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Peters, Katherine Barnett

Positions:

Associate Professor of Neurology

Neurology, General & Community Neurology
School of Medicine

Associate Professor in Neurosurgery

Neurosurgery
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2003

M.D. — Stanford University

Ph.D. 2003

Ph.D. — Stanford University

Intern, Medicine

Johns Hopkins University

Resident And Fellow In Neurology, Neurology

Johns Hopkins University

Fellow In Neuro Oncology, Surgery

Duke University

News:

Grants:

A Phase I, Multicenter, open-label, doese-escalation and expansion study of orally administered AG-881

Administered By
Duke Cancer Institute
AwardedBy
Agios Pharmaceuticals, Inc.
Role
Principal Investigator
Start Date
October 01, 2015
End Date
September 30, 2019

Assessment of Nonenhancing Tumor Volume Change Before and After Chemoradiation Treatment: Low Grade Glioma

Administered By
Duke Cancer Institute
AwardedBy
Brigham and Women's Hospital
Role
Principal Investigator
Start Date
November 01, 2016
End Date
October 31, 2018

A Phase II Study of Pembrolizumab (MK3475) with and without Bevacizumab

Administered By
Duke Cancer Institute
AwardedBy
Dana Farber Cancer Institute
Role
Principal Investigator
Start Date
June 01, 2015
End Date
May 31, 2018

Ph 1/2 trial BMX-001

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

Algorithmic three-dimensional analysis of tumor shape in MRI improves prognosis of survival in glioblastoma: a multi-institutional study.

In this retrospective, IRB-exempt study, we analyzed data from 68 patients diagnosed with glioblastoma (GBM) in two institutions and investigated the relationship between tumor shape, quantified using algorithmic analysis of magnetic resonance images, and survival. Each patient's Fluid Attenuated Inversion Recovery (FLAIR) abnormality and enhancing tumor were manually delineated, and tumor shape was analyzed by automatic computer algorithms. Five features were automatically extracted from the images to quantify the extent of irregularity in tumor shape in two and three dimensions. Univariate Cox proportional hazard regression analysis was performed to determine how prognostic each feature was of survival. Kaplan Meier analysis was performed to illustrate the prognostic value of each feature. To determine whether the proposed quantitative shape features have additional prognostic value compared with standard clinical features, we controlled for tumor volume, patient age, and Karnofsky Performance Score (KPS). The FLAIR-based bounding ellipsoid volume ratio (BEVR), a 3D complexity measure, was strongly prognostic of survival, with a hazard ratio of 0.36 (95% CI 0.20-0.65), and remained significant in regression analysis after controlling for other clinical factors (P = 0.0061). Three enhancing-tumor based shape features were prognostic of survival independently of clinical factors: BEVR (P = 0.0008), margin fluctuation (P = 0.0013), and angular standard deviation (P = 0.0078). Algorithmically assessed tumor shape is statistically significantly prognostic of survival for patients with GBM independently of patient age, KPS, and tumor volume. This shows promise for extending the utility of MR imaging in treatment of GBM patients.

Authors
Czarnek, N; Clark, K; Peters, KB; Mazurowski, MA
MLA Citation
Czarnek, N, Clark, K, Peters, KB, and Mazurowski, MA. "Algorithmic three-dimensional analysis of tumor shape in MRI improves prognosis of survival in glioblastoma: a multi-institutional study." Journal of neuro-oncology (January 10, 2017).
PMID
28074320
Source
epmc
Published In
Journal of Neuro-Oncology
Publish Date
2017
DOI
10.1007/s11060-016-2359-7

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

Antiangiogenic virotherapy: VB-111 targeting glioma

Authors
Khagi, S; Peters, KB
MLA Citation
Khagi, S, and Peters, KB. "Antiangiogenic virotherapy: VB-111 targeting glioma." Expert Opinion on Orphan Drugs 4.11 (November 2016): 1099-1103.
Source
crossref
Published In
Expert opinion on orphan drugs
Volume
4
Issue
11
Publish Date
2016
Start Page
1099
End Page
1103
DOI
10.1080/21678707.2016.1235971

Single-Agent Carboplatin for a Rare Case of Pilomyxoid Astrocytoma of the Spinal Cord in an Adult with Neurofibromatosis Type 1.

Pilomyxoid astrocytoma (PMA) is a rare and more aggressive variant of pilocytic astrocytoma, which usually affects young children and is most often located in the hypothalamic/chiasmatic region. The association of PMA with underlying genetic disorders is not well known.We identified a 23-year-old woman with a PMA of the spinal cord who was simultaneously diagnosed with neurofibromatosis type 1. Diagnosis of neurofibromatosis type 1 was made clinically and confirmed with genetic testing that revealed a heterozygous one-amino-acid deletion (c.2970-2972 delAAT) in exon 17 of the NF1 gene, which is correlated with a milder phenotype. The patient underwent a partial surgical resection of the spinal cord tumor followed by adjuvant carboplatin 560 mg/m2 every 4 weeks. Radiation was avoided due to risks associated with neurofibromatosis type 1.At the 11-month follow-up, the patient maintained a partial radiographic response as well as complete resolution of her neurologic deficits.To our knowledge, this is the first reported case of an adult patient with neurofibromatosis type 1 and a spinal cord PMA. Single-agent carboplatin was effective and well-tolerated.

Authors
Dunn-Pirio, AM; Howell, E; McLendon, RE; Peters, KB
MLA Citation
Dunn-Pirio, AM, Howell, E, McLendon, RE, and Peters, KB. "Single-Agent Carboplatin for a Rare Case of Pilomyxoid Astrocytoma of the Spinal Cord in an Adult with Neurofibromatosis Type 1." Case reports in oncology 9.3 (September 2016): 568-573.
PMID
27920686
Source
epmc
Published In
Case Reports in Oncology
Volume
9
Issue
3
Publish Date
2016
Start Page
568
End Page
573

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

Postictal Magnetic Resonance Imaging Changes Masquerading as Brain Tumor Progression: A Case Series.

