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Wang, Xiaofei

Overview:

Design and Analysis of Clinical Trials
Nonparametric and Semiparametric Methods
Survival Analysis
Statistical Methods for Diagnostic and Predictive Medicine
Biomarker Discovery and Validation
Health Outcomes Research

Positions:

Associate Professor of Biostatistics and Bioinformatics

Biostatistics & Bioinformatics
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 2003

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

Graduate Research Assistant, Computer Sciences

University of North Carolina at Chapel Hill

Graduate Research Assistant, Biostatistics

University of North Carolina at Chapel Hill

Grants:

Administrative Core

Administered By
Biostatistics & Bioinformatics
AwardedBy
University of North Carolina - Chapel Hill
Role
Co Investigator
Start Date
May 15, 2015
End Date
March 31, 2017

Methods for Discovery and Analysis of Dynamic Treatment Regimes

Administered By
Biostatistics & Bioinformatics
AwardedBy
University of North Carolina - Chapel Hill
Role
Investigator
Start Date
May 15, 2015
End Date
March 31, 2017

Innovative Biomarker-Integrated Clinical Trial Design and Analysis

Administered By
Biostatistics & Bioinformatics
AwardedBy
University of North Carolina - Chapel Hill
Role
Principal Investigator
Start Date
May 15, 2015
End Date
March 31, 2017

National Clinical Trials Network - Network Group Statistics and DMCs

Administered By
Duke Cancer Institute
AwardedBy
Mayo Clinic
Role
Statistician
Start Date
April 17, 2014
End Date
February 28, 2017

Translational meta-analysis for elderly lung cancer patients

Administered By
Biostatistics & Bioinformatics
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
August 01, 2013
End Date
May 31, 2016

Cancer and Leukemia Group B Statistical Center

Administered By
Duke Cancer Institute
AwardedBy
National Institutes of Health
Role
Statistician
Start Date
December 01, 1982
End Date
September 30, 2010

Semiparametric ROC Curve Regression for Cancer Screening Studies

Administered By
Biostatistics & Bioinformatics
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 27, 2007
End Date
August 31, 2010
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Publications:

The Role of Extent of Surgical Resection and Lymph Node Assessment for Clinical Stage I Pulmonary Lepidic Adenocarcinoma: An Analysis of 1991 Patients.

This study examined the association of extent of lung resection, pathologic nodal evaluation, and survival for patients with clinical stage I (cT1-2N0M0) adenocarcinoma with lepidic histologic features in the National Cancer Data Base.The association between extent of surgical resection and long-term survival for patients in the National Cancer Data Base with clinical stage I lepidic adenocarcinoma who underwent lobectomy or sublobar resection was evaluated using Kaplan-Meier and Cox proportional hazards regression analyses.Of the 1991 patients with cT1-2N0M0 lepidic adenocarcinoma who met the study criteria, 1544 underwent lobectomy and 447 underwent sublobar resection. Patients treated with sublobar resection were older, more likely to be female, and had higher Charlson/Deyo comorbidity scores, but they had smaller tumors and lower T status. Of the patients treated with lobectomy, 6% (n = 92) were upstaged because of positive nodal disease, with a median of seven lymph nodes sampled (interquartile range 4-10). In an analysis of the entire cohort, lobectomy was associated with a significant survival advantage over sublobar resection in univariate analysis (median survival 9.2 versus 7.5 years, p = 0.022, 5-year survival 70.5% versus 67.8%) and after multivariable adjustment (hazard ratio = 0.81, 95% confidence interval: 0.68-0.95, p = 0.011). However, lobectomy was no longer independently associated with improved survival when compared with sublobar resection (hazard ratio = 0.99, 95% confidence interval: 0.77-1.27, p = 0.905) in a multivariable analysis of a subset of patients in which only those patients who had undergone a sublobar resection including lymph node sampling were compared with patients treated with lobectomy.Surgeons treating patients with stage I lung adenocarcinoma with lepidic features should cautiously utilize sublobar resection rather than lobectomy, and they must always perform adequate pathologic lymph node evaluation.

Authors
Cox, ML; Yang, C-FJ; Speicher, PJ; Anderson, KL; Fitch, ZW; Gu, L; Davis, RP; Wang, X; D'Amico, TA; Hartwig, MG; Harpole, DH; Berry, MF
MLA Citation
Cox, ML, Yang, C-FJ, Speicher, PJ, Anderson, KL, Fitch, ZW, Gu, L, Davis, RP, Wang, X, D'Amico, TA, Hartwig, MG, Harpole, DH, and Berry, MF. "The Role of Extent of Surgical Resection and Lymph Node Assessment for Clinical Stage I Pulmonary Lepidic Adenocarcinoma: An Analysis of 1991 Patients." Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (January 7, 2017).
PMID
28082103
Source
epmc
Published In
Journal of Thoracic Oncology
Publish Date
2017
DOI
10.1016/j.jtho.2017.01.003

Patterns of Distant Metastases After Surgical Management of Non-Small-cell Lung Cancer.

Patients with limited metastases, oligometastases (OMs), might have improved outcomes compared with patients with widespread distant metastases (DMs). The incidence and behavior of OMs from non-small-cell lung cancer (NSCLC) need further characterization.The medical records of patients who had undergone surgery for stage I-III NSCLC from 1995 to 2009 were retrospectively reviewed. All information pertaining to development of the first metastatic progression was recorded and analyzed. Patients with DMs were categorized into OMs (1-3 lesions potentially amenable to local therapy) and DM subgroups.Of 1719 patients reviewed, 368 (21%) developed DMs with a median follow-up period of 39 months. A single lesion was diagnosed in 115 patients (31%) and 69 (19%) had 2 to 3 lesions (50% oligometastatic). The median survival from the DM diagnosis for oligometastatic and diffuse DM was 12.4 and 6.1 months, respectively (hazard ratio, 0.54; 95% confidence interval, 0.42-0.68; P < .001). Patients with a single metastasis had the longest median survival at 14.7 months. Younger age, OM, the use of chemotherapy for the primary tumor, and DM detection by surveillance imaging were independently associated with improved survival.DMs and OMs are common in surgically managed NSCLC. Overall survival appears to be prolonged with OM.

Authors
Torok, JA; Gu, L; Tandberg, DJ; Wang, X; Harpole, DH; Kelsey, CR; Salama, JK
MLA Citation
Torok, JA, Gu, L, Tandberg, DJ, Wang, X, Harpole, DH, Kelsey, CR, and Salama, JK. "Patterns of Distant Metastases After Surgical Management of Non-Small-cell Lung Cancer." Clinical lung cancer 18.1 (January 2017): e57-e70.
PMID
27477488
Source
epmc
Published In
Clinical lung cancer
Volume
18
Issue
1
Publish Date
2017
Start Page
e57
End Page
e70
DOI
10.1016/j.cllc.2016.06.011

Reply to T.-H. Wang et al.

Authors
Yang, C-FJ; Chan, DY; Wang, X; D'Amico, TA; Harpole, DH; Berry, MF
MLA Citation
Yang, C-FJ, Chan, DY, Wang, X, D'Amico, TA, Harpole, DH, and Berry, MF. "Reply to T.-H. Wang et al." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 35.1 (January 2017): 118-120.
PMID
28034078
Source
epmc
Published In
Journal of Clinical Oncology
Volume
35
Issue
1
Publish Date
2017
Start Page
118
End Page
120

Value of Propensity Score Matching to Study Surgical Outcomes.

Authors
Hwang, ES; Wang, X
MLA Citation
Hwang, ES, and Wang, X. "Value of Propensity Score Matching to Study Surgical Outcomes." Annals of surgery (December 30, 2016).
PMID
28045717
Source
epmc
Published In
Annals of Surgery
Publish Date
2016
DOI
10.1097/sla.0000000000002125

Small Cell Lung Cancer Exhibits Frequent Inactivating Mutations in the Histone Methyltransferase KMT2D/MLL2: CALGB 151111 (Alliance).

SCLC is a lethal neuroendocrine tumor type that is highly prone to metastasis. There is an urgency to understand the mutated genes that promote SCLC, as there are no approved targeted therapies yet available. SCLC is rarely resected, limiting the number of samples available for genomic analyses of somatic mutations.To identify potential driver mutations in human SCLC we sequenced the whole exomes of 18 primary SCLCs and seven cell lines along with matched normal controls. We extended these data by resequencing a panel of genes across 40 primary SCLCs and 48 cell lines.We report frequent mutations in the lysine methyltransferase 2D gene (KMT2D) (also known as MLL2), a key regulator of transcriptional enhancer function. KMT2D exhibited truncating nonsense/frameshift/splice site mutations in 8% of SCLC tumors and 17% of SCLC cell lines. We found that KMT2D mutation in human SCLC cell lines was associated with reduced lysine methyltransferase 2D protein levels and reduced monomethylation of histone H3 lysine 4, a mark associated with transcriptional enhancers. We also found mutations in other genes associated with transcriptional enhancer control, including CREB binding protein gene (CREBBP), E1A binding protein p300 gene (EP300), and chromodomain helicase DNA binding protein 7 gene (CHD7), and we report mutations in additional chromatin remodeling genes such as polybromo 1 gene (PBRM1).These data indicate that KMT2D is one of the major mutated genes in SCLC, and they point to perturbation of transcriptional enhancer control as potentially contributing to SCLC.

Authors
Augert, A; Zhang, Q; Bates, B; Cui, M; Wang, X; Wildey, G; Dowlati, A; MacPherson, D
MLA Citation
Augert, A, Zhang, Q, Bates, B, Cui, M, Wang, X, Wildey, G, Dowlati, A, and MacPherson, D. "Small Cell Lung Cancer Exhibits Frequent Inactivating Mutations in the Histone Methyltransferase KMT2D/MLL2: CALGB 151111 (Alliance)." Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (December 19, 2016).
PMID
28007623
Source
epmc
Published In
Journal of Thoracic Oncology
Publish Date
2016
DOI
10.1016/j.jtho.2016.12.011

Impact of thoracic radiotherapy timing in limited-stage small-cell lung cancer: usefulness of the individual patient data meta-analysis.

Chemotherapy (CT) combined with radiotherapy is the standard treatment of 'limited-stage' small-cell lung cancer. However, controversy persists over the optimal timing of thoracic radiotherapy and CT.We carried out a meta-analysis of individual patient data in randomized trials comparing earlier versus later radiotherapy, or shorter versus longer radiotherapy duration, as defined in each trial. We combined the results from trials using the stratified log-rank test to calculate pooled hazard ratios (HRs). The primary outcome was overall survival.Twelve trials with 2668 patients were eligible. Data from nine trials comprising 2305 patients were available for analysis. The median follow-up was 10 years. When all trials were analysed together, 'earlier or shorter' versus 'later or longer' thoracic radiotherapy did not affect overall survival. However, the HR for overall survival was significantly in favour of 'earlier or shorter' radiotherapy among trials with a similar proportion of patients who were compliant with CT (defined as having received 100% or more of the planned CT cycles) in both arms (HR 0.79, 95% CI 0.69-0.91), and in favour of 'later or longer' radiotherapy among trials with different rates of CT compliance (HR 1.19, 1.05-1.34, interaction test, P < 0.0001). The absolute gain between 'earlier or shorter' versus 'later or longer' thoracic radiotherapy in 5-year overall survival for similar and for different CT compliance trials was 7.7% (95% CI 2.6-12.8%) and -2.2% (-5.8% to 1.4%), respectively. However, 'earlier or shorter' thoracic radiotherapy was associated with a higher incidence of severe acute oesophagitis than 'later or longer' radiotherapy.'Earlier or shorter' delivery of thoracic radiotherapy with planned CT significantly improves 5-year overall survival at the expense of more acute toxicity, especially oesophagitis.

Authors
De Ruysscher, D; Lueza, B; Le Péchoux, C; Johnson, DH; O'Brien, M; Murray, N; Spiro, S; Wang, X; Takada, M; Lebeau, B; Blackstock, W; Skarlos, D; Baas, P; Choy, H; Price, A; Seymour, L; Arriagada, R; Pignon, J-P
MLA Citation
De Ruysscher, D, Lueza, B, Le Péchoux, C, Johnson, DH, O'Brien, M, Murray, N, Spiro, S, Wang, X, Takada, M, Lebeau, B, Blackstock, W, Skarlos, D, Baas, P, Choy, H, Price, A, Seymour, L, Arriagada, R, and Pignon, J-P. "Impact of thoracic radiotherapy timing in limited-stage small-cell lung cancer: usefulness of the individual patient data meta-analysis." Annals of oncology : official journal of the European Society for Medical Oncology 27.10 (October 2016): 1818-1828. (Review)
PMID
27436850
Source
epmc
Published In
Annals of Oncology
Volume
27
Issue
10
Publish Date
2016
Start Page
1818
End Page
1828
DOI
10.1093/annonc/mdw263

Enrollment Trends and Disparity Among Patients With Lung Cancer in National Clinical Trials, 1990 to 2012.

Under-representation of elderly, women, and racial/ethnic minority patients with cancer in clinical trials is of national concern. The goal of this study was to characterize enrollment trends and disparities by age, sex, and race/ethnicity in lung cancer trials.We analyzed data for 23,006 National Cancer Institute cooperative group lung cancer trial participants and 578,476 patients with lung cancer from the SEER registry from 1990 to 2012. The enrollment disparity difference (EDD) and enrollment disparity ratio (EDR) were calculated on the basis of the proportion of each subgroup in the trial population and the US lung cancer population. Annual percentage changes (APCs) in the subgroup proportions in each population were compared over time.Enrollment disparity for patients ≥ 70 years of age with non-small-cell lung cancer improved from 1990 to 2012 (test of parallelism, P = .020), with a remaining EDD of 0.22 (95% CI, 0.19 to 0.25) and EDR of 1.65 (95% CI, 1.51 to 1.82) in 2010 to 2012. No improvement was seen for elderly patients with small-cell lung cancer (SCLC), with an APC of 0.20 (P = .714) among trial participants, despite a rising proportion of elderly patients with SCLC in the US population (APC, 0.32; P = .020). Enrollment disparity for women with lung cancer improved overall, with the gap closing by 2012 (EDD, 0.03 [95% CI, 0.00 to 0.06]; EDR, 1.07 [95% CI, 1.00 to 1.16]). Enrollment disparities persisted without significant improvement for elderly women, blacks, Asians/Pacific Islanders, and Hispanics.Under-representation in lung cancer trials improved significantly from 1990 to 2012 for elderly patients with non-small-cell lung cancer and for women, but ongoing efforts to improve the enrollment of elderly patients with SCLC and minorities are needed. Our study highlights the importance of addressing enrollment disparities by demographic and disease subgroups to better target under-represented groups of patients with lung cancer.

Authors
Pang, HH; Wang, X; Stinchcombe, TE; Wong, ML; Cheng, P; Ganti, AK; Sargent, DJ; Zhang, Y; Hu, C; Mandrekar, SJ; Redman, MW; Manola, JB; Schilsky, RL; Cohen, HJ; Bradley, JD; Adjei, AA; Gandara, D; Ramalingam, SS; Vokes, EE
MLA Citation
Pang, HH, Wang, X, Stinchcombe, TE, Wong, ML, Cheng, P, Ganti, AK, Sargent, DJ, Zhang, Y, Hu, C, Mandrekar, SJ, Redman, MW, Manola, JB, Schilsky, RL, Cohen, HJ, Bradley, JD, Adjei, AA, Gandara, D, Ramalingam, SS, and Vokes, EE. "Enrollment Trends and Disparity Among Patients With Lung Cancer in National Clinical Trials, 1990 to 2012." Journal of clinical oncology : official journal of the American Society of Clinical Oncology (September 19, 2016).
PMID
27646951
Source
epmc
Published In
Journal of Clinical Oncology
Publish Date
2016

Cancer Clinical Trials Current and Controversial Issues in Design and Analysis

The book covers topics that are often perplexing and sometimes controversial in cancer clinical trials. Most of the issues addressed are also important for clinical trials in other settings.

Authors
George, SL; Wang, X; Pang, H
MLA Citation
George, SL, Wang, X, and Pang, H. Cancer Clinical Trials Current and Controversial Issues in Design and Analysis. CRC Press, August 3, 2016.
Source
google-books
Publish Date
2016

Toxicity of definitive and post-operative radiation following ipilimumab in non-small cell lung cancer.

To determine the feasibility and toxicity of radiation therapy, delivered either as definitive treatment or following surgery, following neo-adjuvant immune checkpoint inhibition for locally advanced NSCLC sixteen patients who received neo-adjuvant chemotherapy including ipilimumab as part of a phase II study were identified. Patients were analyzed by intent of radiation and toxicity graded based on CTCAE 4.0. There were seven patients identified who received definitive radiation and nine who received post-operative radiation. There was no grade 3 or greater toxicity in the definitive treatment group although one patient stopped treatment early due to back pain secondary to progression outside of the treatment field. In the post-operative treatment group, one patient required a one week break due to grade 2 odynophagia and no grade 3 or greater toxicity was observed. In this study of radiation as definitive or post-operative treatment following neo-adjuvant chemotherapy including ipilimumab for locally advanced NSCLC was feasible and well tolerated with limited toxicity.

Authors
Boyer, MJ; Gu, L; Wang, X; Kelsey, CR; Yoo, DS; Onaitis, MW; Dunphy, FR; Crawford, J; Ready, NE; Salama, JK
MLA Citation
Boyer, MJ, Gu, L, Wang, X, Kelsey, CR, Yoo, DS, Onaitis, MW, Dunphy, FR, Crawford, J, Ready, NE, and Salama, JK. "Toxicity of definitive and post-operative radiation following ipilimumab in non-small cell lung cancer." Lung cancer (Amsterdam, Netherlands) 98 (August 2016): 76-78.
PMID
27393510
Source
epmc
Published In
Lung Cancer
Volume
98
Publish Date
2016
Start Page
76
End Page
78
DOI
10.1016/j.lungcan.2016.05.014

Time-dependent classification accuracy curve under marker-dependent sampling.

Evaluating the classification accuracy of a candidate biomarker signaling the onset of disease or disease status is essential for medical decision making. A good biomarker would accurately identify the patients who are likely to progress or die at a particular time in the future or who are in urgent need for active treatments. To assess the performance of a candidate biomarker, the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) are commonly used. In many cases, the standard simple random sampling (SRS) design used for biomarker validation studies is costly and inefficient. In order to improve the efficiency and reduce the cost of biomarker validation, marker-dependent sampling (MDS) may be used. In a MDS design, the selection of patients to assess true survival time is dependent on the result of a biomarker assay. In this article, we introduce a nonparametric estimator for time-dependent AUC under a MDS design. The consistency and the asymptotic normality of the proposed estimator is established. Simulation shows the unbiasedness of the proposed estimator and a significant efficiency gain of the MDS design over the SRS design.

Authors
Zhu, Z; Wang, X; Saha-Chaudhuri, P; Kosinski, AS; George, SL
MLA Citation
Zhu, Z, Wang, X, Saha-Chaudhuri, P, Kosinski, AS, and George, SL. "Time-dependent classification accuracy curve under marker-dependent sampling." Biometrical journal. Biometrische Zeitschrift 58.4 (July 2016): 974-992.
PMID
27119599
Source
epmc
Published In
Biometrical Journal
Volume
58
Issue
4
Publish Date
2016
Start Page
974
End Page
992
DOI
10.1002/bimj.201500171

Long-term outcomes after lobectomy for non-small cell lung cancer when unsuspected pN2 disease is found: A National Cancer Data Base analysis.

There are few studies evaluating whether to proceed with planned resection when a patient with non-small cell lung cancer (NSCLC) unexpectedly is found to have N2 disease at the time of thoracoscopy or thoracotomy. To help guide management of this clinical scenario, we evaluated outcomes for patients who were upstaged to pN2 after lobectomy without induction therapy using the National Cancer Data Base (NCDB).Survival of NSCLC patients treated with lobectomy for clinically unsuspected mediastinal nodal disease (cT1-cT3 cN0-cN1, pN2 disease) from 1998-2006 in the NCDB was compared with "suspected" N2 disease patients (cT1-cT3 cN2) who were treated with chemotherapy with or without radiation followed by lobectomy, using matched analysis based on propensity scores.Unsuspected pN2 disease was found in 4.4% of patients (2047 out of 46,691) who underwent lobectomy as primary therapy for cT1-cT3 cN0-cN1 NSCLC. The 5-year survival was 42%, 36%, 21%, and 28% for patients who underwent adjuvant chemotherapy (n = 385), chemoradiation (n = 504), radiation (n = 300), and no adjuvant therapy (n = 858), respectively. Five-year survival of the entire unsuspected pN2 cohort was worse than survival of 2302 patients who were treated with lobectomy after induction therapy for clinical N2 disease (30% vs 40%; P < .001), although no significant difference in 5-year survival was found in a matched-analysis of 655 patients from each group (37% vs 37%; P = .95).This population-based analysis suggests that, in the setting of unsuspected pN2 NSCLC, proceeding with lobectomy does not appear to compromise outcomes if adjuvant chemotherapy with or without radiation therapy can be administered following surgery.

Authors
Yang, C-FJ; Kumar, A; Gulack, BC; Mulvihill, MS; Hartwig, MG; Wang, X; D'Amico, TA; Berry, MF
MLA Citation
Yang, C-FJ, Kumar, A, Gulack, BC, Mulvihill, MS, Hartwig, MG, Wang, X, D'Amico, TA, and Berry, MF. "Long-term outcomes after lobectomy for non-small cell lung cancer when unsuspected pN2 disease is found: A National Cancer Data Base analysis." The Journal of thoracic and cardiovascular surgery 151.5 (May 2016): 1380-1388.
PMID
26874598
Source
epmc
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
151
Issue
5
Publish Date
2016
Start Page
1380
End Page
1388
DOI
10.1016/j.jtcvs.2015.12.028

Detection of Occult Micrometastases in Patients With Clinical Stage I Non-Small-Cell Lung Cancer: A Prospective Analysis of Mature Results of CALGB 9761 (Alliance).

Outcomes after resection of stage I non-small-cell lung cancer (NSCLC) are variable, potentially due to undetected occult micrometastases (OM). Cancer and Leukemia Group B 9761 was a prospectively designed study aimed at determining the prognostic significance of OM.Between 1997 and 2002, 502 patients with suspected clinical stage I (T1-2N0M0) NSCLC were prospectively enrolled at 11 institutions. Primary tumor and lymph nodes (LNs) were collected and sent to a central site for molecular analysis. Both were assayed for OM using immunohistochemistry (IHC) for cytokeratin (AE1/AE3) and real-time reverse transcriptase polymerase chain reaction (RT-PCR) for carcinoembryonic antigen.Four hundred eighty-nine of the 502 enrolled patients underwent complete surgical staging. Three hundred four patients (61%) had pathologic stage I NSCLC (T1, 58%; T2, 42%) and were included in the final analysis. Fifty-six percent had adenocarcinomas, 34% had squamous cell carcinomas, and 10% had another histology. LNs from 298 patients were analyzed by IHC; 41 (14%) were IHC-positive (42% in N1 position, 58% in N2 position). Neither overall survival (OS) nor disease-free survival was associated with IHC positivity; however, patients who had IHC-positive N2 LNs had statistically significantly worse survival rates (hazard ratio, 2.04, P = .017). LNs from 256 patients were analyzed by RT-PCR; 176 (69%) were PCR-positive (52% in N1 position, 48% in N2 position). Neither OS nor disease-free survival was associated with PCR positivity.NSCLC tumor markers can be detected in histologically negative LNs by AE1/AE3 IHC and carcinoembryonic antigen RT-PCR. In this prospective, multi-institutional trial, the presence of OM by IHC staining in N2 LNs of patients with NSCLC correlated with decreased OS. The clinical significance of this warrants further investigation.

