleevec® plus hydroxyurea (HU) in adults with progressive or recurrent meningioma." J Neurooncol 106.2 (January 2012): 409-415.
PMID
21938530
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
106
Issue
2
Publish Date
2012
Start Page
409
End Page
415
DOI
10.1007/s11060-011-0687-1

A pilot study of IL-2Rα blockade during lymphopenia depletes regulatory T-cells and correlates with enhanced immunity in patients with glioblastoma.

BACKGROUND: Preclinical studies in mice have demonstrated that the prophylactic depletion of immunosuppressive regulatory T-cells (T(Regs)) through targeting the high affinity interleukin-2 (IL-2) receptor (IL-2Rα/CD25) can enhance anti-tumor immunotherapy. However, therapeutic approaches are complicated by the inadvertent inhibition of IL-2Rα expressing anti-tumor effector T-cells. OBJECTIVE: To determine if changes in the cytokine milieu during lymphopenia may engender differential signaling requirements that would enable unarmed anti-IL-2Rα monoclonal antibody (MAbs) to selectively deplete T(Regs) while permitting vaccine-stimulated immune responses. METHODOLOGY: A randomized placebo-controlled pilot study was undertaken to examine the ability of the anti-IL-2Rα MAb daclizumab, given at the time of epidermal growth factor receptor variant III (EGFRvIII) targeted peptide vaccination, to safely and selectively deplete T(Regs) in patients with glioblastoma (GBM) treated with lymphodepleting temozolomide (TMZ). RESULTS AND CONCLUSIONS: Daclizumab treatment (n = 3) was well-tolerated with no symptoms of autoimmune toxicity and resulted in a significant reduction in the frequency of circulating CD4+Foxp3+ TRegs in comparison to saline controls (n = 3)( p = 0.0464). A significant (p<0.0001) inverse correlation between the frequency of TRegs and the level of EGFRvIII specific humoral responses suggests the depletion of TRegs may be linked to increased vaccine-stimulated humoral immunity. These data suggest this approach deserves further study. TRIAL REGISTRATION: ClinicalTrials.gov NCT00626015.

Authors
Sampson, JH; Schmittling, RJ; Archer, GE; Congdon, KL; Nair, SK; Reap, EA; Desjardins, A; Friedman, AH; Friedman, HS; Herndon, JE; Coan, A; McLendon, RE; Reardon, DA; Vredenburgh, JJ; Bigner, DD; Mitchell, DA
MLA Citation
Sampson, JH, Schmittling, RJ, Archer, GE, Congdon, KL, Nair, SK, Reap, EA, Desjardins, A, Friedman, AH, Friedman, HS, Herndon, JE, Coan, A, McLendon, RE, Reardon, DA, Vredenburgh, JJ, Bigner, DD, and Mitchell, DA. "A pilot study of IL-2Rα blockade during lymphopenia depletes regulatory T-cells and correlates with enhanced immunity in patients with glioblastoma." PLoS One 7.2 (2012): e31046-.
PMID
22383993
Source
pubmed
Published In
PloS one
Volume
7
Issue
2
Publish Date
2012
Start Page
e31046
DOI
10.1371/journal.pone.0031046

Outcome after bevacizumab clinical trial therapy among recurrent grade III malignant glioma patients

Although outcome following bevacizumab among recurrent grade IV malignant glioma patients is documented as poor by several analyses, outcome for recurrent grade III patients following bevacizumab therapy has not been specifically evaluated. We performed a pooled analysis of 96 recurrent grade III malignant glioma patients enrolled on three consecutive phase II bevacizumab salvage trials to evaluate overall outcome following bevacizumab trial discontinuation. Outcome on the three bevacizumab trials, which included similar eligibility, treatment and assessment criteria, was comparable. Fortynine patients who progressed on bevacizumab trial therapy and remained alive for at least 30 days elected to receive additional therapy. These patients achieved a median PFS- 6 and OS of 30.6% (95% CI: 18.4, 43.6) and 10.3 months (95% CI: 5.2, 11.7), respectively. Among patients who continued bevacizumab therapy (n = 23) after study progression, PFS-6 and median OS were 39.1% (95% CI: 19.9, 58.0) and 9.2 months (95% CI: 5.2, 13.6), respectively, compared to 23.1% (95% CI: 9.4, 40.3; P = 0.51) and 10.3 months (95% CI: 2.5, 14.4; P = 0.91) for patients who initiated non-bevacizumab containing therapy (n = 26). Outcome after discontinuation of bevacizumab therapy for recurrent grade III malignant glioma patients is associated with improved outcome compared to historical data for recurrent grade IV malignant glioma patients. Salvage therapies following bevacizumab failure have modest activity for grade III malignant glioma patients that is independent of further bevacizumab continuation. © Springer Science+Business Media, LLC. 2011.

Authors
Reardon, DA; Ii, JEH; Peters, K; Desjardins, A; Coan, A; Lou, E; Sumrall, A; Turner, S; Sathornsumetee, S; Rich, JN; Boulton, S; Lipp, ES; Friedman, HS; Vredenburgh, JJ
MLA Citation
Reardon, DA, Ii, JEH, Peters, K, Desjardins, A, Coan, A, Lou, E, Sumrall, A, Turner, S, Sathornsumetee, S, Rich, JN, Boulton, S, Lipp, ES, Friedman, HS, and Vredenburgh, JJ. "Outcome after bevacizumab clinical trial therapy among recurrent grade III malignant glioma patients." Journal of Neuro-Oncology 107.1 (2012): 213-221.
PMID
21997879
Source
scival
Published In
Journal of Neuro-Oncology
Volume
107
Issue
1
Publish Date
2012
Start Page
213
End Page
221
DOI
10.1007/s11060-011-0740-0

Phase 2 study of carboplatin, irinotecan, and bevacizumab for recurrent glioblastoma after progression on bevacizumab therapy.

BACKGROUND: The efficacy of carboplatin, irinotecan, and bevacizumab among recurrent glioblastoma (GBM) patients after prior progression on bevacizumab therapy in a phase 2, open-label, single-arm trial was evaluated. METHODS: Eligible patients received carboplatin (area under the plasma curve [AUC] 4 mg/ml-min) on day 1, whereas bevacizumab (10 mg/kg) and irinotecan (340 mg/m(2) for patients on CYP3A enzyme-inducing anti-epileptics [EIAEDs] and 125 mg/m(2) for patients not on EIAEDs) were administered on days 1 and 14 of every 28-day cycle. Patients were evaluated after each of the first 2 cycles and then after every other cycle. Treatment continued until progressive disease, unacceptable toxicity, noncompliance, or voluntary withdrawal. The primary end point was progression-free survival at 6 months (PFS-6), and secondary end points included safety and median overall survival (OS). RESULTS: All patients had progression on at least 1 prior bevacizumab regimen and 56% enrolled after either second or third overall progression. The median OS was 5.8 months (95% confidence interval [CI], 4.0-7.0 months) and PFS-6 rate was 16% (95% CI, 5.0%-32.5%). The most common grade 3 or 4 events were hematologic and occurred in 29% of cycles. Nine patients (38%) required dose modification. There were no treatment-related deaths. CONCLUSIONS: Carboplatin, irinotecan, and bevacizumab was associated with modest activity and adequate safety among recurrent GBM patients who progressed on bevacizumab previously.

Authors
Reardon, DA; Desjardins, A; Peters, KB; Vredenburgh, JJ; Gururangan, S; Sampson, JH; McLendon, RE; Herndon, JE; Coan, A; Threatt, S; Friedman, AH; Friedman, HS
MLA Citation
Reardon, DA, Desjardins, A, Peters, KB, Vredenburgh, JJ, Gururangan, S, Sampson, JH, McLendon, RE, Herndon, JE, Coan, A, Threatt, S, Friedman, AH, and Friedman, HS. "Phase 2 study of carboplatin, irinotecan, and bevacizumab for recurrent glioblastoma after progression on bevacizumab therapy." Cancer 117.23 (December 1, 2011): 5351-5358.
PMID
21590689
Source
pubmed
Published In
Cancer
Volume
117
Issue
23
Publish Date
2011
Start Page
5351
End Page
5358
DOI
10.1002/cncr.26188

Phase I study of sunitinib and irinotecan for patients with recurrent malignant glioma.

We determined the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of the oral vascular endothelial growth factor receptor (VEGFR) inhibitor, sunitinib, when administered with irinotecan among recurrent malignant glioma (MG) patients. For each 42-day cycle, sunitinib was administered once a day for four consecutive weeks followed by a 2 week rest. Irinotecan was administered intravenously every other week. Each agent was alternatively escalated among cohorts of 3-6 patients enrolled at each dose level. Patients on CYP3A-inducing anti-epileptic drugs were not eligible. Twenty-five patients with recurrent MG were enrolled, including 15 (60%) with glioblastoma (GBM) and 10 (40%) with grade 3 MG. Five patients progressed previously on bevacizumab and two had received prior VEGFR tyrosine kinase inhibitor therapy. The MTD was 50 mg of sunitinib combined with 75 mg/m(2) of irinotecan. DLT were primarily hematologic and included grade 4 neutropenia in 3 patients and one patient with grade 4 thrombocytopenia. Non-hematologic DLT included grade 3 mucositis (n = 1) and grade 3 dehydration (n = 1). Progression-free survival (PFS)-6 was 24% and only one patient achieved a radiographic response. The combination of sunitinib and irinotecan was associated with moderate toxicity and limited anti-tumor activity. Further studies with this regimen using the dosing schedules evaluated in this study are not warranted.

Authors
Reardon, DA; Vredenburgh, JJ; Coan, A; Desjardins, A; Peters, KB; Gururangan, S; Sathornsumetee, S; Rich, JN; Herndon, JE; Friedman, HS
MLA Citation
Reardon, DA, Vredenburgh, JJ, Coan, A, Desjardins, A, Peters, KB, Gururangan, S, Sathornsumetee, S, Rich, JN, Herndon, JE, and Friedman, HS. "Phase I study of sunitinib and irinotecan for patients with recurrent malignant glioma." J Neurooncol 105.3 (December 2011): 621-627.
PMID
21744079
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
105
Issue
3
Publish Date
2011
Start Page
621
End Page
627
DOI
10.1007/s11060-011-0631-4

A phase I trial of the farnesyl transferase inhibitor, SCH 66336, with temozolomide for patients with malignant glioma.

We conducted a phase I clinical trial of the combination of SCH 66336 with temozolomide administered on the standard 5-day dosing schedule. The primary objective was to determine the maximum tolerated dose and dose limiting toxicity (DLT) of twice daily SCH 66336 when administered with temozolomide to adults with malignant glioma previously treated with radiation therapy. Patients were enrolled to two strata: stratum A, patients not on enzyme-inducing antiepileptic drugs (EIAEDs); stratum B, patients receiving EIAEDs. Temozolomide was administered at a dose of 150 mg/m(2) daily for five days for the first 28-day cycle and escalated to 200 mg/m(2), during subsequent cycles. SCH 66336 was administered twice daily on a continuous daily dosing schedule. The starting dose of SCH 66336 was 75 mg twice daily for stratum A and 125 mg twice daily for stratum B. Cohorts of 3-6 patients were treated per dose level until DLT was observed. Thirty six patients were enrolled on study, including 21 patients on stratum A and 15 on stratum B. All DLTs were grade 3 events and included hepatic, gastrointestinal, renal, thrombotic and constitutional events. No grade 4 or 5 toxicities were observed. The phase II dose of SCH 66336 when combined with temozolomide is 150 mg twice daily for patients not on EIAEDs and 175 mg twice daily for patients on EIAEDs.

Authors
Desjardins, A; Reardon, DA; Peters, KB; Threatt, S; Coan, AD; Herndon, JE; Friedman, AH; Friedman, HS; Vredenburgh, JJ
MLA Citation
Desjardins, A, Reardon, DA, Peters, KB, Threatt, S, Coan, AD, Herndon, JE, Friedman, AH, Friedman, HS, and Vredenburgh, JJ. "A phase I trial of the farnesyl transferase inhibitor, SCH 66336, with temozolomide for patients with malignant glioma." J Neurooncol 105.3 (December 2011): 601-606.
PMID
21735117
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
105
Issue
3
Publish Date
2011
Start Page
601
End Page
606
DOI
10.1007/s11060-011-0627-0

Phase I study of sunitinib and irinotecan for patients with recurrent malignant glioma

Authors
Reardon, DA; Vredenburgh, JJ; Coan, A; Desjardins, A; Peters, KB; Gururangan, S; Sathornsumetee, S; Rich, JN; Herndon, JE; Friedman, HS
MLA Citation
Reardon, DA, Vredenburgh, JJ, Coan, A, Desjardins, A, Peters, KB, Gururangan, S, Sathornsumetee, S, Rich, JN, Herndon, JE, and Friedman, HS. "Phase I study of sunitinib and irinotecan for patients with recurrent malignant glioma." JOURNAL OF NEURO-ONCOLOGY 105.3 (December 2011): 621-627.
Source
wos-lite
Published In
Journal of Neuro-Oncology
Volume
105
Issue
3
Publish Date
2011
Start Page
621
End Page
627
DOI
10.1007/s11060-011-0631-4

DENDRITIC CELL VACCINES TARGETING CYTOMEGALOVIRUS IN GLIOBLASTOMA

Authors
Mitchell, DA; Archer, GE; Friedman, HS; Herndon, JE; Bigner, DD; Sampson, JH
MLA Citation
Mitchell, DA, Archer, GE, Friedman, HS, Herndon, JE, Bigner, DD, and Sampson, JH. "DENDRITIC CELL VACCINES TARGETING CYTOMEGALOVIRUS IN GLIOBLASTOMA." NEURO-ONCOLOGY 13 (November 2011): 39-39.
Source
wos-lite
Published In
Neuro-Oncology
Volume
13
Publish Date
2011
Start Page
39
End Page
39

TRUNCATED NEUROKININ 1 RECEPTOR: EXPRESSION IN PRIMARY GLIOBLASTOMAS AND RELATIONSHIP WITH PATIENT SURVIVAL

Authors
Kwatra, MM; Porter, TM; Brown, KE; Herndon, JE; Bigner, DD
MLA Citation
Kwatra, MM, Porter, TM, Brown, KE, Herndon, JE, and Bigner, DD. "TRUNCATED NEUROKININ 1 RECEPTOR: EXPRESSION IN PRIMARY GLIOBLASTOMAS AND RELATIONSHIP WITH PATIENT SURVIVAL." NEURO-ONCOLOGY 13 (November 2011): 82-82.
Source
wos-lite
Published In
Neuro-Oncology
Volume
13
Publish Date
2011
Start Page
82
End Page
82

PHASE II STUDY OF PANITUMUMAB IN COMBINATION WITH IRINOTECAN FOR MALIGNANT GLIOMA PATIENTS

Authors
Desjardins, A; Reardon, DA; Peters, KB; II, HJE; Gururangan, S; Norfleet, J; Friedman, HS; Vredenburgh, JJ
MLA Citation
Desjardins, A, Reardon, DA, Peters, KB, II, HJE, Gururangan, S, Norfleet, J, Friedman, HS, and Vredenburgh, JJ. "PHASE II STUDY OF PANITUMUMAB IN COMBINATION WITH IRINOTECAN FOR MALIGNANT GLIOMA PATIENTS." NEURO-ONCOLOGY 13 (November 2011): 90-90.
Source
wos-lite
Published In
Neuro-Oncology
Volume
13
Publish Date
2011
Start Page
90
End Page
90

THE ADDITION OF BEVACIZUMAB TO TEMOZOLOMIDE AND RADIATION THERAPY FOLLOWED BY BEVACIZUMAB, TEMOZOLOMIDE, AND ORAL TOPOTECAN FOR NEWLY DIAGNOSED GLIOBLASTOMA MULTIFORME

Authors
Vredenburgh, JJ; Desjardins, A; Reardon, DA; Peters, KB; Kirkpatrick, JP; II, HJE; Coan, AD; Bailey, L; Janney, D; Lu, C; Friedman, HS
MLA Citation
Vredenburgh, JJ, Desjardins, A, Reardon, DA, Peters, KB, Kirkpatrick, JP, II, HJE, Coan, AD, Bailey, L, Janney, D, Lu, C, and Friedman, HS. "THE ADDITION OF BEVACIZUMAB TO TEMOZOLOMIDE AND RADIATION THERAPY FOLLOWED BY BEVACIZUMAB, TEMOZOLOMIDE, AND ORAL TOPOTECAN FOR NEWLY DIAGNOSED GLIOBLASTOMA MULTIFORME." NEURO-ONCOLOGY 13 (November 2011): 89-90.
Source
wos-lite
Published In
Neuro-Oncology
Volume
13
Publish Date
2011
Start Page
89
End Page
90

The Association of Intratumoral Germinal Centers with early-stage non-small cell lung cancer.

INTRODUCTION: Lung cancers can display immune cell infiltration although the role of an adaptive immune response in disease pathogenesis is unknown. To investigate the possibility of a functional humoral response to the tumor, we surveyed histologic sections from non-small cell lung cancer (NSCLC) tumors for germinal centers (GCs) and assessed whether there was an association between the presence of GCs and tumor stage. METHODS: Tumor sections from 91 patients with all stages of NSCLC were examined by a pathologist blinded to clinical data. GCs were identified by hematoxylin and eosin staining patterns and confirmed by immunohistochemical staining for B-cell markers, BCL-6 and CD21. The distribution of GCs within the tumor or the tumor margin was recorded. Statistical analysis was performed to evaluate the association between stage and presence of GCs. RESULTS: Thirty-five percent of all tumors evaluated contained GCs, and sections evaluated by immunohistochemistry showed positive staining for both B-cell markers. GCs were seen both within the tumor and the tumor margin, consistent with an immune response to antigen stimulation. Patients with stage I NSCLC had a higher prevalence of intratumoral GCs than patients with stages II to IV (Cochran-Armitage Trend Test p = 0.02011). There was no association of stage with GCs in the tumor margin. CONCLUSIONS: Intratumoral GCs are associated with early-stage NSCLC. Further characterization of intratumoral GCs may lead to new diagnostic and therapeutic strategies based on manipulation of the adaptive immune response.

Authors
Gottlin, EB; Bentley, RC; Campa, MJ; Pisetsky, DS; Herndon, JE; Patz, EF
MLA Citation
Gottlin, EB, Bentley, RC, Campa, MJ, Pisetsky, DS, Herndon, JE, and Patz, EF. "The Association of Intratumoral Germinal Centers with early-stage non-small cell lung cancer." J Thorac Oncol 6.10 (October 2011): 1687-1690.
PMID
21642860
Source
pubmed
Published In
Journal of Thoracic Oncology
Volume
6
Issue
10
Publish Date
2011
Start Page
1687
End Page
1690
DOI
10.1097/JTO.0b013e3182217bec

Monoclonal antibody blockade of IL-2 receptor α during lymphopenia selectively depletes regulatory T cells in mice and humans.

Lymphodepletion augments adoptive cell transfer during antitumor immunotherapy, producing dramatic clinical responses in patients with malignant melanoma. We report that the lymphopenia induced by the chemotherapeutic agent temozolomide (TMZ) enhances vaccine-driven immune responses and significantly reduces malignant growth in an established model of murine tumorigenesis. Unexpectedly, despite the improved antitumor efficacy engendered by TMZ-induced lymphopenia, there was a treatment related increase in the frequency of immunosuppressive regulatory T cells (T(Regs); P = .0006). Monoclonal antibody (mAb)-mediated inhibition of the high-affinity IL-2 receptor α (IL-2Rα/CD25) during immunotherapy in normal mice depleted T(Regs) (73% reduction; P = .0154) but also abolished vaccine-induced immune responses. However, during lymphodepletion, IL-2Rα blockade decreased T(Regs) (93% reduction; P = .0001) without impairing effector T-cell responses, to augment therapeutic antitumor efficacy (66% reduction in tumor growth; P = .0024). Of clinical relevance, we also demonstrate that anti-IL-2Rα mAb administration during recovery from lymphodepletive TMZ in patients with glioblastoma reduced T(Reg) frequency (48% reduction; P = .0061) while permitting vaccine-stimulated antitumor effector cell expansion. To our knowledge, this is the first report of systemic antibody-mediated T(Reg) depletion during lymphopenia and the consequent synergistic enhancement of vaccine-driven cellular responses, as well as the first demonstration that anti-IL-2Rα mAbs function differentially in nonlymphopenic versus lymphopenic contexts.

Authors
Mitchell, DA; Cui, X; Schmittling, RJ; Sanchez-Perez, L; Snyder, DJ; Congdon, KL; Archer, GE; Desjardins, A; Friedman, AH; Friedman, HS; Herndon, JE; McLendon, RE; Reardon, DA; Vredenburgh, JJ; Bigner, DD; Sampson, JH
MLA Citation
Mitchell, DA, Cui, X, Schmittling, RJ, Sanchez-Perez, L, Snyder, DJ, Congdon, KL, Archer, GE, Desjardins, A, Friedman, AH, Friedman, HS, Herndon, JE, McLendon, RE, Reardon, DA, Vredenburgh, JJ, Bigner, DD, and Sampson, JH. "Monoclonal antibody blockade of IL-2 receptor α during lymphopenia selectively depletes regulatory T cells in mice and humans." Blood 118.11 (September 15, 2011): 3003-3012.
PMID
21768296
Source
pubmed
Published In
Blood
Volume
118
Issue
11
Publish Date
2011
Start Page
3003
End Page
3012
DOI
10.1182/blood-2011-02-334565

Epidemiology.

Authors
Sampson, JH; Herndon, JE; Friedman, AH; Abernethy, AP
MLA Citation
Sampson, JH, Herndon, JE, Friedman, AH, and Abernethy, AP. "Epidemiology." J Neurosurg 115.2 (August 2011): 256-257.
PMID
21529133
Source
pubmed
Published In
Journal of neurosurgery
Volume
115
Issue
2
Publish Date
2011
Start Page
256
End Page
257
DOI
10.3171/2011.1.JNS102066

Exercise behavior, functional capacity, and survival in adults with malignant recurrent glioma.

PURPOSE: Identifying strong markers of prognosis are critical to optimize treatment and survival outcomes in patients with malignant recurrent glioma. We investigated the prognostic significance of exercise behavior and functional capacity in this population. PATIENTS AND METHODS: Using a prospective design, 243 patients with WHO grades 3 to 4 recurrent malignant glioma and Karnofsky performance status (KPS) ≥ 70 completed a self-administered questionnaire that assessed exercise behavior and performed a 6-minute walk test (6MWT) to assess functional capacity. Cox proportional models were used to estimate the risk of all-cause mortality according to 6MWT distance (6MWD; < 390 meters, 390-489 meters, > 489 meters) and exercise behavior (metabolic equivalent [MET] -h/wk) adjusted for KPS and other important clinical factors. RESULTS: Median follow-up was 27.43 months. During this period, 149 deaths were recorded (61% of the total sample). Exercise behavior was an independent predictor of survival (P = .0081). Median survival was 13.03 months for patients reporting < 9 MET-h/wk relative to 21.84 months for those reporting ≥ 9 MET-h/wk. Exercise behavior added incremental prognostic value beyond that provided by KPS, age, sex, grade, and number of prior progressions (P < .001). Compared with patients reporting < 9 MET-h/wk, the adjusted hazard ratio for mortality was 0.64 (95% CI, 0.46 to 0.91) for patients reporting ≥ 9 MET-h/wk. Functional capacity was not an independent predictor of prognosis. CONCLUSION: Exercise behavior is a strong independent predictor of survival that provides incremental prognostic value to KPS as well as traditional markers of prognosis in malignant recurrent glioma.

Authors
Ruden, E; Reardon, DA; Coan, AD; Herndon, JE; Hornsby, WE; West, M; Fels, DR; Desjardins, A; Vredenburgh, JJ; Waner, E; Friedman, AH; Friedman, HS; Peters, KB; Jones, LW
MLA Citation
Ruden, E, Reardon, DA, Coan, AD, Herndon, JE, Hornsby, WE, West, M, Fels, DR, Desjardins, A, Vredenburgh, JJ, Waner, E, Friedman, AH, Friedman, HS, Peters, KB, and Jones, LW. "Exercise behavior, functional capacity, and survival in adults with malignant recurrent glioma." J Clin Oncol 29.21 (July 20, 2011): 2918-2923.
PMID
21690470
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
29
Issue
21
Publish Date
2011
Start Page
2918
End Page
2923
DOI
10.1200/JCO.2011.34.9852

Affinity-matured anti-glycoprotein NMB recombinant immunotoxins targeting malignant gliomas and melanomas.

Glycoprotein NMB (GPNMB), a transmembrane glycoprotein highly expressed in high-grade gliomas (HGGs), is an attractive target in cancer immunotherapy. We isolated a GPNMB-specific scFv clone, G49, from a human synthetic phage-display library. To obtain mutant single-chain variable-fragment antibodies (scFvs) with improved affinity and immunotoxins with increased activity, we subjected G49 to in vitro affinity maturation by a complementarity-determining-region (CDR) random-mutagenesis technique. Using light-chain CDR3 mutagenesis, cell-based panning by phage display, subsequent heavy-chain CDR1 mutagenesis, and flow-cytometric selection by yeast-surface display, we generated the mutant scFv clone 902V, with an overall 11-fold increase in affinity for GPNMB. Clone 902V was further randomized throughout the whole scFv by error-prone PCR, and one mutant, F6V, was selected by yeast-surface display. F6V scFv, differing from 902V by one amino-acid change in the light-chain CDR2, exhibited an affinity for GPNMB of 0.30 nM. The F6V mutant scFv clone was fused with a truncated form of Pseudomonas exotoxin A to form the immunotoxin F6V-PE38. F6V-PE38 demonstrated significant protein-synthesis-inhibition activity on GPNMB-expressing glioma and malignant melanoma cells (IC(50) = 0.5 ng/ml [8 pM]), a 60-fold improvement over G49 activity, but no cytotoxicity on GPNMB-negative cells. Furthermore, F6V-PE38 exhibited significant antitumor activity against subcutaneous malignant glioma xenografts in two nude-mouse models and a melanoma neoplastic meningitis model in athymic rats. These GPNMB-specific scFv antibodies and immunotoxins hold promise as reagents in targeted therapy for HGGs and other GPNMB-expressing malignancies.

Authors
Kuan, C-T; Wakiya, K; Keir, ST; Li, J; Herndon, JE; Pastan, I; Bigner, DD
MLA Citation
Kuan, C-T, Wakiya, K, Keir, ST, Li, J, Herndon, JE, Pastan, I, and Bigner, DD. "Affinity-matured anti-glycoprotein NMB recombinant immunotoxins targeting malignant gliomas and melanomas." Int J Cancer 129.1 (July 1, 2011): 111-121.
PMID
20824708
Source
pubmed
Published In
International Journal of Cancer
Volume
129
Issue
1
Publish Date
2011
Start Page
111
End Page
121
DOI
10.1002/ijc.25645

The addition of bevacizumab to standard radiation therapy and temozolomide followed by bevacizumab, temozolomide, and irinotecan for newly diagnosed glioblastoma.

PURPOSE: To determine if the addition of bevacizumab to radiation therapy and temozolomide, followed by bevacizumab, temozolomide, and irinotecan, for newly diagnosed glioblastoma patients is safe and effective. EXPERIMENTAL DESIGN: A total of 75 patients with newly diagnosed glioblastoma were enrolled in the phase II trial that investigated the addition of bevacizumab to standard radiation therapy and daily temozolomide followed by the addition of bevacizumab and irinotecan to adjuvant temozolomide. The bevacizumab was given at 10 mg/kg every 14 days beginning a minimum of 4 weeks postcraniotomy. Two weeks after radiation therapy, the patients began 6 to 12 cycles of 5-day temozolomide with bevacizumab and irinotecan every 14 days. The primary endpoint was the proportion of patients alive 16 months after informed consent. RESULTS: The therapy had moderate toxicity. Three patients, one of whom had a grade 2 central nervous system hemorrhage, came off study during radiation therapy. Seventy patients started the postradiation therapy, and 16 (23%) terminated this adjuvant therapy early because of toxicity. The median overall survival was 21.2 months (95% CI: 17.2-25.4), and 65% of the patients were alive at 16 months (95% CI: 53.4-74.9). The median progression-free survival was 14.2 months (95% CI: 12-16). CONCLUSION: The addition of bevacizumab to standard radiation therapy and temozolomide, followed by bevacizumab, irinotecan, and temozolomide, for the treatment of newly diagnosed glioblastoma has moderate toxicity and may improve efficacy compared with historical controls. The results from phase III trials are required before the role of bevacizumab for newly diagnosed glioblastoma is established.

Authors
Vredenburgh, JJ; Desjardins, A; Reardon, DA; Peters, KB; Herndon, JE; Marcello, J; Kirkpatrick, JP; Sampson, JH; Bailey, L; Threatt, S; Friedman, AH; Bigner, DD; Friedman, HS
MLA Citation
Vredenburgh, JJ, Desjardins, A, Reardon, DA, Peters, KB, Herndon, JE, Marcello, J, Kirkpatrick, JP, Sampson, JH, Bailey, L, Threatt, S, Friedman, AH, Bigner, DD, and Friedman, HS. "The addition of bevacizumab to standard radiation therapy and temozolomide followed by bevacizumab, temozolomide, and irinotecan for newly diagnosed glioblastoma." Clin Cancer Res 17.12 (June 15, 2011): 4119-4124.
PMID
21531816
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
17
Issue
12
Publish Date
2011
Start Page
4119
End Page
4124
DOI
10.1158/1078-0432.CCR-11-0120

Phase II study of metronomic chemotherapy with bevacizumab for recurrent glioblastoma after progression on bevacizumab therapy.

We evaluated the efficacy of metronomic etoposide or temozolomide administered with bevacizumab among recurrent glioblastoma (GBM) patients who progressed on prior bevacizumab therapy in a phase 2, open-label, two-arm trial. Twenty-three patients received bevacizumab (10 mg/kg) every 2 weeks with either oral etoposide (50 mg/m2) daily for 21 consecutive days each month or daily temozolomide (50 mg/m2). The primary endpoint was 6-month progression-free survival (PFS-6) and secondary endpoints included safety and overall survival. Both the etoposide and temozolomide arms of the study closed at the interim analysis due to lack of adequate anti-tumor activity. No radiographic responses were observed. Although 12 patients (52%) achieved stable disease, PFS-6 was 4.4% and the median PFS was 7.3 weeks. The only grade 4 adverse event was reversible neutropenia. Grade 3 toxicities included fatigue (n = 2) and infection (n = 1). Metronomic etoposide or temozolomide is ineffective when administered with bevacizumab among recurrent GBM patients who have progressed on prior bevacizumab therapy. Alternative treatment strategies remain critically needed for this indication.

Authors
Reardon, DA; Desjardins, A; Peters, K; Gururangan, S; Sampson, J; Rich, JN; McLendon, R; Herndon, JE; Marcello, J; Threatt, S; Friedman, AH; Vredenburgh, JJ; Friedman, HS
MLA Citation
Reardon, DA, Desjardins, A, Peters, K, Gururangan, S, Sampson, J, Rich, JN, McLendon, R, Herndon, JE, Marcello, J, Threatt, S, Friedman, AH, Vredenburgh, JJ, and Friedman, HS. "Phase II study of metronomic chemotherapy with bevacizumab for recurrent glioblastoma after progression on bevacizumab therapy." J Neurooncol 103.2 (June 2011): 371-379.
PMID
20853132
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
103
Issue
2
Publish Date
2011
Start Page
371
End Page
379
DOI
10.1007/s11060-010-0403-6

Safety results from a prospective study of concurrent radiosurgery and bevacizumab for recurrent malignant glioma.

Authors
Cuneo, KC; Cabrera, AR; Sampson, JH; Allen, KJ; Vredenburgh, JJ; Peters, K; Chang, Z; Herndon, JE; Desjardins, A; Reardon, DA; Kirkpatrick, J
MLA Citation
Cuneo, KC, Cabrera, AR, Sampson, JH, Allen, KJ, Vredenburgh, JJ, Peters, K, Chang, Z, Herndon, JE, Desjardins, A, Reardon, DA, and Kirkpatrick, J. "Safety results from a prospective study of concurrent radiosurgery and bevacizumab for recurrent malignant glioma." JOURNAL OF CLINICAL ONCOLOGY 29.15 (May 20, 2011).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
29
Issue
15
Publish Date
2011

Upfront bevacizumab with temozolomide or with temozolomide and irinotecan for unresectable or multifocal glioblastoma.

Authors
Lou, E; Reardon, DA; Peters, K; Desjardins, A; Herndon, JE; Coan, AD; Turner, SG; Sumrall, AL; Bailey, L; Friedman, HS; Vredenburgh, JJ
MLA Citation
Lou, E, Reardon, DA, Peters, K, Desjardins, A, Herndon, JE, Coan, AD, Turner, SG, Sumrall, AL, Bailey, L, Friedman, HS, and Vredenburgh, JJ. "Upfront bevacizumab with temozolomide or with temozolomide and irinotecan for unresectable or multifocal glioblastoma." JOURNAL OF CLINICAL ONCOLOGY 29.15 (May 20, 2011).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
29
Issue
15
Publish Date
2011

A pharmacokinetic (PK) study of AC480 administered twice daily in patients with surgically resectable, recurrent malignant glioma (MG) not on enzyme-inducing antiepileptic drug (EIAED).

Authors
Desjardins, A; Reardon, DA; Vredenburgh, JJ; Peters, K; Trikha, M; James, J; Gardner, M; Brickhouse, A; Herndon, JE; Friedman, HS
MLA Citation
Desjardins, A, Reardon, DA, Vredenburgh, JJ, Peters, K, Trikha, M, James, J, Gardner, M, Brickhouse, A, Herndon, JE, and Friedman, HS. "A pharmacokinetic (PK) study of AC480 administered twice daily in patients with surgically resectable, recurrent malignant glioma (MG) not on enzyme-inducing antiepileptic drug (EIAED)." JOURNAL OF CLINICAL ONCOLOGY 29.15 (May 20, 2011).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
29
Issue
15
Publish Date
2011

Bevacizumab (BV) continuation following BV progression: Meta-analysis of five consecutive recurrent glioblastoma (GBM) trials.

Authors
Reardon, DA; Vredenburgh, JJ; Desjardins, A; Peters, K; Coan, AD; Herndon, JE; Friedman, HS
MLA Citation
Reardon, DA, Vredenburgh, JJ, Desjardins, A, Peters, K, Coan, AD, Herndon, JE, and Friedman, HS. "Bevacizumab (BV) continuation following BV progression: Meta-analysis of five consecutive recurrent glioblastoma (GBM) trials." JOURNAL OF CLINICAL ONCOLOGY 29.15 (May 20, 2011).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
29
Issue
15
Publish Date
2011

Safety results from a prospective study of concurrent radiosurgery and bevacizumab for recurrent malignant glioma.

2082 Background: Most patients with a malignant glioma recur after primary chemoradiation. Bevacizumab (BVZ) has been shown in phase II trials to improve disease-free survival in patients with recurrent glioma. Retrospective studies of stereotactic radiosurgery (SRS) for recurrent glioma have also suggested improved outcomes, particularly when BVZ is administered after SRS.Patients with a recurrent unifocal malignant glioma who were treated with chemoradiation at diagnosis and failed salvage chemotherapy were eligible for this IRB-approved study. MRI and CT imaging were used for SRS planning. The contrast-enhancing lesion on the T1-weighted MRI was expanded by 1 mm for the planning target volume. Lesions <2 cm and 2-2.9 cm in size were prescribed 24 and 18 Gy in a single fraction, respectively. Lesions measuring 3-5 cm were prescribed 25 Gy in 5 fractions. Subjects received BVZ 10 mg/kg the day of SRS and 14 days later. The primary endpoint of the study was toxicity. Secondary endpoints included survival, cognitive function, and quality of life. Adverse events were scored using the NCI Common Terminology Criteria. Patients underwent baseline cognitive testing which was repeated 1 week and 2 months after SRS using the Mini-Mental State Exam and Trail Making Test.15 subjects were enrolled between 1/2010 and 1/2011. Median age and KPS were 53 years (range 25-66) and 90 (range 80-100). Median time from primary diagnosis to salvage SRS was 19.6 months. There were 5 treatment-related grade 2 adverse events including neuropathy, cognitive disturbance, dizziness, and fatigue. One patient experienced grade 3 headache requiring hospitalization. No patient experienced a cerebrovascular accident or thrombotic event. No grade 4/5 adverse events were seen. Cognitive testing scores did not significantly decrease 1 week or 2 months following SRS compared to baseline. After a median follow up of 5.7 months 14 of the 15 patients are alive.Treatment with concurrent SRS and BVZ in heavily pre-treated patients with a recurrent malignant glioma appears well tolerated. Further follow up in this and a larger patient cohort is needed to test the efficacy of this approach.

Authors
Cuneo, KC; Cabrera, AR; Sampson, JH; Allen, KJ; Vredenburgh, JJ; Peters, K; Chang, Z; Herndon, JE; Desjardins, A; Reardon, DA; Kirkpatrick, J
MLA Citation
Cuneo, KC, Cabrera, AR, Sampson, JH, Allen, KJ, Vredenburgh, JJ, Peters, K, Chang, Z, Herndon, JE, Desjardins, A, Reardon, DA, and Kirkpatrick, J. "Safety results from a prospective study of concurrent radiosurgery and bevacizumab for recurrent malignant glioma." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 29.15_suppl (May 2011): 2082-.
PMID
28019873
Source
epmc
Published In
Journal of Clinical Oncology
Volume
29
Issue
15_suppl
Publish Date
2011
Start Page
2082

Bevacizumab (BV) continuation following BV progression: Meta-analysis of five consecutive recurrent glioblastoma (GBM) trials.

2030 Background: Although BV benefits most recurrent GBM patients, the duration of benefit is limited and subsequent survival after BV progression is poor due to lack of effective therapeutic options.We performed a meta-analysis of five consecutive phase II BV salvage trials conducted at our institution to evaluate potential prognostic factors and to assess outcome following BV trial progression for recurrent GBM patients.The five BV salvage trials included similar eligibility, treatment and assessment criteria and enrolled 172 recurrent GBM patients. Outcome across the trials was comparable and traditional prognostic factors including age, KPS and degree of prior treatment did not predict outcome. Following progression on BV trial therapy, 95 patients (68%) received additional therapy including 42 patients who were initially treated with a non-BV regimen and 53 who received a BV regimen. Patients who received non-BV therapy did not differ from those who received BV therapy with regard to age, number of prior episodes of progression, time from original diagnosis or duration on BV trial therapy. The median overall survival (OS) and OS at 6 months (OS-6) for patients who received a BV regimen after progression on a BV trial was 6.1 months (95% CI: 5.2, 7.6) and 51.1% (95% CI: 36.7, 63.8), while the median OS and OS-6 for patients treated with a non-BV regimen were 4.5 months (95% CI: 2.5, 5.4) and 31.0% (95% CI: 17.8, 45.0), respectively (p=0.0135). After adjusting for known risk factors, BV therapy was the only factor associated with OS for patients undergoing further therapy after BV trial progression (hazard ratio 0.564; p-value 0.0287).Among recurrent GBM patients, clinical factors may poorly predict outcome for BV therapy. Outcome following BV failure is poor, but continuation of BV improves OS compared to available non-BV therapy.

Authors
Reardon, DA; Vredenburgh, JJ; Desjardins, A; Peters, K; Coan, AD; Herndon, JE; Friedman, HS
MLA Citation
Reardon, DA, Vredenburgh, JJ, Desjardins, A, Peters, K, Coan, AD, Herndon, JE, and Friedman, HS. "Bevacizumab (BV) continuation following BV progression: Meta-analysis of five consecutive recurrent glioblastoma (GBM) trials." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 29.15_suppl (May 2011): 2030-.
PMID
28023816
Source
epmc
Published In
Journal of Clinical Oncology
Volume
29
Issue
15_suppl
Publish Date
2011
Start Page
2030

Upfront bevacizumab with temozolomide or with temozolomide and irinotecan for unresectable or multifocal glioblastoma.

2055 Background: Patients with unresectable or multifocal glioblastomas (GBs) have a poor prognosis with median survival of 6-10 months. Given the angiogenic phenotype of GB, we conducted two phase II trials of upfront 5-day temozolomide (TMZ) and Bevacizumab (BV) with or without Irinotecan in patients with newly diagnosed unresectable or multifocal GB.Before radiation, patients received up to 4 cycles of temozolomide at 200 mg/m2/d days 1-5 and BV at 10 mg/kg on days 1 and 15 in each 28-day cycle. In the second trial, Irinotecan was added on days 1 and 15 at 125 mg/M2 for patients not on an enzyme-inducing anti-epileptic drug (EIAED), or 340 mg/M2 for patients on an EIAED. An MRI was performed monthly and therapy continued as long as there was no tumor progression, grade 4 non-hematologic toxicity, or recurrent grade 4 hematologic toxicity after dose reduction. The primary endpoint was tumor response using the RANO criteria.In the initial trial of TMZ and BV, 41 patients were enrolled from 10/07 to 9/08. MRI's were available from 31 patients. There were 8 (25.8%) partial responses, 19 (61.3 %) patients with stable disease, and 4 (12.9 %) had disease progression. 19 of the 41 patients enrolled completed four cycles without tumor progression. The regimen was tolerable, with three grade 4 hematologic toxicities. There were 3 venous thromboembolic complications. There were 2 CNS hemorrhages. The median PFS was 5.2 mos (3.2, 9.0 months) and the median OS was 11.7 months (7.1, 15.6 months). In the second trial, Irinotecan was added to TMZ and BV and 41 patients were enrolled between 12/09 and 11/10. The partial response rate was 41%, 44% had stable disease and 15% had progression. 16 of 41 patients completed four cycles without tumor progression. There were 4 patients with grade 4 hematologic toxicity, 7 patients with venous thromboembolic complications and 1 with CNS hemorrhage. The median PFS was 6.7 months (2.0, 10.5 months) and median OS was 10.5 months (7.2, ND months).Upfront TMZ and BV was well tolerated. Adding Irinotecan to TMZ and BV does not appear to improve survival. Upfront therapy for unresectable or multifocal GB is an excellent platform to determine clinical activity.

Authors
Lou, E; Reardon, DA; Peters, K; Desjardins, A; Herndon, JE; Coan, AD; Turner, SG; Sumrall, AL; Bailey, L; Friedman, HS; Vredenburgh, JJ
MLA Citation
Lou, E, Reardon, DA, Peters, K, Desjardins, A, Herndon, JE, Coan, AD, Turner, SG, Sumrall, AL, Bailey, L, Friedman, HS, and Vredenburgh, JJ. "Upfront bevacizumab with temozolomide or with temozolomide and irinotecan for unresectable or multifocal glioblastoma." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 29.15_suppl (May 2011): 2055-.
PMID
28019946
Source
epmc
Published In
Journal of Clinical Oncology
Volume
29
Issue
15_suppl
Publish Date
2011
Start Page
2055

A pharmacokinetic (PK) study of AC480 administered twice daily in patients with surgically resectable, recurrent malignant glioma (MG) not on enzyme-inducing antiepileptic drug (EIAED).

2070 Background: AC480 is a novel oral tyrosine kinase inhibitor of the human epidermal growth factor receptor family, especially EGFR and HER2. EGFR is an important therapeutic target in MG. We performed a pilot study to evaluate the tumor and plasma PK of AC480 among patients with recurrent MG.Eligibility included: adult patients with < three recurrences of a WHO grade 3 or 4 MG; candidate to surgical resection; prior treatment with radiotherapy and chemotherapy; Karnofsky >60%; adequate hematologic, renal and liver function. Exclusion included use of EIAED and prior targeted therapies to EGFR and HER2. FDG-PET was obtained at baseline, then AC480 was initiated at 300 mg orally BID. FDG-PET was repeated on day 14. Patients remained on treatment until surgery (day16). Plasma PK were obtained on days 1, 14 and 16. Tumor specimen for tumor PK was obtained at surgery. Patients resumed AC480 7 to 21 days post-surgery.As planned, 5 patients were enrolled on study (WHO grade 4, n=4; WHO grade 3, n=1). Median age was 58 (range, 36-65). All patients completed FDG-PET and surgery. Three patients had same or decreased metabolic activity on day 14 FDG-PET; two had increased metabolic activity. Following surgery, 4 patients resumed therapy, one patient refused, as pathology showed WHO grade 2. One patient remains on therapy after 45+ weeks. Two patients progressed 4 weeks after resuming AC480 and one after 8 weeks. One patient each experienced grade 3 proteinuria and leukopenia. Tumor PK levels were variable, but AC480 was present in all samples. Concentrations ranged from 2561 to 8703 ng/mL (5 to 16 uM). Tumor/Plasma PK ratios ranged from 3 to 11, indicating tumor levels exceeded plasma levels in all patients.AC480 is well tolerated and reaches the brain with tumor PK levels exceeding plasma. Further trials combining AC480 with chemotherapy or other targeted therapies are warranted.

Authors
Desjardins, A; Reardon, DA; Vredenburgh, JJ; Peters, K; Trikha, M; James, J; Gardner, M; Brickhouse, A; Herndon, JE; Friedman, HS
MLA Citation
Desjardins, A, Reardon, DA, Vredenburgh, JJ, Peters, K, Trikha, M, James, J, Gardner, M, Brickhouse, A, Herndon, JE, and Friedman, HS. "A pharmacokinetic (PK) study of AC480 administered twice daily in patients with surgically resectable, recurrent malignant glioma (MG) not on enzyme-inducing antiepileptic drug (EIAED)." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 29.15_suppl (May 2011): 2070-.
PMID
28019891
Source
epmc
Published In
Journal of Clinical Oncology
Volume
29
Issue
15_suppl
Publish Date
2011
Start Page
2070

Correlates of quality of life-related outcomes in breast cancer patients participating in the Pathfinders pilot study.

OBJECTIVE: In a pilot study, participation in the Pathfinders program was associated with reductions in distress and despair and improvements in quality of life (QOL) among advanced breast cancer patients. This study explores the relationship between psychosocial resources invoked through the Pathfinders intervention and outcomes. METHODS: Advanced breast cancer patients were enrolled in a prospective, single-arm, pilot study of the Pathfinders psychosocial program. Participants met at least monthly with a licensed clinical social worker who administered the Pathfinders intervention, which focused on strengthening adaptive coping skills, identifying inner strengths, and developing a self-care plan. Longitudinal assessments over 6 months used validated instruments to assess changes in Pathfinders targets (coping, social support, self-efficacy, spirituality, and optimism) and outcomes (distress, despair, QOL, and fatigue). Multiple linear regression models examined the joint effect of average changes in target subscales on average outcome changes, adjusted for baseline outcome scores and patient characteristics. RESULTS: Participants (n=44) were: mean age 51 (SD, 12), 20% non-Caucasian, 50% college degree, and 75% married. Improvements in active coping skills, self-efficacy, and spiritual meaning/peace significantly correlated with an improvement in despair after adjustment for demographic characteristics (all P<0.05). Improvements in social support significantly correlated with positive changes in distress (P<0.05). Gains in learned optimism independently correlated with an increase in overall QOL (P<0.01). CONCLUSIONS: In this pilot assessment, changes in pre-defined Pathfinders targets such as coping skills, social support, self-efficacy, spirituality, and optimism correlated with improvements in patient-reported outcomes.

Authors
Smith, SK; Herndon, JE; Lyerly, HK; Coan, A; Wheeler, JL; Staley, T; Abernethy, AP
MLA Citation
Smith, SK, Herndon, JE, Lyerly, HK, Coan, A, Wheeler, JL, Staley, T, and Abernethy, AP. "Correlates of quality of life-related outcomes in breast cancer patients participating in the Pathfinders pilot study." Psychooncology 20.5 (May 2011): 559-564.
PMID
20878862
Source
pubmed
Published In
Psycho-Oncology
Volume
20
Issue
5
Publish Date
2011
Start Page
559
End Page
564
DOI
10.1002/pon.1770

A review of VEGF/VEGFR-targeted therapeutics for recurrent glioblastoma.

Glioblastoma, the most common primary malignant brain tumor among adults, is a highly angiogenic and deadly tumor. Angiogenesis in glioblastoma, driven by hypoxia-dependent and independent mechanisms, is primarily mediated by vascular endothelial growth factor (VEGF), and generates blood vessels with distinctive features. The outcome for patients with recurrent glioblastoma is poor because of ineffective therapies. However, recent encouraging rates of radiographic response and progression-free survival, and adequate safety, led the FDA to grant accelerated approval of bevacizumab, a humanized monoclonal antibody against VEGF, for the treatment of recurrent glioblastoma in May 2009. These results have triggered significant interest in additional antiangiogenic agents and therapeutic strategies for patients with both recurrent and newly diagnosed glioblastoma. Given the potent antipermeability effect of VEGF inhibitors, the Radiologic Assessment in Neuro-Oncology (RANO) criteria were recently implemented to better assess response among patients with glioblastoma. Although bevacizumab improves survival and quality of life, eventual tumor progression is the norm. Better understanding of resistance mechanisms to VEGF inhibitors and identification of effective therapy after bevacizumab progression are currently a critical need for patients with glioblastoma.

Authors
Reardon, DA; Turner, S; Peters, KB; Desjardins, A; Gururangan, S; Sampson, JH; McLendon, RE; Herndon, JE; Jones, LW; Kirkpatrick, JP; Friedman, AH; Vredenburgh, JJ; Bigner, DD; Friedman, HS
MLA Citation
Reardon, DA, Turner, S, Peters, KB, Desjardins, A, Gururangan, S, Sampson, JH, McLendon, RE, Herndon, JE, Jones, LW, Kirkpatrick, JP, Friedman, AH, Vredenburgh, JJ, Bigner, DD, and Friedman, HS. "A review of VEGF/VEGFR-targeted therapeutics for recurrent glioblastoma." J Natl Compr Canc Netw 9.4 (April 2011): 414-427. (Review)
PMID
21464146
Source
pubmed
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
9
Issue
4
Publish Date
2011
Start Page
414
End Page
427

Greater chemotherapy-induced lymphopenia enhances tumor-specific immune responses that eliminate EGFRvIII-expressing tumor cells in patients with glioblastoma.

Epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific mutation widely expressed in glioblastoma multiforme (GBM) and other neoplasms, but absent from normal tissues. Immunotherapeutic targeting of EGFRvIII could eliminate neoplastic cells more precisely but may be inhibited by concurrent myelosuppressive chemotherapy like temozolomide (TMZ), which produces a survival benefit in GBM. A phase II, multicenter trial was undertaken to assess the immunogenicity of an experimental EGFRvIII-targeted peptide vaccine in patients with GBM undergoing treatment with serial cycles of standard-dose (STD) (200 mg/m(2) per 5 days) or dose-intensified (DI) TMZ (100 mg/m(2) per 21 days). All patients receiving STD TMZ exhibited at least a transient grade 2 lymphopenia, whereas those receiving DI TMZ exhibited a sustained grade 3 lymphopenia (<500 cells/μL). CD3(+) T-cell (P = .005) and B-cell (P = .004) counts were reduced significantly only in the DI cohort. Patients in the DI cohort had an increase in the proportion of immunosuppressive regulatory T cells (T(Reg); P = .008). EGFRvIII-specific immune responses developed in all patients treated with either regimen, but the DI TMZ regimen produced humoral (P = .037) and delayed-type hypersensitivity responses (P = .036) of greater magnitude. EGFRvIII-expressing tumor cells were also eradicated in nearly all patients (91.6%; CI(95): 64.0%-99.8%; P < .0001). The median progression-free survival (15.2 months; CI(95): 11.0-18.5 months; hazard ratio [HR] = 0.35; P = .024) and overall survival (23.6 months; CI(95): 18.5-33.1 months; HR = 0.23; P = .019) exceeded those of historical controls matched for entry criteria and adjusted for known prognostic factors. EGFRvIII-targeted vaccination induces patient immune responses despite therapeutic TMZ-induced lymphopenia and eliminates EGFRvIII-expressing tumor cells without autoimmunity.

Authors
Sampson, JH; Aldape, KD; Archer, GE; Coan, A; Desjardins, A; Friedman, AH; Friedman, HS; Gilbert, MR; Herndon, JE; McLendon, RE; Mitchell, DA; Reardon, DA; Sawaya, R; Schmittling, R; Shi, W; Vredenburgh, JJ; Bigner, DD; Heimberger, AB
MLA Citation
Sampson, JH, Aldape, KD, Archer, GE, Coan, A, Desjardins, A, Friedman, AH, Friedman, HS, Gilbert, MR, Herndon, JE, McLendon, RE, Mitchell, DA, Reardon, DA, Sawaya, R, Schmittling, R, Shi, W, Vredenburgh, JJ, Bigner, DD, and Heimberger, AB. "Greater chemotherapy-induced lymphopenia enhances tumor-specific immune responses that eliminate EGFRvIII-expressing tumor cells in patients with glioblastoma." Neuro Oncol 13.3 (March 2011): 324-333.
PMID
21149254
Source
pubmed
Published In
Neuro-Oncology
Volume
13
Issue
3
Publish Date
2011
Start Page
324
End Page
333
DOI
10.1093/neuonc/noq157

O6-Methylguanine-DNA Methytransferase (MGMT) Immunohistochemistry as a Predictor of Resistance to Temozolomide in Primary CNS Lymphoma.

Authors
Jiang, X; Reardon, DA; Desjardins, A; Vredenburgh, JJ; Quinn, JA; Austin, AD; Herndon, JE; McLendon, RE; Friedman, HS
MLA Citation
Jiang, X, Reardon, DA, Desjardins, A, Vredenburgh, JJ, Quinn, JA, Austin, AD, Herndon, JE, McLendon, RE, and Friedman, HS. "O6-Methylguanine-DNA Methytransferase (MGMT) Immunohistochemistry as a Predictor of Resistance to Temozolomide in Primary CNS Lymphoma." February 2011.
PMID
23686298
Source
wos-lite
Published In
Modern Pathology
Volume
24
Publish Date
2011
Start Page
382A
End Page
382A

O6-Methylguanine-DNA Methytransferase (MGMT) Immunohistochemistry as a Predictor of Resistance to Temozolomide in Primary CNS Lymphoma

Authors
Jiang, X; Reardon, DA; Desjardins, A; Vredenburgh, JJ; Quinn, JA; Austin, AD; Herndon, JE; McLendon, RE; Friedman, HS
MLA Citation
Jiang, X, Reardon, DA, Desjardins, A, Vredenburgh, JJ, Quinn, JA, Austin, AD, Herndon, JE, McLendon, RE, and Friedman, HS. "O6-Methylguanine-DNA Methytransferase (MGMT) Immunohistochemistry as a Predictor of Resistance to Temozolomide in Primary CNS Lymphoma." February 2011.
Source
wos-lite
Published In
Laboratory Investigation
Volume
91
Publish Date
2011
Start Page
382A
End Page
382A

Effect of CYP3A-inducing anti-epileptics on sorafenib exposure: results of a phase II study of sorafenib plus daily temozolomide in adults with recurrent glioblastoma.

Sorafenib, an oral VEGFR-2, Raf, PDGFR, c-KIT and Flt-3 inhibitor, is active against renal cell and hepatocellular carcinomas, and has recently demonstrated promising activity for lung and breast cancers. In addition, various protracted temozolomide dosing schedules have been evaluated as a strategy to further enhance its anti-tumor activity. We reasoned that sorafenib and protracted, daily temozolomide may provide complementary therapeutic benefit, and therefore performed a phase 2 trial among recurrent glioblastoma patients. Adult glioblastoma patients at any recurrence after standard temozolomide chemoradiotherapy received sorafenib (400 mg twice daily) and continuous daily temozolomide (50 mg/m²/day). Assessments were performed every eight weeks. The primary endpoint was progression-free survival at 6 months (PFS-6) and secondary end points were radiographic response, overall survival (OS), safety and sorafenib pharmacokinetics. Of 32 enrolled patients, 12 (38%) were on CYP3-A inducing anti-epileptics (EIAEDs), 17 (53%) had 2 or more prior progressions, 15 had progressed while receiving 5-day temozolomide, and 12 (38%) had failed either prior bevacizumab or VEGFR inhibitor therapy. The most common grade ≥ 3 toxicities were palmer-planter erythrodysesthesia (19%) and elevated amylase/lipase (13%). Sorafenib pharmacokinetic exposures were comparable on day 1 regardless of EIAED status, but significantly lower on day 28 for patients on EIAEDs (P = 0.0431). With a median follow-up of 93 weeks, PFS-6 was 9.4%. Only one patient (3%) achieved a partial response. In conclusion, sorafenib can be safely administered with daily temozolomide, but this regimen has limited activity for recurrent GBM. Co-administration of EIAEDs can lower sorafenib exposures in this population.

Authors
Reardon, DA; Vredenburgh, JJ; Desjardins, A; Peters, K; Gururangan, S; Sampson, JH; Marcello, J; Herndon, JE; McLendon, RE; Janney, D; Friedman, AH; Bigner, DD; Friedman, HS
MLA Citation
Reardon, DA, Vredenburgh, JJ, Desjardins, A, Peters, K, Gururangan, S, Sampson, JH, Marcello, J, Herndon, JE, McLendon, RE, Janney, D, Friedman, AH, Bigner, DD, and Friedman, HS. "Effect of CYP3A-inducing anti-epileptics on sorafenib exposure: results of a phase II study of sorafenib plus daily temozolomide in adults with recurrent glioblastoma." J Neurooncol 101.1 (January 2011): 57-66.
PMID
20443129
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
101
Issue
1
Publish Date
2011
Start Page
57
End Page
66
DOI
10.1007/s11060-010-0217-6

Erratum: Phase 2 pilot study of Pathfinders: A psychosocial intervention for cancer patients (Support Care Center DOI 10.1007/s00520-010-0823-z)

Authors
Abernethy, AP; II, JEH; Coan, A; Staley, T; Wheeler, JL; Rowe, K; Smith, SK; Shaw, H; Lyerly, HK
MLA Citation
Abernethy, AP, II, JEH, Coan, A, Staley, T, Wheeler, JL, Rowe, K, Smith, SK, Shaw, H, and Lyerly, HK. "Erratum: Phase 2 pilot study of Pathfinders: A psychosocial intervention for cancer patients (Support Care Center DOI 10.1007/s00520-010-0823-z)." Supportive Care in Cancer 19.3 (2011): 439--.
Source
scival
Published In
Supportive Care in Cancer
Volume
19
Issue
3
Publish Date
2011
Start Page
439-
DOI
10.1007/s00520-010-1076-6

Reply to M.S. Lesniak

Authors
Mehta, AI; Persson, O; II, JEH; Archer, GE; McLendon, R; Heimberger, AB; Mitchell, DA; Bigner, DD; Sampson, JH
MLA Citation
Mehta, AI, Persson, O, II, JEH, Archer, GE, McLendon, R, Heimberger, AB, Mitchell, DA, Bigner, DD, and Sampson, JH. "Reply to M.S. Lesniak." Journal of Clinical Oncology 29.22 (2011): 3105-3106.
Source
scival
Published In
Journal of Clinical Oncology
Volume
29
Issue
22
Publish Date
2011
Start Page
3105
End Page
3106
DOI
10.1200/JCO.2011.35.0256

Reply to M.C. Chamberlain

Authors
Heimberger, AB; Bigner, DD; II, JEH; Sampson, JH
MLA Citation
Heimberger, AB, Bigner, DD, II, JEH, and Sampson, JH. "Reply to M.C. Chamberlain." Journal of Clinical Oncology 29.17 (2011): e519-e520.
Source
scival
Published In
Journal of Clinical Oncology
Volume
29
Issue
17
Publish Date
2011
Start Page
e519
End Page
e520
DOI
10.1200/JCO.2010.34.1453

Resection of vestibular schwannomas

Authors
Sampson, JH; II, JEH
MLA Citation
Sampson, JH, and II, JEH. "Resection of vestibular schwannomas." Journal of Neurosurgery 114.5 (2011): 1216-1217.
PMID
21250806
Source
scival
Published In
Journal of neurosurgery
Volume
114
Issue
5
Publish Date
2011
Start Page
1216
End Page
1217
DOI
10.3171/2010.8.JNS10765

Phase II trial of bevacizumab and erlotinib in patients with recurrent malignant glioma.

Vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) signaling are established contributors to malignant glioma (MG) biology. We, therefore, evaluated bevacizumab, a humanized anti-VEGF monoclonal antibody, in combination with the EGFR tyrosine kinase inhibitor erlotinib, in this phase 2 study for recurrent MG patients (www.ClinicalTrials.gov, NCT00671970). Fifty-seven patients (n = 25, glioblastoma [GBM]; n = 32, anaplastic glioma [AG]) were enrolled. The primary endpoint was 6-month progression-free survival (PFS-6). Overall survival (OS), radiographic response, pharmacokinetics, and correlative biomarkers were the secondary endpoints. Patients were stratified based on the concurrent use of enzyme-inducing antiepileptic drugs (EIAEDs). Bevacizumab (10 mg/kg) was given intravenously every 2 weeks. Erlotinib was orally administered daily at 200 mg/day for patients not on EIAEDs and 500 mg/day for patients on EIAEDs. PFS-6 and median OS were 28% and 42 weeks for GBM patients and 44% and 71 weeks for AG patients, respectively. Twelve (48%) GBM patients and 10 (31%) AG patients achieved a radiographic response. Erlotinib pharmacokinetic exposures were comparable between EIAED and non-EIAED groups. Rash, mucositis, diarrhea, and fatigue were common but mostly grades 1 and 2. Among GBM patients, grade 3 rash, observed in 32%, was associated with survival benefit, whereas elevated hypoxia-inducible factor-2 alpha and VEGF receptor-2 levels were associated with poor survival. Bevacizumab plus erlotinib was adequately tolerated in recurrent MG patients. However, this regimen was associated with similar PFS benefit and radiographic response when compared with other historical bevacizumab-containing regimens.

Authors
Sathornsumetee, S; Desjardins, A; Vredenburgh, JJ; McLendon, RE; Marcello, J; Herndon, JE; Mathe, A; Hamilton, M; Rich, JN; Norfleet, JA; Gururangan, S; Friedman, HS; Reardon, DA
MLA Citation
Sathornsumetee, S, Desjardins, A, Vredenburgh, JJ, McLendon, RE, Marcello, J, Herndon, JE, Mathe, A, Hamilton, M, Rich, JN, Norfleet, JA, Gururangan, S, Friedman, HS, and Reardon, DA. "Phase II trial of bevacizumab and erlotinib in patients with recurrent malignant glioma." Neuro Oncol 12.12 (December 2010): 1300-1310.
PMID
20716591
Source
pubmed
Published In
Neuro-Oncology
Volume
12
Issue
12
Publish Date
2010
Start Page
1300
End Page
1310
DOI
10.1093/neuonc/noq099

Immunologic escape after prolonged progression-free survival with epidermal growth factor receptor variant III peptide vaccination in patients with newly diagnosed glioblastoma.

PURPOSE: Immunologic targeting of tumor-specific gene mutations may allow precise eradication of neoplastic cells without toxicity. Epidermal growth factor receptor variant III (EGFRvIII) is a constitutively activated and immunogenic mutation not expressed in normal tissues but widely expressed in glioblastoma multiforme (GBM) and other neoplasms. PATIENTS AND METHODS: A phase II, multicenter trial was undertaken to assess the immunogenicity of an EGFRvIII-targeted peptide vaccine and to estimate the progression-free survival (PFS) and overall survival (OS) of vaccinated patients with newly diagnosed EGFRvIII-expressing GBM with minimal residual disease. Intradermal vaccinations were given until toxicity or tumor progression was observed. Sample size was calculated to differentiate between PFS rates of 20% and 40% 6 months after vaccination. RESULTS: There were no symptomatic autoimmune reactions. The 6-month PFS rate after vaccination was 67% (95% CI, 40% to 83%) and after diagnosis was 94% (95% CI, 67% to 99%; n = 18). The median OS was 26.0 months (95% CI, 21.0 to 47.7 months). After adjustment for age and Karnofsky performance status, the OS of vaccinated patients was greater than that observed in a control group matched for eligibility criteria, prognostic factors, and temozolomide treatment (hazard ratio, 5.3; P = .0013; n = 17). The development of specific antibody (P = .025) or delayed-type hypersensitivity (P = .03) responses to EGFRvIII had a significant effect on OS. At recurrence, 82% (95% CI, 48% to 97%) of patients had lost EGFRvIII expression (P < .001). CONCLUSION: EGFRvIII-targeted vaccination in patients with GBM warrants investigation in a phase III, randomized trial.

Authors
Sampson, JH; Heimberger, AB; Archer, GE; Aldape, KD; Friedman, AH; Friedman, HS; Gilbert, MR; Herndon, JE; McLendon, RE; Mitchell, DA; Reardon, DA; Sawaya, R; Schmittling, RJ; Shi, W; Vredenburgh, JJ; Bigner, DD
MLA Citation
Sampson, JH, Heimberger, AB, Archer, GE, Aldape, KD, Friedman, AH, Friedman, HS, Gilbert, MR, Herndon, JE, McLendon, RE, Mitchell, DA, Reardon, DA, Sawaya, R, Schmittling, RJ, Shi, W, Vredenburgh, JJ, and Bigner, DD. "Immunologic escape after prolonged progression-free survival with epidermal growth factor receptor variant III peptide vaccination in patients with newly diagnosed glioblastoma." J Clin Oncol 28.31 (November 1, 2010): 4722-4729.
PMID
20921459
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
28
Issue
31
Publish Date
2010
Start Page
4722
End Page
4729
DOI
10.1200/JCO.2010.28.6963

SURVIVAL AND TOXICITY UPDATE OF THE PHASE 2 TRIAL OF BEVACIZUMAB (BV) IN COMBINATION WITH TEMOZOLOMIDE (TMZ) AND RADIATION THERAPY (RT) FOLLOWED BY BV, TMZ, AND IRINOTECAN (CPT-11) FOR NEWLY DIAGNOSED GLIOBLASTOMA MULTIFORME (GBM) PATIENTS

Authors
Desjardins, A; Reardon, DA; Peters, KB; II, HJE; Kirkpatrick, JP; Friedman, HS; Vredenburgh, JJ
MLA Citation
Desjardins, A, Reardon, DA, Peters, KB, II, HJE, Kirkpatrick, JP, Friedman, HS, and Vredenburgh, JJ. "SURVIVAL AND TOXICITY UPDATE OF THE PHASE 2 TRIAL OF BEVACIZUMAB (BV) IN COMBINATION WITH TEMOZOLOMIDE (TMZ) AND RADIATION THERAPY (RT) FOLLOWED BY BV, TMZ, AND IRINOTECAN (CPT-11) FOR NEWLY DIAGNOSED GLIOBLASTOMA MULTIFORME (GBM) PATIENTS." November 2010.
Source
wos-lite
Published In
Neuro-Oncology
Volume
12
Publish Date
2010
Start Page
77
End Page
77

Peak oxygen consumption and long-term all-cause mortality in nonsmall cell lung cancer.