Seizures are common among patients with brain tumors. Transient, postictal magnetic resonance imaging abnormalities are a long recognized phenomenon. However, these radiographic changes are not as well studied in the brain tumor population. Moreover, reversible neuroimaging abnormalities following seizure activity may be misinterpreted for tumor progression and could consequently result in unnecessary tumor-directed treatment. Here, we describe two cases of patients with brain tumors who developed peri-ictal pseudoprogression and review the relevant literature.

Authors
Dunn-Pirio, AM; Billakota, S; Peters, KB
MLA Citation
Dunn-Pirio, AM, Billakota, S, and Peters, KB. "Postictal Magnetic Resonance Imaging Changes Masquerading as Brain Tumor Progression: A Case Series." Case reports in oncology 9.2 (May 2016): 358-362.
PMID
27462237
Source
epmc
Published In
Case Reports in Oncology
Volume
9
Issue
2
Publish Date
2016
Start Page
358
End Page
362
DOI
10.1159/000447350

Radiogenomics of glioblastoma: A pilot multi-institutional study to investigate a relationship between tumor shape features and tumor molecular subtype

© 2016 SPIE.Genomic subtype has been shown to be an important predictor of therapy response for patients with glioblastomas. Unfortunately, obtaining the genomic subtype is an expensive process that is not typically included in the standard of care. It is therefore of interest to investigate potential surrogates of molecular subtypes that use standard diagnostic data such as magnetic resonance (MR) imaging. In this study, we analyze the relationship between tumor genomic subtypes, proposed by Verhaak et al, 2010, and novel features that capture the shape of abnormalities as seen in fluid attenuated inversion recovery (FLAIR) MR images. In our study, we used data from 54 patients with glioblastomas from four institutions provided by The Cancer Genome Atlas (TCGA) and The Cancer Imaging Archive (TCIA). We explore five shape features calculated by computer algorithms implemented in our laboratory that assess shape both in individual slices and in rendered three-dimensional tumor volumes. The association between each feature and molecular subtype was assessed using area under the receiver operating characteristic curve analysis. We show that the two dimensional measures of edge complexity are significant discriminators between mesenchymal and classical tumors. These preliminary findings show promise for an imaging-based surrogate of molecular subtype and contribute to the understanding of the relationship between tumor biology and its radiology phenotype.

Authors
Czarnek, NM; Clark, K; Peters, KB; Collins, LM; Mazurowski, MA
MLA Citation
Czarnek, NM, Clark, K, Peters, KB, Collins, LM, and Mazurowski, MA. "Radiogenomics of glioblastoma: A pilot multi-institutional study to investigate a relationship between tumor shape features and tumor molecular subtype." January 1, 2016.
Source
scopus
Published In
Proceedings of SPIE
Volume
9785
Publish Date
2016
DOI
10.1117/12.2217084

Predicting outcomes in glioblastoma patients using computerized analysis of tumor shape - Preliminary data

© 2016 SPIE.Glioblastoma (GBM) is the most common primary brain tumor characterized by very poor survival. However, while some patients survive only a few months, some might live for multiple years. Accurate prognosis of survival and stratification of patients allows for making more personalized treatment decisions and moves treatment of GBM one step closer toward the paradigm of precision medicine. While some molecular biomarkers are being investigated, medical imaging remains significantly underutilized for prognostication in GBM. In this study, we investigated whether computer analysis of tumor shape can contribute toward accurate prognosis of outcomes. Specifically, we implemented applied computer algorithms to extract 5 shape features from magnetic resonance imaging (MRI) for 22 GBM patients. Then, we determined whether each one of the features can accurately distinguish between patients with good and poor outcomes. We found that that one of the 5 analyzed features showed prognostic value of survival. The prognostic feature describes how well the 3D tumor shape fills its minimum bounding ellipsoid. Specifically, for low values (less or equal than the median) the proportion of patients that survived more than a year was 27% while for high values (higher than median) the proportion of patients with survival of more than 1 year was 82%. The difference was statistically significant (p < 0.05) even though the number of patients analyzed in this pilot study was low. We concluded that computerized, 3D analysis of tumor shape in MRI may strongly contribute to accurate prognostication and stratification of patients for therapy in GBM.

Authors
Mazurowski, MA; Czarnek, NM; Collins, LM; Peters, KB; Clark, K
MLA Citation
Mazurowski, MA, Czarnek, NM, Collins, LM, Peters, KB, and Clark, K. "Predicting outcomes in glioblastoma patients using computerized analysis of tumor shape - Preliminary data." January 1, 2016.
Source
scopus
Published In
Proceedings of SPIE
Volume
9785
Publish Date
2016
DOI
10.1117/12.2217098

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

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

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

Supratentorial tanycytic ependymoma in an adult male: case report and review of literature.

Ependymomas, tumors of the ependymal cells, are very rare and usually present in the pediatric population. Furthermore, there are even rarer variants of ependymomas that can include cellular, papillary, clear cell, and tanycytic subtypes. We present a case of a supratentorial tanycytic ependymoma in an adult male and review the literature in regard to this rare primary central nervous system neoplasm.

Authors
Lopez, G; McLendon, RE; Peters, KB
MLA Citation
Lopez, G, McLendon, RE, and Peters, KB. "Supratentorial tanycytic ependymoma in an adult male: case report and review of literature." Case reports in oncology 8.1 (January 2015): 159-163.
PMID
25873884
Source
epmc
Published In
Case Reports in Oncology
Volume
8
Issue
1
Publish Date
2015
Start Page
159
End Page
163
DOI
10.1159/000380906

Use of bevacizumab in recurrent glioblastoma.

