tbuckley/cabot-search huggingface dataset:
Effect of prior cancer on outcomes in early stage lung cancer: Implications for clinical trial eligibility and accrual.
Authors: David E. Gerber, Andrew L. Laccetti, Sandi Pruitt, Lei Xuan, Ethan Halm
Journal: Journal of Clinical Oncology (2016)

6573 Background: Early-stage lung cancer represents a key focus of numerous multicenter clinical trials, but stringent eligibility criteria may limit enrollment. We examined the impact of and rationale for exclusion of patients with a prior cancer, a common practice among clinical trials in this population. Methods: We identified patients > 65 years of age with early stage lung cancer diagnosed 1996-2009 in the Surveillance, Epidemiology, and End Results-Medicare linked registry. Prior cancer diagnoses were isolated and characterized by type, stage, and timing with respect to the lung cancer diagnosis. All-cause and lung cancer specific-survival rates were compared between patients with and without prior cancer using Cox regression analyses and propensity scores. Results: 42,910 patients with early-stage lung cancer were identified, of whom 21% had a prior cancer. The most common prior cancers were prostate (21%), breast (18%), gastrointestinal (17%), and other genitourinary (15%). Most prior cancers were localized stage, and 61% were diagnosed within 5 years of the lung cancer diagnosis. There was no difference in overall survival between patients with and without prior cancer (hazard ratio [HR] 1.01; P= 0.52). Lung cancer specific survival was improved among patients with prior cancer (HR 0.79; P< 0.001). Prior cancer was not associated with inferior survival regardless of stage, type, or timing of the prior cancer. Conclusions: A history of prior cancer may exclude a substantial proportion of patients with early-stage lung cancer from enrollment in clinical trials. However, history of prior cancer does not appear to convey adverse clinical outcomes. Inclusion of these patients in clinical trials to improve study accrual, completion rates, and generalizability should be considered.
Retrospective analysis of phase 1 study duration and symptom burden among patients at a comprehensive cancer center.
Authors: Michelle Treasure, Barbara J. Daly, Afshin Dowlati, Neal J. Meropol
Journal: Journal of Clinical Oncology (2016)

e14058 Background: Phase I clinical trials are a critical first step in the development of new cancer therapeutics. While the average duration on study is reported to be approximately 2 months, many patients stop therapy after only a few weeks. Adverse events (AEs) or uncontrolled symptom burden likely contribute to early treatment withdrawal, and it is often difficult to ascertain whether these events or symptoms are disease or treatment-related. Regardless, early withdrawal may delay determination of the effectiveness of potential new therapies. We sought to characterize the reasons for early treatment termination in order to identify potential modifiable causes. Methods: A retrospective chart review was conducted on solid tumor patients enrolled on institutional phase I clinical trials from 2003 to 2013 at University Hospitals Case Medical Center Seidman Cancer Center. Results: 254 patients were included in the analysis. The mean duration on study was 80.7 days (SD 68.6). All patients experienced AE with a mean of 25.3 events and a median of 19 (range 1-101). Of these, 46.6% were non-laboratory events and potentially addressable with supportive interventions. Constitutional symptoms (26%), gastrointestinal symptoms (25%) and pain (12%) were the most common non-laboratory AEs. Disease progression (59.1%) was the most common reason for study withdrawal. Notably, 15.4% of patients came off study because of AEs. An additional 14.1% discontinued for other reasons (e.g. physician decision, patient withdrawal/refusal after beginning protocol treatment, other complicating disease) which may have been attributable to symptom burden. A significant correlation was found between the frequency of AEs and shorter duration on study (r = -.308; p < .01). Conclusions: Physical AEs along with undertreated emotional distress may lead to early termination of trial participation and confound clinical assessment of investigational treatments. Designing interventions that reduce the burden of AEs may extend time on trial and improve the quality of life of participants on phase I trials, thus contributing to advances in cancer care.
Individual patient data meta-analysis of the IMPACT of treatment site on the outcome of head and neck cancer patients treated within 6 randomized trials.
Authors: Paolo Bossi, Rosalba Miceli, Marco Benasso, Renzo Corvò, Almalina Bacigalupo, Giuseppe Sanguineti, Carlo Fallai, Marco Carlo Merlano, Gabriele Infante, Carla Dani, Lisa F. Licitra
Journal: Journal of Clinical Oncology (2016)