BACKGROUND: Identifying strong markers of prognosis is critical to optimize treatment and survival outcomes in patients with nonsmall cell lung cancer (NSCLC). The authors investigated the prognostic significance of preoperative cardiorespiratory fitness (peak oxygen consumption [VO(2peak)]) among operable candidates with NSCLC. METHODS: By using a prospective design, 398 patients with potentially resectable NSCLC enrolled in Cancer and Leukemia Group B 9238 were recruited between 1993 and 1998. Participants performed a cardiopulmonary exercise test to assess VO(2peak) and were observed until death or June 2008. Cox proportional models were used to estimate the risk of all-cause mortality according to cardiorespiratory fitness category defined by VO(2peak) tertiles (<0.96 of 0.96-1.29/>1.29 L/min⁻¹) with adjustment for age, sex, and performance status. RESULTS: Median follow-up was 30.8 months; 294 deaths were reported during this period. Compared with patients achieving a VO(2peak) <0.96 L/min⁻¹, the adjusted hazard ratio (HR) for all-cause mortality was 0.64 (95% confidence interval [CI], 0.46-0.88) for a VO(2peak) of 0.96 to 1.29 L/min⁻¹, and 0.56 (95% CI, 0.39-0.80) for a VO(2peak) of >1.29 L/min⁻¹) (P(trend) = .0037). The corresponding HRs for resected patients were 0.66 (95% CI, 0.46-0.95) and 0.59 (95% CI, 0.40-0.89) relative to the lowest VO(2peak) category (P(trend) = .0247), respectively. For nonresected patients, the HRs were 0.78 (95% CI, 0.34-1.79) and 0.39 (95% CI, 0.16-0.94) relative to the lowest category (P(trend) = .0278). CONCLUSIONS: VO(2peak) is a strong independent predictor of survival in NSCLC that may complement traditional markers of prognosis to improve risk stratification and prognostication.

Authors
Jones, LW; Watson, D; Herndon, JE; Eves, ND; Haithcock, BE; Loewen, G; Kohman, L
MLA Citation
Jones, LW, Watson, D, Herndon, JE, Eves, ND, Haithcock, BE, Loewen, G, and Kohman, L. "Peak oxygen consumption and long-term all-cause mortality in nonsmall cell lung cancer." Cancer 116.20 (October 15, 2010): 4825-4832.
PMID
20597134
Source
pubmed
Published In
Cancer
Volume
116
Issue
20
Publish Date
2010
Start Page
4825
End Page
4832
DOI
10.1002/cncr.25396

Rationale and design of the Exercise Intensity Trial (EXCITE): A randomized trial comparing the effects of moderate versus moderate to high-intensity aerobic training in women with operable breast cancer.

BACKGROUND: The Exercise Intensity Trial (EXcITe) is a randomized trial to compare the efficacy of supervised moderate-intensity aerobic training to moderate to high-intensity aerobic training, relative to attention control, on aerobic capacity, physiologic mechanisms, patient-reported outcomes, and biomarkers in women with operable breast cancer following the completion of definitive adjuvant therapy. METHODS/DESIGN: Using a single-center, randomized design, 174 postmenopausal women (58 patients/study arm) with histologically confirmed, operable breast cancer presenting to Duke University Medical Center (DUMC) will be enrolled in this trial following completion of primary therapy (including surgery, radiation therapy, and chemotherapy). After baseline assessments, eligible participants will be randomized to one of two supervised aerobic training interventions (moderate-intensity or moderate/high-intensity aerobic training) or an attention-control group (progressive stretching). The aerobic training interventions will include 150 mins.wk⁻¹ of supervised treadmill walking per week at an intensity of 60%-70% (moderate-intensity) or 60% to 100% (moderate to high-intensity) of the individually determined peak oxygen consumption (VO₂peak) between 20-45 minutes/session for 16 weeks. The progressive stretching program will be consistent with the exercise interventions in terms of program length (16 weeks), social interaction (participants will receive one-on-one instruction), and duration (20-45 mins/session). The primary study endpoint is VO₂peak, as measured by an incremental cardiopulmonary exercise test. Secondary endpoints include physiologic determinants that govern VO₂peak, patient-reported outcomes, and biomarkers associated with breast cancer recurrence/mortality. All endpoints will be assessed at baseline and after the intervention (16 weeks). DISCUSSION: EXCITE is designed to investigate the intensity of aerobic training required to induce optimal improvements in VO₂peak and other pertinent outcomes in women who have completed definitive adjuvant therapy for operable breast cancer. Overall, this trial will inform and refine exercise guidelines to optimize recovery in breast and other cancer survivors following the completion of primary cytotoxic therapy. TRIAL REGISTRATION: NCT01186367.

Authors
Jones, LW; Douglas, PS; Eves, ND; Marcom, PK; Kraus, WE; Herndon, JE; Inman, BA; Allen, JD; Peppercorn, J
MLA Citation
Jones, LW, Douglas, PS, Eves, ND, Marcom, PK, Kraus, WE, Herndon, JE, Inman, BA, Allen, JD, and Peppercorn, J. "Rationale and design of the Exercise Intensity Trial (EXCITE): A randomized trial comparing the effects of moderate versus moderate to high-intensity aerobic training in women with operable breast cancer. (Published online)" BMC Cancer 10 (October 6, 2010): 531-.
Website
http://hdl.handle.net/10161/4358
PMID
20925920
Source
pubmed
Published In
BMC Cancer
Volume
10
Publish Date
2010
Start Page
531
DOI
10.1186/1471-2407-10-531

Long-term safety of combined intracerebral delivery of free gadolinium and targeted chemotherapeutic agent PRX321.

OBJECTIVES: While convection enhanced delivery (CED) is an effective delivery method that bypasses the blood-brain barrier, its utility is limited by infusate leakage due to catheter misplacement. Therefore, it is critical to evaluate drug distribution during CED infusion. Gadolinium conjugated to diethylenetriamine penta-acetic acid (Gd-DTPA) is a common, readily available MRI contrast agent, which may be able to predict and actively monitor drug distribution. In this study, we assess the long-term safety and toxicity of intracerebrally infused Gd-DTPA along with an experimental targeted agent PRX321. METHODS: Fifty-four immunocompetent rats were implanted with intracerebral cannulas linked to subcutaneously placed osmotic pumps. After pump implantation, the rats were randomized into six groups of nine rats each in order to assess the toxicities of six different concentrations of human serum albumin (HSA) with and without Gd-DTPA and PRX321. The rats were monitored clinically for 6 weeks before they were autopsied and assessed for histological toxicity to their central nervous system (CNS). RESULTS: There was one unexplained death in a group infusing low concentration HSA, Gd-DTPA and PRX321. Upon microscopic examination of the CNS in that animal, no unexpected histological toxicity was found. Additionally, there were no signs of clinical or histological toxicity in any of the remaining rats, which all survived until the end of the 6 week observation period. DISCUSSION: Free Gd-DTPA can be safely infused via CED in a pre-clinical animal model. Future studies should include its use in predicting and actively monitoring CED drug infusions in early phase human clinical trials.

Authors
Ding, D; Kanaly, CW; Cummings, TJ; Herndon, JE; Raghavan, R; Sampson, JH
MLA Citation
Ding, D, Kanaly, CW, Cummings, TJ, Herndon, JE, Raghavan, R, and Sampson, JH. "Long-term safety of combined intracerebral delivery of free gadolinium and targeted chemotherapeutic agent PRX321." Neurol Res 32.8 (October 2010): 810-815.
PMID
20021739
Source
pubmed
Published In
Neurological Research
Volume
32
Issue
8
Publish Date
2010
Start Page
810
End Page
815
DOI
10.1179/174367509X12581069052090

Validation of the Patient Care Monitor (Version 2.0): a review of system assessment instrument for cancer patients.

CONTEXT: The Patient Care Monitor (PCM) is a review of systems survey delivered by means of an electronic patient-reported outcomes (ePRO) data capture system that uses wireless tablet computers. Although the PCM 1.0 is validated, the updated PCM 2.0 has not been validated nor tested in the academic setting. OBJECTIVES: To validate and test the PCM 2.0 in three cancer populations. METHODS: Two hundred seventy-five individuals participated in three clinical trials enrolling breast (n=65), gastrointestinal (n=113), and lung (n=97) cancer patients. Internal consistency was evaluated using Cronbach's alpha coefficients calculated for six PCM subscales (general physical symptoms, treatment side effects, distress, despair, impaired performance, and impaired ambulation) and a Quality-of-Life Index. Construct validity was evaluated through Pearson's correlation between PCM subscales and subscales of the Functional Assessment of Cancer Therapy--General (FACT-G), the M.D. Anderson Symptom Inventory (MDASI), and the Functional Assessment of Chronic Illness Therapy--Fatigue (FACIT-F). The participants had the following characteristics: mean age was 58 years (standard deviation: 11), 52% were females, 79% were whites, 17% were blacks, 62% had no college degree, and 78% had metastatic or recurrent disease. RESULTS: Raw and normalized scores for PCM 2.0 subscales were internally consistent across study cohorts. PCM 2.0 subscales correlated significantly (P<0.05) with the corresponding subscales on FACT-G, MDASI, and FACIT-F, with the exception of FACT-G social well-being, particularly for the lung cancer population. These correlations demonstrated construct validity. PCM 2.0 results followed expected patterns by cancer etiology. Prior reports demonstrate patient satisfaction with PCM 2.0. CONCLUSION: Within three unique academic oncology populations, PCM 2.0 is a valid ePRO instrument for assessing symptoms with seven patient-centered subscale or index domains.

Authors
Abernethy, AP; Zafar, SY; Uronis, H; Wheeler, JL; Coan, A; Rowe, K; Shelby, RA; Fowler, R; Herndon, JE
MLA Citation
Abernethy, AP, Zafar, SY, Uronis, H, Wheeler, JL, Coan, A, Rowe, K, Shelby, RA, Fowler, R, and Herndon, JE. "Validation of the Patient Care Monitor (Version 2.0): a review of system assessment instrument for cancer patients." J Pain Symptom Manage 40.4 (October 2010): 545-558.
PMID
20579839
Source
pubmed
Published In
Journal of Pain and Symptom Management
Volume
40
Issue
4
Publish Date
2010
Start Page
545
End Page
558
DOI
10.1016/j.jpainsymman.2010.01.017

Effect of palliative oxygen versus room air in relief of breathlessness in patients with refractory dyspnoea: a double-blind, randomised controlled trial.

BACKGROUND: Palliative oxygen therapy is widely used for treatment of dyspnoea in individuals with life-limiting illness who are ineligible for long-term oxygen therapy. We assessed the effectiveness of oxygen compared with room air delivered by nasal cannula for relief of breathlessness in this population of patients. METHODS: Adults from outpatient clinics at nine sites in Australia, the USA, and the UK were eligible for enrolment in this double-blind, randomised controlled trial if they had life-limiting illness, refractory dyspnoea, and partial pressure of oxygen in arterial blood (PaO(2)) more than 7.3 kPa. Participants were randomly assigned in a 1:1 ratio by a central computer-generated system to receive oxygen or room air via a concentrator through a nasal cannula at 2 L per min for 7 days. Participants were instructed to use the concentrator for at least 15 h per day. The randomisation sequence was stratified by baseline PaO(2) with balanced blocks of four patients. The primary outcome measure was breathlessness (0-10 numerical rating scale [NRS]), measured twice a day (morning and evening). All randomised patients who completed an assessment were included in the primary analysis for that data point (no data were imputed). This study is registered, numbers NCT00327873 and ISRCTN67448752. FINDINGS: 239 participants were randomly assigned to treatment (oxygen, n=120; room air, n=119). 112 (93%) patients assigned to receive oxygen and 99 (83%) assigned to receive room air completed all 7 days of assessments. From baseline to day 6, mean morning breathlessness changed by -0.9 points (95% CI -1.3 to -0.5) in patients assigned to receive oxygen and by -0.7 points (-1.2 to -0.2) in patients assigned to receive room air (p=0.504). Mean evening breathlessness changed by -0.3 points (-0.7 to 0.1) in the oxygen group and by -0.5 (-0.9 to -0.1) in the room air group (p=0.554). The frequency of side-effects did not differ between groups. Extreme drowsiness was reported by 12 (10%) of 116 patients assigned to receive oxygen compared with 14 (13%) of 108 patients assigned to receive room air. Two (2%) patients in the oxygen group reported extreme symptoms of nasal irritation compared with seven (6%) in the room air group. One patient reported an extremely troublesome nose bleed (oxygen group). INTERPRETATION: Since oxygen delivered by a nasal cannula provides no additional symptomatic benefit for relief of refractory dyspnoea in patients with life-limiting illness compared with room air, less burdensome strategies should be considered after brief assessment of the effect of oxygen therapy on the individual patient. FUNDING: US National Institutes of Health, Australian National Health and Medical Research Council, Duke Institute for Care at the End of Life, and Doris Duke Charitable Foundation.

Authors
Abernethy, AP; McDonald, CF; Frith, PA; Clark, K; Herndon, JE; Marcello, J; Young, IH; Bull, J; Wilcock, A; Booth, S; Wheeler, JL; Tulsky, JA; Crockett, AJ; Currow, DC
MLA Citation
Abernethy, AP, McDonald, CF, Frith, PA, Clark, K, Herndon, JE, Marcello, J, Young, IH, Bull, J, Wilcock, A, Booth, S, Wheeler, JL, Tulsky, JA, Crockett, AJ, and Currow, DC. "Effect of palliative oxygen versus room air in relief of breathlessness in patients with refractory dyspnoea: a double-blind, randomised controlled trial." Lancet 376.9743 (September 4, 2010): 784-793.
PMID
20816546
Source
pubmed
Published In
The Lancet
Volume
376
Issue
9743
Publish Date
2010
Start Page
784
End Page
793
DOI
10.1016/S0140-6736(10)61115-4

MRP3: a molecular target for human glioblastoma multiforme immunotherapy.

BACKGROUND: Glioblastoma multiforme (GBM) is refractory to conventional therapies. To overcome the problem of heterogeneity, more brain tumor markers are required for prognosis and targeted therapy. We have identified and validated a promising molecular therapeutic target that is expressed by GBM: human multidrug-resistance protein 3 (MRP3). METHODS: We investigated MRP3 by genetic and immunohistochemical (IHC) analysis of human gliomas to determine the incidence, distribution, and localization of MRP3 antigens in GBM and their potential correlation with survival. To determine MRP3 mRNA transcript and protein expression levels, we performed quantitative RT-PCR, raising MRP3-specific antibodies, and IHC analysis with biopsies of newly diagnosed GBM patients. We used univariate and multivariate analyses to assess the correlation of RNA expression and IHC of MRP3 with patient survival, with and without adjustment for age, extent of resection, and KPS. RESULTS: Real-time PCR results from 67 GBM biopsies indicated that 59/67 (88%) samples highly expressed MRP3 mRNA transcripts, in contrast with minimal expression in normal brain samples. Rabbit polyvalent and murine monoclonal antibodies generated against an extracellular span of MRP3 protein demonstrated reactivity with defined MRP3-expressing cell lines and GBM patient biopsies by Western blotting and FACS analyses, the latter establishing cell surface MRP3 protein expression. IHC evaluation of 46 GBM biopsy samples with anti-MRP3 IgG revealed MRP3 in a primarily membranous and cytoplasmic pattern in 42 (91%) of the 46 samples. Relative RNA expression was a strong predictor of survival for newly diagnosed GBM patients. Hazard of death for GBM patients with high levels of MRP3 RNA expression was 2.71 (95% CI: 1.54-4.80) times that of patients with low/moderate levels (p = 0.002). CONCLUSIONS: Human GBMs overexpress MRP3 at both mRNA and protein levels, and elevated MRP3 mRNA levels in GBM biopsy samples correlated with a higher risk of death. These data suggest that the tumor-associated antigen MRP3 has potential use for prognosis and as a target for malignant glioma immunotherapy.

Authors
Kuan, C-T; Wakiya, K; Herndon, JE; Lipp, ES; Pegram, CN; Riggins, GJ; Rasheed, A; Szafranski, SE; McLendon, RE; Wikstrand, CJ; Bigner, DD
MLA Citation
Kuan, C-T, Wakiya, K, Herndon, JE, Lipp, ES, Pegram, CN, Riggins, GJ, Rasheed, A, Szafranski, SE, McLendon, RE, Wikstrand, CJ, and Bigner, DD. "MRP3: a molecular target for human glioblastoma multiforme immunotherapy. (Published online)" BMC Cancer 10 (September 1, 2010): 468-.
Website
http://hdl.handle.net/10161/4357
PMID
20809959
Source
pubmed
Published In
BMC Cancer
Volume
10
Publish Date
2010
Start Page
468
DOI
10.1186/1471-2407-10-468

Poor drug distribution as a possible explanation for the results of the PRECISE trial.

OBJECT: Convection-enhanced delivery (CED) is a novel intracerebral drug delivery technique with considerable promise for delivering therapeutic agents throughout the CNS. Despite this promise, Phase III clinical trials employing CED have failed to meet clinical end points. Although this may be due to inactive agents or a failure to rigorously validate drug targets, the authors have previously demonstrated that catheter positioning plays a major role in drug distribution using this technique. The purpose of the present work was to retrospectively analyze the expected drug distribution based on catheter positioning data available from the CED arm of the PRECISE trial. METHODS: Data on catheter positioning from all patients randomized to the CED arm of the PRECISE trial were available for analyses. BrainLAB iPlan Flow software was used to estimate the expected drug distribution. RESULTS: Only 49.8% of catheters met all positioning criteria. Still, catheter positioning score (hazard ratio 0.93, p = 0.043) and the number of optimally positioned catheters (hazard ratio 0.72, p = 0.038) had a significant effect on progression-free survival. Estimated coverage of relevant target volumes was low, however, with only 20.1% of the 2-cm penumbra surrounding the resection cavity covered on average. Although tumor location and resection cavity volume had no effect on coverage volume, estimations of drug delivery to relevant target volumes did correlate well with catheter score (p < 0.003), and optimally positioned catheters had larger coverage volumes (p < 0.002). Only overall survival (p = 0.006) was higher for investigators considered experienced after adjusting for patient age and Karnofsky Performance Scale score. CONCLUSIONS: The potential efficacy of drugs delivered by CED may be severely constrained by ineffective delivery in many patients. Routine use of software algorithms and alternative catheter designs and infusion parameters may improve the efficacy of drugs delivered by CED.

Authors
Sampson, JH; Archer, G; Pedain, C; Wembacher-Schröder, E; Westphal, M; Kunwar, S; Vogelbaum, MA; Coan, A; Herndon, JE; Raghavan, R; Brady, ML; Reardon, DA; Friedman, AH; Friedman, HS; Rodríguez-Ponce, MI; Chang, SM; Mittermeyer, S; Croteau, D; Puri, RK; PRECISE Trial Investigators,
MLA Citation
Sampson, JH, Archer, G, Pedain, C, Wembacher-Schröder, E, Westphal, M, Kunwar, S, Vogelbaum, MA, Coan, A, Herndon, JE, Raghavan, R, Brady, ML, Reardon, DA, Friedman, AH, Friedman, HS, Rodríguez-Ponce, MI, Chang, SM, Mittermeyer, S, Croteau, D, Puri, RK, and PRECISE Trial Investigators, . "Poor drug distribution as a possible explanation for the results of the PRECISE trial." J Neurosurg 113.2 (August 2010): 301-309.
PMID
20020841
Source
pubmed
Published In
Journal of neurosurgery
Volume
113
Issue
2
Publish Date
2010
Start Page
301
End Page
309
DOI
10.3171/2009.11.JNS091052

Informational needs assessment of non-Hodgkin lymphoma survivors and their physicians.

Authors
Friedman, DR; Coan, AD; Smith, SK; Herndon, JE; Abernethy, AP
MLA Citation
Friedman, DR, Coan, AD, Smith, SK, Herndon, JE, and Abernethy, AP. "Informational needs assessment of non-Hodgkin lymphoma survivors and their physicians." Am J Hematol 85.7 (July 2010): 528-532. (Letter)
PMID
20575038
Source
pubmed
Published In
American Journal of Hematology
Volume
85
Issue
7
Publish Date
2010
Start Page
528
End Page
532
DOI
10.1002/ajh.21725

Phase 2 pilot study of Pathfinders: a psychosocial intervention for cancer patients.

PURPOSE: Pathfinders is a multi-faceted psychosocial care program for cancer patients; it was developed in community oncology and adapted to the academic oncology setting. This prospective, single-arm, phase 2 pilot study examined the acceptability and feasibility of Pathfinders for women with metastatic breast cancer. METHODS: Over 3 months, participants completed patient-reported surveys including the Patient Care Monitor (PCM, review of systems), Functional Assessment of Chronic Illness Therapy-Breast Cancer (FACT-B), Self Efficacy, and a single-item survey asking patients whether the program was helpful to them. A technology-based data collection system was used to capture electronic patient-reported outcomes at point of care, report symptoms in real time to clinicians, and collect warehouse data to provide a detailed longitudinal picture of the patient experience when receiving Pathfinders. RESULTS: Participants (n = 50) were: mean age 51 (SD 11); 76% white, 20% black; 74% married; 50% college degree. Forty-two (n = 42) patients completed baseline and 3-month assessments. Statistically significant improvements (all P < 0.05) occurred in PCM subscales for Distress (mean [SE] = -3.42 [1.21]), Despair (-4.53 [1.56]), and Quality of Life (2.88 [0.97]), and the FACT-B Emotional Wellbeing subscale (2.07 [0.46]). Of the 29 participants asked if Pathfinders was helpful, 27 (93%) responded positively and two did not respond. Other instruments measuring symptoms, quality of life, and self-efficacy showed improvement. CONCLUSIONS: In a phase 2 pilot study, Pathfinders was helpful to patients and is feasible in an academic medical center. Follow-up data collected at the 3-month assessment suggest that the program impacts various psychological outcomes, notably distress and despair.

Authors
Abernethy, AP; Herndon, JE; Coan, A; Staley, T; Wheeler, JL; Rowe, K; Smith, SK; Shaw, H; Lyerly, HK
MLA Citation
Abernethy, AP, Herndon, JE, Coan, A, Staley, T, Wheeler, JL, Rowe, K, Smith, SK, Shaw, H, and Lyerly, HK. "Phase 2 pilot study of Pathfinders: a psychosocial intervention for cancer patients." Support Care Cancer 18.7 (July 2010): 893-898.
PMID
20143102
Source
pubmed
Published In
Supportive Care in Cancer
Volume
18
Issue
7
Publish Date
2010
Start Page
893
End Page
898
DOI
10.1007/s00520-010-0823-z

Phase I trial of the addition of oral topotecan to standard 5-day temozolomide for malignant gliomas

Authors
Kirkpatrick, J; Vredenburgh, JJ; Reardon, DA; Desjardins, A; Peters, K; Gururangan, S; Herndon, JE; Marceilo, J; Woodring, S; Friedman, HS
MLA Citation
Kirkpatrick, J, Vredenburgh, JJ, Reardon, DA, Desjardins, A, Peters, K, Gururangan, S, Herndon, JE, Marceilo, J, Woodring, S, and Friedman, HS. "Phase I trial of the addition of oral topotecan to standard 5-day temozolomide for malignant gliomas." JOURNAL OF CLINICAL ONCOLOGY 28.15 (May 20, 2010).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
28
Issue
15
Publish Date
2010

CYP3A-inducing antiepileptics decrease sorafenib exposures: Results of a phase II study in adults with recurrent glioblastoma.

Authors
Gururangan, S; Vredenburgh, JJ; Desjardins, A; Peters, K; Herndon, JE; McLendon, RE; Janney, D; Friedman, HS; Reardon, DA
MLA Citation
Gururangan, S, Vredenburgh, JJ, Desjardins, A, Peters, K, Herndon, JE, McLendon, RE, Janney, D, Friedman, HS, and Reardon, DA. "CYP3A-inducing antiepileptics decrease sorafenib exposures: Results of a phase II study in adults with recurrent glioblastoma." JOURNAL OF CLINICAL ONCOLOGY 28.15 (May 20, 2010).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
28
Issue
15
Publish Date
2010

Phase II trial of bevacizumab plus erlotinib for patients with recurrent malignant gliomas: Final results.

Authors
Sathornsumetee, S; Desjardins, A; Vredenburgh, JJ; McLendon, RE; Marcello, J; Herndon, JE; Norfleet, J; Gururangan, S; Friedman, HS; Reardon, DA
MLA Citation
Sathornsumetee, S, Desjardins, A, Vredenburgh, JJ, McLendon, RE, Marcello, J, Herndon, JE, Norfleet, J, Gururangan, S, Friedman, HS, and Reardon, DA. "Phase II trial of bevacizumab plus erlotinib for patients with recurrent malignant gliomas: Final results." JOURNAL OF CLINICAL ONCOLOGY 28.15 (May 20, 2010).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
28
Issue
15
Publish Date
2010

Bevacizumab (BEV) in combination with temozolomide (TMZ) and radiation therapy (XRT) followed by BEV, TMZ, and irinotecan for newly diagnosed glioblastoma multiforme (GBM)

Authors
Vredenburgh, JJ; Desjardins, A; Reardon, DA; Peters, K; Kirkpatrick, J; Herndon, JE; Marcello, J; Bailey, L; Threatt, S; Friedman, HS
MLA Citation
Vredenburgh, JJ, Desjardins, A, Reardon, DA, Peters, K, Kirkpatrick, J, Herndon, JE, Marcello, J, Bailey, L, Threatt, S, and Friedman, HS. "Bevacizumab (BEV) in combination with temozolomide (TMZ) and radiation therapy (XRT) followed by BEV, TMZ, and irinotecan for newly diagnosed glioblastoma multiforme (GBM)." JOURNAL OF CLINICAL ONCOLOGY 28.15 (May 20, 2010).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
28
Issue
15
Publish Date
2010

Phase I trial of vandetanib and oral etoposide (VP-16) for recurrent malignant gliomas (MG).

Authors
Brickhouse, A; Vredenburgh, JJ; Gururangan, S; Reardon, DA; Desjardins, A; Peters, K; Herndon, JE; Norfleet, J; Marcello, J; Friedman, HS
MLA Citation
Brickhouse, A, Vredenburgh, JJ, Gururangan, S, Reardon, DA, Desjardins, A, Peters, K, Herndon, JE, Norfleet, J, Marcello, J, and Friedman, HS. "Phase I trial of vandetanib and oral etoposide (VP-16) for recurrent malignant gliomas (MG)." JOURNAL OF CLINICAL ONCOLOGY 28.15 (May 20, 2010).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
28
Issue
15
Publish Date
2010

Long-term survival from the initial trial of bevacizumab and irinotecan.

Authors
Desjardins, A; Vredenburgh, JJ; Reardon, DA; Herndon, JE; Marcello, J; Peters, K; Gururangan, S; Sathornsumetee, S; Rich, JN; Friedman, HS
MLA Citation
Desjardins, A, Vredenburgh, JJ, Reardon, DA, Herndon, JE, Marcello, J, Peters, K, Gururangan, S, Sathornsumetee, S, Rich, JN, and Friedman, HS. "Long-term survival from the initial trial of bevacizumab and irinotecan." JOURNAL OF CLINICAL ONCOLOGY 28.15 (May 20, 2010).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
28
Issue
15
Publish Date
2010

Convection-enhanced delivery of free gadolinium with the recombinant immunotoxin MR1-1.

A major obstacle in glioblastoma (GBM) therapy is the restrictive nature of the blood-brain barrier (BBB). Convection-enhanced delivery (CED) is a novel method of drug administration which allows direct parenchymal infusion of therapeutics, bypassing the BBB. MR1-1 is a novel recombinant immunotoxin that targets the GBM tumor-specific antigen EGFRvIII and can be delivered via CED infusion. However, drug distribution via CED varies dramatically, which necessitates active monitoring. Gadolinium conjugated to diethylenetriamine penta-acetic acid (Gd-DTPA) is a commonly used MRI contrast agent which can be co-infused with therapies using CED and may be useful in monitoring infusion leak and early distribution. Forty immunocompetent rats were implanted with intracerebral cannulas that were connected to osmotic pumps and subsequently randomized into four groups that each received 0.2% human serum albumin (HSA) mixed with a different experimental infusion: (1) 25 ng/ml MR1-1; (2) 0.1 micromol/ml Gd-DTPA; (3) 25 ng/ml MR1-1 and 0.1 micromol/ml Gd-DTPA; (4) 250 ng/ml MR1-1 and 0.1 micromol/ml Gd-DTPA. The rats were monitored clinically for 6 weeks then necropsied and histologically assessed for CNS toxicity. All rats survived the entirety of the study without clinical or histological toxicity attributable to the study drugs. There was no statistically significant difference in weight change over time among groups (P > 0.999). MR1-1 co-infused with Gd-DTPA via CED is safe in the long-term setting in a pre-clinical animal model. Our data supports the use of Gd-DTPA, as a surrogate tracer, co-infused with MR1-1 for drug distribution monitoring in patients with GBM.

Authors
Ding, D; Kanaly, CW; Bigner, DD; Cummings, TJ; Herndon, JE; Pastan, I; Raghavan, R; Sampson, JH
MLA Citation
Ding, D, Kanaly, CW, Bigner, DD, Cummings, TJ, Herndon, JE, Pastan, I, Raghavan, R, and Sampson, JH. "Convection-enhanced delivery of free gadolinium with the recombinant immunotoxin MR1-1." J Neurooncol 98.1 (May 2010): 1-7.
PMID
19898744
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
98
Issue
1
Publish Date
2010
Start Page
1
End Page
7
DOI
10.1007/s11060-009-0046-7

Effect of aerobic exercise on tumor physiology in an animal model of human breast cancer.

Recent epidemiologic studies report that regular exercise may be associated with substantial reductions in cancer-specific and all-cause mortality following a breast cancer diagnosis. The mechanisms underlying this relationship have not been identified. We investigated the effects of long-term voluntary wheel running on growth and progression using an animal model of human breast cancer. We also examined effects on the central features of tumor physiology, including markers of tumor blood perfusion/vascularization, hypoxia, angiogenesis, and metabolism. Athymic female mice fed a high-fat diet were orthotopically (direct into the mammary fat pad) implanted with human breast cancer cells (MDA-MB-231 at 1 x 10(6)) into the right dorsal mammary fat pad and randomly assigned (1:1) to voluntary wheel running (n = 25) or a nonintervention (sedentary) control group (n = 25). Tumor volume was measured every three days using digital calipers. All experimental animals were killed when tumor volume reached > or = 1,500 mm(3). Kaplan-Meier (KM) analysis indicated that tumor growth (survival) was comparable between the experimental groups (exercise 44 days vs. control 48 days; KM proportional hazard ratio = 1.41, 95% confidence interval, 0.77-2.58, P = 0.14). However, tumors from exercising animals had significantly improved blood perfusion/vascularization relative to the sedentary control group (P < 0.05). Histological analyses indicated that intratumoral hypoxia levels (as assessed by hypoxia-inducible factor 1) were significantly higher in the exercise group relative to sedentary control (P < 0.05). Aerobic exercise can significantly increase intratumoral vascularization, leading to "normalization" of the tissue microenvironment in human breast tumors. Such findings may have important implications for inhibiting tumor metastasis and improving the efficacy of conventional cancer therapies.

Authors
Jones, LW; Viglianti, BL; Tashjian, JA; Kothadia, SM; Keir, ST; Freedland, SJ; Potter, MQ; Moon, EJ; Schroeder, T; Herndon, JE; Dewhirst, MW
MLA Citation
Jones, LW, Viglianti, BL, Tashjian, JA, Kothadia, SM, Keir, ST, Freedland, SJ, Potter, MQ, Moon, EJ, Schroeder, T, Herndon, JE, and Dewhirst, MW. "Effect of aerobic exercise on tumor physiology in an animal model of human breast cancer." J Appl Physiol (1985) 108.2 (February 2010): 343-348.
PMID
19959769
Source
pubmed
Published In
Journal of applied physiology (Bethesda, Md. : 1985)
Volume
108
Issue
2
Publish Date
2010
Start Page
343
End Page
348
DOI
10.1152/japplphysiol.00424.2009

Patterns of Recurrence in Melanoma and the Impact on Survival

Authors
De Rosa, N; II, HJE; Marcello, J; Tyler, DS; Scheri, RP; Pruitt, SK; Wheeler, JL; Abernethy, AP
MLA Citation
De Rosa, N, II, HJE, Marcello, J, Tyler, DS, Scheri, RP, Pruitt, SK, Wheeler, JL, and Abernethy, AP. "Patterns of Recurrence in Melanoma and the Impact on Survival." February 2010.
Source
wos-lite
Published In
Annals of Surgical Oncology
Volume
17
Publish Date
2010
Start Page
S104
End Page
S105

Phase 2 trial of erlotinib plus sirolimus in adults with recurrent glioblastoma.

We evaluated the anti-tumor activity and safety of erlotinib, a receptor tyrosine kinase inhibitor of the epidermal growth factor receptor, plus sirolimus, an inhibitor of the mammalian target of rapamycin, among patients with recurrent glioblastoma (GBM) in a phase 2, open-label, single-arm trial. Thirty-two patients received daily erlotinib and sirolimus. The doses of erlotinib and sirolimus were 150 mg and 5 mg for patients not on concurrent CYP3A-inducing anti-epileptics (EIAEDS), and 450 mg and 10 mg for patients on EIAEDS. Evaluations were performed every two months. The primary endpoint was 6-month progression-free survival and secondary endpoints included safety and overall survival. Archival tumor samples were assessed for EGFR, EGFRvIII, PTEN, pAKT and pS6. Enrolled patients were heavily pre-treated including 53% who had received three or more prior chemotherapy agents and 28% who had received prior bevacizumab therapy. The most common grade > or = 2 adverse events were rash (59%), mucositis (34%) and diarrhea (31%). Grade 3 or higher events were rare. Best radiographic response included stable disease in 15 patients (47%); no patients achieved either a CR or PR. The estimated 6-month progression-free survival was 3.1% for all patients. Progression-free survival was better for patients not on EIAEDs (P = 0.03). Tumor markers failed to show an association with PFS except for increased pAKT expression which achieved borderline significance (P = 0.045). Although neither rash nor diarrhea had an association with outcome, hyperlipidemia was associated with longer PFS (P = 0.029). Erlotinib plus sirolimus was well tolerated but had negligible activity among unselected recurrent GBM patients. (ClinicalTrials.gov number: NCT0062243).

Authors
Reardon, DA; Desjardins, A; Vredenburgh, JJ; Gururangan, S; Friedman, AH; Herndon, JE; Marcello, J; Norfleet, JA; McLendon, RE; Sampson, JH; Friedman, HS
MLA Citation
Reardon, DA, Desjardins, A, Vredenburgh, JJ, Gururangan, S, Friedman, AH, Herndon, JE, Marcello, J, Norfleet, JA, McLendon, RE, Sampson, JH, and Friedman, HS. "Phase 2 trial of erlotinib plus sirolimus in adults with recurrent glioblastoma." J Neurooncol 96.2 (January 2010): 219-230.
PMID
19562254
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
96
Issue
2
Publish Date
2010
Start Page
219
End Page
230
DOI
10.1007/s11060-009-9950-0

Treatment-related toxicity and supportive care in metastatic colorectal cancer.

As survival of metastatic colorectal cancer (mCRC) increases, patients have more exposure to chemotherapy and related toxicity. The objective is to determine how toxicity patterns affect care. Via a population-based strategy, mCRC cases diagnosed between June 2003 and June 2006 were identified from one academic and nine community oncology practices in the southeastern United States. Demographic, disease, treatment, hospitalization, and toxicity data were abstracted by retrospective chart review, double-entered, and verified for accuracy. Of the 738 charts screened, 110 were eligible based upon preidentified inclusion criteria. As part of first-line chemotherapy, 87% received oxaliplatin, 12% received irinotecan, and 74% received bevacizumab. Gastrointestinal toxicity was the most common toxicity-related cause of drug discontinuation (16 of 61 events) and hospitalization (19 of 54 events). Both neurologic and hematologic toxicities were identified more frequently when oxaliplatin-containing regimens were administered (50% and 48%, respectively) than with irinotecan-containing regimens (10% and 24%, respectively). Dose reduction was most commonly associated with hematologic toxicity (22 of 55 events). Oxaliplatin and irinotecan required similar rates of antidiarrheal, antinausea, erythropoiesis-stimulating, and granulocyte-stimulating treatments. These data, obtained from a usual-practice setting, provide benchmarks to improve clinical practice.

Authors
Zafar, SY; Marcello, JE; Wheeler, JL; Rowe, KL; Morse, MA; Herndon, JE; Abernethy, AP
MLA Citation
Zafar, SY, Marcello, JE, Wheeler, JL, Rowe, KL, Morse, MA, Herndon, JE, and Abernethy, AP. "Treatment-related toxicity and supportive care in metastatic colorectal cancer." J Support Oncol 8.1 (January 2010): 15-20.
PMID
20235419
Source
pubmed
Published In
The Journal of Supportive Oncology
Volume
8
Issue
1
Publish Date
2010
Start Page
15
End Page
20

Erratum: Convection-enhanced delivery of free gadolinium with the recombinant immunotoxin MR1-1 (Journal of Neuro-Oncology DOI 10.1007/s11060-009-0046-7)

Authors
Ding, D; Kanaly, CW; Bigner, DD; Cummings, TJ; II, JEH; Pastan, I; Raghavan, R; Sampson, JH
MLA Citation
Ding, D, Kanaly, CW, Bigner, DD, Cummings, TJ, II, JEH, Pastan, I, Raghavan, R, and Sampson, JH. "Erratum: Convection-enhanced delivery of free gadolinium with the recombinant immunotoxin MR1-1 (Journal of Neuro-Oncology DOI 10.1007/s11060-009-0046-7)." Journal of Neuro-Oncology 98.1 (2010): 9--.
Source
scival
Published In
Journal of Neuro-Oncology
Volume
98
Issue
1
Publish Date
2010
Start Page
9-
DOI
10.1007/s11060-010-0183-z

Erratum: Effect of aerobic exercise on tumor physiology in an animal model of human breast cancer (Journal of Applied Physiology (2010) 108: (343-348) DOI: 10.1152/japplphysiol.00424.2009)

Authors
Jones, LW; Viglianti, BL; Tashjian, JA; Kothadia, SM; Keir, ST; Freedland, SJ; Potter, MQ; Moon, EJ; Schroeder, T; Herndon, JE; Dewhirst, MW
MLA Citation
Jones, LW, Viglianti, BL, Tashjian, JA, Kothadia, SM, Keir, ST, Freedland, SJ, Potter, MQ, Moon, EJ, Schroeder, T, Herndon, JE, and Dewhirst, MW. "Erratum: Effect of aerobic exercise on tumor physiology in an animal model of human breast cancer (Journal of Applied Physiology (2010) 108: (343-348) DOI: 10.1152/japplphysiol.00424.2009)." Journal of Applied Physiology 108.4 (2010): 1021--.
Source
scival
Published In
Journal of applied physiology (Bethesda, Md. : 1985)
Volume
108
Issue
4
Publish Date
2010
Start Page
1021-
DOI
10.1152/japplphysiol.zdg-9024-corr.2010

Metronomic chemotherapy with daily, oral etoposide plus bevacizumab for recurrent malignant glioma: a phase II study.

BACKGROUND: We evaluated bevacizumab with metronomic etoposide among recurrent malignant glioma patients in a phase 2, open-label trial. METHODS: A total of 59 patients, including 27 with glioblastoma (GBM) and 32 with grade 3 malignant glioma, received 10 mg kg(-1) bevacizumab biweekly and 50 mg m(-2) etoposide daily for 21 consecutive days each month. The primary end point was a 6-month progression-free survival, and secondary end points included safety and overall survival. Vascular endothelial growth factor (VEGF), VEGFR-2, carbonic anhydrase 9 (CA9) and hypoxia-inducible factor-2alpha (HIF-2alpha) were assessed semiquantitatively in archival tumours using immunohistochemistry and were correlated with outcome. RESULTS: Among grade 3 and GBM patients, the 6-month progression-free survivals were 40.6% and 44.4%, the radiographic response rates were 22% and 37% and the median survivals were 63.1 and 44.4 weeks, respectively. Hypertension predicted better outcome among both grade 3 and GBM patients, whereas high CA9 and low VEGF were associated with poorer progression-free survival (PFS) among those with GBM. The most common grade > or = 3 adverse events included neutropaenia (24%), thrombosis (12%), infection (8%) and hypertension (3%). Two patients had asymptomatic, grade 1 intracranial haemorrhage and one on-study death occurred because of pulmonary embolism. CONCLUSION: Bevacizumab with metronomic etoposide has increased toxicity compared with previous reports of bevacizumab monotherapy. Its anti-tumour activity is similar to that of bevacizumab monotherapy or bevacizumab plus irinotecan. (ClinicalTrials.gov: NCT00612430).

Authors
Reardon, DA; Desjardins, A; Vredenburgh, JJ; Gururangan, S; Sampson, JH; Sathornsumetee, S; McLendon, RE; Herndon, JE; Marcello, JE; Norfleet, J; Friedman, AH; Bigner, DD; Friedman, HS
MLA Citation
Reardon, DA, Desjardins, A, Vredenburgh, JJ, Gururangan, S, Sampson, JH, Sathornsumetee, S, McLendon, RE, Herndon, JE, Marcello, JE, Norfleet, J, Friedman, AH, Bigner, DD, and Friedman, HS. "Metronomic chemotherapy with daily, oral etoposide plus bevacizumab for recurrent malignant glioma: a phase II study." Br J Cancer 101.12 (December 15, 2009): 1986-1994.
PMID
19920819
Source
pubmed
Published In
British Journal of Cancer
Volume
101
Issue
12
Publish Date
2009
Start Page
1986
End Page
1994
DOI
10.1038/sj.bjc.6605412

Phase II trial of temozolomide (TMZ) plus irinotecan (CPT-11) in adults with newly diagnosed glioblastoma multiforme before radiotherapy.

This phase II trial evaluated efficacy and safety of temozolomide (TMZ) in combination with irinotecan (CPT-11) before radiotherapy in patients with newly diagnosed glioblastoma multiforme (GBM). Prior to radiotherapy, patients were treated with a maximum of three 6-week cycles of TMZ and CPT-11. Patients received TMZ at a dose of 200 mg/m(2)/day on days 1-5 and CPT-11 on days 1, 8, 22, and 29, with a dose adjustment for enzyme-inducing antiepileptic drug use. The primary end point was objective response rate (ORR). Secondary end points included progression-free survival (PFS), overall survival (OS), safety, and tumor O(6)-methylguanine-DNA methyltransferase (MGMT) expression. Of the 42 patients treated, 8 (19%) patients achieved a partial response. Median PFS and median OS were 3.1 and 13.8 months, respectively. Grade 3 or 4 AEs were documented in 36% of patients, most of which were hematologic (29%). Twenty-four percent of patients had grade 3 or 4 non-hematologic AEs, with gastrointestinal AEs being the most common (12%) Two patients died, one of intracranial hemorrhage and one of treatment-related renal failure. Low MGMT expression, compared with high MGMT expression, showed no significant difference in ORR (25 vs. 8%), median PFS (14 vs. 5 months) or OS (21 vs. 15 months). Although TMZ plus CPT-11 is at least comparable in efficacy to TMZ alone, this combination appears more toxic and poorly tolerated. The lack of correlation of activity with MGMT expression is intriguing, but needs further evaluation in subsequent trials.

Authors
Quinn, JA; Jiang, SX; Reardon, DA; Desjardins, A; Vredenburgh, JJ; Friedman, AH; Sampson, JH; McLendon, RE; Herndon, JE; Friedman, HS
MLA Citation
Quinn, JA, Jiang, SX, Reardon, DA, Desjardins, A, Vredenburgh, JJ, Friedman, AH, Sampson, JH, McLendon, RE, Herndon, JE, and Friedman, HS. "Phase II trial of temozolomide (TMZ) plus irinotecan (CPT-11) in adults with newly diagnosed glioblastoma multiforme before radiotherapy." J Neurooncol 95.3 (December 2009): 393-400.
PMID
19533023
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
95
Issue
3
Publish Date
2009
Start Page
393
End Page
400
DOI
10.1007/s11060-009-9937-x

An epidermal growth factor receptor variant III-targeted vaccine is safe and immunogenic in patients with glioblastoma multiforme.

Conventional therapies for glioblastoma multiforme (GBM) fail to target tumor cells exclusively, such that their efficacy is ultimately limited by nonspecific toxicity. Immunologic targeting of tumor-specific gene mutations, however, may allow more precise eradication of neoplastic cells. The epidermal growth factor receptor variant III (EGFRvIII) is a consistent and tumor-specific mutation widely expressed in GBMs and other neoplasms. The safety and immunogenicity of a dendritic cell (DC)-based vaccine targeting the EGFRvIII antigen was evaluated in this study. Adults with newly diagnosed GBM, who had undergone gross-total resection and standard conformal external beam radiotherapy, received three consecutive intradermal vaccinations with autologous mature DCs pulsed with an EGFRvIII-specific peptide conjugated to keyhole limpet hemocyanin. The dose of DCs was escalated in cohorts of three patients. Patients were monitored for toxicity, immune response, radiographic and clinical progression, and death. No allergic reactions or serious adverse events were seen. Adverse events were limited to grade 2 toxicities. The maximum feasible dose of antigen-pulsed mature DCs was reached at 5.7 x 10(7) +/- 2.9 x 10(7) SD without dose-limiting toxicity. EGFRvIII-specific immune responses were evident in most patients. The mean time from histologic diagnosis to vaccination was 3.6 +/- 0.6 SD months. Median time to progression from vaccination was 6.8 months [95% confidence interval (C.I.(95)), 2.5-8.8], and median survival time from vaccination was 18.7 months (C.I.(95), 14.5-25.6). Overall median survival from time of histologic diagnosis was 22.8 months (C.I.(95), 17.5-29). This study establishes the EGFRvIII mutation as a safe and immunogenic tumor-specific target for immunotherapy.

Authors
Sampson, JH; Archer, GE; Mitchell, DA; Heimberger, AB; Herndon, JE; Lally-Goss, D; McGehee-Norman, S; Paolino, A; Reardon, DA; Friedman, AH; Friedman, HS; Bigner, DD
MLA Citation
Sampson, JH, Archer, GE, Mitchell, DA, Heimberger, AB, Herndon, JE, Lally-Goss, D, McGehee-Norman, S, Paolino, A, Reardon, DA, Friedman, AH, Friedman, HS, and Bigner, DD. "An epidermal growth factor receptor variant III-targeted vaccine is safe and immunogenic in patients with glioblastoma multiforme." Mol Cancer Ther 8.10 (October 2009): 2773-2779.
PMID
19825799
Source
pubmed
Published In
Molecular cancer therapeutics
Volume
8
Issue
10
Publish Date
2009
Start Page
2773
End Page
2779
DOI
10.1158/1535-7163.MCT-09-0124

Phase I trial of temozolomide plus O6-benzylguanine 5-day regimen with recurrent malignant glioma.

This phase I clinical trial conducted with patients who had recurrent or progressive malignant glioma (MG) was designed to determine the maximum tolerated dose (MTD) and toxicity of three different 5-day dosing regimens of temozolomide (TMZ) in combination with O(6)-benzylguanine (O(6)-BG). Both TMZ and O(6)-BG were administered on days 1-5 of a 28-day treatment cycle. A bolus infusion of O(6)-BG was administered at 120 mg/m(2) over 1 h on days 1, 3, and 5, along with a continuous infusion of O(6)-BG at 30 mg/m(2)/day. TMZ was administered at the end of the first bolus infusion of O(6)-BG and then every 24 h for 5 days during the continuous infusion of O(6)-BG. Patients were accrued to one of three 5-day dosing regimens of TMZ. Twenty-nine patients were enrolled into this study. The dose-limiting toxicities (DLTs) were grade 4 neutropenia, leukopenia, and thrombocytopenia. The MTD for TMZ for the three different 5-day dosing schedules was determined as follows: schedule 1, 200 mg/m(2) on day 1 and 50 mg/m(2)/day on days 2-5; schedule 2, 50 mg/m(2)/day on days 1-5; and schedule 3, 50 mg/m(2)/day on days 1-5 while receiving pegfilgrastim. Thus, the 5-day TMZ dosing schedule that maximized the total dose of TMZ when combined with O(6)-BG was schedule 1. This study provides the foundation for a phase II trial of O(6)-BG in combination with a 5-day dosing schedule of TMZ in TMZ-resistant MG.

Authors
Quinn, JA; Jiang, SX; Reardon, DA; Desjardins, A; Vredenburgh, JJ; Rich, JN; Gururangan, S; Friedman, AH; Bigner, DD; Sampson, JH; McLendon, RE; Herndon, JE; Walker, A; Friedman, HS
MLA Citation
Quinn, JA, Jiang, SX, Reardon, DA, Desjardins, A, Vredenburgh, JJ, Rich, JN, Gururangan, S, Friedman, AH, Bigner, DD, Sampson, JH, McLendon, RE, Herndon, JE, Walker, A, and Friedman, HS. "Phase I trial of temozolomide plus O6-benzylguanine 5-day regimen with recurrent malignant glioma." Neuro Oncol 11.5 (October 2009): 556-561.
PMID
19289491
Source
pubmed
Published In
Neuro-Oncology
Volume
11
Issue
5
Publish Date
2009
Start Page
556
End Page
561
DOI
10.1215/15228517-2009-007

Treatment outcomes of different prognostic groups of patients on cancer and leukemia group B trial 39801: induction chemotherapy followed by chemoradiotherapy compared with chemoradiotherapy alone for unresectable stage III non-small cell lung cancer.

BACKGROUND: In Cancer and Leukemia Group B 39801, we evaluated whether induction chemotherapy before concurrent chemoradiotherapy would result in improved survival and demonstrated no significant benefit from the addition of induction chemotherapy. The primary objective of this analysis was to dichotomize patients into prognostic groups using factors predictive of survival and to investigate whether induction chemotherapy was beneficial in either prognostic group. PATIENTS AND METHODS: A Cox proportional hazard model was used to assess the impact on survival of the following factors: (>or=70 versus <70 years), gender, race, stage (IIIB versus IIIA), hemoglobin (hgb) (<13 versus >or=13 g/dl), performance status (PS) (1 versus 0), weight loss (>or=5% versus <5%), treatment arm, and the interaction between weight loss and hgb. RESULTS: Factors predictive of decreased survival were weight loss >or=5%, age >or=70 years, PS of 1, and hgb <13 g/dl (p < 0.05). Patients were classified as having >or=2 poor prognostic factors (n = 165) or or=2 versus patients with or=2 factors (HR = 0.86, 95% CI, 0.63-1.17; p = 0.34) or

Authors
Stinchcombe, TE; Hodgson, L; Herndon, JE; Kelley, MJ; Cicchetti, MG; Ramnath, N; Niell, HB; Atkins, JN; Akerley, W; Green, MR; Vokes, EE; Cancer and Leukemia Group B,
MLA Citation
Stinchcombe, TE, Hodgson, L, Herndon, JE, Kelley, MJ, Cicchetti, MG, Ramnath, N, Niell, HB, Atkins, JN, Akerley, W, Green, MR, Vokes, EE, and Cancer and Leukemia Group B, . "Treatment outcomes of different prognostic groups of patients on cancer and leukemia group B trial 39801: induction chemotherapy followed by chemoradiotherapy compared with chemoradiotherapy alone for unresectable stage III non-small cell lung cancer." J Thorac Oncol 4.9 (September 2009): 1117-1125.
PMID
19652624
Source
pubmed
Published In
Journal of Thoracic Oncology
Volume
4
Issue
9
Publish Date
2009
Start Page
1117
End Page
1125
DOI
10.1097/JTO.0b013e3181b27b33

Longitudinal patterns of chemotherapy use in metastatic colorectal cancer.

Multiple agents and combination therapies available to patients with advanced colorectal cancer have significantly improved survival and provided an opportunity for individualization of care, allowing clinicians and patients to prioritize risks and benefits of comparable regimens.

Authors
Zafar, SY; Marcello, JE; Wheeler, JL; Rowe, KL; Morse, MA; Herndon, JE; Abernethy, AP
MLA Citation
Zafar, SY, Marcello, JE, Wheeler, JL, Rowe, KL, Morse, MA, Herndon, JE, and Abernethy, AP. "Longitudinal patterns of chemotherapy use in metastatic colorectal cancer." J Oncol Pract 5.5 (September 2009): 228-233.
PMID
20856733
Source
pubmed
Published In
Journal of Oncology Practice
Volume
5
Issue
5
Publish Date
2009
Start Page
228
End Page
233
DOI
10.1200/JOP.091010

Identification of prognostic groups in patients (pts) with unresectable stage III non-small cell lung cancer (NSCLC) treated with chemoradiotherapy on Cancer and Leukemia and Group B trial (CALGB) 39801

Authors
Stinchcombe, TE; Hodgson, L; Herndon, IIJE; Kelley, M; Cicchetti, MG; Ramnath, N; Niell, H; Atkins, JN; Akerley, W; Green, MR; Vokes, EE
MLA Citation
Stinchcombe, TE, Hodgson, L, Herndon, IIJE, Kelley, M, Cicchetti, MG, Ramnath, N, Niell, H, Atkins, JN, Akerley, W, Green, MR, and Vokes, EE. "Identification of prognostic groups in patients (pts) with unresectable stage III non-small cell lung cancer (NSCLC) treated with chemoradiotherapy on Cancer and Leukemia and Group B trial (CALGB) 39801." JOURNAL OF THORACIC ONCOLOGY 4.9 (September 2009): S522-S523.
Source
wos-lite
Published In
Journal of Thoracic Oncology
Volume
4
Issue
9
Publish Date
2009
Start Page
S522
End Page
S523

Overall survival of newly diagnosed glioblastoma patients receiving carmustine wafers followed by radiation and concurrent temozolomide plus rotational multiagent chemotherapy.

BACKGROUND: Glioblastoma multiforme (GBM), the most lethal type of brain tumor, has a 1-year median survival. The effect of carmustine wafers on the survival of newly diagnosed GBM patients treated with radiotherapy (RT) and concurrent temozolomide (TMZ) plus RT plus rotational chemotherapy was investigated. METHODS: An institutional review board-approved retrospective study was conducted in 85 newly diagnosed GBM patients who received surgical resection with and without carmustine wafers followed by RT and concurrent TMZ plus rotational chemotherapy. Treatment group comparisons were conducted using the log-rank test. Survival experience of the Duke cohort was examined within specific patient subgroups defined by the original Radiation Therapy Oncology Group (RTOG) recursive partition analysis (RPA) class and compared with the European Organization for Research and Treatment of Cancer (Stupp) and RTOG trial. RESULTS: Overall 1- and 2-year survival for the noncarmustine wafer cohort were 69% and 29%, respectively, with a median survival of 72.7 weeks. One- and 2-year survival for the carmustine wafer cohort were 81% and 47%, with median survival of 89.5 weeks. Carmustine wafer was not an independent predictor (P=.110) of survival after adjustment for RPA class. The proportion of patients in the carmustine wafer cohort who lived longer than predicted based upon Stupp regimen results was significantly greater than 0.5 (P<.006); similar results based upon the RTOG trial data were observed (P<.001). CONCLUSIONS: Carmustine wafer with concurrent TMZ and radiation followed by rotational chemotherapy is a well tolerated, effective therapy, and has a survival benefit compared with radiation alone. Prospective randomized trials are needed to rigorously compare the carmustine wafer regimen to the Stupp and postradiation multimodality regimens.

Authors
Affronti, ML; Heery, CR; Herndon, JE; Rich, JN; Reardon, DA; Desjardins, A; Vredenburgh, JJ; Friedman, AH; Bigner, DD; Friedman, HS
MLA Citation
Affronti, ML, Heery, CR, Herndon, JE, Rich, JN, Reardon, DA, Desjardins, A, Vredenburgh, JJ, Friedman, AH, Bigner, DD, and Friedman, HS. "Overall survival of newly diagnosed glioblastoma patients receiving carmustine wafers followed by radiation and concurrent temozolomide plus rotational multiagent chemotherapy." Cancer 115.15 (August 1, 2009): 3501-3511.
PMID
19514083
Source
pubmed
Published In
Cancer
Volume
115
Issue
15
Publish Date
2009
Start Page
3501
End Page
3511
DOI
10.1002/cncr.24398

Phase 1 trial of temozolomide plus irinotecan plus O6-benzylguanine in adults with recurrent malignant glioma.

BACKGROUND: The current study was a phase 1 clinical trial conducted with patients who had recurrent or progressive malignant glioma (MG). The trial was designed to determine the maximum tolerated dose (MTD) and toxicity of irinotecan (CPT-11) when administered with temozolomide (TMZ) and O(6)-benzylguanine (O(6)-BG). METHODS: All 3 drugs, CPT-11, TMZ, and O(6)-BG, were administered on Day 1 of a 21-day treatment. First, patients were treated with a 1-hour bolus infusion of O(6)-BG at a dose of 120 mg/m(2) followed immediately by a 48-hour continuous infusion of O(6)-BG at a dose of 30 mg/m(2)/d. Second, within 60 minutes of the end of the 1-hour bolus infusion of O(6)-BG, TMZ was administered orally at a dose of 355 mg/m(2). Third, 1 hour after administration of TMZ, CPT-11 was infused over 90 minutes. Patients were accrued to 1 of 2 strata based on CYP3A1- and CYP3A4-inducing antiepileptic drug (EIAED) use; dose escalation was conducted independently within these strata. RESULTS: Fifty-five patients were enrolled. In both strata, the dose-limiting toxicities were hematologic and included grade 4 neutropenia, febrile neutropenia, leukopenia, and/or thrombocytopenia. For Stratum 1 (EIAEDs), when TMZ was administered at a dose of 355 mg/m(2), the MTD of CPT-11 was determined to be 120 mg/m(2). In contrast, for Stratum 2 (no EIAEDs), when TMZ was administered at a dose of 200 mg/m(2), the MTD of CPT-11 was determined to be 80 mg/m(2). CONCLUSIONS: The authors believe that the results of the current study provide the foundation for a phase 2 trial of O(6)-BG in combination with CPT-11 and TMZ in patients with MG.

Authors
Quinn, JA; Jiang, SX; Reardon, DA; Desjardins, A; Vredenburgh, JJ; Gururangan, S; Sampson, JH; McLendon, RE; Herndon, JE; Friedman, HS
MLA Citation
Quinn, JA, Jiang, SX, Reardon, DA, Desjardins, A, Vredenburgh, JJ, Gururangan, S, Sampson, JH, McLendon, RE, Herndon, JE, and Friedman, HS. "Phase 1 trial of temozolomide plus irinotecan plus O6-benzylguanine in adults with recurrent malignant glioma." Cancer 115.13 (July 1, 2009): 2964-2970.
PMID
19402172
Source
pubmed
Published In
Cancer
Volume
115
Issue
13
Publish Date
2009
Start Page
2964
End Page
2970
DOI
10.1002/cncr.24336

Poor documentation prevents adequate assessment of quality metrics in colorectal cancer.

To standardize oncology clinical practice and improve patient outcomes, multiple organizations have developed cancer-specific metrics on the basis of a systematic background review, expert guidance, and fundamental elements of cancer care-staging and treatment.

Authors
Abernethy, AP; Herndon, JE; Wheeler, JL; Rowe, K; Marcello, J; Patwardhan, M
MLA Citation
Abernethy, AP, Herndon, JE, Wheeler, JL, Rowe, K, Marcello, J, and Patwardhan, M. "Poor documentation prevents adequate assessment of quality metrics in colorectal cancer." J Oncol Pract 5.4 (July 2009): 167-174.
PMID
20856630
Source
pubmed
Published In
Journal of Oncology Practice
Volume
5
Issue
4
Publish Date
2009
Start Page
167
End Page
174
DOI
10.1200/JOP.0942003

Feasibility and acceptability to patients of a longitudinal system for evaluating cancer-related symptoms and quality of life: pilot study of an e/Tablet data-collection system in academic oncology.

Programmed, notebook-style, personal computers ("e/Tablets") can collect symptom and quality-of-life (QOL) data at the point of care. Patients use an e/Tablet in the clinic waiting area to complete electronic surveys. Information then travels wirelessly to a server, which generates a real-time report for use during the clinical visit. The objective of this study was to determine whether academic oncology patients find e/Tablets logistically acceptable and a satisfactory means of communicating symptoms to providers during repeated clinic visits. Sixty-six metastatic breast cancer patients at Duke Breast Cancer Clinic participated. E/Tablets were customized to electronically administer a satisfaction/acceptability survey, several validated questionnaires, and the Patient Care Monitor (PCM) review of symptoms survey. At each of the four visits within six months, participants completed the patient satisfaction/acceptability survey, which furnished data for the current analysis. Participant demographics were: mean age of 54 years, 77% Caucasian, and 47% with less than a college education. Participants reported that e/Tablets were easy to read (94%), easy to navigate (99%), and had a comfortable weight (90%); they found it easy to respond to questions using the e/Tablet (98%). Seventy-five percent initially indicated satisfaction with PCM for reporting symptoms; this proportion increased over time. By the last visit, 88% of participants indicated that they would recommend the PCM to other patients; 74% felt that the e/Tablet helped them remember symptoms to report to their clinician. E/Tablets offered a feasible and acceptable method for collecting longitudinal patient-reported symptom and QOL data within an academic, tertiary care, breast cancer clinic.

Authors
Abernethy, AP; Herndon, JE; Wheeler, JL; Day, JM; Hood, L; Patwardhan, M; Shaw, H; Lyerly, HK
MLA Citation
Abernethy, AP, Herndon, JE, Wheeler, JL, Day, JM, Hood, L, Patwardhan, M, Shaw, H, and Lyerly, HK. "Feasibility and acceptability to patients of a longitudinal system for evaluating cancer-related symptoms and quality of life: pilot study of an e/Tablet data-collection system in academic oncology." J Pain Symptom Manage 37.6 (June 2009): 1027-1038.
PMID
19394793
Source
pubmed
Published In
Journal of Pain and Symptom Management
Volume
37
Issue
6
Publish Date
2009
Start Page
1027
End Page
1038
DOI
10.1016/j.jpainsymman.2008.07.011

Quality management of potential chemotherapy-induced neutropenic complications: evaluation of practice in an academic medical center.

GOALS: Management of the risk of potential chemotherapy-induced neutropenic complications such as febrile neutropenia (FN) and severe neutropenia (SN) is a quality of care priority. How frequently does care at our institution conform to established guidelines? MATERIALS AND METHODS: This retrospective chart review study included a random sample of 305 cancer patients receiving care at a single US academic medical center. Abstracted data included demographics, risk factors, and outcome variables (e.g., development of FN/SN, administration of myeloid growth factors). To evaluate quality of care, we assessed conformance between actual practice and established clinical practice guidelines for the use of myeloid growth factors from the National Comprehensive Cancer Network (NCCN). MAIN RESULTS: Of the 305 cases reviewed, 8% were classified as low risk (<10%), 48% as intermediate risk (10-20%), and 44% as high risk (>20%), using the risk classifications in the NCCN guidelines modified to accommodate illness and other risk factors. Thirty-four percent received prophylactic administration of myeloid growth factors. Half of the cases had adequate documentation of mid-cycle absolute neutrophil count to determine whether FN/SN developed. Among these cases with adequate documentation, 21% developed FN/SN. Use of growth factors did not conform to established quality guidelines. Overall, 77 of 133 (58%) high-risk cases received myeloid growth factors, whereas six of 25 (24%) low-risk cases received myeloid growth factors. CONCLUSIONS: Routine clinical practice in this academic oncology setting was poorly aligned with established guidelines; there is substantial opportunity to standardize clinical strategies and increase conformance with evidence-based guidelines.