Glioblastoma (GBM) is the most common adult primary brain neoplasm. Despite advances in treatment, GBM continues to be associated with considerable morbidity and mortality as compared with other malignancies. Standard treatment for GBM results in survival of 12.9 months (95% CI: 12.3-13.7 months) with a median progression-free survival of 7.2 months (95% CI: 6.4-8.2 months) in a modern GBM cohort. These aggressive tumors recur and treatment for recurrent GBM continues to have very poor outcomes. Prior to the use of bevacizumab, monoclonal antibody to VEGF, 6-month progression-free survival in clinical trials for recurrent GBM ranged from 9 to 15%. Trials utilizing bevacizumab and its subsequent US FDA approval have given more hope to recurrent GBM and this concise review discusses bevacizumab in recurrent GBM. This review focuses on time-to-event outcomes (overall survival, progression-free survival and 6-month progression-free survival) in clinical trials utilizing bevacizumab for the treatment of recurrent GBM. For this review, we have chosen to focus primarily on Phase II clinical trials that have been published and available in the literature (PubMed). While we focused primarily on time-to-event variables, toxicity and safety of bevacizumab is very important and this agent can be associated with serious life-threatening toxicities. We have included a general section of toxicities but for a more lengthy review please see the excellent study by Odia and colleagues.

Authors
Ghiaseddin, A; Peters, KB
MLA Citation
Ghiaseddin, A, and Peters, KB. "Use of bevacizumab in recurrent glioblastoma." CNS oncology 4.3 (January 2015): 157-169.
PMID
25906439
Source
epmc
Published In
CNS Oncology
Volume
4
Issue
3
Publish Date
2015
Start Page
157
End Page
169
DOI
10.2217/cns.15.8

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

Computer-extracted MR imaging features are associated with survival in glioblastoma patients.

Automatic survival prognosis in glioblastoma (GBM) could result in improved treatment planning for the patient. The purpose of this research is to investigate the association of survival in GBM patients with tumor features in pre-operative magnetic resonance (MR) images assessed using a fully automatic computer algorithm. MR imaging data for 68 patients from two US institutions were used in this study. The images were obtained from the Cancer Imaging Archive. A fully automatic computer vision algorithm was applied to segment the images and extract eight imaging features from the MRI studies. The features included tumor side, proportion of enhancing tumor, proportion of necrosis, T1/FLAIR ratio, major axis length, minor axis length, tumor volume, and thickness of enhancing margin. We constructed a multivariate Cox proportional hazards regression model and used a likelihood ratio test to establish whether the imaging features are prognostic of survival. We also evaluated the individual prognostic value of each feature through multivariate analysis using the multivariate Cox model and univariate analysis using univariate Cox models for each feature. We found that the automatically extracted imaging features were predictive of survival (p = 0.031). Multivariate analysis of individual features showed that two individual features were predictive of survival: proportion of enhancing tumor (p = 0.013), and major axis length (p = 0.026). Univariate analysis indicated the same two features as significant (p = 0.021, and p = 0.017 respectively). We conclude that computer-extracted MR imaging features can be used for survival prognosis in GBM patients.

Authors
Mazurowski, MA; Zhang, J; Peters, KB; Hobbs, H
MLA Citation
Mazurowski, MA, Zhang, J, Peters, KB, and Hobbs, H. "Computer-extracted MR imaging features are associated with survival in glioblastoma patients." Journal of neuro-oncology 120.3 (December 2014): 483-488.
PMID
25151504
Source
epmc
Published In
Journal of Neuro-Oncology
Volume
120
Issue
3
Publish Date
2014
Start Page
483
End Page
488
DOI
10.1007/s11060-014-1580-5

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

Computer-extracted MR imaging features are associated with survival in glioblastoma patients

© 2014, Springer Science+Business Media New York.Automatic survival prognosis in glioblastoma (GBM) could result in improved treatment planning for the patient. The purpose of this research is to investigate the association of survival in GBM patients with tumor features in pre-operative magnetic resonance (MR) images assessed using a fully automatic computer algorithm. MR imaging data for 68 patients from two US institutions were used in this study. The images were obtained from the Cancer Imaging Archive. A fully automatic computer vision algorithm was applied to segment the images and extract eight imaging features from the MRI studies. The features included tumor side, proportion of enhancing tumor, proportion of necrosis, T1/FLAIR ratio, major axis length, minor axis length, tumor volume, and thickness of enhancing margin. We constructed a multivariate Cox proportional hazards regression model and used a likelihood ratio test to establish whether the imaging features are prognostic of survival. We also evaluated the individual prognostic value of each feature through multivariate analysis using the multivariate Cox model and univariate analysis using univariate Cox models for each feature. We found that the automatically extracted imaging features were predictive of survival (p = 0.031). Multivariate analysis of individual features showed that two individual features were predictive of survival: proportion of enhancing tumor (p = 0.013), and major axis length (p = 0.026). Univariate analysis indicated the same two features as significant (p = 0.021, and p = 0.017 respectively). We conclude that computer-extracted MR imaging features can be used for survival prognosis in GBM patients.

Authors
Mazurowski, MA; Zhang, J; Peters, KB; Hobbs, H
MLA Citation
Mazurowski, MA, Zhang, J, Peters, KB, and Hobbs, H. "Computer-extracted MR imaging features are associated with survival in glioblastoma patients." Journal of Neuro-Oncology 120.3 (January 1, 2014): 483-488.
Source
scopus
Published In
Journal of Neuro-Oncology
Volume
120
Issue
3
Publish Date
2014
Start Page
483
End Page
488
DOI
10.1007/s11060-014-1580-5

Tumor progression and transformation of low-grade glial tumors associated with pregnancy.

Brain tumor growth or progression has been shown to occur in low-grade glial tumors and meningiomas. While progression has been documented in this population, transformation to a more aggressive high-grade glial tumor that can lead to increased morbidity and mortality has not been identified. In this case series, we document transformation from low-grade gliomas to high-grade gliomas (WHO grade III and IV) in young women during pregnancy. We further discuss the possible etiologies of this phenomenon.