Authors
Martin, LW; D'Cunha, J; Wang, X; Herzan, D; Gu, L; Abraham, N; Demmy, TL; Detterbeck, FC; Groth, SS; Harpole, DH; Krasna, MJ; Kernstine, K; Kohman, LJ; Patterson, GA; Sugarbaker, DJ; Vollmer, RT; Maddaus, MA; Kratzke, RA
MLA Citation
Martin, LW, D'Cunha, J, Wang, X, Herzan, D, Gu, L, Abraham, N, Demmy, TL, Detterbeck, FC, Groth, SS, Harpole, DH, Krasna, MJ, Kernstine, K, Kohman, LJ, Patterson, GA, Sugarbaker, DJ, Vollmer, RT, Maddaus, MA, and Kratzke, RA. "Detection of Occult Micrometastases in Patients With Clinical Stage I Non-Small-Cell Lung Cancer: A Prospective Analysis of Mature Results of CALGB 9761 (Alliance)." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 34.13 (May 2016): 1484-1491.
PMID
26926677
Source
epmc
Published In
Journal of Clinical Oncology
Volume
34
Issue
13
Publish Date
2016
Start Page
1484
End Page
1491
DOI
10.1200/jco.2015.63.4543

Role of Adjuvant Therapy in a Population-Based Cohort of Patients With Early-Stage Small-Cell Lung Cancer.

Data on optimal adjuvant therapy after complete resection of small-cell lung cancer (SCLC) are limited, and in particular, there have been no studies evaluating the role of adjuvant chemotherapy, with or without prophylactic cranial irradiation, relative to no adjuvant therapy for stage T1-2N0M0 SCLC. This National Cancer Data Base analysis was performed to determine the potential benefits of adjuvant chemotherapy with and without prophylactic cranial irradiation in patients who undergo complete resection for early-stage small-cell lung cancer.Overall survival of patients with pathologic T1-2N0M0 SCLC who underwent complete resection in the National Cancer Data Base from 2003 to 2011, stratified by adjuvant therapy regimen, was evaluated using Kaplan-Meier and Cox proportional hazards analysis. Patients treated with induction therapy and those who died within 30 days of surgery were excluded from analysis.Of 1,574 patients who had pT1-2N0M0 SCLC during the study period, 954 patients (61%) underwent complete R0 resection with a 5-year survival of 47%. Adjuvant therapy was administered to 59% of patients (n = 566), including chemotherapy alone (n = 354), chemoradiation (n = 190, including 99 patients who underwent cranial irradiation), and radiation alone (n = 22). Compared with surgery alone, adjuvant chemotherapy with or without radiation was associated with significantly improved survival. In addition, multivariable Cox modeling demonstrated that treatment with adjuvant chemotherapy (hazard ratio [HR], 0.78; 95% CI, 0.63 to 0.95) or chemotherapy with radiation directed at the brain (HR, 0.52; 95% CI, 0.36 to 0.75) was associated with improved survival when compared with no adjuvant therapy.Patients with pT1-2N0M0 SCLC treated with surgical resection alone have worse outcomes than those who undergo resection with adjuvant chemotherapy alone or chemotherapy with cranial irradiation.

Authors
Yang, C-FJ; Chan, DY; Speicher, PJ; Gulack, BC; Wang, X; Hartwig, MG; Onaitis, MW; Tong, BC; D'Amico, TA; Berry, MF; Harpole, DH
MLA Citation
Yang, C-FJ, Chan, DY, Speicher, PJ, Gulack, BC, Wang, X, Hartwig, MG, Onaitis, MW, Tong, BC, D'Amico, TA, Berry, MF, and Harpole, DH. "Role of Adjuvant Therapy in a Population-Based Cohort of Patients With Early-Stage Small-Cell Lung Cancer." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 34.10 (April 2016): 1057-1064.
PMID
26786925
Source
epmc
Published In
Journal of Clinical Oncology
Volume
34
Issue
10
Publish Date
2016
Start Page
1057
End Page
1064
DOI
10.1200/jco.2015.63.8171

Traveling to a High-volume Center is Associated With Improved Survival for Patients With Esophageal Cancer.

An association between volume and outcomes has been observed for esophagectomy, though little is known about why or how patients choose low- or high-volume centers. The purpose of this study was to evaluate how travel burden and hospital volume influence treatment and outcomes of patients with locally advanced esophageal cancer.Predictors of receiving esophagectomy for patients with T1-3N1M0 mid or distal esophageal cancer in the National Cancer Data Base from 2006 to 2011 were identified using multivariable logistic regression. Survival was compared using propensity score-matched groups: patients in the bottom quartile of travel distance who underwent treatment at low-volume facilities (Local) and patients in the top quartile of travel distance who underwent treatment at high-volume facilities (Travel).Of 4979 patients who met inclusion criteria, we identified 867 Local patients who traveled 2.7 [interquartile range (IQR): 1.6-4 miles] miles to centers that treated 2.6 (IQR: 1.9-3.3) esophageal cancers per year, and 317 Travel patients who traveled 107.1 (IQR: 65-247) miles to centers treating 31.9 (IQR: 30.9-38.5) cases. Travel patients were more likely to undergo esophagectomy (67.8% vs 42.9%, P < 0.001) and had significantly better 5-year survival (39.8% vs 20.6%, P < 0.001) than Local patients.Patients who travel longer distances to high-volume centers have significantly different treatment and better outcomes than patients who stay close to home at low-volume centers. Strategies that support patient travel for treatment at high-volume centers may improve esophageal cancer outcomes.

Authors
Speicher, PJ; Englum, BR; Ganapathi, AM; Wang, X; Hartwig, MG; D'Amico, TA; Berry, MF
MLA Citation
Speicher, PJ, Englum, BR, Ganapathi, AM, Wang, X, Hartwig, MG, D'Amico, TA, and Berry, MF. "Traveling to a High-volume Center is Associated With Improved Survival for Patients With Esophageal Cancer." Annals of surgery (March 15, 2016).
PMID
26982688
Source
epmc
Published In
Annals of Surgery
Publish Date
2016

Positive Interaction between Prophylactic Cranial Irradiation and Maintenance Sunitinib for Untreated Extensive-Stage Small Cell Lung Cancer Patients After Standard Chemotherapy: A Secondary Analysis of CALGB 30504 (ALLIANCE).

Prophylactic cranial irradiation (PCI) has become a standard option for patients with extensive-stage small cell lung cancer (ES-SCLC). The Cancer and Leukemia Group B 30504 trial was a randomized phase II study of the effect of sunitinib versus placebo in ES-SCLC patients responding to platinum-based systemic therapy. The study required preenrollment brain imaging. PCI was provided at the discretion of treating physicians. We performed a secondary analysis of the Cancer and Leukemia Group B trial to determine the impact of PCI on patients with ES-SCLC.Fisher's exact test and the Wilcoxon rank-sum test were conducted to identify the differences between patients receiving PCI and patients not receiving PCI. Kaplan-Meier analyses described progression-free survival (PFS) and overall survival (OS) for patients in the PCI and non-PCI groups.A total of 85 patients received maintenance therapy (41 received placebo and 44 received sunitinib). Patient characteristics were balanced between the PCI and non-PCI groups. The patients receiving PCI plus sunitinib had a nonsignificant 2.7-month improvement in PFS (5.0 months versus 2.3 months, p = 0.14, hazard risk [HR] = 0.62, 95% confidence interval [CI]: 0.33-1.18) trending toward improved OS (8.9 months versus 5.4 months, p = 0.053, HR = 0.47, 95% CI: 0.22-1.03). PCI was associated with a trend toward improved median PFS (2.9 months versus 2.2 months, p = 0.096, HR = 0.69, 95% CI: 0.45-1.07) but not median OS (8.3 months in the PCI group versus 8.7 months in the non-PCI group, p = 0.76, HR = 1.07, 95% CI: 0.67-1.71). The patients receiving placebo had no improvement in PFS or OS with PCI.Trends toward improved PFS and OS were seen in patients receiving PCI and sunitinib, thus supporting the need for further prospective research evaluating the integration of maintenance systemic therapy and PCI for patients with ES-SCLC. Improved outcomes for patients with ES-SCLC after induction chemotherapy may require PCI, thoracic radiotherapy, and maintenance systemic therapy to achieve control of both intracranial and extracranial disease.

Authors
Salama, JK; Gu, L; Wang, X; Pang, HH; Bogart, JA; Crawford, J; Schild, SE; Vokes, EE; Ready, NE
MLA Citation
Salama, JK, Gu, L, Wang, X, Pang, HH, Bogart, JA, Crawford, J, Schild, SE, Vokes, EE, and Ready, NE. "Positive Interaction between Prophylactic Cranial Irradiation and Maintenance Sunitinib for Untreated Extensive-Stage Small Cell Lung Cancer Patients After Standard Chemotherapy: A Secondary Analysis of CALGB 30504 (ALLIANCE)." Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 11.3 (March 2016): 361-369.
PMID
26723241
Source
epmc
Published In
Journal of Thoracic Oncology
Volume
11
Issue
3
Publish Date
2016
Start Page
361
End Page
369
DOI
10.1016/j.jtho.2015.11.001

Risk calculators are useful but....

Authors
Wang, X; Berry, MF
MLA Citation
Wang, X, and Berry, MF. "Risk calculators are useful but.." The Journal of thoracic and cardiovascular surgery 151.3 (March 2016): 706-707.
PMID
26896356
Source
epmc
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
151
Issue
3
Publish Date
2016
Start Page
706
End Page
707
DOI
10.1016/j.jtcvs.2015.09.058

Statistical aspect of translational and correlative studies in clinical trials.

In this article, we describe statistical issues related to the conduct of translational and correlative studies in cancer clinical trials. In the era of personalized medicine, proper biomarker discovery and validation is crucial for producing groundbreaking research. In order to carry out the framework outlined in this article, a team effort between oncologists and statisticians is the key for success.

Authors
Pang, H; Wang, X
MLA Citation
Pang, H, and Wang, X. "Statistical aspect of translational and correlative studies in clinical trials." Chinese clinical oncology 5.1 (February 2016): 11-.
PMID
26932435
Source
epmc
Published In
Chinese clinical oncology
Volume
5
Issue
1
Publish Date
2016
Start Page
11
DOI
10.3978/j.issn.2304-3865.2014.07.04

Sublobar Resection for Clinical Stage IA Non-small-cell Lung Cancer in the United States.

This study evaluated the use of lobectomy and sublobar resection for clinical stage IA non-small-cell lung cancer (NSCLC) in the National Cancer Data Base (NCDB).The NCDB from 2003 to 2011 was analyzed to determine factors associated with the use of a sublobar resection versus a lobectomy for the treatment of clinical stage IA NSCLC. Overall survival was assessed using the Kaplan-Meier method and Cox proportional hazard modeling.Among 39,403 patients included for analysis, 29,736 (75.5%) received a lobectomy and 9667 (24.5%) received a sublobar resection: 84.7% wedge resection (n = 8192) and 15.3% segmental resection (n = 1475). Lymph node evaluation was not performed in 2788 (28.8%) of sublobar resection patients, and 7298 (75.5%) of sublobar resections were for tumors ≤ 2 cm. After multivariable logistic regression, older age, higher Charlson-Deyo comorbidity scores, smaller tumor size, and treatment at lower-volume institutions were associated with sublobar resection (all P < .001). Overall, lobectomy was associated with significantly improved 5-year survival compared to sublobar resection (66.2% vs. 51.2%; P < .001, adjusted hazard ratio 0.66; P < .001). However among sublobar resection patients, nodal sampling was associated with significantly better 5-year survival (58.2% vs. 46.4%; P < .001).Despite adjustment for patient and tumor related characteristics, a sublobar resection is associated with significantly reduced long-term survival compared to a formal surgical lobectomy among patients with NSCLC, even for stage 1A tumors. For patients who cannot tolerate lobectomy and who are treated with sublobar resection, lymph node evaluation is essential to help guide further treatment.

Authors
Speicher, PJ; Gu, L; Gulack, BC; Wang, X; D'Amico, TA; Hartwig, MG; Berry, MF
MLA Citation
Speicher, PJ, Gu, L, Gulack, BC, Wang, X, D'Amico, TA, Hartwig, MG, and Berry, MF. "Sublobar Resection for Clinical Stage IA Non-small-cell Lung Cancer in the United States." Clinical lung cancer 17.1 (January 2016): 47-55.
PMID
26602547
Source
epmc
Published In
Clinical lung cancer
Volume
17
Issue
1
Publish Date
2016
Start Page
47
End Page
55
DOI
10.1016/j.cllc.2015.07.005

A Multi-state Model for Designing Clinical Trials for Testing Overall Survival Allowing for Crossover after Progression.

In designing a clinical trial for comparing two or more treatments with respect to overall survival (OS), a proportional hazards assumption is commonly made. However, in many cancer clinical trials, patients pass through various disease states prior to death and because of this may receive treatments other than originally assigned. For example, patients may crossover from the control treatment to the experimental treatment at progression. Even without crossover, the survival pattern after progression may be very different than the pattern prior to progression. The proportional hazards assumption will not hold in these situations and the design power calculated on this assumption will not be correct. In this paper we describe a simple and intuitive multi-state model allowing for progression, death before progression, post-progression survival and crossover after progression and apply this model to the design of clinical trials for comparing the OS of two treatments. For given values of the parameters of the multi-state model, we simulate the required number of deaths to achieve a specified power and the distribution of time required to achieve the requisite number of deaths. The results may be quite different from those derived using the usual PH assumption.

Authors
Xia, F; George, SL; Wang, X
MLA Citation
Xia, F, George, SL, and Wang, X. "A Multi-state Model for Designing Clinical Trials for Testing Overall Survival Allowing for Crossover after Progression." Statistics in biopharmaceutical research 8.1 (January 2016): 12-21.
PMID
27239255
Source
epmc
Published In
Statistics in Biopharmaceutical Research
Volume
8
Issue
1
Publish Date
2016
Start Page
12
End Page
21

Adding radiation to induction chemotherapy does not improve survival of patients with operable clinical N2 non-small cell lung cancer.

Radiotherapy is commonly used in induction regimens for patients with non-small cell lung cancer with operable mediastinal nodal disease, although evidence has not shown a benefit over induction chemotherapy alone. We compared outcomes between induction chemotherapy and induction chemoradiation using the National Cancer Data Base.Induction radiation use and survival of patients who underwent lobectomy or pneumonectomy after induction chemotherapy for clinical T1-3N2M0 non-small cell lung cancer in the National Cancer Data Base from 2003 to 2006 were assessed using logistic regression, general linear regression, Kaplan-Meier, and Cox proportional hazard analysis.Of 1362 patients who met study criteria, 834 (61%) underwent induction chemoradiation and 528 (39%) underwent induction chemotherapy. Lobectomy was performed in 82% of patients (n = 1111), and pneumonectomy was performed in 18% of patients (n = 251). Pneumonectomy was performed more often after induction chemoradiation than after induction chemotherapy (20% vs 16%, P = .04). Downstaging from N2 to N0/N1 was more common with induction chemoradiation compared with induction chemotherapy (58% vs 46%, P < .01), but 5-year survival of patients receiving induction chemoradiation and patients receiving induction chemotherapy was similar in unadjusted analysis (41% vs 41%, P = .41). In multivariable analysis, the addition of radiation to induction chemotherapy also was not associated with a survival benefit (hazard ratio, 1.03; 95% confidence interval, 0.89-1.18; P = .73).Induction chemoradiation is used in the majority of patients with non-small cell lung cancer with N2 disease who undergo induction therapy before surgical resection, but it is not associated with improved survival compared with induction chemotherapy.

Authors
Yang, C-FJ; Gulack, BC; Gu, L; Speicher, PJ; Wang, X; Harpole, DH; Onaitis, MW; D'Amico, TA; Berry, MF; Hartwig, MG
MLA Citation
Yang, C-FJ, Gulack, BC, Gu, L, Speicher, PJ, Wang, X, Harpole, DH, Onaitis, MW, D'Amico, TA, Berry, MF, and Hartwig, MG. "Adding radiation to induction chemotherapy does not improve survival of patients with operable clinical N2 non-small cell lung cancer." The Journal of thoracic and cardiovascular surgery 150.6 (December 2015): 1484-1492.
PMID
26259994
Source
epmc
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
150
Issue
6
Publish Date
2015
Start Page
1484
End Page
1492
DOI
10.1016/j.jtcvs.2015.06.062

The impact of tumor size on the association of the extent of lymph node resection and survival in clinical stage I non-small cell lung cancer.

Lymph node evaluation for node-negative non-small cell lung cancer (NSCLC) is associated with long-term survival but it is not clear if smaller tumors require as extensive a pathologic nodal assessment as larger tumors. This study evaluated the relationship of tumor size and optimal extent of lymph node resection using the National Cancer Data Base (NCDB).The incremental survival benefit of each additional lymph node that was evaluated for patients in the NCDB who underwent lobectomy for clinical Stage I NSCLC from 2003 to 2006 was evaluated using Cox multivariable proportional hazards regression modeling. The impact of tumor size was assessed by repeating the Cox analysis with patients stratified by tumor size ≥2 cm vs <2 cm.A median of 7 [interquartile range: 4,11] lymph nodes were examined in 13,827 patients who met study criteria. Following adjustment, the evaluation of each additional lymph node demonstrated a significant survival benefit through 11 lymph nodes. After grouping patients by tumor size, patients with tumors <2 cm demonstrated a significant survival benefit for the incremental resection of each additional lymph node through 4 lymph nodes while patients with tumors ≥2 cm had a significant survival benefit through 14 lymph nodes.Pathologic lymph node evaluation is associated with improved survival for clinically node-negative NSCLC, but the extent of the necessary evaluation varies by tumor size. These results have implications for guidelines for lymph node assessment as well as the choice of surgery vs other ablative techniques for clinical stage I NSCLC.

Authors
Gulack, BC; Yang, C-FJ; Speicher, PJ; Meza, JM; Gu, L; Wang, X; D'Amico, TA; Hartwig, MG; Berry, MF
MLA Citation
Gulack, BC, Yang, C-FJ, Speicher, PJ, Meza, JM, Gu, L, Wang, X, D'Amico, TA, Hartwig, MG, and Berry, MF. "The impact of tumor size on the association of the extent of lymph node resection and survival in clinical stage I non-small cell lung cancer." Lung cancer (Amsterdam, Netherlands) 90.3 (December 2015): 554-560.
PMID
26519122
Source
epmc
Published In
Lung Cancer
Volume
90
Issue
3
Publish Date
2015
Start Page
554
End Page
560
DOI
10.1016/j.lungcan.2015.10.011

Surrogate clinical endpoints to predict overall survival in non-small cell lung cancer trials-are we in a new era?

Surrogate endpoints for clinical trials in oncology offer an alternative metric for measuring clinical benefit, allowing for shorter trial duration, smaller patient cohorts, and single arm design. The correlation of surrogate endpoints with overall survival (OS) in therapeutic studies is a central consideration to their validity. The Food and Drug Administration (FDA) recently published an analysis of fourteen clinical trials in advanced non-small cell lung cancer (NSCLC), and discovered a strong association between response rate and progression free survival. Furthermore, a correlation between response rate and OS is demonstrated when analyzing the experimental treatment arm separately, minimizing bias from patient crossover. We also highlight multiple, important considerations when using response as an endpoint in clinical trials involving NSCLC patients.

Authors
Clarke, JM; Wang, X; Ready, NE
MLA Citation
Clarke, JM, Wang, X, and Ready, NE. "Surrogate clinical endpoints to predict overall survival in non-small cell lung cancer trials-are we in a new era?." Translational lung cancer research 4.6 (December 2015): 804-808.
PMID
26798592
Source
epmc
Published In
Translational lung cancer research
Volume
4
Issue
6
Publish Date
2015
Start Page
804
End Page
808
DOI
10.3978/j.issn.2218-6751.2015.05.03

Induction chemoradiation therapy prior to esophagectomy is associated with superior long-term survival for esophageal cancer.

The purpose of this study was to examine the role of induction chemoradiation in the treatment of potentially resectable locally advanced (T2-3N0 and T1-3N+) esophageal cancer utilizing a large national database. The National Cancer Data Base (NCDB) was queried for all patients undergoing esophagectomy for clinical T2-3N0 and T1-3N+ esophageal cancer of the mid- or lower esophagus. Patients were stratified by the use of induction chemoradiation therapy versus surgery-first. Trends were assessed with the Cochran-Armitage test. Predictors of receiving induction therapy were evaluated with multivariable logistic regression. A propensity-matched analysis was conducted to compare outcomes between groups, and the Kaplan-Meier method was used to estimate long-term survival. Within the NCDB, 7921 patients were identified, of which 6103 (77.0%) were treated with chemoradiation prior to esophagectomy, while the remaining 1818 (23.0%) were managed with surgery-first. Use of induction therapy increased over time, with an absolute increase of 11.8% from 2003-2011 (P < 0.001). As revealed by the propensity model, induction therapy was associated with higher rates of negative margins and shorter hospital length of stay, but no differences in unplanned readmission and 30-day mortality rates. In unadjusted survival analysis, induction therapy was associated with better long-term survival compared to a strategy of surgery-first, with 5-year survival rates of 37.2% versus 28.6%, P < 0.001. Following propensity score matching analysis, the use of induction therapy maintained a significant survival advantage over surgery-first (5-year survival: 37.9% vs. 28.7%, P < 0.001). Treatment with induction chemoradiation therapy prior to surgical resection is associated with significant improvement in long-term survival, even after adjusting for confounders with a propensity model. Induction therapy should be considered in all medically appropriate patients with resectable cT2-3N0 and cT1-3N+ esophageal cancer, prior to esophagectomy.

Authors
Speicher, PJ; Wang, X; Englum, BR; Ganapathi, AM; Yerokun, B; Hartwig, MG; D'Amico, TA; Berry, MF
MLA Citation
Speicher, PJ, Wang, X, Englum, BR, Ganapathi, AM, Yerokun, B, Hartwig, MG, D'Amico, TA, and Berry, MF. "Induction chemoradiation therapy prior to esophagectomy is associated with superior long-term survival for esophageal cancer." Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus 28.8 (November 2015): 788-796.
PMID
25212528
Source
epmc
Published In
Diseases of the Esophagus
Volume
28
Issue
8
Publish Date
2015
Start Page
788
End Page
796
DOI
10.1111/dote.12285

Validation of survival prognostic models for non-small-cell lung cancer in stage- and age-specific groups.

Prognostic models have been proposed to predict survival for non-small-cell lung cancer (NSCLC). It is important to evaluate whether these models perform better than performance status (PS) alone in stage- and age-specific subgroups.The validation cohort included 2060 stage I and 1611 stage IV NSCLC patients from 23CALGB studies. For stage I, Blanchon (B), Chansky (C) and Gail (G) models were evaluated along with the PS only model. For stage IV, Blanchon (B) and Mandrekar (M) models were compared with the PS only model. The c-index was used to assess the concordance between survival and risk scores. The c-index difference (c-difference) and the integrated discrimination improvement (IDI) were used to determine the improvement of these models over the PS only model.For stage I, B and PS have better survival separation. The c-index for B, PS, C and G are 0.61, 0.58, 0.57 and 0.52, respectively, and B performs significantly better than PS with c-difference=0.034. For stage IV, B, M and PS have c-index 0.61, 0.64 and 0.60, respectively; B and M perform significantly better than PS with c-difference=0.015 and 0.033, respectively.Although some prognostic models have better concordance with survival than the PS only model, the absolute improvement is small. More accurate prognostic models should be developed; the inclusion of tumor genetic variants may improve prognostic models.