Authors
Abernethy, AP; Barbour, SY; Uronis, H; Zafar, SY; Coan, A; Rowe, K; Pupa, MR; Wheeler, JL; Herndon, JE
MLA Citation
Abernethy, AP, Barbour, SY, Uronis, H, Zafar, SY, Coan, A, Rowe, K, Pupa, MR, Wheeler, JL, and Herndon, JE. "Quality management of potential chemotherapy-induced neutropenic complications: evaluation of practice in an academic medical center." Support Care Cancer 17.6 (June 2009): 735-744.
PMID
19096882
Source
pubmed
Published In
Supportive Care in Cancer
Volume
17
Issue
6
Publish Date
2009
Start Page
735
End Page
744
DOI
10.1007/s00520-008-0562-6

Effect of daclizumab on T-Reg counts and EGFRvIII-specific immune responses in GBM

Authors
Sampson, JH; Archer, GE; Bigner, DD; Schmittling, RJ; II, HJE; Davis, T; Friedman, HS; Keler, T; Reardon, DA; Mitchell, DA
MLA Citation
Sampson, JH, Archer, GE, Bigner, DD, Schmittling, RJ, II, HJE, Davis, T, Friedman, HS, Keler, T, Reardon, DA, and Mitchell, DA. "Effect of daclizumab on T-Reg counts and EGFRvIII-specific immune responses in GBM." May 20, 2009.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
27
Issue
15
Publish Date
2009

Epidermal growth factor receptor variant III (EGFRvIII) vaccine ( CDX-110) in GBM

Authors
Heimberger, AB; Archer, GE; Mitchell, DA; Bigner, DD; Schmittling, RJ; II, HJE; Davis, T; Friedman, HS; Keler, T; Reardon, DA; Sampson, JH
MLA Citation
Heimberger, AB, Archer, GE, Mitchell, DA, Bigner, DD, Schmittling, RJ, II, HJE, Davis, T, Friedman, HS, Keler, T, Reardon, DA, and Sampson, JH. "Epidermal growth factor receptor variant III (EGFRvIII) vaccine ( CDX-110) in GBM." May 20, 2009.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
27
Issue
15
Publish Date
2009

Temozolomide (TMZ) and bevacizumab (BV) as initial treatment for unresectable or multifocal glioblastoma multiforme (GBM)

Authors
Peters, K; Desjardins, A; Reardon, DA; Perry, S; II, HJE; Bailey, L; Friedman, AH; Friedman, HS; Bigner, DD; Vredenburgh, JJ
MLA Citation
Peters, K, Desjardins, A, Reardon, DA, Perry, S, II, HJE, Bailey, L, Friedman, AH, Friedman, HS, Bigner, DD, and Vredenburgh, JJ. "Temozolomide (TMZ) and bevacizumab (BV) as initial treatment for unresectable or multifocal glioblastoma multiforme (GBM)." May 20, 2009.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
27
Issue
15
Publish Date
2009

Safety and efficacy of the addition of bevacizumab (BV) to temozolomide (TMZ) and radiation therapy (RT) followed by BV, TMZ, and irinotecan (CPT-11) for newly diagnosed glioblastoma multiforme (GBM)

Authors
Vredenburgh, JJ; Desjardins, A; Reardon, DA; Peters, K; II, HJE; Kirkpatrick, J; Gururangan, S; Bailey, L; Friedman, AH; Friedman, HS
MLA Citation
Vredenburgh, JJ, Desjardins, A, Reardon, DA, Peters, K, II, HJE, Kirkpatrick, J, Gururangan, S, Bailey, L, Friedman, AH, and Friedman, HS. "Safety and efficacy of the addition of bevacizumab (BV) to temozolomide (TMZ) and radiation therapy (RT) followed by BV, TMZ, and irinotecan (CPT-11) for newly diagnosed glioblastoma multiforme (GBM)." May 20, 2009.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
27
Issue
15
Publish Date
2009

Clinical factors predictive of overall survival (OS) and the identification of prognostic groups in patients (pts) with unresectable stage III non-small cell lung cancer (NSCLC) treated with chemoradiotherapy on Cancer and Leukemia and Group B trial (CALGB) 39801

Authors
Stinchcombe, TE; Hodgson, L; Herndon, JE; Kelley, MJ; Cicchetti, M; Ramnath, N; Niell, HB; Atkins, JN; Green, MR; Vokes, EE
MLA Citation
Stinchcombe, TE, Hodgson, L, Herndon, JE, Kelley, MJ, Cicchetti, M, Ramnath, N, Niell, HB, Atkins, JN, Green, MR, and Vokes, EE. "Clinical factors predictive of overall survival (OS) and the identification of prognostic groups in patients (pts) with unresectable stage III non-small cell lung cancer (NSCLC) treated with chemoradiotherapy on Cancer and Leukemia and Group B trial (CALGB) 39801." May 20, 2009.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
27
Issue
15
Publish Date
2009

Impact of a psychosocial intervention on performance status and coping

Authors
Lyerly, HK; Staley, T; II, HJE; Coan, A; Wheeler, JL; Rowe, K; Horne, B; Abernethy, AP
MLA Citation
Lyerly, HK, Staley, T, II, HJE, Coan, A, Wheeler, JL, Rowe, K, Horne, B, and Abernethy, AP. "Impact of a psychosocial intervention on performance status and coping." May 20, 2009.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
27
Issue
15
Publish Date
2009

Survivorship care planning needs in diffuse large B-cell lymphoma (DLBCL)

Authors
Friedman, DR; Dupont, AH; Coan, AD; II, HJE; Rowe, KL; Abernethy, AP
MLA Citation
Friedman, DR, Dupont, AH, Coan, AD, II, HJE, Rowe, KL, and Abernethy, AP. "Survivorship care planning needs in diffuse large B-cell lymphoma (DLBCL)." May 20, 2009.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
27
Issue
15
Publish Date
2009

Phase I pharmacokinetic study of the vascular endothelial growth factor receptor tyrosine kinase inhibitor vatalanib (PTK787) plus imatinib and hydroxyurea for malignant glioma.

BACKGROUND: This study determined the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of the oral vascular endothelial growth factor receptor (VEGFR) inhibitor, vatalanib, when administered with imatinib and hydroxyurea on a continuous daily schedule among recurrent malignant glioma patients. METHODS: All patients received 500 mg of hydroxyurea twice daily. Imatinib was dosed at 400 mg per day for patients not taking enzyme-inducing antiepileptic drugs (EIAEDs; stratum A) and at 500 mg twice-a-day for patients taking EIAEDs (stratum B). Vatalanib was escalated from 500 mg to 1250 mg twice daily in successive cohorts, independently for each stratum. Pharmacokinetics of each drug were assessed. RESULTS: A total of 37 recurrent patients, 34 (92%) with glioblastoma and 3 (8%) with grade 3 malignant glioma, were enrolled. Nineteen patients (51%) were taking EIAEDs. The MTD of vatalanib for all patients was 1000 mg twice-a-day. DLTs were hematologic, gastrointestinal, renal, and hepatic. No patients developed intracranial hemorrhage. Concurrent administration of imatinib and hydroxyurea did not affect vatalanib exposure, but EIAEDs decreased vatalanib and imatinib plasma exposures. CONCLUSIONS: Vatalanib doses up to 1000 mg twice-a-day combined with imatinib and hydroxyurea were well tolerated. Strategies to target tumor blood vessel endothelial cells and pericytes by inhibiting VEGFR and platelet-derived growth factor, respectively, were safe among recurrent malignant glioma patients and may enhance antiangiogenesis activity.

Authors
Reardon, DA; Egorin, MJ; Desjardins, A; Vredenburgh, JJ; Beumer, JH; Lagattuta, TF; Gururangan, S; Herndon, JE; Salvado, AJ; Friedman, HS
MLA Citation
Reardon, DA, Egorin, MJ, Desjardins, A, Vredenburgh, JJ, Beumer, JH, Lagattuta, TF, Gururangan, S, Herndon, JE, Salvado, AJ, and Friedman, HS. "Phase I pharmacokinetic study of the vascular endothelial growth factor receptor tyrosine kinase inhibitor vatalanib (PTK787) plus imatinib and hydroxyurea for malignant glioma." Cancer 115.10 (May 15, 2009): 2188-2198.
PMID
19248046
Source
pubmed
Published In
Cancer
Volume
115
Issue
10
Publish Date
2009
Start Page
2188
End Page
2198
DOI
10.1002/cncr.24213

Clinical factors predictive of overall survival (OS) and the identification of prognostic groups in patients (pts) with unresectable stage III non-small cell lung cancer (NSCLC) treated with chemoradiotherapy on Cancer and Leukemia and Group B trial (CALGB) 39801.

7535 Background: CALGB 39801 was designed to test whether treatment with induction chemotherapy and concurrent chemoradiotherapy (arm B) would improve OS in comparison to identical chemoradiotherapy alone (arm A), and demonstrated no significant benefit in OS for induction therapy. The objective of this analysis was to identify factors predictive of OS, and to use relevant factors to dichotomize pts into prognostic groups.Between July 1998 and May 2002, 331 pts were studied and included in a Cox proportional hazard regression analysis investigating previously identified prognostic factors: age (< 70 vs. ≥ 70 years), gender, race/ethnicity, hemoglobin (hgb) (< 13 vs. ≥13), performance status (PS) (0 vs.1), pretreatment weight loss (wt loss) (<5% vs. ≥ 5%), and treatment arm.Cox regression analysis identified weight loss ≥ 5%, age ≥ 70, PS of 1, and hgb < 13 as predictive of worse survival (p<0.05), but not treatment arm (p=0.55). The median survival for pts with 0 (n=66), 1 (n=100), 2 (n=100), or ≥ 3 (n=65) risk factors were 24, 18, 10, and 8 months, respectively (p=0.0001). The pts were dichotomized into "poor prognosis" (PP) defined as ≥2 factors (n=165) and "good prognosis" (GP) defined as ≤ 1 factors (n=166). The hazard ratio (HR) for overall survival for the PP in comparison GP was 1.88 (95% CI, 1.49 to 2.37; p-value < 0.0001); the median survival times (MST) observed were 9 and 18 months, respectively (p<0.0001). The reasons for discontinuing treatment, and the rates of hematologic and non-hematologic adverse events were similar between the two groups. In the PP group the OS was similar between arms A (n=82) and B (n=83) (HR=0.97, 95% CI, 0.70 to 1.4; p=0.34); MST of 8.7 and 9.5 months, respectively. In the GP the OS was similar between arms A (n=79) and B (n=87) (HR=0.86, 95% CI, 0.63 to 1.1; p=0.87); MST of 19.3 and 17.6 months, respectively.Factors predictive of OS can be used to dichotomize pts into prognostic groups. Induction chemotherapy was not beneficial in either prognostic group. No significant financial relationships to disclose.

Authors
Stinchcombe, TE; Hodgson, L; Herndon, JE; Kelley, MJ; Cicchetti, M; Ramnath, N; Niell, HB; Atkins, JN; Green, MR; Vokes, EE
MLA Citation
Stinchcombe, TE, Hodgson, L, Herndon, JE, Kelley, MJ, Cicchetti, M, Ramnath, N, Niell, HB, Atkins, JN, Green, MR, and Vokes, EE. "Clinical factors predictive of overall survival (OS) and the identification of prognostic groups in patients (pts) with unresectable stage III non-small cell lung cancer (NSCLC) treated with chemoradiotherapy on Cancer and Leukemia and Group B trial (CALGB) 39801." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 27.15_suppl (May 2009): 7535-.
PMID
27963304
Source
epmc
Published In
Journal of Clinical Oncology
Volume
27
Issue
15_suppl
Publish Date
2009
Start Page
7535

Impact of a psychosocial intervention on performance status and coping.

9611 Background: Psychosocial distress is a critical cancer comorbidity; new interventions are needed. Pathfinders, a manualized psychosocial care program, provides patient navigation, counseling, coping skills training, mind/body techniques, and lifestyle advice.This prospective, single-arm, pilot study enrolled adult metastatic breast cancer patients with prognosis ≥6 months. Consenting participants met with a Pathfinder (trained social worker) at least monthly, with interim phone/email contact. Pathfinders worked with patients to identify inner strengths, teach coping skills, engage complementary/alternative providers, employ mind/body techniques, and support healthy lifestyle. At baseline, month 3 and month 6, patients completed surveys including Patient Care Monitor (PCM; a review of systems with 6 subscales and a global quality of life [QOL] score), and Functional Assessment of Chronic Illness Therapy - Fatigue subscale (FACIT-F).Participants (n=50) were: mean age 51.2 years (SD 11.5); 24% non-white; 74% married; 50% did not complete college; the cohort had advanced cancer and short prognosis with 6-month attrition from death, 18%. Scores on the PCM Distress subscale improved from baseline to 3 months with a mean change of -3.42 (n=36; p=0.008) and from baseline to 6 months of -4.11 (n=28; p=0.002). PCM Despair subscale scores also improved: mean change of -4.53 (p=0.006) and -6.93 (p=0.016), respectively. PCM QOL and FACIT-F scores improved from baseline to 3 months; however, the change at 6 months, with smaller sample, was not statistically significant. Mean change in QOL from baseline to 3 and 6 months was 2.88 (n=30; p=0.006) and 2.66 (n=25; p=0.079), respectively. Mean change in FACIT-F from baseline to 3 and 6 months was 2.91 (n=39; p=0.020) and 1.29 (n=32; p=0.407), respectively.Pathfinders had significant positive effect on key psychosocial and QOL outcomes, notably distress and despair, for cancer patients despite advanced disease and worsening symptoms. No significant financial relationships to disclose.

Authors
Lyerly, HK; Staley, T; Herndon, JE; Coan, A; Wheeler, JL; Rowe, K; Horne, B; Abernethy, AP
MLA Citation
Lyerly, HK, Staley, T, Herndon, JE, Coan, A, Wheeler, JL, Rowe, K, Horne, B, and Abernethy, AP. "Impact of a psychosocial intervention on performance status and coping." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 27.15_suppl (May 2009): 9611-.
PMID
27963859
Source
epmc
Published In
Journal of Clinical Oncology
Volume
27
Issue
15_suppl
Publish Date
2009
Start Page
9611

Effect of daclizumab on TReg counts and EGFRvIII-specific immune responses in GBM.

2034 Background: TRegs are increased in patients with GBM and constitutively express the high affinity interleukin-2 receptor (IL-2Rα). Treatment with an antibody that blocks IL-2Rα signaling functionally inactivates and eliminates TRegs without inducing autoimmune toxicity in murine models. We hypothesized that daclizumab, a commercially-available, IL-2Rα-specific antibody would function identically.A randomized phase II clinical trial assessed the effects of daclizumab in the context of the cancer vaccine, CDX-110, which is comprised of an EGFRvIII-specific peptide sequence linked to KLH. EGFRvIII is a constitutively activated and immunogenic mutation not expressed in normal tissues, but widely expressed in GBMs and other neoplasms. In patients with newly-diagnosed, EGFRvIII+ GBM, after resection and radiation/TMZ, patients received CDX-110 vaccinations biweekly x 3, then monthly until tumor progression in combination with TMZ (200 mg/m2 x 5/28 days). Half the patients were randomized to receive daclizumab (1mg/Kg x1) at the first vaccine. The others received saline in a double-blinded fashion.There were no drug related SAEs. EGFRvIII-specific immune responses were generated in all patients, and all immune responses were sustained or enhanced during subsequent TMZ cycles. Preliminary analysis (n = 4) suggests that daclizumab reduces Treg (CD4+CD25+CD45RO+FOXP3+) numbers [change 82.4 ± 7.1% from baseline (p = 0.011; t-test)] without reducing overall CD8+ or CD4+ T-cell counts. Tregs decreased only 3.7 + 11.0% after vaccination in the saline treated group during the same interval. Preliminary analysis (n = 4) also suggest that daclizumab enhanced EGFRvIII-specific immune responses (p = 0.01; t-test) and enhanced the titer of cytotoxic EGFRvIII-specific IgG1 isotype antibodies compared to the saline treated group (p = 0.003; t-test) and compared to previously vaccinated patients who did not receive daclizumab (p = 0.0015; t-test). TTP and OS survival in both arms has not been reached.Daclizumab may reduce Treg counts in patients with GBM. TMZ and daclizumab may enhance EGFRvIII-targeted immune responses despite lymphodepletion. These combinations are currently under further investigation. [Table: see text].

Authors
Sampson, JH; Archer, GE; Bigner, DD; Schmittling, RJ; Herndon, JE; Davis, T; Friedman, HS; Keler, T; Reardon, DA; Mitchell, DA
MLA Citation
Sampson, JH, Archer, GE, Bigner, DD, Schmittling, RJ, Herndon, JE, Davis, T, Friedman, HS, Keler, T, Reardon, DA, and Mitchell, DA. "Effect of daclizumab on TReg counts and EGFRvIII-specific immune responses in GBM." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 27.15_suppl (May 2009): 2034-.
PMID
27964629
Source
epmc
Published In
Journal of Clinical Oncology
Volume
27
Issue
15_suppl
Publish Date
2009
Start Page
2034

Epidermal growth factor receptor variant III (EGFRvIII) vaccine (CDX-110) in GBM.

2021 Background: Unlike conventional therapies for GBM, immunologic targeting of tumor-specific gene mutations allows precise eradication of neoplastic cells with reduced toxicity. EGFRvIII is a constitutively activated and immunogenic mutation not expressed in normal tissues, but widely expressed in GBM and other neoplasms. The cancer vaccine CDX-110 is comprised of an EGFRvIII-specific peptide sequence linked to keyhole limpet hemocyanin (KLH).A phase II multi-center trial assessed the immunogenicity and efficacy of CDX-110 in patients with newly-diagnosed, EGFRvIII+ GBM. After resection and radiation / TMZ, patients received CDX-110 vaccinations biweekly x 3, then monthly until tumor progression. Sequential cohorts received CDX-110 alone [ACTIVATE (n = 18)] or in combination with TMZ (200 mg/m2 x 5/28 days [ACT II A (n = 13)]) or (100 mg/m2 x 21/28 days [ACT II B (n=10)]).Reversible systemic drug hypersensitivity reactions were seen in 1 ACTIVATE and 4 ACT II patients. Two patients had non-specific changes on MRI which were possibly due to the vaccine but which resolved. Despite grade 2 or 3 lymphopenia in all ACT II patients, EGFRvIII-specific immune responses were generated in all patients, and all immune responses were sustained or enhanced during subsequent TMZ cycles. Although ACT II B patients had more severe TMZ-induced lymphopenia, they developed greater EGFRvIII-specific immune responses (p = 0.028) when compared to ACT II A. EGFRvIII-specific IgG1 also increased in avidity with vaccination (Ka>>2x109M-1) in a randomly selected subset of 4 patients (p = 0.000068). Of the 23 recurrent tumors studied, 18 lost EGFRvIII expression (p = 0.001). There are no significant differences between ACT II A and B in estimated median TTP (18.5 vs. 14.9 months, p = 0.31) and OS (23.6 vs. 19.9 months, p = 0.75). ACTIVATE TTP (14.2 months) and OS (26.0 months) and ACT II TTP (15.2 months) and OS (23.6 months) compare favorably to a TMZ-treated, matched historical control group (TTP: 6.3 months; OS: 15.0 months).CDX-110 vaccination in patients with GBM appears very promising. TMZ enhances immune responses despite lymphodepletion. CDX-110 with simultaneous TMZ is under further investigation in a larger phase II trial. [Table: see text].

Authors
Heimberger, AB; Archer, GE; Mitchell, DA; Bigner, DD; Schmittling, RJ; Herndon, JE; Davis, T; Friedman, HS; Keler, T; Reardon, DA; Sampson, JH
MLA Citation
Heimberger, AB, Archer, GE, Mitchell, DA, Bigner, DD, Schmittling, RJ, Herndon, JE, Davis, T, Friedman, HS, Keler, T, Reardon, DA, and Sampson, JH. "Epidermal growth factor receptor variant III (EGFRvIII) vaccine (CDX-110) in GBM." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 27.15_suppl (May 2009): 2021-.
PMID
27964605
Source
epmc
Published In
Journal of Clinical Oncology
Volume
27
Issue
15_suppl
Publish Date
2009
Start Page
2021

Temozolomide (TMZ) and bevacizumab (BV) as initial treatment for unresectable or multifocal glioblastoma multiforme (GBM).

e13025 Background: GBMs are vascular tumors and inherently resistant to therapy. The prognosis for patients is poor with a median survival of 9-15 months. Patients with unresectable or multifocal GBMs have an even poorer prognosis, with a median survival of 6-8 months. Given the angiogenic phenotype of GBM, we conducted a phase II trial of upfront BV and 5-day TMZ in newly diagnosed unresectable or multifocal GBMs.Patients had histologically documented newly diagnosed GBMs that were unresectable or multifocal. Patients received up to 4 cycles of temozolomide at 200 mg/m2/d days 1-5 and BV at 10 mg/kg on days 1 and 14 in a 28 day cycle. An MRI was performed after every cycle and patients continued on therapy as long as there was no tumor progression, grade 4 non-hematologic toxicity or recurrent grade 4 hematologic toxicity after a dose reduction to 150 mg/m2/d. The primary endpoint was tumor response using the modified MacDonald criteria plus FLAIR and T2 sequences to evaluate non-enhancing tumor. Results were evaluated by two independent reviewers.41 patients were enrolled between October 2007 and September 2008 and 31 patients were analyzed after completion of cycle 2. As the best response, there were 8 (25.8%) partial responses, 19 (61.3 %) patients with stable disease, and 4(12.9 %) had disease progression. 19 of the 41 patients enrolled completed four cycles without tumor progression. The regimen was tolerable, with 3 grade 4 hematologic toxicities including neutropenia and thrombocytopenia. There were 2 grade 4 non-hematologic toxicities, including pulmonary embolism. There were two CNS hemorrhages. The median PFS was 3.6 months (2.9 months, 4.4 months) and the median OS was 4.5 months (3.7 months, 5.3 months).Upfront temozolomide and bevacizumab was well tolerated, but synergistic chemotherapy or growth factor inhibitors need to be added to produce meaningful clinical benefit, particularly for unresectable or multifocal GBM. No significant financial relationships to disclose.

Authors
Peters, K; Desjardins, A; Reardon, DA; Perry, S; Herndon, JE; Bailey, L; Friedman, AH; Friedman, HS; Bigner, DD; Vredenburgh, JJ
MLA Citation
Peters, K, Desjardins, A, Reardon, DA, Perry, S, Herndon, JE, Bailey, L, Friedman, AH, Friedman, HS, Bigner, DD, and Vredenburgh, JJ. "Temozolomide (TMZ) and bevacizumab (BV) as initial treatment for unresectable or multifocal glioblastoma multiforme (GBM)." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 27.15_suppl (May 2009): e13025-.
PMID
27962792
Source
epmc
Published In
Journal of Clinical Oncology
Volume
27
Issue
15_suppl
Publish Date
2009
Start Page
e13025

Survivorship care planning needs in diffuse large B-cell lymphoma (DLBCL).

e20703 Background: Cancer survivorship care plans inform and direct care in the survivorship setting. These care plans should be tailored to individual medical information, needs, and circumstances, as providing excess information can be overwhelming. According to survivors of DLBCL, what are important components of care plans?We developed a 22-question survey to define and rate important survivorship health and psychosocial concerns; items were developed based upon literature review and experience in survivorship clinics. Through the tumor registry, 178 patients were identified who had been treated with curative intent (including stem cell transplant) without evidence of recurrence since 1/2006 and who continue to receive care at Duke University Medical Center.Sixty-five survivors consented and returned a completed IRB approved survey (response rate 37%). Responders: 58% female, 88% white, and 75% from North Carolina, with mean age at diagnosis of 59.7 years; 42% had stage four disease at diagnosis and 12% had had a transplant. The majority of survey participants (62%) indicated that they preferred their oncologist and primary care provider to jointly manage their survivorship care. On a 1-10 scale, the top scoring issue (mean 9.67) was "A plan to screen for possible return of your cancer." Other top scoring issues (mean 8.81 - 9.48) related to cancer history (treatment, complications, stage or late effects) and non-cancer health monitoring. The lowest scoring needs related to social support, sexuality, financial/legal issues, alternative medicine, and mental health services (mean 5.45 - 7.12). There was greater agreement among responders on the importance ratings of the higher scoring issues than the lower scoring ones (standard deviation 1.01 - 2.34 vs. 3.18 - 3.56).DLBCL survivors prefer care plans focused on medical issues, and health care coordinated jointly by oncologists and primary care physicians. The lower importance of psychosocial issues and alternative medicine in this population differs from survivors of other cancers, underscoring the importance of tailoring care plans by cancer subgroup. No significant financial relationships to disclose.

Authors
Friedman, DR; Dupont, AH; Coan, AD; Herndon, JE; Rowe, KL; Abernethy, AP
MLA Citation
Friedman, DR, Dupont, AH, Coan, AD, Herndon, JE, Rowe, KL, and Abernethy, AP. "Survivorship care planning needs in diffuse large B-cell lymphoma (DLBCL)." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 27.15_suppl (May 2009): e20703-.
PMID
27961990
Source
epmc
Published In
Journal of Clinical Oncology
Volume
27
Issue
15_suppl
Publish Date
2009
Start Page
e20703

Safety and efficacy of the addition of bevacizumab (BV) to temozolomide (TMZ) and radiation therapy (RT) followed by BV, TMZ, and irinotecan (CPT-11) for newly diagnosed glioblastoma multiforme (GBM).

2015 Background: Standard GBM treatment includes TMZ and RT, and results in a median progression-free survival and median survival of 6.9 and 15.8 months, respectively. GBM have high concentrations of vascular endothelial growth factor (VEGF), higher levels are associated with poorer prognosis. BV is a humanized antibody to VEGF with activity in recurrent GBMs. This study aims to improve the survival of newly diagnosed GBM patients by incorporating an anti-angiogenic agent with RT and TMZ, and adding a topoisomerase I inhibitor, and an anti-angiogenic agent to TMZ post-RT therapy.Patients received standard RT and TMZ at 75 mg/m2/day, with BV at 10 mg/kg every 14 days beginning a minimum of 28 days post-operatively. Following the completion of RT, patients received 6 cycles of BV, TMZ and CPT-11. Each cycle was 28 days. BV was given at a dose of 10 mg/kg on days 1 and 15, TMZ at 200 mg/m2 on days 1-5 and CPT-11 on days 1 and 15 at 125 mg/m2 for patients not on an enzyme inducing anti-epileptic drug (EIAED) and 340 mg/m2 for patients on an EIAED. The study was designed to differentiate between a 16-month survival rate of 45% and 60% with type I and II error rates of 0.05.75 patients were enrolled between 8/07 and 9/08. All the patients have completed RT; 40 patients continue to receive BV, TMZ, and CPT-11. Twenty-two patients have completed 6 cycles of BV, TMZ, and CPT-11; 17 of them had a cold PET One patient developed a CNS hemorrhage (grade 2) necessitating stopping BV. Five patients developed thrombocytopenia for which TMZ was held (grade 3, n = 1; grade 4, n = 4). There were no other ≥ grade 3 toxicities, including no wound dehiscence during RT. Twelve patients had tumor progression, and 14 stopped because of toxicity, including: 6 with fatigue; 3 with PEs; 2 with grade 4 thrombocytopenia; the patient with CNS hemorrhage, and one each with a rectal abscess and sepsis. There have been 7 deaths: 5 from tumor progression; one each from sepsis and PEs. At a median follow-up of 9 months, 81% remain alive and progression-free.Adding BV to TMZ and RT followed by BV, TMZ with CPT-11 is tolerable and efficacious. No significant financial relationships to disclose.

Authors
Vredenburgh, JJ; Desjardins, A; Reardon, DA; Peters, K; Herndon, JE; Kirkpatrick, J; Gururangan, S; Bailey, L; Friedman, AH; Friedman, HS
MLA Citation
Vredenburgh, JJ, Desjardins, A, Reardon, DA, Peters, K, Herndon, JE, Kirkpatrick, J, Gururangan, S, Bailey, L, Friedman, AH, and Friedman, HS. "Safety and efficacy of the addition of bevacizumab (BV) to temozolomide (TMZ) and radiation therapy (RT) followed by BV, TMZ, and irinotecan (CPT-11) for newly diagnosed glioblastoma multiforme (GBM)." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 27.15_suppl (May 2009): 2015-.
PMID
27964581
Source
epmc
Published In
Journal of Clinical Oncology
Volume
27
Issue
15_suppl
Publish Date
2009
Start Page
2015

Use of tablet personal computers for sensitive patient-reported information.

Notebook-style computers (e/Tablets) are increasingly replacing paper methods for collecting patient-reported information. Discrepancies in data between these methods have been found in oncology for sexuality-related questions. A study was performed to formulate hypotheses regarding causes for discrepant responses and to analyze whether electronic data collection adds value over paper-based methods when collecting data on sensitive topics. A total of 56 breast cancer patients visiting Duke Breast Clinic (North Carolina) participated by responding to 12 subscales of 5 survey instruments in electronic (e/Tablet) format and to a paper version of 1 of these surveys, at each visit. Twenty-one participants (38%) provided dissimilar responses on paper and electronic surveys to one item of the Functional Assessment of Cancer Therapy-General (FACT-G) Social Well-Being scale that asked patients to rate their satisfaction with their current sex life. Among these 21 patients were 8 patients who answered the question in the electronic environment, and 13 patients who answered both paper and electronic versions but with different responses. Eleven patients (29%) did not respond to the item on either e/Tablet or paper; 45 patients (80%) answered it on e/Tablet; and 37 patients (66%) responded on the paper version. The e/Tablet electronic system may provide a "safer" environment than paper questionnaires for cancer patients to answer private or highly personal questions on sensitive topics such as sexuality.

Authors
Dupont, A; Wheeler, J; Herndon, JE; Coan, A; Zafar, SY; Hood, L; Patwardhan, M; Shaw, HS; Lyerly, HK; Abernethy, AP
MLA Citation
Dupont, A, Wheeler, J, Herndon, JE, Coan, A, Zafar, SY, Hood, L, Patwardhan, M, Shaw, HS, Lyerly, HK, and Abernethy, AP. "Use of tablet personal computers for sensitive patient-reported information." J Support Oncol 7.3 (May 2009): 91-97.
PMID
19507456
Source
pubmed
Published In
The Journal of Supportive Oncology
Volume
7
Issue
3
Publish Date
2009
Start Page
91
End Page
97

RNA Transfected Dendritic Cell Vaccines Targeting Human Cytomegalovirus Antigens in Patients with Glioblastoma

Authors
Mitchell, DA; Archer, GE; Bigner, DD; Friedman, HS; Lally-Goss, D; Perry, B; II, HJE; McGehee, S; McLendon, RE; Reardon, D; Sampson, JH
MLA Citation
Mitchell, DA, Archer, GE, Bigner, DD, Friedman, HS, Lally-Goss, D, Perry, B, II, HJE, McGehee, S, McLendon, RE, Reardon, D, and Sampson, JH. "RNA Transfected Dendritic Cell Vaccines Targeting Human Cytomegalovirus Antigens in Patients with Glioblastoma." May 2009.
Source
wos-lite
Published In
Molecular Therapy
Volume
17
Publish Date
2009
Start Page
S93
End Page
S93

RECOMBINANT ANTIBODY-BASED MOLECULAR THERAPEUTICS FOR BRAIN TUMOR IMMUNOTHERAPY

Authors
Kuan, C-T; Wakiya, K; II, HJE; Wikstrand, CJ; McLendon, RE; Zalutsky, MR; Pastan, IH; Bigner, DD
MLA Citation
Kuan, C-T, Wakiya, K, II, HJE, Wikstrand, CJ, McLendon, RE, Zalutsky, MR, Pastan, IH, and Bigner, DD. "RECOMBINANT ANTIBODY-BASED MOLECULAR THERAPEUTICS FOR BRAIN TUMOR IMMUNOTHERAPY." NEURO-ONCOLOGY 11.2 (April 2009): 224-224.
Source
wos-lite
Published In
Neuro-Oncology
Volume
11
Issue
2
Publish Date
2009
Start Page
224
End Page
224

Phase II trial of temozolomide plus o6-benzylguanine in adults with recurrent, temozolomide-resistant malignant glioma.

PURPOSE: This phase II trial was designed to define the role of O(6)-benzylguanine (O(6)-BG) in restoring temozolomide sensitivity in patients with recurrent or progressive, temozolomide-resistant malignant glioma and to evaluate the safety of administering O(6)-BG in combination with temozolomide. PATIENTS AND METHODS: Patients were accrued into two independent strata on the basis of histology: glioblastoma multiforme (GBM) and anaplastic glioma. Both temozolomide and O(6)-BG were administered on day 1 of a 28-day treatment cycle. Patients were administered a 1-hour O(6)-BG infusion at a dose of 120 mg/m(2) followed immediately by a 48-hour infusion at a dose of 30 mg/m(2)/d. Temozolomide was administered orally within 60 minutes of the end of the 1-hour O(6)-BG infusion at a dose of 472 mg/m(2). The primary end point was objective response rate. Secondary end points included progression-free survival, overall survival, and safety. RESULTS: Sixty-six of 67 patients who enrolled were treated with temozolomide and O(6)-BG. One of 34 patients (3%) with GBM (95% CI, 0.1% to 15%) and five of 32 assessable patients (16%) with anaplastic glioma (95% CI, 5% to 33%) were responders. The most commonly reported adverse events were grade 4 hematologic events experienced in 48% of the patients. CONCLUSION: O(6)-BG when added to a 1-day dosing regimen of temozolomide was able to restore temozolomide sensitivity in patients with temozolomide-resistant anaplastic glioma, but there seemed to be no significant restoration of temozolomide sensitivity in patients with temozolomide-resistant GBM.

Authors
Quinn, JA; Jiang, SX; Reardon, DA; Desjardins, A; Vredenburgh, JJ; Rich, JN; Gururangan, S; Friedman, AH; Bigner, DD; Sampson, JH; McLendon, RE; Herndon, JE; Walker, A; Friedman, HS
MLA Citation
Quinn, JA, Jiang, SX, Reardon, DA, Desjardins, A, Vredenburgh, JJ, Rich, JN, Gururangan, S, Friedman, AH, Bigner, DD, Sampson, JH, McLendon, RE, Herndon, JE, Walker, A, and Friedman, HS. "Phase II trial of temozolomide plus o6-benzylguanine in adults with recurrent, temozolomide-resistant malignant glioma." J Clin Oncol 27.8 (March 10, 2009): 1262-1267.
PMID
19204199
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
27
Issue
8
Publish Date
2009
Start Page
1262
End Page
1267
DOI
10.1200/JCO.2008.18.8417

Health-related quality of life in long-term breast cancer survivors: differences by adjuvant chemotherapy dose in Cancer and Leukemia Group B study 8541.

BACKGROUND: The Survivor's Health and Reaction (SHARE) study examined health-related quality of life (HRQL) in breast cancer patients who had participated in Cancer and Leukemia Group B Trial 8541 from 1985 to 1991. METHODS: In total, 245 survivors (78% of eligible patients) who were 9.4 to 16.5 years postdiagnosis (mean, 12.5 years postdiagnosis) completed HRQL surveys relating to 5 domains. Analyses examined HRQL domains according to 3 different chemotherapy dose levels that were administered in the original treatment trial: low-dose cyclophosphamide, doxorubicin, and fluorouracil (CAF) at 300 mg/m(2), 30 mg/m(2), and 300 x 2 mg/m(2), respectively, over 4 cycles; standard-dose CAF at 400 mg/m(2), 40 mg/m(2), and 400 x 2 mg/m(2), respectively, over 6 cycles; and high-dose CAF at 600 mg/m(2), 60 mg/m(2) and 600 x 2 mg/m(2), respectively, over 4 cycles. RESULTS: In univariate analyses, a statistically significant difference was observed on the Medical Outcomes Study 36-item short form Physical Role Functioning subscale by treatment group, with lower mean scores in the standard treatment arm (mean, 65.05) compared with mean scores in the low-dose arm (mean, 74.66) and the high-dose arm (mean, 84.94; P.0001). However, multivariate analysis revealed that treatment arm no longer was statistically significant, whereas the following factors were associated with decreased physical role functioning: age >or=60 years (odds ratio [OR], 3.55; P = .006), increased comorbidity interference total score (OR, 1.64; P = .005), lower vitality (OR, 1.05; P = .0002), and increased menopausal symptoms (OR, 1.04 P = .02). CONCLUSIONS: At 9.4-16.5 years after their original diagnosis, differences in physical role functioning among breast cancer survivors who had received 3 different dose levels of chemotherapy were explained by clinical and demographic variables, such as age, fatigue, menopausal symptoms, and comorbidities. Prospective studies are needed to further assess the role of these factors in explaining HRQL and physical role functioning among long-term survivors.

Authors
Paskett, E; Herndon, J; Donohue, K; Naughton, M; Grubbs, S; Pavy, M; Hensley, M; Stark, N; Kornblith, A; Bittoni, M; for Cancer and Leukemia Group B,
MLA Citation
Paskett, E, Herndon, J, Donohue, K, Naughton, M, Grubbs, S, Pavy, M, Hensley, M, Stark, N, Kornblith, A, Bittoni, M, and for Cancer and Leukemia Group B, . "Health-related quality of life in long-term breast cancer survivors: differences by adjuvant chemotherapy dose in Cancer and Leukemia Group B study 8541." Cancer 115.5 (March 1, 2009): 1109-1120.
PMID
19170232
Source
pubmed
Published In
Cancer
Volume
115
Issue
5
Publish Date
2009
Start Page
1109
End Page
1120
DOI
10.1002/cncr.24140

IDH1 and IDH2 mutations in gliomas.

BACKGROUND: A recent genomewide mutational analysis of glioblastomas (World Health Organization [WHO] grade IV glioma) revealed somatic mutations of the isocitrate dehydrogenase 1 gene (IDH1) in a fraction of such tumors, most frequently in tumors that were known to have evolved from lower-grade gliomas (secondary glioblastomas). METHODS: We determined the sequence of the IDH1 gene and the related IDH2 gene in 445 central nervous system (CNS) tumors and 494 non-CNS tumors. The enzymatic activity of the proteins that were produced from normal and mutant IDH1 and IDH2 genes was determined in cultured glioma cells that were transfected with these genes. RESULTS: We identified mutations that affected amino acid 132 of IDH1 in more than 70% of WHO grade II and III astrocytomas and oligodendrogliomas and in glioblastomas that developed from these lower-grade lesions. Tumors without mutations in IDH1 often had mutations affecting the analogous amino acid (R172) of the IDH2 gene. Tumors with IDH1 or IDH2 mutations had distinctive genetic and clinical characteristics, and patients with such tumors had a better outcome than those with wild-type IDH genes. Each of four tested IDH1 and IDH2 mutations reduced the enzymatic activity of the encoded protein. CONCLUSIONS: Mutations of NADP(+)-dependent isocitrate dehydrogenases encoded by IDH1 and IDH2 occur in a majority of several types of malignant gliomas.

Authors
Yan, H; Parsons, DW; Jin, G; McLendon, R; Rasheed, BA; Yuan, W; Kos, I; Batinic-Haberle, I; Jones, S; Riggins, GJ; Friedman, H; Friedman, A; Reardon, D; Herndon, J; Kinzler, KW; Velculescu, VE; Vogelstein, B; Bigner, DD
MLA Citation
Yan, H, Parsons, DW, Jin, G, McLendon, R, Rasheed, BA, Yuan, W, Kos, I, Batinic-Haberle, I, Jones, S, Riggins, GJ, Friedman, H, Friedman, A, Reardon, D, Herndon, J, Kinzler, KW, Velculescu, VE, Vogelstein, B, and Bigner, DD. "IDH1 and IDH2 mutations in gliomas." N Engl J Med 360.8 (February 19, 2009): 765-773.
PMID
19228619
Source
pubmed
Published In
The New England journal of medicine
Volume
360
Issue
8
Publish Date
2009
Start Page
765
End Page
773
DOI
10.1056/NEJMoa0808710

Cancer surveillance behaviors and psychosocial factors among long-term survivors of breast cancer. Cancer and Leukemia Group B 79804.

BACKGROUND: Little is known about cancer surveillance (mammography, clinical breast examination, and pelvic examination) behaviors in long-term (9-16 years) breast cancer survivors. This report describes the relation of these behaviors to demographic and clinical characteristics, psychological symptoms, body satisfaction, and social support. METHODS: Survivors who had participated in Cancer and Leukemia Group B treatment Trial 8541 completed a survey that included questions on breast cancer surveillance and pelvic examination, psychological well being, body satisfaction, and social support. RESULTS: The participation rate was 78% and included 245 breast cancer survivors. Survivors (n = 107; 44%) reported completing breast cancer surveillance (mammography and clinical breast examination) and completing pelvic examination (n = 162; 68%) within recommended guidelines. There were no significant associations between breast cancer surveillance and breast cancer anxiety, depression, stressful life events, body satisfaction, social support, or demographic characteristics. Survivors within recommended guidelines for pelvic examinations were younger (P = .05), married (P = .003), had health insurance (P = .004), and had lower depression scores (P = .005) than survivors who underused or overused pelvic examination. In addition, survivors within recommended pelvic examination guidelines had significantly lower levels of breast cancer anxiety (P = .03) compared with survivors who underused pelvic examination. CONCLUSIONS: Many long-term breast cancer survivors were not within recommended cancer surveillance guidelines. Private health insurance was associated with following recommendations for pelvic examinations, although such a relation did not exist for breast cancer surveillance. The results of this study have implications for the development of educational programs to improve cancer surveillance among the growing population of long-term breast cancer survivors.

Authors
Katz, ML; Donohue, KA; Alfano, CM; Day, JM; Herndon, JE; Paskett, ED
MLA Citation
Katz, ML, Donohue, KA, Alfano, CM, Day, JM, Herndon, JE, and Paskett, ED. "Cancer surveillance behaviors and psychosocial factors among long-term survivors of breast cancer. Cancer and Leukemia Group B 79804." Cancer 115.3 (February 1, 2009): 480-488.
PMID
19133656
Source
pubmed
Published In
Cancer
Volume
115
Issue
3
Publish Date
2009
Start Page
480
End Page
488
DOI
10.1002/cncr.24063

Early changes in tumor size in patients treated for advanced stage nonsmall cell lung cancer do not correlate with survival.

BACKGROUND: In clinical trials, change in tumor size is used to stratify patients into response categories. The objective of the current study was to: 1) determine whether early change in the tumor size were correlated with survival in patients with advanced nonsmall cell lung cancer (NSCLC) using modified response categories from the Response Evaluation Criteria in Solid Tumors (RECIST), and 2) to determine whether there was an optimal percentage change in tumor size that could be used to define a partial response that also correlated with survival. METHODS: A total of 99 consecutive patients presenting for the treatment of advanced NSCLC during the year 2003 who had computed tomography (CT) scans before and after treatment available for review were included in the study. The largest target thoracic lesion was measured on CT before treatment, and again 2 months to 3 months after the initiation of treatment. Percent change in tumor size was calculated. The relation between tumor response and patient survival was investigated. RESULTS: There was no definite relation noted between early tumor response and patient survival (P = .754). Patients who had any initial reduction in tumor size were not found to have a significantly different survival compared with patients with initial disease progression (P = .580). In addition, there was no particular percent reduction in tumor size that was found to optimally correlate with survival. CONCLUSIONS: There is no evidence of a relation between early changes in tumor size and survival among patients with advanced stage NSCLC. To predict survival in patients with advanced NSCLC, response criteria other than change in lesion size are needed.

Authors
Birchard, KR; Hoang, JK; Herndon, JE; Patz, EF
MLA Citation
Birchard, KR, Hoang, JK, Herndon, JE, and Patz, EF. "Early changes in tumor size in patients treated for advanced stage nonsmall cell lung cancer do not correlate with survival." Cancer 115.3 (February 1, 2009): 581-586.
PMID
19117348
Source
pubmed
Published In
Cancer
Volume
115
Issue
3
Publish Date
2009
Start Page
581
End Page
586
DOI
10.1002/cncr.24060

Phase II trial of Gliadel plus O6-benzylguanine in adults with recurrent glioblastoma multiforme.

PURPOSE: This phase II trial was designed to define the efficacy of Gliadel wafers in combination with an infusion of O6-benzylguanine (O6-BG) that suppresses tumor O6-alkylguanine-DNA alkyltransferase (AGT) levels in patients with recurrent glioblastoma multiforme for 5 days and to evaluate the safety of this combination therapy. EXPERIMENTAL DESIGN: This was a phase II, open-label, single center trial. On gross total resection of the tumor, up to eight Gliadel wafers were implanted. Bolus infusion of O6-BG was administered at 120 mg/m2 over 1 hour on days 1, 3, and 5, along with a continuous infusion at 30 mg/m2/d. The primary end points were 6-month overall survival (OS) and safety, and the secondary end points were 1-year, 2-year, and median OS. RESULTS: Fifty-two patients were accrued. The 6-month OS was 82% [95% confidence interval (95% CI), 72-93%]. The 1- and 2-year OS rates were 47% (95% CI, 35-63%) and 10% (95% CI, 3-32%), respectively. The median OS was 50.3 weeks (95% CI, 36.1-69.4 weeks). Treatment-related toxicity with this drug combination included grade 3 hydrocephalus (9.6%), grade 3 cerebrospinal fluid (CSF) leak (19.2%), and grade 3 CSF/brain infection (13.4%). CONCLUSION: The efficacy of implanted Gliadel wafers may be improved with the addition of O6-BG. Although systemically administered O6-BG can be coadministered with Gliadel wafers safely, it may increase the risk of hydrocephalus, CSF leak, and CSF/brain infection. Future trials are required to verify that inhibition of tumor AGT levels by O6-BG results in increased efficacy of Gliadel wafers without added toxicity.

Authors
Quinn, JA; Jiang, SX; Carter, J; Reardon, DA; Desjardins, A; Vredenburgh, JJ; Rich, JN; Gururangan, S; Friedman, AH; Bigner, DD; Sampson, JH; McLendon, RE; Herndon, JE; Threatt, S; Friedman, HS
MLA Citation
Quinn, JA, Jiang, SX, Carter, J, Reardon, DA, Desjardins, A, Vredenburgh, JJ, Rich, JN, Gururangan, S, Friedman, AH, Bigner, DD, Sampson, JH, McLendon, RE, Herndon, JE, Threatt, S, and Friedman, HS. "Phase II trial of Gliadel plus O6-benzylguanine in adults with recurrent glioblastoma multiforme." Clin Cancer Res 15.3 (February 1, 2009): 1064-1068.
PMID
19188181
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
15
Issue
3
Publish Date
2009
Start Page
1064
End Page
1068
DOI
10.1158/1078-0432.CCR-08-2130

Exercise and dietary change after diagnosis and cancer-related symptoms in long-term survivors of breast cancer: CALGB 79804.

OBJECTIVE: Improving diet and exercise can reduce survivors' risk of cancer-related fatigue, poor physical functioning, and potential recurrence. A cancer diagnosis can represent a 'teachable moment', leading survivors to make positive changes in diet and exercise behaviors; however, little is known about how often this occurs or about factors that enhance or limit survivors' ability to make these changes. This cross-sectional descriptive study investigated both the prevalence and clustering of self-reported changes in diet and exercise and how these changes related to ongoing cancer-related symptoms, social support, and stressful life events among long-term breast cancer survivors. METHODS: Survivors (n=227, response rate=72%) of a prior Cancer and Leukemia Group B treatment trial, on average 12 years post-diagnosis, completed a mailed survey assessing health behavior changes since diagnosis and current symptoms, social support, and stressful life events. RESULTS: Over half of survivors reported making positive exercise or diet changes since diagnosis: over 25% reported making exercise and diet changes. Analyses of covariance models showed that survivors who reported increasing their exercise also reported lower fatigue. Trends were also found between increased fruit and vegetable intake and decreased fatigue and between increased exercise and increased social support. CONCLUSIONS: These results underscore the need for health promotion efforts among survivors. Exercise promotion is especially needed since more survivors attempted to change dietary behaviors than exercise on their own. Further, fatigue may limit survivors' ability to change their health behaviors; alternatively, survivors who increase their exercise may experience less fatigue.

Authors
Alfano, CM; Day, JM; Katz, ML; Herndon, JE; Bittoni, MA; Oliveri, JM; Donohue, K; Paskett, ED
MLA Citation
Alfano, CM, Day, JM, Katz, ML, Herndon, JE, Bittoni, MA, Oliveri, JM, Donohue, K, and Paskett, ED. "Exercise and dietary change after diagnosis and cancer-related symptoms in long-term survivors of breast cancer: CALGB 79804." Psychooncology 18.2 (February 2009): 128-133.
PMID
18536022
Source
pubmed
Published In
Psycho-Oncology
Volume
18
Issue
2
Publish Date
2009
Start Page
128
End Page
133
DOI
10.1002/pon.1378

Determination of utility scores for control of chemotherapy-induced nausea or vomiting - CALGB 309801

Utility scores for temporary health states are not well defined. We investigated two techniques to define utilities for chemotherapy-induced nausea and vomiting. Patients receiving cyclic chemotherapy evaluated various hypothetical health states, each assuming 2-year overall survival with 1 year of chemotherapy followed by 1 year of good health. Health states included perfect health, no nausea/vomiting, limited nausea, limited vomiting, limited nausea/vomiting, and continuous nausea/vomiting. Subjects scored each health state with a rating scale and a standard gamble, using perfect health and continuous nausea/vomiting as positive and negative anchors. In addition, continuous nausea/vomiting was compared with a standard gamble between perfect health and immediate death. The study included 96 evaluable subjects. With perfect health and continuous nausea/vomiting anchors, rating scale scores for intermediate health states ranged from 43-84 whereas standard gamble scores clustered at approximately 55. However, using a standard gamble between perfect health and death, continuous nausea/vomiting had a utility score of 53. The decrement in utility for severe nausea/vomiting can be well characterized, but utility scores for less extreme health states of nausea/vomiting are not as distinct. Although the rating scale suggests some differentiation, the standard gamble reveals clustering of intermediate health state scores. Evaluation of the effect of varying duration and intensity of nausea/vomiting on standard gamble utility scores will provide greater insight into the impact of such temporary health states on quality of life. © 2009 Elsevier Inc. All rights reserved.

Authors
Grunberg, SM; Weeks, J; Magnan, WF; Herndon, J; Naughton, ML; Blackwell, KL; Wood, ME; Christian, DL; Perry, MC; Dees, EC; Reed, E; Marshall, ME
MLA Citation
Grunberg, SM, Weeks, J, Magnan, WF, Herndon, J, Naughton, ML, Blackwell, KL, Wood, ME, Christian, DL, Perry, MC, Dees, EC, Reed, E, and Marshall, ME. "Determination of utility scores for control of chemotherapy-induced nausea or vomiting - CALGB 309801." Journal of Supportive Oncology 7.5 (2009): W17-W22.
Source
scival
Published In
The Journal of Supportive Oncology
Volume
7
Issue
5
Publish Date
2009
Start Page
W17
End Page
W22

Reply to A. Katz et al

Authors
Strauss, GM; II, JEH; Maddaus, MA; Schilsky, RL; Vokes, EE; Green, MR
MLA Citation
Strauss, GM, II, JEH, Maddaus, MA, Schilsky, RL, Vokes, EE, and Green, MR. "Reply to A. Katz et al." Journal of Clinical Oncology 27.13 (2009): 2301-2302.
Source
scival
Published In
Journal of Clinical Oncology
Volume
27
Issue
13
Publish Date
2009
Start Page
2301
End Page
2302
DOI
10.1200/JCO.2008.21.2126

Arm/hand swelling and perceived functioning among breast cancer survivors 12 years post-diagnosis: CALGB 79804.

INTRODUCTION: Lymphedema is an under-reported and debilitating consequence of axillary node dissection among breast cancer survivors. This study describes the characteristics of arm and hand swelling in relation to perceived physical and mental health functioning among breast cancer survivors 9-16 years post-diagnosis who previously participated in a clinical trial coordinated by the Cancer and Leukemia Group B (CALGB 8541). METHODS: Eligible survivors of CALGB 8541 completed questionnaires assessing demographics, arm/hand swelling, perceived physical functioning, and mental health. RESULTS: Two hundred forty-five women (94% white, mean age = 63, on average 12.4 years post-diagnosis) completed questionnaires (participation rate = 78%). Seventy-five women (31%) reported arm/hand swelling since their surgery. Of these women, 76% reported current swelling and half reported constant swelling, mainly in the upper arm. Swelling was reported as mild or moderate in 88% of the women. Women who reported severe swelling had significantly worse physical functioning and trended toward worse depressive symptoms and poorer mental health (lower mental SF-36 scores) as well. Activity-limiting swelling was also significantly associated with worse physical functioning. Although swelling interfered with wearing clothing (36%) and perceptions about general appearance (32%), only 37% of women sought treatment for swelling. CONCLUSIONS: Arm/hand swelling is a chronic problem for a subgroup of long-term survivors of breast cancer, negatively affecting physical functioning. IMPLICATIONS FOR CANCER SURVIVORS: Educational efforts are needed as part of a comprehensive survivorship care plan to raise awareness about lymphedema so that survivors may identify this complication, seek treatment early, and potentially improve their physical functioning.

Authors
Oliveri, JM; Day, JM; Alfano, CM; Herndon, JE; Katz, ML; Bittoni, MA; Donohue, K; Paskett, ED
MLA Citation
Oliveri, JM, Day, JM, Alfano, CM, Herndon, JE, Katz, ML, Bittoni, MA, Donohue, K, and Paskett, ED. "Arm/hand swelling and perceived functioning among breast cancer survivors 12 years post-diagnosis: CALGB 79804." J Cancer Surviv 2.4 (December 2008): 233-242.
PMID
18792786
Source
pubmed
Published In
Journal of Cancer Survivorship
Volume
2
Issue
4
Publish Date
2008
Start Page
233
End Page
242
DOI
10.1007/s11764-008-0065-y

Improving health care efficiency and quality using tablet personal computers to collect research-quality, patient-reported data.

OBJECTIVE: To determine whether e/Tablets (wireless tablet computers used in community oncology clinics to collect review of systems information at point of care) are feasible, acceptable, and valid for collecting research-quality data in academic oncology. DATA/SETTING: Primary/Duke Breast Cancer Clinic. DESIGN: Pilot study enrolling sample of 66 breast cancer patients. METHODS: Data were collected using paper- and e/Tablet-based surveys: Functional Assessment of Cancer Therapy General, Functional Assessment of Cancer Therapy-Breast, MD Anderson Symptom Inventory, Functional Assessment of Chronic Illness Therapy (FACIT), Self-Efficacy; and two questionnaires: feasibility, satisfaction. PRINCIPAL FINDINGS: Patients supported e/Tablets as: easy to read (94 percent), easy to respond to (98 percent), comfortable weight (87 percent). Generally, electronic responses validly reflected responses provided by standard paper data collection on nearly all subscales tested. CONCLUSIONS: e/Tablets offer a valid, feasible, acceptable method for collecting research-quality, patient-reported outcomes data in outpatient academic oncology.

Authors
Abernethy, AP; Herndon, JE; Wheeler, JL; Patwardhan, M; Shaw, H; Lyerly, HK; Weinfurt, K
MLA Citation
Abernethy, AP, Herndon, JE, Wheeler, JL, Patwardhan, M, Shaw, H, Lyerly, HK, and Weinfurt, K. "Improving health care efficiency and quality using tablet personal computers to collect research-quality, patient-reported data." Health Serv Res 43.6 (December 2008): 1975-1991.
PMID
18761678
Source
pubmed
Published In
Health Services Research
Volume
43
Issue
6
Publish Date
2008
Start Page
1975
End Page
1991
DOI
10.1111/j.1475-6773.2008.00887.x

Detection of humoral response in patients with glioblastoma receiving EGFRvIII-KLH vaccines.

The epidermal growth factor receptor variant III (EGFRvIII) is a consistent tumor-specific mutation that is widely expressed in glioblastoma multiforme (GBM) and other neoplasms. As such it represents a truly tumor-specific target for antitumor immunotherapy. Although endogenous humoral responses to EGFRvIII have been reported in patients with EGFRvIII-expressing breast cancer, it is not known whether de novo responses can be generated or endogenous responses enhanced with an EGFRvIII-specific vaccine. To assess this in clinical trials, we have developed and validated an immunoassay to measure and isolate anti-EGFRvIII and anti-KLH antibodies from the serum of patients vaccinated with an EGFRvIII-specific peptide (PEPvIII) conjugated to keyhole limpet hemocyanin (KLH). Using magnetic beads with immobilized antigen we captured and detected anti-EGFRvIII and anti-KLH antibodies in serum from patients before and after vaccinations. Using this assay, we found that significant levels of antibody for tumor-specific antigen EGFRvIII (>4 microg/mL) and KLH could be induced after vaccination with PEPvIII-KLH.

Authors
Schmittling, RJ; Archer, GE; Mitchell, DA; Heimberger, A; Pegram, C; Herndon, JE; Friedman, HS; Bigner, DD; Sampson, JH
MLA Citation
Schmittling, RJ, Archer, GE, Mitchell, DA, Heimberger, A, Pegram, C, Herndon, JE, Friedman, HS, Bigner, DD, and Sampson, JH. "Detection of humoral response in patients with glioblastoma receiving EGFRvIII-KLH vaccines." J Immunol Methods 339.1 (November 30, 2008): 74-81.
PMID
18775433
Source
pubmed
Published In
Journal of Immunological Methods
Volume
339
Issue
1
Publish Date
2008
Start Page
74
End Page
81
DOI
10.1016/j.jim.2008.08.004

Comorbidity, age, race and stage at diagnosis in colorectal cancer: a retrospective, parallel analysis of two health systems.

BACKGROUND: Stage at diagnosis plays a significant role in colorectal cancer (CRC) survival. Understanding which factors contribute to a more advanced stage at diagnosis is vital to improving overall survival. Comorbidity, race, and age are known to impact receipt of cancer therapy and survival, but the relationship of these factors to stage at diagnosis of CRC is less clear. The objective of this study is to investigate how comorbidity, race and age influence stage of CRC diagnosis. METHODS: Two distinct healthcare populations in the United States (US) were retrospectively studied. Using the Cancer Care Outcomes Research and Surveillance Consortium database, we identified CRC patients treated at 15 Veterans Administration (VA) hospitals from 2003-2007. We assessed metastatic CRC patients treated from 2003-2006 at 10 non-VA, fee-for-service (FFS) practices. Stage at diagnosis was dichotomized (non-metastatic, metastatic). Race was dichotomized (white, non-white). Charlson comorbidity index and age at diagnosis were calculated. Associations between stage, comorbidity, race, and age were determined by logistic regression. RESULTS: 342 VA and 340 FFS patients were included. Populations differed by the proportion of patients with metastatic CRC at diagnosis (VA 27% and FFS 77%) reflecting differences in eligibility criteria for inclusion. VA patients were mean (standard deviation; SD) age 67 (11), Charlson index 2.0 (1.0), and were 63% white. FFS patients were mean age 61 (13), Charlson index 1.6 (1.0), and were 73% white. In the VA cohort, higher comorbidity was associated with earlier stage at diagnosis after adjusting for age and race (odds ratio (OR) 0.76, 95% confidence interval (CI) 0.58-1.00; p = 0.045); no such significant relationship was identified in the FFS cohort (OR 1.09, 95% CI 0.82-1.44; p = 0.57). In both cohorts, no association was found between stage at diagnosis and either age or race. CONCLUSION: Higher comorbidity may lead to earlier stage of CRC diagnosis. Multiple factors, perhaps including increased interactions with the healthcare system due to comorbidity, might contribute to this finding. Such increased interactions are seen among patients within a healthcare system like the VA system in the US versus sporadic interactions which may be seen with FFS healthcare.

Authors
Zafar, SY; Abernethy, AP; Abbott, DH; Grambow, SC; Marcello, JE; Herndon, JE; Rowe, KL; Kolimaga, JT; Zullig, LL; Patwardhan, MB; Provenzale, DT
MLA Citation
Zafar, SY, Abernethy, AP, Abbott, DH, Grambow, SC, Marcello, JE, Herndon, JE, Rowe, KL, Kolimaga, JT, Zullig, LL, Patwardhan, MB, and Provenzale, DT. "Comorbidity, age, race and stage at diagnosis in colorectal cancer: a retrospective, parallel analysis of two health systems. (Published online)" BMC Cancer 8 (November 25, 2008): 345-.
PMID
19032772
Source
pubmed
Published In
BMC Cancer
Volume
8
Publish Date
2008
Start Page
345
DOI
10.1186/1471-2407-8-345

Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non-small-cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups.

PURPOSE: Adjuvant chemotherapy for resected non-small-cell lung cancer (NSCLC) is now accepted on the basis of several randomized clinical trials (RCTs) that demonstrated improved survival. Although there is strong evidence that adjuvant chemotherapy is effective in stages II and IIIA NSCLC, its utility in stage IB disease is unclear. This report provides a mature analysis of Cancer and Leukemia Group B (CALGB) 9633, the only RCT designed specifically for stage IB NSCLC. PATIENTS AND METHODS: Within 4 to 8 weeks of resection, patients were randomly assigned to adjuvant chemotherapy or observation. Eligible patients had pathologically confirmed T2N0 NSCLC and had undergone lobectomy or pneumonectomy. Chemotherapy consisted of paclitaxel 200 mg/m(2) intravenously over 3 hours and carboplatin at an area under the curve dose of 6 mg/mL per minute intravenously over 45 to 60 minutes every 3 weeks for four cycles. The primary end point was overall survival. RESULTS: Three hundred-forty-four patients were randomly assigned. Median follow-up was 74 months. Groups were well-balanced with regard to demographics, histology, and extent of surgery. Grades 3 to 4 neutropenia were the predominant toxicity; there were no treatment-related deaths. Survival was not significantly different (hazard ratio [HR], 0.83; CI, 0.64 to 1.08; P = .12). However, exploratory analysis demonstrated a significant survival difference in favor of adjuvant chemotherapy for patients who had tumors > or = 4 cm in diameter (HR, 0.69; CI, 0.48 to 0.99; P = .043). CONCLUSION: Because a significant survival advantage was not observed across the entire cohort, adjuvant chemotherapy should not be considered standard care in stage IB NSCLC. Given the magnitude of observed survival differences, CALGB 9633 was underpowered to detect small but clinically meaningful improvements. A statistically significant survival advantage for patients who had tumors > or = 4 cm supports consideration of adjuvant paclitaxel/carboplatin for stage IB patients who have large tumors.

Authors
Strauss, GM; Herndon, JE; Maddaus, MA; Johnstone, DW; Johnson, EA; Harpole, DH; Gillenwater, HH; Watson, DM; Sugarbaker, DJ; Schilsky, RL; Vokes, EE; Green, MR
MLA Citation
Strauss, GM, Herndon, JE, Maddaus, MA, Johnstone, DW, Johnson, EA, Harpole, DH, Gillenwater, HH, Watson, DM, Sugarbaker, DJ, Schilsky, RL, Vokes, EE, and Green, MR. "Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non-small-cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups." J Clin Oncol 26.31 (November 1, 2008): 5043-5051.
PMID
18809614
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
26
Issue
31
Publish Date
2008
Start Page
5043
End Page
5051
DOI
10.1200/JCO.2008.16.4855

Bevacizumab plus irinotecan in recurrent WHO grade 3 malignant gliomas.

PURPOSE: Although patients with newly diagnosed WHO grade 3 malignant glioma have a more favorable prognosis than those with WHO grade 4 malignant glioma, salvage therapies following recurrence offer essentially palliative benefit. We did a phase II trial of bevacizumab, a monoclonal antibody to vascular endothelial growth factor, in combination with irinotecan for patients with recurrent grade 3 malignant glioma. EXPERIMENTAL DESIGN: Upon documentation of adequate safety among an initial cohort of nine patients treated with bevacizumab (10 mg/kg) and irinotecan every 14 days, a second cohort (n=24) was treated with bevacizumab (15 mg/kg) every 3 weeks with irinotecan on days 1, 8, 22, and 29 of each 42-day cycle. For both cohorts, the dose of irinotecan was 340 mg/m(2) for patients on enzyme-inducing antiepileptic drugs (EIAED) and 125 mg/m(2) for patients not on EIAEDs. After each 6-week cycle, patients were evaluated with a physical examination and magnetic resonance imaging. RESULTS: The 6-month progression-free survival was 55% (95% confidence interval, 36-70%). The 6-month overall survival was 79% (95% confidence interval, 61-89%). Twenty patients (61%) had at least a partial response. Outcome did not differ between the two treatment cohorts. Significant adverse events were infrequent and included a central nervous system hemorrhage in one patient, and one patient who developed thrombotic thrombocytopenic purpura. CONCLUSION: Bevacizumab and irinotecan is an active regimen with acceptable toxicity for patients with recurrent WHO grade 3 malignant glioma.

Authors
Desjardins, A; Reardon, DA; Herndon, JE; Marcello, J; Quinn, JA; Rich, JN; Sathornsumetee, S; Gururangan, S; Sampson, J; Bailey, L; Bigner, DD; Friedman, AH; Friedman, HS; Vredenburgh, JJ
MLA Citation
Desjardins, A, Reardon, DA, Herndon, JE, Marcello, J, Quinn, JA, Rich, JN, Sathornsumetee, S, Gururangan, S, Sampson, J, Bailey, L, Bigner, DD, Friedman, AH, Friedman, HS, and Vredenburgh, JJ. "Bevacizumab plus irinotecan in recurrent WHO grade 3 malignant gliomas." Clin Cancer Res 14.21 (November 1, 2008): 7068-7073.
PMID
18981004
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
14
Issue
21
Publish Date
2008
Start Page
7068
End Page
7073
DOI
10.1158/1078-0432.CCR-08-0260

Applying a conceptual model for examining health-related quality of life in long-term breast cancer survivors: CALGB study 79804.

OBJECTIVES: The Survivor's Health and Reaction study used a quality-of-life model adapted for cancer survivors by Dow and colleagues to identify factors related to global health-related quality of life (HRQL) and to document the prevalence of problems and health-oriented behaviors in a follow-up study of breast cancer patients who participated in CALGB 8541. METHODS: A total of 245 survivors (78% of those invited) who were 9.4-16.5 years post-diagnosis completed surveys that inquired about current HRQL, economic, spiritual, physical and psychosocial concerns, and health-oriented behaviors (e.g. smoking, exercise, and supplement use). A regression model was developed to examine factors related to global HRQL across all domains. RESULTS: The regression model revealed that decreased energy levels (odds ratio (OR)=1.05, 95% confidence interval (CI): 1.03, 1.07), having heart disease (OR=5.01, 95% CI: 1.39, 18.1), having two or more co-morbidities (OR=2.39, 95% CI: 1.10, 5.19), and lower social support (OR=1.03, 95% CI: 1.02, 1.05) were associated with lower global HRQL. Factors related to psychological, spiritual, and economic domains were not predictive of global HRQL. Regarding lifestyle changes, some women reported engaging in health-oriented behaviors since their cancer diagnosis, such as improving eating habits (54%), increasing exercise (32%), and reducing/quitting smoking (20%). The most prevalent problems reported by women at follow-up were menopausal symptoms (64%), such as hot flashes and vaginal dryness, osteoporosis (25%), and lymphedema (23%). CONCLUSION: Suggestions are provided to target interventions, such as provider-based strategies, in order to improve HRQL in long-term breast cancer survivors.

Authors
Paskett, ED; Herndon, JE; Day, JM; Stark, NN; Winer, EP; Grubbs, SS; Pavy, MD; Shapiro, CL; List, MA; Hensley, ML; Naughton, MA; Kornblith, AB; Habin, KR; Fleming, GF; Bittoni, MA; Cancer and Leukemia Group B,
MLA Citation
Paskett, ED, Herndon, JE, Day, JM, Stark, NN, Winer, EP, Grubbs, SS, Pavy, MD, Shapiro, CL, List, MA, Hensley, ML, Naughton, MA, Kornblith, AB, Habin, KR, Fleming, GF, Bittoni, MA, and Cancer and Leukemia Group B, . "Applying a conceptual model for examining health-related quality of life in long-term breast cancer survivors: CALGB study 79804." Psychooncology 17.11 (November 2008): 1108-1120.
PMID
18314912
Source
pubmed
Published In
Psycho-Oncology
Volume
17
Issue
11
Publish Date
2008
Start Page
1108
End Page
1120
DOI
10.1002/pon.1329

Phase II trial of paclitaxel and cisplatin in patients with extensive stage small cell lung cancer: Cancer and Leukemia Group B Trial 9430.