Authors
Daras, M; Cone, C; Peters, KB
MLA Citation
Daras, M, Cone, C, and Peters, KB. "Tumor progression and transformation of low-grade glial tumors associated with pregnancy." Journal of neuro-oncology 116.1 (January 2014): 113-117.
PMID
24078174
Source
epmc
Published In
Journal of Neuro-Oncology
Volume
116
Issue
1
Publish Date
2014
Start Page
113
End Page
117
DOI
10.1007/s11060-013-1261-9

Acquired stuttering due to recurrent anaplastic astrocytoma.

Acquired (neurogenic) stuttering is a rare phenomenon seen after cerebral infarction or brain injury. Aetiology of this symptom is unclear, but recent evidence supports that it is a disturbance in the left hemispheric neural network involving the interplay between the cortex and basal ganglia. We present the case of a patient who develops acquired stuttering after a recurrence of a right temporoparietal anaplastic astrocytoma (WHO grade III). We also review other cases of acquired stuttering and known anatomical correlates.

Authors
Peters, KB; Turner, S
MLA Citation
Peters, KB, and Turner, S. "Acquired stuttering due to recurrent anaplastic astrocytoma." BMJ case reports 2013 (December 1, 2013).
Source
scopus
Published In
BMJ Case Reports
Volume
2013
Publish Date
2013

Acquired stuttering due to recurrent anaplastic astrocytoma.

Acquired (neurogenic) stuttering is a rare phenomenon seen after cerebral infarction or brain injury. Aetiology of this symptom is unclear, but recent evidence supports that it is a disturbance in the left hemispheric neural network involving the interplay between the cortex and basal ganglia. We present the case of a patient who develops acquired stuttering after a recurrence of a right temporoparietal anaplastic astrocytoma (WHO grade III). We also review other cases of acquired stuttering and known anatomical correlates.

Authors
Peters, KB; Turner, S
MLA Citation
Peters, KB, and Turner, S. "Acquired stuttering due to recurrent anaplastic astrocytoma. (Published online)" BMJ Case Rep 2013 (November 19, 2013).
PMID
24252834
Source
pubmed
Published In
BMJ Case Reports
Volume
2013
Publish Date
2013
DOI
10.1136/bcr-2013-009562

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

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

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

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

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

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

Disseminated Intracranial Ewing's Sarcoma in an Adult: A Rare and Difficult Diagnosis.

The Ewing sarcoma family of tumors comprises a rare class of cancers of mesenchymal origin. Cases of Ewing's sarcoma in the central nervous system - specifically, intracranial Ewing's - are extremely rare. Almost all reported cases have occurred in children. However, this rare presentation can also occur in the adult population. It is important to distinguish these tumors from primitive neuroectodermal tumors at the time of diagnosis. Testing for EWSR1(22q12) gene rearrangement using fluorescence in situ hybridization is a useful tool for making the distinction between these 2 similar but distinct entities. We present here the case of a middle-aged male patient with intracranial Ewing's sarcoma, and discuss diagnostic challenges and potential new treatment approaches for this rare disease.

Authors
Lou, E; Sumrall, AL; Cummings, TJ; Korones, DN; Weaver, SA; Peters, KB
MLA Citation
Lou, E, Sumrall, AL, Cummings, TJ, Korones, DN, Weaver, SA, and Peters, KB. "Disseminated Intracranial Ewing's Sarcoma in an Adult: A Rare and Difficult Diagnosis." Case Rep Oncol 5.2 (May 2012): 325-331.
PMID
22933997
Source
pubmed
Published In
Case Reports in Oncology
Volume
5
Issue
2
Publish Date
2012
Start Page
325
End Page
331
DOI
10.1159/000339721

Safety and efficacy of stereotactic radiosurgery and adjuvant bevacizumab in patients with recurrent malignant gliomas.

PURPOSE: Patients with recurrent malignant gliomas treated with stereotactic radiosurgery (SRS) and multiagent systemic therapies were reviewed to determine the effects of patient- and treatment-related factors on survival and toxicity. METHODS AND MATERIALS: A retrospective analysis was performed on patients with recurrent malignant gliomas treated with salvage SRS from September 2002 to March 2010. All patients had experienced progression after treatment with temozolomide and radiotherapy. Salvage SRS was typically administered only after multiple postchemoradiation salvage systemic therapies had failed. RESULTS: 63 patients were treated with SRS for recurrent high-grade glioma; 49 patients had World Health Organization (WHO) Grade 4 disease. Median follow-up was 31 months from primary diagnosis and 7 months from SRS. Median overall survival from primary diagnosis was 41 months for all patients. Median progression-free survival (PFS) and overall survival from SRS (OS-SRS) were 6 and 10 months for all patients, respectively. The 1-year OS-SRS for patients with Grade 4 glioma who received adjuvant (concurrent with or after SRS) bevacizumab was 50% vs. 22% for patients not receiving adjuvant bevacizumab (p = 0.005). Median PFS for patients with a WHO Grade 4 glioma who received adjuvant bevacizumab was 5.2 months vs. 2.1 months for patients who did not receive adjuvant bevacizumab (p = 0.014). Karnofsky performance status (KPS) and age were not significantly different between treatment groups. Treatment-related Grade 3/4 toxicity for patients receiving and not receiving adjuvant BVZ was 10% and 14%, respectively (p = 0.58).On multivariate analysis, the relative risk of death and progression with adjuvant bevacizumab was 0.37 (confidence interval [CI] 0.17-0.82) and 0.45 (CI 0.21-0.97). KPS >70 and age <50 years were significantly associated with improved survival. CONCLUSIONS: The combination of salvage radiosurgery and bevacizumab to treat recurrent malignant gliomas is well tolerated and seems to be associated with improved outcomes. Prospective multiinstitutional studies are required to determine efficacy and long-term toxicity with this approach.