Authors
Wang, X; Gu, L; Zhang, Y; Sargent, DJ; Richards, W; Ganti, AK; Crawford, J; Cohen, HJ; Stinchcombe, T; Vokes, E; Pang, H
MLA Citation
Wang, X, Gu, L, Zhang, Y, Sargent, DJ, Richards, W, Ganti, AK, Crawford, J, Cohen, HJ, Stinchcombe, T, Vokes, E, and Pang, H. "Validation of survival prognostic models for non-small-cell lung cancer in stage- and age-specific groups." Lung cancer (Amsterdam, Netherlands) 90.2 (November 2015): 281-287.
PMID
26319317
Source
epmc
Published In
Lung Cancer
Volume
90
Issue
2
Publish Date
2015
Start Page
281
End Page
287
DOI
10.1016/j.lungcan.2015.08.007

PCI Survival Improvement for Extensive Stage SCLC Limited to Patients on Maintenance Systemic Therapy: A Secondary Analysis of CALGB 30504

Authors
Salama, JK; Gu, L; Wang, X; Bogart, J; Crawford, J; Schild, S; Ready, N; Vokes, E
MLA Citation
Salama, JK, Gu, L, Wang, X, Bogart, J, Crawford, J, Schild, S, Ready, N, and Vokes, E. "PCI Survival Improvement for Extensive Stage SCLC Limited to Patients on Maintenance Systemic Therapy: A Secondary Analysis of CALGB 30504." JOURNAL OF THORACIC ONCOLOGY 10.9 (September 2015): S401-S401.
Source
wos-lite
Published In
Journal of Thoracic Oncology
Volume
10
Issue
9
Publish Date
2015
Start Page
S401
End Page
S401

Multitrial Evaluation of Progression-Free Survival as a Surrogate End Point for Overall Survival in First-Line Extensive-Stage Small-Cell Lung Cancer.

We previously reported that progression-free survival (PFS) may be a candidate surrogate end point for overall survival (OS) in first-line extensive-stage small-cell lung cancer (ES-SCLC) using data from three randomized trials (Foster, Cancer 2011). In this validation study (N0424-Alliance), we assessed the patient-level and trial-level surrogacy of PFS using data from seven new first-line phase II/III ES-SCLC trials and across all 10 trials as well (seven new, three previous).Individual patient data were utilized across the seven new trials (2259 patients) and all 10 trials (2855 patients). Patient-level surrogacy (Kendall's τ) was assessed using the Clayton copula bivariate survival model. Trial-level surrogacy was assessed through association of the log hazard ratios on OS and PFS across trials, including weighted (by trial size) least squares regression (WLS R²) of Cox model effects and correlation of the copula effects (copula R²). The minimum effect on the surrogate (MES) needed to detect a nonzero treatment effect on OS was also calculated.The median OS and PFS across all 10 trials were 9.8 and 5.9 months, respectively. PFS showed strong surrogacy within the 7 new trials (copula R² = 0.90 [standard error = 0.27], WLS R² = 0.83 [95% confidence interval: 0.43, 0.95]; MES = 0.67, and Kendall's τ = 0.58) and across all 10 trials (copula R² = 0.81 [standard errors = 0.25], WLS R² = 0.77 [95% confidence interval: 0.47-0.91], MES = 0.70, and Kendall's τ = 0.57).PFS demonstrated strong surrogacy for OS in first-line ES-SCLC based on this external validation study of individual patient data. PFS is a good alternative end point to OS and should be considered when resource constraints (time or patient) might make it useful or desirable in place of OS. Additional analyses are needed to assess its appropriateness for targeted agents in this disease setting.

Authors
Foster, NR; Renfro, LA; Schild, SE; Redman, MW; Wang, XF; Dahlberg, SE; Ding, K; Bradbury, PA; Ramalingam, SS; Gandara, DR; Shibata, T; Saijo, N; Vokes, EE; Adjei, AA; Mandrekar, SJ
MLA Citation
Foster, NR, Renfro, LA, Schild, SE, Redman, MW, Wang, XF, Dahlberg, SE, Ding, K, Bradbury, PA, Ramalingam, SS, Gandara, DR, Shibata, T, Saijo, N, Vokes, EE, Adjei, AA, and Mandrekar, SJ. "Multitrial Evaluation of Progression-Free Survival as a Surrogate End Point for Overall Survival in First-Line Extensive-Stage Small-Cell Lung Cancer." Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 10.7 (July 2015): 1099-1106.
PMID
26134227
Source
epmc
Published In
Journal of Thoracic Oncology
Volume
10
Issue
7
Publish Date
2015
Start Page
1099
End Page
1106
DOI
10.1097/jto.0000000000000548

Adjuvant Chemotherapy After Lobectomy for T1-2N0 Non-Small Cell Lung Cancer: Are the Guidelines Supported?

Evidence guiding adjuvant chemotherapy (AC) use after lobectomy for stage I non-small cell lung cancer (NSCLC) is limited. This study evaluated the impact of AC use and tumor size on outcomes using a large, nationwide cancer database.The effect of AC on long-term survival among patients who underwent lobectomy for margin-negative pathologic T1-2N0M0 NSCLC in the National Cancer Data Base from 2003 to 2006 was estimated using the Kaplan-Meier method. The specific tumor size threshold at which AC began providing benefit was estimated with multivariable Cox proportional hazards modeling.Overall 3,496 of 34,360 patients (10.2%) who met inclusion criteria were treated with AC, although AC use increased over time from 2003, when only 2.7% of patients with tumors less than 4 cm and 6.2% of patients with tumors of 4 cm or larger received AC. In unadjusted survival analysis, AC was associated with a significant 5-year survival benefit for patients with tumors less than 4 cm (74.3% vs 66.9%; P<.0001) and 4 cm or greater (64.8% vs 49.8%; P<.0001). In subanalyses of patients grouped by strata of 0.5-cm increments in tumor size, AC was associated with a survival advantage for tumor sizes ranging from 3.0 to 8.5 cm.Use of AC among patients with stage I NSCLC has increased over time but remains uncommon. The results of this study support current treatment guidelines that recommend AC use after lobectomy for stage I NSCLC tumors larger than 4 cm. These results also suggest that AC use is associated with superior survival for patients with tumors ranging from 3.0 to 8.5 cm in diameter.

Authors
Speicher, PJ; Gu, L; Wang, X; Hartwig, MG; D'Amico, TA; Berry, MF
MLA Citation
Speicher, PJ, Gu, L, Wang, X, Hartwig, MG, D'Amico, TA, and Berry, MF. "Adjuvant Chemotherapy After Lobectomy for T1-2N0 Non-Small Cell Lung Cancer: Are the Guidelines Supported?." Journal of the National Comprehensive Cancer Network : JNCCN 13.6 (June 2015): 755-761.
PMID
26085391
Source
epmc
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
13
Issue
6
Publish Date
2015
Start Page
755
End Page
761

VATS lobectomy has better perioperative outcomes than open lobectomy: CALGB 31001, an ancillary analysis of CALGB 140202 (Alliance).

BACKGROUND: The short-term superiority of video-assisted thoracoscopic surgery lobectomy compared with open lobectomy for early-stage lung cancer has been suggested by single-institution studies. Lack of equipoise limits the feasibility of a randomized study to confirm this. The hypothesis of this study (CALGB 31001) was that VATS lobectomy results in shorter length of hospital stay and fewer complications compared with open lobectomy in stages I and II non-small cell lung cancer in a multi-institutional setting. METHODS: Five hundred nineteen patients whose tumors had been collected as part of CALGB 140202 (lung cancer tissue bank) were eligible. Propensity-scoring using age, race, sex, performance status, comorbidities, histology, tumor stage, and size as independent variables was used to create a 1:1 matched group of 175 pairs of patients. McNemar's test for binary variables and Wilcoxon signed-rank test for continuous variables were used to assess differences in length of hospital stay, complications, and discharge dispositions between the groups. Comparison of disease-free and overall survival between the two approaches was done using the log-rank test. Probability values of less than 0.05 were considered significant. RESULTS: The matched data on length of hospital stay, complications, and discharge dispositions significantly favored the video-assisted thoracoscopic surgery group. There was no statistically significant difference in survival between the two approaches. CONCLUSIONS: This multi-institutional study supports the assertion that thoracoscopic lobectomy results in shorter hospital length of stay, fewer perioperative complications, and greater likelihood of independent home discharge compared with open lobectomy for early-stage lung cancer. Survival was comparable between the two groups.

Authors
Nwogu, CE; D'Cunha, J; Pang, H; Gu, L; Wang, X; Richards, WG; Veit, LJ; Demmy, TL; Sugarbaker, DJ; Kohman, LJ; Swanson, SJ
MLA Citation
Nwogu, CE, D'Cunha, J, Pang, H, Gu, L, Wang, X, Richards, WG, Veit, LJ, Demmy, TL, Sugarbaker, DJ, Kohman, LJ, and Swanson, SJ. "VATS lobectomy has better perioperative outcomes than open lobectomy: CALGB 31001, an ancillary analysis of CALGB 140202 (Alliance)." The Annals of thoracic surgery 99.2 (February 2015): 399-405.
PMID
25499481
Source
epmc
Published In
The Annals of Thoracic Surgery
Volume
99
Issue
2
Publish Date
2015
Start Page
399
End Page
405
DOI
10.1016/j.athoracsur.2014.09.018

VATS lobectomy has better perioperative outcomes than open lobectomy: CALGB 31001, an ancillary analysis of CALGB 140202 (Alliance)

© 2015 The Society of Thoracic Surgeons.Background The short-term superiority of video-assisted thoracoscopic surgery lobectomy compared with open lobectomy for early-stage lung cancer has been suggested by single-institution studies. Lack of equipoise limits the feasibility of a randomized study to confirm this. The hypothesis of this study (CALGB 31001) was that VATS lobectomy results in shorter length of hospital stay and fewer complications compared with open lobectomy in stages I and II non-small cell lung cancer in a multi-institutional setting. Methods Five hundred nineteen patients whose tumors had been collected as part of CALGB 140202 (lung cancer tissue bank) were eligible. Propensity-scoring using age, race, sex, performance status, comorbidities, histology, tumor stage, and size as independent variables was used to create a 1:1 matched group of 175 pairs of patients. McNemar's test for binary variables and Wilcoxon signed-rank test for continuous variables were used to assess differences in length of hospital stay, complications, and discharge dispositions between the groups. Comparison of disease-free and overall survival between the two approaches was done using the log-rank test. Probability values of less than 0.05 were considered significant. Results The matched data on length of hospital stay, complications, and discharge dispositions significantly favored the video-assisted thoracoscopic surgery group. There was no statistically significant difference in survival between the two approaches. Conclusions This multi-institutional study supports the assertion that thoracoscopic lobectomy results in shorter hospital length of stay, fewer perioperative complications, and greater likelihood of independent home discharge compared with open lobectomy for early-stage lung cancer. Survival was comparable between the two groups.

Authors
Nwogu, CE; D'Cunha, J; Pang, H; Gu, L; Wang, X; Richards, WG; Veit, LJ; Demmy, TL; Sugarbaker, DJ; Kohman, LJ; Swanson, SJ
MLA Citation
Nwogu, CE, D'Cunha, J, Pang, H, Gu, L, Wang, X, Richards, WG, Veit, LJ, Demmy, TL, Sugarbaker, DJ, Kohman, LJ, and Swanson, SJ. "VATS lobectomy has better perioperative outcomes than open lobectomy: CALGB 31001, an ancillary analysis of CALGB 140202 (Alliance)." Annals of Thoracic Surgery 99.2 (January 1, 2015): 399-405.
Source
scopus
Published In
The Annals of Thoracic Surgery
Volume
99
Issue
2
Publish Date
2015
Start Page
399
End Page
405
DOI
10.1016/j.athoracsur.2014.09.018

A phase II study of induction chemotherapy followed by thoracic radiotherapy and erlotinib in poor-risk stage III non-small-cell lung cancer: results of CALGB 30605 (Alliance)/RTOG 0972 (NRG).

Patients with stage III non-small-cell lung cancer and poor performance status and/or weight loss do not seem to benefit from standard therapy. Based on the preclinical interaction between epidermal growth factor receptor inhibitors and radiation, we designed a trial of induction chemotherapy followed by thoracic radiotherapy and concurrent erlotinib.Patients with poor-risk unresectable stage III non-small-cell lung cancer received two cycles of carboplatin at an AUC of 5 and nab-paclitaxel at 100 mg/m on days 1 and 8 every 21 days, followed by erlotinib administered concurrently with thoracic radiotherapy. Maintenance was not permitted. Molecular analysis was performed in available specimens. Seventy-two eligible patients were required to test whether the 1-year survival rate was less than 50% or greater than or equal to 65% with approximately 90% power at a significance level of 0.10.From March 2008 to October 2011, 78 patients were enrolled, three of whom were ineligible. The median age was 68 (range, 39-88) and 32% were aged greater than or equal to 75 years. Patients were evenly distributed between stages IIIA and IIIB and the majority had performance status 2. The overall response rate was 67% and the disease control rate was 93%. Treatment was well tolerated. The median PFS and OS were 11 and 17 months, respectively. The overall 12-month OS was 57%, which narrowly missed the prespecified target for significance.Patients with poor-risk stage III non-small-cell lung cancer had better than expected outcomes with a regimen of induction carboplatin/nab-paclitaxel followed by thoracic radiotherapy and erlotinib. However, as per the statistical design, the 12-month OS was not sufficiently high to warrant further studies.

Authors
Lilenbaum, R; Samuels, M; Wang, X; Kong, FM; Jänne, PA; Masters, G; Katragadda, S; Hodgson, L; Bogart, J; Bradley, J; Vokes, E
MLA Citation
Lilenbaum, R, Samuels, M, Wang, X, Kong, FM, Jänne, PA, Masters, G, Katragadda, S, Hodgson, L, Bogart, J, Bradley, J, and Vokes, E. "A phase II study of induction chemotherapy followed by thoracic radiotherapy and erlotinib in poor-risk stage III non-small-cell lung cancer: results of CALGB 30605 (Alliance)/RTOG 0972 (NRG)." Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 10.1 (January 2015): 143-147.
PMID
25384173
Source
epmc
Published In
Journal of Thoracic Oncology
Volume
10
Issue
1
Publish Date
2015
Start Page
143
End Page
147
DOI
10.1097/jto.0000000000000347

Abstract CT238: Phase III randomized, placebo controlled trial of COX-2 inhibition in addition to standard chemotherapy for advanced non-small cell lung cancer (NSCLC):CALGB 30801 (Alliance)

Authors
Edelman, MJ; Wang, X; Hodgson, L; Cheney, RT; Baggstrom, M; Sachdev, T; Gajra, A; Bertino, E; Reckamp, K; Molina, J; Schiller, J; Mitchell-Richards, K; Friedman, P; Ritter, J; Vokes, E
MLA Citation
Edelman, MJ, Wang, X, Hodgson, L, Cheney, RT, Baggstrom, M, Sachdev, T, Gajra, A, Bertino, E, Reckamp, K, Molina, J, Schiller, J, Mitchell-Richards, K, Friedman, P, Ritter, J, and Vokes, E. "Abstract CT238: Phase III randomized, placebo controlled trial of COX-2 inhibition in addition to standard chemotherapy for advanced non-small cell lung cancer (NSCLC):CALGB 30801 (Alliance)." October 1, 2014.
Source
crossref
Published In
Cancer Research
Volume
74
Issue
19 Supplement
Publish Date
2014
Start Page
CT238
End Page
CT238
DOI
10.1158/1538-7445.AM2014-CT238

Sunitinib (S) switch maintenance in advanced non-small cell lung cancer (NSCLC): An ALLIANCE (CALGB 30607), randomized, placebo-controlled phase III trial.

Authors
Socinski, MA; Wang, XF; Baggstrom, MQ; Gu, L; Stinchcombe, TE; Edelman, MJ; Jr, BS; Mannuel, HD; Crawford, J; Vokes, EE
MLA Citation
Socinski, MA, Wang, XF, Baggstrom, MQ, Gu, L, Stinchcombe, TE, Edelman, MJ, Jr, BS, Mannuel, HD, Crawford, J, and Vokes, EE. "Sunitinib (S) switch maintenance in advanced non-small cell lung cancer (NSCLC): An ALLIANCE (CALGB 30607), randomized, placebo-controlled phase III trial." May 20, 2014.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
32
Issue
15
Publish Date
2014

CALGB 30704 (Alliance): A randomized phase II study to assess the efficacy of pemetrexed or sunitinib or pemetrexed plus sunitinib in the second-line treatment of advanced non-small-cell lung cancer.

BACKGROUND: Second-line chemotherapy for advanced non-small cell lung cancer (NSCLC) improves survival modestly but new strategies are needed. This trial was designed to evaluate an antivascular endothelial growth factor strategy with or without standard chemotherapy in previously treated NSCLC. METHODS: Patients with stage IIIB/IV NSCLC with performance status 0 to 1 progressive after first-line chemotherapy were eligible for randomization to pemetrexed, sunitinib, or the combination. Patients were stratified by performance status, stage, and sex. Primary objective was 18-week progression-free survival (PFS) rate; secondary objectives included response, overall survival (OS), and toxicity. Target accrual was 225. The study was terminated early because of decreasing accrual rates. RESULTS: Between April 2008 and September 2011, 130 patients were registered and randomized; of this, 125 patients were treated. Baseline characteristics in the three arms were well balanced. Toxicity was higher in the sunitinib-containing arms. The 18-week PFS rate in the pemetrexed, sunitinib, and combination arms was 54% (95% confidence interval [CI], 40-71), 37% (95% CI, 25-54), and 48% (95% CI, 35-66), respectively (p = 0.25). Median PFS in the pemetrexed, sunitinib, and combination arms in months was 4.9 (2.1-8.8), 3.3 (2.3-4.2), and 3.7 (2.5-5.8), respectively (p = 0.18). There was an overall statistically significant difference in OS between the three arms: median OS in months was 10.5 (8.3-20.2) for pemetrexed, 8.0 (6.8-13.5) for sunitinib, and 6.7 (4.1-10.1) for the combination (p = 0.03). CONCLUSION: Pemetrexed had a superior toxicity profile to either sunitinib or the combination of pemetrexed and sunitinib. The 18-week PFS rate was not significantly different between the arms. OS was significantly better with pemetrexed alone compared with the two sunitinib-containing arms, with the doublet performing worst for OS.

Authors
Heist, RS; Wang, X; Hodgson, L; Otterson, GA; Stinchcombe, TE; Gandhi, L; Villalona-Calero, MA; Watson, P; Vokes, EE; Socinski, MA; Alliance for Clinical Trials in Oncology,
MLA Citation
Heist, RS, Wang, X, Hodgson, L, Otterson, GA, Stinchcombe, TE, Gandhi, L, Villalona-Calero, MA, Watson, P, Vokes, EE, Socinski, MA, and Alliance for Clinical Trials in Oncology, . "CALGB 30704 (Alliance): A randomized phase II study to assess the efficacy of pemetrexed or sunitinib or pemetrexed plus sunitinib in the second-line treatment of advanced non-small-cell lung cancer." J Thorac Oncol 9.2 (February 2014): 214-221.
PMID
24419419
Source
pubmed
Published In
Journal of Thoracic Oncology
Volume
9
Issue
2
Publish Date
2014
Start Page
214
End Page
221
DOI
10.1097/JTO.0000000000000071

Sleeve lobectomy for non-small cell lung cancer with N1 nodal disease does not compromise survival

Background We evaluated if sleeve lobectomy had worse survival compared with pneumonectomy for non-small cell lung cancer (NSCLC) with N1 disease, which may be a risk factor for locoregional recurrence. Methods Patients who underwent pneumonectomy or sleeve lobectomy without induction treatment for T2-3 N1 M0 NSCLC at a single institution from 1999 to 2011 were reviewed. Survival distribution was estimated with the Kaplan-Meier method, and multivariable Cox proportional hazards regression was used to evaluate the effect of resection extent on survival. Results During the study period, 87 patients underwent pneumonectomy (52 [60%]) or sleeve lobectomy (35 [40%]) for T2-3 N1 M0 NSCLC. Pneumonectomy and sleeve lobectomy patients had similar mean ages (60.9 ± 10.7 vs 63.5 ± 12.7 years, p = 0.30), gender distribution (69.2% [36 of 52] vs 60.0% [21 of 35] male, p = 0.37), mean forced expiratory volume in 1 second (66.3 ± 15.9 vs 63.5 ± 17.6, p = 0.47), stage (61.5% [32 of 52] vs 62.9% [22 of 35] stage II, p = 0.90), and tumor grade (51.9% [27 of 52] vs 31.4% [11 of 35] well/moderately differentiated, p = 0.17). Postoperative mortality (3.8% [2 of 52] vs 5.7% [2 of 35], p = 0.68) and median (interquartile range) length of stay (5 [4 to 7] vs 5 [4 to 7] days, p = 0.68) were similar between the two groups. The 3-year survival after pneumonectomy (46.8% [95% CI, 31.8% to 60.4%]) and sleeve lobectomy (65.2% [95% CI, 45.5% to 79.3%]) was not significantly different (p = 0.23). In multivariable survival analysis that included resection extent, age, stage, and grade, only increasing age predicted worse survival (hazard ratio, 1.03/year; p = 0.03). Conclusions Performing sleeve lobectomy instead of pneumonectomy for NSCLC with N1 nodal disease does not compromise long-term survival. © 2014 by The Society of Thoracic Surgeons.

Authors
Berry, MF; Worni, M; Wang, X; Harpole, DH; D'Amico, TA; Onaitis, MW
MLA Citation
Berry, MF, Worni, M, Wang, X, Harpole, DH, D'Amico, TA, and Onaitis, MW. "Sleeve lobectomy for non-small cell lung cancer with N1 nodal disease does not compromise survival." Annals of Thoracic Surgery 97.1 (January 1, 2014): 230-235.
Source
scopus
Published In
The Annals of Thoracic Surgery
Volume
97
Issue
1
Publish Date
2014
Start Page
230
End Page
235
DOI
10.1016/j.athoracsur.2013.09.016

Sleeve lobectomy for non-small cell lung cancer with N1 nodal disease does not compromise survival.

BACKGROUND: We evaluated if sleeve lobectomy had worse survival compared with pneumonectomy for non-small cell lung cancer (NSCLC) with N1 disease, which may be a risk factor for locoregional recurrence. METHODS: Patients who underwent pneumonectomy or sleeve lobectomy without induction treatment for T2-3 N1 M0 NSCLC at a single institution from 1999 to 2011 were reviewed. Survival distribution was estimated with the Kaplan-Meier method, and multivariable Cox proportional hazards regression was used to evaluate the effect of resection extent on survival. RESULTS: During the study period, 87 patients underwent pneumonectomy (52 [60%]) or sleeve lobectomy (35 [40%]) for T2-3 N1 M0 NSCLC. Pneumonectomy and sleeve lobectomy patients had similar mean ages (60.9 ± 10.7 vs 63.5 ± 12.7 years, p = 0.30), gender distribution (69.2% [36 of 52] vs 60.0% [21 of 35] male, p = 0.37), mean forced expiratory volume in 1 second (66.3 ± 15.9 vs 63.5 ± 17.6, p = 0.47), stage (61.5% [32 of 52] vs 62.9% [22 of 35] stage II, p = 0.90), and tumor grade (51.9% [27 of 52] vs 31.4% [11 of 35] well/moderately differentiated, p = 0.17). Postoperative mortality (3.8% [2 of 52] vs 5.7% [2 of 35], p = 0.68) and median (interquartile range) length of stay (5 [4 to 7] vs 5 [4 to 7] days, p = 0.68) were similar between the two groups. The 3-year survival after pneumonectomy (46.8% [95% CI, 31.8% to 60.4%]) and sleeve lobectomy (65.2% [95% CI, 45.5% to 79.3%]) was not significantly different (p = 0.23). In multivariable survival analysis that included resection extent, age, stage, and grade, only increasing age predicted worse survival (hazard ratio, 1.03/year; p = 0.03). CONCLUSIONS: Performing sleeve lobectomy instead of pneumonectomy for NSCLC with N1 nodal disease does not compromise long-term survival.