BACKGROUND: Cancer and Leukemia Group B trial 9430 was a randomized phase II trial which investigated the safety and activity of four novel doublets in untreated extensive stage small cell lung cancer. The results of the paclitaxel and cisplatin arm have not been reported. PATIENTS AND METHODS: Patients received paclitaxel 230 mg/m followed by cisplatin 75 mg/m on day 1 every 21 days. All patients received granulocyte colony stimulating factor 5 microg/kg/d beginning on day 3 of each cycle. RESULTS: The patient characteristics of the 34 patients assigned to this treatment arm were: median age 61.5 years (range 41-82), male (76%), performance status 0 (41%), 1 (32%), and 2 (26%). An objective response was observed in 23 patients (68%; 95% confidence interval (CI): 49-83%); 2 complete responses (6%) and 21 partial responses (62%). Median progression-free survival time was 5.6 months (95% CI: 4.8-7.1 month), and median overall survival time was 7.7 months (95% CI: 7.2-12.6 months). The 1-year survival rate observed was 29% (95% CI: 15-45%). Grade 3/4 neutropenia and thrombocytopenia was observed in 5 (15%) and 4 (12%) patients, respectively. Two patients developed febrile neutropenia including one patient who died of neutropenic sepsis. Grade 3/4 nonhematologic observed were: sensory neuropathy in eight patients (24%); and hyperglycemia, malaise and nausea were all observed in four patients (12%). CONCLUSIONS: Cancer and Leukemia Group B will not pursue further investigation of paclitaxel and cisplatin due to the modest activity and the toxicity observed on this trial.

Authors
Stinchcombe, TE; Mauer, AM; Hodgson, LD; Herndon, JE; Lynch, TJ; Green, MR; Vokes, EE; Cancer and Leukemia Group B,
MLA Citation
Stinchcombe, TE, Mauer, AM, Hodgson, LD, Herndon, JE, Lynch, TJ, Green, MR, Vokes, EE, and Cancer and Leukemia Group B, . "Phase II trial of paclitaxel and cisplatin in patients with extensive stage small cell lung cancer: Cancer and Leukemia Group B Trial 9430." J Thorac Oncol 3.11 (November 2008): 1301-1307.
PMID
18978566
Source
pubmed
Published In
Journal of Thoracic Oncology
Volume
3
Issue
11
Publish Date
2008
Start Page
1301
End Page
1307
DOI
10.1097/JTO.0b013e318187494a

Interruptions of once-daily thoracic radiotherapy do not correlate with outcomes in limited stage small cell lung cancer: analysis of CALGB phase III trial 9235.

PURPOSE: Retrospective data suggests prolonging the time to complete thoracic radiotherapy (TRT) may negatively impact tumor control and survival in limited stage small cell lung cancer (LSCLC). We examined the association between TRT duration and outcomes on a prospective phase III study. MATERIAL AND METHODS: This review included 267 patients who received protocol TRT on a phase III CALGB LSCLC study assessing the addition of tamoxifen to standard chemo-radiotherapy. TRT, to a planned dose of 50Gy in 2Gy daily fractions, was initiated with the fourth chemotherapy cycle. TRT interruptions were mandated for hematologic toxicity (granulocytes<1000/mm3 or platelets<75,000/mm3) and esophageal toxicity (dysphagia necessitating intravenous hydration). RESULTS: TRT interruptions > or =3 days occurred in 115 patients (43%), most frequently during the 4th week of TRT, and did not differ between treatment arms. Hematologic toxicity and esophageal toxicity were the most frequent indications for interrupting TRT. Variables including advanced age (>70 years), gender, race, or radiotherapy treatment volume did not predict for TRT interruptions. Overall survival (OS) and local tumor control did not correlate with the administration of TRT interruptions or with TRT duration. CONCLUSION: Toxicity mandated interruptions of conventional dose, once-daily, TRT may not adversely affect outcomes for patients receiving TRT concurrent with chemotherapy (cycle 4) for LSCLC. The implications for accelerated or high dose TRT regimens are not clear.

Authors
Bogart, JA; Watson, D; McClay, EF; Evans, L; Herndon, JE; Laurie, F; Seagren, SL; Fitzgerald, TJ; Vokes, E; Green, MR
MLA Citation
Bogart, JA, Watson, D, McClay, EF, Evans, L, Herndon, JE, Laurie, F, Seagren, SL, Fitzgerald, TJ, Vokes, E, and Green, MR. "Interruptions of once-daily thoracic radiotherapy do not correlate with outcomes in limited stage small cell lung cancer: analysis of CALGB phase III trial 9235." Lung Cancer 62.1 (October 2008): 92-98.
PMID
18367288
Source
pubmed
Published In
Lung Cancer
Volume
62
Issue
1
Publish Date
2008
Start Page
92
End Page
98
DOI
10.1016/j.lungcan.2008.02.006

Patient education level as a predictor of survival in lung cancer clinical trials.

PURPOSE: To investigate the effect of socioeconomic status, as measured by education, on the survival of 1,577 lung cancer patients treated on 11 studies conducted by the Cancer and Leukemia Group B. PATIENTS AND METHODS: Sociodemographic data, including education, was reported by the patient at the time of clinical trial accrual. Cox proportional hazards model stratified by treatment arm/study was used to examine the effect of education on survival after adjustment for known prognostic factors. RESULTS: The patient population included 1,177 patients diagnosed with non-small-cell lung cancer (NSCLC; stage III or IV) and 400 patients diagnosed with small-cell lung cancer (SCLC; extensive or limited). Patients with less than an eighth grade education (13% of patients) were significantly more likely to be male, nonwhite, and older; have a performance status (PS) of 1 or 2; and have chest pain. Significant predictors of poor survival in the final model included male sex, PS of 1 or 2, dyspnea, weight loss, liver or bone metastases, unmarried, presence of adrenal metastases and high alkaline phosphatase levels among patients with NSCLC, and high WBC levels among patients with advanced disease. Education was not predictive of survival. CONCLUSION: The physical condition of patients with low education who enroll onto clinical trials is worse than patients with higher education. Once enrolled onto a clinical trial, education does not affect the survival of patients with SCLC or stage III or IV NSCLC. The standardization of treatment and follow-up within a clinical trial, regardless of education, is one possible explanation for this lack of effect.

Authors
Herndon, JE; Kornblith, AB; Holland, JC; Paskett, ED
MLA Citation
Herndon, JE, Kornblith, AB, Holland, JC, and Paskett, ED. "Patient education level as a predictor of survival in lung cancer clinical trials." J Clin Oncol 26.25 (September 1, 2008): 4116-4123.
PMID
18757325
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
26
Issue
25
Publish Date
2008
Start Page
4116
End Page
4123
DOI
10.1200/JCO.2008.16.7460

Quality of life outcomes are equivalent after lobectomy in the elderly.

OBJECTIVE: Prospective analyses of quality of life in elderly patients after lobectomy are limited, yet surgeons often recommend suboptimal therapy to these patients on the basis of the belief that lobectomy is poorly tolerated. Surgical decision making in elderly patients with lung cancer is better informed when the benefits to survival and quality of life after lobectomy are understood. METHODS: By using a validated quality of life instrument, 422 patients were prospectively assessed preoperatively and 3, 6, and 12 months after lobectomy. Outcomes were analyzed with respect to age (group 1: < 70 years and group 2: > or = 70 years). The outcome domains of physical functioning, role functioning, emotional functioning, cognitive functioning, social functioning, global health, and pain in the chest were analyzed using a mixed model. The trend in quality of life was determined according to age. The Kaplan-Meier method was used for analysis of overall survival. RESULTS: The mean age was 60.1 years in group 1 (N = 256) and 74.7 years in group 2 (N = 166). Baseline demographics and quality of life were similar except that group 2 had better emotional functioning scores and worse pain in the chest scores. Postoperatively, both groups demonstrated significant decreases in quality of life at 3 months. However, at 6 and 12 months, all domains had returned to baseline except physical functioning, which remained below baseline in group 2. Emotional functioning improved postoperatively for both groups. Overall survival at 5 years was not different between groups. CONCLUSION: By using a validated quality of life assessment tool with measurements at baseline and serially after resection in a large patient population, this analysis quantifies the degree of impairment of quality of life after lobectomy and documents time to full recovery for both age groups.

Authors
Burfeind, WR; Tong, BC; O'Branski, E; Herndon, JE; Toloza, EM; D'Amico, TA; Harpole, LH; Harpole, DH
MLA Citation
Burfeind, WR, Tong, BC, O'Branski, E, Herndon, JE, Toloza, EM, D'Amico, TA, Harpole, LH, and Harpole, DH. "Quality of life outcomes are equivalent after lobectomy in the elderly." J Thorac Cardiovasc Surg 136.3 (September 2008): 597-604.
PMID
18805257
Source
pubmed
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
136
Issue
3
Publish Date
2008
Start Page
597
End Page
604
DOI
10.1016/j.jtcvs.2008.02.093

Local excision of distal rectal cancer: an update of cancer and leukemia group B 8984.

PURPOSE: The efficacy of local excision in the treatment of some early-stage distal rectal cancers is still being debated, because few high-quality, long-term prospective data on outcomes are available. METHODS: Fifty-nine patients with T1 lesions were treated with local excision alone, whereas 51 patients with T2 lesions received external beam irradiation (5,400 cGY) and 5-fluorouracil (500 mg/m(2) intravenously Days 1-3, Days 29-31) after local excision. Kaplan-Meier curves were used to estimate the primary outcomes. The log-rank test and Cox's proportional hazards model were used to compare subgroups relative to these outcomes. RESULTS: With a median follow-up of 7.1 (range, 2.1-11.4) years, ten-year rates of overall survival were 84 percent for patients with T1 and 66 percent for T2 rectal cancer. Disease-free survival was 75 percent for T1 and 64 percent for T2 disease. Local recurrence rates for patients with T1 and T2 lesions were 8 and 18 percent, respectively, and rates of distant metastases were 5 percent for T1 and 12 percent for T2 lesions. T stage was a statistically significant predictor of overall survival (P = 0.04) and approached statistical significance as a predictor of disease-free survival (P = 0.07). CONCLUSIONS: Local excision alone for T1 rectal adenocarcinomas is associated with low recurrence and good survival rates that remain durable with long-term follow-up. T2 lesions treated via local excision and adjuvant therapy are associated with higher recurrence rates.

Authors
Greenberg, JA; Shibata, D; Herndon, JE; Steele, GD; Mayer, R; Bleday, R
MLA Citation
Greenberg, JA, Shibata, D, Herndon, JE, Steele, GD, Mayer, R, and Bleday, R. "Local excision of distal rectal cancer: an update of cancer and leukemia group B 8984." Dis Colon Rectum 51.8 (August 2008): 1185-1191.
PMID
18536973
Source
pubmed
Published In
Diseases of the Colon and Rectum
Volume
51
Issue
8
Publish Date
2008
Start Page
1185
End Page
1191
DOI
10.1007/s10350-008-9231-6

Intracerebral infusion of an EGFR-targeted toxin in recurrent malignant brain tumors.

The purpose of this study is to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and intracerebral distribution of a recombinant toxin (TP-38) targeting the epidermal growth factor receptor in patients with recurrent malignant brain tumors using the intracerebral infusion technique of convection-enhanced delivery (CED). Twenty patients were enrolled and stratified for dose escalation by the presence of residual tumor from 25 to 100 ng/ml in a 40-ml infusion volume. In the last eight patients, coinfusion of (123)I-albumin was performed to monitor distribution within the brain. The MTD was not reached in this study. Dose escalation was stopped at 100 ng/ml due to inconsistent drug delivery as evidenced by imaging the coinfused (123)I-albumin. Two DLTs were seen, and both were neurologic. Median survival after TP-38 was 28 weeks (95% confidence interval, 26.5-102.8). Of 15 patients treated with residual disease, two (13.3%) demonstrated radiographic responses, including one patient with glioblastoma multiforme who had a nearly complete response and remains alive >260 weeks after therapy. Coinfusion of (123)I-albumin demonstrated that high concentrations of the infusate could be delivered >4 cm from the catheter tip. However, only 3 of 16 (19%) catheters produced intraparenchymal infusate distribution, while the majority leaked infusate into the cerebrospinal fluid spaces. Intracerebral CED of TP-38 was well tolerated and produced some durable radiographic responses at doses

Authors
Sampson, JH; Akabani, G; Archer, GE; Berger, MS; Coleman, RE; Friedman, AH; Friedman, HS; Greer, K; Herndon, JE; Kunwar, S; McLendon, RE; Paolino, A; Petry, NA; Provenzale, JM; Reardon, DA; Wong, TZ; Zalutsky, MR; Pastan, I; Bigner, DD
MLA Citation
Sampson, JH, Akabani, G, Archer, GE, Berger, MS, Coleman, RE, Friedman, AH, Friedman, HS, Greer, K, Herndon, JE, Kunwar, S, McLendon, RE, Paolino, A, Petry, NA, Provenzale, JM, Reardon, DA, Wong, TZ, Zalutsky, MR, Pastan, I, and Bigner, DD. "Intracerebral infusion of an EGFR-targeted toxin in recurrent malignant brain tumors." Neuro Oncol 10.3 (June 2008): 320-329.
PMID
18403491
Source
pubmed
Published In
Neuro-Oncology
Volume
10
Issue
3
Publish Date
2008
Start Page
320
End Page
329
DOI
10.1215/15228517-2008-012

Safety and pharmacokinetics of dose-intensive imatinib mesylate plus temozolomide: phase 1 trial in adults with malignant glioma.

We determined the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of imatinib mesylate, an inhibitor of the receptor tyrosine kinases platelet-derived growth factor receptor (PDGFR), the proto-oncogene product c-kit, and the fusion protein Bcr-Abl, when administered for 8 days in combination with temozolomide (TMZ) to malignant glioma (MG) patients. MG patients who had not failed prior TMZ were eligible to receive TMZ at a dose of 150-200 mg/m(2) per day on days 4-8 plus imatinib mesylate administered orally on days 1-8 of each 4-week cycle. Patients were stratified based on concurrent administration of CYP3A4-inducing antiepileptic drugs (EIAEDs). The imatinib dose was escalated in successive cohorts of patients independently for each stratum. Imatinib, at doses ranging from 400 mg to 1,200 mg, was administered with TMZ to 65 patients: 52 (80%) with glioblastoma multiforme (GBM) and 13 (20%) with grade III MG. At enrollment, 34 patients (52%) had stable disease, and 33 (48%) had progressive disease; 30 patients (46%) were on EIAEDs. The MTD of imatinib for patients concurrently receiving or not receiving EIAEDs was 1,000 mg. DLTs were hematologic, gastrointestinal, renal, and hepatic. Pharmacokinetic analyses revealed lowered exposures and enhanced clearance among patients on EIAEDs. Among GBM patients with stable disease at enrollment (n=28), the median progression-free and overall survival times were 41.7 and 56.1 weeks, respectively. Imatinib doses up to 1,000 mg/day for 8 consecutive days are well tolerated when combined with standard TMZ dosing for MG patients. A subsequent phase 2 study is required to further evaluate the efficacy of this regimen for this patient population.

Authors
Reardon, DA; Desjardins, A; Vredenburgh, JJ; Sathornsumetee, S; Rich, JN; Quinn, JA; Lagattuta, TF; Egorin, MJ; Gururangan, S; McLendon, R; Herndon, JE; Friedman, AH; Salvado, AJ; Friedman, HS
MLA Citation
Reardon, DA, Desjardins, A, Vredenburgh, JJ, Sathornsumetee, S, Rich, JN, Quinn, JA, Lagattuta, TF, Egorin, MJ, Gururangan, S, McLendon, R, Herndon, JE, Friedman, AH, Salvado, AJ, and Friedman, HS. "Safety and pharmacokinetics of dose-intensive imatinib mesylate plus temozolomide: phase 1 trial in adults with malignant glioma." Neuro Oncol 10.3 (June 2008): 330-340.
PMID
18359865
Source
pubmed
Published In
Neuro-Oncology
Volume
10
Issue
3
Publish Date
2008
Start Page
330
End Page
340
DOI
10.1215/15228517-2008-003

E/Tablets to collect research-quality, patient-reported data.

17528 Background: Programmed, wireless, notebook-and-pen style, computers ("e/Tablets") can collect review of systems data at the point of care, for use in the clinic visit. Can e/Tablets deployed in outpatient oncology clinics be used to collect research survey data that are comparable to paper-based data? METHODS: We used PACE e/Tablets (SOS, Inc.) to administer the disease-specific Functional Assessment of Cancer Therapy (FACT), MD Anderson Symptom Inventory (MDASI), and FACT-GOG-Neurotoxicity (NTX) scales. Participants were 113 gastrointestinal (GI) cancer patients in Duke GI Oncology Clinic. At each of 4 visits in 6 months, participants completed all surveys in electronic format and 1 survey on paper. Subscales (electronic vs. paper) were compared using paired t-tests. Patients completed an electronic satisfaction survey. RESULTS: Mean age, 57 (SD 11); 67% male; 80% Caucasian; 47% no college degree; 67% metastatic cancer. Patients strongly supported e/Tablets: easy to read (97%), easy to respond to questions (97%), weight of computer comfortable (92%). Patients reported e/Tablets to be helpful for reporting symptoms (82%), and would recommend them to other patients (88%). After Bonferonni corrections (0.05/10=0.005), survey subscale scores for paper and electronic were similar except for the NTX scale. CONCLUSIONS: Patients are satisfied with e/Tablets to collect survey data. Preliminary results show that e/Tablets furnish comparable data to those collected by paper questionnaires on nearly all subscales tested. These results in GI cancers support our previous breast cancer study results, suggesting that e/Tablets offer a valid, feasible method for collecting research-quality, clinically relevant data from patients in outpatient academic oncology. [Table: see text] [Table: see text].

Authors
Uronis, HE; Herndon, JE; Coan, A; Bronson, K; Wheeler, J; Lyerly, HK; Morse, MA; Abernethy, AP
MLA Citation
Uronis, HE, Herndon, JE, Coan, A, Bronson, K, Wheeler, J, Lyerly, HK, Morse, MA, and Abernethy, AP. "E/Tablets to collect research-quality, patient-reported data." J Clin Oncol 26.15_suppl (May 20, 2008): 17528-.
PMID
27950469
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
26
Issue
15_suppl
Publish Date
2008
Start Page
17528

Longitudinal patterns of chemotherapy (CT) use in metastatic colorectal cancer (mCRC).

15082 Background: As mCRC survival increases beyond 2 years, patients (pts) have more exposure to multiple CT regimens. Insight into patterns of care in mCRC treatment is crucial to understanding physician and patient decision-making priorities. METHODS: Using a population-based strategy, we identified CRC cases from 1 academic and 9 community oncology practices in the southeastern US with mCRC diagnosed between 6/03-6/06, and treatment with an oxaliplatin- (O) or irinotecan- (IR) based CT regimen during that period. Demographic, disease, treatment, and toxicity data were abstracted by retrospective chart review, double-entered and verified for accuracy. RESULTS: Of 743 charts screened, 110 were eligible: mean age 57.9 (SD 12.2), 74% Stage IV at diagnosis, 39% male, 53% white, 26% black, and 13% ≥70 years. As part of 1st-line mCRC CT, 100% of pts received regimens containing 5-fluorouracil (5-FU), 87% (95% CI 81-93%) received O, 12% (95% CI 6-18%) received IR, and 74% (95% CI 66-82%) received bevacizumab (B). The proportions of pts receiving subsequent lines of CT were: 2nd-line 48% (n=53), 3rd-line 26% (n=29), 4th-line 14% (n=15), and 5th-line 5% (n=5). From 1st to 3rd line, the use of O and B decreased, while IR use increased (see Table ). Therapy was discontinued 29% of the time for disease progression (PD) and 19% of the time for toxicity; 27% had no reason documented. 22% (n=25/114) of O- and 34% (n=20/59) of IR-containing regimens were discontinued for PD. 19% (n=21/114) of O- and 20% (n=12/59) of IR-containing regimens were discontinued for toxicity. CONCLUSIONS: Along with 5-FU, O and B were most commonly used in 1st-line for mCRC. Use of O decreased and IR increased as treatment progressed beyond 1st-line. [Table: see text] [Table: see text].

Authors
Herndon, JE; Zafar, Y; Marcello, J; Wheeler, J; Rowe, K; Morse, MA; Abernethy, AP
MLA Citation
Herndon, JE, Zafar, Y, Marcello, J, Wheeler, J, Rowe, K, Morse, MA, and Abernethy, AP. "Longitudinal patterns of chemotherapy (CT) use in metastatic colorectal cancer (mCRC)." J Clin Oncol 26.15_suppl (May 20, 2008): 15082-.
PMID
27950330
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
26
Issue
15_suppl
Publish Date
2008
Start Page
15082

Treatment-related toxicity and supportive care in metastatic colorectal cancer (mCRC).

15087 Background: As mCRC survival increases, patients have more exposure to chemotherapy (CT) and related toxicity. How do toxicity patterns affect care? METHODS: Using a population-based strategy, we identified CRC cases from 1 academic and 9 community oncology practices with mCRC diagnosed between 6/03-6/06, and initial mCRC treatment with an oxaliplatin- (O) or irinotecan- (IR) based CT. Demographic, disease, treatment, and toxicity data were abstracted by retrospective chart review, double-entered and verified. Hospitalization, drug discontinuation, and drug reduction events were per clinician report; one case could have had multiple events. RESULTS: Of 743 charts screened, 110 were eligible based upon pre-identified inclusion criteria: mean age 58 (SD 12), 74% Stage IV at diagnosis, 39% male, 53% white, 26% black, and 13% ≥70 years. As part of 1st-line mCRC CT, 87% received O [all FOLFOX], 12% received IR [all FOLFIRI], and 74% received bevacizumab (B). When treated with 1st-line O, 50% did not receive 2nd-line CT; when treated with 1st-line IR, 38% did not receive 2nd-line CT. Gastrointestinal (GI) toxicity was documented across 52% of all regimens (57% O, 59% IR), and was the most common toxicity-related cause of drug discontinuation (16 of 61 events) and hospitalization (19 of 54 events). Dose reduction was most commonly due to hematologic toxicity (22 of 55 events). When treated with O (n=114 total treatment lines), dose reduction was due to hematologic toxicity (16%) and drug discontinuation due to neurotoxicity (8%). When treated with IR (n=59 total treatment lines), dose reduction and discontinuation were primarily due to GI toxicity, 12% and 10% respectively. O and IR required similar rates of anti-diarrheal (O 22%, IR 20%), anti-nausea (O 20%, IR 26%), erythropoiesis- (O 19%, IR 9%), and granulocyte-stimulating (O 25%, IR 11%,) treatments (all p's NS). CONCLUSIONS: In this mCRC sample, GI toxicity was the most common driver of toxicity-related drug discontinuation and hospitalization; dose reduction was most commonly due to hematologic toxicity. Third was neurotoxicity, but when present it prompted drug discontinuation. These real-world data provide benchmarks to improve practice. [Table: see text].

Authors
Abernethy, AP; Zafar, Y; Marcello, J; Wheeler, J; Rowe, K; Morse, MA; Herndon, JE
MLA Citation
Abernethy, AP, Zafar, Y, Marcello, J, Wheeler, J, Rowe, K, Morse, MA, and Herndon, JE. "Treatment-related toxicity and supportive care in metastatic colorectal cancer (mCRC)." J Clin Oncol 26.15_suppl (May 20, 2008): 15087-.
PMID
27950327
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
26
Issue
15_suppl
Publish Date
2008
Start Page
15087

Mortality burden of melanoma: Metastatic site-specific and temporal trends.

9076 Background: Metastatic melanoma has high disease-specific mortality burden, as measured by Years of Life Lost (YLL). Has mortality burden shifted over time? METHODS: This was a retrospective analysis of a prospective database of 14,029 melanoma cases treated at Duke between 1970-2004. Metastatic analyses focused on cases that developed recurrences after initial diagnosis. YLL was calculated by subtracting the survival since diagnosis from the individual's life expectancy without cancer at an equivalent time of diagnosis, based on U.S. Life Tables, 2003. Average YLL (AYLL) was calculated by group. Survival was calculated by Kaplan Meier method. RESULTS: Of 14,029 cases, 6,810 (49%) had metastases, and of metastatic cases 4,636 (68%) developed recurrences after initial diagnosis; metastatic cases were mean age 49 (SD 15), 60% male, and 99% white. First metastatic sites were lymph nodes 55%, skin 23%, lung 10%, brain 5%, liver 3%, bone 2%, and other 3%. Lymph nodes as first site of metastasis increased in frequency over time (1970s: 51%, 1980s: 54%, and 1990s: 61%). Among metastatic cases, AYLL increased by decade of diagnosis and differed by site of first metastasis ( Table ). CONCLUSIONS: Although a retrospective analysis of a US referral melanoma population, this large-scale analysis suggests that the mortality burden of metastatic melanoma may be increasing over time. This could be due to several factors, including later diagnosis, higher risk of death with initial recurrence in lymph nodes and brain, and lack of available treatments that extend survival. This analysis highlights the continued unmet need to improve survival outcomes in metastatic melanoma. [Table: see text] [Table: see text].

Authors
Scheri, RP; Herndon, JE; Marcello, J; Wheeler, J; Tyler, DS; Abernethy, AP
MLA Citation
Scheri, RP, Herndon, JE, Marcello, J, Wheeler, J, Tyler, DS, and Abernethy, AP. "Mortality burden of melanoma: Metastatic site-specific and temporal trends." J Clin Oncol 26.15_suppl (May 20, 2008): 9076-.
PMID
27950873
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
26
Issue
15_suppl
Publish Date
2008
Start Page
9076

Efficacy of a phase II vaccine targeting Cytomegalovirus antigens in newly diagnosed GBM

Authors
Mitchell, D; Archer, GE; Bigner, DD; Friedman, HS; Lally-Goss, D; II, HJE; McGehee, S; McLendon, R; Reardon, DA; Sampson, JH
MLA Citation
Mitchell, D, Archer, GE, Bigner, DD, Friedman, HS, Lally-Goss, D, II, HJE, McGehee, S, McLendon, R, Reardon, DA, and Sampson, JH. "Efficacy of a phase II vaccine targeting Cytomegalovirus antigens in newly diagnosed GBM." JOURNAL OF CLINICAL ONCOLOGY 26.15 (May 20, 2008).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
26
Issue
15
Publish Date
2008

Effect of bevacizumab (BEV) and irinotecan (CPT-11) on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in glioblastoma (GBM) patients

Authors
Desjardins, A; Barboriak, DP; II, HJE; Marcello, J; Reardon, DA; Quinn, JA; Rich, JN; Sathornsumetee, S; Friedman, HS; Vredenburgh, JJ
MLA Citation
Desjardins, A, Barboriak, DP, II, HJE, Marcello, J, Reardon, DA, Quinn, JA, Rich, JN, Sathornsumetee, S, Friedman, HS, and Vredenburgh, JJ. "Effect of bevacizumab (BEV) and irinotecan (CPT-11) on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in glioblastoma (GBM) patients." JOURNAL OF CLINICAL ONCOLOGY 26.15 (May 20, 2008).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
26
Issue
15
Publish Date
2008

A phase II prospective study evaluating the role of pemetrexed plus gemcitabine (Pem/Gem) chemotherapy as intial treatment in patients with stage IIIB/IV non-small cell lung cancer (NSCLC) using a genomic predictor of cisplatin-resistance to guide therapy

Authors
Garst, J; Datto, M; II, HJE; Barry, WT; Shoemaker, D; Bjurstrom, A; Andrews, C; Ginsburg, G; Nevins, JR; Potti, A
MLA Citation
Garst, J, Datto, M, II, HJE, Barry, WT, Shoemaker, D, Bjurstrom, A, Andrews, C, Ginsburg, G, Nevins, JR, and Potti, A. "A phase II prospective study evaluating the role of pemetrexed plus gemcitabine (Pem/Gem) chemotherapy as intial treatment in patients with stage IIIB/IV non-small cell lung cancer (NSCLC) using a genomic predictor of cisplatin-resistance to guide therapy." JOURNAL OF CLINICAL ONCOLOGY 26.15 (May 20, 2008).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
26
Issue
15
Publish Date
2008

Update on survival from the original phase II trial of bevacizumab and irinotecan in recurrent malignant gliomas

Authors
Wagner, SA; Desjardins, A; Reardon, DA; Marcello, J; II, HJE; Quinn, JA; Rich, JN; Sathornsumetee, S; Friedman, HS; Vredenburgh, JJ
MLA Citation
Wagner, SA, Desjardins, A, Reardon, DA, Marcello, J, II, HJE, Quinn, JA, Rich, JN, Sathornsumetee, S, Friedman, HS, and Vredenburgh, JJ. "Update on survival from the original phase II trial of bevacizumab and irinotecan in recurrent malignant gliomas." JOURNAL OF CLINICAL ONCOLOGY 26.15 (May 20, 2008).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
26
Issue
15
Publish Date
2008

Mortality burden of melanoma: Metastatic site-specific and temporal trends

Authors
Scheri, RP; II, HJE; Marcello, J; Wheeler, J; Tyler, DS; Abernethy, AP
MLA Citation
Scheri, RP, II, HJE, Marcello, J, Wheeler, J, Tyler, DS, and Abernethy, AP. "Mortality burden of melanoma: Metastatic site-specific and temporal trends." May 20, 2008.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
26
Issue
15
Publish Date
2008

Treatment-related toxicity and supportive care in metastatic colorectal cancer (mCRC)

Authors
Abernethy, AP; Zafar, Y; Marcello, J; Wheeler, J; Rowe, K; Morse, MA; II, HJE
MLA Citation
Abernethy, AP, Zafar, Y, Marcello, J, Wheeler, J, Rowe, K, Morse, MA, and II, HJE. "Treatment-related toxicity and supportive care in metastatic colorectal cancer (mCRC)." JOURNAL OF CLINICAL ONCOLOGY 26.15 (May 20, 2008).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
26
Issue
15
Publish Date
2008

E/Tablets to collect research-quality, patient-reported data

Authors
Uronis, HE; II, HJE; Coan, A; Bronson, K; Wheeler, J; Lyerly, HK; Morse, MA; Abernethy, AP
MLA Citation
Uronis, HE, II, HJE, Coan, A, Bronson, K, Wheeler, J, Lyerly, HK, Morse, MA, and Abernethy, AP. "E/Tablets to collect research-quality, patient-reported data." May 20, 2008.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
26
Issue
15
Publish Date
2008

Longitudinal patterns of chemotherapy (CT) use in metastatic colorectal cancer (mCRC)

Authors
II, HJE; Zafar, Y; Marcello, J; Wheeler, J; Rowe, K; Morse, MA; Abernethy, AP
MLA Citation
II, HJE, Zafar, Y, Marcello, J, Wheeler, J, Rowe, K, Morse, MA, and Abernethy, AP. "Longitudinal patterns of chemotherapy (CT) use in metastatic colorectal cancer (mCRC)." JOURNAL OF CLINICAL ONCOLOGY 26.15 (May 20, 2008).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
26
Issue
15
Publish Date
2008

Evaluation and characterization of generalized anxiety and depression in patients with primary brain tumors.

To determine clinical and sociodemographic factors that are associated with major neuropsychiatric illnesses among brain tumor patients, we administered a modified version of the Brief Patient Health Questionnaire and a demographic data form to 363 adult neuro-oncology patients. Responses were analyzed to assess for associations between demographic variables, clinical variables, and symptoms consistent with diagnoses of generalized anxiety disorder and/or depression. Multivariate logistic regression analyses showed that female gender was associated with the presence of symptoms of anxiety, depression, and combined anxiety and depression. Lower WHO tumor grade classifications, lower education level, and a history of psychiatric illness also emerged as important predictors of symptoms consistent with anxiety and/or depression. Marital status and presence of past/current medical illness trended toward being significantly associated with depression alone. Patient use of psychiatric medication was not associated with any study variables. Results of the present study suggest several hypotheses to test with neuro-oncology patients in further longitudinal analyses, which would benefit from the inclusion of a wider range of neuropsychiatric symptoms in conjunction with neurocognitive and functional impairment variables.

Authors
Arnold, SD; Forman, LM; Brigidi, BD; Carter, KE; Schweitzer, HA; Quinn, HE; Guill, AB; Herndon, JE; Raynor, RH
MLA Citation
Arnold, SD, Forman, LM, Brigidi, BD, Carter, KE, Schweitzer, HA, Quinn, HE, Guill, AB, Herndon, JE, and Raynor, RH. "Evaluation and characterization of generalized anxiety and depression in patients with primary brain tumors." Neuro Oncol 10.2 (April 2008): 171-181.
PMID
18314416
Source
pubmed
Published In
Neuro-Oncology
Volume
10
Issue
2
Publish Date
2008
Start Page
171
End Page
181
DOI
10.1215/15228517-2007-057

A pilot study: 131I-antitenascin monoclonal antibody 81c6 to deliver a 44-Gy resection cavity boost.

The purpose of this study was to determine the feasibility and assess the efficacy and toxicity, among newly diagnosed malignant glioma patients, of administering (131)I-labeled murine antitenascin monoclonal antibody 81C6 ((131)I-81C6) into a surgically created resection cavity (SCRC) to achieve a patient-specific, 44-Gy boost to the 2-cm SCRC margin. A radioactivity dose of (131)I-81C6 calculated to achieve a 44-Gy boost to the SCRC was administered, followed by conventional external beam radiotherapy (XRT) and chemotherapy. Twenty-one patients were enrolled in the study: 16 with glioblastoma multiforme (GBM) and 5 with anaplastic astrocytoma. Twenty patients received the targeted 44-Gy boost (+/-10%) to the SCRC. Attributable toxicity was mild and limited to reversible grade 3 neutropenia or thrombocytopenia (n = 3; 14%), CNS wound infections (n = 3; 14%), and headache (n = 2; 10%). With a median follow-up of 151 weeks, median overall survival times for all patients and those with GBM are 96.6 and 90.6 weeks, respectively; 87% of GBM patients are alive at 1 year. It is feasible to consistently achieve a 44-Gy boost dose to the SCRC margin with patient-specific dosing of (131)I-81C6. Our study regimen ((131)I-81C6 + XRT + temozolomide) was well tolerated and had encouraging survival. To determine if selection of good-prognosis patients affects outcome associated with this approach, the U.S. Food and Drug Administration has approved a trial randomizing newly diagnosed GBM patients to either our study regimen or standard XRT plus temozolomide.

Authors
Reardon, DA; Zalutsky, MR; Akabani, G; Coleman, RE; Friedman, AH; Herndon, JE; McLendon, RE; Pegram, CN; Quinn, JA; Rich, JN; Vredenburgh, JJ; Desjardins, A; Guruangan, S; Boulton, S; Raynor, RH; Dowell, JM; Wong, TZ; Zhao, X-G; Friedman, HS; Bigner, DD
MLA Citation
Reardon, DA, Zalutsky, MR, Akabani, G, Coleman, RE, Friedman, AH, Herndon, JE, McLendon, RE, Pegram, CN, Quinn, JA, Rich, JN, Vredenburgh, JJ, Desjardins, A, Guruangan, S, Boulton, S, Raynor, RH, Dowell, JM, Wong, TZ, Zhao, X-G, Friedman, HS, and Bigner, DD. "A pilot study: 131I-antitenascin monoclonal antibody 81c6 to deliver a 44-Gy resection cavity boost." Neuro Oncol 10.2 (April 2008): 182-189.
PMID
18287339
Source
pubmed
Published In
Neuro-Oncology
Volume
10
Issue
2
Publish Date
2008
Start Page
182
End Page
189
DOI
10.1215/15228517-2007-053

Prognostic value of fluorine-18 fluorodeoxyglucose positron emission tomography imaging in patients with advanced-stage non-small-cell lung carcinoma.

PURPOSE: To determine whether the amount of fluorine-18 fluorodeoxyglucose (FDG) uptake in the primary lung cancer on positron emission tomography (PET) imaging at the time of presentation has prognostic significance in patients with advanced-stage non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A retrospective review identified 214 patients with advanced-stage NSCLC (stage IIIA, IIIB, and IV) who underwent FDG PET study at the time of diagnosis. Extensive clinical data, including tumor histologic cell type, pathologic stage at presentation, and treatment, were recorded. The maximum standardized uptake value (SUV(max)) in the primary tumor on FDG PET on survival was examined using Cox proportional hazards regression. RESULTS: One hundred fifty-eight (74%) of the 214 patients died and 56 patients were reported alive at 27 months (range, 3 to 140 months) after the diagnosis of NSCLC. Using the median SUV(max) of 11.1, the patient population was subdivided. The median survival of the 106 patients with the primary tumor having an SUV(max) less than 11.1 was 16 months (95% CI, 12 to 21 months), whereas the median survival of the 108 patients with the primary tumor having an SUV(max) > or = 11.1 was 12 months (95% CI, 10 to 15 months). Univariate and multivariate analysis did not provide evidence that survival for patient subgroups defined by the median SUV(max) were significantly different (univariate P = .11; multivariate P = .45). CONCLUSION: FDG uptake of the primary lesions in patients with a new diagnosis of advanced-stage NSCLC does not have a significant relationship with survival.

Authors
Hoang, JK; Hoagland, LF; Coleman, RE; Coan, AD; Herndon, JE; Patz, EF
MLA Citation
Hoang, JK, Hoagland, LF, Coleman, RE, Coan, AD, Herndon, JE, and Patz, EF. "Prognostic value of fluorine-18 fluorodeoxyglucose positron emission tomography imaging in patients with advanced-stage non-small-cell lung carcinoma." J Clin Oncol 26.9 (March 20, 2008): 1459-1464.
PMID
18349396
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
26
Issue
9
Publish Date
2008
Start Page
1459
End Page
1464
DOI
10.1200/JCO.2007.14.3628

Measuring clinically significant chemotherapy-related toxicities using Medicare claims from Cancer and Leukemia Group B (CALGB) trial participants.

BACKGROUND: Because the elderly are underrepresented on clinical trials, physicians have few sources of information to estimate the risks (ie, toxicities) and benefits of chemotherapy administration to the elderly. OBJECTIVE: Our goal was to determine whether the standard measures of toxicity used in clinical trials could be captured from observational Medicare claims data. METHODS: We identified 175 elderly clinical trial patients treated on 2 Cancer and Leukemia Group B (CALGB) trials (9344, adjuvant breast study and 9730, advanced lung cancer study) and merged participants' CALGB data with their Medicare data. From CALGB data, we identified the most frequent Extended Clinical Toxicity Critieria grade III/IV toxicities. We reviewed diagnostic and procedure codes from Medicare manuals, developed algorithms to measure the toxicities, and then finalized the algorithms after empiric review of patients' codes. We compared results of Medicare algorithms to gold standard CALGB toxicity information to calculate test characteristics. RESULTS: CALGB data documented that 15 grade III/IV chemotherapy-related toxicities occurred in > or =3% of the 175 patients: white blood cell, hemoglobin, platelets, anorexia, nausea, vomiting, diarrhea, stomatitis, sensory neuropathy, motor neuropathy, motor or sensory neuropathy, dyspnea, hyperglycemia, infection, and malaise. Vomiting was the only toxicity identified by the Medicare-based algorithm with a sensitivity, specificity, and area under the receiver operator curve of > or =80%. CONCLUSIONS: The results of this preliminary study suggest that Medicare diagnostic and procedure codes may be of only limited value in measuring clinically significant chemotherapy-related toxicities in elderly Medicare beneficiaries. Future research includes confirming these findings in a larger and more diverse sample.

Authors
Lamont, EB; Herndon, JE; Weeks, JC; Henderson, IC; Lilenbaum, R; Schilsky, RL; Christakis, NA; Cancer and Leukemia Group B,
MLA Citation
Lamont, EB, Herndon, JE, Weeks, JC, Henderson, IC, Lilenbaum, R, Schilsky, RL, Christakis, NA, and Cancer and Leukemia Group B, . "Measuring clinically significant chemotherapy-related toxicities using Medicare claims from Cancer and Leukemia Group B (CALGB) trial participants." Med Care 46.3 (March 2008): 303-308.
PMID
18388845
Source
pubmed
Published In
Medical Care
Volume
46
Issue
3
Publish Date
2008
Start Page
303
End Page
308
DOI
10.1097/MLR.0b013e31815cecc3

Phase II trial of weekly dose-dense paclitaxel in extensive-stage small cell lung cancer: cancer and leukemia group B study 39901.

INTRODUCTION: Paclitaxel is an active agent in extensive-stage (ES) small cell lung cancer (SCLC). Nevertheless, the optimal schedule is uncertain. A dose-dense schedule was previously evaluated in a Cancer and Leukemia Group B study of patients with non-SCLC, resulting in a 42% response rate and median survival of 12.3 months. Because of these promising results, this dose and schedule of paclitaxel was evaluated in patients with ES-SCLC. METHODS: Patients were eligible for this phase II trial (Cancer and Leukemia Group B 39901) if they had documented ES-SCLC, no prior chemotherapy, and performance status of 0 to 2. Paclitaxel was administered as an intravenous infusion at 150 mg/m2 over 3 hours weekly for 6 consecutive weeks every 8 weeks. RESULTS: Thirty-six patients with median age of 65 were enrolled. Of them 25 were men and 33 with a performance status 0 to 1. A median of two 8-week cycles were delivered. The percent of patients with grade 3/4 toxicity included neutropenia 22%, anemia 9%, febrile neutropenia 6%, fatigue 20%, sensory neuropathy 26%, motor neuropathy 11%, and dyspnea 17%. There were two treatment-related deaths, both from pneumonitis. The overall response rate was 33% (3% complete response and 30% partial response). Median progression-free and overall survivals were 3.7 and 9.2 months, respectively. One-year progression-free and overall survivals were 17% and 36%, respectively. CONCLUSIONS: For patients with ES-SCLC, dose-dense weekly paclitaxel was associated with fairly mild hematologic toxicity. Nevertheless, nonhematologic toxicities, including neuropathy, fatigue, and dyspnea required frequent dose delays and reductions. The overall response rate is disappointing and much lower than that seen with standard platinum-based combinations. Paclitaxel in this dose and schedule should not be used as front-line therapy for patients with ES-SCLC.

Authors
Graziano, SL; Herndon, JE; Socinski, MA; Wang, X; Watson, D; Vokes, E; Green, MR; Cancer and Leukemia Group B,
MLA Citation
Graziano, SL, Herndon, JE, Socinski, MA, Wang, X, Watson, D, Vokes, E, Green, MR, and Cancer and Leukemia Group B, . "Phase II trial of weekly dose-dense paclitaxel in extensive-stage small cell lung cancer: cancer and leukemia group B study 39901." J Thorac Oncol 3.2 (February 2008): 158-162.
PMID
18303437
Source
pubmed
Published In
Journal of Thoracic Oncology
Volume
3
Issue
2
Publish Date
2008
Start Page
158
End Page
162
DOI
10.1097/JTO.0b013e318161225e

Tumor angiogenic and hypoxic profiles predict radiographic response and survival in malignant astrocytoma patients treated with bevacizumab and irinotecan.

PURPOSE: The combination of a vascular endothelial growth factor (VEGF) -neutralizing antibody, bevacizumab, and irinotecan is associated with high radiographic response rates and improved survival outcomes in patients with recurrent malignant gliomas. The aim of these retrospective studies was to evaluate tumor vascularity and expression of components of the VEGF pathway and hypoxic responses as predictive markers for radiographic response and survival benefit from the bevacizumab and irinotecan therapy. PATIENTS AND METHODS: In a phase II trial, 60 patients with recurrent malignant astrocytomas were treated with bevacizumab and irinotecan. Tumor specimens collected at the time of diagnosis were available for further pathologic studies in 45 patients (75%). VEGF, VEGF receptor-2, CD31, hypoxia-inducible carbonic anhydrase 9 (CA9), and hypoxia-inducible factor-2alpha were semiquantitatively assessed by immunohistochemistry. Radiographic response and survival outcomes were correlated with these angiogenic and hypoxic markers. RESULTS: Of 45 patients, 27 patients had glioblastoma multiforme, and 18 patients had anaplastic astrocytoma. Twenty-six patients (58%) had at least partial radiographic response. High VEGF expression was associated with increased likelihood of radiographic response (P = .024) but not survival benefit. Survival analysis revealed that high CA9 expression was associated with poor survival outcome (P = .016). CONCLUSION: In this patient cohort, tumor expression levels of VEGF, the molecular target of bevacizumab, were associated with radiographic response, and the upstream promoter of angiogenesis, hypoxia, determined survival outcome, as measured from treatment initiation. Validation in a larger clinical trial is warranted.

Authors
Sathornsumetee, S; Cao, Y; Marcello, JE; Herndon, JE; McLendon, RE; Desjardins, A; Friedman, HS; Dewhirst, MW; Vredenburgh, JJ; Rich, JN
MLA Citation
Sathornsumetee, S, Cao, Y, Marcello, JE, Herndon, JE, McLendon, RE, Desjardins, A, Friedman, HS, Dewhirst, MW, Vredenburgh, JJ, and Rich, JN. "Tumor angiogenic and hypoxic profiles predict radiographic response and survival in malignant astrocytoma patients treated with bevacizumab and irinotecan." J Clin Oncol 26.2 (January 10, 2008): 271-278.
PMID
18182667
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
26
Issue
2
Publish Date
2008
Start Page
271
End Page
278
DOI
10.1200/JCO.2007.13.3652

EGFRvIII-targeted immunotoxin induces antitumor immunity that is inhibited in the absence of CD4+ and CD8+ T cells.

PURPOSE: Immunotoxins as anti-cancer therapeutics have several potential advantages over conventional agents including a high specificity, extraordinary potency, and a lack of an identified mechanism for resistance. It has been clearly demonstrated that Pseudomonas-based immunotoxins have a direct cytotoxic effect. However, delayed and often dramatic antitumor responses seen in human studies with targeted toxins led us to hypothesize that immunologic responses may be a secondary mechanism that enhances the therapeutic efficacy of these novel drugs. EXPERIMENTAL DESIGN: This hypothesis was tested in a murine system using an immunotoxin, MR1-1 [MR1-1(dsFv)-PE38KDEL], that targets a syngeneic murine homologue of the tumor-specific human epidermal growth factor mutation, EGFRvIII, expressed on a murine cell line. RESULTS: Intratumoral treatment with MR1-1 eliminated EGFRvIII-expressing tumors (P < 0.0001). The antitumor activity of MR1-1 was dependent on the expression of EGFRvIII on some, but not all tumors cells, and was significantly inhibited in the absence of CD4+ (P = 0.0193) and CD8+ (P = 0.0193) T cells. MR1-1 induced EGFRvIII-specific immunity (P < 0.0005) and produced long lasting immunity against tumors expressing EGFRvIII as well as EGFRvIII-negative tumors. CONCLUSIONS: These data suggest that immunotoxins may not be strictly dependent on direct cytotoxicity for their efficacy, but may also be potent inducers of antitumor immunity active even against cells that do not express the targeted antigen.

Authors
Ochiai, H; Archer, GE; Herndon, JE; Kuan, C-T; Mitchell, DA; Bigner, DD; Pastan, IH; Sampson, JH
MLA Citation
Ochiai, H, Archer, GE, Herndon, JE, Kuan, C-T, Mitchell, DA, Bigner, DD, Pastan, IH, and Sampson, JH. "EGFRvIII-targeted immunotoxin induces antitumor immunity that is inhibited in the absence of CD4+ and CD8+ T cells." Cancer Immunol Immunother 57.1 (January 2008): 115-121.
PMID
17634939
Source
pubmed
Published In
Cancer Immunology, Immunotherapy
Volume
57
Issue
1
Publish Date
2008
Start Page
115
End Page
121
DOI
10.1007/s00262-007-0363-7

Comorbidity, age, race and stage at diagnosis in colorectal cancer: a retrospective, parallel analysis of two health systems.

BACKGROUND: Stage at diagnosis plays a significant role in colorectal cancer (CRC) survival. Understanding which factors contribute to a more advanced stage at diagnosis is vital to improving overall survival. Comorbidity, race, and age are known to impact receipt of cancer therapy and survival, but the relationship of these factors to stage at diagnosis of CRC is less clear. The objective of this study is to investigate how comorbidity, race and age influence stage of CRC diagnosis. METHODS: Two distinct healthcare populations in the United States (US) were retrospectively studied. Using the Cancer Care Outcomes Research and Surveillance Consortium database, we identified CRC patients treated at 15 Veterans Administration (VA) hospitals from 2003-2007. We assessed metastatic CRC patients treated from 2003-2006 at 10 non-VA, fee-for-service (FFS) practices. Stage at diagnosis was dichotomized (non-metastatic, metastatic). Race was dichotomized (white, non-white). Charlson comorbidity index and age at diagnosis were calculated. Associations between stage, comorbidity, race, and age were determined by logistic regression. RESULTS: 342 VA and 340 FFS patients were included. Populations differed by the proportion of patients with metastatic CRC at diagnosis (VA 27% and FFS 77%) reflecting differences in eligibility criteria for inclusion. VA patients were mean (standard deviation; SD) age 67 (11), Charlson index 2.0 (1.0), and were 63% white. FFS patients were mean age 61 (13), Charlson index 1.6 (1.0), and were 73% white. In the VA cohort, higher comorbidity was associated with earlier stage at diagnosis after adjusting for age and race (odds ratio (OR) 0.76, 95% confidence interval (CI) 0.58-1.00; p = 0.045); no such significant relationship was identified in the FFS cohort (OR 1.09, 95% CI 0.82-1.44; p = 0.57). In both cohorts, no association was found between stage at diagnosis and either age or race. CONCLUSION: Higher comorbidity may lead to earlier stage of CRC diagnosis. Multiple factors, perhaps including increased interactions with the healthcare system due to comorbidity, might contribute to this finding. Such increased interactions are seen among patients within a healthcare system like the VA system in the US versus sporadic interactions which may be seen with FFS healthcare.

Authors
Zafar, SY; Abernethy, AP; Abbott, DH; Grambow, SC; Marcello, JE; 2nd, JEH; Rowe, KL; Kolimaga, JT; Zullig, LL; Patwardhan, MB; Provenzale, DT
MLA Citation
Zafar, SY, Abernethy, AP, Abbott, DH, Grambow, SC, Marcello, JE, 2nd, JEH, Rowe, KL, Kolimaga, JT, Zullig, LL, Patwardhan, MB, and Provenzale, DT. "Comorbidity, age, race and stage at diagnosis in colorectal cancer: a retrospective, parallel analysis of two health systems." BMC cancer 8 (2008): 345--.
Source
scival
Published In
BMC Cancer
Volume
8
Publish Date
2008
Start Page
345-
DOI
10.1186/1471-2407-8-345

The authors reply

Authors
Bleday, R; Greenberg, JA; Mayer, R; Shibata, D; II, JEH; Jr, GDS
MLA Citation
Bleday, R, Greenberg, JA, Mayer, R, Shibata, D, II, JEH, and Jr, GDS. "The authors reply." Diseases of the Colon and Rectum 51.8 (2008): 1193-1194.
Source
scival
Published In
Diseases of the Colon and Rectum
Volume
51
Issue
8
Publish Date
2008
Start Page
1193
End Page
1194
DOI
10.1007/s10350-008-9231-6

Panel of serum biomarkers for the diagnosis of lung cancer.

PURPOSE: Currently, a blood test for lung cancer does not exist. Serum biomarkers that could aid clinicians in making case management decisions would be enormously valuable. We used two proteomic platforms and a literature search to select candidate serum markers for the diagnosis of lung cancer. METHODS: We initially assayed six serum proteins, four discovered by proteomics and two previously known to be cancer associated, on a training set of sera from 100 patients (50 with a new diagnosis of lung cancer and 50 age- and sex-matched controls). Classification and Regression Tree (CART) analysis selected a panel of four markers that most efficiently predicted which patients had lung cancer. An independent, blinded validation set of sera from 97 patients (49 lung cancer patients and 48 matched controls) determined the accuracy of the four markers to predict which patients had lung cancer. RESULTS: Four serum proteins-carcinoembryonic antigen, retinol binding protein, alpha1-antitrypsin, and squamous cell carcinoma antigen-were collectively found to correctly classify the majority of lung cancer and control patients in the training set (sensitivity, 89.3%; specificity, 84.7%). These markers also accurately classified patients in the independent validation set (sensitivity, 77.8%; specificity, 75.4%). Remarkably, 90% of patients who fell into any one of three groupings in the CART analysis had lung cancer. CONCLUSION: This panel of four serum proteins is valuable in suggesting the diagnosis of lung cancer. These data may be useful for treating patients with an indeterminate pulmonary lesion, and potentially in predicting individuals at high risk for lung cancer.

Authors
Patz, EF; Campa, MJ; Gottlin, EB; Kusmartseva, I; Guan, XR; Herndon, JE
MLA Citation
Patz, EF, Campa, MJ, Gottlin, EB, Kusmartseva, I, Guan, XR, and Herndon, JE. "Panel of serum biomarkers for the diagnosis of lung cancer." J Clin Oncol 25.35 (December 10, 2007): 5578-5583.
PMID
18065730
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
25
Issue
35
Publish Date
2007
Start Page
5578
End Page
5583
DOI
10.1200/JCO.2007.13.5392

Haptoglobin and posttranslational glycan-modified derivatives as serum biomarkers for the diagnosis of nonsmall cell lung cancer.

BACKGROUND: The purpose was to evaluate the clinical utility of serum haptoglobin (Hp) and posttranslational glycan modifications of Hp for the diagnosis of nonsmall cell lung cancer (NSCLC). METHODS: Serum proteins from patients with a new diagnosis of NSCLC and age- and sex-matched controls without cancer were compared using 2-dimensional difference gel electrophoresis (2D-DIGE). Four of the differentially expressed gel spots were identified as the beta chain of Hp. Immunoblots confirmed sialyl and fucosyl group posttranslational modifications (PTMs) of Hp. Serum enzyme-linked immunosorbent assays (ELISAs) for total Hp, sialylated Hp (SAHp), and fucosylated Hp (FHp) were designed, and levels of each were measured in an independent sample set of 74 patients. Receiver operating characteristic (ROC) analysis assessed the clinical diagnostic utility of each marker. RESULTS: Statistically significant differences between lung cancer patients and matched controls were found by ELISA for Hp (P < .002), SAHp (P < .001), and FHp (P < .04). ROC analysis determined an area under the curve (AUC) of 0.754 for Hp, 0.740 for SAHp, and 0.794 for FHp. In addition, serum concentrations correlated with stage; Hp (r = 0.388; P = .018), SAHp (r = 0.300; P = .072), and FHp (r = 0.363; P = .027). CONCLUSIONS: Hp and 2 of its glycoforms, SAHp and FHp, are potentially useful in the clinical diagnosis of NSCLC. The markers increase with stage, suggesting they may also be useful in stratifying patients at presentation and in following patients after treatment.

Authors
Hoagland, LFM; Campa, MJ; Gottlin, EB; Herndon, JE; Patz, EF
MLA Citation
Hoagland, LFM, Campa, MJ, Gottlin, EB, Herndon, JE, and Patz, EF. "Haptoglobin and posttranslational glycan-modified derivatives as serum biomarkers for the diagnosis of nonsmall cell lung cancer." Cancer 110.10 (November 15, 2007): 2260-2268.
PMID
17918261
Source
pubmed
Published In
Cancer
Volume
110
Issue
10
Publish Date
2007
Start Page
2260
End Page
2268
DOI
10.1002/cncr.23049

Video-assisted thoracic surgery lobectomy: report of CALGB 39802--a prospective, multi-institution feasibility study.

PURPOSE: To evaluate the technical feasibility and safety of video-assisted thoracic surgery (VATS) lobectomy for small lung cancers. PATIENTS AND METHODS: The Cancer and Leukemia Group B 39802 trial was a prospective, multi-institutional study designed to elucidate the technical feasibility of VATS in early non-small-cell lung cancer (NSCLC) using a standard definition for VATS lobectomy (one 4- to 8-cm access and two 0.5-cm port incisions) that mandated videoscopic guidance and a traditional hilar dissection without rib spreading. Between 1998 and 2001, 128 patients with peripheral lung nodules < or = 3 cm in size with suspected NSCLC were prospectively registered for VATS lobectomy. RESULTS: One hundred twenty-seven patients (66 males and 61 females; median age, 66 years; range, 37 to 86 years), with a performance status of 0 (74%) or 1 (26%), underwent surgery. Patients with lymph nodes more than 1 cm by computed tomography scan underwent mediastinal lymph node sampling to rule out N2 disease. One hundred eleven patients (87%) had stage I lung cancer, and 96 (86.5%) of these 111 patients underwent successful VATS lobectomies. The median procedure length was 130 minutes (range, 47 to 428 minutes), and median chest tube duration was 3 days (range, 1 to 14 days). Fifty-eight (60%) of 97 patients underwent diagnostic biopsy at lobectomy. Within 30 days, three (2.7%) of 111 patient deaths occurred, none of which were directly related to VATS technique; seven (7.4%) of 95 patients had grade 3 or greater complications, with only one case of bleeding. CONCLUSION: A standardized approach to VATS lobectomy as specifically defined with avoidance of rib spreading is feasible.

Authors
Swanson, SJ; Herndon, JE; D'Amico, TA; Demmy, TL; McKenna, RJ; Green, MR; Sugarbaker, DJ
MLA Citation
Swanson, SJ, Herndon, JE, D'Amico, TA, Demmy, TL, McKenna, RJ, Green, MR, and Sugarbaker, DJ. "Video-assisted thoracic surgery lobectomy: report of CALGB 39802--a prospective, multi-institution feasibility study." J Clin Oncol 25.31 (November 1, 2007): 4993-4997.
PMID
17971599
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
25
Issue
31
Publish Date
2007
Start Page
4993
End Page
4997
DOI
10.1200/JCO.2007.12.6649

Bevacizumab plus irinotecan in recurrent glioblastoma multiforme.

PURPOSE: The prognosis for patients with recurrent glioblastoma multiforme is poor, with a median survival of 3 to 6 months. We performed a phase II trial of bevacizumab, a monoclonal antibody to vascular endothelial growth factor, in combination with irinotecan. PATIENTS AND METHODS: This phase II trial included two cohorts of patients. The initial cohort, comprising 23 patients, received bevacizumab at 10 mg/kg plus irinotecan every 2 weeks. The dose of irinotecan was based on the patient's anticonvulsant: Patients taking enzyme-inducing antiepileptic drugs (EIAEDs) received 340 mg/m2, and patients not taking EIAEDs received 125 mg/m2. After this regimen was deemed safe and effective, the irinotecan schedule was changed to an accepted brain tumor regimen of four doses in 6 weeks, in anticipation of a phase III randomized trial of irinotecan versus irinotecan and bevacizumab. The second cohort, comprising 12 patients, received bevacizumab 15 mg/kg every 21 days and irinotecan on days 1, 8, 22, and 29. Each cycle was 6 weeks long and concluded with patient evaluations, including magnetic resonance imaging. RESULTS: The 6-month progression-free survival among all 35 patients was 46% (95% CI, 32% to 66%). The 6-month overall survival was 77% (95% CI, 64% to 92%). Twenty of the 35 patients (57%; 95% CI, 39% to 74%) had at least a partial response. One patient developed a CNS hemorrhage, which occurred in his 10th cycle. Four patients developed thromboembolic complications (deep venous thrombosis and/or pulmonary emboli). CONCLUSION: Bevacizumab and irinotecan is an effective treatment for recurrent glioblastoma multiforme and has moderate toxicity.

Authors
Vredenburgh, JJ; Desjardins, A; Herndon, JE; Marcello, J; Reardon, DA; Quinn, JA; Rich, JN; Sathornsumetee, S; Gururangan, S; Sampson, J; Wagner, M; Bailey, L; Bigner, DD; Friedman, AH; Friedman, HS
MLA Citation
Vredenburgh, JJ, Desjardins, A, Herndon, JE, Marcello, J, Reardon, DA, Quinn, JA, Rich, JN, Sathornsumetee, S, Gururangan, S, Sampson, J, Wagner, M, Bailey, L, Bigner, DD, Friedman, AH, and Friedman, HS. "Bevacizumab plus irinotecan in recurrent glioblastoma multiforme." J Clin Oncol 25.30 (October 20, 2007): 4722-4729.
PMID
17947719
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
25
Issue
30
Publish Date
2007
Start Page
4722
End Page
4729
DOI
10.1200/JCO.2007.12.2440

Evaluation of tumor response by dynamic contrast-enhanced magnetic resonance imaging in glioblastoma (gbm) patients treated with bevacizumab (bev) and irinotecan (CPT-11)

Authors
Desjardins, A; Barboriak, D; II, HJE; Reardon, D; Quinn, J; Rich, J; Sathornsumetee, S; Friedman, H; Vredenburgh, J
MLA Citation
Desjardins, A, Barboriak, D, II, HJE, Reardon, D, Quinn, J, Rich, J, Sathornsumetee, S, Friedman, H, and Vredenburgh, J. "Evaluation of tumor response by dynamic contrast-enhanced magnetic resonance imaging in glioblastoma (gbm) patients treated with bevacizumab (bev) and irinotecan (CPT-11)." October 2007.
Source
wos-lite
Published In
Neuro-Oncology
Volume
9
Issue
4
Publish Date
2007
Start Page
573
End Page
574

The PAX3-FKHR fusion gene of rhabdomyosarcoma cooperates with loss of p16INK4A to promote bypass of cellular senescence.

Rhabdomyosarcoma is the most common soft tissue sarcoma of childhood and adolescence. Despite advances in therapy, patients with a histologic variant of rhabdomyosarcoma known as alveolar rhabdomyosarcoma (ARMS) have a 5-year survival of <30%. ARMS is characterized by a chromosomal translocation generating the PAX3-FKHR fusion gene. However, ectopic expression of PAX3-FKHR often induces inhibition of cell proliferation, or cell death, when expressed in nonmuscle cells. This prompted us to explore the effect of expressing PAX3-FKHR in more relevant cells, specifically primary human skeletal muscle cells because these cells can be converted to a tumorigenic state that mimics rhabdomyosarcoma. PAX3-FKHR expression promoted both fetal and postnatal primary human skeletal muscle cell precursors to bypass the senescence growth arrest checkpoint. This bypass was accompanied by epigenetic DNA methylation of the p16(INK4A) promoter and correspondingly a loss of expression of this tumor suppressor. Knockdown of p16(INK4A) cooperated with PAX3-FKHR to drive proliferation past senescence, whereas reintroduction of wild-type p16(INK4A) in post-senescent cells caused growth arrest. Thus, PAX3-FKHR acts in concert with loss of p16(INK4A) to promote inappropriate proliferation of skeletal muscle cells. This association between PAX3-FKHR expression and p16(INK4A) loss was seen in human ARMS tumor tissue, as both human rhabdomyosarcoma cell lines and tissue microarrays showed a trend toward down-regulation of p16(INK4A) protein in alveolar subsets. We surmise that the generation of the PAX3-FKHR fusion protein may require loss of p16(INK4A) to promote malignant proliferation of skeletal muscle cells as an early step in ARMS tumorigenesis.

Authors
Linardic, CM; Naini, S; Herndon, JE; Kesserwan, C; Qualman, SJ; Counter, CM
MLA Citation
Linardic, CM, Naini, S, Herndon, JE, Kesserwan, C, Qualman, SJ, and Counter, CM. "The PAX3-FKHR fusion gene of rhabdomyosarcoma cooperates with loss of p16INK4A to promote bypass of cellular senescence." Cancer Res 67.14 (July 15, 2007): 6691-6699.
PMID
17638879
Source
pubmed
Published In
Cancer Research
Volume
67
Issue
14
Publish Date
2007
Start Page
6691
End Page
6699
DOI
10.1158/0008-5472.CAN-06-3210

Preoperative exercise Vo2 measurement for lung resection candidates: results of Cancer and Leukemia Group B Protocol 9238.

INTRODUCTION: A stepwise approach to the functional assessment of lung resection candidates is widely accepted, and this approach incorporates the measurement of exercise peak Vo2 when spirometry and radionuclear studies suggest medical inoperability. A new functional operability (FO) algorithm incorporates peak exercise Vo2 earlier in the preoperative assessment to determine which patients require preoperative radionuclear studies. This algorithm has not been studied in a multicenter study. METHODS: The CALGB (Cancer and Leukemia Group B) performed a prospective multi-institutional study to investigate the use of primary exercise Vo2 measurement for the prediction of surgical risk. Patients with known or suspected resectable non-small cell lung cancer (NSCLC) were eligible. Exercise testing including measurement of peak oxygen uptake (Vo2), spirometry, and single breath diffusion capacity (DLCO) was performed on each patient. Nuclear perfusion scans were obtained on selected high-risk patients. After surgery, morbidity and mortality data were collected and correlated with preoperative data. Mortality and morbidity were retrospectively compared by algorithm-based risk groups. RESULTS: Three hundred forty-six patients with suspected lung cancer from nine institutions underwent thoracotomy with or without resection; 57 study patients did not undergo thoracotomy. Patients who underwent surgery had a median survival time of 30.9 months, whereas patients who did not undergo surgery had a median survival time of 15.6 months. Among the 346 patients who underwent thoracotomy, 15 patients died postoperatively (4%), and 138 patients (39%) exhibited at least one cardiorespiratory complication postoperatively. We found that patients who had a peak exercise Vo2 of <65% of predicted (or a peak Vo2/kg <16 ml/min/kg) were more likely to suffer complications (p = 0.0001) and were also more likely to have a poor outcome (respiratory failure or death) if the peak Vo2 was <15 ml/min/kg (p = 0.0356). We also found a subset of 58 patients who did not meet FO algorithm criteria for operability, but who still tolerated lung resection with a 2% mortality rate. CONCLUSIONS: Our data provide multicenter validation for the use of exercise Vo2 for preoperative assessment of lung cancer patients, and we encourage an aggressive approach when evaluating these patients for surgery.

Authors
Loewen, GM; Watson, D; Kohman, L; Herndon, JE; Shennib, H; Kernstine, K; Olak, J; Mador, MJ; Harpole, D; Sugarbaker, D; Green, M; Cancer and Leukemia Group B,
MLA Citation
Loewen, GM, Watson, D, Kohman, L, Herndon, JE, Shennib, H, Kernstine, K, Olak, J, Mador, MJ, Harpole, D, Sugarbaker, D, Green, M, and Cancer and Leukemia Group B, . "Preoperative exercise Vo2 measurement for lung resection candidates: results of Cancer and Leukemia Group B Protocol 9238." J Thorac Oncol 2.7 (July 2007): 619-625.
PMID
17607117
Source
pubmed
Published In
Journal of Thoracic Oncology
Volume
2
Issue
7
Publish Date
2007
Start Page
619
End Page
625
DOI
10.1097/JTO.0b013e318074bba7

Clinical utility of a patient-specific algorithm for simulating intracerebral drug infusions.