Authors
Cuneo, KC; Vredenburgh, JJ; Sampson, JH; Reardon, DA; Desjardins, A; Peters, KB; Friedman, HS; Willett, CG; Kirkpatrick, JP
MLA Citation
Cuneo, KC, Vredenburgh, JJ, Sampson, JH, Reardon, DA, Desjardins, A, Peters, KB, Friedman, HS, Willett, CG, and Kirkpatrick, JP. "Safety and efficacy of stereotactic radiosurgery and adjuvant bevacizumab in patients with recurrent malignant gliomas." Int J Radiat Oncol Biol Phys 82.5 (April 1, 2012): 2018-2024.
PMID
21489708
Source
pubmed
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
82
Issue
5
Publish Date
2012
Start Page
2018
End Page
2024
DOI
10.1016/j.ijrobp.2010.12.074

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

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

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

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

Bevacizumab-induced reversible posterior leukoencephalopathy syndrome and successful retreatment in a patient with glioblastoma.

Authors
Lou, E; Turner, S; Sumrall, A; Reardon, DA; Desjardins, A; Peters, KB; Sampson, JH; Friedman, HS; Vredenburgh, JJ
MLA Citation
Lou, E, Turner, S, Sumrall, A, Reardon, DA, Desjardins, A, Peters, KB, Sampson, JH, Friedman, HS, and Vredenburgh, JJ. "Bevacizumab-induced reversible posterior leukoencephalopathy syndrome and successful retreatment in a patient with glioblastoma." J Clin Oncol 29.28 (October 1, 2011): e739-e742.
PMID
21900098
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
29
Issue
28
Publish Date
2011
Start Page
e739
End Page
e742
DOI
10.1200/JCO.2011.36.1865

Everolimus tablets for patients with subependymal giant cell astrocytoma.

INTRODUCTION: Better understanding of aberrantly active molecular pathways in tumors offers potential to develop more specific and less toxic therapies. Abnormal mammalian target of rapamycin (mTOR) complex signaling and defects in TSC1 and TSC2 have been associated with the development of subependymal giant cell astrocytomas (SEGAs) in tuberous sclerosis complex (TSC) patients. Recently, mTOR inhibitors such as everolimus have shown encouraging benefit for patients with SEGAs. AREAS COVERED: The authors discuss a molecular genetic pathway linked with TSC, specifically the role of two proteins whose functional absence is responsible for most SEGA tumors that arise in TSC patients. The authors also examine the rationale for targeted agents against this pathway therapeutically and describe the clinical evidence underlying the FDA approval of everolimus for patients with inoperable SEGAs. EXPERT OPINION: Everolimus (Afinitor) selectively targets a molecular defect of SEGAs in TSC patients. Although surgery is effective, most SEGAs recur. An agent that inhibits an underlying molecular abnormality represents a particularly attractive therapeutic option for patients with inoperable or recurrent tumors. Studies are also underway to assess everolimus in treating other sequelae of TSC, and other gliomas. Finally, additional research aimed at better understanding aberrant cell signaling pathways may lead to the development of more effective therapeutics.

Authors
Turner, SG; Peters, KB; Vredenburgh, JJ; Desjardins, A; Friedman, HS; Reardon, DA
MLA Citation
Turner, SG, Peters, KB, Vredenburgh, JJ, Desjardins, A, Friedman, HS, and Reardon, DA. "Everolimus tablets for patients with subependymal giant cell astrocytoma." Expert Opin Pharmacother 12.14 (October 2011): 2265-2269. (Review)
PMID
21806479
Source
pubmed
Published In
Expert Opinion on Pharmacotherapy
Volume
12
Issue
14
Publish Date
2011
Start Page
2265
End Page
2269
DOI
10.1517/14656566.2011.601742

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

Transformation of juvenile pilocytic astrocytoma to anaplastic pilocytic astrocytoma in patients with neurofibromatosis type I.

Patients with juvenile pilocytic astrocytoma (JPA) and neurofibromatosis type I (NF-1) tend to have a more indolent course than those with sporadic tumors. In rare circumstances, transformation to anaplastic pilocytic astrocytoma (APA) has been known to occur in sporadic cases and is associated with exposure to ionizing radiation. We present 2 patients with NF-1 who were initially diagnosed with JPA that later transformed to APA. Both patients were not exposed to ionizing radiation but instead received alkylator chemotherapy before transformation. Possibility of conversion to APA should be considered in patients with NF-1 and JPA who have rapid tumor recurrence.

Authors
Peters, KB; Cummings, TJ; Gururangan, S
MLA Citation
Peters, KB, Cummings, TJ, and Gururangan, S. "Transformation of juvenile pilocytic astrocytoma to anaplastic pilocytic astrocytoma in patients with neurofibromatosis type I." J Pediatr Hematol Oncol 33.5 (July 2011): e198-e201.
PMID
21572348
Source
pubmed
Published In
Journal of Pediatric Hematology/Oncology
Volume
33
Issue
5
Publish Date
2011
Start Page
e198
End Page
e201
DOI
10.1097/MPH.0b013e318205e230

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

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

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

Ulceration of Striae distensae in high-grade glioma patients on concurrent systemic corticosteroid and bevacizumab therapy.

Striae distensae (stretch marks) are a common complication seen in patients on chronic corticosteroid therapy. Under certain circumstances, primary brain tumor patients require chronic corticosteroid therapy and can suffer from striae distensae. Bevacizumab, a humanized monoclonal antibody to vascular endothelial growth factor-A (VEGF-A) is now more widely used for the treatment of primary brain tumors. In this paper, we present four cases of ulcerated striae distensae in primary brain tumor patients on concurrent corticosteroid and bevacizumab therapy. Because of bevacizumab's effects on wound healing and its recent accelerated approval for recurrent glioblastoma multiforme (GBM), the most common malignant primary brain tumor in adults, this novel skin complication should be considered in patients on concurrent corticosteroid and bevacizumab therapy.