Authors
Berry, MF; Worni, M; Wang, X; Harpole, DH; D'Amico, TA; Onaitis, MW
MLA Citation
Berry, MF, Worni, M, Wang, X, Harpole, DH, D'Amico, TA, and Onaitis, MW. "Sleeve lobectomy for non-small cell lung cancer with N1 nodal disease does not compromise survival." Ann Thorac Surg 97.1 (January 2014): 230-235.
PMID
24206972
Source
pubmed
Published In
Annals of Thoracic Surgery
Volume
97
Issue
1
Publish Date
2014
Start Page
230
End Page
235
DOI
10.1016/j.athoracsur.2013.09.016

Surgical techniques and results of the pulmonary artery reconstruction for patients with central non-small cell lung cancer

Background: It is difficult to achieve a margin-negative resection (R0) for non-small cell lung cancer (NSCLC) patients with infiltration of the pulmonary artery. We report our experience of the pulmonary artery reconstruction with regard to long-term survival.Methods: Clinical records of 118 patients with NSCLC who underwent partial or circumferential pulmonary artery resection during a 21-year period were reviewed retrospectively. Techniques and survival outcomes were analyzed.Results: We performed 22 pulmonary artery sleeve resections, 51 reconstructions by autologous pericardial patch, 36 tangential resections, 3 left main pulmonary artery (PA) angioplasties during pneumonectomy without cardiopulmonary bypass, and 6 by only preserving the apical and anterior (1st) branch of pulmonary arterial trunk. In 41 patients, bronchial sleeve resection was associated; in 7 cases, superior vena cava reconstruction was also required. Thirty-one patients received induction therapy. Thirteen patients had stage IB disease, 41 stage II, 53 IIIA, and 11 IIIB. Ninety-three patients had squamous cell carcinoma, 22 adenocarcinoma, 2 mixed and 1 large cell carcinoma. Negative vascular margins were achieved in all. 5 positive bronchial margins were due to limited lung function. The analysis of 118 cases yielded follow-up data in 94 cases. The mean follow-up was 70 months (range 1-156 months). There was no in hospital death, and the overall 5-year survival was 50.2%. Five-year survivals for stages I and II versus III were 63.9% versus 37.0% (p = 0.0059). Multivariate analysis yielded non-squamous cell carcinoma, stage III and patch pulmonary arterioplasty as negative prognosis factors. PA reconstruction associated with bronchial sleeve resection was the positive prognostic factor.Conclusions: Pulmonary artery resection and reconstruction is feasible and safe, with favorable long-term survival. Our results support this technique as an effective alternative to selected patients with infiltration of the pulmonary artery, such as stage I and II and those who proved down-staged from stage III. Accurate preoperative evaluation, precise and suitable surgical techniques are crucial to achieve good results. Only preserving the anterior and apical pulmonary arteries and reconstruction of the main pulmonary artery by using the artery conduit technique without cardiopulmonary bypass in association with left pneumonectomy can be performed successfully. Postoperative anticoagulation is unnecessary. © 2013 Ma et al.; licensee BioMed Central Ltd.

Authors
Ma, Q; Liu, D; Guo, Y; Shi, B; Tian, Y; Song, Z; Zhang, Z; Ge, B; Wang, X; D'Amico, TA
MLA Citation
Ma, Q, Liu, D, Guo, Y, Shi, B, Tian, Y, Song, Z, Zhang, Z, Ge, B, Wang, X, and D'Amico, TA. "Surgical techniques and results of the pulmonary artery reconstruction for patients with central non-small cell lung cancer." Journal of Cardiothoracic Surgery 8.1 (December 1, 2013).
PMID
24289720
Source
scopus
Published In
Journal of Cardiothoracic Surgery
Volume
8
Issue
1
Publish Date
2013
DOI
10.1186/1749-8090-8-219

VALIDATION OF THE CALGB AND EORTC PROGNOSTIC MODELS FOR MESOTHELIOMA BASED ON MULTIPLE CALGB TRIALS (ALLIANCE)

Authors
Pang, H; Hodgson, L; Kratzke, R; Crawford, J; Kindler, H; Vokes, E; Wang, X
MLA Citation
Pang, H, Hodgson, L, Kratzke, R, Crawford, J, Kindler, H, Vokes, E, and Wang, X. "VALIDATION OF THE CALGB AND EORTC PROGNOSTIC MODELS FOR MESOTHELIOMA BASED ON MULTIPLE CALGB TRIALS (ALLIANCE)." JOURNAL OF THORACIC ONCOLOGY 8 (November 2013): S934-S935.
Source
wos-lite
Published In
Journal of Thoracic Oncology
Volume
8
Publish Date
2013
Start Page
S934
End Page
S935

SURGICAL TECHNIQUES AND RESULTS OF RECONSTRUCTION OF THE PULMONARY ARTERY FOR PATIENTS WITH CENTRAL NON-SMALL CELL LUNG CANCER

Authors
Ma, Q; Liu, D; Guo, Y; Shi, B; Song, Z; Tian, Y-C; Ge, B; Wang, X; Amico, TAD
MLA Citation
Ma, Q, Liu, D, Guo, Y, Shi, B, Song, Z, Tian, Y-C, Ge, B, Wang, X, and Amico, TAD. "SURGICAL TECHNIQUES AND RESULTS OF RECONSTRUCTION OF THE PULMONARY ARTERY FOR PATIENTS WITH CENTRAL NON-SMALL CELL LUNG CANCER." JOURNAL OF THORACIC ONCOLOGY 8 (November 2013): S217-S217.
Source
wos-lite
Published In
Journal of Thoracic Oncology
Volume
8
Publish Date
2013
Start Page
S217
End Page
S217

Prospective phase II trial of preresection thoracoscopic mediastinal restaging after neoadjuvant therapy for IIIA (N2) non-small cell lung cancer: results of CALGB Protocol 39803.

OBJECTIVE: Accurate pathologic restaging of N2 stations after neoadjuvant therapy in stage IIIA (N2) non-small cell lung cancer is needed. METHODS: A prospective multi-institutional trial was designed to judge the feasibility of videothoracoscopy to restage the ipsilateral nodes in mediastinoscopy-proven stage IIIA (N2) non-small cell lung cancer after 2 cycles of platinum-based chemotherapy and/or 40 Gy or more of radiotherapy. The goals included biopsy of 3 negative N2 node stations or to identify 1 positive N2 node or pleural carcinomatosis. RESULTS: Ten institutions accrued 68 subjects. Of the 68 subjects, 46 (68%) underwent radiotherapy and 66 (97%) underwent chemotherapy. Videothoracoscopy successfully met the prestudy feasibility in 27 patients (40%): 3 negative stations confirmed at thoracotomy in 7, persistent stage N2 disease in 16, and pleural carcinomatosis in 4. In 20 procedures (29%), no N2 disease was found, 3 stations were not biopsied because of unanticipated nodal obliteration. Thus, 47 videothoracoscopy procedures (69%, 95% confidence interval, 57%-80%) restaged the mediastinum. Videothoracoscopy was unsuccessful in 21 patients (31%) because the procedure had to be aborted (n = 11) or because of false-negative stations (n = 10). Of the 21 failures, 15 were right-sided, and 10 had a positive 4R node. The sensitivity of videothoracoscopy was 67% (95% confidence interval, 47%-83%), and the negative predictive value was 73% (95% confidence interval, 56%-86%) if patients with obliterated nodal tissue were included. The sensitivity was 83% (95% confidence interval, 63%-95%) and the negative predictive value was 64% (95% confidence interval, 31%-89%) if those patients were excluded. The specificity was 100%. One death occurred after thoracotomy. CONCLUSIONS: Videothoracoscopy restaging was "feasible" in this prospective multi-institutional trial and provided pathologic specimens of the ipsilateral nodes. Videothoracoscopy restaging was limited by radiation and the 4R nodal station.

Authors
Jaklitsch, MT; Gu, L; Demmy, T; Harpole, DH; D'Amico, TA; McKenna, RJ; Krasna, MJ; Kohman, LJ; Swanson, SJ; DeCamp, MM; Wang, X; Barry, S; Sugarbaker, DJ; CALGB Thoracic Surgeons,
MLA Citation
Jaklitsch, MT, Gu, L, Demmy, T, Harpole, DH, D'Amico, TA, McKenna, RJ, Krasna, MJ, Kohman, LJ, Swanson, SJ, DeCamp, MM, Wang, X, Barry, S, Sugarbaker, DJ, and CALGB Thoracic Surgeons, . "Prospective phase II trial of preresection thoracoscopic mediastinal restaging after neoadjuvant therapy for IIIA (N2) non-small cell lung cancer: results of CALGB Protocol 39803." J Thorac Cardiovasc Surg 146.1 (July 2013): 9-16.
PMID
23768804
Source
pubmed
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
146
Issue
1
Publish Date
2013
Start Page
9
End Page
16
DOI
10.1016/j.jtcvs.2012.12.069

An analysis of the prevalence of HER2 and KRAS mutations, and ALK rearrangements and clinical outcomes in Cancer and Leukemia Group B [CALGB (Alliance)] trial 30406 in advanced non-small cell lung cancer (NSCLC).

Authors
Stinchcombe, T; Sholl, LM; Wang, XF; Gu, L; Socinski, MA; Rodig, SJ; Capelletti, M; Crawford, J; Edelman, MJ; Villalona-Calero, MA; Kratzke, RA; Vokes, EE; Miller, VA; Janne, PA
MLA Citation
Stinchcombe, T, Sholl, LM, Wang, XF, Gu, L, Socinski, MA, Rodig, SJ, Capelletti, M, Crawford, J, Edelman, MJ, Villalona-Calero, MA, Kratzke, RA, Vokes, EE, Miller, VA, and Janne, PA. "An analysis of the prevalence of HER2 and KRAS mutations, and ALK rearrangements and clinical outcomes in Cancer and Leukemia Group B [CALGB (Alliance)] trial 30406 in advanced non-small cell lung cancer (NSCLC)." May 20, 2013.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
31
Issue
15
Publish Date
2013

Abstract 4707: Validation of survival prognostic models for non-small-cell lung cancer instage- and age-specific groups.

Authors
Pang, H; Gu, L; Richards, W; Crawford, J; Green, M; Vokes, E; Wang, X
MLA Citation
Pang, H, Gu, L, Richards, W, Crawford, J, Green, M, Vokes, E, and Wang, X. "Abstract 4707: Validation of survival prognostic models for non-small-cell lung cancer instage- and age-specific groups." April 15, 2013.
Source
crossref
Published In
Cancer Research
Volume
73
Issue
8 Supplement
Publish Date
2013
Start Page
4707
End Page
4707
DOI
10.1158/1538-7445.AM2013-4707

ROC curve estimation under test-result-dependent sampling.

The receiver operating characteristic (ROC) curve is often used to evaluate the performance of a biomarker measured on continuous scale to predict the disease status or a clinical condition. Motivated by the need for novel study designs with better estimation efficiency and reduced study cost, we consider a biased sampling scheme that consists of a SRC and a supplemental TDC. Using this approach, investigators can oversample or undersample subjects falling into certain regions of the biomarker measure, yielding improved precision for the estimation of the ROC curve with a fixed sample size. Test-result-dependent sampling will introduce bias in estimating the predictive accuracy of the biomarker if standard ROC estimation methods are used. In this article, we discuss three approaches for analyzing data of a test-result-dependent structure with a special focus on the empirical likelihood method. We establish asymptotic properties of the empirical likelihood estimators for covariate-specific ROC curves and covariate-independent ROC curves and give their corresponding variance estimators. Simulation studies show that the empirical likelihood method yields good properties and is more efficient than alternative methods. Recommendations on number of regions, cutoff points, and subject allocation is made based on the simulation results. The proposed methods are illustrated with a data example based on an ongoing lung cancer clinical trial.

Authors
Wang, X; Ma, J; George, SL
MLA Citation
Wang, X, Ma, J, and George, SL. "ROC curve estimation under test-result-dependent sampling." Biostatistics 14.1 (January 2013): 160-172.
PMID
22723502
Source
pubmed
Published In
Biostatistics
Volume
14
Issue
1
Publish Date
2013
Start Page
160
End Page
172
DOI
10.1093/biostatistics/kxs020

Detection of human telomerase reverse transcriptase mRNA in cells obtained by lavage of the pleura is not associated with worse outcome in patients with stage I/II non-small cell lung cancer: Results from Cancer and Leukemia Group B 159902

Objective: Previous studies suggest that cytologic analysis of cells obtained by lavage of the pleural surfaces at the time of resection of non-small cell lung cancer can identify patients at risk for recurrence. Because telomerase gene expression has been associated with worse outcome in non-small cell lung cancer, we hypothesized that identification of cells obtained from pleural lavage that express telomerase would identify patients at risk for recurrent disease. Methods: Patients with presumed non-small cell lung cancer underwent thoracotomy with curative intent. Cells obtained by lavage of the pleural surfaces were analyzed for telomerase catalytic subunit human telomerase reverse transcriptase mRNA expression using reverse transcriptase polymerase chain reaction. Results: A total of 194 patients with stage I/II non-small cell lung cancer had adequate samples, and median follow-up was 60 months (17-91 months). By using Cox models, no statistical differences were found between human telomerase reverse transcriptase-negative and positive patients in disease-free survival (hazard ratio, 1.28; 95% confidence interval, 0.85-1.94; log-rank test, P =.2349) or overall survival (hazard ratio, 1.13; 95% confidence interval, 0.72-1.79; log-rank test, P =.5912) Conclusions: Detection of human telomerase reverse transcriptase in cells obtained from pleural lavage of patients with stage I/II non-small cell lung cancer does not identify patients at risk for recurrent disease. © 2013 by The American Association for Thoracic Surgery.

Authors
Boylan, AM; Wang, XF; Ko, R; Watson, PM; Gu, L; Harpole, D; Bueno, R; Kelly, R; Kohman, L; Kratzke, R
MLA Citation
Boylan, AM, Wang, XF, Ko, R, Watson, PM, Gu, L, Harpole, D, Bueno, R, Kelly, R, Kohman, L, and Kratzke, R. "Detection of human telomerase reverse transcriptase mRNA in cells obtained by lavage of the pleura is not associated with worse outcome in patients with stage I/II non-small cell lung cancer: Results from Cancer and Leukemia Group B 159902." Journal of Thoracic and Cardiovascular Surgery 146.1 (2013): 206-211.
Source
scival
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
146
Issue
1
Publish Date
2013
Start Page
206
End Page
211
DOI
10.1016/j.jtcvs.2012.08.059

Optimal management of malignant pleural effusions (results of CALGB 30102).

The optimal strategy to achieve palliation of malignant pleural effusions (MPEs) is unknown. This multi-institutional, prospective, randomized trial compares 2 established methods for controlling symptomatic unilateral MPEs. Patients with unilateral MPEs were randomized to either daily tunneled catheter drainage (TCD) or bedside talc pleurodesis (TP). This trial is patterned after a previous randomized trial that showed that bedside TP was equivalent to thoracoscopic TP (CALGB 9334). The primary end point of the current study was combined success: consistent/reliable drainage/pleurodesis, lung expansion, and 30-day survival. A secondary end point, survival with effusion control, was added retrospectively. This trial randomized 57 patients who were similar in terms of age (62 years), active chemotherapy (28%), and histologic diagnosis (lung, 63%; breast, 12%; other/unknown cancers, 25%) to either bedside TP or TCD. Combined success was higher with TCD (62%) than with TP (46%; odds ratio, 5.0; P = .064). Multivariate regression analysis revealed that patients treated with TCD had better 30-day activity without dyspnea scores (8.7 vs. 5.9; P = .036), especially in the subgroup with impaired expansion (9.1 vs. 4.6; P = .042). Patients who underwent TCD had better survival with effusion control at 30 days compared with those who underwent TP (82% vs. 52%, respectively; P = .024). In this prospective randomized trial, TCD achieved superior palliation of unilateral MPEs than TP, particularly in patients with trapped lungs.

Authors
Demmy, TL; Gu, L; Burkhalter, JE; Toloza, EM; D'Amico, TA; Sutherland, S; Wang, X; Archer, L; Veit, LJ; Kohman, L; Cancer and Leukemia Group B,
MLA Citation
Demmy, TL, Gu, L, Burkhalter, JE, Toloza, EM, D'Amico, TA, Sutherland, S, Wang, X, Archer, L, Veit, LJ, Kohman, L, and Cancer and Leukemia Group B, . "Optimal management of malignant pleural effusions (results of CALGB 30102)." J Natl Compr Canc Netw 10.8 (August 2012): 975-982.
PMID
22878823
Source
pubmed
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
10
Issue
8
Publish Date
2012
Start Page
975
End Page
982

CALGB 30704: A randomized phase II study to assess the efficacy of pemetrexed or sunitinib or pemetrexed plus sunitinib in the second-line treatment of advanced non-small cell lung cancer (NSCLC)

Authors
Heist, RS; Wang, XF; Hodgson, L; Otterson, GA; Stinchcombe, T; Vokes, EE; Socinski, MA
MLA Citation
Heist, RS, Wang, XF, Hodgson, L, Otterson, GA, Stinchcombe, T, Vokes, EE, and Socinski, MA. "CALGB 30704: A randomized phase II study to assess the efficacy of pemetrexed or sunitinib or pemetrexed plus sunitinib in the second-line treatment of advanced non-small cell lung cancer (NSCLC)." May 20, 2012.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
30
Issue
15
Publish Date
2012

Estimation of AUC or Partial AUC under Test-Result-Dependent Sampling.

The area under the ROC curve (AUC) and partial area under the ROC curve (pAUC) are summary measures used to assess the accuracy of a biomarker in discriminating true disease status. The standard sampling approach used in biomarker validation studies is often inefficient and costly, especially when ascertaining the true disease status is costly and invasive. To improve efficiency and reduce the cost of biomarker validation studies, we consider a test-result-dependent sampling (TDS) scheme, in which subject selection for determining the disease state is dependent on the result of a biomarker assay. We first estimate the test-result distribution using data arising from the TDS design. With the estimated empirical test-result distribution, we propose consistent nonparametric estimators for AUC and pAUC and establish the asymptotic properties of the proposed estimators. Simulation studies show that the proposed estimators have good finite sample properties and that the TDS design yields more efficient AUC and pAUC estimates than a simple random sampling (SRS) design. A data example based on an ongoing cancer clinical trial is provided to illustrate the TDS design and the proposed estimators. This work can find broad applications in design and analysis of biomarker validation studies.

Authors
Wang, X; Ma, J; George, S; Zhou, H
MLA Citation
Wang, X, Ma, J, George, S, and Zhou, H. "Estimation of AUC or Partial AUC under Test-Result-Dependent Sampling." Stat Biopharm Res 4.4 (January 1, 2012): 313-323.
PMID
23393612
Source
pubmed
Published In
Stat Biopharm Res
Volume
4
Issue
4
Publish Date
2012
Start Page
313
End Page
323
DOI
10.1080/19466315.2012.692514

Randomized phase II trial of erlotinib alone or with carboplatin and paclitaxel in patients who were never or light former smokers with advanced lung adenocarcinoma: CALGB 30406 trial

Purpose: Erlotinib is clinically effective in patients with non-small-cell lung cancer (NSCLC) who have adenocarcinoma, are never or limited former smokers, or have EGFR mutant tumors. We investigated the efficacy of erlotinib alone or in combination with chemotherapy in patients with these characteristics. Patients and Methods: Patients with advanced NSCLC (adenocarcinoma) who were epidermal growth factor receptor tyrosine kinase inhibitor and chemotherapy naive never or light former smokers (smokers of > 100 cigarettes and ≤ 10 pack years and quit ≥ 1 year ago) were randomly assigned to continuous erlotinib or in combination with carboplatin and paclitaxel (ECP) for six cycles followed by erlotinib alone. The primary end point was progression-free survival (PFS). Tissue collection was mandatory. Results PFS was similar (5.0 v 6.6 months; P = .1988) in patients randomly assigned to erlotinib alone (arm A; n = 81) or to ECP (arm B; n = 100). EGFR mutation analysis was possible in 91% (164 of 181) of patients, and EGFR mutations were detected in 40% (51 of 128) of never smokers and in 42% (15 of 36) of light former smokers. In arm A, response rate (70% v 9%), PFS (14.1 v 2.6 months), and overall survival (OS; 31.3 v 18.1 month) favored EGFR-mutant patients. In arm B, response rate (73% v 30%), PFS (17.2 v 4.8 months), and OS (38.1 v 14.4 months) favored EGFR-mutant patients. Incidence of grades 3 to 4 hematologic (2% v 49%; P = .001) and nonhematologic (24% v 52%; P < .001) toxicity was greater in patients treated with ECP. Conclusion Erlotinib and erlotinib plus chemotherapy have similar efficacy in clinically selected populations of patients with advanced NSCLC. EGFR mutations identify patients most likely to benefit. © 2012 by American Society of Clinical Oncology.

Authors
Jänne, PA; Wang, X; Socinski, MA; Crawford, J; Stinchcombe, TE; Gu, L; Capelletti, M; Edelman, MJ; Villalona-Calero, MA; Kratzke, R; Vokes, EE; Miller, VA
MLA Citation
Jänne, PA, Wang, X, Socinski, MA, Crawford, J, Stinchcombe, TE, Gu, L, Capelletti, M, Edelman, MJ, Villalona-Calero, MA, Kratzke, R, Vokes, EE, and Miller, VA. "Randomized phase II trial of erlotinib alone or with carboplatin and paclitaxel in patients who were never or light former smokers with advanced lung adenocarcinoma: CALGB 30406 trial." Journal of Clinical Oncology 30.17 (2012): 2063-2069.
PMID
22547605
Source
scival
Published In
Journal of Clinical Oncology
Volume
30
Issue
17
Publish Date
2012
Start Page
2063
End Page
2069
DOI
10.1200/JCO.2011.40.1315

Detection of human telomerase reverse transcriptase mRNA in cells obtained by lavage of the pleura is not associated with worse outcome in patients with stage I/II non-small cell lung cancer: Results from Cancer and Leukemia Group B 159902

Objective: Previous studies suggest that cytologic analysis of cells obtained by lavage of the pleural surfaces at the time of resection of non-small cell lung cancer can identify patients at risk for recurrence. Because telomerase gene expression has been associated with worse outcome in non-small cell lung cancer, we hypothesized that identification of cells obtained from pleural lavage that express telomerase would identify patients at risk for recurrent disease. Methods: Patients with presumed non-small cell lung cancer underwent thoracotomy with curative intent. Cells obtained by lavage of the pleural surfaces were analyzed for telomerase catalytic subunit human telomerase reverse transcriptase mRNA expression using reverse transcriptase polymerase chain reaction. Results: A total of 194 patients with stage I/II non-small cell lung cancer had adequate samples, and median follow-up was 60 months (17-91 months). By using Cox models, no statistical differences were found between human telomerase reverse transcriptase-negative and positive patients in disease-free survival (hazard ratio, 1.28; 95% confidence interval, 0.85-1.94; log-rank test, P = .2349) or overall survival (hazard ratio, 1.13; 95% confidence interval, 0.72-1.79; log-rank test, P = .5912). Conclusions: Detection of human telomerase reverse transcriptase in cells obtained from pleural lavage of patients with stage I/II non-small cell lung cancer does not identify patients at risk for recurrent disease. © 2012 The American Association for Thoracic Surgery.