6022 Background: The impact of centre expertise on outcome of head and neck cancer (HNC) patients (pts) treated with chemotherapy (CT) +/- radiotherapy (RT) has been sparsely evaluated. Pts selection, RT quality, compliance with full dose administration, kind and extent of supportive care implementation may all explain possible benefits of being treated in highly experienced centers. Methods: We performed an individual patient data meta-analysis of 6 randomized trials in HNC conducted in Italy between 1983 and 2001. Different RT approaches (curative, postoperative), fractionations (conventional, altered) and combinations with CT (sequential, alternated, concomitant) were administered. The main aim was the association between center type (coordinating site- CS - vs non-coordinating site - NCS) and overall survival (OS), progression-free survival (PFS) and death within 3 months since treatment start (3MD). In univariable analyses center type was the main investigated variable and the trial was modeled as a random factor. Multivariable covariates analysed were: site of disease, performance status, T and N stage, treatment type; interaction between CS, NCS and treatment was also considered. Results: Globally, the outcome of 1022 patients was analyzed. Median follow up was 76 months (48-224). CS enrolled a higher median number of pts in respect to NCS (178 vs 115). In univariable analysis, NCS showed a higher risk of 3MD (OR 1.82; 1.09-3.04). In multivariable analysis, no difference was observed in OS, PFS and 3MD between CS and NCS; models with interaction centre-treatment showed that pts treated with RT and CT in NCS had a significantly worse OS (HR 1.47; 1.08-2.02) and PFS (HR 1.54; 1.09-2.18). On the contrary no difference on outcome was identified with conventional/altered RT as single treatment. Conclusions: In this pooled analyses of several trials on advanced HNC, we saw that OS was significantly better at CS as compared to NCS when treatment consisted of combination of CT and RT. Our study adds to available evidence suggesting that high case volumes correlate with clinical outcome in HNC. In clinical trials on RT and CT, case volume may need to be a stratifying factor.
Comparison of comorbidity measures to predict postoperative lung cancer survival in the National Cancer Database (AFT-03).
Authors: Melisa L. Wong, Timothy L. McMurry, George J. Stukenborg, Amanda B. Francescatti, Carla Amato-Martz, Jessica R. Schumacher, Caprice Christian Greenberg, George J. Chang, David P Winchester, Daniel P. McKellar, Louise Christie Walter, Benjamin D. Kozower
Journal: Journal of Clinical Oncology (2017)

6519 Background: Comprehensive assessment of comorbidity in cancer registries is critical for comparative effectiveness research. The National Cancer Database (NCDB) measures comorbidity with a diagnosis code-based Charlson Comorbidity Index (CCI) abstracted from discharge abstracts or billing face sheets. However, the prognostic performance of this code-based CCI has not been compared with a medical chart-based CCI or individual comorbid conditions in a nationally representative sample of patients with lung cancer. Methods: Through a special study of the NCDB, cancer registrars performed chart abstraction for 18 perioperative comorbid conditions for 9,640 randomly selected patients with stage I-III non-small cell lung cancer resected in 2006-07 at 1,150 Commission on Cancer-accredited facilities. We compared the prognostic performance of the NCDB code-based categorical CCI (0, 1, 2+), special study chart-based continuous CCI, and individual comorbid conditions in 3 separate Cox proportional hazards models for 5-year postoperative overall survival. All models adjusted for demographic and clinical characteristics. Results: Median age was 67 (IQR 60-74). The most common comorbidities were COPD (40%) and CAD (21%). Five-year postoperative overall survival was 55.5%. Agreement between the code- and chart-based CCIs was 51.9% with the code-based CCI underestimating comorbidity for 36.2% patients. The model including individual comorbid conditions had the best prognostic performance (R 2 0.196, C index 0.654). COPD, CAD, CHF, dementia, diabetes, moderate/severe renal and liver disease, peripheral vascular disease, psychiatric disorder, and substance abuse were independently associated with decreased survival. The chart-based CCI model (R 2 0.189, C index 0.650) predicted postoperative survival better than the code-based CCI model (R 2 0.181, C index 0.645). Conclusions: The NCDB code-based CCI underestimates comorbidity in patients with surgically resected lung cancer. The chart-based CCI and data on individual comorbid conditions improved prognostic performance and would be valuable additions to the NCDB to strengthen comparative effectiveness research.
Comparison of efficacy among nab-paclitaxel, paclitaxel and irinotecan monotherapies as the second-line chemotherapy following S-1-containing regimens in patients with advanced gastric cancer.
Authors: Tetsuya Kusumoto, Akinori Egashira, Kenkichi Hashimoto, Eiji Kusumoto, Norifumi Tsutsumi, Mitsuhiko Ota, Yoshihisa Sakaguchi, Koji Ikejiri, Yoshihiko Maehara
Journal: Journal of Clinical Oncology (2016)