Authors
Peters, KB; Coyle, TE; Vredenburgh, JJ; Desjardins, A; Friedman, HS; Reardon, DA
MLA Citation
Peters, KB, Coyle, TE, Vredenburgh, JJ, Desjardins, A, Friedman, HS, and Reardon, DA. "Ulceration of Striae distensae in high-grade glioma patients on concurrent systemic corticosteroid and bevacizumab therapy." J Neurooncol 101.1 (January 2011): 155-159.
PMID
20524043
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
101
Issue
1
Publish Date
2011
Start Page
155
End Page
159
DOI
10.1007/s11060-010-0239-0

Dural venous sinus thrombosis in anaplastic astrocytoma following concurrent temozolomide and focal brain radiotherapy plus bevacizumab

Malignant gliomas have long been a therapeutic dilemma in neuro-oncology, with a poor overall prognosis. Standard treatment, consisting of primary resection, followed by radiation therapy and temozolomide, has improved prognosis. Recently, studies have looked at the addition of bevacizumab (Avastin), a humanized murine IgG1 monoclonal antibody against vascular endothelial growth factor-A, to conventional regiments. Bevacizumab gained US FDA approval for single agent use in recurrent glioblastoma in 2009. Known side effects of bevacizumab include increased risk of arterial and venous thromboembolism, as well as hemorrhage. With emerging data for the use of bevacizumab in malignant gliomas, the extent of risks such as bleeding and thrombosis in patients with primary brain tumors treated with bevacizumab remains unknown. Here, we present only the second reported case of dural venous sinus thrombosis during treatment with bevacizumab and the first reported case for a primary glioma treated with temozolomide, radiation, and bevacizumab. © 2011 Springer Science+Business Media, LLC.

Authors
Vargo, JA; Snelling, BM; Ghareeb, ER; John, K; Frame, JN; Schmidt, JH; Peters, KB
MLA Citation
Vargo, JA, Snelling, BM, Ghareeb, ER, John, K, Frame, JN, Schmidt, JH, and Peters, KB. "Dural venous sinus thrombosis in anaplastic astrocytoma following concurrent temozolomide and focal brain radiotherapy plus bevacizumab." Journal of Neuro-Oncology 104.2 (2011): 595-598.
PMID
21221711
Source
scival
Published In
Journal of Neuro-Oncology
Volume
104
Issue
2
Publish Date
2011
Start Page
595
End Page
598
DOI
10.1007/s11060-010-0519-8

A comparison of performance-based measures of function in HIV-associated neurocognitive disorders

The objectives of this study are to compare the results of newer performance-based functional assessments in the study of HIV-associated neurocognitive disorders (HAND) and to correlate these functional assessments with specific levels of severity of HAND. One hundred fourteen HIV+ subjects in an existing cohort were evaluated with a medical history, neurological exam, neuropsychological test battery as well as subjective and novel objective measures of functional abilities. Self-reported measures of functional performance included the Karnofsky Performance Scale, a questionnaire for instrumental activities of daily living, and a questionnaire for physical quality of life measures. The newer objective functional performance assessments included the Columbia Medication Management and the San Diego Finances tests. These newer performance-based measures of function were assessed for their ability to predict level of HAND. The two objective measures of functional performance, The Columbia Medication Management Scale and the San Diego Finances Test, were both associated with levels of severity of HAND. The Karnofsky Performance Scale and the questionnaires for role and physical quality of life were subjective measures that were also associated with specific levels of HAND. Newer measures of functional performance can be used to objectively evaluate functional impairment in HAND and validate different levels of HAND. © Journal of NeuroVirology, Inc. 2011.

Authors
Gandhi, NS; Skolasky, RL; Peters, KB; IV, RTM; Creighton, J; Roosa, HV; Selnes, OA; McArthur, J; Sacktor, N
MLA Citation
Gandhi, NS, Skolasky, RL, Peters, KB, IV, RTM, Creighton, J, Roosa, HV, Selnes, OA, McArthur, J, and Sacktor, N. "A comparison of performance-based measures of function in HIV-associated neurocognitive disorders." Journal of NeuroVirology 17.2 (2011): 159-165.
PMID
21437751
Source
scival
Published In
Journal of NeuroVirology
Volume
17
Issue
2
Publish Date
2011
Start Page
159
End Page
165
DOI
10.1007/s13365-011-0023-8

Treatment of Recurrent Intracranial Hemangiopericytoma with SRC-Related Tyrosine Kinase Targeted Therapy: A Case Report.

Hemangiopericytoma (HPC) is a rare sarcomatous tumor arising from pericytes, a support cell found in blood vessels. These tumors can occur throughout the body, particularly in the lower extremities and retroperitoneum. In rare circumstances, HPCs can arise from the meninges. In these cases, they behave similar to meningiomas, in particular angiomatous meningiomas, but tend to be more aggressive and are likely to recur. Treatment usually focuses on surgical resection and radiotherapy with possible inclusion of chemotherapy for control of recurrent disease. We describe a case of recurrent right temporal HPC that first manifested as a paraneoplastic syndrome of oncogenic osteomalacia. Despite maximum therapy, this patient experienced multiple recurrences of the tumor, and immunohistochemical analysis revealed overexpression of platelet-derived growth factor receptor, a member of the SRC-related tyrosine kinases. After multiple recurrences, the patient's tumor has been stable with treatment with monotherapy utilizing molecularly targeted therapy to SRC-related tyrosine kinases. This is the first case report of the treatment of recurrent meningeal HPC with molecularly targeted therapy to SRC-related tyrosine kinases.