Convection-enhanced delivery (CED) is a novel drug delivery technique that uses positive infusion pressure to deliver therapeutic agents directly into the interstitial spaces of the brain. Despite the promise of CED, clinical trials have demonstrated that target-tissue anatomy and patient-specific physiology play a major role in drug distribution using this technique. In this study, we retrospectively tested the ability of a software algorithm using MR diffusion tensor imaging to predict patient-specific drug distributions by CED. A tumor-targeted cytotoxin, cintredekin besudotox (interleukin 13-PE38QQR), was coinfused with iodine 123-labeled human serum albumin (123I-HSA), in patients with recurrent malignant gliomas. The spatial distribution of 123I-HSA was then compared to a drug distribution simulation provided by the software algorithm. The algorithm had a high sensitivity (71.4%) and specificity (100%) for identifying the high proportion (7 of 14) of catheter trajectories that failed to deliver drug into the desired anatomical region (p = 0.021). This usually occurred when catheter trajectories crossed deep sulci, resulting in leak of the infusate into the subarachnoid cerebrospinal fluid space. The mean concordance of the volume of distribution at the 50% isodose level between the actual 123I-HSA distribution and simulation was 65.75% (95% confidence interval [CI], 52.0%-79.5%), and the mean maximal inplane deviation was less than 8.5 mm (95% CI, 4.0-13.0 mm). The use of this simulation algorithm was considered clinically useful in 84.6% of catheters. Routine use of this algorithm, and its further developments, should improve prospective selection of catheter trajectories, and thereby improve the efficacy of drugs delivered by this promising technique.

Authors
Sampson, JH; Raghavan, R; Brady, ML; Provenzale, JM; Herndon, JE; Croteau, D; Friedman, AH; Reardon, DA; Coleman, RE; Wong, T; Bigner, DD; Pastan, I; Rodríguez-Ponce, MI; Tanner, P; Puri, R; Pedain, C
MLA Citation
Sampson, JH, Raghavan, R, Brady, ML, Provenzale, JM, Herndon, JE, Croteau, D, Friedman, AH, Reardon, DA, Coleman, RE, Wong, T, Bigner, DD, Pastan, I, Rodríguez-Ponce, MI, Tanner, P, Puri, R, and Pedain, C. "Clinical utility of a patient-specific algorithm for simulating intracerebral drug infusions." Neuro Oncol 9.3 (July 2007): 343-353.
PMID
17435179
Source
pubmed
Published In
Neuro-Oncology
Volume
9
Issue
3
Publish Date
2007
Start Page
343
End Page
353
DOI
10.1215/15228517-2007-007

Clinical stage I non-small cell lung cancer including FDG-PET Imaging: sites and time to recurrence.

INTRODUCTION: Positron emission tomography (PET) has improved the accuracy of staging non-small cell lung cancer (NSCLC), although some early-stage patients will still relapse. The purpose of this study was to determine the sites and time to recurrence in patients with clinical stage I NSCLC whose initial staging evaluation included conventional imaging and fluorodeoxyglucose-PET. METHODS: This study was approved by our institutional review board and complies with the Health Insurance Portability and Accountability Act. We retrospectively searched our PET database and identified 231 patients (125 women, 106 men; ages 36-93 years) with primary NSCLC and clinical stage I disease. The sites and time to recurrence were recorded. The average follow-up time was 33 months. RESULTS: Of the 231 patients with clinical stage I tumors, 196 patients (85%) had pathological stage I disease. Two patients developed a second primary lung cancer, and 40 patients (20%) developed local or distant recurrence. Ninety-three percent of all patients remained disease free at 1 year, and 27% (11/40) of those who recur do so in the first year. The most common site of first recurrence was the thorax, followed by the brain, bone, and adrenal glands. CONCLUSIONS: Twenty percent of stage I NSCLC patients staged with conventional imaging and PET will develop recurrent NSCLC. The sites of recurrence with the addition of PET are similar to those reported with staging by conventional imaging alone. Additional studies are needed to determine the optimal time for follow-up imaging if intervention for recurrent disease is shown to improve survival.

Authors
Gauger, J; Patz, EF; Coleman, RE; Herndon, JE
MLA Citation
Gauger, J, Patz, EF, Coleman, RE, and Herndon, JE. "Clinical stage I non-small cell lung cancer including FDG-PET Imaging: sites and time to recurrence." J Thorac Oncol 2.6 (June 2007): 499-505.
PMID
17545844
Source
pubmed
Published In
Journal of Thoracic Oncology
Volume
2
Issue
6
Publish Date
2007
Start Page
499
End Page
505
DOI
10.1097/JTO.0b013e3180600990

A phase II trial of carboplatin/vinorelbine with pegfilgrastim support for the treatment of patients with advanced non-small cell lung cancer.

INTRODUCTION: The impact of chemotherapy dose delivery has not been well studied in patients with non-small cell lung cancer (NSCLC). Overlapping hematologic toxicities commonly limit planned dose intensity of combination chemotherapy regimens. A phase II study investigating carboplatin and vinorelbine, supported by pegfilgrastim, in the treatment of patients with advanced NSCLC was performed. METHODS: Chemotherapy-naïve patients with locally advanced or metastatic NSCLC were treated with carboplatin area under the curve (AUC) 6 mg/ml per minute intravenously on day 1 and vinorelbine 30 mg/m2 intravenously on days 1 and 8 every 3 weeks for four planned cycles. Pegfilgrastim was administered on day 9 of each cycle as a 6-mg subcutaneous injection. The primary endpoint was incidence of cycle 1 febrile neutropenia. Secondary endpoints included incidence of grade 3/4 hematologic and nonhematologic toxicities, delivered dose intensity, and overall survival. RESULTS: Thirty patients (21 men, 9 women) with a median age of 61 years (range, 43-79) were enrolled. Of 120 planned patient cycles, 101 (84%) were completed. There was one episode of cycle 1 febrile neutropenia. Overall response rate was 27%. Median dose delivered for vinorelbine was 17.2 mg/m2 per week, representing a delivered dose intensity of 86%. Median survival was 9.4 months (95% confidence interval: 6.1-18.0) with a 3-year survival rate of 20%. CONCLUSIONS: This regimen of carboplatin and vinorelbine with pegfilgrastim support was associated with a low rate of febrile neutropenia and good maintenance of planned dose intensity. Although response and survival are similar to other chemotherapy regimens in advanced NSCLC, studies optimizing chemotherapy delivery in this setting may help inform treatment approaches in patients with earlier stage disease.

Authors
Riedel, RF; Andrews, C; Garst, J; Dunphy, F; Herndon, JE; Blackwell, S; Barbour, S; Crawford, J
MLA Citation
Riedel, RF, Andrews, C, Garst, J, Dunphy, F, Herndon, JE, Blackwell, S, Barbour, S, and Crawford, J. "A phase II trial of carboplatin/vinorelbine with pegfilgrastim support for the treatment of patients with advanced non-small cell lung cancer." Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 2.6 (June 2007): 520-525. (Academic Article)
PMID
17545847
Source
manual
Published In
Journal of Thoracic Oncology
Volume
2
Issue
6
Publish Date
2007
Start Page
520
End Page
525

Induction chemotherapy followed by chemoradiotherapy compared with chemoradiotherapy alone for regionally advanced unresectable stage III Non-small-cell lung cancer: Cancer and Leukemia Group B.

PURPOSE: Standard therapy for unresectable stage III non-small-cell lung cancer includes concomitant chemoradiotherapy. In Cancer and Leukemia Group B 39801, we evaluated whether induction chemotherapy before concurrent chemoradiotherapy would result in improved survival. PATIENTS AND METHODS: Between July 1998 and May 2002, 366 patients were randomly assigned to arm A, which involved immediate concurrent chemoradiotherapy with carboplatin area under the concentration-time curve (AUC) of 2 and paclitaxel 50 mg/m2 given weekly during 66 Gy of chest radiotherapy, or arm B, which involved two cycles of carboplatin AUC 6 and paclitaxel 200 mg/m2 administered every 21 days followed by identical chemoradiotherapy. The accrual goal was 360 patients. RESULTS: Thirty-four percent of patients were female, 66% were male, and the median age was 63 years. Grade 3 or 4 toxicities during induction chemotherapy on arm B consisted mainly of neutropenia (18% and 20%, respectively). During concurrent chemoradiotherapy, there was no difference in severity of in-field toxicities of esophagitis (grade 3 and 4 were, respectively, 30% and 2% for arm A v 28% and 8% for arm B) and dyspnea (grade 3 and 4 were, respectively, 11% and 3% for arm A v 15% and 4% for arm B). Survival differences were not statistically significant (P = .3), with a median survival on arm A of 12 months (95% CI, 10 to 16 months) versus 14 months (95% CI, 11 to 16 months) on arm B and a 2-year survival of 29% (95% CI, 22% to 35%) and 31% (95% CI, 25% to 38%). Age, weight loss before therapy, and performance status were statistically significant predictive factors. CONCLUSION: The addition of induction chemotherapy to concurrent chemoradiotherapy added toxicity and provided no survival benefit over concurrent chemoradiotherapy alone. The median survival achieved in each of the treatment groups is low, and the routine use of weekly carboplatin and paclitaxel with simultaneous radiotherapy should be re-examined.

Authors
Vokes, EE; Herndon, JE; Kelley, MJ; Cicchetti, MG; Ramnath, N; Neill, H; Atkins, JN; Watson, DM; Akerley, W; Green, MR; Cancer and Leukemia Group B,
MLA Citation
Vokes, EE, Herndon, JE, Kelley, MJ, Cicchetti, MG, Ramnath, N, Neill, H, Atkins, JN, Watson, DM, Akerley, W, Green, MR, and Cancer and Leukemia Group B, . "Induction chemotherapy followed by chemoradiotherapy compared with chemoradiotherapy alone for regionally advanced unresectable stage III Non-small-cell lung cancer: Cancer and Leukemia Group B." J Clin Oncol 25.13 (May 1, 2007): 1698-1704.
PMID
17404369
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
25
Issue
13
Publish Date
2007
Start Page
1698
End Page
1704
DOI
10.1200/JCO.2006.07.3569

Tumor resection cavity administered iodine-131-labeled antitenascin 81C6 radioimmunotherapy in patients with malignant glioma: neuropathology aspects.

INTRODUCTION: The neurohistological findings in patients treated with targeted beta emitters such as (131)I are poorly described. We report a histopathologic analysis from patients treated with combined external beam therapy and a brachytherapy consisting of a (131)I-labeled monoclonal antibody (mAb) injected into surgically created resection cavities during brain tumor resections. METHODS: Directed tissue samples of the cavity walls were obtained because of suspected tumor recurrence from 28 patients. Samples and clinical follow-up were evaluated on all patients (Group A) based on total radiation dose received and a subset of these (n=18; Group B, proximal therapy subset) who had received external beam therapy within

Authors
McLendon, RE; Akabani, G; Friedman, HS; Reardon, DA; Cleveland, L; Cokgor, I; Herndon, JE; Wikstrand, C; Boulton, ST; Friedman, AH; Bigner, DD; Zalutsky, MR
MLA Citation
McLendon, RE, Akabani, G, Friedman, HS, Reardon, DA, Cleveland, L, Cokgor, I, Herndon, JE, Wikstrand, C, Boulton, ST, Friedman, AH, Bigner, DD, and Zalutsky, MR. "Tumor resection cavity administered iodine-131-labeled antitenascin 81C6 radioimmunotherapy in patients with malignant glioma: neuropathology aspects." Nucl Med Biol 34.4 (May 2007): 405-413.
PMID
17499730
Source
pubmed
Published In
Nuclear Medicine and Biology
Volume
34
Issue
4
Publish Date
2007
Start Page
405
End Page
413
DOI
10.1016/j.nucmedbio.2007.01.009

Phase II study of imatinib mesylate and hydroxyurea for recurrent grade III malignant gliomas.

PURPOSE: Recent reports demonstrate the activity of imatinib mesylate, an ATP-mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiforme. We performed the current phase 2 study to evaluate this regimen among patients with recurrent WHO grade III malignant glioma (MG). PATIENTS AND METHOD: Patients with grade III MG at any recurrence, received imatinib mesylate plus hydroxyurea (500 mg twice a day) orally on a continuous, daily schedule. The imatinib mesylate dose was 500 mg twice a day for patients on enzyme inducing anti-epileptic drugs (EIAEDs) and 400 mg once a day for those not on EIAEDs. Clinical assessments were performed monthly and radiographic assessments were obtained at least every 2 months. The primary endpoint was 6-month progression-free survival (PFS) rate. RESULTS: Thirty-nine patients were enrolled. All patients had progressive disease after prior radiotherapy and at least temozolomide-based chemotherapy. The median number of episodes of prior progression was 2 (range, 1-7) and the median number of prior treatment regimens was 3 (range, 1-8). With a median follow-up of 82.9 weeks, 24% of patients were progression-free at 6 months. The radiographic response rate was 10%, while 33% achieved stable disease. Among patients who achieved at least stable disease at first evaluation, the 6-month and 12-month PFS rates were 53% and 29%, respectively. The most common grade 3 or greater toxicities were hematologic and complicated less than 4% of administered courses. CONCLUSION: Imatinib mesylate plus hydroxyurea, is well tolerated and associated with anti-tumor activity in some patients with recurrent grade 3 MG.

Authors
Desjardins, A; Quinn, JA; Vredenburgh, JJ; Sathornsumetee, S; Friedman, AH; Herndon, JE; McLendon, RE; Provenzale, JM; Rich, JN; Sampson, JH; Gururangan, S; Dowell, JM; Salvado, A; Friedman, HS; Reardon, DA
MLA Citation
Desjardins, A, Quinn, JA, Vredenburgh, JJ, Sathornsumetee, S, Friedman, AH, Herndon, JE, McLendon, RE, Provenzale, JM, Rich, JN, Sampson, JH, Gururangan, S, Dowell, JM, Salvado, A, Friedman, HS, and Reardon, DA. "Phase II study of imatinib mesylate and hydroxyurea for recurrent grade III malignant gliomas." J Neurooncol 83.1 (May 2007): 53-60.
PMID
17245623
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
83
Issue
1
Publish Date
2007
Start Page
53
End Page
60
DOI
10.1007/s11060-006-9302-2

Temozolomide in children with progressive low-grade glioma.

We conducted a phase II study to assess the efficacy of oral temozolomide (TMZ) in children with progressive low-grade glioma. Thirty eligible patients were enrolled on this study. Median age at enrollment was 10 years (range, 4-18 years). Eligible patients received TMZ (200 mg/m(2) per day) by mouth for five days every four weeks. Patients received a median of nine cycles (range, 2-12 cycles) of treatment. Best responses in the 26 patients (86%) with optic pathway glioma (OPG)/pilocytic astrocytoma (PA) included partial response in 3 patients (11%), minor response in 1 (4%), stable disease in 10 (38%), and progressive disease in 12 (46%). Only one of four patients with fibrillary astrocytoma had stable disease for 29 months after TMZ. The overall disease stabilization rate in patients with OPG/PA was 54%, and disease control was maintained for a median interval of 34 months. Seventeen of 26 patients had progressive disease either on or off therapy, and three have died of disease. The two-year progression-free and overall survivals in patients with OPG/PA were 49% (95% CI, 30%-67%) and 96% (95% CI, 89%-100%), respectively. Worst toxicity related to TMZ in all 30 patients included grade 2-4 thrombocytopenia in seven patients, grade 2-4 neutropenia in seven, grade 2 skin rash in one, and intratumor hemorrhage in one. TMZ given in this schedule was successful in stabilizing disease in a significant proportion of the patients with OPG/PA, with manageable toxicity.

Authors
Gururangan, S; Fisher, MJ; Allen, JC; Herndon, JE; Quinn, JA; Reardon, DA; Vredenburgh, JJ; Desjardins, A; Phillips, PC; Watral, MA; Krauser, JM; Friedman, AH; Friedman, HS
MLA Citation
Gururangan, S, Fisher, MJ, Allen, JC, Herndon, JE, Quinn, JA, Reardon, DA, Vredenburgh, JJ, Desjardins, A, Phillips, PC, Watral, MA, Krauser, JM, Friedman, AH, and Friedman, HS. "Temozolomide in children with progressive low-grade glioma." Neuro Oncol 9.2 (April 2007): 161-168.
PMID
17347491
Source
pubmed
Published In
Neuro-Oncology
Volume
9
Issue
2
Publish Date
2007
Start Page
161
End Page
168
DOI
10.1215/15228517-2006-030

Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma.

PURPOSE: Recurrent grade III-IV gliomas have a dismal prognosis with minimal improvements in survival seen following currently available salvage therapy. This study was conducted to determine if the combination of a novel antiangiogenic therapy, bevacizumab, and a cytotoxic agent, irinotecan, is safe and effective for patients with recurrent grade III-IV glioma. EXPERIMENTAL DESIGN: We conducted a phase II trial of bevacizumab and irinotecan in adults with recurrent grade III-IV glioma. Patients with evidence of intracranial hemorrhage on initial brain magnetic resonance imaging were excluded. Patients were scheduled to receive bevacizumab and irinotecan i.v. every 2 weeks of a 6-week cycle. Bevacizumab was administered at 10 mg/kg. The dose of irinotecan was determined based on antiepileptic use: patients taking enzyme-inducing antiepileptic drugs received 340 mg/m(2), whereas patients not taking enzyme-inducing antiepileptic drugs received 125 mg/m(2). Toxicity and response were assessed. RESULTS: Thirty-two patients were assessed (23 with grade IV glioma and 9 with grade III glioma). Radiographic responses were noted in 63% (20 of 32) of patients (14 of 23 grade IV patients and 6 of 9 grade III patients). The median progression-free survival was 23 weeks for all patients (95% confidence interval, 15-30 weeks; 20 weeks for grade IV patients and 30 weeks for grade III patients). The 6-month progression-free survival probability was 38% and the 6-month overall survival probability was 72%. No central nervous system hemorrhages occurred, but three patients developed deep venous thromboses or pulmonary emboli, and one patient had an arterial ischemic stroke. CONCLUSIONS: The combination of bevacizumab and irinotecan is an active regimen for recurrent grade III-IV glioma with acceptable toxicity.

Authors
Vredenburgh, JJ; Desjardins, A; Herndon, JE; Dowell, JM; Reardon, DA; Quinn, JA; Rich, JN; Sathornsumetee, S; Gururangan, S; Wagner, M; Bigner, DD; Friedman, AH; Friedman, HS
MLA Citation
Vredenburgh, JJ, Desjardins, A, Herndon, JE, Dowell, JM, Reardon, DA, Quinn, JA, Rich, JN, Sathornsumetee, S, Gururangan, S, Wagner, M, Bigner, DD, Friedman, AH, and Friedman, HS. "Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma." Clin Cancer Res 13.4 (February 15, 2007): 1253-1259.
PMID
17317837
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
13
Issue
4
Publish Date
2007
Start Page
1253
End Page
1259
DOI
10.1158/1078-0432.CCR-06-2309

Phase II trial of irinotecan/gemcitabine as second-line therapy for relapsed and refractory small-cell lung cancer: Cancer and Leukemia Group B Study 39902.

BACKGROUND: This phase II study evaluated the efficacy and safety of the irinotecan/gemcitabine combination in patients with relapsed/refractory small-cell lung cancer (SCLC). PATIENTS AND METHODS: Patients with measurable tumor who had received one previous chemotherapy or chemotherapy/radiation regimen were eligible. Gemcitabine 1000 mg/m(2) was administered i.v. over 30 min followed immediately by irinotecan 100 mg/m(2) i.v. over 90 min, both on days 1 and 8 every 21 days. Patients were stratified based on response to initial treatment [i.e. primary sensitive disease with progression >or=3 months (group A), or refractory disease (group B)]. RESULTS: Seventy-three patients were enrolled but one never received treatment and one ineligible patient did not have SCLC. Median patient ages of the remaining patients were 61 and 63 years in groups A (n = 35) and B (n = 36), respectively, with performance status of 0 or 1 in 85% of 71 patients. Primary grade 3/4 toxic effects in groups A versus B were neutropenia (36% versus 43%), thrombocytopenia (36% versus 26%), nausea (12% versus 11%), vomiting (0 versus 11%), diarrhea (12% versus 9%), and pulmonary (12% versus 12%). Two patients had fatal events including pneumonitis (n = 1) and acute respiratory distress syndrome (n = 1). Responses occurred in 11 group A [two complete responses and nine partial responses (PRs)] and four group B (all PRs) patients, for response rates of 31% [95% confidence interval (CI) 17%, 49%) and 11% (95% CI 3%, 26%), respectively. Median survival and progression-free survival times were 7.1 (95% CI 6, 10.5) versus 3.5 (95% CI 3.1, 5.7) months, and 3.1 (95% CI 1.6, 5.3) versus 1.6 (95% CI 1.4, 2.8) months for group A versus B. CONCLUSION: The irinotecan/gemcitabine combination is active and well tolerated as second-line therapy in SCLC patients. Additional studies are warranted as second-line therapy in patients who progressed 90 days or more after first-line therapy. However, the observed efficacy results in refractory SCLC patients indicate that this regimen should not be further explored in this population.

Authors
Rocha-Lima, CM; Herndon, JE; Lee, ME; Atkins, JN; Mauer, A; Vokes, E; Green, MR; Cancer and Leukemia Group B,
MLA Citation
Rocha-Lima, CM, Herndon, JE, Lee, ME, Atkins, JN, Mauer, A, Vokes, E, Green, MR, and Cancer and Leukemia Group B, . "Phase II trial of irinotecan/gemcitabine as second-line therapy for relapsed and refractory small-cell lung cancer: Cancer and Leukemia Group B Study 39902." Ann Oncol 18.2 (February 2007): 331-337.
PMID
17065590
Source
pubmed
Published In
Annals of Oncology
Volume
18
Issue
2
Publish Date
2007
Start Page
331
End Page
337
DOI
10.1093/annonc/mdl375

Phase II study of Cloretazine for the treatment of adults with recurrent glioblastoma multiforme.

Cloretazine (VNP40101M) is a newly synthesized alkylating agent belonging to a novel class of alkylating agents called 1,2-bis(sulfonyl)hydrazines. Agents that belong to this class do not produce vinylating and chloroethylating species, and hence this class of alkylating agents is thought to have minimal systemic toxicity. Cloretazine produces two short-lived active species: 1,2-bis(methylsulfonyl)-1-(2-chloroethyl) hydrazine (a chloroethylating species) and a thiophilic carbamoylating methylisocyanate species. The chloroethylating species preferentially produces lesions at the O(6) position of guanine. The methylisocyanate species may inhibit O(6)-alkylguanine-DNA alkyltransferase, an important mechanism of resistance against alkylating agents. The purpose of this study was to determine the efficacy and tolerability of Cloretazine in patients with recurrent glioblastoma multiforme. The basis for the determination of efficacy was the proportion of patients alive without evidence of disease progression six months after initiation of treatment. Patients with recurrent glioblastoma multiforme received Cloretazine (300 mg/m(2)) intravenously every six weeks. Radiographic response, survival data, and toxicity were assessed. Thirty-two patients were enrolled. Median age was 56 years; 24 patients (75%) were men. At six months, two patients were alive and progression free, so the six-month progression-free survival (PFS) was 6%. The median PFS was 6.3 weeks. There were no objective radiographic responses. Twelve patients had stable disease for at least one cycle, but only two patients received more than three cycles. Nine patients experienced grade 4 thrombocytopenia and three patients experienced grade 4 neutropenia. Cloretazine administered every six weeks was relatively well tolerated, although this schedule has insignificant activity for patients with recurrent glioblastoma multiforme.

Authors
Badruddoja, MA; Penne, K; Desjardins, A; Reardon, DA; Rich, JN; Quinn, JA; Sathornsumetee, S; Friedman, AH; Bigner, DD; Herndon, JE; Cahill, A; Friedman, HS; Vredenburgh, JJ
MLA Citation
Badruddoja, MA, Penne, K, Desjardins, A, Reardon, DA, Rich, JN, Quinn, JA, Sathornsumetee, S, Friedman, AH, Bigner, DD, Herndon, JE, Cahill, A, Friedman, HS, and Vredenburgh, JJ. "Phase II study of Cloretazine for the treatment of adults with recurrent glioblastoma multiforme." Neuro Oncol 9.1 (January 2007): 70-74.
PMID
17108065
Source
pubmed
Published In
Neuro-Oncology
Volume
9
Issue
1
Publish Date
2007
Start Page
70
End Page
74
DOI
10.1215/15228517-2006-022

In reply [8]

Authors
Cornett, WR; McCall, LM; Petersen, RP; II, JEH; Tyler, DS
MLA Citation
Cornett, WR, McCall, LM, Petersen, RP, II, JEH, and Tyler, DS. "In reply [8]." Journal of Clinical Oncology 25.11 (2007): 1450-1451.
Source
scival
Published In
Journal of Clinical Oncology
Volume
25
Issue
11
Publish Date
2007
Start Page
1450
End Page
1451
DOI
10.1200/JCO.2006.10.4331

In reply [14]

Authors
Cornett, WR; McCall, LM; Petersen, RP; II, JEH; Tyler, DS
MLA Citation
Cornett, WR, McCall, LM, Petersen, RP, II, JEH, and Tyler, DS. "In reply [14]." Journal of Clinical Oncology 25.9 (2007): 1149-1151.
Source
scival
Published In
Journal of Clinical Oncology
Volume
25
Issue
9
Publish Date
2007
Start Page
1149
End Page
1151
DOI
10.1200/JCO.2006.09.9440

Telephone monitoring of distress in patients aged 65 years or older with advanced stage cancer: a cancer and leukemia group B study.

BACKGROUND: Significant barriers to cancer patients receiving mental health treatment for distress have been reported in the literature. The objective of the current study was to determine whether distress in older patients (aged 65 years and older) would be reduced with educational materials (EM) supplemented by monthly telephone monitoring (TM) (TM + EM) compared with the use of EM alone because of more timely referrals to appropriate health professionals. METHODS: One hundred ninety-two older patients with breast, prostate, and colorectal cancers who had advanced disease and currently were receiving treatment were randomized to receive either TM + EM or EM alone. One hundred thirty-one patients were evaluated by telephone interview for psychologic and physical distress and for social support at baseline and at 6 months using the Hospital Anxiety and Depression Scale (HADS), the European Organization for Research and Treatment of Cancer (EORTC)-QLQ-C30 quality-of-life questionnaire, and the Medical Outcomes Study (MOS) Social Support Survey. Patients who in the TM + EM group were called monthly for 6 months to monitor their distress using the HADS and EORTC physical symptom items and the MOS Social Support Survey items, with cutoff levels were established to indicate which patients were in greater distress. Those patients who scored above the cutoff levels were referred to their oncology nurse for referral to the appropriate professional. Patients in the EM group received written materials regarding cancer-related psychosocial issues and available resources. RESULTS: At 6 months, patients in the TM + EM group reported significantly less anxiety (HADS; P < .0001), depression (HADS; P = .0004), and overall distress (HADS; P < .0001) compared with patients in the EM group. CONCLUSIONS: Monthly monitoring of older patients' distress with TM and EM along with referral for appropriate help was found to be an efficient means of reducing patients' anxiety and depression compared with patients who received only EM.

Authors
Kornblith, AB; Dowell, JM; Herndon, JE; Engelman, BJ; Bauer-Wu, S; Small, EJ; Morrison, VA; Atkins, J; Cohen, HJ; Holland, JC
MLA Citation
Kornblith, AB, Dowell, JM, Herndon, JE, Engelman, BJ, Bauer-Wu, S, Small, EJ, Morrison, VA, Atkins, J, Cohen, HJ, and Holland, JC. "Telephone monitoring of distress in patients aged 65 years or older with advanced stage cancer: a cancer and leukemia group B study." Cancer 107.11 (December 1, 2006): 2706-2714.
PMID
17078057
Source
pubmed
Published In
Cancer
Volume
107
Issue
11
Publish Date
2006
Start Page
2706
End Page
2714
DOI
10.1002/cncr.22296

Nodal downstaging predicts survival following induction chemotherapy for stage IIIA (N2) non-small cell lung cancer in CALGB protocol #8935.

BACKGROUND AND OBJECTIVES: CALGB 8935 was a phase II protocol for mediastinoscopically staged IIIA (N2) non-small cell lung cancer. Induction cisplatin/vinblastine chemotherapy was followed by surgical resection, adjuvant cisplatin/vinblastine, and radiotherapy. We now evaluate the prognosis of pathologic nodes. METHODS: Failure-free survival was calculated from a landmark 3 months after resection to account for heterogeneity in adjuvant therapy. RESULTS: Nine of 42 (21%) resected patients had no residual N2 disease. This subset of 9 had a median failure-free interval of 47.8 months from landmark, whereas the 33 patients (79%) with persistent N2 disease had a median failure-free survival of 8.2 months from landmark (P=0.01). Although 21/42 (50%) had an incomplete resection (positive highest resected node and/or margin), completeness of resection did not influence failure-free survival. There were 3 distant and no local recurrences among the N2 negative group, and 12 local recurrences among patients with residual N2 disease (P=0.041). CONCLUSIONS: These data suggest: (1) persistent N2 disease following induction chemotherapy is unfavorable; (2) patients downstaged to N2 negative may benefit from surgical resection; however, (3) 33% of N2 negative patients suffered disease relapse.

Authors
Jaklitsch, MT; Herndon, JE; DeCamp, MM; Richards, WG; Kumar, P; Krasna, MJ; Green, MR; Sugarbaker, DJ
MLA Citation
Jaklitsch, MT, Herndon, JE, DeCamp, MM, Richards, WG, Kumar, P, Krasna, MJ, Green, MR, and Sugarbaker, DJ. "Nodal downstaging predicts survival following induction chemotherapy for stage IIIA (N2) non-small cell lung cancer in CALGB protocol #8935." J Surg Oncol 94.7 (December 1, 2006): 599-606.
PMID
17039491
Source
pubmed
Published In
Journal of Surgical Oncology
Volume
94
Issue
7
Publish Date
2006
Start Page
599
End Page
606
DOI
10.1002/jso.20644

Phase II study of carboplatin, irinotecan, and thalidomide combination in patients with extensive stage small-cell lung cancer.

Authors
Riedel, RF; Crawford, J; Dunphy, F; Herndon, JE; Garst, J; Kelley, MJ
MLA Citation
Riedel, RF, Crawford, J, Dunphy, F, Herndon, JE, Garst, J, and Kelley, MJ. "Phase II study of carboplatin, irinotecan, and thalidomide combination in patients with extensive stage small-cell lung cancer." Lung cancer (Amsterdam, Netherlands) 54.3 (December 2006): 431-432. (Academic Article)
PMID
17005294
Source
manual
Published In
Lung Cancer
Volume
54
Issue
3
Publish Date
2006
Start Page
431
End Page
432

Treatment with Imatinib in NSCLC is associated with decrease of phosphorylated PDGFR-beta and VEGF expression, decrease in interstitial fluid pressure and improvement of oxygenation.

Elevated intratumoral interstitial fluid pressure (IFP) and tumour hypoxia are independent predictive factors for poor survival and poor treatment response in cancer patients. However, the relationship between IFP and tumour hypoxia has not yet been clearly established. Preclinical studies have shown that lowering IFP improves treatment response to cytotoxic therapy. Interstitial fluid pressure can be reduced by inhibition of phosphorylated platelet-derived growth factor receptor-beta (p-PDGFR-beta), a tyrosine kinase receptor frequently overexpressed in cancer stroma, and/or by inhibition of VEGF, a growth factor commonly overexpressed in tumours overexpressing p-PDGFR-beta. We hypothesised that Imatinib, a specific PDGFR-beta inhibitor will, in addition to p-PDGFR-beta inhibition, downregulate VEGF, decrease IFP and improve tumour oxygenation. A549 human lung adenocarcinoma xenografts overexpressing PDGFR-beta were grown in nude mice. Tumour-bearing animals were randomised to control and treatment groups (Imatinib 50 mg kg(-1) via gavage for 4 days). Interstitial fluid pressure was measured in both groups before and after treatment. EF5, a hypoxia marker, was administered 3 h before being killed. Tumours were sectioned and stained for p-PDGFR-beta, VEGF and EF5 binding. Stained sections were viewed with a fluorescence microscope and image analysis was performed. Imatinib treatment resulted in significant reduction of p-PDGFR-beta, VEGF and IFP. Tumour oxygenation was also significantly improved. This study shows that p-PDGFR-beta-overexpressing tumours can be effectively treated with Imatinib to decrease tumour IFP. Importantly, this is the first study demonstrating that Imatinib treatment improves tumour oxygenation and downregulates tumour VEGF expression.

Authors
Vlahovic, G; Rabbani, ZN; Herndon, JE; Dewhirst, MW; Vujaskovic, Z
MLA Citation
Vlahovic, G, Rabbani, ZN, Herndon, JE, Dewhirst, MW, and Vujaskovic, Z. "Treatment with Imatinib in NSCLC is associated with decrease of phosphorylated PDGFR-beta and VEGF expression, decrease in interstitial fluid pressure and improvement of oxygenation." Br J Cancer 95.8 (October 23, 2006): 1013-1019.
PMID
17003785
Source
pubmed
Published In
British Journal of Cancer
Volume
95
Issue
8
Publish Date
2006
Start Page
1013
End Page
1019
DOI
10.1038/sj.bjc.6603366

Quantitative analysis of O6-alkylguanine-DNA alkyltransferase in malignant glioma.

Promoter hypermethylation of the DNA repair protein O(6)-alkylguanine-DNA alkyltransferase (AGT) has been associated with an enhanced response to chloroethylating and methylating agents in patients with malignant glioma. The purpose of this study was to compare three distinct yet related indices for measuring AGT to determine if these assays could be used interchangeably when AGT status is to be used to guide chemotherapeutic decisions. Real-time methylation-specific PCR (MSP), assessed as the ratio of methylated AGT copies to internal beta-actin control, was used to quantitate AGT hypermethylation in 32 glioma samples. Data were compared with AGT enzyme activity as well as immunohistochemical detection of AGT protein from the same samples. Hypermethylation of the AGT promoter was detected in 19 of 31 (61%) samples evaluable by MSP. Low-level AGT, defined as <20% nuclear AGT staining by immunohistochemistry, was found in 10 of 32 samples (31%), whereas 12 of 32 (38%) had low levels of AGT activity. Correlation of immunohistochemistry to AGT activity was statistically significant (P = 0.014) as was the correlation of immunohistochemistry to MSP (P = 0.043), whereas MSP compared with AGT activity (P = 0.246) was not significant. Cross-tabulation of immunohistochemistry and MSP data based on prognostic groups, where good prognosis was represented by an immunohistochemistry of <20% and an MSP ratio >12, showed no significant relationship (P = 0.214), suggesting that one assay cannot be used interchangeably for another. The observed discordance between respective measures of AGT based on prognosis supports further standardization of AGT assays designed to guide therapeutic practice. The data also suggest that consideration be given to the large population of AGT-expressing cells within samples when therapeutic strategies based on tumor methylation are used.

Authors
Maxwell, JA; Johnson, SP; Quinn, JA; McLendon, RE; Ali-Osman, F; Friedman, AH; Herndon, JE; Bierau, K; Bigley, J; Bigner, DD; Friedman, HS
MLA Citation
Maxwell, JA, Johnson, SP, Quinn, JA, McLendon, RE, Ali-Osman, F, Friedman, AH, Herndon, JE, Bierau, K, Bigley, J, Bigner, DD, and Friedman, HS. "Quantitative analysis of O6-alkylguanine-DNA alkyltransferase in malignant glioma." Mol Cancer Ther 5.10 (October 2006): 2531-2539.
PMID
17041097
Source
pubmed
Published In
Molecular cancer therapeutics
Volume
5
Issue
10
Publish Date
2006
Start Page
2531
End Page
2539
DOI
10.1158/1535-7163.MCT-06-0106

Bevacizumab and irinotecan is an effective treatment for malignant gliomas

Authors
Vredenburgh, J; Desjardins, A; II, HJE; Reardon, D; Quinn, J; Sathornsumetee, S; Gururangan, S; Friedman, A; Bigner, D; Friedman, H
MLA Citation
Vredenburgh, J, Desjardins, A, II, HJE, Reardon, D, Quinn, J, Sathornsumetee, S, Gururangan, S, Friedman, A, Bigner, D, and Friedman, H. "Bevacizumab and irinotecan is an effective treatment for malignant gliomas." October 2006.
Source
wos-lite
Published In
Neuro-Oncology
Volume
8
Issue
4
Publish Date
2006
Start Page
454
End Page
454

Overall survival of primary glioblastoma (GBM) patients receiving radiation and concurrent temozolomide followed by rotational multi-agent chemotherapy

Authors
Affronti, ML; Dowell, JM; II, HJE; Cahill, J; Rich, JN; Quinn, JA; Reardon, DA; Vredenburgh, JJ; Desjardins, A; Gururangan, S; Friedman, HS
MLA Citation
Affronti, ML, Dowell, JM, II, HJE, Cahill, J, Rich, JN, Quinn, JA, Reardon, DA, Vredenburgh, JJ, Desjardins, A, Gururangan, S, and Friedman, HS. "Overall survival of primary glioblastoma (GBM) patients receiving radiation and concurrent temozolomide followed by rotational multi-agent chemotherapy." October 2006.
Source
wos-lite
Published In
Neuro-Oncology
Volume
8
Issue
4
Publish Date
2006
Start Page
437
End Page
437

Measuring disease-free survival and cancer relapse using Medicare claims from CALGB breast cancer trial participants (companion to 9344).

To determine the accuracy with which Medicare claims data measure disease-free survival in elderly Medicare beneficiaries with cancer, we performed a criterion validation study. We merged gold-standard clinical trial data of 45 elderly patients with node-positive breast cancer who were treated on the Cancer and Leukemia Group B (CALGB) adjuvant breast trial 9344 with Centers for Medicare and Medicaid Services (CMS) data files and compared the results of a CMS-based algorithm with the CALGB disease-free survival information to determine sensitivity and specificity. For 5-year disease-free survival, the sensitivity of the CMS-based algorithm was 100% (95% confidence interval [CI] = 81% to 100%), the specificity was 97% (95% CI = 83% to 100%), and the area under the receiver operator curve was 98[corrected]% (95% CI = 95[corrected]% to 100%). For 2-year disease-free survival, the test characteristics were less favorable: sensitivity was 83% (95% CI = 36% to 100%), specificity was 95% (95% CI = 83% to 100%), and area under the receiver operator curve was 89[corrected]% (95% CI = 72[corrected]% to 100%).

Authors
Lamont, EB; Herndon, JE; Weeks, JC; Henderson, IC; Earle, CC; Schilsky, RL; Christakis, NA; Cancer and Leukemia Group B,
MLA Citation
Lamont, EB, Herndon, JE, Weeks, JC, Henderson, IC, Earle, CC, Schilsky, RL, Christakis, NA, and Cancer and Leukemia Group B, . "Measuring disease-free survival and cancer relapse using Medicare claims from CALGB breast cancer trial participants (companion to 9344)." J Natl Cancer Inst 98.18 (September 20, 2006): 1335-1338.
PMID
16985253
Source
pubmed
Published In
Journal of the National Cancer Institute
Volume
98
Issue
18
Publish Date
2006
Start Page
1335
End Page
1338
DOI
10.1093/jnci/djj363

Randomized multicenter trial of hyperthermic isolated limb perfusion with melphalan alone compared with melphalan plus tumor necrosis factor: American College of Surgeons Oncology Group Trial Z0020.

PURPOSE: To determine in a randomized prospective multi-institutional trial whether the addition of tumor necrosis factor alpha (TNF-alpha) to a melphalan-based hyperthermic isolated limb perfusion (HILP) treatment would improve the complete response rate for locally advanced extremity melanoma. PATIENTS AND METHODS: Patients with locally advanced extremity melanoma were randomly assigned to receive melphalan or melphalan plus TNF-alpha during standard HILP. Patient randomization was stratified according to disease/treatment status and regional nodal disease status. RESULTS: The intervention was completed in 124 patients of the 133 enrolled. Grade 4 adverse events were observed in 14 (12%) of 129 patients, with three (4%) of 64 in the melphalan-alone arm and 11 (16%) of 65 in the melphalan-plus-TNF-alpha arm (P = .0436). There were two toxicity-related lower extremity amputations in the melphalan-plus-TNF-alpha arm, and one disease progression-related upper extremity amputation in the melphalan-alone arm. There was no treatment-related mortality in either arm of the study. One hundred sixteen patients were assessable at 3 months postoperatively. Sixty-four percent of patients (36 of 58) in the melphalan-alone arm and 69% of patients (40 of 58) in the melphalan-plus-TNF-alpha arm showed a response to treatment at 3 months, with a complete response rate of 25% (14 of 58 patients) in the melphalan-alone arm and 26% (15 of 58 patients) in the melphalan-plus-TNF-alpha arm (P = .435 and P = .890, respectively). CONCLUSION: In locally advanced extremity melanoma treated with HILP, the addition of TNF-alpha to melphalan did not demonstrate a significant enhancement of short-term response rates over melphalan alone by the 3-month follow-up, and TNF-alpha plus melphalan was associated with a higher complication rate.

Authors
Cornett, WR; McCall, LM; Petersen, RP; Ross, MI; Briele, HA; Noyes, RD; Sussman, JJ; Kraybill, WG; Kane, JM; Alexander, HR; Lee, JE; Mansfield, PF; Pingpank, JF; Winchester, DJ; White, RL; Chadaram, V; Herndon, JE; Fraker, DL; Tyler, DS; American College of Surgeons Oncology Group Trial Z0020,
MLA Citation
Cornett, WR, McCall, LM, Petersen, RP, Ross, MI, Briele, HA, Noyes, RD, Sussman, JJ, Kraybill, WG, Kane, JM, Alexander, HR, Lee, JE, Mansfield, PF, Pingpank, JF, Winchester, DJ, White, RL, Chadaram, V, Herndon, JE, Fraker, DL, Tyler, DS, and American College of Surgeons Oncology Group Trial Z0020, . "Randomized multicenter trial of hyperthermic isolated limb perfusion with melphalan alone compared with melphalan plus tumor necrosis factor: American College of Surgeons Oncology Group Trial Z0020." J Clin Oncol 24.25 (September 1, 2006): 4196-4201.
PMID
16943537
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
24
Issue
25
Publish Date
2006
Start Page
4196
End Page
4201
DOI
10.1200/JCO.2005.05.5152

Chimeric murine/human IgG(2) anti-tenascin 81C6 monoclonal antibody: phase I trial in patients with malignant glioma of a construct with improved stability

Authors
Zalutsky, MR; Reardon, DA; Quinn, JA; Coleman, RE; Akabani, G; Friedman, AH; Friedman, HS; II, HJE; McLendon, RE; Wong, TZ; Bigner, DD
MLA Citation
Zalutsky, MR, Reardon, DA, Quinn, JA, Coleman, RE, Akabani, G, Friedman, AH, Friedman, HS, II, HJE, McLendon, RE, Wong, TZ, and Bigner, DD. "Chimeric murine/human IgG(2) anti-tenascin 81C6 monoclonal antibody: phase I trial in patients with malignant glioma of a construct with improved stability." EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING 33 (September 2006): S194-S194.
Source
wos-lite
Published In
European Journal of Nuclear Medicine and Molecular Imaging
Volume
33
Publish Date
2006
Start Page
S194
End Page
S194

Radioimmunotherapy of patients with malignant brain tumors: patient-specific dosing of I-131-labeled anti-tenacin antibody to achieve 44 Gy boost dose to resection cavity margins

Authors
Reardon, DA; Zalutsky, MR; Akabani, G; Coleman, RE; Friedman, AH; McLendon, RE; Friedman, HS; II, HJE; Kirkpatrick, J; Bigner, DD
MLA Citation
Reardon, DA, Zalutsky, MR, Akabani, G, Coleman, RE, Friedman, AH, McLendon, RE, Friedman, HS, II, HJE, Kirkpatrick, J, and Bigner, DD. "Radioimmunotherapy of patients with malignant brain tumors: patient-specific dosing of I-131-labeled anti-tenacin antibody to achieve 44 Gy boost dose to resection cavity margins." EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING 33 (September 2006): S194-S194.
Source
wos-lite
Published In
European Journal of Nuclear Medicine and Molecular Imaging
Volume
33
Publish Date
2006
Start Page
S194
End Page
S194

Bevacizumab, a monoclonal antibody to vascular endothelial growth factor (VEGF), and irinotecan for treatment of malignant gliomas.

1506 Background: The prognosis for recurrent malignant gliomas is poor, with a median survival <12 months, median progression-free survival <12 weeks and response rates <20%. Malignant gliomas have high concentrations of VEGF receptors, and the higher the VEGF receptor concentration, the worse the prognosis. Bevacizumab is a humanized IgG1 monoclonal antiblody to VEGF, which is synergistic with chemotherapy for most malignancies. Irinotecan is a topoisomerase 1 inhibitor, and has modest activity against recurrent malignant gliomas. METHODS: We report a FDA approved phase II trial of bevacizumab and irinotecan for the treatment of recurrent malignant gliomas. 32 patients were enrolled, 23 with grade IV tumors (glioblastoma multiforme) and 9 with grade III tumors (anaplastic astrocytomas or oligodendrogliomas). All the patients had progressive disease and every patient had received prior radiation therapy and chemotherapy. Patients were treated every other week with bevacizumab 10 mg/kg and irinotecan 125 mg/m(2) for patients not taking enzyme inducing anti-epileptic drugs or 340 mg/m(2) for patients taking enzyme inducing anti-epileptic drugs. RESULTS: The regimen was well tolerated with no CNS hemorrhages or >grade 1 systemic hemorrhages. Four patients were taken off study for thrombotic complications, 2 pulmonary emboli, 1 deep venous thrombus, and one thrombotic stroke. Two patients were discontinued secondary to grade 2 proteinuria and three were discontinued because they required non-neurosurgical surgery, appendectomy, repair of anal fissures and hip stabilization. The response rate was 63% (19 PRs and 1 CR). The median progression-free survival is 24 weeks. The median overall survival has not been reached, and exceeds 6 months. There have been ten deaths due to disease progression. CONCLUSIONS: The combination of bevacizumab and irinotecan is safe and one of the most active regimens against malignant gliomas. [Table: see text].

Authors
Vredenburgh, JJ; Desjardins, A; Herndon, JE; Quinn, J; Rich, J; Sathornsumetee, S; Friedman, HS; Reardon, D; Gururangan, S; Friedman, A
MLA Citation
Vredenburgh, JJ, Desjardins, A, Herndon, JE, Quinn, J, Rich, J, Sathornsumetee, S, Friedman, HS, Reardon, D, Gururangan, S, and Friedman, A. "Bevacizumab, a monoclonal antibody to vascular endothelial growth factor (VEGF), and irinotecan for treatment of malignant gliomas." J Clin Oncol 24.18_suppl (June 20, 2006): 1506-.
PMID
27952313
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
24
Issue
18_suppl
Publish Date
2006
Start Page
1506

Adjuvant chemotherapy in stage IB non-small cell lung cancer (NSCLC): Update of Cancer and Leukemia Group B (CALGB) protocol 9633.

7007 Background: In 2004, preliminary results of CALGB 9633 demonstrated statistically significant evidence that adjuvant chemotherapy with paclitaxel and carboplatin (PC) improved disease-free (DFS) and overall survival (OS) in resected stage IB NSCLC. Indeed, the study was closed early by the DSMB after a planned interim analysis demonstrated a p value for OS less than a prespecified stopping boundary. However, two larger trials, NCIC-JBR10 and ANITA, have shown significant OS advantages with adjuvant chemo, but failed to demonstrate improved survival in the stage IB subset. This report provides more mature data from CALGB 9633. METHODS: InCALGB 9633, stage IB patients (pts) were randomized following resection to paclitaxel 200 mg/m(2) and carboplatin AUC 6 q3wks ×4 cycles or to observation. While initially planned to accrue 500 pts, the accrual rate was <50% of expected. Because slow accrual allowed longer observation times for each pt, the accrual target was reduced to 384 pts. OS is the primary endpoint. The redesigned study had 80% power to detect a hazard ratio (HR) of 0.67 after 150 observed deaths using a 1-tailed logrank test conducted at the 0.05 level of significance. RESULTS: Between 9/15/96 and 11/26/03, 344 pts were randomized. Median follow-up is 54 mo. Demographics and toxicity has been previously reported (JCO Sup, 22:621a, 2004). The current intent-to-treat analysis shows a significant improvement in DFS favoring adjuvant chemo (HR=0.74; 90% 2-sided CI: 0.57-0.96; p=0.027). There is a trend toward improvement in OS that is not significant (HR=0.80; 90% CI: 0.60-1.07; p=0.10). There is, however, a significant advantage in 3-yr survival (79% vs. 70%; p=0.045). Five-yr survival is not different (60% vs. 57%; p=0.32), although median follow-up is <5 yrs and CIs are wide. Continued follow-up is planned since only 131 of 150 deaths required for final analysis have been observed. CONCLUSIONS: This updated but "preliminary" analysis no longer shows a significant OS advantage for adjuvant chemotherapy in stage IB NSCLC. However, the re-designed study does not have adequate power to detect small differences in OS that may be clinically significant. Advantages in DFS and 3-yr survival support continued consideration of adjuvant PC in stage IB NSCLC. [Table: see text].

Authors
Strauss, GM; Herndon, JE; Maddaus, MA; Johnstone, DW; Johnson, EA; Watson, DM; Sugarbaker, DJ; Schilsky, RA; Vokes, EE; Green, MR; CALGB, Radiation Therapy Oncology Group,
MLA Citation
Strauss, GM, Herndon, JE, Maddaus, MA, Johnstone, DW, Johnson, EA, Watson, DM, Sugarbaker, DJ, Schilsky, RA, Vokes, EE, Green, MR, CALGB, and Radiation Therapy Oncology Group, . "Adjuvant chemotherapy in stage IB non-small cell lung cancer (NSCLC): Update of Cancer and Leukemia Group B (CALGB) protocol 9633." J Clin Oncol 24.18_suppl (June 20, 2006): 7007-.
PMID
27953235
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
24
Issue
18_suppl
Publish Date
2006
Start Page
7007

Bevacizumab, a monoclonal antibody to vascular endothelial growth factor (VEGF), and irinotecan for treatment of malignant gliomas.

Authors
Vredenburgh, JJ; Desjardins, A; II, HJE; Quinn, J; Rich, J; Sathornsumetee, S; Friedman, HS; Reardon, D; Gururangan, S; Friedman, A
MLA Citation
Vredenburgh, JJ, Desjardins, A, II, HJE, Quinn, J, Rich, J, Sathornsumetee, S, Friedman, HS, Reardon, D, Gururangan, S, and Friedman, A. "Bevacizumab, a monoclonal antibody to vascular endothelial growth factor (VEGF), and irinotecan for treatment of malignant gliomas." June 20, 2006.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
24
Issue
18
Publish Date
2006
Start Page
59S
End Page
59S

Adjuvant chemotherapy in stage IB non-small cell lung cancer (NSCLC): Update of Cancer and Leukemia Group B (CALGB) protocol 9633.

Authors
Strauss, GM; II, HJE; Maddaus, MA; Johnstone, DW; Johnson, EA; Watson, DM; Sugarbaker, DJ; Schilsky, RA; Vokes, EE; Green, MR; CALGB, RTOG
MLA Citation
Strauss, GM, II, HJE, Maddaus, MA, Johnstone, DW, Johnson, EA, Watson, DM, Sugarbaker, DJ, Schilsky, RA, Vokes, EE, Green, MR, and CALGB, RTOG. "Adjuvant chemotherapy in stage IB non-small cell lung cancer (NSCLC): Update of Cancer and Leukemia Group B (CALGB) protocol 9633." June 20, 2006.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
24
Issue
18
Publish Date
2006
Start Page
365S
End Page
365S

Serum protein expression predicts recurrence in patients with early-stage lung cancer after resection.

BACKGROUND: Patients with early stage nonsmall-cell lung cancer who have undergone complete resection have a recurrence rate of approximately 50%, predominately due to the development of systemic metastases. This study is a prospective analysis of the expression of seven serum protein markers of invasion and metastasis, collected preoperatively (baseline) and serially after resection, to determine the relationship between marker expression and recurrence. METHODS: Serum was collected from 196 patients with clinical stage I nonsmall-cell lung cancer who underwent resection over a 5-year period (1996 to 2000). Samples were drawn before resection and 1, 4, 6, 12, 18, and 24 months postoperatively. All patients were followed for at least 24 months or until death. Serum protein levels of vascular endothelial growth factor, hepatocyte growth factor), E-selectin, CD44, basic fibroblast growth factor, urokinase plasminogen activator, and urokinase plasminogen activator receptor were determined using enzyme-linked immunosorbent assay. RESULTS: To date, 73 patients (37%) have demonstrated recurrence. Baseline levels of only 1 marker (CD44) correlated with pathologic stage (p = 0.02). Analysis of the serial samples demonstrated that recurrence was predicted (before clinical or radiographic determination) by decreasing levels of E-selectin (p = 0.002), increasing levels of CD44 (p = 0.001), and increasing levels of urokinase plasminogen activator receptor (p = 0.03). CONCLUSIONS: This study demonstrates the potential to predict recurrence after resection in patients with early-stage nonsmall-cell lung cancer using a panel of serum protein markers. Early identification of patients with recurrence may improve the efficacy of systemic therapy.

Authors
D'Amico, TA; Brooks, KR; Joshi, M-BM; Conlon, D; Herndon, J; Petersen, RP; Harpole, DH
MLA Citation
D'Amico, TA, Brooks, KR, Joshi, M-BM, Conlon, D, Herndon, J, Petersen, RP, and Harpole, DH. "Serum protein expression predicts recurrence in patients with early-stage lung cancer after resection." Ann Thorac Surg 81.6 (June 2006): 1982-1987.
PMID
16731117
Source
pubmed
Published In
Annals of Thoracic Surgery
Volume
81
Issue
6
Publish Date
2006
Start Page
1982
End Page
1987
DOI
10.1016/j.athoracsur.2006.01.042

Novel human IgG2b/murine chimeric antitenascin monoclonal antibody construct radiolabeled with 131I and administered into the surgically created resection cavity of patients with malignant glioma: phase I trial results.

UNLABELLED: Results from animal experiments have shown that human IgG2/mouse chimeric antitenascin 81C6 (ch81C6) monoclonal antibody exhibited higher tumor accumulation and enhanced stability compared with its murine parent. Our objective was to determine the effect of these differences on the maximum tolerated dose (MTD), pharmacokinetics, dosimetry, and antitumor activity of (131)I-ch81C6 administered into the surgically created resection cavity (SCRC) of malignant glioma patients. METHODS: In this phase I trial, eligible patients received a single injection of (131)I-ch81C6 administered through a Rickham catheter into the SCRC. Patients were stratified as newly diagnosed and untreated (stratum A), newly diagnosed after external beam radiotherapy (XRT) (stratum B), and recurrent (stratum C). (131)I-ch81C6 was administered either before (stratum A) or after (stratum B) conventional XRT for newly diagnosed patients. In addition, chemotherapy was prescribed for all patients after (131)I-ch81C6 administration. Dose escalation was performed independently for each stratum. Patients were observed for toxicity and response until death or progressive disease. RESULTS: We treated 47 patients with (131)I-ch81C6 doses up to 4.44 GBq (120 mCi), including 35 with newly diagnosed tumors (strata A and B) and 12 with recurrent disease (stratum C). Dose-limiting hematologic toxicity defined the MTD to be 2.96 GBq (80 mCi) for all patients, regardless of treatment strata. Neurologic dose-limiting toxicity developed in 3 patients; however, none required further surgery to debulk radiation necrosis. Median survival was 88.6 wk and 65.0 wk for newly diagnosed and recurrent patients, respectively. CONCLUSION: The MTD of (131)I-ch81C6 is 2.96 GBq (80 mCi) because of dose-limiting hematologic toxicity. Although encouraging survival was observed, (131)I-ch81C6 was associated with greater hematologic toxicity, probably due to the enhanced stability of the IgG2 construct, than previously observed with (131)I-murine 81C6.

Authors
Reardon, DA; Quinn, JA; Akabani, G; Coleman, RE; Friedman, AH; Friedman, HS; Herndon, JE; McLendon, RE; Pegram, CN; Provenzale, JM; Dowell, JM; Rich, JN; Vredenburgh, JJ; Desjardins, A; Sampson, JH; Gururangan, S; Wong, TZ; Badruddoja, MA; Zhao, X-G; Bigner, DD; Zalutsky, MR
MLA Citation
Reardon, DA, Quinn, JA, Akabani, G, Coleman, RE, Friedman, AH, Friedman, HS, Herndon, JE, McLendon, RE, Pegram, CN, Provenzale, JM, Dowell, JM, Rich, JN, Vredenburgh, JJ, Desjardins, A, Sampson, JH, Gururangan, S, Wong, TZ, Badruddoja, MA, Zhao, X-G, Bigner, DD, and Zalutsky, MR. "Novel human IgG2b/murine chimeric antitenascin monoclonal antibody construct radiolabeled with 131I and administered into the surgically created resection cavity of patients with malignant glioma: phase I trial results." J Nucl Med 47.6 (June 2006): 912-918.
PMID
16741299
Source
pubmed
Published In
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
Volume
47
Issue
6
Publish Date
2006
Start Page
912
End Page
918

Glycoprotein nonmetastatic melanoma protein B, a potential molecular therapeutic target in patients with glioblastoma multiforme.

PURPOSE: More brain tumor markers are required for prognosis and targeted therapy. We have identified and validated promising molecular therapeutic glioblastoma multiforme (GBM) targets: human transmembrane glycoprotein nonmetastatic melanoma protein B (GPNMB(wt)) and a splice variant form (GPNMB(sv), a 12-amino-acid in-frame insertion in the extracellular domain). EXPERIMENTAL DESIGN: We have done genetic and immunohistochemical evaluation of human GBM to determine incidence, distribution, and pattern of localization of GPNMB antigens in brain tumors as well as survival analyses. RESULTS: Quantitative real-time PCR on 50 newly diagnosed GBM patient tumor samples indicated that 35 of 50 GBMs (70%) were positive for GPNMB(wt+sv) transcripts and 15 of 50 GBMs (30%) were positive for GPNMB(sv) transcripts. Normal brain samples expressed little or no GPNMB mRNA. We have isolated and characterized an anti-GPNMB polyclonal rabbit antiserum (2640) and two IgG2b monoclonal antibodies (mAb; G11 and U2). The binding affinity constants of the mAbs ranged from 0.27 x 10(8) to 9.6 x 10(8) M(-1) measured by surface plasmon resonance with immobilized GPNMB, or 1.7 to 2.1 x 10(8) M(-1) by Scatchard analyses with cell-expressed GPNMB. Immunohistochemical analysis detected GPNMB in a membranous and cytoplasmic pattern in 52 of 79 GBMs (66%), with focal perivascular reactivity in approximately 27%. Quantitative flow cytometric analysis revealed GPNMB cell surface molecular density of 1.1 x 10(4) to 7.8 x 10(4) molecules per cell, levels sufficient for mAb targeting. Increased GPNMB mRNA levels correlated with elevated GPNMB protein expression in GBM biopsy samples. Univariate and multivariate analyses correlated expression of GPNMB with survival of 39 GBM patients using RNA expression and immunohistochemical data, establishing that patients with relatively high mRNA GPNMB transcript levels (wt+sv and wt), >3-fold over normal brain, as well as positive immunohistochemistry, have a significantly higher risk of death (hazard ratios, 3.0, 2.2, and 2.8, respectively). CONCLUSIONS: Increased mRNA and protein levels in GBM patient biopsy samples correlated with higher survival risk; as a detectable surface membrane protein in glioma cells, the data indicate that GPNMB is a potentially useful tumor-associated antigen and prognostic predictor for therapeutic approaches with malignant gliomas or any malignant tumor that expresses GPNMB.

Authors
Kuan, C-T; Wakiya, K; Dowell, JM; Herndon, JE; Reardon, DA; Graner, MW; Riggins, GJ; Wikstrand, CJ; Bigner, DD
MLA Citation
Kuan, C-T, Wakiya, K, Dowell, JM, Herndon, JE, Reardon, DA, Graner, MW, Riggins, GJ, Wikstrand, CJ, and Bigner, DD. "Glycoprotein nonmetastatic melanoma protein B, a potential molecular therapeutic target in patients with glioblastoma multiforme." Clin Cancer Res 12.7 Pt 1 (April 1, 2006): 1970-1982.
PMID
16609006
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
12
Issue
7 Pt 1
Publish Date
2006
Start Page
1970
End Page
1982
DOI
10.1158/1078-0432.CCR-05-2797

Surgical complications associated with sentinel lymph node biopsy: results from a prospective international cooperative group trial.

BACKGROUND: American College of Surgeons Oncology Group Z0010 is a prospective multicenter trial designed to evaluate the prognostic significance of micrometastases in the sentinel lymph nodes and bone marrow aspirates of women with early-stage breast cancer. Surgical complications associated with the sentinel lymph node biopsy surgical procedure are reported. METHODS: Eligible patients included women with clinical T1/2N0M0 breast cancer. Surgical outcomes were available at 30 days and 6 months after surgery for 5327 patients. Patients who had a failed sentinel node mapping (n=71, 1.4%) or a completion lymph node dissection (n=814, 15%) were excluded. Univariate and multivariate analyses were performed to identify predictors for the measured surgical complications. RESULTS: In patients who received isosulfan blue dye alone (n=783) or a combination of blue dye and radiocolloid (n=4192), anaphylaxis was reported in .1% of subjects (5 of 4975). Other complications included axillary wound infection in 1.0%, axillary seroma in 7.1%, and axillary hematoma in 1.4% of subjects. Only increasing age and an increasing number of sentinel lymph nodes removed were significantly associated with an increasing incidence of axillary seroma. At 6 months, 8.6% of patients reported axillary paresthesias, 3.8% had a decreased upper extremity range of motion, and 6.9% demonstrated proximal upper extremity lymphedema (change from baseline arm circumference of >2 cm). Significant predictors for surgical complications at 6 months were a decreasing age for axillary paresthesias and increasing body mass index and increasing age for upper extremity lymphedema. CONCLUSIONS: This study provides a prospective assessment of the sentinel lymph node biopsy procedure, as performed by a wide range of surgeons, demonstrating a low complication rate.

Authors
Wilke, LG; McCall, LM; Posther, KE; Whitworth, PW; Reintgen, DS; Leitch, AM; Gabram, SGA; Lucci, A; Cox, CE; Hunt, KK; Herndon, JE; Giuliano, AE
MLA Citation
Wilke, LG, McCall, LM, Posther, KE, Whitworth, PW, Reintgen, DS, Leitch, AM, Gabram, SGA, Lucci, A, Cox, CE, Hunt, KK, Herndon, JE, and Giuliano, AE. "Surgical complications associated with sentinel lymph node biopsy: results from a prospective international cooperative group trial." Ann Surg Oncol 13.4 (April 2006): 491-500.
PMID
16514477
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
13
Issue
4
Publish Date
2006
Start Page
491
End Page
500
DOI
10.1245/ASO.2006.05.013

Hepatic arterial infusion versus systemic therapy for hepatic metastases from colorectal cancer: a randomized trial of efficacy, quality of life, and molecular markers (CALGB 9481).

PURPOSE: Hepatic metastases derive most of their blood supply from the hepatic artery; therefore, for patients with hepatic metastases from colorectal cancer, hepatic arterial infusion (HAI) of chemotherapy may improve outcome. METHODS: In a multi-institutional trial, 135 patients were randomly assigned to receive HAI versus systemic bolus fluorouracil and leucovorin. The primary end point was survival; secondary end points were response, recurrence, toxicity, quality of life, cost, and the influence of molecular markers. RESULTS: Overall survival was significantly longer for HAI versus systemic treatment (median, 24.4 v 20 months; P = .0034), as were response rates (47% and 24%; P = .012) and time to hepatic progression (THP; 9.8 v 7.3 months; P = .034). Time to extrahepatic progression (7.7 v 14.8 months; P = .029) was significantly shorter in the HAI group. Quality-of-life measurements showed improved physical functioning in the HAI group at the 3- and 6-month follow-up assessments. Toxicity included grade > or = 3 neutropenia (2% and 45%; P < .01), stomatitis (0% and 24%; P < .01), and bilirubin elevation (18.6% and 0; P < .01) in the HAI and systemic treatment groups, respectively. A greater proportion of men versus women receiving HAI experienced biliary toxicity (37% and 15%, respectively; P = .05). For HAI patients with thymidylate synthase levels in tumor less than or > or = 4, the median survival was 24 and 14 months, respectively (P = .17). CONCLUSION: HAI therapy increased overall survival, response rate, THP, and was associated with better physical functioning compared with systemic therapy. Additional studies need to address the overall benefit and cost of new chemotherapy agents versus HAI alone or the combination of HAI with new agents.

Authors
Kemeny, NE; Niedzwiecki, D; Hollis, DR; Lenz, H-J; Warren, RS; Naughton, MJ; Weeks, JC; Sigurdson, ER; Herndon, JE; Zhang, C; Mayer, RJ
MLA Citation
Kemeny, NE, Niedzwiecki, D, Hollis, DR, Lenz, H-J, Warren, RS, Naughton, MJ, Weeks, JC, Sigurdson, ER, Herndon, JE, Zhang, C, and Mayer, RJ. "Hepatic arterial infusion versus systemic therapy for hepatic metastases from colorectal cancer: a randomized trial of efficacy, quality of life, and molecular markers (CALGB 9481)." J Clin Oncol 24.9 (March 20, 2006): 1395-1403.
PMID
16505413
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
24
Issue
9
Publish Date
2006
Start Page
1395
End Page
1403
DOI
10.1200/JCO.2005.03.8166

Increased regulatory T-cell fraction amidst a diminished CD4 compartment explains cellular immune defects in patients with malignant glioma.