Authors
Boylan, AM; Wang, XF; Ko, R; Watson, PM; Gu, L; Harpole, D; Bueno, R; Kelly, R; Kohman, L; Kratzke, R
MLA Citation
Boylan, AM, Wang, XF, Ko, R, Watson, PM, Gu, L, Harpole, D, Bueno, R, Kelly, R, Kohman, L, and Kratzke, R. "Detection of human telomerase reverse transcriptase mRNA in cells obtained by lavage of the pleura is not associated with worse outcome in patients with stage I/II non-small cell lung cancer: Results from Cancer and Leukemia Group B 159902." Journal of Thoracic and Cardiovascular Surgery (2012).
PMID
23026566
Source
scival
Published In
Journal of Thoracic and Cardiovascular Surgery
Publish Date
2012
DOI
10.1016/j.jtcvs.2012.08.059

Vatalanib in malignant mesothelioma: A phase II trial by the Cancer and Leukemia Group B (CALGB 30107)

Introduction: The Cancer and Leukemia Group B (CALGB) conducted a multi-center phase II trial to evaluate the efficacy and safety of vatalanib in previously untreated patients with malignant mesothelioma and to evaluate potential biomarkers of disease response (CALGB 30107). Methods: Treatment consisted of vatalanib 1250. mg given orally once daily. CT scans were obtained at baseline and every 6 weeks thereafter. Baseline serum levels of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), thrombospondin-1 (TSP-1), and mesothelin were obtained. The primary endpoint was 3-month progression-free survival (PFS). Results: Forty-seven patients enrolled at 19 centers. The median age was 75 years, and the majority of patients (79%) had an ECOG performance status of 1. Tumors were classified as epithelial (77%), sarcomatoid (10%), or mixed (9%) histology. Toxicity was mild; the most common grade 3/4 adverse events were neutropenia (2%), nausea (15%), elevated alanine aminotransferase (11%), hypertension (2%), and gastrointestinal bleeding (2%). Partial responses were observed in 6% of patients and stable disease in 72% of patients. The 3-month PFS rate was 55% (95% CI: 40%, 68%). The median PFS was 4.1 months. Median overall survival was 10.0 months. There was no correlation between serum levels of VEGF, PDGF, TSP-1, or mesothelin and treatment response, PFS, or survival. Conclusions: Vatalanib as a single agent with this dose and schedule does not warrant further study in this disease. © 2011 Elsevier Ireland Ltd.

Authors
Jahan, T; Gu, L; Kratzke, R; Dudek, A; Otterson, GA; Wang, X; Green, M; Vokes, EE; Kindler, HL
MLA Citation
Jahan, T, Gu, L, Kratzke, R, Dudek, A, Otterson, GA, Wang, X, Green, M, Vokes, EE, and Kindler, HL. "Vatalanib in malignant mesothelioma: A phase II trial by the Cancer and Leukemia Group B (CALGB 30107)." Lung Cancer 76.3 (2012): 393-396.
PMID
22197613
Source
scival
Published In
Lung Cancer
Volume
76
Issue
3
Publish Date
2012
Start Page
393
End Page
396
DOI
10.1016/j.lungcan.2011.11.014

Cyclooxygenase-2 (COX-2) as a predictive marker for the use of COX-2 inhibitors in advanced non-small-cell lung cancer

Authors
Edelman, MJ; Hodgson, L; Wang, X; Kratzke, RA; Vokes, EE
MLA Citation
Edelman, MJ, Hodgson, L, Wang, X, Kratzke, RA, and Vokes, EE. "Cyclooxygenase-2 (COX-2) as a predictive marker for the use of COX-2 inhibitors in advanced non-small-cell lung cancer." Journal of Clinical Oncology 30.16 (2012): 2019-2020.
PMID
22473168
Source
scival
Published In
Journal of Clinical Oncology
Volume
30
Issue
16
Publish Date
2012
Start Page
2019
End Page
2020
DOI
10.1200/JCO.2011.41.4581

CYFRA 21-1 as a prognostic and predictive marker in advanced non-small-cell lung cancer in a prospective trial: CALGB 150304

BACKGROUND:: Cytokeratin 19 and its soluble fragment CYFRA have been studied as markers that may be associated with response to therapy and survival in non-small-cell lung cancer (NSCLC). As a prospective correlative study of Cancer and Leukemia Group B 30203, a randomized phase II trial of carboplatin/gemcitabine with eicosanoid modulators (celecoxib, zileuton, or both) in advanced NSCLC, serum CYFRA levels were obtained before and during treatment. METHODS:: Serum CYFRA levels were measured at baseline and after the first cycle of treatment using an electrochemoluminescent assay. Paired specimens were available from 88 patients. The logarithms of the initial concentration and of the difference in concentrations were analyzed for association with overall survival (OS) and failure-free survival (FFS). RESULTS:: Lower baseline CYFRA levels were associated with both longer OS and FFS (p < 0.0001 and p = 0.0003). In addition, larger reductions in CYFRA levels correlated with longer OS and FFS (p = 0.0255 and p = 0.0068). CONCLUSION:: CYFRA and change in CYFRA were found to be reliable markers for response to chemotherapy for NSCLC; however, a precise threshold to mark response has yet to be determined. © 2012 by the International Association for the Study of Lung Cancer.

Authors
Edelman, MJ; Hodgson, L; Rosenblatt, PY; Christenson, RH; Vokes, EE; Wang, X; Kratzke, R
MLA Citation
Edelman, MJ, Hodgson, L, Rosenblatt, PY, Christenson, RH, Vokes, EE, Wang, X, and Kratzke, R. "CYFRA 21-1 as a prognostic and predictive marker in advanced non-small-cell lung cancer in a prospective trial: CALGB 150304." Journal of Thoracic Oncology 7.4 (2012): 649-654.
PMID
22425913
Source
scival
Published In
Journal of Thoracic Oncology
Volume
7
Issue
4
Publish Date
2012
Start Page
649
End Page
654
DOI
10.1097/JTO.0b013e31824a8db0

Nonparametric modeling auxiliary covariates in random coefficient models

Random coefficient model (RCM) is a powerful statistical tool in analyzing correlated data collected from studies with different clusters or from longitudinal studies. In practice, there is a need for statistical methods that allow biomedical researchers to adjust for the measured and unmeasured covariates that might affect the regression model. This article studies two nonparametric methods dealing with auxiliary covariate data in linear random coefficient models. We demonstrate how to estimate the coefficients of the models and how to predict the random effects when the covariates are missing or mismeasured. We employ empirical estimator and kernel smoother to handle a discrete and continuous auxiliary, respectively. Simulation results show that the proposed methods perform better than an alternative method that only uses data in the validation data set and ignores the random effects in the random coefficient model. Copyright © Taylor & Francis Group, LLC.

Authors
Chen, J; Wang, X; Yang, D; Fan, B
MLA Citation
Chen, J, Wang, X, Yang, D, and Fan, B. "Nonparametric modeling auxiliary covariates in random coefficient models." Communications in Statistics: Simulation and Computation 41.8 (2012): 1271-1281.
Source
scival
Published In
Communication in Statistics Part B - Simulation & Computation
Volume
41
Issue
8
Publish Date
2012
Start Page
1271
End Page
1281
DOI
10.1080/03610918.2011.594535

Achieving sufficient accrual to address the primary endpoint in phase III clinical trials from U.S. Cooperative Oncology Groups

Purpose: Assessing impact of poor accrual on premature trial closure requires a relevant metric. We propose defining accrual sufficiency on apparent ability to address primary endpoints (PE) rather than attaining accrual targets. Experimental Design: All phase III trials open January 1, 1993, to December 31, 2002, by five U.S. oncology Clinical Trials Cooperative Groups (CTCG) were evaluated for accrual sufficiency and scientific results. Sufficient accrual included meeting accrual target, CTCGs documentation attesting adequate accrual, or conclusive results at interim analysis; insufficient accrual included poor accrual as cited closure reason or other reasons rendering a trial unable to address its primary endpoints. Closure rates based on our accrual sufficiency definition are compared with rates of meeting accrual targets and addressing the primary endpoints. A percentage of target accrual above which trials commonly answer the intended scientific question was identified to serve as an alternative to meeting full target accrual in designating accrual success. Results: Of 238 eligible trials, 158 (66%) closed with sufficient accrual. Among 80 trials with insufficient accrual, 70 (29%) closed specifically because of poor accrual. Inadequate accrual rates are overemphasized when defining accrual success solely by meeting accrual targets. Nearly 75% of trials conclusively addressed the primary endpoints with positive results in 39% of trials. Exceeding 80% of target accrual serves as a reliable proxy for answering the intended scientific question. Conclusions: Approximately one third of phase III trials closed with insufficient accrual to address the primary endpoints, primarily due to poor accrual. Defining accrual sufficiency broader than meeting accrual targets represents a fairer account of trial closures. ©2011 AACR.

Authors
Schroen, AT; Petroni, GR; Wang, H; Thielen, MJ; Gray, R; Benedetti, J; Wang, XF; Sargent, DJ; Wickerham, DL; Cronin, W; Djulbegovic, B; Jr, CLS
MLA Citation
Schroen, AT, Petroni, GR, Wang, H, Thielen, MJ, Gray, R, Benedetti, J, Wang, XF, Sargent, DJ, Wickerham, DL, Cronin, W, Djulbegovic, B, and Jr, CLS. "Achieving sufficient accrual to address the primary endpoint in phase III clinical trials from U.S. Cooperative Oncology Groups." Clinical Cancer Research 18.1 (2012): 256-262.
PMID
21976533
Source
scival
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
18
Issue
1
Publish Date
2012
Start Page
256
End Page
262
DOI
10.1158/1078-0432.CCR-11-1633

Pulmonary toxicity in Stage III non-small cell lung cancer patients treated with high-dose (74 Gy) 3-dimensional conformal thoracic radiotherapy and concurrent chemotherapy following induction chemotherapy: a secondary analysis of Cancer and Leukemia Group B (CALGB) trial 30105.

PURPOSE: Cancer and Leukemia Group B (CALGB) 30105 tested two different concurrent chemoradiotherapy platforms with high-dose (74 Gy) three-dimensional conformal radiotherapy (3D-CRT) after two cycles of induction chemotherapy for Stage IIIA/IIIB non-small cell lung cancer (NSCLC) patients to determine if either could achieve a primary endpoint of >18-month median survival. Final results of 30105 demonstrated that induction carboplatin and gemcitabine and concurrent gemcitabine 3D-CRT was not feasible because of treatment-related toxicity. However, induction and concurrent carboplatin/paclitaxel with 74 Gy 3D-CRT had a median survival of 24 months, and is the basis for the experimental arm in CALGB 30610/RTOG 0617/N0628. We conducted a secondary analysis of all patients to determine predictors of treatment-related pulmonary toxicity. METHODS AND MATERIALS: Patient, tumor, and treatment-related variables were analyzed to determine their relation with treatment-related pulmonary toxicity. RESULTS: Older age, higher N stage, larger planning target volume (PTV)1, smaller total lung volume/PTV1 ratio, larger V20, and larger mean lung dose were associated with increasing pulmonary toxicity on univariate analysis. Multivariate analysis confirmed that V20 and nodal stage as well as treatment with concurrent gemcitabine were associated with treatment-related toxicity. A high-risk group comprising patients with N3 disease and V20 >38% was associated with 80% of Grades 3-5 pulmonary toxicity cases. CONCLUSIONS: Elevated V20 and N3 disease status are important predictors of treatment related pulmonary toxicity in patients treated with high-dose 3D-CRT and concurrent chemotherapy. Further studies may use these metrics in considering patients for these treatments.

Authors
Salama, JK; Stinchcombe, TE; Gu, L; Wang, X; Morano, K; Bogart, JA; Crawford, JC; Socinski, MA; Blackstock, AW; Vokes, EE; Cancer and Leukemia Group B,
MLA Citation
Salama, JK, Stinchcombe, TE, Gu, L, Wang, X, Morano, K, Bogart, JA, Crawford, JC, Socinski, MA, Blackstock, AW, Vokes, EE, and Cancer and Leukemia Group B, . "Pulmonary toxicity in Stage III non-small cell lung cancer patients treated with high-dose (74 Gy) 3-dimensional conformal thoracic radiotherapy and concurrent chemotherapy following induction chemotherapy: a secondary analysis of Cancer and Leukemia Group B (CALGB) trial 30105." Int J Radiat Oncol Biol Phys 81.4 (November 15, 2011): e269-e274.
PMID
21477940
Source
pubmed
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
81
Issue
4
Publish Date
2011
Start Page
e269
End Page
e274
DOI
10.1016/j.ijrobp.2011.01.056

OUTCOME OF ADVANCED NSCLC PATIENTS WITH EGFR EXON 19 AND 21 MUTATIONS TREATED WITH ERLOTINIB (E) ALONE OR IN COMBINATION WITH CARBOPLATIN/PACLITAXEL (CP) IN CALGB 30406.

Authors
Janne, PA; Wang, X; Socinski, MA; Crawford, J; Gu, L; Capelletti, M; Edelman, MJ; Villalona-Calero, MA; Kratzke, RA; Vokes, E; Miller, VA
MLA Citation
Janne, PA, Wang, X, Socinski, MA, Crawford, J, Gu, L, Capelletti, M, Edelman, MJ, Villalona-Calero, MA, Kratzke, RA, Vokes, E, and Miller, VA. "OUTCOME OF ADVANCED NSCLC PATIENTS WITH EGFR EXON 19 AND 21 MUTATIONS TREATED WITH ERLOTINIB (E) ALONE OR IN COMBINATION WITH CARBOPLATIN/PACLITAXEL (CP) IN CALGB 30406." JOURNAL OF THORACIC ONCOLOGY 6.6 (June 2011): S447-S448.
Source
wos-lite
Published In
Journal of Thoracic Oncology
Volume
6
Issue
6
Publish Date
2011
Start Page
S447
End Page
S448

Stratified multivariate Mann-Whitney estimators for the comparison of two treatments with randomization based covariance adjustment

Methodology for comparing two randomly assigned treatments for strictly ordinal response variables has been discussed throughout the literature on multivariate Mann-Whitney estimators with stratification adjustment. Although such estimators can be computed directly as weighted linear combinations of within-stratum Mann-Whitney estimators, consistent estimation of their covariance matrix is done using methods for multivariate U-statistics. The scope of these methods includes ways of managing randomly missing data and ways to invoke randomization-based covariance adjustment for no differences between treatments for background or baseline covariables. The assessment of treatment differences can be done using confidence intervals or statistical tests for the adjusted Mann-Whitney estimators. The methods in this article are illustrated using three examples. The first example is a randomized clinical trial with eight strata and a univariate ordinal response variable. The second example is a randomized clinical trial with four strata, two covariables, and four ordinal response variables. The third example is a randomized two-period crossover clinical trial with four strata, three covariables (as age, screening, first baseline), three response variables (as first period response, second baseline, second period response), and missing data. For these examples, the results are interpretable through the probability of better outcomes for one treatment over the other. © American Statistical Association Statistics in Biopharmaceutical Research.

Authors
Kawaguchi, A; Koch, GG; Wang, X
MLA Citation
Kawaguchi, A, Koch, GG, and Wang, X. "Stratified multivariate Mann-Whitney estimators for the comparison of two treatments with randomization based covariance adjustment." Statistics in Biopharmaceutical Research 3.2 (2011): 217-231.
Source
scival
Published In
Statistics in Biopharmaceutical Research
Volume
3
Issue
2
Publish Date
2011
Start Page
217
End Page
231
DOI
10.1198/sbr.2010.10007

Serum vascular endothelial growth factor and COX-2/5-LOX inhibition in advanced non-small cell lung cancer: Cancer and leukemia group B 150304

Introduction: Eicosanoids, including PGE-2 and 5-HETE, can increase levels of plasma vascular endothelial growth factor (VEGF). Overexpression of COX-2 or 5-LOX increases levels of PGE-2 and 5-HETE, respectively. Elevated levels of VEGF are common in patients with non-small cell lung cancer (NSCLC). We prospectively measured VEGF in serum collected from patients enrolled in Cancer and Leukemia Group B 30203, a randomized phase II study of eicosanoid modulation in addition to chemotherapy in patients with advanced NSCLC, to determine whether these levels had prognostic significance and whether they correlated with COX-2 expression and/or responded to inhibition of COX-2 or 5-LOX. Methods: Pre- and post-treatment serum was collected from patients enrolled in CALGB 30203. Serum VEGF levels were determined using enzyme-linked immunosorbent assay methodology. Statistical analyses were performed to determine the correlation between pretreatment serum VEGF levels and time of overall survival. Pretreatment formalin fixed tissue was stained for 5-LOX and COX-2 by immunohistochemistry. Results: The median baseline VEGF level was 502 pg/ml (range, 55-3453 pg/ml). Dichotomized serum VEGF levels at median inversely correlated with survival time (p = 0.008), as did VEGF levels as a continuous variable in multivariate analysis (p = 0.035). VEGF levels were significantly correlated neither with baseline COX-2 expression (Pearson r = 0.1524, p = 0.271) nor with 5-LOX expression. Treatment with COX-2 or 5-LOX inhibitors did not alter the levels. Conclusion: These data indicate that elevated serum VEGF is a negative prognostic variable in NSCLC. VEGF levels are neither correlated with baseline tumor COX-2 expression nor do they respond to COX-2 and/or 5-LOX inhibition plus chemotherapy. Copyright © 2011 by the International Association for the Study of Lung Cancer.

Authors
Edelman, MJ; Hodgson, L; Wang, X; Christenson, R; Jewell, S; Vokes, E; Kratzke, R
MLA Citation
Edelman, MJ, Hodgson, L, Wang, X, Christenson, R, Jewell, S, Vokes, E, and Kratzke, R. "Serum vascular endothelial growth factor and COX-2/5-LOX inhibition in advanced non-small cell lung cancer: Cancer and leukemia group B 150304." Journal of Thoracic Oncology 6.11 (2011): 1902-1906.
PMID
21964530
Source
scival
Published In
Journal of Thoracic Oncology
Volume
6
Issue
11
Publish Date
2011
Start Page
1902
End Page
1906
DOI
10.1097/JTO.0b013e31822a7383

Challenges to accrual predictions to phase III cancer clinical trials: A survey of study chairs and lead statisticians of 248 NCI-sponsored trials

Background Research on barriers to accrual has typically emphasized factors influencing participation after trial activation.Purpose We sought to identify factors influencing trial design and accrual predictions prior to trial activation associated with sufficient accrual.Methods A 30-question web-based survey was sent to the study chair and lead statistician for all 248 phase III trials open in 1993-2002 by five Clinical Trials Cooperative Groups. Questions addressed prior trial experience, trial design elements, accrual predictions, and perceived accrual influences. Accrual sufficiency categorization was derived from Clinical Trials Cooperative Group records: sufficient accrual included trials closed with complete accrual or at interim analysis, insufficient accrual included trials closed with inadequate accrual. Responses were analyzed by respondent role (study chair/lead statistician) and accrual sufficiency.Results Three hundred and nine eligible responses were included (response rate, 63%; lead statisticians, 81%; and study chairs, 45%), representing trials with sufficient (63%) and insufficient accruals (37%). Study chair seniority or lead statistician experience was not linked to accrual sufficiency. Literature review, study chair's personal experience, and expert opinion within Clinical Trials Cooperative Group most commonly influenced control arm selection. Clinical Trials Cooperative Group experience most influenced accrual predictions. These influences were not associated with accrual sufficiency. Among respondents citing accrual difficulties (41%), factors negatively influencing accrual were not consistently identified. Respondents credited three factors with positively influencing accrual: clinical relevance of study, lack of competing trials, and protocol paralleling normal practice.Limitations Perceptions of lead statisticians and study chairs may not accurately reflect accrual barriers encountered by participating physicians or patients. Survey responses may be subject to recall bias.Conclusion Consistent factors explaining poor accrual were not identified, suggesting reasons for poor accrual are not well understood and warrant further study. Alternate strategies for accrual prediction are needed since Clinical Trials Cooperative Group experience is linked to successful and unsuccessful accrual. © 2011 The Author(s).

Authors
Schroen, AT; Petroni, GR; Wang, H; Thielen, MJ; Sargent, D; Benedetti, JK; Cronin, WM; Wickerham, DL; Wang, XF; Gray, R; Cohn, WF; Slingluff, CL; Djulbegovic, B
MLA Citation
Schroen, AT, Petroni, GR, Wang, H, Thielen, MJ, Sargent, D, Benedetti, JK, Cronin, WM, Wickerham, DL, Wang, XF, Gray, R, Cohn, WF, Slingluff, CL, and Djulbegovic, B. "Challenges to accrual predictions to phase III cancer clinical trials: A survey of study chairs and lead statisticians of 248 NCI-sponsored trials." Clinical Trials 8.5 (2011): 591-600.
PMID
21878447
Source
scival
Published In
Clinical Trials
Volume
8
Issue
5
Publish Date
2011
Start Page
591
End Page
600
DOI
10.1177/1740774511419683

Optimal weight in estimating and comparing areas under the receiver operating characteristic curve using longitudinal data

In the setting of longitudinal study, subjects are followed for the occurrence of some dichotomous outcome. In many of these studies, some markers are also obtained repeatedly during the study period. Emir et al. introduced a non-parametric approach to the estimation of the area under the ROC curve of a repeated marker. Their non-parametric estimate involves assigning a weight to each subject. There are two weighting schemes suggested in their paper: one for the case when within-patient correlation is low, and the other for the case when within-subject correlation is high. However, it is not clear how to assign weights to marker measurements when within-patient correlation is modest. In this paper, we consider the optimal weights that minimize the variance of the estimate of the area under the ROC curve (AUC) of a repeated marker, as well as the optimal weights that minimize the variance of the AUC difference between two repeated markers. Our results in this paper show that the optimal weights depend not only on the within-patient control-case correlation in the longitudinal data, but also on the proportion of subjects that become cases. More importantly, we show that the loss of efficiency by using the two weighting schemes suggested by Emir et al. instead of our optimal weights can be severe when there is a large within-subject control-case correlation and the proportion of subjects that become cases is small, which is often the case in longitudinal study settings. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Authors
Wu, Y; Wang, X
MLA Citation
Wu, Y, and Wang, X. "Optimal weight in estimating and comparing areas under the receiver operating characteristic curve using longitudinal data." Biometrical Journal 53.5 (2011): 764-778.
PMID
21805488
Source
scival
Published In
Biometrical Journal
Volume
53
Issue
5
Publish Date
2011
Start Page
764
End Page
778
DOI
10.1002/bimj.201100033

Randomized phase II study of pemetrexed, carboplatin, and thoracic radiation with or without cetuximab in patients with locally advanced unresectable non-small-cell lung cancer: Cancer and leukemia group B trial 30407

Purpose: Cancer and Leukemia Group B conducted a randomized phase II trial to investigate two novel chemotherapy regimens in combination with concurrent thoracic radiation therapy (TRT). Patients and Methods: Patients with unresectable stage III non-small-cell lung cancer (NSCLC) were randomly assigned to carboplatin (area under the curve, 5) and pemetrexed (500 mg/m2) every 21 days for four cycles and TRT (70 Gy; arm A) or the same treatment with cetuximab administered concurrent only with TRT (arm B). Patients in both arms received up to four cycles of pemetrexed as consolidation therapy. The primary end point was the 18-month overall survival (OS) rate; if the 18-month OS rate was ≥ 55%, the regimen(s) would be considered for further study. Results: Of the 101 eligible patients enrolled (48 in arm A and 53 in arm B), 60% were male; the median age was 66 years (range, 32 to 81 years); 44% and 35% had adenocarcinoma and squamous carcinoma, respectively; and more patients enrolled onto arm A compared with arm B had a performance status of 0 (58% v 34%, respectively; P = .04). The 18-month OS rate was 58% (95% CI, 46% to 74%) in arm A and 54% (95% CI, 42% to 70%) in arm B. No significant difference in OS between patients with squamous and nonsquamous NSCLC was observed (P = .667). The toxicities observed were consistent with toxicities associated with concurrent chemoradiotherapy. Conclusion: The combination of pemetrexed, carboplatin, and TRT met the prespecified criteria for further evaluation. This regimen should be studied further in patients with locally advanced unresectable nonsquamous NSCLC. © 2011 by American Society of Clinical Oncology.