Authors
Peters, KB; McLendon, R; Morse, MA; Vredenburgh, JJ
MLA Citation
Peters, KB, McLendon, R, Morse, MA, and Vredenburgh, JJ. "Treatment of Recurrent Intracranial Hemangiopericytoma with SRC-Related Tyrosine Kinase Targeted Therapy: A Case Report. (Published online)" Case Rep Oncol 3.1 (April 8, 2010): 93-97.
PMID
20740166
Source
pubmed
Published In
Case Rep Oncol
Volume
3
Issue
1
Publish Date
2010
Start Page
93
End Page
97
DOI
10.1159/000307468

Changes in functional performance measures in adults undergoing chemoradiation for primary malignant glioma: a feasibility study.

PURPOSE: To investigate the feasibility of longitudinal assessment of functional performance measures in newly diagnosed postsurgical malignant glioma patients. METHODS: Patients with histologically confirmed, clinically stable, postsurgical, and previously untreated high-grade glioma (HGG) or low-grade glioma (LGG) were studied. Using a prospective design, all participants performed a cardiopulmonary exercise test with expired gas analysis to assess cardiorespiratory function (VO(2peak)) immediately following surgical resection (mean, 10 days). Additional functional outcomes were skeletal muscle cross-sectional area (CSA) via magnetic resonance imaging, isokinetic muscle strength (isokinetic dynamometry), and body composition (air displacement plethysmography). Quality of life (QOL) was assessed by the Functional Assessment of Cancer Therapy-Brain scale. All study assessments were repeated at 6 and 24 weeks following surgery. RESULTS: Thirty-five patients (HGG, n = 25; LGG, n = 10) completed baseline assessments. Of these, 20 HGG (80%) and nine LGG (90%) and 15 HGG (60%) and nine LGG (90%) patients completed study assessments at 6 weeks and 24 weeks, respectively. Intention-to-treat analyses indicated several significant time-by-group interactions, with favorable improvements in functional and QOL endpoints from baseline to 24 weeks in the LGG cohort and unfavorable changes in the HGG cohort. Per-protocol analyses including participants assessed at all three study timepoints indicated significant improvements in VO(2peak) and fatigue from baseline to 24 weeks in the HGG cohort; peak workload, body composition, and muscle strength improved from baseline to 6 weeks (all p-values < .05). CONCLUSIONS: Longitudinal quantitative functional assessments are safe and feasible among select patients undergoing chemoradiation for primary malignant glioma. Large prospective studies investigating the clinical importance of these measures appear warranted.

Authors
Jones, LW; Mourtzakis, M; Peters, KB; Friedman, AH; West, MJ; Mabe, SK; Kraus, WE; Friedman, HS; Reardon, DA
MLA Citation
Jones, LW, Mourtzakis, M, Peters, KB, Friedman, AH, West, MJ, Mabe, SK, Kraus, WE, Friedman, HS, and Reardon, DA. "Changes in functional performance measures in adults undergoing chemoradiation for primary malignant glioma: a feasibility study." Oncologist 15.6 (2010): 636-647.
PMID
20484122
Source
pubmed
Published In
The oncologist
Volume
15
Issue
6
Publish Date
2010
Start Page
636
End Page
647
DOI
10.1634/theoncologist.2009-0265

Connective Tissue, Endocrine, Toxic, and Psychiatric Disorders

Authors
Peters, KB; Irani, DN
MLA Citation
Peters, KB, and Irani, DN. "Connective Tissue, Endocrine, Toxic, and Psychiatric Disorders." Cerebrospinal Fluid in Clinical Practice (2009): 135-143.
Source
scival
Published In
Cerebrospinal Fluid in Clinical Practice
Publish Date
2009
Start Page
135
End Page
143
DOI
10.1016/B978-141602908-3.50020-0

Neurologic complications of head and neck cancer

Cancers of the oral cavity, nasal cavity, salivary glands, pharynx, and larynx comprise head and neck cancers. These cancers are present not only in the United States but also around the world. Risk factors such as smoking, alcohol, and human papillomavirus are clearly linked to the prevalence of these cancers. Because of the obvious close anatomical proximity of structures involved in head and neck tumors, neurologic complications-in particular involving the cranial nerves and brain-can occur. The most common neurologic complication is cranial nerve dysfunction, but in rare instances the brain, spine, leptomeninges, vascular structures, and immune system through paraneoplastic processes can be affected. Neurologic dysfunction can occur not only secondary to direct involvement of head and neck malignancies but also from the treatment of the disease, particular from radiation and surgery. © 2008 Humana Press, Totowa, NJ.

Authors
Peters, KB; Schiff, D
MLA Citation
Peters, KB, and Schiff, D. "Neurologic complications of head and neck cancer." (December 1, 2008): 507-521. (Chapter)
Source
scopus
Publish Date
2008
Start Page
507
End Page
521
DOI
10.1007/978-1-59745-412-4_27

Tirapazamine: A hypoxia-activated topoisomerase II poison

Tirapazamine (TPZ), a hypoxia-selective cytotoxin, has demonstrated activity in cancer clinical trials. Under hypoxic conditions, TPZ is reduced to a radical that leads to DNA double-strand breaks (DSBs), single-strand breaks, and base damage. A previous finding of an association of the DSBs with protein led us to investigate the involvement of topoisomerase II (topo II) in their formation. Nuclear extracts from human lung cancer cells treated with either the topo II poison etoposide or TPZ under hypoxic conditions had markedly reduced topo II activity as judged by an inability to convert kinetoplast DNA from the catenated to the decatenated form. Because topo II poisons, such as etoposide, cause DNA DSBs, we hypothesized that pretreatment of cells with merbarone or aclarubicin, known catalytic inhibitors of topo II, would abrogate DNA DSBs caused by topo II. Cells pretreated with these catalytic inhibitors abrogated both DNA DSBs and cell kill induced by etoposide or by TPZ. Etoposide- and TPZ-mediated DSBs were also greatly reduced in a small cell lung cancer cell line with low levels of nuclear topo IIα. We also showed that topo IIα becomes covalently bound to DNA after TPZ treatment under hypoxic conditions, and that the cleavable complexes formed by TPZ are more stable over time than those formed by etoposide. Taken together, these data suggest that TPZ exerts its cytotoxic effect at least in part through poisoning topo II. Because TPZ is activated only under hypoxic conditions, which are characteristic of solid tumors, these data implicate TPZ as a tumor-specific topo II poison.