Immunosuppression is frequently associated with malignancy and is particularly severe in patients with malignant glioma. Anergy and counterproductive shifts toward T(H)2 cytokine production are long-recognized T-cell defects in these patients whose etiology has remained elusive for >30 years. We show here that absolute counts of both CD4(+) T cells and CD4(+)CD25(+)FOXP3(+)CD45RO(+) T cells (T(regs)) are greatly diminished in patients with malignant glioma, but T(regs) frequently represent an increased fraction of the remaining CD4 compartment. This increased T(reg) fraction, despite reduced counts, correlates with and is sufficient to elicit the characteristic manifestations of impaired patient T-cell responsiveness in vitro. Furthermore, T(reg) removal eradicates T-cell proliferative defects and reverses T(H)2 cytokine shifts, allowing T cells from patients with malignant glioma to function in vitro at levels equivalent to those of normal, healthy controls. Such restored immune function may give license to physiologic antiglioma activity, as in vivo, T(reg) depletion proves permissive for spontaneous tumor rejection in a murine model of established intracranial glioma. These findings dramatically alter our understanding of depressed cellular immune function in patients with malignant glioma and advance a role for T(regs) in facilitating tumor immune evasion in the central nervous system.

Authors
Fecci, PE; Mitchell, DA; Whitesides, JF; Xie, W; Friedman, AH; Archer, GE; Herndon, JE; Bigner, DD; Dranoff, G; Sampson, JH
MLA Citation
Fecci, PE, Mitchell, DA, Whitesides, JF, Xie, W, Friedman, AH, Archer, GE, Herndon, JE, Bigner, DD, Dranoff, G, and Sampson, JH. "Increased regulatory T-cell fraction amidst a diminished CD4 compartment explains cellular immune defects in patients with malignant glioma." Cancer Res 66.6 (March 15, 2006): 3294-3302.
PMID
16540683
Source
pubmed
Published In
Cancer Research
Volume
66
Issue
6
Publish Date
2006
Start Page
3294
End Page
3302
DOI
10.1158/0008-5472.CAN-05-3773

Morbidity and mortality of major pulmonary resections in patients with early-stage lung cancer: initial results of the randomized, prospective ACOSOG Z0030 trial.

BACKGROUND: Little prospective, multiinstitutional data exist regarding the morbidity and mortality after major pulmonary resections for lung cancer or whether a mediastinal lymph node dissection increases morbidity and mortality. METHODS: Prospectively collected 30-day postoperative data was analyzed from 1,111 patients undergoing pulmonary resection who were enrolled from July 1999 to February 2004 in a randomized trial comparing lymph node sampling versus mediastinal lymph node dissection for early stage lung cancer. RESULTS: Of the 1,111 patients randomized, 1,023 were included in the analysis. Median age was 68 years (range, 23 to 89 years); 52% were men. Lobectomy was performed in 766 (75%) and pneumonectomy in 42 (4%). Pathologic stage was IA in 424 (42%), IB in 418 (41%), IIA in 37 (4%), IIB in 97 (9%), and III in 45 (5%). Lymph node sampling was performed in 498 patients and lymph node dissection in 525. Operative mortality was 2.0% (10 of 498) for lymph node sampling and 0.76% (4 of 525) for lymph node dissection. Complications occurred in 38% of patients in each group. Lymph node dissection had a longer median operative time and greater total chest tube drainage (15 minutes, 121 mL, respectively). There was no difference in the median hospitalization, which was 6 days in each group (p = 0.404). CONCLUSIONS: Complete mediastinal lymphadenectomy adds little morbidity to a pulmonary resection for lung cancer. These data from a current, multiinstitutional cohort of patients who underwent a major pulmonary resection constitute a new baseline with which to compare results in the future.

Authors
Allen, MS; Darling, GE; Pechet, TTV; Mitchell, JD; Herndon, JE; Landreneau, RJ; Inculet, RI; Jones, DR; Meyers, BF; Harpole, DH; Putnam, JB; Rusch, VW; ACOSOG Z0030 Study Group,
MLA Citation
Allen, MS, Darling, GE, Pechet, TTV, Mitchell, JD, Herndon, JE, Landreneau, RJ, Inculet, RI, Jones, DR, Meyers, BF, Harpole, DH, Putnam, JB, Rusch, VW, and ACOSOG Z0030 Study Group, . "Morbidity and mortality of major pulmonary resections in patients with early-stage lung cancer: initial results of the randomized, prospective ACOSOG Z0030 trial." Ann Thorac Surg 81.3 (March 2006): 1013-1019.
PMID
16488712
Source
pubmed
Published In
Annals of Thoracic Surgery
Volume
81
Issue
3
Publish Date
2006
Start Page
1013
End Page
1019
DOI
10.1016/j.athoracsur.2005.06.066

Phase 1 trial of gefitinib plus sirolimus in adults with recurrent malignant glioma.

PURPOSE: To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of gefitinib, a receptor tyrosine kinase inhibitor of the epidermal growth factor receptor, plus sirolimus, an inhibitor of the mammalian target of rapamycin, among patients with recurrent malignant glioma. PATIENTS AND METHODS: Gefitinib and sirolimus were administered on a continuous daily dosing schedule at dose levels that were escalated in successive cohorts of malignant glioma patients at any recurrence who were stratified based on concurrent use of CYP3A-inducing anticonvulsants [enzyme-inducing antiepileptic drugs, (EIAED)]. Pharmacokinetic and archival tumor biomarker data were also assessed. RESULTS: Thirty-four patients with progressive disease after prior radiation therapy and chemotherapy were enrolled, including 29 (85%) with glioblastoma multiforme and 5 (15%) with anaplastic glioma. The MTD was 500 mg of gefitinib plus 5 mg of sirolimus for patients not on EIAEDs and 1,000 mg of gefitinib plus 10 mg of sirolimus for patients on EIAEDs. DLTs included mucositis, diarrhea, rash, thrombocytopenia, and hypertriglyceridemia. Gefitinib exposure was not affected by sirolimus administration but was significantly lowered by concurrent EIAED use. Two patients (6%) achieved a partial radiographic response, and 13 patients (38%) achieved stable disease. CONCLUSION: We show that gefitinib plus sirolimus can be safely coadministered on a continuous, daily dosing schedule, and established the recommended dose level of these agents in combination for future phase 2 clinical trials.

Authors
Reardon, DA; Quinn, JA; Vredenburgh, JJ; Gururangan, S; Friedman, AH; Desjardins, A; Sathornsumetee, S; Herndon, JE; Dowell, JM; McLendon, RE; Provenzale, JM; Sampson, JH; Smith, RP; Swaisland, AJ; Ochs, JS; Lyons, P; Tourt-Uhlig, S; Bigner, DD; Friedman, HS; Rich, JN
MLA Citation
Reardon, DA, Quinn, JA, Vredenburgh, JJ, Gururangan, S, Friedman, AH, Desjardins, A, Sathornsumetee, S, Herndon, JE, Dowell, JM, McLendon, RE, Provenzale, JM, Sampson, JH, Smith, RP, Swaisland, AJ, Ochs, JS, Lyons, P, Tourt-Uhlig, S, Bigner, DD, Friedman, HS, and Rich, JN. "Phase 1 trial of gefitinib plus sirolimus in adults with recurrent malignant glioma." Clin Cancer Res 12.3 Pt 1 (February 1, 2006): 860-868.
PMID
16467100
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
12
Issue
3 Pt 1
Publish Date
2006
Start Page
860
End Page
868
DOI
10.1158/1078-0432.CCR-05-2215

Telephone monitoring: Early identification of psychological, physical and social distress in older advanced-stage cancer patients

Authors
Kornblith, AB; Dowell, JM; Herndon, JE; Rosenberg, S; Engelman, B; Small, EJ; Morrison, VA; Atkins, J; Muss, H; Holland, JC
MLA Citation
Kornblith, AB, Dowell, JM, Herndon, JE, Rosenberg, S, Engelman, B, Small, EJ, Morrison, VA, Atkins, J, Muss, H, and Holland, JC. "Telephone monitoring: Early identification of psychological, physical and social distress in older advanced-stage cancer patients." PSYCHO-ONCOLOGY 15.1 (February 2006): S21-S22.
Source
wos-lite
Published In
Psycho-Oncology
Volume
15
Issue
1
Publish Date
2006
Start Page
S21
End Page
S22

Similar outcomes between African American and non-African American patients with extensive-stage small-cell lung carcinoma: report from the Cancer and Leukemia Group B.

PURPOSE: Among patients with small-cell lung carcinoma, African Americans have lower survival rates than non-African Americans. We investigated whether the disparity in survival would persist when patients were treated with similar therapies (ie, phase II/III Cancer and Leukemia Group B [CALGB] trials). PATIENTS AND METHODS: We assessed 995 patients (928 non-African American and 67 African American) receiving chemotherapy in CALGB studies for extensive-stage small-cell lung cancer (ES-SCLC). Clinical and demographic characteristics, treatment received, and survival data were obtained from the CALGB database. The Cox proportional hazards model was used to assess the effect of race/ethnicity on survival after adjustment for other known prognostic factors. All statistical tests were two sided. RESULTS: The unadjusted survival distribution of African American patients was not significantly different from that of non-African American patients; median survival was 11.5 months (95% CI, 9.4 to 13.4 months) for African American patients versus 9.9 months (95% CI, 9.6 to 10.3 months) for non-African American patients. Multivariable adjustment for the effect of treatment arm, histology, and metastatic site at presentation did not alter the outcome for African American patients. Survival was similar even though African American patients were more likely to have a poorer performance status, present with significant weight loss, and be Medicaid recipients (20% v 6%), which is an indicator of lower socioeconomic status. CONCLUSION: African American patients tended to present with prognostic features associated with a worse survival. However, when offered equivalent therapy, the outcome for African American patients was the same as that observed for non-African American patients.

Authors
Blackstock, AW; Herndon, JE; Paskett, ED; Miller, AA; Lathan, C; Niell, HB; Socinski, MA; Vokes, EE; Green, MR; Cancer and Leukemia Group B,
MLA Citation
Blackstock, AW, Herndon, JE, Paskett, ED, Miller, AA, Lathan, C, Niell, HB, Socinski, MA, Vokes, EE, Green, MR, and Cancer and Leukemia Group B, . "Similar outcomes between African American and non-African American patients with extensive-stage small-cell lung carcinoma: report from the Cancer and Leukemia Group B." J Clin Oncol 24.3 (January 20, 2006): 407-412.
PMID
16365181
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
24
Issue
3
Publish Date
2006
Start Page
407
End Page
412
DOI
10.1200/JCO.2005.02.1436

Salvage radioimmunotherapy with murine iodine-131-labeled antitenascin monoclonal antibody 81C6 for patients with recurrent primary and metastatic malignant brain tumors: phase II study results.

PURPOSE: To assess the efficacy and toxicity of intraresection cavity iodine-131-labeled murine antitenascin monoclonal antibody 81C6 (131I-m81C6) among recurrent malignant brain tumor patients. PATIENTS AND METHODS: In this phase II trial, 100 mCi of 131I-m81C6 was injected directly into the surgically created resection cavity (SCRC) of 43 patients with recurrent malignant glioma (glioblastoma multiforme [GBM], n = 33; anaplastic astrocytoma [AA], n = 6; anaplastic oligodendroglioma [AO], n = 2; gliosarcoma [GS], n = 1; and metastatic adenocarcinoma, n = 1) followed by chemotherapy. RESULTS: With a median follow-up of 172 weeks, 63% and 59% of patients with GBM/GS and AA/AO tumors were alive at 1 year. Median overall survival for patients with GBM/GS and AA/AO tumors was 64 and 99 weeks, respectively. Ten patients (23%) developed acute hematologic toxicity. Five patients (12%) developed acute reversible neurotoxicity. One patient (2%) developed irreversible neurotoxicity. No patients required reoperation for radionecrosis. CONCLUSION: In this single-institution phase II study, administration of 100 mCi of 131I-m81C6 to recurrent malignant glioma patients followed by chemotherapy is associated with a median survival that is greater than that of historical controls treated with surgery plus iodine-125 brachytherapy. Furthermore, toxicity was acceptable. Administration of a fixed millicurie dose resulted in a wide range of absorbed radiation doses to the SCRC. We are now conducting a phase II trial, approved by the US Food and Drug Administration, using patient-specific 131I-m81C6 dosing, to deliver 44 Gy to the SCRC followed by standardized chemotherapy. A phase III multicenter trial with patient-specific dosing is planned.

Authors
Reardon, DA; Akabani, G; Coleman, RE; Friedman, AH; Friedman, HS; Herndon, JE; McLendon, RE; Pegram, CN; Provenzale, JM; Quinn, JA; Rich, JN; Vredenburgh, JJ; Desjardins, A; Gururangan, S; Badruddoja, M; Dowell, JM; Wong, TZ; Zhao, X-G; Zalutsky, MR; Bigner, DD
MLA Citation
Reardon, DA, Akabani, G, Coleman, RE, Friedman, AH, Friedman, HS, Herndon, JE, McLendon, RE, Pegram, CN, Provenzale, JM, Quinn, JA, Rich, JN, Vredenburgh, JJ, Desjardins, A, Gururangan, S, Badruddoja, M, Dowell, JM, Wong, TZ, Zhao, X-G, Zalutsky, MR, and Bigner, DD. "Salvage radioimmunotherapy with murine iodine-131-labeled antitenascin monoclonal antibody 81C6 for patients with recurrent primary and metastatic malignant brain tumors: phase II study results." J Clin Oncol 24.1 (January 1, 2006): 115-122.
PMID
16382120
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
24
Issue
1
Publish Date
2006
Start Page
115
End Page
122
DOI
10.1200/JCO.2005.03.4082

A phase I study of dose-dense topotecan given upfront to standard therapy in patients with small cell lung cancer.

OBJECTIVE: To determine the feasibility and maximum tolerated dose of dose-dense topotecan as induction chemotherapy before standard therapy (carboplatin plus etoposide alone or in combination with radiotherapy) in patients with small cell lung cancer (SCLC). PATIENTS AND METHODS: Chemotherapy-naive patients with SCLC and good performance status were eligible. Three 2-week cycles of dose-dense topotecan administered on days 1-3 with granulocyte colony-stimulating factor support were followed by four cycles of standard carboplatin plus etoposide therapy alone (extensive-stage SCLC) or with radiotherapy (limited-stage SCLC). The dose of topotecan was escalated from 1.5 mg/m2/day to 2.5 mg/m2/day in increments of 0.25 mg/m2/day within cohorts of 3-5 patients each. Dose-limiting toxicity was defined as any grade 3 or 4 toxicity resulting in a treatment reduction or a delay of >3 days. RESULTS: Twenty-two patients with SCLC (5 limited-stage, 17 extensive-stage) were enrolled. Treatment was well tolerated. The dose-limiting toxicities were thrombocytopenia and neutropenia, and the maximum tolerated dose of dose-dense topotecan induction therapy was 2.25 mg/m2/day. Overall, topotecan-related grade 3/4 haematological toxicities included neutropenia (n = 4), thrombocytopenia (n = 3) and febrile neutropenia (n = 1). No grade 4 non-haematological toxicities occurred. Grade 3 adverse events included nausea (n = 2), renal toxicity (n = 1) and anorexia (n = 1). Toxicity during the carboplatin plus etoposide +/- radiotherapy phase of therapy was consistent with that reported in previous trials. The overall response rate was 80% for limited-stage and 76% for extensive-stage SCLC. Median survival was 8 months in patients with limited-stage SCLC and 13.5 months for patients with extensive-stage SCLC. CONCLUSION: The results of this phase I study suggest that a regimen of sequential dose-dense topotecan and carboplatin plus etoposide is feasible, and the preliminary activity observed in patients with SCLC warrants further investigation at a starting dose of topotecan 2.25 mg/m2/day.

Authors
Garst, J; Herndon, JE; Shafman, T; Campagna, L; Blackwell, S; Padilla, K; Bjurstrom, T; Andrews, C; Maravich May, D; Anderson, E; Crawford, J
MLA Citation
Garst, J, Herndon, JE, Shafman, T, Campagna, L, Blackwell, S, Padilla, K, Bjurstrom, T, Andrews, C, Maravich May, D, Anderson, E, and Crawford, J. "A phase I study of dose-dense topotecan given upfront to standard therapy in patients with small cell lung cancer." Clinical drug investigation 26.5 (2006): 257-266. (Academic Article)
PMID
17163259
Source
manual
Published In
Clinical drug investigation
Volume
26
Issue
5
Publish Date
2006
Start Page
257
End Page
266

Assessing the ability of the antiangiogenic and anticytokine agent thalidomide to modulate radiation-induced lung injury

Purpose: Thalidomide has broad anticytokine properties, which might protect normal tissues in patients undergoing chemoradiotherapy. The purpose of this study was to determine the maximal tolerated dose of thalidomide when used in combination with vinorelbine plus thoracic radiotherapy. Methods and Materials: Eligible patients had inoperable Stage III non-small-cell lung cancer, a Karnofsky Performance Status ⩾70, and life expectancy ⩾6 months. Patients underwent pretreatment evaluation of lung function. Radiotherapy consisted of 66 Gy in 6.5 weeks. Vinorelbine was administered i.v. (5 mg/m2) 3 times per week just before radiotherapy. Thalidomide was begun at 50 mg, p.o., on day 1 of chemoradiotherapy and continued once daily for 6 months. Side effects were scored using National Cancer Institute Common Toxicity Criteria. Results: Ten patients were enrolled. Of the first 6 patients, 2 developed major thrombotic events that were believed to be possibly related to thalidomide. The study was suspended and modified to require prophylactic anticoagulation. Of the last 4 patients, 2 developed dose-limiting toxicity attributable to thalidomide; both patients required a dose reduction of thalidomide to <50 mg/day. Because the drug is not available in an oral product providing <50 mg/day, the study was closed. Conclusions: The combination of thalidomide concurrently with thoracic radiotherapy and vinorelbine resulted in excessive toxicity. [All rights reserved Elsevier]

Authors
Anscher, MS; Garst, J; Marks, LB; Larrier, N; Dunphy, F; II, HJE; Clough, R; Marino, C; Vujaskovic, Z; Zhou, S; Dewhirst, MW; Shafman, TD; Crawford, J
MLA Citation
Anscher, MS, Garst, J, Marks, LB, Larrier, N, Dunphy, F, II, HJE, Clough, R, Marino, C, Vujaskovic, Z, Zhou, S, Dewhirst, MW, Shafman, TD, and Crawford, J. "Assessing the ability of the antiangiogenic and anticytokine agent thalidomide to modulate radiation-induced lung injury." Int. J. Radiat. Oncol. Biol. Phys. (USA) 66.2 (2006): 477-482. (Academic Article)
PMID
16904841
Source
manual
Published In
Int. J. Radiat. Oncol. Biol. Phys. (USA)
Volume
66
Issue
2
Publish Date
2006
Start Page
477
End Page
482
DOI
10.1016/j.ijrobp.2006.05.031

Phase II study of imatinib mesylate plus hydroxyurea in adults with recurrent glioblastoma multiforme.

PURPOSE: We performed a phase II study to evaluate the combination of imatinib mesylate, an adenosine triphosphate mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiforme (GBM). PATIENTS AND METHODS: Patients with GBM at any recurrence received imatinib mesylate plus hydroxyurea (500 mg twice a day) orally on a continuous, daily schedule. The imatinib mesylate dose was 500 mg twice a day for patients on enzyme-inducing antiepileptic drugs (EIAEDs) and 400 mg once a day for those not on EIAEDs. Assessments were performed every 28 days. The primary end point was 6-month progression-free survival (PFS). RESULTS: Thirty-three patients enrolled with progressive disease after prior radiotherapy and at least temozolomide-based chemotherapy. With a median follow-up of 58 weeks, 27% of patients were progression-free at 6 months, and the median PFS was 14.4 weeks. Three patients (9%) achieved radiographic response, and 14 (42%) achieved stable disease. Cox regression analysis identified concurrent EIAED use and no more than one prior progression as independent positive prognostic factors of PFS. The most common toxicities included grade 3 neutropenia (16%), thrombocytopenia (6%), and edema (6%). There were no grade 4 or 5 events. Concurrent EIAED use lowered imatinib mesylate exposure. Imatinib mesylate clearance was decreased at day 28 compared with day 1 in all patients, suggesting an effect of hydroxyurea. CONCLUSION: Imatinib mesylate plus hydroxyurea is well tolerated and associated with durable antitumor activity in some patients with recurrent GBM.

Authors
Reardon, DA; Egorin, MJ; Quinn, JA; Rich, JN; Gururangan, S; Vredenburgh, JJ; Desjardins, A; Sathornsumetee, S; Provenzale, JM; Herndon, JE; Dowell, JM; Badruddoja, MA; McLendon, RE; Lagattuta, TF; Kicielinski, KP; Dresemann, G; Sampson, JH; Friedman, AH; Salvado, AJ; Friedman, HS
MLA Citation
Reardon, DA, Egorin, MJ, Quinn, JA, Rich, JN, Gururangan, S, Vredenburgh, JJ, Desjardins, A, Sathornsumetee, S, Provenzale, JM, Herndon, JE, Dowell, JM, Badruddoja, MA, McLendon, RE, Lagattuta, TF, Kicielinski, KP, Dresemann, G, Sampson, JH, Friedman, AH, Salvado, AJ, and Friedman, HS. "Phase II study of imatinib mesylate plus hydroxyurea in adults with recurrent glioblastoma multiforme." J Clin Oncol 23.36 (December 20, 2005): 9359-9368.
PMID
16361636
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
23
Issue
36
Publish Date
2005
Start Page
9359
End Page
9368
DOI
10.1200/JCO.2005.03.2185

Quality of life among patients with Stage II and III breast carcinoma randomized to receive high-dose chemotherapy with autologous bone marrow support or intermediate-dose chemotherapy: results from Cancer and Leukemia Group B 9066.

BACKGROUND: The objective of this study was to compare the quality of life (QOL) after treatment among patients who had breast carcinoma with multiple positive lymph nodes. The patients were randomized to receive either high-dose chemotherapy with autologous stem cell support (HDC) or intermediate-dose chemotherapy (IDC) in the adjuvant setting. METHODS: Two hundred forty-six patients with AJCC Stage IIA, IIB, or IIIA breast carcinoma who had > or = 10 positive lymph nodes and who were participants in Cancer and Leukemia Group B (CALGB) 9082 were enrolled in this companion study, CALGB 9066. Patients were randomized to receive either high-dose cyclophosphamide, carmustine, and cisplatin (CPA/cDDP/BCNU) and autologous bone marrow transplantation (the HDC arm) or intermediate-dose CPA/cDDP/BCNU as consolidation to adjuvant chemotherapy (the IDC arm). QOL was assessed at baseline and at 3 months, 12 months, 24 months, and 36 months using the Functional Living Index-Cancer (FLIC), the Psychosocial Adjustment to Illness Scale (PAIS)-Self Report, and the McCorkle Symptom Distress Scale (SDS). RESULTS: At the 3-month assessment, patients in the HDC arm demonstrated significant worsening of QOL compared with the IDC arm in terms of their physical well being (FLIC, P = 0.023), social functioning (FLIC, P = 0.026; PAIS, P < 0.0001), symptom distress (SDS, P = 0.0002), and total QOL scores (FLIC, P = 0.042). At 12 months, the differences in QOL scores between the HDC arm and the IDC arm had resolved. CONCLUSIONS: Patients who received more intensive adjuvant therapy experienced transient declines in QOL. By 12 months after therapy, QOL was comparable between the 2 arms, regardless of therapy intensity, and many QOL areas were improved from baseline.

Authors
Peppercorn, J; Herndon, J; Kornblith, AB; Peters, W; Ahles, T; Vredenburgh, J; Schwartz, G; Shpall, E; Hurd, DD; Holland, J; Winer, E
MLA Citation
Peppercorn, J, Herndon, J, Kornblith, AB, Peters, W, Ahles, T, Vredenburgh, J, Schwartz, G, Shpall, E, Hurd, DD, Holland, J, and Winer, E. "Quality of life among patients with Stage II and III breast carcinoma randomized to receive high-dose chemotherapy with autologous bone marrow support or intermediate-dose chemotherapy: results from Cancer and Leukemia Group B 9066." Cancer 104.8 (October 15, 2005): 1580-1589.
PMID
16118805
Source
pubmed
Published In
Cancer
Volume
104
Issue
8
Publish Date
2005
Start Page
1580
End Page
1589
DOI
10.1002/cncr.21363

Survival analysis of presumptive prognostic markers among oligodendrogliomas.

BACKGROUND: Allelic losses of 1p and 19q arms correlate with the oligodendroglial phenotype as well as with sensitivity to radiotherapy and chemotherapy. Furthermore, the DNA repair gene, methylguanine methyltransferase (MGMT), is diminished in 80% of oligodendroglial tumors and represents a possible mechanism for this therapeutic sensitivity. However, the authors questioned the relevance of genetic testing and measuring MGMT levels in tumors that were diagnostic of oligodendroglioma. METHODS: The authors performed a retrospective analysis of 1p, 19q, 9p21, TP53, and MGMT status in 46 patients with oligodendrogliomas to address any relations that may exist among these markers with regard to progression-free survival (PFS) and total survival. Methodologies included comparative genomic hybridization; loss of heterozygosity (LOH) on 1p, 19q, and 9p21; TP53 mutational analysis; and immunohistochemistry for MGMT. RESULTS: The authors found that survival among patients with light microscopically diagnosed oligodendroglial tumors demonstrating LOH of 1p and 19q trended toward statistical significance (P = 0.102 and P = 0.058, respectively). 9p21 LOH was significant as a predictor of PFS only among anaplastic oligodendrogliomas in this cohort (P = 0.033). TP53 mutation was found to be significantly predictive of a shorter survival (P = 0.027) among all patients and exhibited a strong trend toward a shorter PFS (P = 0.060). Low-level MGMT labeling index (LI) (< 20%) was noted in 86% of all oligodendroglial tumors. MGMT LI was not found to correlate with an improved PFS or total survival in this cohort, recognizing that median survival was not reached after a median follow-up of 104 months. CONCLUSIONS: 9p21 and TP53 mutational status assisted in developing a stricter subclassification of these tumors with prognostic significance. MGMT levels were decreased in a majority of oligodendrogliomas.

Authors
McLendon, RE; Herndon, JE; West, B; Reardon, D; Wiltshire, R; Rasheed, BKA; Quinn, J; Friedman, HS; Friedman, AH; Bigner, DD
MLA Citation
McLendon, RE, Herndon, JE, West, B, Reardon, D, Wiltshire, R, Rasheed, BKA, Quinn, J, Friedman, HS, Friedman, AH, and Bigner, DD. "Survival analysis of presumptive prognostic markers among oligodendrogliomas." Cancer 104.8 (October 15, 2005): 1693-1699.
PMID
16116609
Source
pubmed
Published In
Cancer
Volume
104
Issue
8
Publish Date
2005
Start Page
1693
End Page
1699
DOI
10.1002/cncr.21362

Phase I trial of irinotecan plus temozolomide in adults with recurrent malignant glioma.

BACKGROUND: The authors determined the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of irinotecan (CPT-11), a topoisomerase I inhibitor, when administered with temozolomide among patients with recurrent malignant glioma (MG). METHODS: Patients with MG at any recurrence received temozolomide (TMZ) at a dose of 200 mg/m(2)/day on Days 1-5 plus CPT-11 administered as a 90-minute intravenous infusion during Weeks 1, 2, 4, and 5 of each 6-week cycle. Patients were stratified based on concurrent administration of CYP3A4-inducing anticonvulsants (enzyme-inducing antiepileptic drugs [EIAEDs]). The CPT-11 dose was escalated in successive cohorts of patients independently for each stratum. RESULTS: CPT-11, at doses ranging from 40 mg/m(2) to 375 mg/m(2), was administered with TMZ to 107 patients. Ninety-one patients (85%) had recurrent glioblastoma multiforme (GBM) and 16 (15%) had recurrent anaplastic glioma. Sixty-eight patients (64%) were given EIAEDs. The MTD of CPT-11 for patients concurrently receiving and not receiving EIAEDs was 325 mg/m(2) and 125 mg/m(2), respectively. The DLTs were hematologic, gastrointestinal, and hepatic. Fifteen patients (14%) achieved either a radiographic complete (n = 5) or partial (n = 10) response across a wide range of CPT-11 dose levels. Patients with recurrent GBM who achieved radiographic response had a median time to disease progression of 54.9 weeks. CONCLUSIONS: The current study built on preclinical observations designed to increase the clinical activity of topoisomerase I inhibitors. CPT-11, administered at full dose levels, was well tolerated in combination with TMZ. Furthermore, durable responses were observed in this recurrent population. Ongoing Phase II studies will evaluate the efficacy of this regimen and its application to other malignancies.

Authors
Reardon, DA; Quinn, JA; Rich, JN; Desjardins, A; Vredenburgh, J; Gururangan, S; Sathornsumetee, S; Badruddoja, M; McLendon, R; Provenzale, J; Herndon, JE; Dowell, JM; Burkart, JL; Newton, HB; Friedman, AH; Friedman, HS
MLA Citation
Reardon, DA, Quinn, JA, Rich, JN, Desjardins, A, Vredenburgh, J, Gururangan, S, Sathornsumetee, S, Badruddoja, M, McLendon, R, Provenzale, J, Herndon, JE, Dowell, JM, Burkart, JL, Newton, HB, Friedman, AH, and Friedman, HS. "Phase I trial of irinotecan plus temozolomide in adults with recurrent malignant glioma." Cancer 104.7 (October 1, 2005): 1478-1486.
PMID
16088964
Source
pubmed
Published In
Cancer
Volume
104
Issue
7
Publish Date
2005
Start Page
1478
End Page
1486
DOI
10.1002/cncr.21316

Phase I trial of temozolomide plus O6-benzylguanine for patients with recurrent or progressive malignant glioma.

PURPOSE: We conducted a two-phase clinical trial in patients with progressive malignant glioma (MG). The first phase of this trial was designed to determine the dose of O6-BG effective in producing complete depletion of tumor AGT activity for 48 hours. The second phase of the trial was designed to define the maximum tolerated dose (MTD) of a single dose of temozolomide when combined with O6-BG. In addition, plasma concentrations of O6-BG and O6-benzyl-8-oxoguanine were evaluated after O6-BG. PATIENTS AND METHODS: For our first phase of the clinical trial, patients were scheduled to undergo craniotomy for AGT determination after receiving a 1-hour O6-BG infusion at 120 mg/m2 followed by a continuous infusion at an initial dose of 30 mg/m2/d for 48 hours. The dose of the continuous infusion of O6-BG escalated until tumor AGT was depleted. Once the O6-BG dose was established a separate group of patients was enrolled in the second phase of clinical trial, in which temozolomide, administered as a single dose at the end of the 1-hour O6-BG infusion, was escalated until the MTD was determined. RESULTS: The O6-BG dose found to be effective in depleting tumor AGT activity at 48 hours was an IV bolus of 120 mg/m2 over 1 hour followed by a continuous infusion of 30 mg/m2/d for 48 hours. On enrolling 38 patients in six dose levels of temozolomide, the MTD was established at 472 mg/m2 with dose-limiting toxicities limited to myelosuppression. CONCLUSION: This study provides the foundation for a phase II trial of O6-BG plus temozolomide in temozolomide-resistant MG.

Authors
Quinn, JA; Desjardins, A; Weingart, J; Brem, H; Dolan, ME; Delaney, SM; Vredenburgh, J; Rich, J; Friedman, AH; Reardon, DA; Sampson, JH; Pegg, AE; Moschel, RC; Birch, R; McLendon, RE; Provenzale, JM; Gururangan, S; Dancey, JE; Maxwell, J; Tourt-Uhlig, S; Herndon, JE; Bigner, DD; Friedman, HS
MLA Citation
Quinn, JA, Desjardins, A, Weingart, J, Brem, H, Dolan, ME, Delaney, SM, Vredenburgh, J, Rich, J, Friedman, AH, Reardon, DA, Sampson, JH, Pegg, AE, Moschel, RC, Birch, R, McLendon, RE, Provenzale, JM, Gururangan, S, Dancey, JE, Maxwell, J, Tourt-Uhlig, S, Herndon, JE, Bigner, DD, and Friedman, HS. "Phase I trial of temozolomide plus O6-benzylguanine for patients with recurrent or progressive malignant glioma." J Clin Oncol 23.28 (October 1, 2005): 7178-7187.
PMID
16192602
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
23
Issue
28
Publish Date
2005
Start Page
7178
End Page
7187
DOI
10.1200/JCO.2005.06.502

Sentinel node skills verification and surgeon performance: data from a multicenter clinical trial for early-stage breast cancer.

OBJECTIVE: Marked variations in sentinel lymph node dissection (SLND) technique have been identified, and definitive qualifications for SLND performance remain controversial. Based on previous reports and expert opinion, we predicted that 20 to 30 cases of SLND with axillary lymph node dissection (ALND) would enable surgeons to identify sentinel lymph nodes (SLN). SUMMARY BACKGROUND DATA: In 1999, the American College of Surgeons Oncology Group initiated a prospective trial, Z0010, to evaluate micrometastatic disease in the SLN and bone marrow of women with early-stage breast cancer. Eligible patients included women with biopsy-proven T1/T2 breast cancer and clinically negative lymph nodes who were candidates for lumpectomy and SLND. METHODS: Participating surgeons were required to document 20 to 30 SLNDs followed by immediate ALND with failure rates less than 15%. Prior fellowship or residency training in SLND provided exemption from skill requirements. Data for 5237 subjects and 198 surgeons were available for analysis. RESULTS: Surgeons from academic (48.4%), community (28.6%), or teaching-affiliated (19.8%) institutions qualified with 30 SLND + ALND cases (64.6%), 20 cases (22.2%), or exemption (13.1%). Participants used blue dye + radiocolloid in 79.4%, blue dye alone in 14.8%, and radiocolloid alone in 5.7% of cases, achieving a 98.7% SLN identification rate. Patient factors associated with increased SLND failure included increased body mass index and age, whereas tumor location, stage, and histology, presence of nodal metastases, and number of positive nodes were not. Surgeon accrual of fewer than 50 patients was associated with increased SLND failure; however, SLND technique, specific skill qualification, and institution type were not. CONCLUSIONS: Using a standard skill requirement, surgeons from a variety of institutions achieved an acceptably low SLND failure rate in the setting of a large multicenter trial, validating the incorporation of SLND into clinical practice.

Authors
Posther, KE; McCall, LM; Blumencranz, PW; Burak, WE; Beitsch, PD; Hansen, NM; Morrow, M; Wilke, LG; Herndon, JE; Hunt, KK; Giuliano, AE
MLA Citation
Posther, KE, McCall, LM, Blumencranz, PW, Burak, WE, Beitsch, PD, Hansen, NM, Morrow, M, Wilke, LG, Herndon, JE, Hunt, KK, and Giuliano, AE. "Sentinel node skills verification and surgeon performance: data from a multicenter clinical trial for early-stage breast cancer." Ann Surg 242.4 (October 2005): 593-599.
PMID
16192820
Source
pubmed
Published In
Annals of Surgery
Volume
242
Issue
4
Publish Date
2005
Start Page
593
End Page
599

Patterns of participation and successful patient recruitment to American College of Surgeons Oncology Group Z0010, a phase II trial for patients with early-stage breast cancer.

BACKGROUND: Historically, fewer than 5% of cancer patients enroll in clinical trials and lack of physician participation is a contributing factor. In 1999, the American College of Surgeons Oncology Group (ACOSOG) conducted a multicenter breast cancer trial evaluating the prognostic value of sentinel lymph node (SLN) and bone marrow micrometastases. This report elucidates factors influencing patient accrual. METHODS: Demographics of investigators (N = 198) and their success in accruing patients (N = 5327) were reviewed. ACOSOG Breast Committee members (N = 1136) were surveyed to identify factors influencing participation. RESULTS: Surgeons from 126 institutions participated in Z0010 (academic [48%], teaching-affiliated [20%], and community [29%] practices), and 28% of surgeons accrued 75% of the subjects. Twenty-four percent of surgeons accrued 75% of minority patients. Female surgeons accrued 24% of patients and accounted for 30% of investigators. On survey, 16% of respondents reported no prior experience with clinical trials and a number of factors were identified that influenced participation. CONCLUSIONS: ACOSOG successfully accrued 5327 patients to a SLN trial with surgeon participation from all practice settings. However, significant barriers to participation remain.

Authors
Leitch, AM; Beitsch, PD; McCall, LM; Posther, K; Newman, LA; Herndon, JE; Hunt, KK; Giuliano, AE
MLA Citation
Leitch, AM, Beitsch, PD, McCall, LM, Posther, K, Newman, LA, Herndon, JE, Hunt, KK, and Giuliano, AE. "Patterns of participation and successful patient recruitment to American College of Surgeons Oncology Group Z0010, a phase II trial for patients with early-stage breast cancer." Am J Surg 190.4 (October 2005): 539-542.
PMID
16164916
Source
pubmed
Published In
The American Journal of Surgery
Volume
190
Issue
4
Publish Date
2005
Start Page
539
End Page
542
DOI
10.1016/j.amjsurg.2005.06.024

Criterion validity of Medicare chemotherapy claims in Cancer and Leukemia Group B breast and lung cancer trial participants.

To determine the accuracy with which Medicare claims data measure chemotherapy use in elderly Medicare beneficiaries with cancer, we performed a criterion validation study. We compared gold-standard clinical trial data for 175 elderly cancer patients treated in two Cancer and Leukemia Group B (CALGB) breast and lung cancer trials (i.e., 45 from trial 9344 and 130 from trial 9730) with contemporaneous ambulatory and in-patient Medicare health insurance claims data from Centers for Medicare and Medicaid Services (CMS). The breast trial participants studied were those elderly enrolled between 1995 and 1997 and treated with doxorubicin and cyclophosphamide or this combination with paclitaxel. The lung trial participants studied were those elderly enrolled between 1998 and 2000 and treated with paclitaxel and carboplatin or paclitaxel alone. Comparing CALGB data with Medicare claims, we found the crude sensitivity for chemotherapy administration was 93% (95% confidence interval [CI] = 88% to 96%). Individual chemotherapy agents had similarly high sensitivities, ranging from 81% (95% CI = 70% to 89%) for carboplatin to 91% (95% CI = 79% to 98%) for cyclophosphamide. Agent-specific specificities were 100%. CMS data reliably captured repeat administration of chemotherapy to within one cycle. Administrative Medicare claims data appear to be a valid source of information for chemotherapy administered to elderly Medicare beneficiaries with cancer.

Authors
Lamont, EB; Herndon, JE; Weeks, JC; Henderson, IC; Lilenbaum, R; Schilsky, RL; Christakis, NA
MLA Citation
Lamont, EB, Herndon, JE, Weeks, JC, Henderson, IC, Lilenbaum, R, Schilsky, RL, and Christakis, NA. "Criterion validity of Medicare chemotherapy claims in Cancer and Leukemia Group B breast and lung cancer trial participants." J Natl Cancer Inst 97.14 (July 20, 2005): 1080-1083.
PMID
16030306
Source
pubmed
Published In
Journal of the National Cancer Institute
Volume
97
Issue
14
Publish Date
2005
Start Page
1080
End Page
1083
DOI
10.1093/jnci/dji189

Induction paclitaxel/carboplatin followed by concurrent chemoradiation therapy for unresectable stage III non-small-cell lung cancer: a limited-access study--CALGB 9534.

BACKGROUND: This phase II cooperative group study of patients with unresectable stage III non-small-cell lung cancer was designed to treat patients with induction chemotherapy with paclitaxel and carboplatin (PC) followed by concurrent chemotherapy with the same chemotherapy plus thoracic irradiation to 66 Gy. PATIENTS AND METHODS: All enrolled patients were scheduled to receive 2 cycles of induction PC at conventional doses. All nonprogressing patients were subsequently treated with concurrent chemoradiation, including 7 weekly doses of PC and once-daily thoracic irradiation. The eligibility criteria allowed treatment of an expanded population of patients, unrestricted by previous weight loss. RESULTS: Despite the fact that 22% of patients had experienced > 5% weight loss in the preceding 6 months, 23 of the 40 eligible patients (58%) responded to the overall regimen. A 3-year failure-free survival rate of 15% and a 3-year overall survival rate of 27% were achieved. The 3-year overall survival rate is consistent with landmark cooperative group results for the combined modality treatment of a more highly selected patient population. CONCLUSION: The feasibility of this therapeutic approach in a cooperative group setting and inclusive of patients who were representative of the general population of stage III lung cancer patients was established.

Authors
Akerley, W; Herndon, JE; Lyss, AP; Choy, H; Turrisi, A; Graziano, S; Williams, T; Zhang, C; Vokes, EE; Green, MR
MLA Citation
Akerley, W, Herndon, JE, Lyss, AP, Choy, H, Turrisi, A, Graziano, S, Williams, T, Zhang, C, Vokes, EE, and Green, MR. "Induction paclitaxel/carboplatin followed by concurrent chemoradiation therapy for unresectable stage III non-small-cell lung cancer: a limited-access study--CALGB 9534." Clin Lung Cancer 7.1 (July 2005): 47-53.
PMID
16098244
Source
pubmed
Published In
Clinical lung cancer
Volume
7
Issue
1
Publish Date
2005
Start Page
47
End Page
53
DOI
10.3816/CLC.2005.n.021

Prevalence and prognostic significance of polymorphisms at the glutathione S-transferase M1, M3, P1, and T1 gene loci in human astrocytomas

Authors
Ali-Osman, F; Herndon, JE; Stephenson, L; Davis, F; McCarthy, B; Reardon, D; Friedman, A; McClendon, R; Friedman, H; Bigner, DD
MLA Citation
Ali-Osman, F, Herndon, JE, Stephenson, L, Davis, F, McCarthy, B, Reardon, D, Friedman, A, McClendon, R, Friedman, H, and Bigner, DD. "Prevalence and prognostic significance of polymorphisms at the glutathione S-transferase M1, M3, P1, and T1 gene loci in human astrocytomas." July 2005.
Source
wos-lite
Published In
Neuro-Oncology
Volume
7
Issue
3
Publish Date
2005
Start Page
304
End Page
304

Randomized phase III intergroup trial of etoposide and cisplatin with or without paclitaxel and granulocyte colony-stimulating factor in patients with extensive-stage small-cell lung cancer: Cancer and Leukemia Group B Trial 9732.

PURPOSE: To determine, in a randomized comparison, whether the addition of paclitaxel to etoposide and cisplatin improves the time to progression and overall survival in patients with extensive small-cell lung cancer (SCLC) compared with standard etoposide and cisplatin and to compare the regimens' toxicity. PATIENTS AND METHODS: Eligible patients (N=587) with untreated extensive SCLC were randomly assigned to receive either cisplatin 80 mg/m2 on day 1 and etoposide 80 mg/m2 on days 1 through 3 administered every 3 weeks for six cycles (EP) or cisplatin 80 mg/m2 on day 1, paclitaxel 175 mg/m2 over 4 hours on day 1, and etoposide 80 mg/m2 on days 1 to 3 followed by recombinant human granulocyte colony-stimulating factor on days 4 to 18 administered every 3 weeks for six cycles (PET). RESULTS: Reporting of demographics, response, and survival included 565 patients, of whom 282 were randomly assigned to receive EP and 283 were assigned to receive PET. Overall response rates were 68% for the EP arm and 75% for the PET arm. Median failure-free survival time was 5.9 months for the EP arm and 6 months for the PET arm (P = .179). Median overall survival time was 9.9 months for patients on EP and 10.6 months for patients on PET (P = .169). Toxic deaths occurred in 2.4% of the patients on EP and 6.5% of patients on PET. CONCLUSION: PET did not improve the time to progression or survival in patients with extensive SCLC compared with EP alone and was associated with unacceptable toxicity.

Authors
Niell, HB; Herndon, JE; Miller, AA; Watson, DM; Sandler, AB; Kelly, K; Marks, RS; Perry, MC; Ansari, RH; Otterson, G; Ellerton, J; Vokes, EE; Green, MR; Cancer and Leukemia Group,
MLA Citation
Niell, HB, Herndon, JE, Miller, AA, Watson, DM, Sandler, AB, Kelly, K, Marks, RS, Perry, MC, Ansari, RH, Otterson, G, Ellerton, J, Vokes, EE, Green, MR, and Cancer and Leukemia Group, . "Randomized phase III intergroup trial of etoposide and cisplatin with or without paclitaxel and granulocyte colony-stimulating factor in patients with extensive-stage small-cell lung cancer: Cancer and Leukemia Group B Trial 9732." J Clin Oncol 23.16 (June 1, 2005): 3752-3759.
PMID
15923572
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
23
Issue
16
Publish Date
2005
Start Page
3752
End Page
3759
DOI
10.1200/JCO.2005.09.071

Criterion validity of Medicare chemotherapy claims in breast and lung cancer patients.

Authors
Lamont, EB; Herndon, JE; Weeks, JC; Henderson, IC; Lilenbaum, R; Schilsky, RL; Christakis, NA
MLA Citation
Lamont, EB, Herndon, JE, Weeks, JC, Henderson, IC, Lilenbaum, R, Schilsky, RL, and Christakis, NA. "Criterion validity of Medicare chemotherapy claims in breast and lung cancer patients." June 1, 2005.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
23
Issue
16
Publish Date
2005
Start Page
533S
End Page
533S

A phase II study of carboplatin, etoposide and exisulind in patients with extensive stage small cell lung cancer: CALGB 30104.

Authors
Wang, XF; Govindan, R; Herndon, JE; Barrier, RC; Watson, D; Vokes, RFEE; Green, MR
MLA Citation
Wang, XF, Govindan, R, Herndon, JE, Barrier, RC, Watson, D, Vokes, RFEE, and Green, MR. "A phase II study of carboplatin, etoposide and exisulind in patients with extensive stage small cell lung cancer: CALGB 30104." June 1, 2005.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
23
Issue
16
Publish Date
2005
Start Page
660S
End Page
660S

Phase II trial of karenitecin in patients with relapsed or refractory non-small cell lung cancer (CALGB 30004).

PURPOSE: This Phase II trial was designed to determine the response rate, survival, failure-free survival, and toxicity of second-line therapy with karenitecin in patients with relapsed or refractory non-small cell lung cancer (NSCLC). METHODS: Eligibility criteria included: only one prior chemotherapy program, measurable disease, performance status 0-1, adequate hematologic, renal, and hepatic function. Cases were stratified as relapsed or refractory. RESULTS: Fifty-five patients were accrued and 52 were eligible of whom 28 had relapsed and 24 had refractory disease. Overall patient characteristics were: median age 63 years (range, 45-79 years), 52% males, 63% performance status 1, 50% adenocarcinoma, 21% squamous, 15% large cell, and 12% undifferentiated NSCLC. In both strata, one patient each (4%) had a partial response and 12 patients each (43% for relapsed, 50% for refractory) had stable disease. Median survival was 10.4 months (95% CI, 8.5-17.0) for relapsed NSCLC and 6.0 months (95% CI, 3.7-9.7) for refractory NSCLC. One-year survival was 36% (95% CI, 14-58%) and 21% (95% CI, 5-37%) for relapsed and refractory NSCLC, respectively. Frequent toxicities were neutropenia (grade 3/4 in 15/15%) and thrombocytopenia (grade 3/4 in 17/8%). No patient had lethal toxicity. CONCLUSION: Second-line treatment with karenitecin was tolerable with reversible bone marrow suppression as the major toxicity. The partial response rates, median survival times, and 1-year survival rates in the relapsed and refractory subgroups are comparable to overall second-line outcomes for other agents considered active in this clinical setting.

Authors
Miller, AA; Herndon, JE; Gu, L; Green, MR; Cancer and Leukemia Group B,
MLA Citation
Miller, AA, Herndon, JE, Gu, L, Green, MR, and Cancer and Leukemia Group B, . "Phase II trial of karenitecin in patients with relapsed or refractory non-small cell lung cancer (CALGB 30004)." Lung Cancer 48.3 (June 2005): 399-407.
PMID
15893009
Source
pubmed
Published In
Lung Cancer
Volume
48
Issue
3
Publish Date
2005
Start Page
399
End Page
407
DOI
10.1016/j.lungcan.2004.11.019

Irinotecan for malignant mesothelioma A phase II trial by the Cancer and Leukemia Group B.

PURPOSE: The Cancer and Leukemia Group B (CALGB) conducted a multi-center phase II trial to evaluate the activity of irinotecan in malignant mesothelioma (CALGB protocol 9733). PATIENTS AND METHODS: Twenty-eight patients accrued between January 1998 and January 1999 received irinotecan 125 mg/m2 by intravenous infusion over 90 min weekly for 4 weeks, every 6 weeks. Eligibility included a performance status of 0-2 by CALGB criteria, and no prior chemotherapy. Twenty-five patients had pleural mesothelioma; two patients had peritoneal mesothelioma, and one patient had pericardial mesothelioma. Sixty-one percent of patients had epithelial histology. RESULTS: There were no complete or partial responders. Thirty-three percent of patients had stable disease and 52% were shown to have progressive disease at the first reassessment. One patient was not evaluable for response. Median survival from study entry was 9.3 months (95% CI 4.5-13.2 months); 1-year survival was estimated at 46% (95% CI 28-65%). Toxicity was moderately severe. Grade 3 or 4 toxicities included neutropenia in 28% of patients, lymphopenia in 43%, and diarrhea in 18%. Three patients died of treatment-related toxicities. All three experienced grade 4 diarrhea, two also had neutropenic sepsis. CONCLUSION: Single-agent irinotecan in this dose and schedule has considerable toxicity in patients with malignant mesothelioma and has no anti-tumor activity. The relatively long median survival seen in this study principally reflects the prognostic features of the accrued patients.

Authors
Kindler, HL; Herndon, JE; Zhang, C; Green, MR; Cancer and Leukemia Group B,
MLA Citation
Kindler, HL, Herndon, JE, Zhang, C, Green, MR, and Cancer and Leukemia Group B, . "Irinotecan for malignant mesothelioma A phase II trial by the Cancer and Leukemia Group B." Lung Cancer 48.3 (June 2005): 423-428.
PMID
15893012
Source
pubmed
Published In
Lung Cancer
Volume
48
Issue
3
Publish Date
2005
Start Page
423
End Page
428
DOI
10.1016/j.lungcan.2004.12.002

Economic outcomes of breast cancer survivorship: CALGB study 79804.

BACKGROUND: Over 80% of women diagnosed with breast cancer will be survivors. We sought to determine the economic consequences of surviving breast cancer. METHODS: Disease-free survivors who had received adjuvant chemotherapy for stage II breast cancer on CALGB study 8541 participated in a study of long-term outcomes. Survey responses were used to determine the types and frequency of medical resources used in follow-up, annual direct medical costs, and survivor perceptions of the personal economic impact of breast cancer. RESULTS: 245 of 314 (78%) invited breast cancer survivors (median follow-up 12.2 years, range 9.3-16.4) completed the surveys. Eighty-seven percent reported having cancer specialist follow-up in the past year. The following percentages of survivors reported having had, for breast cancer follow-up, at least once in the past year: breast examination 92%, mammogram 88%, bone scan 18%, chest radiograph 59%, tumor marker studies 37%. When follow-up care included a medical oncologist, resources were more likely to be used at least according to published follow-up guidelines, or over-used. Median annual cost of follow-up per survivor was US 630 dollars (range US 0-10,817 dollars) with higher costs associated with medical oncology follow-up, lower income, and younger age. Few women reported a negative impact of breast cancer on employment, but 16% reported being denied life insurance. CONCLUSIONS: Among long-term breast cancer survivors, patient self-report data suggest that over-use of medical resources for follow-up appears common. When follow-up care included a medical oncologist, resources were more likely to be used appropriately, or over-used. Costs of follow-up are higher with medical oncology follow-up, lower income and among younger survivors. The annual cost of follow-up varies widely and may be driven by over-use of follow-up tests.

Authors
Hensley, ML; Dowell, J; Herndon, JE; Winer, E; Stark, N; Weeks, JC; Paskett, E
MLA Citation
Hensley, ML, Dowell, J, Herndon, JE, Winer, E, Stark, N, Weeks, JC, and Paskett, E. "Economic outcomes of breast cancer survivorship: CALGB study 79804." Breast Cancer Res Treat 91.2 (May 2005): 153-161.
PMID
15868443
Source
pubmed
Published In
Breast Cancer Research and Treatment
Volume
91
Issue
2
Publish Date
2005
Start Page
153
End Page
161
DOI
10.1007/s10549-004-6497-9

Poor correspondence between clinical and pathologic staging in stage 1 non-small cell lung cancer: results from CALGB 9761, a prospective trial.

PURPOSE: A major problem with the staging system for non-small cell lung cancer (NSCLC) is clinical underestimation of the extent of disease. Many patients with clinical stage 1 disease do not retain that designation following surgical resection. Herein, we present data from Cancer and Leukemia Group B (CALGB) protocol 9761 evaluating the correspondence between clinical and pathologic analysis in early stage NSCLC. METHODS: Five hundred and two patients with suspected or biopsy-proven NSCLC classified as clinical stage 1 (T1-2, N0) by computed tomography (CT) scan or cervical mediastinoscopy were prospectively enrolled in CALGB 9761. The purpose of CALGB 9761 was to prospectively evaluate molecular markers of micrometastatic disease in stage 1 NSCLC. Enrollment occurred at 11 selected institutions within the CALGB. Patients with clinically suspected resectable early stage lung cancer were eligible for enrollment if they had no evidence of mediastinal or hilar adenopathy on CT scan or if they had CT evidence of potential N2 or N3 disease (lymph node > or =1.0 cm) but with negative mediastinoscopy. No prior chemotherapy or radiotherapy was permitted. RESULTS: Of the 502 patients felt to have clinical stage 1 NSCLC enrolled in CALGB 9761, 489 underwent resection with complete surgical staging and routine histopathologic analysis. From these 489 patients, only 422 (86.3%) turned out to have pathologically documented NSCLC. Of these 422 patients, 302 (71.6%) had pathologic stage 1 disease (173 stage 1A and 129 stage 1B). Despite clinical assessment of stage 1 disease, 59 (14%) patients had pathologic stage 2 disease, 57 (13.5%) had stage 3 disease, and four (0.9%) patients had stage 4 disease. Of the patients undergoing resection for clinical stage 1 NSCLC, 65 patients did not have NSCLC (44 had benign disease and 21 had malignancies other than NSCLC) and two additional patients had dual synchronous primary NSCLC tumors and were not eligible for the study. Overall, only 61.7% (302 of 489) of patients with suspected stage 1 NSCLC disease retained that stage and diagnosis after complete surgical staging, while 38.3% had an inaccurate pre-operative clinical stage or diagnosis. CONCLUSIONS: The results from this prospective trial demonstrate the poor predictive value of current clinical staging techniques in early stage NSCLC. These findings will serve as a benchmark for comparison of future clinical imaging modalities and other tests evaluating early stage NSCLC.

Authors
D'Cunha, J; Herndon, JE; Herzan, DL; Patterson, GA; Kohman, LJ; Harpole, DH; Kernstine, KH; Kern, JA; Green, MR; Maddaus, MA; Kratzke, RA; Cancer and Leukemia Group B,
MLA Citation
D'Cunha, J, Herndon, JE, Herzan, DL, Patterson, GA, Kohman, LJ, Harpole, DH, Kernstine, KH, Kern, JA, Green, MR, Maddaus, MA, Kratzke, RA, and Cancer and Leukemia Group B, . "Poor correspondence between clinical and pathologic staging in stage 1 non-small cell lung cancer: results from CALGB 9761, a prospective trial." Lung Cancer 48.2 (May 2005): 241-246.
PMID
15829324
Source
pubmed
Published In
Lung Cancer
Volume
48
Issue
2
Publish Date
2005
Start Page
241
End Page
246
DOI
10.1016/j.lungcan.2004.11.006

Lack of trastuzumab activity in nonsmall cell lung carcinoma with overexpression of erb-B2: 39810: a phase II trial of Cancer and Leukemia Group B.

BACKGROUND: The overexpression of HER-2 occurs in a minority of patients with nonsmall cell lung carcinoma. Trastuzumab, which is a monoclonal antibody to HER-2, is an effective treatment in some women with breast carcinomas that overexpress HER-2, as demonstrated by immunohistochemistry. The objective of this Phase II study was to determine whether trastuzumab would effect responses in patients with nonsmall cell lung carcinoma who had tumors that overexpressed HER-2. METHODS: Patients were required to have Stage IIIB or Stage IV nonsmall cell lung carcinoma and tumors with 2+ or 3+ expression of HER-2, as determined with immunohistochemistry, and they may have received up to 1 prior chemotherapy regimen. Trastuzumab at a dose of 4 mg/kg was given intravenously on Week 1; then, weekly doses of 2 mg/kg were given. Response revaluation was performed every 8 weeks. RESULTS: Among 209 screened patients, 24 patients (11%) had tumors with 2+ or 3+ expression of HER-2. One patient achieved a partial response, and one patient experienced a treatment-related death due to pulmonary toxicity. CONCLUSIONS: Single-agent trastuzumab did not exhibit significant clinical activity against nonsmall cell lung carcinoma when HER-2 expression levels were measured by immunohistochemistry.

Authors
Clamon, G; Herndon, J; Kern, J; Govindan, R; Garst, J; Watson, D; Green Cancer, M; Leukemia Group, B
MLA Citation
Clamon, G, Herndon, J, Kern, J, Govindan, R, Garst, J, Watson, D, Green Cancer, M, and Leukemia Group, B. "Lack of trastuzumab activity in nonsmall cell lung carcinoma with overexpression of erb-B2: 39810: a phase II trial of Cancer and Leukemia Group B." Cancer 103.8 (April 2005): 1670-1675. (Academic Article)
PMID
15751020
Source
manual
Published In
Cancer
Volume
103
Issue
8
Publish Date
2005
Start Page
1670
End Page
1675

Safety and efficacy of weekly oral oltipraz in chronic smokers.

Cigarette smoking is thought to contribute to carcinogenesis by formation of DNA adducts of tobacco smoke constituents leading to genotoxic damage. The dithiolethione, oltipraz, is a putative cancer chemopreventive agent that induces phase II detoxifying enzymes in preclinical models and reduces aflatoxin adducts in humans living in areas with high dietary levels. To determine if oltipraz could reduce adduct levels of tobacco smoke constituents in the lungs and other target organs, chronic smokers were enrolled to one of three arms: 400 or 200 mg/wk oral oltipraz or placebo. Endobronchial tissue and bronchoalveolar lavage were done before and after 12 weeks of drug treatment; peripheral blood, urine, and oral saline rinse were also collected. Toxicity was assessed every 4 weeks. Fifty-nine of the 77 enrolled subjects completed the study. Of those receiving oltipraz, 15% experienced grade 2/3 toxicity, which was predominantly gastrointestinal. All subject withdrawals occurred in the oltipraz groups. There was no significant difference between pre- and post-polycyclic aromatic hydrocarbon-DNA adduct levels in lung epithelial cells measured by immunoperoxidase staining between treatment and placebo groups. Likewise, no significant differences were found in polycyclic aromatic hydrocarbon or benzo(a)pyrene-7,8-diol-9,10-epoxide adducts measured in blood, oral lining cells, or bladder lining cells. There was also no increase in mRNA or enzymatic activity of phase II enzymes and no change in glutathione levels. Thus, despite moderate drug-related toxicity, there was no significant effect on pharmacodynamic or surrogate risk biomarkers. Other agents with lower toxicity and greater activity to induce phase II enzymes are needed to definitively test the detoxification-induction paradigm in smokers.

Authors
Kelley, MJ; Glaser, EM; Herndon, JE; Becker, F; Bhagat, R; Zhang, Y-J; Santella, RM; Carmella, SG; Hecht, SS; Gallot, L; Schilder, L; Crowell, JA; Perloff, M; Folz, RJ; Bergan, RC
MLA Citation
Kelley, MJ, Glaser, EM, Herndon, JE, Becker, F, Bhagat, R, Zhang, Y-J, Santella, RM, Carmella, SG, Hecht, SS, Gallot, L, Schilder, L, Crowell, JA, Perloff, M, Folz, RJ, and Bergan, RC. "Safety and efficacy of weekly oral oltipraz in chronic smokers." Cancer Epidemiol Biomarkers Prev 14.4 (April 2005): 892-899.
PMID
15824161
Source
pubmed
Published In
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume
14
Issue
4
Publish Date
2005
Start Page
892
End Page
899
DOI
10.1158/1055-9965.EPI-04-0585

Video-assisted wedge resection and local radiotherapy for peripheral lung cancer in high-risk patients: the Cancer and Leukemia Group B (CALGB) 9335, a phase II, multi-institutional cooperative group study.

OBJECTIVES: This study examined the feasibility of thoracoscopic wedge resection and radiotherapy for clinical T1 lesions in patients with compromised cardiopulmonary status. METHODS: In this phase II, prospective, multicenter, cooperative group trial, high-risk patients had one or more of the following risk factors: forced expiratory volume in 1 second less than 40%, carbon monoxide diffusing capacity in lung less than 50%, and maximum oxygen consumption less than 45 mm Hg. Patients underwent video-assisted wedge resection followed by local (56 Gy) radiotherapy. The primary end point was the proportion of patients whose disease could be completely resected and who received radiotherapy without treatment complications. RESULTS: Between September 1995 and September 1999, a total of 65 patients were accrued, of which 58 were eligible (52% male, median age 69 years). Pathologic staging resulted in upgrading to T2 or greater in 16 of 58 cases (28%) and in reassessment as benign in 10 of 58 cases (17%). Conversion to thoracotomy was required in 10 cases (17%), including 1 of 10 benign T1-size lesion (10%), 4 of 35 non-small cell lung cancer T1 lesions (13%), and 5 of 14 non-small cell lung cancer T2 lesions (31%). Resection margins were positive in 5 patients: 6% of T1 and 23% of T2. Surgery was aborted in 2 cases (3.5%), and operative mortality was 4%. Overall operative failure rates of video-assisted wedge resection were 20% for benign T1-size lesions, 22% for T1 non-small cell lung cancer, 21% for all T1 lesions, 50% for T2 non-small cell lung cancer, and 29% for all lesions in this study (clinical T1). Prolonged air leaks occurred in 10%, pneumonia in 6%, and respiratory failure in 4%. Thirty-one patients were eligible for radiotherapy; 3 of them refused, and 1 died before treatment. Among the 28 patients who received radiotherapy, severe dyspnea was noted in 3 patients (11%) and moderate pneumonitis in 4 (14%). CONCLUSIONS: Clinical staging in high-risk patients is often inaccurate (45% difference from pathologic staging). Intention to treat clinically staged T1 disease by video-assisted wedge resection is associated with a high failure rate. Pathologically staged T1 lesions can be successfully resected in 75% of cases; however, narrow resection margins remain a concern.

Authors
Shennib, H; Bogart, J; Herndon, JE; Kohman, L; Keenan, R; Green, M; Sugarbaker, D; Cancer and Leukemia Group B, ; Eastern Cooperative Oncology Group,
MLA Citation
Shennib, H, Bogart, J, Herndon, JE, Kohman, L, Keenan, R, Green, M, Sugarbaker, D, Cancer and Leukemia Group B, , and Eastern Cooperative Oncology Group, . "Video-assisted wedge resection and local radiotherapy for peripheral lung cancer in high-risk patients: the Cancer and Leukemia Group B (CALGB) 9335, a phase II, multi-institutional cooperative group study." J Thorac Cardiovasc Surg 129.4 (April 2005): 813-818.
PMID
15821648
Source
pubmed
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
129
Issue
4
Publish Date
2005
Start Page
813
End Page
818
DOI
10.1016/j.jtcvs.2004.05.011

Pulmonary vein diameter, cross-sectional area, and shape: CT analysis.

PURPOSE: To retrospectively establish normal values for pulmonary vein diameter, cross-sectional area, and shape depicted at computed tomography (CT). MATERIALS AND METHODS: Institutional review board waived patient consent requirement and approved the study. Thin-section contrast material-enhanced spiral chest CT scans in 104 patients, 68 women and 36 men (age range, 19-86 years; mean, 49 years) referred to exclude pulmonary embolism, were retrospectively reviewed. Short-axis diameter and cross-sectional area of the four major pulmonary veins (right inferior and superior, left inferior and superior) were measured at a workstation by using oblique reconstructions. Each vein was measured at six locations, 5 mm apart, starting at atrial ostium. Each measurement was performed three times by an experienced thoracic radiologist, and the mean value was recorded. Roundness was estimated by comparing the ratio of the calculated cross-sectional area to that measured. Mixed effects model was used to compare men and women relative to the distribution of diameters and surface areas and to compare roundness of the right and left veins. RESULTS: Mean pulmonary vein diameters at the ostia were variable: right superior, 11.4-12.4 mm; left superior, 9.6-10.5 mm; right inferior, 12.3-13.1 mm; and left inferior, 9.0-9.9 mm. Diameter and cross-sectional area of the left superior pulmonary vein were significantly larger in men than in women (P < .005). As expected, the caliber of three of the four veins gradually increased as they approached the left atrium. Caliber of the left inferior pulmonary vein decreased as it entered the left atrium. None of the veins were round; all were ovoid. Left-sided veins and venous ostia were less round than right-sided veins (P < .001). CONCLUSION: Pulmonary vein diameter, cross-sectional area, and shape vary. Particular care must be taken when the left inferior pulmonary vein is evaluated for stenosis, as it normally narrows as it enters the left atrium.

Authors
Kim, Y-H; Marom, EM; Herndon, JE; McAdams, HP
MLA Citation
Kim, Y-H, Marom, EM, Herndon, JE, and McAdams, HP. "Pulmonary vein diameter, cross-sectional area, and shape: CT analysis." Radiology 235.1 (April 2005): 43-49.
PMID
15731371
Source
pubmed
Published In
Radiology
Volume
235
Issue
1
Publish Date
2005
Start Page
43
End Page
49
DOI
10.1148/radiol.2351032106

Gefitinib in patients with malignant mesothelioma: a phase II study by the Cancer and Leukemia Group B.