Authors
Govindan, R; Bogart, J; Stinchcombe, T; Wang, X; Hodgson, L; Kratzke, R; Garst, J; Brotherton, T; Vokes, EE
MLA Citation
Govindan, R, Bogart, J, Stinchcombe, T, Wang, X, Hodgson, L, Kratzke, R, Garst, J, Brotherton, T, and Vokes, EE. "Randomized phase II study of pemetrexed, carboplatin, and thoracic radiation with or without cetuximab in patients with locally advanced unresectable non-small-cell lung cancer: Cancer and leukemia group B trial 30407." Journal of Clinical Oncology 29.23 (2011): 3120-3125.
PMID
21747084
Source
scival
Published In
Journal of Clinical Oncology
Volume
29
Issue
23
Publish Date
2011
Start Page
3120
End Page
3125
DOI
10.1200/JCO.2010.33.4979

A phase II trial of high dose carboplatin and paclitaxel with G-CSF and peripheral blood stem cell support followed by surgery and/or chest radiation in patients with stage III non-small cell lung cancer: CALGB 9531

Purpose: We designed a phase II trial to evaluate the efficacy and tolerability of high dose induction chemotherapy with carboplatin and paclitaxel with G-CSF and stem cell support followed by surgical resection and/or chest radiotherapy in patients with stage III non-small cell lung cancer (NSCLC). Patients and methods: Patients had pathologically confirmed stage IIIA-IIIB NSCLC, adequate end-organ function, no prior chemotherapy or radiation, and performance status 0-1. Peripheral stem cells were mobilized with G-CSF stimulation on days 1-5 and collected prior to chemotherapy. Chemotherapy consisted of 2 cycles of paclitaxel 250mg/m 2 over 3h and carboplatin at an AUC 18 on days 11 and 32, each followed by stem cell reinfusion. Stable and responding patients went on to surgical resection (in patients deemed resectable) followed by post-operative radiation, or to conventional chest radiotherapy to 66Gy in unresectable patients. Results: Twelve patients (11 eligible) were accrued from 1996 to 1999. The 11 patients were predominately male (64%), white (82%), of performance status 0 (64%), and with weight loss less than 5% (55%). The median age was 51 (range 31-63). Ten (10) patients (91%) experienced grade 4 toxicity. There were no lethal toxicities. Grade 3-4 toxicities most commonly reported included: platelets (100%), lymphocytopenia (91%), leukopenia (91%), neutropenia (73%), anemia (55%), pain (45%), and nausea (27%). Three patients (27%) had a partial response to induction chemotherapy. Of the 11 patients, 7 underwent surgical exploration, and 10 received radiation. Two patients were completely resected, 3 patients had incomplete resections, and 2 patients had no resection. There were 4 complete responses and 3 partial responses following surgery and/or radiation. The median overall survival time was 17.8 months. The median failure-free survival time was 8.3 months. One-year and 2-year overall survival are estimated at 64% and 27%, respectively. Conclusions: High dose induction chemotherapy with carboplatin and paclitaxel and stem cell support in patients with stage IIIA-IIIB NSCLC produced response rates and survival similar to standard therapy. Excessive toxicity (and cost) suggests that this approach does not merit further investigation. © 2011 Elsevier Ireland Ltd.

Authors
Masters, GA; Wang, X; Hodgson, L; Shea, T; Vokes, E; Green, M
MLA Citation
Masters, GA, Wang, X, Hodgson, L, Shea, T, Vokes, E, and Green, M. "A phase II trial of high dose carboplatin and paclitaxel with G-CSF and peripheral blood stem cell support followed by surgery and/or chest radiation in patients with stage III non-small cell lung cancer: CALGB 9531." Lung Cancer 74.2 (2011): 258-263.
PMID
21529989
Source
scival
Published In
Lung Cancer
Volume
74
Issue
2
Publish Date
2011
Start Page
258
End Page
263
DOI
10.1016/j.lungcan.2011.03.015

A phase II study of sorafenib in malignant mesothelioma: results of Cancer and Leukemia Group B 30307.

HYPOTHESIS: Malignant mesotheliomas (MMs) express vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, and cKIT. Sorafenib is a potent inhibitor of the ras/raf/MEK pathway and also targets VEGFR and cKIT. We evaluated the activity of sorafenib in patients with unresectable mesothelioma. METHODS: MM patients who had received 0 to 1 prior chemotherapy regimens were treated with sorafenib 400 mg orally twice daily continuously. The primary end point was objective response. ERK1/2 phosphorylation in archival tissues was correlated with response and survival. RESULTS: A total of 51 patients were enrolled, 50 were evaluable and included in the analysis. Three patients had a partial response (6% [95% confidence interval = 1.3-16.6%]), and 27 (54% [95% confidence interval = 39.3-68.2%]) had stable disease. Median progression-free survival and median overall survival (OS) were 3.6 and 9.7 months, respectively. Median survival was superior in epithelioid histology versus other types (10.7 versus 3.7 months, p = 0.0179). The difference in median OS between pretreated and chemonaive patients was not statistically significant (13.2 versus 5 months, p = 0.3117). Low/negative baseline tumor phospho-ERK1/2 levels were associated with improved OS (13.9 versus 5.2 months, p = 0.0066). CONCLUSION: Sorafenib has limited activity in advanced MM patients, similar to that seen with other VEGFR tyrosine kinase inhibitors. Additional studies of sorafenib in MM are not warranted.

Authors
Dubey, S; Jänne, PA; Krug, L; Pang, H; Wang, X; Heinze, R; Watt, C; Crawford, J; Kratzke, R; Vokes, E; Kindler, HL
MLA Citation
Dubey, S, Jänne, PA, Krug, L, Pang, H, Wang, X, Heinze, R, Watt, C, Crawford, J, Kratzke, R, Vokes, E, and Kindler, HL. "A phase II study of sorafenib in malignant mesothelioma: results of Cancer and Leukemia Group B 30307." J Thorac Oncol 5.10 (October 2010): 1655-1661.
PMID
20736856
Source
pubmed
Published In
Journal of Thoracic Oncology
Volume
5
Issue
10
Publish Date
2010
Start Page
1655
End Page
1661
DOI
10.1097/JTO.0b013e3181ec18db

Chemoradiotherapy and gefitinib in stage III non-small cell lung cancer with epidermal growth factor receptor and KRAS mutation analysis: cancer and leukemia group B (CALEB) 30106, a CALGB-stratified phase II trial.

INTRODUCTION: This study evaluated the addition of gefitinib to sequential or concurrent chemoradiotherapy (CRT) in unresectable stage III non-small cell lung cancer. METHODS: Between May 2002 and April 2005, 63 patients were entered before the study closing early. All received two cycles paclitaxel 200 mg/m and carboplatin area under the curve 6 intravenous plus gefitinib 250 mg daily. Poor risk stratum 1 (> or =5% weight loss and/or performance status 2) received radiotherapy 200 cGy for 33 fractions (6600 cGy) and gefitinib 250 mg daily. Good-risk stratum 2 (performance status: 0-1 weight loss and <5%) received the same RT with gefitinib 250 mg daily and weekly paclitaxel 50 mg/m plus carboplatin AUC 2. Consolidation gefitinib until progression was started after all toxicities were grade < or =2. RESULTS: Acute high-grade infield toxicities were not clearly increased compared with historical CRT data. Poor-risk (N = 21) median progression-free survival was 13.4 months (95% confidence interval [CI]: 6.4-25.2) and median overall survival 19.0 months (95% CI: 9.9-28.4). Good-risk (N = 39) median progression-free survival was 9.2 months (95% CI: 6.7-12.2), and median overall survival was 13 months (95% CI: 8.5-17.2). Thirteen of 45 tumors analyzed had activating epidermal growth factor receptor (EGFR) mutations, and 2 of 13 also had T790M mutations. Seven tumors of 45 had KRAS mutations. There was no apparent survival difference with EGFR-activating mutations versus wild type or KRAS mutation versus wild type. CONCLUSIONS: Survival of poor-risk patients with wild type or mutated EGFR receiving sequential CRT with gefitinib was promising. Survival for good-risk patients receiving concurrent CRT plus gefitinib was disappointing even for tumors with activating EGFR mutations.

Authors
Ready, N; Jänne, PA; Bogart, J; Dipetrillo, T; Garst, J; Graziano, S; Gu, L; Wang, X; Green, MR; Vokes, EE; Cancer, Leukemia Group B, Chicago, IL,
MLA Citation
Ready, N, Jänne, PA, Bogart, J, Dipetrillo, T, Garst, J, Graziano, S, Gu, L, Wang, X, Green, MR, Vokes, EE, Cancer, Leukemia Group B, Chicago, and IL, . "Chemoradiotherapy and gefitinib in stage III non-small cell lung cancer with epidermal growth factor receptor and KRAS mutation analysis: cancer and leukemia group B (CALEB) 30106, a CALGB-stratified phase II trial." J Thorac Oncol 5.9 (September 2010): 1382-1390.
PMID
20686428
Source
pubmed
Published In
Journal of Thoracic Oncology
Volume
5
Issue
9
Publish Date
2010
Start Page
1382
End Page
1390
DOI
10.1097/JTO.0b013e3181eba657

Preliminary evaluation of factors associated with premature trial closure and feasibility of accrual benchmarks in phase III oncology trials

Authors
Schroen, AT; Petroni, GR; Wang, H; Gray, R; Wang, XF; Cronin, W; Sargent, DJ; Benedetti, J; Wickerham, DL; Djulbegovic, B; Jr, SCL
MLA Citation
Schroen, AT, Petroni, GR, Wang, H, Gray, R, Wang, XF, Cronin, W, Sargent, DJ, Benedetti, J, Wickerham, DL, Djulbegovic, B, and Jr, SCL. "Preliminary evaluation of factors associated with premature trial closure and feasibility of accrual benchmarks in phase III oncology trials." CLINICAL TRIALS 7.4 (August 2010): 312-321.
PMID
20595245
Source
wos-lite
Published In
Clinical Trials
Volume
7
Issue
4
Publish Date
2010
Start Page
312
End Page
321
DOI
10.1177/1740774510374973

Design and inference for cancer biomarker study with an outcome and auxiliary-dependent subsampling.

In cancer research, it is important to evaluate the performance of a biomarker (e.g., molecular, genetic, or imaging) that correlates patients' prognosis or predicts patients' response to treatment in a large prospective study. Due to overall budget constraint and high cost associated with bioassays, investigators often have to select a subset from all registered patients for biomarker assessment. To detect a potentially moderate association between the biomarker and the outcome, investigators need to decide how to select the subset of a fixed size such that the study efficiency can be enhanced. We show that, instead of drawing a simple random sample from the study cohort, greater efficiency can be achieved by allowing the selection probability to depend on the outcome and an auxiliary variable; we refer to such a sampling scheme as outcome and auxiliary-dependent subsampling (OADS). This article is motivated by the need to analyze data from a lung cancer biomarker study that adopts the OADS design to assess epidermal growth factor receptor (EGFR) mutations as a predictive biomarker for whether a subject responds to a greater extent to EGFR inhibitor drugs. We propose an estimated maximum-likelihood method that accommodates the OADS design and utilizes all observed information, especially those contained in the likelihood score of EGFR mutations (an auxiliary variable of EGFR mutations) that is available to all patients. We derive the asymptotic properties of the proposed estimator and evaluate its finite sample properties via simulation. We illustrate the proposed method with a data example.

Authors
Wang, X; Zhou, H
MLA Citation
Wang, X, and Zhou, H. "Design and inference for cancer biomarker study with an outcome and auxiliary-dependent subsampling." Biometrics 66.2 (June 2010): 502-511.
PMID
19508239
Source
pubmed
Published In
Biometrics
Volume
66
Issue
2
Publish Date
2010
Start Page
502
End Page
511
DOI
10.1111/j.1541-0420.2009.01280.x

Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer.

The previous individual patient data meta-analyses of chemotherapy in locally advanced non-small-cell lung cancer (NSCLC) showed that adding sequential or concomitant chemotherapy to radiotherapy improved survival. The NSCLC Collaborative Group performed a meta-analysis of randomized trials directly comparing concomitant versus sequential radiochemotherapy.Systematic searches for trials were undertaken, followed by central collection, checking, and reanalysis of updated individual patient data. Results from trials were combined using the stratified log-rank test to calculate pooled hazard ratios (HRs). The primary outcome was overall survival; secondary outcomes were progression-free survival, cumulative incidences of locoregional and distant progression, and acute toxicity.Of seven eligible trials, data from six trials were received (1,205 patients, 92% of all randomly assigned patients). Median follow-up was 6 years. There was a significant benefit of concomitant radiochemotherapy on overall survival (HR, 0.84; 95% CI, 0.74 to 0.95; P = .004), with an absolute benefit of 5.7% (from 18.1% to 23.8%) at 3 years and 4.5% at 5 years. For progression-free survival, the HR was 0.90 (95% CI, 0.79 to 1.01; P = .07). Concomitant treatment decreased locoregional progression (HR, 0.77; 95% CI, 0.62 to 0.95; P = .01); its effect was not different from that of sequential treatment on distant progression (HR, 1.04; 95% CI, 0.86 to 1.25; P = .69). Concomitant radiochemotherapy increased acute esophageal toxicity (grade 3-4) from 4% to 18% with a relative risk of 4.9 (95% CI, 3.1 to 7.8; P < .001). There was no significant difference regarding acute pulmonary toxicity.Concomitant radiochemotherapy, as compared with sequential radiochemotherapy, improved survival of patients with locally advanced NSCLC, primarily because of a better locoregional control, but at the cost of manageable increased acute esophageal toxicity.

Authors
Aupérin, A; Le Péchoux, C; Rolland, E; Curran, WJ; Furuse, K; Fournel, P; Belderbos, J; Clamon, G; Ulutin, HC; Paulus, R; Yamanaka, T; Bozonnat, M-C; Uitterhoeve, A; Wang, X; Stewart, L; Arriagada, R; Burdett, S; Pignon, J-P
MLA Citation
Aupérin, A, Le Péchoux, C, Rolland, E, Curran, WJ, Furuse, K, Fournel, P, Belderbos, J, Clamon, G, Ulutin, HC, Paulus, R, Yamanaka, T, Bozonnat, M-C, Uitterhoeve, A, Wang, X, Stewart, L, Arriagada, R, Burdett, S, and Pignon, J-P. "Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 28.13 (May 2010): 2181-2190. (Review)
PMID
20351327
Source
epmc
Published In
Journal of Clinical Oncology
Volume
28
Issue
13
Publish Date
2010
Start Page
2181
End Page
2190
DOI
10.1200/jco.2009.26.2543

Prognostic significance of mucin and P53 expression in stage ib non-small cell lung cancer: A laboratory companion study to CALGB 9633

INTRODUCTION:: Cancer and Leukemia Group B 9633 was a phase III trial that randomized patients with stage IB non-small cell lung cancer to observation or four cycles of carboplatin and paclitaxel. A statistically significant effect in favor of adjuvant chemotherapy was seen for disease-free survival (DFS) and overall survival (OS) in the subgroup of patients with tumors ä4 cm. A laboratory companion study was conducted to see whether molecular and clinical factors could provide additional prognostic information. METHODS:: Formalin-fixed, paraffin-embedded blocks were obtained for 250 of the 344 patients enrolled. Immunohistochemical staining for bcl-2, p53, blood group antigen A, and mucin was correlated with DFS and OS. RESULTS:: The prevalence of the markers was bcl-2, 17%; p53, 47%; blood group antigen A, 25%; and mucin, 45%. Univariate analysis for DFS showed a statistically significant effect for the presence of mucin (p = 0.0005) and p53 (p = 0.05) and for OS showed a significant effect for mucin (p = 0.0005). In the multivariate Cox model, there was a statistically significant association between shorter DFS and presence of mucin (p = 0.002; hazard ratio [HR] 2.05) and p53 (p = 0.003; HR 1.95) and between shorter OS and presence of mucin (p = 0.004; HR 2.03) and p53 (p = 0.0005; HR 2.30). Of the clinical factors, male gender and larger tumor volume were also significant adverse prognostic factors (p < 0.05). CONCLUSIONS:: A statistically significant association between shorter DFS and OS was seen for the patients with p53 protein expression, mucin expression, male gender, and larger tumors in this cohort of patients with stage IB non-small cell lung cancer treated on Cancer and Leukemia Group B 9633. Copyright © 2010 by the International Association for the Study of Lung Cancer.

Authors
Graziano, SL; Gu, L; Wang, X; Tatum, AH; Vollmer, RT; Strauss, GM; Kratzke, R; Dudek, AZ; Vokes, EE; Green, MR
MLA Citation
Graziano, SL, Gu, L, Wang, X, Tatum, AH, Vollmer, RT, Strauss, GM, Kratzke, R, Dudek, AZ, Vokes, EE, and Green, MR. "Prognostic significance of mucin and P53 expression in stage ib non-small cell lung cancer: A laboratory companion study to CALGB 9633." Journal of Thoracic Oncology 5.6 (2010): 810-817.
PMID
20521348
Source
scival
Published In
Journal of Thoracic Oncology
Volume
5
Issue
6
Publish Date
2010
Start Page
810
End Page
817
DOI
10.1097/JTO.0b013e3181d89f95

Phase I study of accelerated conformal radiotherapy for stage I non-small-cell lung cancer in patients with pulmonary dysfunction: CALGB 39904

Purpose: The optimal treatment for medically inoperable stage I non-small-cell lung cancer (NSCLC) has not been defined. Patients and Methods: Cancer and Leukemia Group B trial 39904 prospectively assessed accelerated, once-daily, three-dimensional radiotherapy for early-stage NSCLC. The primary objectives were to define the maximally accelerated course of conformal radiotherapy and to describe the short-term and long-term toxicity of therapy. Entry was limited to patients with clinical stage T1N0 or T2N0 NSCLC (< 4 cm) and pulmonary dysfunction. The nominal total radiotherapy dose remained at 70 Gy, while the number of daily fractions in each successive cohort was reduced. Results: Thirty-nine eligible patients were accrued (eight patients each on cohorts 1 to 4 and seven patients on cohort 5) between January 2001 and July 2005. One grade 3 nonhematologic toxicity was observed in both cohort 3 (dyspnea) and cohort 4 (pain). The major response rate was 77%. After a median follow-up time of 53 months, the actuarial median survival time of all eligible patients was 38.5 months. Local relapse was observed in three patients. Conclusion: Accelerated conformal radiotherapy was well tolerated in a high-risk population with clinical stage I NSCLC. Outcomes are comparable to prospective reports of alternative therapies, including stereotactic body radiation therapy and limited resection, with less apparent severe toxicity. Further investigation of this approach is warranted. © 2009 by American Society of Clinical Oncology.

Authors
Bogart, JA; Hodgson, L; Seagren, SL; Blackstock, AW; Wang, X; Lenox, R; III, ATT; Reilly, J; Gajra, A; Vokes, EE; Green, MR
MLA Citation
Bogart, JA, Hodgson, L, Seagren, SL, Blackstock, AW, Wang, X, Lenox, R, III, ATT, Reilly, J, Gajra, A, Vokes, EE, and Green, MR. "Phase I study of accelerated conformal radiotherapy for stage I non-small-cell lung cancer in patients with pulmonary dysfunction: CALGB 39904." Journal of Clinical Oncology 28.2 (2010): 202-206.
PMID
19933904
Source
scival
Published In
Journal of Clinical Oncology
Volume
28
Issue
2
Publish Date
2010
Start Page
202
End Page
206
DOI
10.1200/JCO.2009.25.0753

Adherence and persistence with oral adjuvant chemotherapy in older women with early-stage breast cancer in CALGB 49907: Adherence companion study 60104

Purpose: Patient adherence is critical in evaluating the effectiveness of an oral therapy. We sought to measure adherence among women randomly assigned to capecitabine in a preplanned substudy of a multicenter clinical trial. Patients and Methods: Cancer and Leukemia Group B study CALGB 49907 was a randomly assigned trial comparing standard chemotherapy versus oral chemotherapy with capecitabine in patients age 65 years or older with early-stage breast cancer. We used microelectronic monitoring system (MEMS) caps on participants' capecitabine bottles to record pill bottle openings. Capecitabine was given in two divided daily doses for 14 consecutive days of a 21-day cycle for six cycles. Adherence was calculated as the number of doses taken divided by doses expected, taking into account toxicity-related dosing changes. A participant was defined as adherent if 80% or more of expected doses were recorded by MEMS. Results: Overall, 161 patients were enrolled. Median age was 71 years (range, 65 to 89 years); 124 patients (83%) persisted with capecitabine to completion of planned protocol therapy. Adherence was 78% across all cycles, and adherence did not vary by cycle (P = .32). Twenty-five percent of participants took fewer than 80% of expected doses and were nonadherent. In a logistic regression model, participants with node-negative disease (P = .01) and mastectomy (P = .01) were more likely to be nonadherent. Adherence was not related to age, tumor stage, or hormone receptor status. Adherence was not significantly associated with relapse-free survival or grade 3 or 4 toxicity. Conclusion: Most older women with early-stage breast cancer were adherent to short-term oral chemotherapy in a randomized clinical trial. Age was not associated with adherence. © 2010 by American Society of Clinical Oncology.

Authors
Partridge, AH; Archer, L; Kornblith, AB; Gralow, J; Grenier, D; Perez, E; Wolff, AC; Wang, X; Kastrissios, H; Berry, D; Hudis, C; Winer, E; Muss, H
MLA Citation
Partridge, AH, Archer, L, Kornblith, AB, Gralow, J, Grenier, D, Perez, E, Wolff, AC, Wang, X, Kastrissios, H, Berry, D, Hudis, C, Winer, E, and Muss, H. "Adherence and persistence with oral adjuvant chemotherapy in older women with early-stage breast cancer in CALGB 49907: Adherence companion study 60104." Journal of Clinical Oncology 28.14 (2010): 2418-2422.
PMID
20368559
Source
scival
Published In
Journal of Clinical Oncology
Volume
28
Issue
14
Publish Date
2010
Start Page
2418
End Page
2422
DOI
10.1200/JCO.2009.26.4671

Outcome- and auxiliary-dependent subsampling and its statistical inference.

The performance of a biomarker predicting clinical outcome is often evaluated in a large prospective study. Due to high costs associated with bioassay, investigators need to select a subset from all available patients for biomarker assessment. We consider an outcome- and auxiliary-dependent subsampling (OADS) scheme, in which the probability of selecting a patient into the subset depends on the patient's clinical outcome and an auxiliary variable. We proposed a semiparametric empirical likelihood method to estimate the association between biomarker and clinical outcome. Asymptotic properties of the estimator are given. Simulation study shows that the proposed method outperforms alternative methods.

Authors
Wang, X; Wu, Y; Zhou, H
MLA Citation
Wang, X, Wu, Y, and Zhou, H. "Outcome- and auxiliary-dependent subsampling and its statistical inference." J Biopharm Stat 19.6 (November 2009): 1132-1150.
PMID
20183468
Source
pubmed
Published In
Journal of Biopharmaceutical Statistics
Volume
19
Issue
6
Publish Date
2009
Start Page
1132
End Page
1150
DOI
10.1080/10543400903243025

A phase II study of pemetrexed, carboplatin and thoracic radiation with or without cetuximab in patients with locally advanced unresectable non-small cell lung cancer: CALGB 30407

Authors
Govindan, R; Bogart, J; Wang, X; Hodgson, L; Kratzke, RA; Vokes, EE
MLA Citation
Govindan, R, Bogart, J, Wang, X, Hodgson, L, Kratzke, RA, and Vokes, EE. "A phase II study of pemetrexed, carboplatin and thoracic radiation with or without cetuximab in patients with locally advanced unresectable non-small cell lung cancer: CALGB 30407." JOURNAL OF THORACIC ONCOLOGY 4.9 (September 2009): S371-S372.
Source
wos-lite
Published In
Journal of Thoracic Oncology
Volume
4
Issue
9
Publish Date
2009
Start Page
S371
End Page
S372

The impact of occult micrometastases on survival following resection of stage I non-small cell lung cancer: final analysis of CALGB 9761

Authors
D'Cunha, J; Xiaofei, W; Groth, SS; Vollmer, RT; Abraham, NZ; Herzan, DL; Lin, G; Patterson, GA; Kohman, LJ; Green, MR; Kratzke, RA; Maddaus, MA; Leukemia, GBC
MLA Citation
D'Cunha, J, Xiaofei, W, Groth, SS, Vollmer, RT, Abraham, NZ, Herzan, DL, Lin, G, Patterson, GA, Kohman, LJ, Green, MR, Kratzke, RA, Maddaus, MA, and Leukemia, GBC. "The impact of occult micrometastases on survival following resection of stage I non-small cell lung cancer: final analysis of CALGB 9761." JOURNAL OF THORACIC ONCOLOGY 4.9 (September 2009): S576-S576.
Source
wos-lite
Published In
Journal of Thoracic Oncology
Volume
4
Issue
9
Publish Date
2009
Start Page
S576
End Page
S576

Intraoperative sentinel node mapping with technitium-99 in lung cancer: results of CALGB 140203 multicenter phase II trial.