Authors
Peters, KB; Brown, JM
MLA Citation
Peters, KB, and Brown, JM. "Tirapazamine: A hypoxia-activated topoisomerase II poison." Cancer Research 62.18 (2002): 5248-5253.
PMID
12234992
Source
scival
Published In
Cancer Research
Volume
62
Issue
18
Publish Date
2002
Start Page
5248
End Page
5253

Inhibition of DNA replication by tirapazamine

Tirapazamine (TPZ) is a hypoxia-selective cytotoxin that is currently being examined in Phase II and III clinical trials in combination with radiotherapy and cisplatin-based chemotherapy. Reductases convert TPZ to a cytotoxic radical that produces DNA damage under hypoxic conditions. Because one or more of the enzymes responsible for the bioactivation of TPZ is/are thought to be at or near the nuclear matrix, we hypothesized that TPZ may have a major affect on DNA replication, a process that is known to occur predominantly at the nuclear matrix. To assess the effect of TPZ on DNA replication, we measured the incorporation of radioactive thymidine into DNA of HCT116 human colon cancer cells and HeLa cells. We show that incorporation of radioactive thymidine is dramatically inhibited in cells that are pretreated with TPZ under hypoxic conditions. TPZ-induced inhibition of DNA synthesis was much greater than that produced by more toxic doses of ionizing radiation. We used the SV40-based in vitro DNA replication assay to study the mechanism of inhibition of DNA synthesis in cells treated with TPZ. Using this assay, we show that extracts prepared from cells treated with TPZ under hypoxic conditions had only 25-50% of the DNA replication activity measured in control cells. This reduction in DNA replication activity was associated with a reduction in levels of replication protein A (RPA) in cytoplasmic extracts used for the in vitro DNA replication assay and could be overcome by addition of recombinant human RPA. Furthermore, we show by indirect immunofluorescence that TPZ leads to a localization of the p34 subunit of RPA (RPA2) to small subnuclear foci. These results show that TPZ dramatically inhibits DNA replication and that the mechanism of inhibition, at least in part, involves changes in RPA that alter its cellular localization.

Authors
Peters, KB; Wang, H; Brown, JM; Iliakis, G
MLA Citation
Peters, KB, Wang, H, Brown, JM, and Iliakis, G. "Inhibition of DNA replication by tirapazamine." Cancer Research 61.14 (2001): 5425-5431.
PMID
11454687
Source
scival
Published In
Cancer Research
Volume
61
Issue
14
Publish Date
2001
Start Page
5425
End Page
5431

A high-performance liquid chromatographic method to measure sphingosine 1-phosphate and related compounds from sphingosine kinase assays and other biological samples.

Sphingosine 1-phosphate is an intermediate of sphingosine catabolism as well as a potent signaling compound. Conditions were established for the extraction and analysis of sphingosine 1-phosphate and other sphingoid base 1-phosphates from in vitro sphingosine kinase assays and other biological samples. The sphingoid base 1-phosphates were extracted in high yield (85%) using small C-18 reverse-phase columns (LiChroprep RP-18). After the extracts were treated with 0.1 N KOH to remove glycerolipids, the sphingoid base 1-phosphates were converted to fluorescent o-phthalaldehyde derivatives that were separated by HPLC using C-18 columns with a mobile phase of methanol:10 mM potassium phosphate (pH 7.2):1 M tetrabutylammonium dihydrogen phosphate (in water) (83:16:1, v/v/v). The o-phthalaldehyde derivative of sphingosine 1-phosphate was reasonably stable (t(1/2) > or = 18 h) when EDTA was present and could be detected in picomole amounts. The HPLC retention time of the sphingoid base 1-phosphates could be shifted by adjusting the mobile phase to pH 5.5, which is useful in separating overlapping compounds (such as sphingosine 1-phosphate and 4-D-hydroxysphinganine) and in confirming the identity of sphingoid base 1-phosphates in biological samples. The extraction procedure and HPLC method facilitated assays of sphingosine kinase with different sphingoid bases as substrates and/or inhibitors and enabled the quantitation of sphingoid base 1-phosphates in human plasma, serum, and platelets as well as in strains of Saccharomyces cerevisae with mutations in sphingolipid metabolism.

Authors
Caligan, TB; Peters, K; Ou, J; Wang, E; Saba, J; Merrill, AH
MLA Citation
Caligan, TB, Peters, K, Ou, J, Wang, E, Saba, J, and Merrill, AH. "A high-performance liquid chromatographic method to measure sphingosine 1-phosphate and related compounds from sphingosine kinase assays and other biological samples." Anal Biochem 281.1 (May 15, 2000): 36-44.
PMID
10847608
Source
pubmed
Published In
Analytical Biochemistry
Volume
281
Issue
1
Publish Date
2000
Start Page
36
End Page
44
DOI
10.1006/abio.2000.4555

Analysis of sphingoid bases and sphingoid base 1-phosphates by high-performance liquid chromatography.

Authors
Merrill, AH; Caligan, TB; Wang, E; Peters, K; Ou, J
MLA Citation
Merrill, AH, Caligan, TB, Wang, E, Peters, K, and Ou, J. "Analysis of sphingoid bases and sphingoid base 1-phosphates by high-performance liquid chromatography." Methods Enzymol 312 (2000): 3-9.
PMID
11070857
Source
pubmed
Published In
Methods in Enzymology
Volume
312
Publish Date
2000
Start Page
3
End Page
9
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