PURPOSE: The Cancer and Leukemia Group B conducted a phase II study of gefitinib, an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, in patients with previously untreated malignant mesothelioma. EXPERIMENTAL DESIGN: Eligible patients had unresectable pleural or peritoneal mesothelioma, measurable disease, no prior therapy, and performance status 0-1 by Cancer and Leukemia Group B criteria. Gefitinib (500 mg p.o.) was administered once a day for 21 days. Patients underwent restaging after every two cycles. Therapy was continued until disease progression or unacceptable toxicity. RESULTS: The most common grade 3 toxicities were diarrhea (16%) and nausea (12%). Of 43 patients enrolled, 1 patient (2%) had a complete response, 1 patient (2%) had a partial response, 21 (49%) had stable disease lasting two to eight cycles, 15 (35%) had progressive disease, and 5 (12%) had early deaths. One-year survival was 32% [95% confidence interval (CI), 21-50%]. Median survival and failure-free survival were 6.8% (95% CI, 3.5-10.3) and 2.6 months (95% CI, 1.5-4.0), respectively. The 3-month failure-free survival was 40% (95% CI, 25-56%). EGFR expression score by immunohistochemistry done in 28 patients was categorized as low (EGFR 1+ or 2+) or high (EGFR 3+) expression: 97% had EGFR overexpression (2+ or 3+). The median and 3-month failure-free survival were 3.6 months and 40% for those patients with low EGFR expression compared with 8.1 and 40% for those with high EGFR expression. CONCLUSIONS: Although 97% of patients with mesothelioma had EGFR overexpression, gefitinib was not active in malignant mesothelioma. EGFR expression does not correlate with failure-free survival.

Authors
Govindan, R; Kratzke, RA; Herndon, JE; Niehans, GA; Vollmer, R; Watson, D; Green, MR; Kindler, HL; Cancer and Leukemia Group B (CALGB 30101),
MLA Citation
Govindan, R, Kratzke, RA, Herndon, JE, Niehans, GA, Vollmer, R, Watson, D, Green, MR, Kindler, HL, and Cancer and Leukemia Group B (CALGB 30101), . "Gefitinib in patients with malignant mesothelioma: a phase II study by the Cancer and Leukemia Group B." Clin Cancer Res 11.6 (March 15, 2005): 2300-2304.
PMID
15788680
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
11
Issue
6
Publish Date
2005
Start Page
2300
End Page
2304
DOI
10.1158/1078-0432.CCR-04-1940

High gene expression of TS1, GSTP1, and ERCC1 are risk factors for survival in patients treated with trimodality therapy for esophageal cancer.

PURPOSE: To assess the relationship between molecular markers associated with chemotherapy resistance and survival in esophageal cancer patients treated with trimodality therapy. EXPERIMENTAL DESIGN: The original pretreatment formalin-fixed, paraffin-embedded endoscopic esophageal tumor biopsy material was obtained from 99 patients treated with concurrent cisplatin plus 5-fluorouracil plus 45 Gy radiation followed by resection at Duke University Medical Center (Durham, NC) from 1986 to 1997. cDNA was derived from the biopsy and analyzed to determine mRNA expression relative to an internal reference gene (beta-actin) using fluorescence-based, real-time reverse transcription-PCR. Possible markers of platinum chemotherapy association [glutathione S-transferase pi (GSTP1) and excision cross-complementing gene 1 (ERCC1)] and 5-fluorouracil association [thymidylate synthase 1 (TS1)] were measured. RESULTS: Cox proportional hazards model revealed a significant inverse, linear effect for TS1 with respect to survival (P = 0.007). An inverse relationship between TS1 expression and treatment response was also detected (P < or = 0.001). Univariate analysis identified an association with decreased survival for GSTP1 > or = 3.0 (P = 0.05). In multivariate analyses, TS1 >6.0, ERCC1 >3, and GSTP1 >3 were statistically significant predictors of decreased survival (P = 0.007). Additionally, the presence of ERCC1 >3.0 or TS1 >6.0 was associated with an approximately 2-fold increase in the risk of cancer recurrence (P = 0.086 and 0.003, respectively). CONCLUSION: The measurement of relative gene expression of molecular markers associated with chemoresistance in endoscopic esophageal tumor biopsies may be a useful tool in assessing outcome in patients with trimodality-treated esophageal cancer. These data should be validated further in larger prospective studies.

Authors
Joshi, M-BM; Shirota, Y; Danenberg, KD; Conlon, DH; Salonga, DS; Herndon, JE; Danenberg, PV; Harpole, DH
MLA Citation
Joshi, M-BM, Shirota, Y, Danenberg, KD, Conlon, DH, Salonga, DS, Herndon, JE, Danenberg, PV, and Harpole, DH. "High gene expression of TS1, GSTP1, and ERCC1 are risk factors for survival in patients treated with trimodality therapy for esophageal cancer." Clin Cancer Res 11.6 (March 15, 2005): 2215-2221.
PMID
15788669
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
11
Issue
6
Publish Date
2005
Start Page
2215
End Page
2221
DOI
10.1158/1078-0432.CCR-04-1387

Phase III intergroup study of talc poudrage vs talc slurry sclerosis for malignant pleural effusion.

STUDY OBJECTIVE: To demonstrate the efficacy, safety, and appropriate mode of instillation of talc for sclerosis in treatment of malignant pleural effusions (MPEs). DESIGN: A prospective, randomized trial was designed to compare thoracoscopy with talc insufflation (TTI) to thoracostomy and talc slurry (TS) for patients with documented MPE. MEASUREMENTS: The primary end point was 30-day freedom from radiographic MPE recurrence among surviving patients whose lungs initially re-expanded > 90%. Morbidity, mortality, and quality of life were also assessed. RESULTS: Of 501 patients registered, those eligible were randomized to TTI (n = 242) or TS (n = 240). Patient demographics and primary malignancies were similar between study arms. Overall, there was no difference between study arms in the percentage of patients with successful 30-day outcomes (TTI, 78%; TS, 71%). However, the subgroup of patients with primary lung or breast cancer had higher success with TTI than with TS (82% vs 67%). Common morbidity included fever, dyspnea, and pain. Treatment-related mortality occurred in nine TTI patients and seven TS patients. Respiratory complications were more common following TTI than TS (14% vs 6%). Respiratory failure was observed in 4% of TS patients and 8% of TTI patients, accounting for five toxic deaths and six toxic deaths, respectively. Quality-of-life measurement demonstrated less fatigue with TTI than TS. Patient ratings of comfort and safety were also higher for TTI, but there were no differences on perceived value or convenience of the procedures. CONCLUSIONS: Both methods of talc delivery are similar in efficacy; TTI may be better for patients with either a lung or breast primary. The etiology and incidence of respiratory complications from talc need further exploration.

Authors
Dresler, CM; Olak, J; Herndon, JE; Richards, WG; Scalzetti, E; Fleishman, SB; Kernstine, KH; Demmy, T; Jablons, DM; Kohman, L; Daniel, TM; Haasler, GB; Sugarbaker, DJ; Cooperative Groups Cancer and Leukemia Group B, ; Eastern Cooperative Oncology Group, ; North Central Cooperative Oncology Group, ; Radiation Therapy Oncology Group,
MLA Citation
Dresler, CM, Olak, J, Herndon, JE, Richards, WG, Scalzetti, E, Fleishman, SB, Kernstine, KH, Demmy, T, Jablons, DM, Kohman, L, Daniel, TM, Haasler, GB, Sugarbaker, DJ, Cooperative Groups Cancer and Leukemia Group B, , Eastern Cooperative Oncology Group, , North Central Cooperative Oncology Group, , and Radiation Therapy Oncology Group, . "Phase III intergroup study of talc poudrage vs talc slurry sclerosis for malignant pleural effusion." Chest 127.3 (March 2005): 909-915.
PMID
15764775
Source
pubmed
Published In
Chest
Volume
127
Issue
3
Publish Date
2005
Start Page
909
End Page
915
DOI
10.1378/chest.127.3.909

A phase III trial evaluating the combination of cisplatin, etoposide, and radiation therapy with or without tamoxifen in patients with limited-stage small cell lung cancer: Cancer and Leukemia Group B Study (9235).

Based on both clinical and laboratory data that suggested that tamoxifen (TAM) enhanced the effectiveness of cisplatin (DDP)-based chemotherapy regimens, the Cancer and Leukemia Group B (CALGB) designed and initiated a prospective, randomized phase III trial to test the efficacy of the addition of high-dose TAM to a standard chemoradiation regimen of DDP and etoposide (VP-16) in patients with limited-stage small cell lung cancer (LS-SCLC). Between August 6, 1993, and January 15, 1999, 319 patients with LSSCLC were accrued to CALGB 9235. Patients were randomized to receive chemotherapy with or without high-dose TAM. Treatment on the non-TAM containing arm (arm 1) included DDP (80 mg/m2 intravenously day 1 only) and VP-16 (80 mg/m2 intravenously days 1-3) given every 3 weeks for a total of 5 cycles. Patients treated on arm 2 received the identical chemotherapy regimen as described here with the addition of high-dose TAM (80 mg orally twice per day), which was given for 5 days each cycle starting 1 day before the DDP. Thoracic radiation (XRT) given at 200 cGy 5 days per week to a total dose of 50 Gy began on day 1 of cycle 4 of chemotherapy and overlapped with cycle 5. Prophylactic cranial irradiation was offered to all patients who achieved a complete response or near-complete response. A total of 307 patients are evaluable for response. After the completion of the chemoradiation portion of the treatment, the overall response rate (ORR) was 88% for 154 patients treated without tamoxifen and 84% for 153 patients treated with tamoxifen with complete response (CR) rates of 49% and 50%, respectively. The median failure-free survivals of 12.3 months and 10.5 months and the overall survivals of 20.6 months and 18.4 months, respectively, were not statistically significant between the 2 arms. Toxicity was similar with and without tamoxifen. This phase III trial failed to demonstrate a positive effect on either the response or survival for the addition of TAM to standard etoposide-cisplatin-radiation management for patients with LS-SCLC. However, these data continue to support a positive effect of chemoradiation in the treatment of patients with LS-SCLC.

Authors
McClay, EF; Bogart, J; Herndon, JE; Watson, D; Evans, L; Seagren, SL; Green, MR; Cancer and Leukemia Group B Study (9235),
MLA Citation
McClay, EF, Bogart, J, Herndon, JE, Watson, D, Evans, L, Seagren, SL, Green, MR, and Cancer and Leukemia Group B Study (9235), . "A phase III trial evaluating the combination of cisplatin, etoposide, and radiation therapy with or without tamoxifen in patients with limited-stage small cell lung cancer: Cancer and Leukemia Group B Study (9235)." Am J Clin Oncol 28.1 (February 2005): 81-90.
PMID
15685040
Source
pubmed
Published In
American Journal of Clinical Oncology: Cancer Clinical Trials
Volume
28
Issue
1
Publish Date
2005
Start Page
81
End Page
90

Surgical complications associated with sentinel lymph node biopsy: Results from a prospective international cooperative group trial

Authors
Wilke, LG; McCall, LM; Whitworth, PW; Reintgen, DS; Leitch, AM; Gabram, SG; Lucci, A; Cox, CE; Herndon, JE; Giuliano, AE
MLA Citation
Wilke, LG, McCall, LM, Whitworth, PW, Reintgen, DS, Leitch, AM, Gabram, SG, Lucci, A, Cox, CE, Herndon, JE, and Giuliano, AE. "Surgical complications associated with sentinel lymph node biopsy: Results from a prospective international cooperative group trial." February 2005.
Source
wos-lite
Published In
Annals of Surgical Oncology
Volume
12
Issue
2
Publish Date
2005
Start Page
S27
End Page
S27

Three month follow up for ACOSOG Z0020, a prospective randomized multicenter trial of hyperthermic isolated limb perfusion with melphalan alone versus melphalan plus tumor necrosis factor

Authors
Cornett, WR; Fraker, DL; Ross, MI; Briele, HA; Boddie, AW; Noyes, RD; Sussman, JJ; McCall, LM; Herndon, JE; Tyler, DS
MLA Citation
Cornett, WR, Fraker, DL, Ross, MI, Briele, HA, Boddie, AW, Noyes, RD, Sussman, JJ, McCall, LM, Herndon, JE, and Tyler, DS. "Three month follow up for ACOSOG Z0020, a prospective randomized multicenter trial of hyperthermic isolated limb perfusion with melphalan alone versus melphalan plus tumor necrosis factor." February 2005.
Source
wos-lite
Published In
Annals of Surgical Oncology
Volume
12
Issue
2
Publish Date
2005
Start Page
S18
End Page
S18

Phase II trial of irinotecan plus celecoxib in adults with recurrent malignant glioma.

BACKGROUND: In the current study, the authors report a Phase II trial of irinotecan (CPT-11), a topoisomerase I inhibitor active against malignant glioma (MG), with celecoxib, a selective COX-2 inhibitor, among MG patients with recurrent disease. METHODS: Patients with MG at any type of recurrence received CPT-11, administered as a 90-minute intravenous infusion on Weeks 1, 2, 4, and 5 of each 6-week cycle plus celecoxib, which was administered continuously at a dose of 400 mg twice a day. CPT-11 was given at a dose of 350 mg/m(2) for patients receiving enzyme-inducing antiepileptic drugs (EIAEDs) and at a dose of 125 mg/m(2) for those patients not receiving EIAEDs. Assessments were performed after every cycle. The primary endpoint was radiographic response and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and therapeutic safety. RESULTS: Thirty-four of the 37 patients enrolled in the current study (92%) were diagnosed with recurrent GBM and 3 patients (8%) were diagnosed with recurrent anaplastic astrocytoma (AA). Twenty-one patients were receiving EIAEDs and 16 patients were not. The median follow-up time was 76.9 weeks. Concomitant CPT-11 plus celecoxib was found to be well tolerated and safe. Hematologic toxicities of >/= Grade 3 (according the second version of the Common Toxicity Criteria of the National Cancer Institute) reportedly complicated 8.6% of treatment courses. Grade 3 diarrhea, the most commonly reported nonhematologic toxicity, occurred with equal frequency (8%), regardless of whether the patient was receiving EIAED. Six patients (16%), all whom were diagnosed with recurrent GBM, achieved an objective radiographic response whereas an additional 13 patients (35%) achieved stable disease. The median PFS was 11.0 weeks and the 6-month PFS was reported to be 25.1%. The median OS was 31.5 weeks. CONCLUSIONS: The results of the current study confirm that CPT-11 plus celecoxib can be safely administered concurrently at full dose levels, and that this regimen has encouraging activity among heavily pretreated patients with recurrent MG.

Authors
Reardon, DA; Quinn, JA; Vredenburgh, J; Rich, JN; Gururangan, S; Badruddoja, M; Herndon, JE; Dowell, JM; Friedman, AH; Friedman, HS
MLA Citation
Reardon, DA, Quinn, JA, Vredenburgh, J, Rich, JN, Gururangan, S, Badruddoja, M, Herndon, JE, Dowell, JM, Friedman, AH, and Friedman, HS. "Phase II trial of irinotecan plus celecoxib in adults with recurrent malignant glioma." Cancer 103.2 (January 15, 2005): 329-338.
PMID
15558802
Source
pubmed
Published In
Cancer
Volume
103
Issue
2
Publish Date
2005
Start Page
329
End Page
338
DOI
10.1002/cncr.20776

Single-agent versus combination chemotherapy in advanced non-small-cell lung cancer: the cancer and leukemia group B (study 9730).

PURPOSE: We compared the efficacy of combination chemotherapy versus single-agent therapy in patients with advanced non-small-cell lung cancer. PATIENTS AND METHODS: A total of 561 eligible patients were randomly assigned to receive paclitaxel alone or in combination with carboplatin. RESULTS: The response rate was 17% in the paclitaxel arm and 30% in the carboplatin-paclitaxel arm (P < .0001). Median failure-free survival was 2.5 months in the paclitaxel arm and 4.6 months in the carboplatin-paclitaxel arm (P = .0002). Median survival times were 6.7 months (95% CI, 5.8 to 7.8) and 8.8 months (95% CI, 8.0 to 9.9), and 1-year survival rates were 32% (95% CI, 27% to 38%), and 37% (95% CI, 32% to 43%), respectively. The overall survival distributions were not statistically different: hazard ratio = 0.91 (95% CI, 0.77 to 1.17; P = .25). Hematological toxicity and nausea were more frequent in the combination arm, but febrile neutropenia and toxic deaths were equally low in both arms. There was no significant survival difference in elderly patients. Performance status 2 patients treated with combination chemotherapy had a better survival rate than those treated with single-agent therapy (P = .019). CONCLUSION: Combination chemotherapy improves response rate and failure-free survival compared with single-agent therapy, but there was no statistically significant difference in the primary end point of overall survival. The results in elderly patients were similar to younger patients. Performance status 2 patients had a superior outcome when treated with combination chemotherapy.

Authors
Lilenbaum, RC; Herndon, JE; List, MA; Desch, C; Watson, DM; Miller, AA; Graziano, SL; Perry, MC; Saville, W; Chahinian, P; Weeks, JC; Holland, JC; Green, MR
MLA Citation
Lilenbaum, RC, Herndon, JE, List, MA, Desch, C, Watson, DM, Miller, AA, Graziano, SL, Perry, MC, Saville, W, Chahinian, P, Weeks, JC, Holland, JC, and Green, MR. "Single-agent versus combination chemotherapy in advanced non-small-cell lung cancer: the cancer and leukemia group B (study 9730)." J Clin Oncol 23.1 (January 1, 2005): 190-196.
PMID
15625373
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
23
Issue
1
Publish Date
2005
Start Page
190
End Page
196
DOI
10.1200/JCO.2005.07.172

In reply [4]

Authors
Jr, EFP; Swensen, SJ; Herndon, JE
MLA Citation
Jr, EFP, Swensen, SJ, and Herndon, JE. "In reply [4]." Journal of Clinical Oncology 23.9 (2005): 2107-2108.
Source
scival
Published In
Journal of Clinical Oncology
Volume
23
Issue
9
Publish Date
2005
Start Page
2107
End Page
2108
DOI
10.1200/JCO.2005.05.267

In reply [12]

Authors
Jr, EFP; Swensen, SJ; II, JEH
MLA Citation
Jr, EFP, Swensen, SJ, and II, JEH. "In reply [12]." Journal of Clinical Oncology 23.10 (2005): 2440-2441.
Source
scival
Published In
Journal of Clinical Oncology
Volume
23
Issue
10
Publish Date
2005
Start Page
2440
End Page
2441
DOI
10.1200/JCO.2005.05.230

Cost-effectiveness of hepatic artery infusion for metastatic colorectal cancer (CALGB 9481)

Authors
Weeks, JC; Romanus, D; Herndon, JE; Schrag, D; Mayer, RJ; Kemeny, N
MLA Citation
Weeks, JC, Romanus, D, Herndon, JE, Schrag, D, Mayer, RJ, and Kemeny, N. "Cost-effectiveness of hepatic artery infusion for metastatic colorectal cancer (CALGB 9481)." VALUE IN HEALTH 8.6 (2005): A37-A37.
Source
wos-lite
Published In
Value in Health
Volume
8
Issue
6
Publish Date
2005
Start Page
A37
End Page
A37
DOI
10.1016/S1098-3015(10)67251-8

[18F]fluorodeoxyglucose-positron emission tomography in patients with medulloblastoma.

OBJECTIVE: We evaluated the [(18)F]fluorodeoxyglucose (FDG) accumulation during positron emission tomography (PET) in patients with medulloblastoma and examined the relationship of intensity of uptake with patient outcome after the initial scan. METHODS: Magnetic resonance imaging and FDG-PET scans of brain and spine were used to assess FDG uptake by visual grade (qualitative analysis) and metabolic activity ratios (T(max)/G(mean) and T(max)/W(mean)). Patients were divided into two groups based on either confirmation of tumor by biopsy and/or death resulting from progressive disease after the initial FDG-PET scan (Group A) or no intervention for the suspected lesion shown on magnetic resonance imaging after the initial FDG-PET scan but currently alive without evidence of disease (Group B). RESULTS: Twenty-two patients with either recurrent (n = 21) or newly diagnosed (n = 1) medulloblastoma underwent brain (n = 18) or whole-body (n = 4) FDG-PET scans after magnetic resonance imaging evidence of suspected tumor. The median qualitative analysis was 3 (range, 0-4) in 17 Group A patients compared with 0 (range, 0-1) in 5 Group B patients (P = 0.0003). The mean T(max)/G(mean) and T(max)/W(mean) ratios for 16 Group A patients were 1.3 (range, 0.1-3.8) and 2.10 (range, 0.4-5.2), respectively, compared with 0.80 (range, 0.20-1.5) and 1.3 (range, 0.5-1.9) in 5 Group B patients (P = 0.2 for both parameters, not significant). There was a significant negative correlation between increased FDG uptake and survival. Higher qualitative analysis and T(max)/W(mean) were associated with significantly poorer 2-year overall survival after the initial scan (71% versus 15% for qualitative analysis grade of <3 versus > or =3, P = 0.001; 46% versus 0% for T(max)/W(mean) < or =2.5 versus >2.5, P = 0.004). CONCLUSION: Increased FDG uptake is observed in medulloblastoma and is correlated negatively with survival.

Authors
Gururangan, S; Hwang, E; Herndon, JE; Fuchs, H; George, T; Coleman, RE
MLA Citation
Gururangan, S, Hwang, E, Herndon, JE, Fuchs, H, George, T, and Coleman, RE. "[18F]fluorodeoxyglucose-positron emission tomography in patients with medulloblastoma." Neurosurgery 55.6 (December 2004): 1280-1288.
PMID
15574210
Source
pubmed
Published In
Neurosurgery
Volume
55
Issue
6
Publish Date
2004
Start Page
1280
End Page
1288

Translating biomarkers into clinical practice: prognostic implications of cyclophilin A and macrophage migratory inhibitory factor identified from protein expression profiles in non-small cell lung cancer.

Biomarkers have the potential to significantly change diagnostic strategies and influence therapeutic management. We developed a MALDI-TOF protein expression profiling platform for biomarker discovery and a proof-of-principle study identified two proteins, cyclophilin A (CyPA) and macrophage migration inhibitory factor (MIF), that were overexpressed in non-small cell lung cancer (NSCLC). The current study focused on evaluating the potential of CyPA and MIF as prognostic markers in patients with a new diagnosis of lung cancer for rapid translation into clinical practice. Two hundred and thirty-four primary NSCLC specimens reflecting a broad range of histologies and stages were examined for CyPA and MIF reactivity by tissue microarray immunohistochemistry (TMA-IHC). The percent tumor cell reactivity, staining intensity and a composite staining score were compared with overall patient survival by Kaplan-Meier curves, log rank test and Cox model statistics. Although both proteins were overexpressed in most NSCLC tumors, neither CypA nor MIF showed a correlation with outcome. This pilot project approach can expedite integration of newly discovered biomarkers into clinical practice, with the goal of improving stratification of patients into appropriate treatment regimens. While both proteins considered in this study were overexpressed in the vast majority of NSCLCs, they were not found to be of prognostic significance.

Authors
Howard, BA; Zheng, Z; Campa, MJ; Wang, MZ; Sharma, A; Haura, E; Herndon, JE; Fitzgerald, MC; Bepler, G; Patz, EF
MLA Citation
Howard, BA, Zheng, Z, Campa, MJ, Wang, MZ, Sharma, A, Haura, E, Herndon, JE, Fitzgerald, MC, Bepler, G, and Patz, EF. "Translating biomarkers into clinical practice: prognostic implications of cyclophilin A and macrophage migratory inhibitory factor identified from protein expression profiles in non-small cell lung cancer." Lung Cancer 46.3 (December 2004): 313-323.
PMID
15541816
Source
pubmed
Published In
Lung Cancer
Volume
46
Issue
3
Publish Date
2004
Start Page
313
End Page
323
DOI
10.1016/j.lungcan.2004.05.013

[F-18] fluorodeoxyglucose-positron emission tomography in patients with medulloblastoma

Authors
Gururangan, S; Hwang, E; Herndon, JE; Fuchs, H; George, T; Coleman, RE
MLA Citation
Gururangan, S, Hwang, E, Herndon, JE, Fuchs, H, George, T, and Coleman, RE. "[F-18] fluorodeoxyglucose-positron emission tomography in patients with medulloblastoma." NEUROSURGERY 55.6 (December 2004): 1280-1289.
Source
wos-lite
Published In
Neurosurgery
Volume
55
Issue
6
Publish Date
2004
Start Page
1280
End Page
1289

Quality of life impact of three different doses of suramin in patients with metastatic hormone-refractory prostate carcinoma: results of Intergroup O159/Cancer and Leukemia Group B 9480.

BACKGROUND: Research has suggested that men with hormone-refractory prostate carcinoma have a lower quality of life (QOL) compared with men who have hormone-sensitive prostate carcinoma and that quality of life (QOL) steadily declines over the last year of life for men with prostate carcinoma. The primary purpose of the current study was to evaluate whether there was evidence of palliative effects associated with suramin at any of the three doses administered in the original clinical trial. METHODS: Patients with histologically confirmed advanced hormone-refractory adenocarcinoma of the prostate were randomized to receive suramin at a low dose (n = 129; median age, 69 years), an intermediate dose (n = 129; median age, 71 years), or a high dose (n = 127; median age, 70 years) as part of the Intergroup 0159/Cancer and Leukemia Group B 9480 trial. Patients completed a battery of assessment tools, including the Functional Assessment of Cancer Therapy (FACT)-Prostate, the Center for Epidemiological Studies-Depression Scale (CES-D), the Brief Pain Inventory, and an opioid medication log, at baseline, on Day 1 of the sixth week of active therapy, during the second week after treatment termination, and 3 months after administration of the final suramin dose. RESULTS: Patients who received low-dose suramin reported improvement in QOL (FACT-General: P < 0.01; FACT-Treatment Outcome Index: P < 0.01) and decreased levels of depression (CES-D: P < 0.0006) during treatment compared with patients in the intermediate- and high-dose arms. After treatment, all groups experienced equal decreases in FACT and CES-D scores. CONCLUSIONS: The pattern of results suggests that the lowest dose of suramin administered had a palliative effect in terms of improvement in QOL and decreased levels of depression and that this effect was lost once suramin was discontinued.

Authors
Ahles, TA; Herndon, JE; Small, EJ; Vogelzang, NJ; Kornblith, AB; Ratain, MJ; Stadler, W; Palchak, D; Marshall, ME; Wilding, G; Petrylak, D; Holland, JC; Cancer and Leukemia Group B,
MLA Citation
Ahles, TA, Herndon, JE, Small, EJ, Vogelzang, NJ, Kornblith, AB, Ratain, MJ, Stadler, W, Palchak, D, Marshall, ME, Wilding, G, Petrylak, D, Holland, JC, and Cancer and Leukemia Group B, . "Quality of life impact of three different doses of suramin in patients with metastatic hormone-refractory prostate carcinoma: results of Intergroup O159/Cancer and Leukemia Group B 9480." Cancer 101.10 (November 15, 2004): 2202-2208.
PMID
15484217
Source
pubmed
Published In
Cancer
Volume
101
Issue
10
Publish Date
2004
Start Page
2202
End Page
2208
DOI
10.1002/cncr.20655

Carboplatin/paclitaxel or carboplatin/vinorelbine followed by accelerated hyperfractionated conformal radiation therapy: report of a prospective phase I dose escalation trial from the Carolina Conformal Therapy Consortium.

PURPOSE: To prospectively determine the maximum-tolerated dose of accelerated hyperfractionated conformal radiotherapy (RT; 1.6 Gy bid) for unresectable locally advanced lung cancer (IIB to IIIA/B) following induction carboplatin/paclitaxel (C/T) or carboplatin/vinorelbine (C/N). METHODS: Induction chemotherapy, C/T or C/N, was followed by escalating doses of conformally-planned RT (73.6 to 86.4 Gy in 6.4-Gy increments). Concurrent boost methods delivered 1.6 and 1.25 Gy bid to the gross and clinical target volumes, respectively. RESULTS: Between November 1997 and February 2002, 44 patients were enrolled (median age, 59 years; 59% male; stage III, 98%; median tumor size, 4 cm). Thirty-nine patients completed induction chemotherapy: 19 had a partial response, seven progressed, 15 had no response, and three were not assessable. Chemotherapy-associated toxicities were similar in the two chemotherapy groups. The incidence of grade > or = 3 RT-induced toxicity was 1/13, 2/14, and 4/12 at 73.6, 80, and 86.4 Gy, respectively, thus defining the maximum tolerated dose at approximately 80 Gy. Toxicities were in both lung and esophagus and were similar in the two chemotherapy arms. With a median followup of 34 months in the survivors, the actuarial 2-year survival was 47%, the median survival was 18 months. Fifteen patients had tumor relapse: 5 local failures in the high-dose volume, 2 regional failures outside of the high-dose volume, and 8 distant metastases. CONCLUSION: High-dose conformal twice-daily radiation therapy to approximately 80 Gy appears tolerable in well-selected patients with unresectable lung cancer following either C/T or C/N. Dose-limiting toxicities are mainly pulmonary and esophageal.

Authors
Marks, LB; Garst, J; Socinski, MA; Sibley, G; Blackstock, AW; Herndon, JE; Zhou, S; Shafman, T; Tisch, A; Clough, R; Yu, X; Turrisi, A; Anscher, M; Crawford, J; Rosenman, J; Consortium, CCT
MLA Citation
Marks, LB, Garst, J, Socinski, MA, Sibley, G, Blackstock, AW, Herndon, JE, Zhou, S, Shafman, T, Tisch, A, Clough, R, Yu, X, Turrisi, A, Anscher, M, Crawford, J, Rosenman, J, and Consortium, CCT. "Carboplatin/paclitaxel or carboplatin/vinorelbine followed by accelerated hyperfractionated conformal radiation therapy: report of a prospective phase I dose escalation trial from the Carolina Conformal Therapy Consortium." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 22.21 (November 2004): 4329-4340. (Academic Article)
PMID
15514374
Source
manual
Published In
Journal of Clinical Oncology
Volume
22
Issue
21
Publish Date
2004
Start Page
4329
End Page
4340

A phase II trial of 6-hydroxymethylacylfulvene (MGI-114, irofulven) in patients with relapsed or refractory non-small cell lung cancer.

PURPOSE: To assess the efficacy and toxicity of 6-hydroxymethylacylfulvene (HMAF; MGI-114, irofulven) as therapy for relapsed or refractory non-small cell lung cancer. METHODS: A two-stage phase II design was employed separately for refractory and relapsed patients to differentiate between ineffective treatment (response rate < or =10%) and active treatment (response rate > or =30%). Eligible patients received HMAF 11 mg/m2 per day intravenously over 5 min on days 1-5, with cycles repeated every 28 days. RESULTS: Thirty-six patients (15 relapsed; 21 refractory) were treated, and no responses were seen. TOXICITY: Grade 3 neutropenia and grade 3 thrombocytopenia each occurred in 11% of the patients. Grade 3 nausea occurred in 47%; grade 3-4 vomiting in 42%. Twenty-two percent developed grade 3 fatigue. Eleven percent developed grade 3 hallucinations. CONCLUSIONS: HMAF, administered at this dose and schedule, is not active as salvage therapy for relapsed or refractory non-small cell lung cancer.

Authors
Sherman, CA; Herndon, JE; Watson, DM; Green, MR; Cancer and Leukemia Group B,
MLA Citation
Sherman, CA, Herndon, JE, Watson, DM, Green, MR, and Cancer and Leukemia Group B, . "A phase II trial of 6-hydroxymethylacylfulvene (MGI-114, irofulven) in patients with relapsed or refractory non-small cell lung cancer." Lung Cancer 45.3 (September 2004): 387-392.
PMID
15301880
Source
pubmed
Published In
Lung Cancer
Volume
45
Issue
3
Publish Date
2004
Start Page
387
End Page
392
DOI
10.1016/j.lungcan.2004.02.017

A randomized clinical trial of adjuvant chemotherapy with paclitaxel and carboplatin following resection in stage IB non-small cell hung cancer (NSCLC): report of cancer and leukemia group b (CALGB) protocol 9633

Authors
Strauss, GM; Herndon, JE; Maddaus, MA; Johnstone, DW; Johnson, EA; Harpole, DH; Gillenwater, HH; Watson, DM; Sugarbaker, DJ; Schilsky, RL; Vokes, EE; CALGB, MRG
MLA Citation
Strauss, GM, Herndon, JE, Maddaus, MA, Johnstone, DW, Johnson, EA, Harpole, DH, Gillenwater, HH, Watson, DM, Sugarbaker, DJ, Schilsky, RL, Vokes, EE, and CALGB, MRG. "A randomized clinical trial of adjuvant chemotherapy with paclitaxel and carboplatin following resection in stage IB non-small cell hung cancer (NSCLC): report of cancer and leukemia group b (CALGB) protocol 9633." September 2004.
Source
wos-lite
Published In
Lung Cancer
Volume
45
Publish Date
2004
Start Page
S75
End Page
S76

Comparative genomic hybridization analysis of astrocytomas: prognostic and diagnostic implications.

Astrocytoma is comprised of a group of common intracranial neoplasms that are classified into four grades based on the World Health Organization histological criteria and patient survival. To date, histological grade, patient age, and clinical performance, as reflected in the Karnofsky score, are the most reliable prognostic predictors. Recently, there has been a significant effort to identify additional prognostic markers using objective molecular genetic techniques. We believe that the identification of such markers will characterize new chromosomal loci important in astrocytoma progression and aid clinical diagnosis and prognosis. To this end, our laboratory used comparative genomic hybridization to identify DNA sequence copy number changes in 102 astrocytomas. Novel losses of 19p loci were detected in low-grade pilocytic astrocytomas and losses of loci on 9p, 10, and 22 along with gains on 7, 19, and 20 were detected in a significant proportion of high-grade astrocytomas. The Cox proportional hazards statistical modeling showed that the presence of +7q and -10q comparative genomic hybridization alterations significantly increased a patient's risk of dying, independent of histological grade. This investigation demonstrates the efficacy of comparative genomic hybridization for identifying tumor suppressor and oncogene loci in different astrocytic grades. The cumulative effect of these loci is an important consideration in their diagnostic and prognostic implications.

Authors
Wiltshire, RN; Herndon, JE; Lloyd, A; Friedman, HS; Bigner, DD; Bigner, SH; McLendon, RE
MLA Citation
Wiltshire, RN, Herndon, JE, Lloyd, A, Friedman, HS, Bigner, DD, Bigner, SH, and McLendon, RE. "Comparative genomic hybridization analysis of astrocytomas: prognostic and diagnostic implications." J Mol Diagn 6.3 (August 2004): 166-179.
PMID
15269292
Source
pubmed
Published In
The Journal of molecular diagnostics : JMD
Volume
6
Issue
3
Publish Date
2004
Start Page
166
End Page
179
DOI
10.1016/S1525-1578(10)60507-7

Induction chemotherapy followed by concomitant chemoradiotherapy (CT/XRT) versus CT/XRT alone for regionally advanced unresectable non-small cell lung cancer (NSCLC): Initial analysis of a randomized phase III trial

Authors
Vokes, EE; Herndon, JE; Kelley, MJ; Watson, D; Cicchetti, MG; Green, MR
MLA Citation
Vokes, EE, Herndon, JE, Kelley, MJ, Watson, D, Cicchetti, MG, and Green, MR. "Induction chemotherapy followed by concomitant chemoradiotherapy (CT/XRT) versus CT/XRT alone for regionally advanced unresectable non-small cell lung cancer (NSCLC): Initial analysis of a randomized phase III trial." July 15, 2004.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
22
Issue
14
Publish Date
2004
Start Page
618S
End Page
618S

Induction chemotherapy followed by concomitant chemoradiotherapy (CT/XRT) versus CT/XRT alone for regionally advanced unresectable non-small cell lung cancer (NSCLC): Initial analysis of a randomized phase III trial.

7005 Background: Standard therapy for unresectable stage III NSCLC includes concomitant chemoradiotherapy. In CALGB 39801, we evaluated whether the addition of induction chemotherapy prior to CT/XRT would result in improved survival.Between 10/1998 and 5/2002, 366 stage III patients (pts) were randomized to either immediate CT/XRT [carboplatin AUC of 2 and paclitaxel 50 mg/m2 each given weekly during 66 Gy chest XRT to; arm 1 (182 pts)] or two cycles of carboplatin AUC 6 and paclitaxel 200 mg/m2 given q 21 days x 2 cycles followed by identical CT/XRT; arm 2 (184 pts). The accrual goal was 360 patients. 290 deaths were required to have 80% power to detect a 40% increase in median survival assuming a one-tailed log-rank test conducted at the 0.025 level of significance.34% of pts were female, 66% male and 63% were age 60 or older. Grade 3 or 4 toxicities during induction chemotherapy consisted mainly of neutropenia (17%/21%). During CT/XRT, grade 3/4 neutropenia was noted in 11%/4% (arm 1) versus 21%/6% (arm 2), grade 3 anemia was 5% vs 11%, grade 3/4 fatigue 16%/1% vs 16%/4%, esophagitis 30%/1% vs 28%/7%, and dyspnea 9%/3% vs 15%/4%. Overall, 4 toxicities were experienced by 24% of patients on arm 1 versus 41% on arm 2 (p=0.001). With 254 of 290 targeted deaths, median survival on arm 1 is 11.4 months versus 14 months on arm 2 (p=0.154). One year survival estimates are 48% (41%-57%) and 54% (47%-62%) respectively.The median survival achieved in each of the treatment groups is low compared to other recent experiences in the literature. The reason(s) for this are uncertain. The addition of induction chemotherapy to immediate concurrent CT/XRT is associated with a 2.6 month increase in median survival. However these findings are not sufficient to reject the null hypothesis of no treatment difference between the two study arms. Further follow up of this data set is required. Our results do not support the use of induction chemotherapy followed by CT/XRT as evidence based standard of care for patients with unresectable stage III NSCLC. [Table: see text].

Authors
Vokes, EE; Herndon, JE; Kelley, MJ; Watson, D; Cicchetti, MG; Green, MR
MLA Citation
Vokes, EE, Herndon, JE, Kelley, MJ, Watson, D, Cicchetti, MG, and Green, MR. "Induction chemotherapy followed by concomitant chemoradiotherapy (CT/XRT) versus CT/XRT alone for regionally advanced unresectable non-small cell lung cancer (NSCLC): Initial analysis of a randomized phase III trial." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 22.14_suppl (July 2004): 7005-.
PMID
28016284
Source
epmc
Published In
Journal of Clinical Oncology
Volume
22
Issue
14_suppl
Publish Date
2004
Start Page
7005

Combined modality trials of the Cancer and Leukemia Group B in stage III non-small-cell lung cancer: analysis of factors influencing survival and toxicity.

BACKGROUND: Combined modality therapy (CMT) is the standard of care for patients with unresectable stage III non-small-cell lung cancer (NSCLC); however, insufficient data are available regarding prognostic factors in this disease setting. PATIENTS AND METHODS: Six hundred and ninety-four patients included in five trials conducted by the Cancer and Leukemia Group B evaluating CMT in stage III NSCLC were included in this analysis. The primary objective was to identify factors that were predictors of survival and selected radiation-related toxicities using Cox regression models and logistic regression analysis. RESULTS: The Cox model shows that performance status (PS) 1 [hazard ratio (HR) 1.24; 95% confidence interval (CI) 1.06-1.45; P=0.009] and thoracic radiation therapy (TRT) only (HR 1.58; 95% CI 1.22-2.05; P=0.001) predicted for poorer survival, while baseline hemoglobin >/=12 g/dl predicted for improved survival (HR 0.67; 95% CI 0.55-0.81; P 5% weight loss (OR 2.9; 95% CI 1.3-6.6; P=0.008) and patients receiving concurrent chemoradiation (OR 7.3; 95% CI 3.4-15.6; P=0.0001). CONCLUSIONS: Baseline hemoglobin and PS, as well as the use of CMT, have the greatest effect on survival in unresectable stage III NSCLC. The use of concurrent chemoradiation increases the risk of esophagitis, which remains the primary radiation-related toxicity.

Authors
Socinski, MA; Zhang, C; Herndon, JE; Dillman, RO; Clamon, G; Vokes, E; Akerley, W; Crawford, J; Perry, MC; Seagren, SL; Green, MR
MLA Citation
Socinski, MA, Zhang, C, Herndon, JE, Dillman, RO, Clamon, G, Vokes, E, Akerley, W, Crawford, J, Perry, MC, Seagren, SL, and Green, MR. "Combined modality trials of the Cancer and Leukemia Group B in stage III non-small-cell lung cancer: analysis of factors influencing survival and toxicity." Ann Oncol 15.7 (July 2004): 1033-1041.
PMID
15205196
Source
pubmed
Published In
Annals of Oncology
Volume
15
Issue
7
Publish Date
2004
Start Page
1033
End Page
1041
DOI
10.1093/annonc/mdh282

70 Gy thoracic radiotherapy is feasible concurrent with chemotherapy for limited-stage small-cell lung cancer: analysis of Cancer and Leukemia Group B study 39808.

PURPOSE: To prospectively evaluate the feasibility of delivering 70 Gy once-daily thoracic radiotherapy (TRT), concurrent with chemotherapy, in the treatment of limited-stage small-cell lung cancer (L-SCLC). MATERIALS AND METHODS: Eligible patients received two cycles of induction paclitaxel (175 mg/m(2) on Day 1) and topotecan (1 mg/m(2) on Days 1-5) with granulocyte colony stimulating factor support, followed by three cycles of carboplatin (area under the curve = 5 on Day 1) and etoposide (100 mg/m(2) on Days 1-3). TRT (70 Gy, 2 Gy/fx/7 weeks) was initiated with the first cycle of carboplatin and etoposide. Prophylactic cranial irradiation was offered to patients achieving a complete response or good partial response. RESULTS: Ninety percent of patients (57 of 63) proceeded to protocol TRT. There was one treatment-related fatality. Nonhematologic Grade 3/4 toxicities affecting more than 10% of patients, during or after TRT, were dysphagia (16%/5%) and febrile neutropenia (12%/4%). The response rate to all therapy was 92% and the median overall survival is 22.4 months (95% confidence interval 16.1, infinity ). Twenty-eight patients remain alive with a median follow-up of 24.7 months. CONCLUSION: 70 Gy once-daily TRT can be delivered safely in the cooperative group setting for patients with L-SCLC. Initial efficacy data are encouraging. The hypothesis that high-dose once-daily TRT results in comparable or improved survival compared with twice-daily accelerated TRT warrants testing in a Phase III trial.

Authors
Bogart, JA; Herndon, JE; Lyss, AP; Watson, D; Miller, AA; Lee, ME; Turrisi, AT; Green, MR; Cancer and Leukemia Group B study 39808,
MLA Citation
Bogart, JA, Herndon, JE, Lyss, AP, Watson, D, Miller, AA, Lee, ME, Turrisi, AT, Green, MR, and Cancer and Leukemia Group B study 39808, . "70 Gy thoracic radiotherapy is feasible concurrent with chemotherapy for limited-stage small-cell lung cancer: analysis of Cancer and Leukemia Group B study 39808." Int J Radiat Oncol Biol Phys 59.2 (June 1, 2004): 460-468.
PMID
15145163
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
59
Issue
2
Publish Date
2004
Start Page
460
End Page
468
DOI
10.1016/j.ijrobp.2003.10.021

Estimate of lung cancer mortality from low-dose spiral computed tomography screening trials: implications for current mass screening recommendations.

PURPOSE: Low-dose computed tomography (CT) has been suggested for lung cancer screening. Several observational trials have published their preliminary results, and some investigators suggest that this technique will save lives. There are no mortality statistics, however, and the current study used published data from these trials to estimate the disease-specific mortality in this high-risk population. PATIENTS AND METHODS: Two nonrandomized CT screening trials were selected from the literature for analysis. The number of trial participants, the number of lung cancers diagnosed per year, and stage distribution of the cancers was recorded. Previously published 5-year survival data were used to calculate the number of predicted lung cancer deaths and estimate the overall lung cancer mortality per 1,000 person-years among participants screened. These statistics were then compared to the previous Mayo Lung Project, which used chest radiographs and sputum cytology for screening high-risk individuals. RESULTS: This study estimates the lung cancer mortality is 4.1 deaths per 1,000 person-years in the Mayo Clinic CT screening trial, and is 5.5 deaths per 1,000 person-years in the Early Lung Cancer Action Program trial. These data are similar to the lung cancer mortality of 4.4 deaths per 1,000 person-years in the interventional arm, and 3.9 deaths per 1,000 person-years in the usual-care arm of the previous Mayo Lung Project. CONCLUSION: These data suggest that CT screening could produce similar outcomes to prior chest radiographic trials in this high-risk group. Results from randomized trials are required, however, before the true utility of mass screening with CT for lung cancer can be determined.

Authors
Patz, EF; Swensen, SJ; Herndon, JE
MLA Citation
Patz, EF, Swensen, SJ, and Herndon, JE. "Estimate of lung cancer mortality from low-dose spiral computed tomography screening trials: implications for current mass screening recommendations." J Clin Oncol 22.11 (June 1, 2004): 2202-2206. (Review)
PMID
15169809
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
22
Issue
11
Publish Date
2004
Start Page
2202
End Page
2206
DOI
10.1200/JCO.2004.12.046

Comparison of whole-body FDG-PET to bone scan for detection of bone metastases in patients with a new diagnosis of lung cancer.

The purpose of this study was to compare the accuracy and agreement of whole-body positron-emission tomography (PET) scan to bone scintigraphy for the detection of bony metastases in staging patients with newly diagnosed lung cancer. The tumor registry and nuclear medicine database at our institution were queried and identified all patients between July 1998 and August 2002 with a new diagnosis of lung cancer, a whole-body 2-deoxy-2-[18F]fluoro-D-glucose (FDG)-PET scan, and a bone scan prior to therapy. All of these patients' radiologic reports were then retrospectively reviewed, and confirmation of bone metastases was determined by consideration of all available clinical information. The sensitivity, specificity, and accuracy for each study were then calculated. Two hundred and fifty-seven patients fulfilled the entrance criteria. One hundred and four patients (40%) presented with stage IV disease, and bone metastases were confirmed in 57 (22%) patients. The accuracies of PET and bone scan were 94 and 85% (P < 0.05), sensitivity values were 91 and 75%, and specificity values were 96 and 95%, respectively. The weighted-kappa statistic suggested moderate agreement between the two modalities KW = 0.510, 95% CI, 0.402-0.618). The use of both whole-body PET and bone scintigraphy as initial staging studies in lung cancer patients provides redundant information about the presence of bony metastases. The improvement in accuracy and sensitivity with PET suggests bone scan can be eliminated from the staging evaluation at presentation. Due to its retrospective nature, the results of this study are subject to several forms of bias including selection bias, verification bias, test review bias, and incorporation bias. A prospective trial with appropriate verification of bony metastases is suggested to confirm the results.

Authors
Cheran, SK; Herndon, JE; Patz, EF
MLA Citation
Cheran, SK, Herndon, JE, and Patz, EF. "Comparison of whole-body FDG-PET to bone scan for detection of bone metastases in patients with a new diagnosis of lung cancer." Lung Cancer 44.3 (June 2004): 317-325.
PMID
15140545
Source
pubmed
Published In
Lung Cancer
Volume
44
Issue
3
Publish Date
2004
Start Page
317
End Page
325
DOI
10.1016/j.lungcan.2003.11.008

Correlation of 1p-19q-defects in human gliomas with the light microscopic appearance of oligodendroglioma.

Authors
McLendon, RE; Rasheed, A; Wiltshire, R; Herndon, J
MLA Citation
McLendon, RE, Rasheed, A, Wiltshire, R, and Herndon, J. "Correlation of 1p-19q-defects in human gliomas with the light microscopic appearance of oligodendroglioma." Mod Pathol 17.5 (May 2004): 604-605. (Letter)
PMID
15105803
Source
pubmed
Published In
Modern Pathology
Volume
17
Issue
5
Publish Date
2004
Start Page
604
End Page
605
DOI
10.1038/modpathol.3800077

Capecitabine in malignant mesothelioma: a phase II trial by the Cancer and Leukemia Group B (39807).

PURPOSE: The CALGB performed a phase II multicenter study to evaluate the activity of oral capecitabine in patients with malignant mesothelioma (CALGB 39807). PATIENTS AND METHODS: Between November 15, 2000 and August 31, 2001, 27 patients with mesothelioma were enrolled in this study. Capecitabine was administered at 2500 mg/m(2) per day divided in two doses for 14 days followed by a seven-day break. Cycles were repeated every 21 days with restaging performed every two cycles and therapy continuing for up to six cycles. One patient withdrew from the study prior to receiving therapy and is removed from further analysis. Eligibility criteria included no prior treatment, PS 0-1 by CALGB criteria and histologically documented mesothelioma. PATIENT CHARACTERISTICS: gender; male 19 (73%), female seven; median age 70 (range 40-81); histology: epithelial 15 (58%), mixed eight (31%), unclassified three; site of origin pleura, 25 (96%); weight loss in previous six months of more than 10% in seven (27%), symptoms longer than six months in five (19%). RESULTS: One patient (4%) had a confirmed PR while 10 (38%) achieved SD for 2-6 cycles. Ten patients (38%) had PD as their best response. There were three patients unevaluable for response and two early deaths. Median survival and failure free survival were 4.9 (95% CI 4-10.8) and 2.4 (95% CI 1.5-4.2) months respectively with a one-year survival of 23% (95% CI 11-49%). Grade three or greater toxicities encountered by at least 10% of patients included lymphopenia (12%), fatigue (12%), dehydration (12%) and diarrhea (15%). Three patients (12%) had grade three skin toxicity or hand-foot syndrome. One patient died of treatment related toxicity during cycle one. CONCLUSION: The antitumor activity of capecitabine is insufficient to warrant further exploration in patients with malignant mesothelioma.

Authors
Otterson, GA; Herndon, JE; Watson, D; Green, MR; Kindler, HL; Cancer and Leukemia Group B,
MLA Citation
Otterson, GA, Herndon, JE, Watson, D, Green, MR, Kindler, HL, and Cancer and Leukemia Group B, . "Capecitabine in malignant mesothelioma: a phase II trial by the Cancer and Leukemia Group B (39807)." Lung Cancer 44.2 (May 2004): 251-259.
PMID
15084390
Source
pubmed
Published In
Lung Cancer
Volume
44
Issue
2
Publish Date
2004
Start Page
251
End Page
259
DOI
10.1016/j.lungcan.2003.10.011

Phase 1 trial of irinotecan plus BCNU in patients with progressive or recurrent malignant glioma.

Irinotecan is a topoisomerase I inhibitor previously shown to be active in the treatment of malignant glioma. We now report the results of a phase 1 trial of irinotecan plus BCNU, or 1,3-bis(2-chloroethyl)-1-nitrosourea, for patients with recurrent or progressive MG. Irinotecan dose escalation occurred independently within 2 strata: patients receiving enzyme-inducing antiepileptic drugs (EIAEDs) and patients not receiving EIAEDs. BCNU was administered at a dose of 100 mg/m2 over 1 h every 6 weeks on the same day as the first irinotecan dose was administered. Irinotecan was administered intravenously over 90 min once weekly. Treatment cycles consisted of 4 weekly administrations of irinotecan followed by a 2-week rest with dose escalation in cohorts of 3 to 6 patients. Seventy-three patients were treated, including 49 patients who were on EIAEDs and 24 who were not on EIAEDs. The maximum tolerated dose for patients not on EIAEDs was 125 mg/m2. The maximum tolerated dose for patients on EIAEDs was 225 mg/m2. Dose-limiting toxicity was evenly distributed among the following organ systems: pulmonary, gastrointestinal, cardiovascular, neurologic, infectious, and hematologic, without a clear predominance of toxicity involving any one organ system. There was no evidence of increasing incidence of toxicity involving one organ system as irinotecan dose was escalated. On the basis of these results, we conclude that the recommended doses of irinotecan for a phase 2 clinical trial when given in combination with BCNU (100 mg/m2) are 225 mg/m2 for patients on EIAEDs and 125 mg/m2 for patients not on EIAEDs.

Authors
Quinn, JA; Reardon, DA; Friedman, AH; Rich, JN; Sampson, JH; Vredenburgh, J; Gururangan, S; Provenzale, JM; Walker, A; Schweitzer, H; Bigner, DD; Tourt-Uhlig, S; Herndon, JE; Affronti, ML; Jackson, S; Allen, D; Ziegler, K; Bohlin, C; Lentz, C; Friedman, HS
MLA Citation
Quinn, JA, Reardon, DA, Friedman, AH, Rich, JN, Sampson, JH, Vredenburgh, J, Gururangan, S, Provenzale, JM, Walker, A, Schweitzer, H, Bigner, DD, Tourt-Uhlig, S, Herndon, JE, Affronti, ML, Jackson, S, Allen, D, Ziegler, K, Bohlin, C, Lentz, C, and Friedman, HS. "Phase 1 trial of irinotecan plus BCNU in patients with progressive or recurrent malignant glioma." Neuro Oncol 6.2 (April 2004): 145-153.
PMID
15134629
Source
pubmed
Published In
Neuro-Oncology
Volume
6
Issue
2
Publish Date
2004
Start Page
145
End Page
153
DOI
10.1215/S1152851703000498

Phase 2 trial of BCNU plus irinotecan in adults with malignant glioma.

In preclinical studies, BCNU, or 1,3-bis(2-chloroethyl)-1-nitrosourea, plus CPT-11 (irinotecan) exhibits schedule-dependent, synergistic activity against malignant glioma (MG). We previously established the maximum tolerated dose of CPT-11 when administered for 4 consecutive weeks in combination with BCNU administered on the first day of each 6-week cycle. We now report a phase 2 trial of BCNU plus CPT-11 for patients with MG. In the current study, BCNU (100 mg/m2) was administered on day 1 of each 6-week cycle. CPT-11 was administered on days 1, 8, 15, and 22 at 225 mg/m2 for patients receiving CYP3A1- or CYP3A4-inducing anticonvulsants and at 125 mg/m2 for those not on these medications. Newly diagnosed patients received up to 3 cycles before radiotherapy, while recurrent patients received up to 8 cycles. The primary end point of this study was radiographic response, while time to progression and overall survival were also assessed. Seventy-six patients were treated, including 37 with newly diagnosed tumors and 39 with recurrent disease. Fifty-six had glioblastoma multiforme, 18 had anaplastic astrocytoma, and 2 had anaplastic oligodendroglioma. Toxicities (grade > or =3) included infections (13%), thromboses (12%), diarrhea (10%), and neutropenia (7%). Interstitial pneumonitis developed in 4 patients. Five newly diagnosed patients (14%; 95% CI, 5%-29%) achieved a radiographic response (1 complete response and 4 partial responses). Five patients with recurrent MG also achieved a response (1 complete response and 4 partial responses; 13%; 95% CI, 4%-27%). More than 40% of both newly diagnosed and recurrent patients achieved stable disease. Median time to progression was 11.3 weeks for recurrent glioblastoma multiforme patients and 16.9 weeks for recurrent anaplastic astrocytoma/ anaplastic oligodendroglioma patients. We conclude that the activity of BCNU plus CPT-11 for patients with MG appears comparable to that of CPT-11 alone and may be more toxic.

Authors
Reardon, DA; Quinn, JA; Rich, JN; Gururangan, S; Vredenburgh, J; Sampson, JH; Provenzale, JM; Walker, A; Badruddoja, M; Tourt-Uhlig, S; Herndon, JE; Dowell, JM; Affronti, ML; Jackson, S; Allen, D; Ziegler, K; Silverman, S; Bohlin, C; Friedman, AH; Bigner, DD; Friedman, HS
MLA Citation
Reardon, DA, Quinn, JA, Rich, JN, Gururangan, S, Vredenburgh, J, Sampson, JH, Provenzale, JM, Walker, A, Badruddoja, M, Tourt-Uhlig, S, Herndon, JE, Dowell, JM, Affronti, ML, Jackson, S, Allen, D, Ziegler, K, Silverman, S, Bohlin, C, Friedman, AH, Bigner, DD, and Friedman, HS. "Phase 2 trial of BCNU plus irinotecan in adults with malignant glioma." Neuro Oncol 6.2 (April 2004): 134-144.
PMID
15134628
Source
pubmed
Published In
Neuro-Oncology
Volume
6
Issue
2
Publish Date
2004
Start Page
134
End Page
144

Randomized phase II trial of gemcitabine plus irinotecan or docetaxel in stage IIIB or stage IV NSCLC.

BACKGROUND: To evaluate the activity and tolerability of gemcitabine plus irinotecan or docetaxel as first-line chemotherapy for advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Eligible patients with chemotherapy-naïve stage IIIB or IV NSCLC were randomized to receive gemcitabine 1000 mg/m2 on days 1 and 8, plus either irinotecan 100 mg/m2 or docetaxel 40 mg/m2 on days 1 and 8. Treatment was administered every 3 weeks. RESULTS: Of the 80 enrolled patients with stage IIIB or IV NSCLC, 78 were evaluable for activity and safety. Overall response rates, consisting of partial responses, were 12.8% [95% confidence interval (CI) 4% to 35%] for gemcitabine-irinotecan and 23.1% (95% CI 10% to 42%) for gemcitabine-docetaxel. Median overall survival was 7.95 months (95% CI 5.2-10.2) and 12.8 months (95% CI 7.9-17.1) for gemcitabine-irinotecan and gemcitabine-docetaxel, respectively. The corresponding estimated 1-year survivals were 23% and 51%, respectively. The 2-year survival rate in arm A (gemcitabine-irinotecan) is not currently estimable. The 2-year survival rate for arm B (gemcitabine-docetaxel) is 22% (95% CI 6% to 37%). Both combinations were well tolerated; the most common hematological toxicity was neutropenia, which occurred in 26% of patients in each treatment arm. CONCLUSIONS: These results suggest that gemcitabine plus docetaxel or irinotecan is well tolerated in patients with chemotherapy-naïve advanced NSCLC. The survival data with the combination gemcitabine-docetaxel are promising. Gemcitabine-docetaxel combination therapy may be particularly useful for patients who have experienced toxicities with a platinum regimen or in patients who may be more susceptible to platinum-related toxicity.

Authors
Rocha Lima, CM; Rizvi, NA; Zhang, C; Herndon, JE; Crawford, J; Govindan, R; King, GW; Green, MR; Cancer Leukemia Group B,
MLA Citation
Rocha Lima, CM, Rizvi, NA, Zhang, C, Herndon, JE, Crawford, J, Govindan, R, King, GW, Green, MR, and Cancer Leukemia Group B, . "Randomized phase II trial of gemcitabine plus irinotecan or docetaxel in stage IIIB or stage IV NSCLC." Ann Oncol 15.3 (March 2004): 410-418. (Review)
PMID
14998842
Source
pubmed
Published In
Annals of Oncology
Volume
15
Issue
3
Publish Date
2004
Start Page
410
End Page
418

Variations in pulmonary venous drainage to the left atrium: implications for radiofrequency ablation.

PURPOSE: To evaluate and classify the various drainage patterns of the pulmonary veins as depicted with thin-section chest computed tomography (CT). MATERIALS AND METHODS: Thin-section (2.5-mm collimation) contrast material-enhanced CT scans of 201 consecutive patients obtained over a 3-month period for diagnosis of pulmonary embolism (n = 197), pulmonary vein stenosis (n = 2), or aortic injury (n = 2) were routinely reviewed in transverse and (if necessary) coronal and coronal-oblique imaging planes. A classification was formulated based on both the number of venous ostia on each side and the drainage patterns of pulmonary veins. The frequency of each pattern was determined, and association with atrial arrhythmia was assessed with the chi(2) and Fisher exact tests. RESULTS: Most patients (n = 142, 71%) had two ostia on the right side for upper and lower lobe veins. Fifty-six patients (28%) had three to five ostia on the right side, which were due to one or two separate middle lobe vein ostia in 52 (26%) patients. Three patients (2%) had a single venous ostium on the right side. Most patients (n = 173, 86%) had two ostia on the left side for upper and lower lobe veins. The remainder (n = 28, 14%) had a single ostium. There was no significant association between any particular venous drainage pattern and atrial arrhythmia; however, patients with a separate ostia for the right middle lobe pulmonary vein(s) tended to have a higher frequency of atrial arrhythmia than those with other patterns (P =.053). CONCLUSION: A classification system to succinctly describe pulmonary venous drainage patterns was developed. Right-sided venous drainage was more variable than left-sided venous drainage. One-quarter of patients had more than two venous ostia on the right side.

Authors
Marom, EM; Herndon, JE; Kim, YH; McAdams, HP
MLA Citation
Marom, EM, Herndon, JE, Kim, YH, and McAdams, HP. "Variations in pulmonary venous drainage to the left atrium: implications for radiofrequency ablation." Radiology 230.3 (March 2004): 824-829.
PMID
14739316
Source
pubmed
Published In
Radiology
Volume
230
Issue
3
Publish Date
2004
Start Page
824
End Page
829
DOI
10.1148/radiol.2303030315

Phase II trial of vinorelbine plus doxorubicin in relapsed small-cell lung cancer: CALGB 9332.

Small-cell lung cancer that progresses after initial response may still be sensitive to systemic treatment. This study assessed doxorubicin plus vinorelbine tartrate (Navelbine Injection) in patients who had no prior exposure to these agents. Treatment consisted of vinorelbine at 25 mg/m2 on days 1 and 8 and doxorubicin at 50 mg/m2 on day 1 of each 21-day cycle. The trial was stopped early because of excessive toxicity. The partial response rate was 26.7%. Toxicities included grade IV neutropenia in 73%, and febrile neutropenia and/or sepsis in 60%. Three patients died from sepsis during cycle 1. Performance status 2 was significantly associated with febrile neutropenia (p = 0.044). Although this regimen had some activity, the toxicity precluded further evaluation.

Authors
Johnson, E; Lake, D; Herndon, JE; Box, JW; Lynch, TJ; Green, MR
MLA Citation
Johnson, E, Lake, D, Herndon, JE, Box, JW, Lynch, TJ, and Green, MR. "Phase II trial of vinorelbine plus doxorubicin in relapsed small-cell lung cancer: CALGB 9332." Am J Clin Oncol 27.1 (February 2004): 19-23.
PMID
14758128
Source
pubmed
Published In
American Journal of Clinical Oncology: Cancer Clinical Trials
Volume
27
Issue
1
Publish Date
2004
Start Page
19
End Page
23

Phase II trial of gefitinib in recurrent glioblastoma.

PURPOSE: To evaluate the efficacy and tolerability of gefitinib (ZD1839, Iressa; AstraZeneca, Wilmington, DE), a novel epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma. PATIENTS AND METHODS: This was an open-label, single-center phase II trial. Fifty-seven patients with first recurrence of a glioblastoma who were previously treated with surgical resection, radiation, and usually chemotherapy underwent an open biopsy or resection at evaluation for confirmation of tumor recurrence. Each patient initially received 500 mg of gefitinib orally once daily; dose escalation to 750 mg then 1,000 mg, if a patient received enzyme-inducing antiepileptic drugs or dexamethasone, was allowed within each patient. RESULTS: Although no objective tumor responses were seen among the 53 assessable patients, only 21% of patients (11 of 53 patients) had measurable disease at treatment initiation. Seventeen percent of patients (nine of 53 patients) underwent at least six 4-week cycles, and the 6-month event-free survival (EFS) was 13% (seven of 53 patients). The median EFS time was 8.1 weeks, and the median overall survival (OS) time from treatment initiation was 39.4 weeks. Adverse events were generally mild (grade 1 or 2) and consisted mainly of skin reactions and diarrhea. Drug-related toxicities were more frequent at higher doses. Withdrawal caused by drug-related adverse events occurred in 6% of patients (three of 53 patients). Although the presence of diarrhea positively predicted favorable OS from treatment initiation, epidermal growth factor receptor expression did not correlate with either EFS or OS. CONCLUSION: Gefitinib is well tolerated and has activity in patients with recurrent glioblastoma. Further study of this agent at higher doses is warranted.

Authors
Rich, JN; Reardon, DA; Peery, T; Dowell, JM; Quinn, JA; Penne, KL; Wikstrand, CJ; Van Duyn, LB; Dancey, JE; McLendon, RE; Kao, JC; Stenzel, TT; Ahmed Rasheed, BK; Tourt-Uhlig, SE; Herndon, JE; Vredenburgh, JJ; Sampson, JH; Friedman, AH; Bigner, DD; Friedman, HS
MLA Citation
Rich, JN, Reardon, DA, Peery, T, Dowell, JM, Quinn, JA, Penne, KL, Wikstrand, CJ, Van Duyn, LB, Dancey, JE, McLendon, RE, Kao, JC, Stenzel, TT, Ahmed Rasheed, BK, Tourt-Uhlig, SE, Herndon, JE, Vredenburgh, JJ, Sampson, JH, Friedman, AH, Bigner, DD, and Friedman, HS. "Phase II trial of gefitinib in recurrent glioblastoma." J Clin Oncol 22.1 (January 1, 2004): 133-142.
PMID
14638850
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
22
Issue
1
Publish Date
2004
Start Page
133
End Page
142
DOI
10.1200/JCO.2004.08.110

[18F]fluorodeoxyglucose-positron emission tomography in patients with medulloblastoma

OBJECTIVE: We evaluated the [18F]fluorodeoxyglucose (FDG) accumulation during positron emission tomography (PET) in patients with medulloblastoma and examined the relationship of intensity of uptake with patient outcome after the initial scan. METHODS: Magnetic resonance imaging and FDG-PET scans of brain and spine were used to assess FDG uptake by visual grade (qualitative analysis) and metabolic activity ratios (Tmax/G mean and Tmax/Wmean). Patients were divided into two groups based on either confirmation of tumor by biopsy and/or death resulting from progressive disease after the initial FDG-PET scan (Group A) or no intervention for the suspected lesion shown on magnetic resonance imaging after the initial FDG-PET scan but currently alive without evidence of disease (Group B). RESULTS: Twenty-two patients with either recurrent (n = 21) or newly diagnosed (n = 1) medulloblastoma underwent brain (n = 18) or whole-body (n = 4) FDG-PET scans after magnetic resonance imaging evidence of suspected tumor. The median qualitative analysis was 3 (range, 0-4) in 17 Group A patients compared with 0 (range, 0-1) in 5 Group B patients (P = 0.0003). The mean T max/Gmean and Tmax/Wmean ratios for 16 Group A patients were 1.3 (range, 0.1-3.8) and 2.10 (range, 0.4-5.2), respectively, compared with 0.80 (range, 0.20-1.5) and 1.3 (range, 0.5-1.9) in 5 Group B patients (P = 0.2 for both parameters, not significant). There was a significant negative correlation between increased FDG uptake and survival. Higher qualitative analysis and Tmax/Wmean were associated with significantly poorer 2-year overall survival after the initial scan (71% versus 15% for qualitative analysis grade of <3 versus ≥3, P = 0.001; 46% versus 0% for Tmax/Wmean ≤2.5 versus >2.5, P = 0.004). CONCLUSION: Increased FDG uptake is observed in medulloblastoma and is correlated negatively with survival.