INTRODUCTION: Sentinel node mapping with radioactive technetium in non-small cell lung cancer has been shown to be feasible in several single institution reports. The Cancer and Leukemia Group B designed a phase II trial to test a standardized method of this technique in a multi-institutional setting. If validated, the technique could provide a more accurate and sensitive way to identify lymph node metastases. METHODS: Patients with clinical stage I non-small cell lung cancer amenable to resection were candidates for this trial. Intraoperatively, tumors were injected with technetium sulfur colloid (0.25 mCi). The tumor and lymph nodes were measured in vivo with a hand held Geiger counter and resection of the tumor and nodes was carried out. Sentinel nodes, all other nodes and the tumor were analyzed with standard histologic assessment. Negative sentinel nodes were also evaluated with immunohistochemistry. RESULTS: In this phase II trial, 8 surgeons participated (1-13 patients enrolled per surgeon), and 46 patients (out of a planned 150) were enrolled. Of these, 43 patients had cancer and an attempted complete resection, and 39 patients underwent sentinel node mapping. One or more sentinel nodes were identified in 24 of the 39 patients (61.5%). The sentinel node(s) were found to be accurate (no other nodes were positive for cancer if the sentinel node was negative) in 20/24 patients (83.3%). In the overall group the sentinel node mapping procedure was found to be accurate in 20/39 patients (51.2%). CONCLUSIONS: Intraoperative sentinel node mapping in lung cancer with radioisotope yielded lower accrual and worse accuracy than expected. The multi-institutional attempt at validating this technique was unsuccessful.

Authors
Liptay, MJ; D'amico, TA; Nwogu, C; Demmy, TL; Wang, XF; Gu, L; Litle, VR; Swanson, SJ; Kohman, LJ; Thoracic Surgery Subcommittee of the Cancer and Leukemia Group B,
MLA Citation
Liptay, MJ, D'amico, TA, Nwogu, C, Demmy, TL, Wang, XF, Gu, L, Litle, VR, Swanson, SJ, Kohman, LJ, and Thoracic Surgery Subcommittee of the Cancer and Leukemia Group B, . "Intraoperative sentinel node mapping with technitium-99 in lung cancer: results of CALGB 140203 multicenter phase II trial." J Thorac Oncol 4.2 (February 2009): 198-202.
PMID
19179896
Source
pubmed
Published In
Journal of Thoracic Oncology
Volume
4
Issue
2
Publish Date
2009
Start Page
198
End Page
202
DOI
10.1097/JTO.0b013e318194a2c3

A phase II study of carboplatin, etoposide, and exisulind in patients with extensive small cell lung cancer CALGB 30104

Purpose: To assess the efficacy and toxicity of carboplatin, etoposide, and exisulind as initial therapy for extensive stage small cell lung cancer. Patients and Methods: The Cancer and Leukemia Group B conducted a phase II study of carboplatin (area under the curve 6) day 1 and etoposide 80 mg/m2 days 1-3 administered intravenously every 21 days with exisulind 250 mg orally twice daily in 44 evaluable patients with previously untreated extensive stage small cell lung cancer. The hypothesis was the addition of a novel cytostatic agent to standard therapy may increase survival time. The primary end point of the study was to evaluate overall survival. The secondary end points were to characterize response rates and toxicity. Results: The majority of the patients were male (64%), Caucasian (95%), and had performance status 0 or 1 (77%). The median age was 61 (range 44-82) years. The percentage of patients alive at 1 year was 36.4% (95% confidence interval CI: 24.6 -53.8%). The median overall survival was 10.6 months (95% CI: 9.1-14.7). The best overall response rate was 77% (95% CI: 62-89%) with 16% of the patients achieving complete response. The most frequent grade 3 or grade 4 hematological toxicities were neutropenia (64%), thrombocytopenia (36%), and febrile neutropenia (16%). The most common grade 3 or grade 4 nonhematological toxicities were gastrointestinal (30%) and electrolyte changes (23%). Conclusions: The addition of exisulind to a standard regimen of carboplatin and etoposide did not improve outcomes compared with historic controls treated with chemotherapy alone. Further evaluation of this regimen in small cell lung cancer is not warranted. © 2009 by the International Association for the Study of Lung Cancer.

Authors
Govindan, R; Wang, X; Baggstrom, MQ; Burdette-Radoux, S; Hodgson, L; Vokes, EE; Green, MR
MLA Citation
Govindan, R, Wang, X, Baggstrom, MQ, Burdette-Radoux, S, Hodgson, L, Vokes, EE, and Green, MR. "A phase II study of carboplatin, etoposide, and exisulind in patients with extensive small cell lung cancer CALGB 30104." Journal of Thoracic Oncology 4.2 (2009): 220-226.
PMID
19179900
Source
scival
Published In
Journal of Thoracic Oncology
Volume
4
Issue
2
Publish Date
2009
Start Page
220
End Page
226
DOI
10.1097/JTO.0b013e3181951eb0

Randomized phase II trial of docetaxel plus cetuximab or docetaxel plus bortezomib in patients with advanced non-small-cell lung cancer and a performance status of 2: CALGB 30402

Purpose: A randomized phase II trial of two novel treatment strategies in the first-line management of advanced non-small-cell lung cancer patients with performance status (PS) 2. Patients and Methods: Patients were assigned to docetaxel 30 mg/m2 on days 1, 8, and 15 every 28 days in combination with either cetuximab 400 mg/m2 loading dose followed by 250 mg/m2 weekly (D + C) or bortezomib 1.6 mg/m2 on days 1, 8, and 15 every 28 days (D + B) for up to 4 cycles. Patients with responding or stable disease continued cetuximab or bortezomib until progression. The primary end point was progression-free survival (PFS) rate at 6 months. Results: Sixty-four patients were enrolled and 59 were included in this analysis. Complete or partial response rates were 13.3% and 10.3% for D + C and D + B, respectively. Median PFS was 3.4 months in the D + C arm and 1.9 months in the D + B arm. Corresponding figures for 6-month PFS were 27.8% and 13.8% and 5.0 and 3.9 months for median survival, respectively. Grade 3/4 hematologic toxicity was 16% for D + C and 21% for D + B, whereas nonhematologic toxicities were observed in 63% and 44% of patients, respectively. There was one treatment-related death in each arm. Conclusion: These results confirm the poor prognosis associated with a PS of 2 and the difficulty in translating recent advances in targeted therapy to this subset of patients. While the results in the D + C arm are numerically superior, neither combination met the prespecified PFS end point to justify further research in this setting. © 2009 by American Society of Clinical Oncology.

Authors
Lilenbaum, R; Wang, X; Gu, L; Kirshner, J; Lerro, K; Vokes, E
MLA Citation
Lilenbaum, R, Wang, X, Gu, L, Kirshner, J, Lerro, K, and Vokes, E. "Randomized phase II trial of docetaxel plus cetuximab or docetaxel plus bortezomib in patients with advanced non-small-cell lung cancer and a performance status of 2: CALGB 30402." Journal of Clinical Oncology 27.27 (2009): 4487-4491.
PMID
19704058
Source
scival
Published In
Journal of Clinical Oncology
Volume
27
Issue
27
Publish Date
2009
Start Page
4487
End Page
4491
DOI
10.1200/JCO.2009.22.7066

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

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

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

Phase II randomized study of dose-dense docetaxel and cisplatin every 2 weeks with pegfilgrastim and darbepoetin alfa with and without the chemoprotector BNP7787 in patients with advanced non-small cell lung cancer (CALGB 30303)

Introduction: We investigated dose-dense docetaxel and cisplatin in patients with measurable non-small cell lung cancer in a randomized phase II study without [A] or with [B] a putative chemoprotective agent, BNP7787. PATIENTS AND Methods: Chemotherapy-naive patients with stage IIIB (effusion) or IV, performance status 0 to 1, and adequate organ function were eligible. Treatment with docetaxel 75 mg/m followed by cisplatin 75 mg/m over 1 hour day 1 with darbepoetin 200 μg day 1 and pegfilgrastim 6 mg day 2 without/with BNP7787 before cisplatin was repeated every other week for up to 6 cycles. The primary end point was to differentiate between grade > 2 neurotoxicity rates of 30% on [A] and 10% on [B]. Feasibility was prospectively defined as febrile neutropenia in <10% of patients and ≤1 treatment delay per cycles 1 to 3 and 4 to 6 in <20% of patients. Results: Of 160 patients enrolled, 5 never started therapy and 4 were ineligible. Neurotoxicity grade > 2 occurred in 32% on [A] and 29% on [B]. The incidence of febrile neutropenia was 4% on [A] and 3% on [B]. Treatment delays occurred in 13% and 20% of patients on [A] and [B], respectively. Completion rates for 3/6 cycles were 84%/51% on [A] and 84%/53% on [B]. Objective response rates were 55% on [A] and 51% on [B]. Median progression-free/overall survival times were 5.5/10.7 on [A] and 6.5/14.1 month on [B]. Conclusions: This dose-dense treatment regimen is active, feasible, and tolerable. Its further investigation in the curative setting in non-small cell lung cancer should be considered. BNP7787 did not result in significant protection from neurotoxicity. © 2008 by the International Association for the Study of Lung Cancer.

Authors
Miller, AA; Wang, XF; Gu, L; Hoffman, P; Khatri, J; Dunphy, F; Edelman, MJ; Bolger, M; Vokes, EE; Green, MR
MLA Citation
Miller, AA, Wang, XF, Gu, L, Hoffman, P, Khatri, J, Dunphy, F, Edelman, MJ, Bolger, M, Vokes, EE, and Green, MR. "Phase II randomized study of dose-dense docetaxel and cisplatin every 2 weeks with pegfilgrastim and darbepoetin alfa with and without the chemoprotector BNP7787 in patients with advanced non-small cell lung cancer (CALGB 30303)." Journal of Thoracic Oncology 3.10 (2008): 1159-1165.
PMID
18827613
Source
scival
Published In
Journal of Thoracic Oncology
Volume
3
Issue
10
Publish Date
2008
Start Page
1159
End Page
1165
DOI
10.1097/JTO.0b013e318186fb0d

Response to the methylation inhibitor dihydro-5-azacytidine in mesothelioma is not associated with methylation of p16INK4a: Results of cancer and leukemia group B 159904

INTRODUCTION: The molecular mechanisms of oncogenesis in mesothelioma involve the loss of negative regulators of cell growth including p16. Absence of expression of the p16 gene product is exhibited in virtually all mesothelioma tumors and cell lines examined to date. Loss of p16 expression has also been frequently observed in more common neoplasms such as lung cancer as well. In a wide variety of these malignancies, including lung cancer, p16 expression is known to be inactivated by hypermethylation of the first exon. This project (CALGB 159904) intended to test the hypothesis that in mesothelioma loss of p16 via methylation would correlate with response to the cytidine analog and methylation inhibitor dihydro-5-azacytidine (DHAC). METHODS: Using tissue samples from CALGB 8833 and 9031, two clinical studies which used DHAC based therapy in mesothelioma, this study tested the hypothesis that tumors possessing methylation of p16 would have a better response and survival following DHAC treatment than their nonmethylated counterparts. RESULTS: Methylation of p16 was identified in 4 of the 20 specimens. Although there was a trend towards improved survival the result was not statistically significant. CONCLUSIONS: There was no significant correlation between the presence of p16 methylation and response to DHAC therapy or overall survival. © 2008International Association for the Study of Lung Cancer.

Authors
Kratzke, RA; Wang, X; Wong, L; Kratzke, MG; Green, MR; Vokes, EE; Vogelzang, NJ; Kindler, HL; Kern, JA
MLA Citation
Kratzke, RA, Wang, X, Wong, L, Kratzke, MG, Green, MR, Vokes, EE, Vogelzang, NJ, Kindler, HL, and Kern, JA. "Response to the methylation inhibitor dihydro-5-azacytidine in mesothelioma is not associated with methylation of p16INK4a: Results of cancer and leukemia group B 159904." Journal of Thoracic Oncology 3.4 (2008): 417-421.
PMID
18379362
Source
scival
Published In
Journal of Thoracic Oncology
Volume
3
Issue
4
Publish Date
2008
Start Page
417
End Page
421
DOI
10.1097/JTO.0b013e318168da0a

Randomized phase II study of carboplatin and etoposide with or without the bcl-2 antisense oligonucleotide oblimersen for extensive-stage small-cell lung cancer: CALGB 30103

Purpose: To assess the efficacy and toxicity of carboplatin, etoposide, and the bcl-2 antisense oligonucleotide oblimersen as initial therapy for extensive-stage small-cell lung cancer (ES-SCLC). bcl-2 has been implicated as a key factor in SCLC oncogenesis and chemotherapeutic resistance. Patients and Methods: A 3:1 randomized phase II study was performed to evaluate carboplatin and etoposide with (arm A) or without oblimersen (arm B) in 56 assessable patients with chemotherapy-na?̈ve ES-SCLC. Outcome measures including toxicity, objective response rate, complete response rate, failurefree survival, overall survival, and 1-year survival rate. Results: Oblimersen was associated with slightly more grade 3 to 4 hematologic toxicity (88% v 60%; P = .05). Response rates were 61% (95% CI, 45% to 76%) for arm A and 60% (95% CI, 32% to 84%) for arm B. The percentage of patients alive at 1 year was 24% (95% CI, 12% to 40%) with oblimersen, and 47% (95% CI, 21% to 73%) without oblimersen. Hazard ratios for failure-free survival (1.79; P = .07) and overall survival (2.13; P = .02) suggested worse outcome for patients receiving oblimersen. These results hold when adjusted for other prognostic factors, such as weight loss, in multivariate regression analysis. Conclusion: Despite extensive data supporting a critical role for Bcl-2 in chemoresistance in SCLC, addition of oblimersen to a standard regimen for this disease did not improve any clinical outcome measure. Emerging data from several groups suggest that this lack of efficacy may be due to insufficient suppression of Bcl-2 in vivo. Additional evaluation of this agent in SCLC is not warranted. © 2008 by American Society of Clinical Oncology.

Authors
Rudin, CM; Salgia, R; Wang, X; Hodgson, LD; Masters, GA; Green, M; Vokes, EE
MLA Citation
Rudin, CM, Salgia, R, Wang, X, Hodgson, LD, Masters, GA, Green, M, and Vokes, EE. "Randomized phase II study of carboplatin and etoposide with or without the bcl-2 antisense oligonucleotide oblimersen for extensive-stage small-cell lung cancer: CALGB 30103." Journal of Clinical Oncology 26.6 (2008): 870-876.
PMID
18281659
Source
scival
Published In
Journal of Clinical Oncology
Volume
26
Issue
6
Publish Date
2008
Start Page
870
End Page
876
DOI
10.1200/JCO.2007.14.3461

Eicosanoid modulation in advanced lung cancer: Cyclooxygenase-2 expression is a positive predictive factor for celecoxib + chemotherapy - Cancer and leukemia group B trial 30203

Purpose: Increased expression of eicosanoids in cancer has been associated with adverse prognosis. We performed a randomized phase II trial to test the hypothesis that inhibitors of two eicosanoid pathways (cyclooxygenase-2 [COX-2], celecoxib and 5-lipoxygenase [5-LOX], zileuton) added to chemotherapy would improve outcome in advanced non-small-cell lung cancer (NSCLC). Patients and Methods: Patients with advanced NSCLC, a performance status of 0 to 2, and no prior therapy were eligible. All patients received carboplatin area under the curve (AUC) 5.5 mg/mL·min day 1 + gemcitabine (1,000 mg/m2) days 1 and 8. Patients were randomly assigned to: (a) zileuton 600 mg PO qid, (b) celecoxib 400 mg PO bid, or (c) celecoxib and zileuton at the same doses. Immunohistochemical staining for COX-2 and 5-LOX was performed without knowledge of outcomes. Results: One hundred forty patients were entered and 134 were eligible and treated. There was no survival difference between the arms. COX-2 expression was a negative prognostic marker for overall survival (OS; hazard ratio [HR] = 2.51, P = .019 for index ≥ 4; HR = 4.16, P = .005 for index = 9) for patients not receiving celecoxib. Patients with increased COX-2 expression (index ≥ 4), receiving celecoxib had better survival than did COX-2-expressing patients not receiving drug (HR = .342, P = .005 for OS; HR = .294, P = .002 for failure-free survival). Multivariate analysis confirmed the interaction of COX-2 and celecoxib on survival. 5-LOX expression was neither prognostic nor predictive. Conclusion: This study failed to demonstrate the value of dual eicosanoid inhibition or benefit from either agent alone in addition to chemotherapy. However, a prospectively defined subset analysis suggests an advantage for celecoxib and chemotherapy for patients with moderate to high COX-2 expression. © 2008 by American Society of Clinical Oncology.

Authors
Edelman, MJ; Watson, D; Wang, X; Morrison, C; Kratzke, RA; Jewell, S; Hodgson, L; Mauer, AM; Gajra, A; Masters, GA; Bedor, M; Vokes, EE; Green, MJ
MLA Citation
Edelman, MJ, Watson, D, Wang, X, Morrison, C, Kratzke, RA, Jewell, S, Hodgson, L, Mauer, AM, Gajra, A, Masters, GA, Bedor, M, Vokes, EE, and Green, MJ. "Eicosanoid modulation in advanced lung cancer: Cyclooxygenase-2 expression is a positive predictive factor for celecoxib + chemotherapy - Cancer and leukemia group B trial 30203." Journal of Clinical Oncology 26.6 (2008): 848-855.
PMID
18281656
Source
scival
Published In
Journal of Clinical Oncology
Volume
26
Issue
6
Publish Date
2008
Start Page
848
End Page
855
DOI
10.1200/JCO.2007.13.8081

Randomized phase II trial of induction chemotherapy followed by concurrent chemotherapy and dose-escalated thoracic conformal radiotherapy (74 Gy) in stage III non-small-cell lung cancer: CALGB 30105

Purpose: To evaluate 74 Gy thoracic radiation therapy (TRT) with induction and concurrent chemotherapy in stage IIIA/B non-small-cell lung cancer (NSCLC). Patients and Methods: Patients with stage IIIA/B NSCLC were randomly assigned to induction chemotherapy with either carboplatin (area under the curve [AUC], 6; days 1 and 22) with paclitaxel (225 mg/m2; days 1 and 22; arm A) or carboplatin (AUC, 5; days 1 and 22) with gemcitabine (1,000 mg/m2; days 1, 8, 22, and 29; arm B). On day 43, arm A received weekly carboplatin (AUC, 2) and paclitaxel (45 mg/m2) while arm B received biweekly gemcitabine (35 mg/m2) both delivered concurrently with 74 Gy of TRT utilizing three-dimensional treatment planning. The primary end point was survival at 18 months. Results: Forty-three and 26 patients were accrued to arms A and B, respectively. Arm B was closed prematurely due to a high rate of grade 4 to 5 pulmonary toxicity. The overall response rate was 66.6% (95% CI, 50.5% to 80.4%) and 69.2% (95% CI, 48.2% to 85.7%) on arm A and B, respectively. The median survival time (MST) and 1-year survival rate was 24.3 months (95% CI, 12.3 to 36.4) and 66.7% (95% CI, 50.3 to 78.7) and 12.5 months (95% CI, 9.4 to 27.6) and 50.0% (95% CI, 29.9 to 67.2) for arms A and B, respectively. The primary toxicities included esophagitis, pulmonary, and fatigue. Conclusion: Arm A reached the primary end point with an estimated MST longer than 18 months and will be compared with a standard dose of TRT in a planned randomized phase III trial in the United States cooperative groups. © 2008 by American Society of Clinical Oncology.

Authors
Socinski, MA; Blackstock, AW; Bogart, JA; Wang, X; Munley, M; Rosenman, J; Gu, L; Masters, GA; Ungaro, P; Sleeper, A; Green, M; Miller, AA; Vokes, EE
MLA Citation
Socinski, MA, Blackstock, AW, Bogart, JA, Wang, X, Munley, M, Rosenman, J, Gu, L, Masters, GA, Ungaro, P, Sleeper, A, Green, M, Miller, AA, and Vokes, EE. "Randomized phase II trial of induction chemotherapy followed by concurrent chemotherapy and dose-escalated thoracic conformal radiotherapy (74 Gy) in stage III non-small-cell lung cancer: CALGB 30105." Journal of Clinical Oncology 26.15 (2008): 2457-2463.
PMID
18487565
Source
scival
Published In
Journal of Clinical Oncology
Volume
26
Issue
15
Publish Date
2008
Start Page
2457
End Page
2463
DOI
10.1200/JCO.2007.14.7371

D5-01: Prognostic significance of molecular markers and clinical factors in stage ib non-small cell lung cancer (NSCLC): a laboratory companion study to CALGB 9633

Authors
Graziano, SL; Gu, L; Wang, XF; Tatum, AH; Vollmer, RT; Strauss, GM; Kratzke, RA; Green, MR; Vokes, EE
MLA Citation
Graziano, SL, Gu, L, Wang, XF, Tatum, AH, Vollmer, RT, Strauss, GM, Kratzke, RA, Green, MR, and Vokes, EE. "D5-01: Prognostic significance of molecular markers and clinical factors in stage ib non-small cell lung cancer (NSCLC): a laboratory companion study to CALGB 9633." Journal of Thoracic Oncology 2.8 (August 2007): S403-S403.
Source
crossref
Published In
Journal of Thoracic Oncology
Volume
2
Issue
8
Publish Date
2007
Start Page
S403
End Page
S403
DOI
10.1097/01.JTO.0000283278.97704.03

Phase II trial of paclitaxel-topotecan-etoposide followed by consolidation chemoradiotherapy for limited-stage small cell lung cancer: CALGB 30002

PURPOSE: We sought to evaluate the activity and tolerance of the rationally designed sequence of paclitaxel-topotecan-etoposide, a nonplatinum regimen, as induction therapy for limited-stage small-cell lung cancer before combined chemo- and radiotherapy. PATIENTS AND METHODS: Patients with measurable disease, performance status 0 to 2, no prior therapy, and adequate organ function were eligible. Paclitaxel (110 mg/m, administered intravenously on day 1), topotecan (1.5 mg/m, administered orally on days 2 to 4), and etoposide (160 mg/m, administered orally on days 5 to 7 every 21 days), with filgrastim for two cycles, were followed by chest irradiation to 70 Gy (to postinduction tumor volume) concurrent with carboplatin (area under the curve of 5, administered intravenously on day 1) and etoposide (100 mg/m on days 1 to 3 every 21 days) without filgrastim for three cycles (five chemotherapy cycles total). We aimed to determine the response rates to induction and overall therapy, overall and failure-free survival, and toxicity. The primary statistical endpoint was to differentiate between complete response rates of 50 and 70% for the overall treatment program. RESULTS: Between June 2001 and January 2003, 65 patients were enrolled, but one never started therapy, and one was ineligible. Patient characteristics included male/female, 27/36; white/black/other/unknown, 58/3/1/1; median age 62 (range, 38-78); performance status 0/1/2, 27/33/3. Induction chemotherapy resulted in six (10%) complete responses and 35 (56%) partial responses. Overall response to chemoradiotherapy included 27 (43%; 95% confidence interval [CI] 30-56%) complete responses and 24 (38%) partial responses. Median progression-free survival is 12 months (95% CI, 9-15 months). Median overall survival is 20 months (95% CI, 16-24 months). Frequent (>20%) grade 3/4 toxicities during all therapy included neutropenia, febrile neutropenia, anemia, thrombocytopenia, fatigue, and dysphagia. One patient died of febrile neutropenia, one died of febrile neutropenia and typhlitis, and one patient who declined transfusion for anemia died of cardiac ischemia. CONCLUSIONS: This treatment regimen has significant activity in limited-stage small-cell lung cancer but did not meet our prospectively defined criteria for further investigation in this setting. The addition of etoposide and the use of a sequenced administration schedule did not seem to improve overall activity beyond our prior experience with a topotecan-paclitaxel doublet. © 2007International Association for the Study of Lung Cancer.