Authors
Gururangan, S; Hwang, E; II, JEH; Fuchs, H; George, T; Coleman, RE
MLA Citation
Gururangan, S, Hwang, E, II, JEH, Fuchs, H, George, T, and Coleman, RE. "[18F]fluorodeoxyglucose-positron emission tomography in patients with medulloblastoma." Neurosurgery 55.6 (2004): 1280-1288.
Source
scival
Published In
Neurosurgery
Volume
55
Issue
6
Publish Date
2004
Start Page
1280
End Page
1288
DOI
10.1227/01.NEU.0000143027.41632.2B

Randomized clinical trial of adjuvant chemotherapy with paclitaxel and carboplatin following resection in stage IB non-small cell lung cancer (NSCLC): Report of Cancer and Leukemia Group B (CALGB) Protocol 9633

Authors
Strauss, GM; Herndon, JE; Maddaus, MA; Johnstone, DW; Johnson, EA; Harpole, DH; Gillenwater, HH; Watson, DM; Sugarbaker, DJ; Schilsky, RL; Vokes, EE; Green, MR
MLA Citation
Strauss, GM, Herndon, JE, Maddaus, MA, Johnstone, DW, Johnson, EA, Harpole, DH, Gillenwater, HH, Watson, DM, Sugarbaker, DJ, Schilsky, RL, Vokes, EE, and Green, MR. "Randomized clinical trial of adjuvant chemotherapy with paclitaxel and carboplatin following resection in stage IB non-small cell lung cancer (NSCLC): Report of Cancer and Leukemia Group B (CALGB) Protocol 9633." 2004.
Source
wos-lite
Published In
Annals of Oncology
Volume
15
Publish Date
2004
Start Page
13
End Page
14

Immunohistochemical detection of occult lymph node metastases in non-small cell lung cancer: anatomical pathology results from Cancer and Leukemia Group B Trial 9761.

PURPOSE: Our purpose was to study the detection of occult metastases (OM) in regional lymph nodes using immunohistochemical stain for cytokeratin, and for this study we targeted clinical stage I patients with non-small cell lung cancer. EXPERIMENTAL DESIGN: The study comprised the first 193 patients entered onto Cancer and Leukemia Group B protocol 9761. All had clinically staged T(1-2)N(0)M(0) non-small cell lung cancer, and all underwent curative resections of their primary tumors. Samples of the primary tumor and lymph nodes were taken from lymph node stations 2-12 and shipped to a central laboratory, where each lymph node was histologically processed and stained with H&E as well as with immunohistochemical stain using antibodies to cytokeratin (AE1/3). RESULTS: Altogether, we examined 825 lymph nodes. Whereas routine H&E staining allowed us to detect 18 positive lymph nodes, immunohistochemical staining allowed us to detect 45 positive lymph nodes (P < 0.0001). There were 28 OM [i.e., those detectable only by immunohistochemistry (IHC)], and there was 1 metastasis detected only by H&E staining. The OM included 9 OM in N1 stations and 19 OM in N2 stations. Twelve patients with OM had skip metastases. Routine H&E staining upstaged six patients to N1, and IHC added another five. Routine H&E upstaged 9 patients to N2, and IHC added another 11. We also uncovered new details about the way in which H&E detection depends on metastatic tumor burden. Specifically, for the probability of detecting metastases by H&E to exceed 0.50, the maximum diameter of the metastasis must be greater than 0.23 mm. CONCLUSIONS: IHC detects greater than twice as many positive regional lymph nodes as does H&E staining, and the foci of tumor it detects are significantly smaller than those detected by H&E staining.

Authors
Vollmer, RT; Herndon, JE; D'Cunha, J; Abraham, NZ; Solberg, J; Fatourechi, M; Maruska, A; Kern, JA; Green, MR; Kratzke, RA; Maddaus, MA; Cancer and Leukemia Group B Trial 9761,
MLA Citation
Vollmer, RT, Herndon, JE, D'Cunha, J, Abraham, NZ, Solberg, J, Fatourechi, M, Maruska, A, Kern, JA, Green, MR, Kratzke, RA, Maddaus, MA, and Cancer and Leukemia Group B Trial 9761, . "Immunohistochemical detection of occult lymph node metastases in non-small cell lung cancer: anatomical pathology results from Cancer and Leukemia Group B Trial 9761." Clin Cancer Res 9.15 (November 15, 2003): 5630-5635.
PMID
14654545
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
9
Issue
15
Publish Date
2003
Start Page
5630
End Page
5635

Establishment of stably EBV-transformed cell lines from residual clinical blood samples for use in performance evaluation and quality assurance in molecular genetic testing.

Positive control materials for clinical molecular genetic testing applications are currently in critically short supply or non-existent for many genetically based diseases of public health importance. Here we demonstrate that anonymous, residual, clinical blood samples are potential sources of viable lymphocytes for establishing Epstein-Barr virus (EBV)-transformed blood lymphocyte cell lines. We attempted to transform 34 residual blood samples, and analyzed transformation success with respect to sample age, anticoagulant, storage temperature, volume, hemolysis, and patient age and sex. In univariate analysis, sample age was significantly associated with transformation success (P = 0.002). The success rate was 67% (6 of 9) for samples 1 to 7 days old, 38% (3 of 8) for samples 8 to 14 days old and 0% for samples 15 to 21 (0 of 11) days old. When we controlled for sample age in multivariate logistic regression, anticoagulant and storage temperature approached significance (P = 0.070 and 0.087, respectively; samples in acid citrate dextrose (ACD) and refrigerated samples were more likely to transform). Based on these findings, we suggest that samples collected in either ACD or ethylene diamine tetraacetic acid, and up to 14 days old (refrigerated) or 7 days old (stored ambient), are reasonable candidates for EBV transformation. The transformation rate for samples that met these criteria was 63% (10 of 16). Implementation of this process could help alleviate the shortage of positive control materials for clinical molecular genetic testing.

Authors
Bernacki, SH; Stankovic, AK; Williams, LO; Beck, JC; Herndon, JE; Snow-Bailey, K; Prior, TW; Matteson, KJ; Wasserman, LM; Cole, EC; Stenzel, TT
MLA Citation
Bernacki, SH, Stankovic, AK, Williams, LO, Beck, JC, Herndon, JE, Snow-Bailey, K, Prior, TW, Matteson, KJ, Wasserman, LM, Cole, EC, and Stenzel, TT. "Establishment of stably EBV-transformed cell lines from residual clinical blood samples for use in performance evaluation and quality assurance in molecular genetic testing." J Mol Diagn 5.4 (November 2003): 227-230.
PMID
14573781
Source
pubmed
Published In
The Journal of molecular diagnostics : JMD
Volume
5
Issue
4
Publish Date
2003
Start Page
227
End Page
230
DOI
10.1016/S1525-1578(10)60478-3

Progress report of a Phase I study of the intracerebral microinfusion of a recombinant chimeric protein composed of transforming growth factor (TGF)-alpha and a mutated form of the Pseudomonas exotoxin termed PE-38 (TP-38) for the treatment of malignant brain tumors.

TP-38 is a recombinant chimeric targeted toxin composed of the EGFR binding ligand TGF-alpha and a genetically engineered form of the Pseudomonas exotoxin, PE-38. After in vitro and in vivo animal studies that showed specific activity and defined the maximum tolerated dose (MTD), we investigated this agent in a Phase I trial. The primary objective of this study was to define the MTD and dose limiting toxicity of TP-38 delivered by convection-enhanced delivery in patients with recurrent malignant brain tumors. Twenty patients were enrolled in the study and doses were escalated from 25 ng/mL to 100 with a 40 mL infusion volume delivered by two catheters. One patient developed Grade IV fatigue at the 100 ng/mL dose, but the MTD has not been established. The overall median survival after TP-38 for all patients was 23 weeks whereas for those without radiographic evidence of residual disease at the time of therapy, the median survival was 31.9 weeks. Overall, 3 of 15 patients, with residual disease at the time of therapy, have demonstrated radiographic responses and one patient with a complete response and has survived greater than 83 weeks.

Authors
Sampson, JH; Akabani, G; Archer, GE; Bigner, DD; Berger, MS; Friedman, AH; Friedman, HS; Herndon, JE; Kunwar, S; Marcus, S; McLendon, RE; Paolino, A; Penne, K; Provenzale, J; Quinn, J; Reardon, DA; Rich, J; Stenzel, T; Tourt-Uhlig, S; Wikstrand, C; Wong, T; Williams, R; Yuan, F; Zalutsky, MR; Pastan, I
MLA Citation
Sampson, JH, Akabani, G, Archer, GE, Bigner, DD, Berger, MS, Friedman, AH, Friedman, HS, Herndon, JE, Kunwar, S, Marcus, S, McLendon, RE, Paolino, A, Penne, K, Provenzale, J, Quinn, J, Reardon, DA, Rich, J, Stenzel, T, Tourt-Uhlig, S, Wikstrand, C, Wong, T, Williams, R, Yuan, F, Zalutsky, MR, and Pastan, I. "Progress report of a Phase I study of the intracerebral microinfusion of a recombinant chimeric protein composed of transforming growth factor (TGF)-alpha and a mutated form of the Pseudomonas exotoxin termed PE-38 (TP-38) for the treatment of malignant brain tumors." J Neurooncol 65.1 (October 2003): 27-35.
PMID
14649883
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
65
Issue
1
Publish Date
2003
Start Page
27
End Page
35

Long-term adjustment of survivors of early-stage breast carcinoma, 20 years after adjuvant chemotherapy.

BACKGROUND: The long-term impact of breast carcinoma and its treatment was assessed in 153 breast carcinoma survivors previously treated on a Phase III randomized trial (Cancer and Leukemia Group B [CALGB 7581]) a median of 20 years after entry to CALGB 7581. METHODS: Survivors were interviewed by telephone using the following standardized measures: Brief Symptom Inventory (BSI), PostTraumatic Stress Disorder Checklist with the trauma defined as survivors' response to having had cancer (PCL-C), Conditioned Nausea, Vomiting and Distress, European Organization for Research and Treatment of Cancer QLQ-C30 (quality of life), Life Experience Survey (stressful events), MOS Social Support Survey, comorbid conditions (Older Americans Resources and Services Questionnaire), and items developed to assess long-term breast carcinoma treatment side effects and their interference with functioning. RESULTS: Only 5% of survivors had scores that were suggestive of clinical levels of distress (BSI), 15% reported 2 or more posttraumatic stress disorder (PTSD) symptoms (PCL-C) that were moderately to extremely bothersome, 1-6% reported conditioned nausea, emesis, and distress as a consequence of sights, smells, and tastes triggered by reminders of their treatment, 29% reported sexual problems attributed to having had cancer, 39% reported lymphedema, and 33%, reported numbness. Survivors who reported greater lymphedema and numbness that interfered with functioning had significantly worse PTSD (PCL-C; P = 0.008) com- pared with survivors who reported less lymphedema and numbness. Survivors with a lower level of education (P = 0.026), less adequate social support (P = 0.0033), more severe negative life events (P = 0.0098), and greater dissatisfaction with their medical care (P = 0.037) had worse PTSD compared with other survivors. CONCLUSIONS: Twenty years after the initial treatment, the impact of breast carcinoma on survivors' adjustment was minimal. However, the higher prevalence of PTSD symptoms in response to having had cancer is indicative of continuing psychologic sequelae long after treatment completion. Findings related to lymphedema and numbness and continued symptoms of PTSD suggest that the long-term psychologic and medical sequelae on adjustment may be underrecognized. To establish in more detail whether survivors' overall psychologic state is any different from that of individuals without cancer, a population of community residents without cancer would need to be studied.

Authors
Kornblith, AB; Herndon, JE; Weiss, RB; Zhang, C; Zuckerman, EL; Rosenberg, S; Mertz, M; Payne, D; Jane Massie, M; Holland, JF; Wingate, P; Norton, L; Holland, JC
MLA Citation
Kornblith, AB, Herndon, JE, Weiss, RB, Zhang, C, Zuckerman, EL, Rosenberg, S, Mertz, M, Payne, D, Jane Massie, M, Holland, JF, Wingate, P, Norton, L, and Holland, JC. "Long-term adjustment of survivors of early-stage breast carcinoma, 20 years after adjuvant chemotherapy." Cancer 98.4 (August 15, 2003): 679-689.
PMID
12910510
Source
pubmed
Published In
Cancer
Volume
98
Issue
4
Publish Date
2003
Start Page
679
End Page
689
DOI
10.1002/cncr.11531

Risk of long-term complications after TFG-beta1-guided very-high-dose thoracic radiotherapy.

PURPOSE: To report the incidence of late complications in long-term survivors of very-high-dose thoracic radiotherapy (RT) treated on a prospective clinical trial. METHODS AND MATERIALS: Patients with locally advanced or medically inoperable non-small-cell lung cancer received three-dimensional conformal RT to the primary tumor and radiographically involved lymph nodes to a dose of 73.6 Gy at 1.6 Gy twice daily. If the plasma transforming growth factor-beta1 (TGF-beta1) level was normal after 73.6 Gy, additional twice-daily RT was delivered to successively higher total doses until the maximal tolerated dose was reached. Patients within a given dose level were followed for 6 months before escalation to the next dose level was permitted. Late complications were defined according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. RESULTS: Thirty-eight patients were enrolled between 1996 and 1999. Twenty-four patients were not eligible for radiation dose escalation beyond 73.6 Gy because of persistently abnormal TGF-beta1 levels. Fourteen patients received dose escalation (80 Gy in 8; 86.4 Gy in 6). Grade 3 or greater late complications occurred in 4 of 24, 1 of 8, and 2 of 6 patients treated to 73.6, 80, and 86.4 Gy, respectively. The corresponding patient numbers with late Grade 4-5 toxicity were 3 of 24, 0 of 6, and 0 of 8. Overall, 7 (18%) of the 38 patients developed Grade 3-5 late toxicity. Nonpulmonary complications predominated (4 of 7). Five (71%) of seven serious complications developed within 11 months after RT; however, the remaining two complications (29%) occurred very late (at 43 and 62 months). The 5-year actuarial risk of late Grade 3-5 complications was 33%. CONCLUSION: Long-term survivors of very-high-dose RT for non-small-cell lung cancer have a significant risk of severe treatment-related complications. At these high dose levels, the predominant toxicity may no longer be pulmonary. All Grade 4-5 complications occurred in patients whose dose was limited to 73.6 Gy because of a persistently elevated TGF-beta1. Thus, persistently elevated plasma TGF-beta1 levels toward the end of RT may identify patients at greatest risk of severe complications.

Authors
Anscher, MS; Marks, LB; Shafman, TD; Clough, R; Huang, H; Tisch, A; Munley, M; Herndon, JE; Garst, J; Crawford, J; Jirtle, RL
MLA Citation
Anscher, MS, Marks, LB, Shafman, TD, Clough, R, Huang, H, Tisch, A, Munley, M, Herndon, JE, Garst, J, Crawford, J, and Jirtle, RL. "Risk of long-term complications after TFG-beta1-guided very-high-dose thoracic radiotherapy." International journal of radiation oncology, biology, physics 56.4 (July 2003): 988-995. (Academic Article)
PMID
12829134
Source
manual
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
56
Issue
4
Publish Date
2003
Start Page
988
End Page
995

Pleural effusions in lung transplant recipients: image-guided small-bore catheter drainage.

PURPOSE: To assess the efficacy of treating pleural effusions in lung transplant recipients with small-bore catheter drainage. MATERIALS AND METHODS: Chest radiographs and computed tomographic (CT) scans obtained in 31 lung transplant recipients who had pleural effusions treated with catheter drainage were retrospectively reviewed. Duration of drainage and volume of fluid drained were recorded. Results were evaluated 1 and 3 months after chest tube removal. There was complete response (CR) when no pleural fluid remained, partial response (PR) when fluid remaining was less than the pretreatment level, and no response (NR) when fluid recurred to a level at or above the pretreatment level. Associations between cause of effusion (empyema, parapneumonic effusion, rejection, other), response (CR, PR, NR), and type of transplantation (unilateral, bilateral) were examined by using chi2 tests. RESULTS: Of 31 patients, 25 had bilateral effusions; eight of these 25 patients had small-bore catheters inserted bilaterally. Nine patients had multiple sequential catheter insertions. Duration of drainage ranged from 2 to 44 days (median, 6 days). Fluid output was 110-9,726 mL (median, 1,350 mL). One-month follow-up data were available for 31 of 39 treated pleural effusions: 11 (35%) had CR, 18 (58%) had PR, and two (6%) had NR (percentages do not add up to 100% due to rounding). Three-month follow-up data were available for 28 of 39 treated effusions: 22 (79%) had CR, five (18%) had PR, and one (4%) had NR (percentages do not add up to 100% due to rounding). One- and 3-month response rates, respectively, were not related to cause of effusion (P =.82 and.535) or type of transplantation (P =.568 and >.999). CONCLUSION: Small-bore catheter drainage of persistent pleural effusions in lung transplant recipients is usually successful, but drainage is often prolonged and may require multiple catheter placements.

Authors
Marom, EM; Palmer, SM; Erasmus, JJ; Herndon, JE; Zhang, C; McAdams, HP
MLA Citation
Marom, EM, Palmer, SM, Erasmus, JJ, Herndon, JE, Zhang, C, and McAdams, HP. "Pleural effusions in lung transplant recipients: image-guided small-bore catheter drainage." Radiology 228.1 (July 2003): 241-245.
PMID
12832585
Source
pubmed
Published In
Radiology
Volume
228
Issue
1
Publish Date
2003
Start Page
241
End Page
245
DOI
10.1148/radiol.2281020847

Measurement of chemoresistance markers in patients with stage III non-small cell lung cancer: a novel approach for patient selection.

BACKGROUND: The long-term survival of patients with stage III non-small cell lung cancer treated with a combination of chemotherapy and radiation is 10% to 20%. Survival could potentially be increased and toxicity limited if one could identify patients most likely to respond to a particular treatment regimen. This project prospectively evaluated a panel of potential immunohistochemical markers of chemoresistance in a population of patients with pathology-confirmed stage III non-small cell lung cancer in order to determine the prognostic value of each marker in relation to response to chemotherapy or survival. METHODS: Immunohistochemical staining was performed on histologically positive mediastinal nodal specimens obtained from 59 patients (mean age, 62 years; range, 41 to 79 years) without evidence of distant metastatic disease treated with navelbine-based chemotherapy and external beam radiation therapy between 1996 and 2001. Included were markers for apoptosis (p53, bcl-2), drug efflux/degradation (MDR, GST-pi), growth factors (EGFr, Her2-neu), and mismatch repair (hMLH1, hMSH2). After chemotherapy, patients underwent radiologic evaluation for response measured by standard criteria. RESULTS: After a median 41 months of follow-up (range, 17 to 55 months), 43 patients had recurrent disease and 38 of these patients were dead of cancer (median cancer-free survival of 10 months and overall survival of 18 months). Patients who demonstrated a complete or partial response (n = 38) had a significantly improved survival (p = 0.002) compared with those with stable or progressive cancer (n = 21). Multivariable Cox step-wise regression analysis of marker expression associated overexpression of p53 and low expression of hMSH2 with poor treatment response and cancer death. CONCLUSIONS: These preliminary data suggest that marker expression may allow the separation of patients into low- and high-risk groups with respect to survival after combined navelbine-based chemotherapy and XRT. This could represent a novel method of selecting patients for a particular treatment regimen if these data are reproduced in a larger prospective trial.

Authors
Brooks, KR; To, K; Joshi, M-BM; Conlon, DH; Herndon, JE; D'Amico, TA; Harpole, DH
MLA Citation
Brooks, KR, To, K, Joshi, M-BM, Conlon, DH, Herndon, JE, D'Amico, TA, and Harpole, DH. "Measurement of chemoresistance markers in patients with stage III non-small cell lung cancer: a novel approach for patient selection." Ann Thorac Surg 76.1 (July 2003): 187-193.
PMID
12842538
Source
pubmed
Published In
The Annals of Thoracic Surgery
Volume
76
Issue
1
Publish Date
2003
Start Page
187
End Page
193

High-dose chemotherapy with autologous stem-cell rescue in children and adults with newly diagnosed pineoblastomas.

PURPOSE: We evaluated the usefulness of a treatment regimen that included high-dose chemotherapy (HDC) with autologous stem-cell rescue (ASCR) in patients with newly diagnosed pineoblastoma (PBL). PATIENTS AND METHODS: Twelve patients with PBL were initially treated with surgery and induction chemotherapy. All but two patients underwent radiotherapy. Subsequently, all patients received HDC using cyclophosphamide (CTX) + melphalan (MEL) or busulfan (Bu) + MEL regimens and ASCR. RESULTS: A total of six children and six adults with median ages of 4.2 (range, 0.3 to 19.8 years) and 23 years (range, 23 to 43.7 years), respectively, were treated according to this strategy. Four patients had metastatic disease confined to the neuraxis. Five of 12 patients (42%) had a complete tumor resection at diagnosis. Ten patients received radiotherapy at median doses of 36.0 and 59.4 Gy to the neuraxis and pineal region, respectively. Eleven patients received HDC with CTX + MEL, and one patient received BU + MEL followed by ASCR. Nine patients are alive with no evidence of disease recurrence at a median of 62 months from diagnosis (range, 28 to 125 months), including three patients with metastatic disease and two infants who did not receive any radiotherapy. Three patients have died of progressive disease at 19, 32, and 37 months from diagnosis, respectively. The actuarial 4-year progression-free and overall survivals are 69% (95% confidence interval [CI], 39% to 99%) and 71% (95% CI, 43% to 99%), respectively. CONCLUSION: The use of HDC in addition to radiotherapy seems to be an effective treatment for patients with newly diagnosed pineoblastoma.

Authors
Gururangan, S; McLaughlin, C; Quinn, J; Rich, J; Reardon, D; Halperin, EC; Herndon, J; Fuchs, H; George, T; Provenzale, J; Watral, M; McLendon, RE; Friedman, A; Friedman, HS; Kurtzberg, J; Vredenbergh, J; Martin, PL
MLA Citation
Gururangan, S, McLaughlin, C, Quinn, J, Rich, J, Reardon, D, Halperin, EC, Herndon, J, Fuchs, H, George, T, Provenzale, J, Watral, M, McLendon, RE, Friedman, A, Friedman, HS, Kurtzberg, J, Vredenbergh, J, and Martin, PL. "High-dose chemotherapy with autologous stem-cell rescue in children and adults with newly diagnosed pineoblastomas." J Clin Oncol 21.11 (June 1, 2003): 2187-2191.
PMID
12775745
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
21
Issue
11
Publish Date
2003
Start Page
2187
End Page
2191
DOI
10.1200/JCO.2003.10.096

Weekly, high-dose paclitaxel in advanced lung carcinoma: a phase II study with pharmacokinetics by the Cancer and Leukemia Group B.

BACKGROUND: The Cancer and Leukemia Group B conducted a Phase II trial to evaluate the efficacy, toxicity, and pharmacokinetics of paclitaxel administered at a maximum dose density for patients with chemotherapy-naïve, advanced-stage non-small cell lung carcinoma (NSCLC). METHODS: Patients with Stage IIIB/IV or recurrent NSCLC, a performance status (PS) score of 0-1, and no history of chemotherapy exposure were eligible. Paclitaxel, 150 mg/m(2), was administered over 3 hours during Weeks 1-6 of an 8-week cycle. Doses were modified for ANC < 1500/microL or for >or= Grade 2 neuropathy on the day of therapy. Treatment continued until toxicity or disease progression. Pharmacokinetics were assessed at Weeks 1, 3, and 5 of Cycle 1. RESULTS: Thirty-eight patients (median age, 64 years; range, 31-81 years) were treated. There were 21 males (PS = 0 for 17). Eleven patients had received previous radiation, 2 had brain metastases, 25 had adenocarcinoma, 23 had Stage IV disease, 6 had StageIIIB disease, and 9 had recurrent disease. Grade 3-4 granulocytopenia occurred in 39% of patients. There were no deaths due to toxicity. Grade 2 or 3 neuropathy occurred in 29% and 24% of patients, respectively. Ten (27%) patients had Grade 3 hyperglycemia (glucose concentration > 250 mg/dL). There were 16 partial responses (42%; 95% confidence interval [CI], 26-59%). The median survival period was 12.3 months (95% CI, 7.9-19.6%), and the 1-year and 2-year survival rates were 52% (95% CI, 39-71%) and 26% (95% CI, 15-45%), respectively. Paclitaxel pharmacokinetics were consistent with published values and clearance was not induced. Older age and hyperglycemia were associated with greater neurotoxicity. CONCLUSIONS: Paclitaxel at 150 mg/m(2) per week x 6 every 8 weeks can be administered safely in the cooperative group setting. These Phase II data are comparable to those associated with combination therapy. The weekly dose-dense schedule may be more active than conventional schedules.

Authors
Akerley, W; Herndon, JE; Egorin, MJ; Lyss, AP; Kindler, HL; Savarese, DM; Sherman, CA; Rosen, DM; Hollis, D; Ratain, MJ; Green, MR
MLA Citation
Akerley, W, Herndon, JE, Egorin, MJ, Lyss, AP, Kindler, HL, Savarese, DM, Sherman, CA, Rosen, DM, Hollis, D, Ratain, MJ, and Green, MR. "Weekly, high-dose paclitaxel in advanced lung carcinoma: a phase II study with pharmacokinetics by the Cancer and Leukemia Group B." Cancer 97.10 (May 15, 2003): 2480-2486.
PMID
12733147
Source
pubmed
Published In
Cancer
Volume
97
Issue
10
Publish Date
2003
Start Page
2480
End Page
2486
DOI
10.1002/cncr.11375

Sub-classification of glioblastoma defined by comparative genomic hybridization alterations.

Authors
McLendon, RE; Wiltshire, RN; Herndon, JE; Lloyd, A; Friedman, HS; Bigner, DD; Bigner, SH
MLA Citation
McLendon, RE, Wiltshire, RN, Herndon, JE, Lloyd, A, Friedman, HS, Bigner, DD, and Bigner, SH. "Sub-classification of glioblastoma defined by comparative genomic hybridization alterations." May 2003.
Source
wos-lite
Published In
Journal of Neuropathology and Experimental Neurology
Volume
62
Issue
5
Publish Date
2003
Start Page
542
End Page
542

Phase II trial of temozolomide in patients with progressive low-grade glioma.

PURPOSE: Temozolomide (Temodar; Schering-Plough Corp, Kenilworth, NJ) is an imidazole tetrazinone that undergoes chemical conversion to the active methylating agent 5-(3-methyltriazen-1yl)imidazole-4-carboximide under physiologic conditions. Previous studies have confirmed activity of Temodar in the treatment of progressive and newly diagnosed malignant gliomas. We have extended these results, and now we report results of a phase II trial of Temodar for patients with progressive, low-grade glioma. PATIENTS AND METHODS: Temodar was administered orally once a day for five consecutive days (in a fasting state) at a starting dose of 200 mg/m(2)/d. Treatment cycles were repeated every 28 days following the first daily dose of Temodar. Response criteria used a combination of magnetic resonance imaging and physical examination to evaluate activity. RESULTS: Forty-six patients with low-grade glioma have been treated to date. The objective response rate was 61% (24% complete response and 37% partial response), with an additional 35% of patients having stable disease. Median progression-free survival (PFS) was 22 months (95% confidence interval [CI], 15 to infinity months) with a 6-month PFS of 98% (95% CI, 94% to 100%) and a 12-month PFS of 76% (95% CI, 63% to 92%). Toxicity observed during the study was limited to only six patients. Three patients experienced grade 3 neutropenia, with a duration greater than 3 weeks in one patient, and two patients experienced grade 3 thrombocytopenia. One patient experienced > or = grade 4 toxicity, with intracerebral hemorrhage, neutropenia, thrombocytopenia, sepsis, and death. CONCLUSION: Initial results indicate that Temodar may be active in the treatment of low-grade glioma, and thus, further evaluation of this agent in the treatment of these tumors is warranted.

Authors
Quinn, JA; Reardon, DA; Friedman, AH; Rich, JN; Sampson, JH; Provenzale, JM; McLendon, RE; Gururangan, S; Bigner, DD; Herndon, JE; Avgeropoulos, N; Finlay, J; Tourt-Uhlig, S; Affronti, ML; Evans, B; Stafford-Fox, V; Zaknoen, S; Friedman, HS
MLA Citation
Quinn, JA, Reardon, DA, Friedman, AH, Rich, JN, Sampson, JH, Provenzale, JM, McLendon, RE, Gururangan, S, Bigner, DD, Herndon, JE, Avgeropoulos, N, Finlay, J, Tourt-Uhlig, S, Affronti, ML, Evans, B, Stafford-Fox, V, Zaknoen, S, and Friedman, HS. "Phase II trial of temozolomide in patients with progressive low-grade glioma." J Clin Oncol 21.4 (February 15, 2003): 646-651.
PMID
12586801
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
21
Issue
4
Publish Date
2003
Start Page
646
End Page
651
DOI
10.1200/JCO.2003.01.009

Randomized phase II study of cisplatin with gemcitabine or paclitaxel or vinorelbine as induction chemotherapy followed by concomitant chemoradiotherapy for stage IIIB non-small-cell lung cancer: cancer and leukemia group B study 9431.

PURPOSE: To evaluate new drugs in combination with cisplatin in unresectable stage III non-small-cell lung cancer, Cancer and Leukemia Group B (CALGB) conducted a randomized phase II study of two cycles of induction chemotherapy followed by two additional cycles of the same drugs with concomitant radiotherapy. PATIENTS AND METHODS: Eligible patients received four cycles of cisplatin at 80 mg/m(2) on days 1, 22, 43, and 64 with arm 1: gemcitabine 1,250 mg/m(2) on days 1, 8, 22, and 29 and 600 mg/m(2) on days 43, 50, 64, and 71; arm 2: paclitaxel 225 mg/m(2) for 3 hours on days 1 and 22 and 135 mg/m(2) on days 43 and 64; and arm 3: vinorelbine 25 mg/m(2) on days 1, 8, 15, 22, and 29 and 15 mg/m(2) on days 43, 50, 64, and 71. Radiotherapy was initiated on day 43 at 2 Gy/d (total dose, 66 Gy). RESULTS: One hundred seventy-five eligible patients were analyzed. Toxicities during induction chemotherapy consisted primarily of grade 3 or 4 granulocytopenia. Grade 3 or 4 toxicities during concomitant chemoradiotherapy consisted of thrombocytopenia, granulo-cytopenia, and esophagitis. Response rates after completion of radiotherapy were 74%, 67%, and 73% for arms 1, 2, and 3, respectively. Median survival for all patients was 17 months. One-, 2-, and 3-year survival rates for the patients on the three arms were 68%/37%/28%, 62%/29%/19%, and 65%/40%/23%. CONCLUSION: Four cycles of gemcitabine, vinorelbine, or paclitaxel in combination with cisplatin can be administered at these doses and schedules. The observed survival rates exceed those of previous CALGB trials and may be attributable to the use of concomitant chemoradiotherapy. Induction chemotherapy added to concomitant chemoradiotherapy is being evaluated in a phase III randomized trial.

Authors
Vokes, EE; Herndon, JE; Crawford, J; Leopold, KA; Perry, MC; Miller, AA; Green, MR
MLA Citation
Vokes, EE, Herndon, JE, Crawford, J, Leopold, KA, Perry, MC, Miller, AA, and Green, MR. "Randomized phase II study of cisplatin with gemcitabine or paclitaxel or vinorelbine as induction chemotherapy followed by concomitant chemoradiotherapy for stage IIIB non-small-cell lung cancer: cancer and leukemia group B study 9431." J Clin Oncol 20.20 (October 15, 2002): 4191-4198.
PMID
12377962
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
20
Issue
20
Publish Date
2002
Start Page
4191
End Page
4198
DOI
10.1200/JCO.2002.03.054

Randomized controlled clinical trial of weekly oltipraz in smokers.

Authors
Kelley, MJ; Folz, RJ; Glaser, EM; Herndon, JE; Crowell, JA; Perloff, M; Ferdman, E; Gallot, L; Becker, R; Bergan, RC
MLA Citation
Kelley, MJ, Folz, RJ, Glaser, EM, Herndon, JE, Crowell, JA, Perloff, M, Ferdman, E, Gallot, L, Becker, R, and Bergan, RC. "Randomized controlled clinical trial of weekly oltipraz in smokers." October 2002.
Source
wos-lite
Published In
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume
11
Issue
10
Publish Date
2002
Start Page
1169S
End Page
1169S

Radiotherapy versus chemotherapy plus radiotherapy in surgically treated IIIA N2 non-small-cell lung cancer.

Preoperative chemotherapy in patients with stage III non-small-cell lung cancer (NSCLC) remains controversial. Phase II trials utilizing preoperative chemotherapy in selected patients have achieved complete resection rates of 50%-70% with 3-5 year failure-free survival rates of 15%-33%. Between October 1992 and November 1994, 57 adults (50 of whom were evaluable) with surgically staged IIIA NSCLC and pathologically documented ipsilateral mediastinal nodal involvement (N2) were enrolled in a Cancer and Leukemia Group B randomized trial. Preoperative therapy was thought to be critical to facilitating surgical resectability. For patients randomized to the radiotherapy/surgery/radiotherapy (RSR) arm (n = 24), treatment consisted of preoperative radiation therapy (RT) at 40 Gy, surgery, and then additional RT at 14-20 Gy. For patients randomized to the chemotherapy/surgery/chemotherapy/radiotherapy (CSCR) arm (n = 26), treatment consisted of 2 cycles of cisplatin/etoposide with filgrastim support (PE) followed by surgery, 2 more cycles of PE, then RT 54-60 Gy. The total dose of RT on either arm was 54 Gy if completely resected or 60 Gy if incompletely resected or unresected. Clinical characteristics were well balanced between the two arms. Thoracotomy was performed in 42 patients (84%), 28 (67%) of whom had complete resection. The median failure-free and overall survival rates were 12 months (95% confidence interval [CI], 9-23 months) and 23 months (95% CI, 19 months-infinity) for the RSR arm and 11 months (95% CI, 5-20 months) and 18 months (95% CI, 12-32 months) for the CSCR arm. The rates of overall and complete surgical resection, downstaging of nodal involvement, and failure-free (P = 0.92) and overall survival (P = 0.41) did not differ between the two treatment arms. Moreover, in this trial, the chemotherapy regimen was sufficiently toxic to have had a lower completion rate of prescribed therapy in the CSCR arm than in the RSR arm.

Authors
Elias, AD; Kumar, P; Herndon, J; Skarin, AT; Sugarbaker, DJ; Green, MR
MLA Citation
Elias, AD, Kumar, P, Herndon, J, Skarin, AT, Sugarbaker, DJ, and Green, MR. "Radiotherapy versus chemotherapy plus radiotherapy in surgically treated IIIA N2 non-small-cell lung cancer." Clin Lung Cancer 4.2 (September 2002): 95-103.
PMID
14653865
Source
pubmed
Published In
Clinical lung cancer
Volume
4
Issue
2
Publish Date
2002
Start Page
95
End Page
103

Phase II study of carboplatin in children with progressive low-grade gliomas.

PURPOSE: To assess the rate of tumor response and activity of carboplatin in stabilizing the growth of progressive low-grade gliomas. PATIENTS AND METHODS: Eligible patients received carboplatin 560 mg/m(2) intravenously every 4 weeks for 1 year after maximum tumor response or until disease progression or unacceptable toxicity. RESULTS: Between October 1993 and October 2000, 81 children (median age, 79 months; range, 6 to 204) were enrolled onto this study. Patients received a median of 11 cycles of carboplatin (range, one to 29). Median follow-up from the time of enrollment was 55 months (range, 10 to 93). The overall objective response (complete response [CR] + partial response [PR] + minor response [MR]) and disease stabilization (CR + PR + stable disease + MR) rates to carboplatin treatment were 28% (95% confidence interval [CI], 18% to 38%) and 85% (95% CI, 74% to 93%), respectively. Eleven and 14 patients suffered progressive disease on study and after stopping therapy, respectively. Toxicity was predominantly myelosuppression and included grade 3/4 neutropenia in 56 patients and grade 3/4 thrombocytopenia in 40 patients. The 3-year failure-free survival (FFS) and overall survival (OS) for all patients were 64% (95% CI, 54% to 76%) and 84% (95% CI, 76% to 93%), respectively. Patients with diencephalic tumors had inferior FFS and OS compared with those with tumor at other sites (38% v 74% for FFS, P =.011; 54% v 91% for OS, P =.004). Neurofibromatosis type 1 patients with progressive low-grade glioma had a significantly better OS (95% v 80%; P =.052). CONCLUSION: Carboplatin, in the schedule used in this study, produced disease stabilization or improvement in a majority of children with progressive low-grade glioma, with manageable toxicity. Improved treatment strategies are particularly required for patients with diencephalic tumors.

Authors
Gururangan, S; Cavazos, CM; Ashley, D; Herndon, JE; Bruggers, CS; Moghrabi, A; Scarcella, DL; Watral, M; Tourt-Uhlig, S; Reardon, D; Friedman, HS
MLA Citation
Gururangan, S, Cavazos, CM, Ashley, D, Herndon, JE, Bruggers, CS, Moghrabi, A, Scarcella, DL, Watral, M, Tourt-Uhlig, S, Reardon, D, and Friedman, HS. "Phase II study of carboplatin in children with progressive low-grade gliomas." J Clin Oncol 20.13 (July 1, 2002): 2951-2958.
PMID
12089224
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
20
Issue
13
Publish Date
2002
Start Page
2951
End Page
2958
DOI
10.1200/JCO.2002.12.008

Usefulness of imaging-guided catheter drainage and talc sclerotherapy in patients with metastatic gynecologic malignancies and symptomatic pleural effusions.

OBJECTIVE: The purpose of our study was to assess the usefulness of imaging-guided catheter drainage and talc sclerotherapy in patients with metastatic gynecologic malignancies and symptomatic pleural effusions and to assess the affect of ascites on the success rate of this treatment. MATERIALS AND METHODS: Twenty-five patients (mean age, 63 years) with metastatic gynecologic malignancies who had 26 symptomatic effusions treated at our institution over a 4-year period with imaging-guided catheter drainage and talc sclerotherapy were included in this study. Response to treatment was assessed by comparing pre-, immediate post-, and 30-day postsclerotherapy chest radiographs. Response to the treatment was graded as complete (no reaccumulation), partial (accumulation above immediate post- but below presclerotherapy level), or no response (reaccumulation to or above the presclerotherapy level). The presence of ascites on CT (n = 23), sonography (n = 1), direct intraoperative visualization (n = 1), or at physical examination (n = 1) was also noted. RESULTS: Of the 25 patients, 13 patients with 14 treated malignant effusions survived at least 30 days after sclerotherapy and formed the final study group. The remaining patients either died (n = 11) or were lost to follow-up (n = 1). At 30 days, 12 of the 14 treated effusions showed complete responses and one showed a partial response. The overall response rate was 86%. Abdominal ascites was present at the time of treatment in 11 patients (79%) and did not affect the success rate (p > 0.999). CONCLUSION: Imaging-guided catheter drainage and talc sclerotherapy are an effective treatment for symptomatic pleural effusions in patients with metastatic gynecologic malignancies. Ascites does not adversely affect the response to pleurodesis.

Authors
Marom, EM; Erasmus, JJ; Herndon, JE; Zhang, C; McAdams, HP
MLA Citation
Marom, EM, Erasmus, JJ, Herndon, JE, Zhang, C, and McAdams, HP. "Usefulness of imaging-guided catheter drainage and talc sclerotherapy in patients with metastatic gynecologic malignancies and symptomatic pleural effusions." AJR Am J Roentgenol 179.1 (July 2002): 105-108.
PMID
12076914
Source
pubmed
Published In
AJR. American journal of roentgenology
Volume
179
Issue
1
Publish Date
2002
Start Page
105
End Page
108
DOI
10.2214/ajr.179.1.1790105

Impact of azacytidine on the quality of life of patients with myelodysplastic syndrome treated in a randomized phase III trial: a Cancer and Leukemia Group B study.

PURPOSE: The impact of azacytidine (Aza C) on the quality of life of 191 patients with myelodysplastic syndrome was assessed in a phase III Cancer and Leukemia Group B trial (9221). PATIENTS AND METHODS: One hundred ninety-one patients (mean age, 67.5 years; 69% male) were randomized to receive either Aza C (75 mg/m(2) subcutaneous for 7 days every 4 weeks) or supportive care, with supportive care patients crossing over to Aza C upon disease progression. Quality of life was assessed by centrally conducted telephone interviews at baseline and days 50, 106, and 182. Overall quality of life, psychological state, and social functioning were assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 and the Mental Health Inventory (MHI). RESULTS: Patients on the Aza C arm experienced significantly greater improvement in fatigue (EORTC, P =.001), dyspnea (EORTC, P =.0014), physical functioning (EORTC, P =.0002), positive affect (MHI, P =.0077), and psychological distress (MHI, P =.015) over the course of the study period than those in the supportive care arm. Particularly striking were improvements in fatigue and psychological state (MHI) in patients treated with Aza C compared with those receiving supportive care for patients who remained on study through at least day 106, corresponding to four cycles of Aza C. Significant differences between the two groups in quality of life were maintained even after controlling for the number of RBC transfusions. CONCLUSION: Improved quality of life for patients treated with Aza C coupled with significantly greater treatment response and delayed time to transformation to acute myeloid leukemia or death compared with patients on supportive care (P <.001) establishes Aza C as an important treatment option for myelodysplastic syndrome.

Authors
Kornblith, AB; Herndon, JE; Silverman, LR; Demakos, EP; Odchimar-Reissig, R; Holland, JF; Powell, BL; DeCastro, C; Ellerton, J; Larson, RA; Schiffer, CA; Holland, JC
MLA Citation
Kornblith, AB, Herndon, JE, Silverman, LR, Demakos, EP, Odchimar-Reissig, R, Holland, JF, Powell, BL, DeCastro, C, Ellerton, J, Larson, RA, Schiffer, CA, and Holland, JC. "Impact of azacytidine on the quality of life of patients with myelodysplastic syndrome treated in a randomized phase III trial: a Cancer and Leukemia Group B study." J Clin Oncol 20.10 (May 15, 2002): 2441-2452.
PMID
12011121
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
20
Issue
10
Publish Date
2002
Start Page
2441
End Page
2452
DOI
10.1200/JCO.2002.04.044

Molecular markers of prognosis in astrocytic tumors.

BACKGROUND: Astrocytoma is a primary brain tumor that affects 20,000 Americans each year. To date, only age and histologic grade stand out as independent predictors of survival. There is now increased interest in the use of molecular markers as objective standards against which to establish diagnosis and grade. METHODS: The study evaluated human glioma tumor suppressor genes and associated loci in fresh snap-frozen gliomas from 63 males and 37 females, with a median age of 42 years, including 19 low-grade astrocytomas. The tumor samples were selected so that about equal numbers of glioblastomas from younger and older patients were represented in the series. Methods for suppressor gene and genetic loci evaluation included loss of heterozygosity (LOH) analysis, multiplex polymerase chain reaction analysis, and gene sequencing. RESULTS: Low-grade astrocytomas had the least number of molecular abnormalities. LOH on 9p and/or CDKN2A deletion occurred more often in glioblastomas (P < 0.001), LOH on 17p/TP53 mutations occurred more frequently in anaplastic astrocytomas (AAs; P = 0.112), and LOH on 10q/PTEN mutation frequency was similar in glioblastomas and AAs (P < 0.001). Poorer survival was associated significantly with the occurrence of either deletion of p16 (P = 0.031), LOH on 9p (P = 0.016), or LOH on 10q (P = 0.0007). The absence of LOH on 17p and the presence of PTEN mutation were associated marginally with survival. Even though TP53 mutations were more frequent among younger patients with glioblastoma, they had no statistically significant effect on survival after adjustment for age (P = 0.62). In all multivariate models, age and grade were the only significant predictors of survival or were nearly significant predictors of survival. CONCLUSIONS: The results suggest that LOH on 9p and p16 deletions may prove to be objective standards for the diagnosis of patients with high-grade gliomas, although the absence of these abnormalities is nonprognostic.

Authors
Rasheed, A; Herndon, JE; Stenzel, TT; Raetz, JGM; Kendelhardt, J; Friedman, HS; Friedman, AH; Bigner, DD; Bigner, SH; McLendon, RE
MLA Citation
Rasheed, A, Herndon, JE, Stenzel, TT, Raetz, JGM, Kendelhardt, J, Friedman, HS, Friedman, AH, Bigner, DD, Bigner, SH, and McLendon, RE. "Molecular markers of prognosis in astrocytic tumors." Cancer 94.10 (May 15, 2002): 2688-2697.
PMID
12173338
Source
pubmed
Published In
Cancer
Volume
94
Issue
10
Publish Date
2002
Start Page
2688
End Page
2697

Phase II trial of carmustine plus O(6)-benzylguanine for patients with nitrosourea-resistant recurrent or progressive malignant glioma.

PURPOSE: We conducted a phase II trial of carmustine (BCNU) plus the O(6)-alkylguanine-DNA alkyltransferase inhibitor O(6)-benzylguanine (O(6)-BG) to define the activity and toxicity of this regimen in the treatment of adults with progressive or recurrent malignant glioma resistant to nitrosoureas. PATIENTS AND METHODS: Patients were treated with O(6)-BG at an intravenous dose of 120 mg/m(2) followed 1 hour later by 40 mg/m(2) of BCNU, with cycles repeated at 6-week intervals. RESULTS: Eighteen patients were treated (15 with glioblastoma multiforme, two with anaplastic astrocytoma, and one with malignant glioma). None of the 18 patients demonstrated a partial or complete response. Two patients exhibited stable disease for 12 weeks before their tumors progressed. Three patients demonstrated stable disease for 6, 12, and 18 weeks before discontinuing therapy because of hematopoietic toxicity. Twelve patients experienced reversible > or = grade 3 hematopoietic toxicity. There was no difference in half-lives (0.56 +/- 0.21 hour v 0.54 +/- 0.20 hour) or area under the curve values (4.8 +/- 1.7 microg/mL/h v 5.0 +/- 1.3 microg/mL/h) of O(6)-BG for patients receiving phenytoin and those not treated with this drug. CONCLUSION: These results indicate that O(6)-BG plus BCNU at the dose schedule used in this trial is unsuccessful in producing tumor regression in patients with nitrosourea-resistant malignant glioma, although stable disease was seen in five patients for 6, 12, 12, 12, and 18 weeks. Future use of this approach will require strategies to minimize dose-limiting toxicity of BCNU such as regional delivery or hematopoietic stem-cell protection.

Authors
Quinn, JA; Pluda, J; Dolan, ME; Delaney, S; Kaplan, R; Rich, JN; Friedman, AH; Reardon, DA; Sampson, JH; Colvin, OM; Haglund, MM; Pegg, AE; Moschel, RC; McLendon, RE; Provenzale, JM; Gururangan, S; Tourt-Uhlig, S; Herndon, JE; Bigner, DD; Friedman, HS
MLA Citation
Quinn, JA, Pluda, J, Dolan, ME, Delaney, S, Kaplan, R, Rich, JN, Friedman, AH, Reardon, DA, Sampson, JH, Colvin, OM, Haglund, MM, Pegg, AE, Moschel, RC, McLendon, RE, Provenzale, JM, Gururangan, S, Tourt-Uhlig, S, Herndon, JE, Bigner, DD, and Friedman, HS. "Phase II trial of carmustine plus O(6)-benzylguanine for patients with nitrosourea-resistant recurrent or progressive malignant glioma." J Clin Oncol 20.9 (May 1, 2002): 2277-2283.
PMID
11980998
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
20
Issue
9
Publish Date
2002
Start Page
2277
End Page
2283
DOI
10.1200/JCO.2002.09.084

T1 lung cancers: sensitivity of diagnosis with fluorodeoxyglucose PET.

PURPOSE: To determine the sensitivity of fluorodeoxyglucose (FDG) positron emission tomography (PET) in patients with T1 (< or =3 cm) lung cancers. MATERIALS AND METHODS: One hundred eighty-five patients with 192 histopathologically proved T1 lung cancers underwent FDG PET imaging at the time of diagnosis. PET results were correlated with tumor size, histopathologic findings, and patient outcome by using the two-sample t test, exact chi(2) test, and log rank test, respectively. RESULTS: Of the 192 lesions, 183 (95%) that ranged in size from 0.5 to 3.0 cm in diameter (mean, 2.0 cm) were positive at PET (ie, demonstrated increased FDG uptake). Of the 192 lesions, nine (5%) that ranged in size from 0.3 to 2.5 cm in diameter (mean, 1.3 cm) were negative at PET (ie, demonstrated low FDG uptake). Patients with small tumors, as well as those with carcinoid tumors and bronchioloalveolar cell carcinoma, were more likely to have a negative PET scan (P =.004, P =.003, respectively). In addition, patients with a negative PET scan who subsequently proved to have cancer had significantly longer survival than did patients with a positive scan and cancer (P =.043). CONCLUSION: Most T1 lung cancers show increased FDG uptake on PET scans.

Authors
Marom, EM; Sarvis, S; Herndon, JE; Patz, EF
MLA Citation
Marom, EM, Sarvis, S, Herndon, JE, and Patz, EF. "T1 lung cancers: sensitivity of diagnosis with fluorodeoxyglucose PET." Radiology 223.2 (May 2002): 453-459.
PMID
11997552
Source
pubmed
Published In
Radiology
Volume
223
Issue
2
Publish Date
2002
Start Page
453
End Page
459
DOI
10.1148/radiol.2232011131

The health-related quality of life and survival of small-cell lung cancer patients: results of a companion study to CALGB 9033.

The purposes of this study were 2-fold: to evaluate the impact of the schedule dependency of etoposide (3-day IV short course vs. a 21-day oral prolonged course) with cisplatin on the quality of life of small-cell lung cancer (SCLC) patients; and to examine the effect of baseline quality of life variables on long-term survival, after adjustment for known demographic and clinical prognostic factors. Participants were 70 patients enrolled in the cancer and leukemia group B (CALGB) protocol 9033. Quality of life was assessed at baseline, 6 and 12 weeks by: the EORTC QLQ-30, the Centers for epidemiology studies--Depression short form, the medical outcomes study (MOS) social support questionnaire, and a scale of sleep quality. Contrary to expectations, study results suggested no significant differences in the patients' life quality and treatment response based on whether they received etoposide in a 3-day IV vs. a 21-day oral regimen. The use of the baseline variables in predicting overall survival indicated that patients who were non-white and with liver involvement had decreased survival. Brain involvement, being male, and higher depressive symptoms were also found to be borderline significant in predicting decreased survival in this patient population.

Authors
Naughton, MJ; Herndon, JE; Shumaker, SA; Miller, AA; Kornblith, AB; Chao, D; Holland, J
MLA Citation
Naughton, MJ, Herndon, JE, Shumaker, SA, Miller, AA, Kornblith, AB, Chao, D, and Holland, J. "The health-related quality of life and survival of small-cell lung cancer patients: results of a companion study to CALGB 9033." Qual Life Res 11.3 (May 2002): 235-248.
PMID
12074261
Source
pubmed
Published In
Quality of Life Research
Volume
11
Issue
3
Publish Date
2002
Start Page
235
End Page
248

Phase II trial of murine (131)I-labeled antitenascin monoclonal antibody 81C6 administered into surgically created resection cavities of patients with newly diagnosed malignant gliomas.

PURPOSE: To assess the efficacy and toxicity of intraresection cavity (131)I-labeled murine antitenascin monoclonal antibody 81C6 and determine its true response rate among patients with newly diagnosed malignant glioma. PATIENTS AND METHODS: In this phase II trial, 120 mCi of (131)I-labeled murine 81C6 was injected directly into the surgically created resection cavity of 33 patients with previously untreated malignant glioma (glioblastoma multiforme [GBM], n = 27; anaplastic astrocytoma, n = 4; anaplastic oligodendroglioma, n = 2). Patients then received conventional external-beam radiotherapy followed by a year of alkylator-based chemotherapy. RESULTS: Median survival for all patients and those with GBM was 86.7 and 79.4 weeks, respectively. Eleven patients remain alive at a median follow-up of 93 weeks (range, 49 to 220 weeks). Nine patients (27%) developed reversible hematologic toxicity, and histologically confirmed, treatment-related neurologic toxicity occurred in five patients (15%). One patient (3%) required reoperation for radionecrosis. CONCLUSION: Median survival achieved with (131)I-labeled 81C6 exceeds that of historical controls treated with conventional radiotherapy and chemotherapy, even after accounting for established prognostic factors including age and Karnofsky performance status. The median survival achieved with (131)I-labeled 81C6 compares favorably with either (125)I interstitial brachy-therapy or stereotactic radiosurgery and is associated with a significantly lower rate of reoperation for radionecrosis. Our results confirm the efficacy of (131)I-labeled 81C6 for patients with newly diagnosed malignant glioma and suggest that a randomized phase III study is indicated.

Authors
Reardon, DA; Akabani, G; Coleman, RE; Friedman, AH; Friedman, HS; Herndon, JE; Cokgor, I; McLendon, RE; Pegram, CN; Provenzale, JM; Quinn, JA; Rich, JN; Regalado, LV; Sampson, JH; Shafman, TD; Wikstrand, CJ; Wong, TZ; Zhao, X-G; Zalutsky, MR; Bigner, DD
MLA Citation
Reardon, DA, Akabani, G, Coleman, RE, Friedman, AH, Friedman, HS, Herndon, JE, Cokgor, I, McLendon, RE, Pegram, CN, Provenzale, JM, Quinn, JA, Rich, JN, Regalado, LV, Sampson, JH, Shafman, TD, Wikstrand, CJ, Wong, TZ, Zhao, X-G, Zalutsky, MR, and Bigner, DD. "Phase II trial of murine (131)I-labeled antitenascin monoclonal antibody 81C6 administered into surgically created resection cavities of patients with newly diagnosed malignant gliomas." J Clin Oncol 20.5 (March 1, 2002): 1389-1397.
PMID
11870184
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
20
Issue
5
Publish Date
2002
Start Page
1389
End Page
1397
DOI
10.1200/JCO.2002.20.5.1389

Molecular staging of lung cancer: real-time polymerase chain reaction estimation of lymph node micrometastatic tumor cell burden in stage I non-small cell lung cancer--preliminary results of Cancer and Leukemia Group B Trial 9761.

OBJECTIVE: The 5-year survival for patients with surgically resected stage I non-small cell lung cancer is only 60% to 70%, probably because of undetected systemic occult micrometastases. Detection of occult micrometastases in lymph nodes by reverse-transcriptase polymerase chain reaction for carcinoembryonic antigen messenger RNA in non-small cell lung cancer has not been reported. Detection of occult micrometastases by standard reverse-transcriptase polymerase chain reaction provides only yes or no answers about their presence, whereas quantitative real-time reverse-transcriptase polymerase chain reaction permits reproducible quantitation of target molecules. This study evaluated the ability of quantitative reverse-transcriptase polymerase chain reaction to quantitate lymph node occult metastases with carcinoembryonic antigen messenger RNA as a tumor marker. METHODS: Standard reverse-transcriptase polymerase chain reaction and quantitative reverse-transcriptase polymerase chain reaction for carcinoembryonic antigen messenger RNA were performed on 232 lymph nodes from 53 patients with stage I disease (node negative according to histologic examination). Quantitative reverse-transcriptase polymerase chain reaction determined carcinoembryonic antigen messenger RNA quantity by detecting fluorescence increase at a threshold polymerase chain reaction cycle. Threshold polymerase chain reaction cycle values were correlated with standard curves created from serially diluted carcinoembryonic antigen-positive HTB-174 tumor cells to estimate the number of micrometastatic tumor cells in a lymph node. RESULTS: Detection rates of occult metastases were similar for standard reverse-transcriptase polymerase chain reaction and quantitative reverse-transcriptase polymerase chain reaction at 38 of 232 (16.4 %) and 59 of 232 (25.4 %), respectively. Upstaging rates among 53 cases of stage I non-small cell lung cancer were also similar for standard reverse-transcriptase polymerase chain reaction and quantitative reverse-transcriptase polymerase chain reaction at 23 of 53 (43.4 %) and 30 of 53 (56.6%), respectively. Comparison of positive lymph node stations according to quantitative reverse-transcriptase polymerase chain reaction (threshold polymerase chain reaction cycle <45) with HTB-174 tumor cell standard curves yielded estimates of metastatic tumor cell burden of 1.07 x 10(3)to 3.24 x 10(5)cells per lymph node station (median 7190 tumor cells per lymph node station). CONCLUSIONS: Standard and quantitative real-time reverse-transcriptase polymerase chain reaction for carcinoembryonic antigen detected occult metastases in patients with stage I non-small cell lung cancer at similar rates; both upstaged about 50% of cases. Quantitative reverse-transcriptase polymerase chain reaction allows estimation of the number of metastatic cells per lymph node, however, which potentially allows greater precision in predicting recurrence risk.

Authors
D'Cunha, J; Corfits, AL; Herndon, JE; Kern, JA; Kohman, LJ; Patterson, GA; Kratzke, RA; Maddaus, MA
MLA Citation
D'Cunha, J, Corfits, AL, Herndon, JE, Kern, JA, Kohman, LJ, Patterson, GA, Kratzke, RA, and Maddaus, MA. "Molecular staging of lung cancer: real-time polymerase chain reaction estimation of lymph node micrometastatic tumor cell burden in stage I non-small cell lung cancer--preliminary results of Cancer and Leukemia Group B Trial 9761." J Thorac Cardiovasc Surg 123.3 (March 2002): 484-491.
PMID
11882819
Source
pubmed
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
123
Issue
3
Publish Date
2002
Start Page
484
End Page
491

Outcomes among African-American/non-African-American patients with advanced non-small-cell lung carcinoma: report from the Cancer and Leukemia Group B.

BACKGROUND: Among patients diagnosed with advanced non-small-cell lung carcinoma (NSCLC), African-Americans have lower survival rates than non-African-Americans. Whether this difference is due to innate characteristics of the disease in the two ethnicities or to disparities in health care is not known. We investigated whether the disparity in survival would persist when patients were treated with similar systemic therapies (i.e., in phase II and phase III Cancer and Leukemia Group B [CALGB] trials). METHODS: We assessed 504 consecutive patients (458 non-African-American and 46 African-American) receiving systemic chemotherapy in CALGB studies for advanced NSCLC during the period from 1989 through 1998. Clinical and demographic characteristics, treatment received, and survival data were obtained from the CALGB database. Cox's proportional hazards model was used to assess the effect of race/ethnicity on survival after adjustment for other known prognostic factors. All statistical tests were two-sided. RESULTS: The unadjusted 1-year survival rate was 22% (95% confidence interval [CI] = 13% to 38%) for African-American patients and 30% (95% CI = 26% to 35%) for non-African-American patients, a statistically significant difference (8%; 95% CI on the difference = 5% to 12%; P =.03). Multivariable adjustment for the effect of treatment arm, histology, and metastatic site at presentation did not alter the worse outcome for African-American patients. However, the effect of race/ethnicity disappeared after adjustment for performance status and weight loss. African-American patients were more likely than non-African-Americans to present with a poor performance status (83% versus 60%) and substantial weight loss (41% versus 27%) and to be unmarried (59% versus 28%), disabled (31% versus 15%), unemployed (17% versus 7%), and Medicaid recipients (30% versus 8%). CONCLUSIONS: The relationship that we observed between poor performance, weight loss, and socioeconomic status suggests that social circumstances lead to African-Americans presenting with poorer prognostic features.

Authors
Blackstock, AW; Herndon, JE; Paskett, ED; Perry, MC; Graziano, SL; Muscato, JJ; Kosty, MP; Akerley, WL; Holland, J; Fleishman, S; Green, MR
MLA Citation
Blackstock, AW, Herndon, JE, Paskett, ED, Perry, MC, Graziano, SL, Muscato, JJ, Kosty, MP, Akerley, WL, Holland, J, Fleishman, S, and Green, MR. "Outcomes among African-American/non-African-American patients with advanced non-small-cell lung carcinoma: report from the Cancer and Leukemia Group B." J Natl Cancer Inst 94.4 (February 20, 2002): 284-290.
PMID
11854390
Source
pubmed
Published In
Journal of the National Cancer Institute
Volume
94
Issue
4
Publish Date
2002
Start Page
284
End Page
290

Novel doublets in extensive-stage small-cell lung cancer: a randomized phase II study of topotecan plus cisplatin or paclitaxel (CALGB 9430).

Chemotherapy for extensive-stage small-cell lung cancer (E-SCLC) produces high response rates and improved survival but few cures. We tested three new regimens for E-SCLC that might merit further investigation in a subsequent phase III trial. Cancer and Leukemia Group B 9430 was a randomized phase II study evaluating 4 treatment arms in 57 evaluable, previously untreated E-SCLC patients. Each arm consisted of the following: Arm 1: cisplatin plus topotecan; Arm 2: cisplatin plus paclitaxel; Arm 3: paclitaxel 230 mg/m2 plus topotecan; and Arm 4: paclitaxel 175 mg/m2 plus topotecan. Because of an accrual time difference, Arm 2 will not be discussed in this manuscript. Arm 1 (12 patients) produced 1 complete response (CR, 8%) and an overall response rate (ORR) of 42%. Toxicity was excessive, with 3 deaths (25%). Arm 3 (13 patients) produced no CRs, 7 partial responses (PRs, 54%), median survival of 13.8 months, and failure-free survival (FFS) of 7.41 months, with 3 toxic deaths (25%). Among 32 evaluable patients on Arm 4, there were 2 CRs (6%) and 20 PRs (63%) for an ORR of 69%, median survival of 9.9 months, FFS of 5.21 months, and 1-year survival of 40%. There was 1 possible treatment-related death (3%). Topotecan plus cisplatin, in the doses and schedule employed, produced excessive toxicity and modest efficacy in E-SCLC patients. Paclitaxel (230 mg/m2 on day 1) plus topotecan (1 mg/m2 on days 1-5) produced excessive toxicity that was ameliorated with an attenuated paclitaxel dose (175 mg/m2). With the latter regimen (Arm 4) in patients with a performance status of 0/1, CR rates, FFS, overall survival, and 1-year survival were similar to standard etoposide plus cisplatin chemotherapy. Further exploration of topoisomerase inhibitors and taxanes in SCLC patients is warranted.

Authors
Lyss, AP; Herndon, JE; Lynch, TJ; Turrisi, AT; Watson, DM; Grethlein, SJ; Green, MR
MLA Citation
Lyss, AP, Herndon, JE, Lynch, TJ, Turrisi, AT, Watson, DM, Grethlein, SJ, and Green, MR. "Novel doublets in extensive-stage small-cell lung cancer: a randomized phase II study of topotecan plus cisplatin or paclitaxel (CALGB 9430)." Clin Lung Cancer 3.3 (February 2002): 205-210.
PMID
14662044
Source
pubmed
Published In
Clinical lung cancer
Volume
3
Issue
3
Publish Date
2002
Start Page
205
End Page
210

Therapy choices among older patients with lung carcinoma: an evaluation of two trials of the Cancer and Leukemia Group B.

BACKGROUND: Despite a greater risk of malignancy and a higher cancer mortality rate for patients age > 65 years, bias in accruing older patients to clinical trials persists. The results from two National Cancer Institute-approved cooperative group trials (Cancer and Leukemia Group B trial 8931 [CALGB 8931] and CALGB 9130) were analyzed retrospectively to determine the participation, tolerance of treatment, and outcome of patients age > 70 years. METHODS: Five hundred fifteen patients with locally advanced or metastatic nonsmall cell lung carcinoma participated in two separate, randomized, Phase III clinical trials conducted by CALGB. Retrospective evaluation of patients by four distinct age cohorts (< 50 years, 50-59 years, 60-69 years, and > 70 years) was carried out to determine differences in toxicity, response, and survival. RESULTS: No patients age > 80 were entered on either study, even though there was no age restriction in the study eligibility criteria. No significant differences were seen in response, survival, or continuation of treatment based on age cohort. Significantly increased leukocyte toxicity was seen in older cohorts without a concomitant increase in severe or worse infectious events. CONCLUSIONS: No patients age > 80 were entered on either trial despite their potential eligibility. Patients in the oldest cohort showed no negative impact of age on treatment tolerance, response to treatment, or survival. The aggregate clinical judgment of patients and physicians can identify septuagenarians who should not be denied active consideration for aggressive management of their advanced nonsmall cell lung carcinoma.

Authors
Rocha Lima, CMS; Herndon, JE; Kosty, M; Clamon, G; Green, MR
MLA Citation
Rocha Lima, CMS, Herndon, JE, Kosty, M, Clamon, G, and Green, MR. "Therapy choices among older patients with lung carcinoma: an evaluation of two trials of the Cancer and Leukemia Group B." Cancer 94.1 (January 1, 2002): 181-187.
PMID
11815975
Source
pubmed
Published In
Cancer
Volume
94
Issue
1
Publish Date
2002
Start Page
181
End Page
187

Aberrant p53 staining does not predict cisplatin resistance in locally advanced non-small cell lung cancer.

Cisplatin based chemotherapies have increased the survival in nonsmall cell lung cancer. A mechanism for identifying tumors resistant to cisplatin would be useful in avoiding unnecessary toxicity of platinum regimens. Mutation of p53 has been shown to induce chemotherapy resistance in vitro. We hypothesized that tumors staining for p53 would be resistant to cisplatin. In Cancer and Leukemia Group B protocol 8935, patients with stage IIIA (N2 node positive) nonsmall cell lung cancer received chemotherapy followed by surgery, then post-operative chemotherapy and/or radiation. All patients underwent pre-treatment staging mediastinoscopy. Twenty-five out of forty-nine pre-treatment mediastinal lymph node specimens stained positively for p53. Positive staining did not correlate with response to chemotherapy or survival. It did predict a slightly higher complete or partial resection rate compared to negative staining (76 vs. 45%) (p = 0.042). A trend toward longer median survivals was seen in patients with positive p53 staining. This study does not support the ability of p53 staining to predict chemotherapy resistance.

Authors
Johnson, EA; Klimstra, DS; Herndon, JE; Catalano, E; Canellos, GP; Graziano, SL; Kern, JA; Green, MR
MLA Citation
Johnson, EA, Klimstra, DS, Herndon, JE, Catalano, E, Cane