Authors
Miller, AA; Wang, XF; Bogart, JA; Hodgson, LD; Lima, CMSR; Radford, JE; Vokes, EE; Green, MR
MLA Citation
Miller, AA, Wang, XF, Bogart, JA, Hodgson, LD, Lima, CMSR, Radford, JE, Vokes, EE, and Green, MR. "Phase II trial of paclitaxel-topotecan-etoposide followed by consolidation chemoradiotherapy for limited-stage small cell lung cancer: CALGB 30002." Journal of Thoracic Oncology 2.7 (2007): 645-651.
PMID
17607121
Source
scival
Published In
Journal of Thoracic Oncology
Volume
2
Issue
7
Publish Date
2007
Start Page
645
End Page
651
DOI
10.1097/JTO.0b013e318074bbf5

A phase III study of surgical resection and paclitaxel/carboplatin chemotherapy with or without adjuvant radiation therapy for resected stage III non-small-cell lung cancer: Cancer and Leukemia Group B 9734

PURPOSE: Patients with completely resected stage IIIA (N2) non-small-cell lung cancer (NSCLC) are at substantial risk for locoregional and systemic recurrence. Adjuvant chemotherapy has recently improved overall control for these patients. We added adjuvant chemotherapy to control presumed micrometastatic disease and then randomized patients to receive radiation therapy (RT) or observation to determine the benefit of local radiation consolidation. PATIENTS AND METHODS: Patient eligibility required histologically documented stage IIIA (radiographically occult N2) NSCLC that was completely resected, with no known residual disease, surgical staging per protocol requirements, Cancer and Leukemia Group B performance status of 0/1, no previous chemotherapy or RT, and minimal laboratory values. All eligible patients received 4 cycles of paclitaxel 200 mg/m2 over 3 hours with carboplatin at an area under the curve of 6 on days 1, 22, 43, and 64 beginning 4-8 weeks after surgery. Two to 4 weeks after chemotherapy, patients were randomized to receive RT as 5000 cGy in 25 fractions over 5 weeks or observation. RESULTS: The study closed after 2 years because of slow accrual. Forty-four patients entered the study; 2 were ineligible, and 5 were not randomized because of progression, adverse reaction, or patient withdrawal. Thirty-seven patients were the basis of this analysis. Median failure-free survival was 16.8 months on the observation arm and 33.7 months on the RT arm, with a 1-year survival rate of 72% on the observation arm and 74% on the RT arm. There were no statistical differences between the observation and RT arms for failure-free survival or overall survival. CONCLUSION: In this small study, consolidation RT after complete resection and adjuvant chemotherapy in stage IIIA NSCLC did not significantly Improve outcome for this high-risk population.

Authors
Perry, MC; Kohman, LJ; Bonner, JA; Gu, L; Wang, X; Vokes, EE; Green, MR
MLA Citation
Perry, MC, Kohman, LJ, Bonner, JA, Gu, L, Wang, X, Vokes, EE, and Green, MR. "A phase III study of surgical resection and paclitaxel/carboplatin chemotherapy with or without adjuvant radiation therapy for resected stage III non-small-cell lung cancer: Cancer and Leukemia Group B 9734." Clinical Lung Cancer 8.4 (2007): 268-272.
PMID
17311692
Source
scival
Published In
Clinical lung cancer
Volume
8
Issue
4
Publish Date
2007
Start Page
268
End Page
272

A semiparametric empirical likelihood method for biased sampling schemes with auxiliary covariates.

We consider a semiparametric inference procedure for data from epidemiologic studies conducted with a two-component sampling scheme where both a simple random sample and multiple outcome- or outcome-/auxiliary-dependent samples are observed. This sampling scheme allows the investigators to oversample certain subpopulations believed to have more information about the regression model while still gaining insights about the underlying population through the simple random sample. We focus on settings where there is no additional information about the parent cohort and the sampling probability is nonidentifiable. We motivate our problem with an ongoing study to assess the association between the mutation level of epidermal growth factor receptor (EGFR) and the antitumor response to EGFR-targeted therapy among nonsmall cell lung cancer patients. The proposed method applies to both binary and multicategorical outcome data and allows an arbitrary link function in the framework of generalized linear models. Simulation studies show that the proposed estimator has nice small sample properties. The proposed method is illustrated with a data example.

Authors
Wang, X; Zhou, H
MLA Citation
Wang, X, and Zhou, H. "A semiparametric empirical likelihood method for biased sampling schemes with auxiliary covariates." Biometrics 62.4 (December 2006): 1149-1160.
PMID
17156290
Source
pubmed
Published In
Biometrics
Volume
62
Issue
4
Publish Date
2006
Start Page
1149
End Page
1160
DOI
10.1111/j.1541-0420.2006.00612.x

Impact of a multidisciplinary thoracic oncology clinic on the timeliness of care.

BACKGROUND: Multidisciplinary clinics have been recommended for the evaluation of patients with lung cancer. Evidence to support this recommendation, however, is limited. A single-center, retrospective review of lung cancer patients at a Veterans Affairs hospital was performed comparing timeliness of diagnostic and treatment decisions during the operation of a multidisciplinary thoracic oncology clinic (MTOC) with a period after it closed (non-MTOC), during which only a weekly multidisciplinary conference was held. METHODS: Patients were identified from a tumor registry. Manual chart reviews were performed on all patients. Outcome measures included time from initial presentation to diagnosis (TTD) and time from diagnosis to treatment initiation (TTT). RESULTS: Three hundred forty-five patients (244 in MTOC, 101 in non-MTOC) diagnosed with lung cancer between 1999 and 2003 were included in the study. Baseline characteristics were similar between the two groups. Median TTD was 48 days (95% confidence interval [CI]: 37-61) and 47 days (95% CI: 39-55) in the MTOC (n = 164) and non-MTOC cohorts (n = 89), respectively (p = 0.09). Median TTT was 22 days (95% CI: 20-27) and 23 days (95% CI: 20-34) in the MTOC (n = 165) and non-MTOC cohorts (n = 89), respectively (p = 0.71). There was no difference in overall survival. CONCLUSION: Retrospective comparison of sequential cohorts failed to reveal benefit in the timeliness of care measures during the time period of MTOC operation. Potential confounders include the absence of a surgeon in the MTOC setting, an ongoing weekly multidisciplinary conference in the non-MTOC cohort, and existing infrastructures based on previous MTOC experiences and past provider experience. Confirmation of these findings in other health care settings is warranted, preferably in a prospective fashion.

Authors
Riedel, RF; Wang, X; McCormack, M; Toloza, E; Montana, GS; Schreiber, G; Kelley, MJ
MLA Citation
Riedel, RF, Wang, X, McCormack, M, Toloza, E, Montana, GS, Schreiber, G, and Kelley, MJ. "Impact of a multidisciplinary thoracic oncology clinic on the timeliness of care." J Thorac Oncol 1.7 (September 2006): 692-696.
PMID
17409938
Source
pubmed
Published In
Journal of Thoracic Oncology
Volume
1
Issue
7
Publish Date
2006
Start Page
692
End Page
696

Phase II trial of sorafenib (bay 43-9006) in malignant mesothelioma: CALGB 30307

Authors
Janne, PA; Wang, XF; Krug, LM; Hodgson, L; Vokes, EE; Kindler, HL
MLA Citation
Janne, PA, Wang, XF, Krug, LM, Hodgson, L, Vokes, EE, and Kindler, HL. "Phase II trial of sorafenib (bay 43-9006) in malignant mesothelioma: CALGB 30307." 2006.
Source
wos-lite
Published In
Annals of Oncology
Volume
17
Publish Date
2006
Start Page
216
End Page
217

Erratum: Patient preference in a crossover clinical trial of patients with osteoarthritis of the knee or hip: Face validity of self-report questionnaire ratings (Journal of Rheumatology (2005) 32 (533-539))

Authors
Pincus, T; Wang, X; Chung, C; Sokka, T; Koch, GG
MLA Citation
Pincus, T, Wang, X, Chung, C, Sokka, T, and Koch, GG. "Erratum: Patient preference in a crossover clinical trial of patients with osteoarthritis of the knee or hip: Face validity of self-report questionnaire ratings (Journal of Rheumatology (2005) 32 (533-539))." Journal of Rheumatology 32.5 (2005): 966--.
Source
scival
Published In
Journal of Rheumatology
Volume
32
Issue
5
Publish Date
2005
Start Page
966-

Patient preference in a crossover clinical trial of patients with osteoarthritis of the knee or hip: Face validity of self-report questionnaire ratings

Objective. To analyze correlational validity of self-report responses regarding patient preference between 2 drugs at the conclusion of a crossover double-blind clinical trial in patients with osteoarthritis (OA) of the knee or hip. Methods. Patients were randomized to 6 weeks' treatment of diclofenac/misoprostol or acetaminophen, followed by crossover to 6 weeks of the other drug. Patient preference was queried at the final visit: "Please compare control of your arthritis during the first and second periods as 'much better' or 'better' in the first period, 'no different' or 'better' or 'much better' in the second period." Patient preference ratings were evaluated in comparisons with 4 independent self-report measures within each treatment period: (1) change in Western Ontario McMaster (WOMAC) questionnaire scores; (2) change in pain visual analog scale (VAS) on a multidimensional Health Assessment Questionnaire (MDHAQ); (3) patient ratings of drug efficacy; and (4) patient report of change in arthritis status, as well as investigator ratings of the more efficacious drug. Results. Among 173 patients, diclofenac/misoprostol was rated as "much better" by 54 and "better" by 45, acetaminophen was rated as "better" by 18 and "much better" by 17, and "no difference" by 39 patients. Spearman rank correlations for patient preferences were significant for changes in WOMAC scores, pain VAS, and independent patient ratings of drug efficacy and changes in arthritis status within each treatment period, as well as with physician ratings of the more efficacious drug (p<0.001). Conclusion. Significant correlational validity is documented for patient self-report of preferences between 2 drugs compared to independent measures within each treatment period in this crossover clinical trial in patients with OA of the knee or hip.

Authors
Pincus, T; Wang, X; Chung, C; Sokka, T; Koch, GG
MLA Citation
Pincus, T, Wang, X, Chung, C, Sokka, T, and Koch, GG. "Patient preference in a crossover clinical trial of patients with osteoarthritis of the knee or hip: Face validity of self-report questionnaire ratings." Journal of Rheumatology 32.3 (2005): 533-539.
PMID
15742449
Source
scival
Published In
The Journal of rheumatology
Volume
32
Issue
3
Publish Date
2005
Start Page
533
End Page
539

How do statistical properties influence findings of tracking (maintenance) in epidemiologic studies? An example of research in tracking of obesity

There is great interest in studying the tracking (maintenance) of health conditions and risk factors over the life span. Tracking is often defined as the maintenance of a distribution position (e.g., quintile or percentile) in a study population over time. This study investigated how statistical properties might influence research findings of tracking with a special attention on the tracking of extreme ranking. Our results show that when repeated measures over time were positively correlated, the probability of tracking in extreme rankings was greater than other rankings and this was closely influenced by the overall correlation (r) and by the categorization. For example, when r = 0.4, 38% remained in the bottom and upper quintile (Q1, Q5) respectively, while only 22% remained in the middle quintile (Q3); when r = 0.8, the figure became 65% vs. 32%. When r = 0.4 and 0.8, 19 and 50% remained in the upper 95th percentile (or under the 5th percentile), respectively. Our real data show that children in the upper body mass index (=weight(kg)/height(M)2) quintile were more likely to maintain their ranking (54%) than others (about 30%), but not significantly higher than the expected (47%, p > 0.05). In conclusion, the overall correlation should be considered when studying tracking. Our proposed methods and predicted probabilities of tracking can help test whether one's observed tracking patterns are different from the statistically predicted ones.

Authors
Wang, Y; Wang, X
MLA Citation
Wang, Y, and Wang, X. "How do statistical properties influence findings of tracking (maintenance) in epidemiologic studies? An example of research in tracking of obesity." European Journal of Epidemiology 18.11 (2003): 1037-1045.
PMID
14620937
Source
scival
Published In
European Journal of Epidemiology
Volume
18
Issue
11
Publish Date
2003
Start Page
1037
End Page
1045
DOI
10.1023/A:1026196310041

Re: "Tracking of cardiovascular risk factors: The Tromsø study, 1979-1995" [2] (multiple letters)

Authors
Wang, Y; Wang, X; Wilsgaard, T; Jacobsen, BK; Schirmer, H; Thune, I; Løchen, M-L; Njølstad, I; Arnesen, E
MLA Citation
Wang, Y, Wang, X, Wilsgaard, T, Jacobsen, BK, Schirmer, H, Thune, I, Løchen, M-L, Njølstad, I, and Arnesen, E. "Re: "Tracking of cardiovascular risk factors: The Tromsø study, 1979-1995" [2] (multiple letters)." American Journal of Epidemiology 155.12 (2002): 1144-1145.
PMID
12048230
Source
scival
Published In
American Journal of Epidemiology
Volume
155
Issue
12
Publish Date
2002
Start Page
1144
End Page
1145
DOI
10.1093/aje/155.12.1144

A randomized, double-blind, crossover clinical trial of diclofenac plus misoprostol versus acetaminophen in patients with osteoarthritis of the hip or knee.

OBJECTIVE: To perform a randomized, double-blind, crossover clinical trial of diclofenac + misoprostol versus acetaminophen in ambulatory patients with osteoarthritis of the hip or knee. METHODS: Patients in 12 ambulatory care settings were eligible if they were age >40 years and if they had Kellgren/Lawrence radiographic grade 2-4 osteoarthritis of the knee or hip and a score of > or =30 mm on a 100-mm visual analog pain scale. Patients were randomized to one of two groups, 75 mg diclofenac + 200 microg misoprostol twice daily or 1,000 mg acetaminophen 4 times daily (each for 6 weeks), and were then crossed over to the other treatment for 6 weeks. A placebo was included in each treatment regimen to enable double blinding. The primary outcome measures were the Western Ontario and McMaster Universities Osteoarthritis Index and the visual analog pain scale of the Multidimensional Health Assessment Questionnaire. Safety was assessed using a standard form to review adverse events. RESULTS: We enrolled 227 patients, of whom 218 provided data for the first treatment period and 181 provided data for both treatment periods. Significantly higher levels of improvement in the primary outcomes were seen for diclofenac + misoprostol than for acetaminophen (P < 0.001). Adverse events were more common when patients took diclofenac + misoprostol (P = 0.046). Diclofenac + misoprostol was rated as "better" or "much better" by 57% of the 174 patients who provided such ratings for both treatment periods, while acetaminophen was rated as "better" or "much better" by 20% of these patients, and 22% reported no difference (P < 0.001). Differences favoring diclofenac + misoprostol over acetaminophen were greater in patients with more severe osteoarthritis according to baseline pain scores, radiographs, or number of involved joints. CONCLUSION: Patients with osteoarthritis of the hip or knee had significantly greater improvements in pain scores over 6 weeks with diclofenac + misoprostol than with acetaminophen, although patients with mild osteoarthritis had similar improvements with both drugs. Acetaminophen was associated with fewer adverse events.

Authors
Pincus, T; Koch, GG; Sokka, T; Lefkowith, J; Wolfe, F; Jordan, JM; Luta, G; Luta, G; Callahan, LF; Wang, X; Schwartz, T; Abramson, SB; Caldwell, JR; Harrell, RA; Kremer, JM; Lautzenheiser, RL; Markenson, JA; Schnitzer, TJ; Weaver, A; Cummins, P; Wilson, A; Morant, S; Fort, J
MLA Citation
Pincus, T, Koch, GG, Sokka, T, Lefkowith, J, Wolfe, F, Jordan, JM, Luta, G, Luta, G, Callahan, LF, Wang, X, Schwartz, T, Abramson, SB, Caldwell, JR, Harrell, RA, Kremer, JM, Lautzenheiser, RL, Markenson, JA, Schnitzer, TJ, Weaver, A, Cummins, P, Wilson, A, Morant, S, and Fort, J. "A randomized, double-blind, crossover clinical trial of diclofenac plus misoprostol versus acetaminophen in patients with osteoarthritis of the hip or knee." Arthritis and rheumatism 44.7 (July 2001): 1587-1598.
PMID
11465710
Source
epmc
Published In
Arthritis and Rheumatism
Volume
44
Issue
7
Publish Date
2001
Start Page
1587
End Page
1598
DOI
10.1002/1529-0131(200107)44:7<1587::aid-art282>3.0.co;2-x

A randomized, double-blind, crossover clinical trial of diclofenac plus misoprostol versus acetaminophen in patients with osteoarthritis of the hip or knee

Objective. To perform a randomized, double-blind, crossover clinical trial of diclofenac + misoprostol versus acetaminophen in ambulatory patients with osteoarthritis of the hip or knee. Methods. Patients in 12 ambulatory care settings were eligible if they were age >40 years and if they had Kellgren/Lawrence radiographic grade 2-4 osteoarthritis of the knee or hip and a score of ≥30mm on a 100-mm visual analog pain scale. Patients were randomized to one of two groups, 75 mg diclofenac + 200 μg misoprostol twice daily or 1,000 mg acetaminophen 4 times daily (each for 6 weeks), and were then crossed over to the other treatment for 6 weeks. A placebo was included in each treatment regimen to enable double blinding. The primary outcome measures were the Western Ontario and McMaster Universities Osteoarthritis Index and the visual analog pain scale of the Multidimensional Health Assessment Questionnaire. Safety was assessed using a standard form to review adverse events. Results. We enrolled 227 patients, of whom 218 provided data for the first treatment period and 181 provided data for both treatment periods. Significantly higher levels of improvement in the primary outcomes were seen for diclofenac + misoprostol than for acetaminophen (P < 0.001). Adverse events were more common when patients took diclofenac + misoprostol (P = 0.046). Diclofenac + misoprostol was rated as "better" or "much better" by 57% of the 174 patients who provided such ratings for both treatment periods, while acetaminophen was rated as "better" or "much better" by 20% of these patients, and 22% reported no difference (P < 0.001). Differences favoring diclofenac + misoprostol over acetaminophen were greater in patients with more severe osteoarthritis according to baseline pain scores, radiographs, or number of involved joints. Conclusion. Patients with osteoarthritis of the hip or knee had significantly greater improvements in pain scores over 6 weeks with diclofenac + misoprostol than with acetaminophen, although patients with mild osteoarthritis had similar improvements with both drugs. Acetaminophen was associated with fewer adverse events.

Authors
Pincus, T; Koch, GG; Sokka, T; Lefkowith, J; Wolfe, F; Jordan, JM; Luta, G; Callahan, LF; Wang, X; Schwartz, T; Abramson, SB; Caldwell, JR; Harrell, RA; Kremer, JM; Lautzenheiser, RL; Markenson, JA; Schnitzer, TJ; Weaver, A; Cummins, P; Wilson, A; Morant, S; Fort, J
MLA Citation
Pincus, T, Koch, GG, Sokka, T, Lefkowith, J, Wolfe, F, Jordan, JM, Luta, G, Callahan, LF, Wang, X, Schwartz, T, Abramson, SB, Caldwell, JR, Harrell, RA, Kremer, JM, Lautzenheiser, RL, Markenson, JA, Schnitzer, TJ, Weaver, A, Cummins, P, Wilson, A, Morant, S, and Fort, J. "A randomized, double-blind, crossover clinical trial of diclofenac plus misoprostol versus acetaminophen in patients with osteoarthritis of the hip or knee." Arthritis and Rheumatism 44.7 (2001): 1587-1598.
Source
scival
Published In
Arthritis and Rheumatism
Volume
44
Issue
7
Publish Date
2001
Start Page
1587
End Page
1598
DOI
10.1002/1529-0131(200107)44:7<1587::AID-ART282>3.0.CO;2-X

Scaled medial axis representation: Evidence from position discrimination task

Previous experimental studies have found enhanced contrast sensitivity at medial locations, supporting theoretical speculations that the visual system represents simple spatial regions by their medial axes. The core model hypothesize that the medial representation arises in a scale-specific way: the scale is determined by local object width, and it controls the resolution at which the medial locus and object width are encoded. Here we look for further evidence for a medial representation and test the idea that the resolution of the axis depends on object width. A new experimental paradigm was developed to infer sensitivity to position within individual figural regions, using circles as the figural regions. A probe dot was presented within a circle along a diameter at one location in one temporal interval and at a slightly different location on that diameter in a second temporal interval. The observer's task was compared to two-dot separation discrimination thresholds. Data were obtained for two circle sizes. It was found that positional sensitivity was strongly enhanced near the center of the circle, and it was enhanced in a scale-dependent way. The results were tested against a scaled medial (core) model and against models assuming no medial representation. The core model was better able to account for the results.

Authors
Wang, X; Burbeck, CA
MLA Citation
Wang, X, and Burbeck, CA. "Scaled medial axis representation: Evidence from position discrimination task." Vision Research 38.13 (1998): 1947-1959.
PMID
9797941
Source
scival
Published In
Vision Research
Volume
38
Issue
13
Publish Date
1998
Start Page
1947
End Page
1959
DOI
10.1016/S0042-6989(97)00299-X

Enhanced position sensitivity at scaled medial loci

Purpose: Kovacs and Julesz (Nature, 1994) found enhanced contrast sensitivity at medial locations, supporting theoretical speculations that the visual system represents regions by medial axes. Burbeck and Pizer's core model (Vis. Res., 1995) hypothesizes that the medial representation arises in a scale-specific way, with scale being determined by local object width, and that the spatial resolution of the medial axis is proportional to that scale. Here we look for further evidence for a medial representation and test the idea that the resolution of the axis depends on object width. Methods: A new experimental paradigm was developed to infer sensitivity to position within individual figural regions. A probe dot was presented within the object (a circle) along a radius; in a second temporal interval the object was presented again with the probe dot in a slightly different location along the same radius. The observer's task was to report the direction in which the probe dot had been displaced. Position discrimination thresholds were calculated and compared to 2-dot separation discrimination thresholds. Data were obtained for three circle sizes. Results: Positional sensitivity was enhanced near the center of the circle and it was enhanced in a size dependent way: the area of enhancement was larger for the larger objects, and the magnitude of the enhancement was greater for the larger objects. Conclusion: Results of this new position discrimination paradigm support the hypothesis that the visual system forms a medial representation and provide evidence for scaling of the spatial resolution of that representation.

Authors
Wang, XF; Burbeck, CA
MLA Citation
Wang, XF, and Burbeck, CA. "Enhanced position sensitivity at scaled medial loci." Investigative Ophthalmology and Visual Science 37.3 (1996): S169-.
Source
scival
Published In
Investigative Ophthalmology and Visual Science
Volume
37
Issue
3
Publish Date
1996
Start Page
S169

Targeted Clinical Trials

Authors
George, ; Wang,
MLA Citation
George, , and Wang, . "Targeted Clinical Trials." Designs for Clinical Trials. Ed. Harrington. Springer. 157-177. (Chapter)
Source
manual
Start Page
157
End Page
177

Endpoints for cancer clinical trials

Authors
George, ; Wang, ; Pang,
MLA Citation
George, , Wang, , and Pang, . "Endpoints for cancer clinical trials." Cancer Clinical Trials: Current and Controversial Issues in Design and Analysis. Ed. George. Chapman & Hall/CRC. 3-36. (Chapter)
Source
manual
Start Page
3
End Page
36

Endpoints for cancer clinical trials

Authors
George, ; Wang, ; Pang,
MLA Citation
George, , Wang, , and Pang, . "Endpoints for cancer clinical trials." Cancer Clinical Trials: Current and Controversial Issues in Design and Analysis. Ed. George. Chapman & Hall/CRC. 3-36. (Chapter)
Source
manual
Start Page
3
End Page
36
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