e15577 Background: Second-line chemotherapy can now be considered as a proven treatment option for patients with metastatic or locally advanced gastric cancer (AGC). Nab-paclitaxel (nab-PTX) is a nanoparticle albumin-bounded paclitaxel (PTX) formulation that does not require Cremophor or anhydrous ethanol. Therefore, it reduces the risk of hypersensitivity reactions and does not require steroidal or antihistamine premedication. The purpose of the study is to evaluate the efficacy and safety of nab-PTX compared with PTX or irinotecan (CPT-11) as the second-line treatment in patients with AGC refractory to the first-line chemotherapy comprising S-1. Methods: We conducted a single-institutional retrospective review of the data of 54 patients with AGC who received nab-PTX (n = 6) PTX (n = 33) or CPT-11 (n = 15) monotherapy as the second-line regimen following S-1 base treatment. The data of adverse events, tumor responses or survival data were collected and compared among the three groups. Results: Although fewer patients in the nab-PTX group terminated the treatment due to adverse events, hematological toxicities, especially neutropenia should be given attention. The nab-PTX group showed an objective response rate (ORR) of 50% and a disease control rate of 83%. The similar data of the ORRs were obtained between the three groups. Survival data showed that the MST was 342 days and the median PFS was 237 days for the administration of nab-PTX, compared with 159 days and 90 days in PTX group, or 333 days and 187 days in CPT-11 group, from the beginning of these drugs administration, were not significantly different. The OS was 495 days in nab-PTX group, compared with 371 days in PTX group or 672 days in CPT-11 group, were not significantly different. Conclusions: The nab-PTX monotherapy might be a candidate for patients with AGC who fail to respond to S-1-containing regimens, similar to the PTX or CPT-11 monotherapy. The optimal schedule of nab-PTX administration is currently under consideration by the ongoing phase III trial.
The activity of crizotinib in chemo-refractory MET-amplified esogastric adenocarcinomas: Results from the AcSé-crizotinib program.
Authors: Thomas Aparicio, Nathalie Cozic, Christelle De La Fouchardiere, Emeline Meriaux, Jérôme Edouard Plaza, Laurent Mineur, Rosine Guimbaud, Emmanuelle Samalin, Florence Mary, Thierry Lecomte, Carlos Alberto Gomez-Roca, Paul Arthur Haineaux, Alain Gratet, Janick Selves, Yves Menu, Nikias Colignon, Celine Mahier - Ait Oukhatar, Frédéric Legrand, Gilles Vassal
Journal: Journal of Clinical Oncology (2018)

4054 Background: Crizotinib (czb) is only registered for treating ALK and ROS1-translocated lung cancer. However, Czb is also a MET inhibitor. Several malignancies are characterized by MET amplification (amp). Czb activity in MET-amplified (+) tumors was explored within the French National Cancer Institute (INCa) AcSé program. This included access to tumor molecular diagnoses and an exploratory multi-tumor 2-stage design phase II trial. We herein report the results in patients (pts) with esogastric MET+ adenocarcinomas (adenoK). Methods: MET expression, on formalin-fixed, paraffin-embedded tumor samples, was screened in 127 centers and analyzed in 28 regional molecular genetic centers. MET+ was evaluated by FISH in tumor samples with IHC scores ≥2+. Pts with tumors showing > 6 MET copies, whatever the MET/CEN7 ratio, were eligible. Pts were treated with czb 250 mg BID. A two-stage Simon design was planned with a 90% power to detect an objective response rate (ORR) at 8 weeks (w) (CR+PR) above 30% against a 10% rate at the 10% level. The disease control rate (DCR) (CR+PR+SD) was assessed at 16 w. Responses were assessed every 8 w by RECIST v1.1. Results: From 08/2013 to 12/2017, MET was prospectively analyzed in 546 esogastric adenoK: amp were found in 33/546 adenoK (28/506 gastric and 5/40 esophagus). Eight pts were enrolled in the trial, median age was 62 years [44–80], WHO performance status 0 in 2 pts, 1 in 5 and 2 in 1 pt. At the cut-off date, 1 pt was still treated, 7 had stopped czb (5 PD, 2 adverse events (AEs)). Among the 7 pts evaluable for response at 8 w, we observed 3 PR and 1 SD, giving an ORR = 42.8% [6.1-79.4]. At 16 w, DCR = 50% [95% CI: 10-90] was achieved in 3/6 evaluable pts. Czb was well tolerated with only 6 grade ≥3 AEs or SAEs. The most common AEs, mainly grade 1, were anemia (87.5%), nausea (75%), hypocalcemia-edema-ASAT increase (62.5% for each), vomiting-constipation-fatigue-loss of appetite-visual disorders (50% for each). Conclusions: National biomarker-driven access to czb for MET+ esogastric adenoK pts is feasible. MET amp was observed in around 5% of gastric adenoK and 12% of the oesophagus adenoK. Preliminary results show Czb activity, with PR and SD, in MET+ esogastric adenoK. Clinical trial information: NCT02034981.
US agency changes alcohol advice after doctor complains
Authors: Owen Dyer
Journal: BMJ (2018)

A Boston University epidemiologist and physician who complained to the director of the National Institutes of Health (NIH) about public advice on drinking and breast cancer risk has told The BMJ that he was pleasantly surprised to see the relevant web page change almost immediately to reflect his concerns.

Mike Siegel, professor of public health at Boston, wrote to Francis Collins, NIH director, criticising the advice offered on the main cancer web page of the National Institute on Alcohol Abuse and Alcoholism (NIAAA), which claimed that “drinking too much alcohol can increase your risk of …
International single-arm phase II trial of pazopanib in advanced extraskeletal myxoid chondrosarcoma: A Collaborative Spanish (GEIS), Italian (ISG) and French (FSG) Sarcoma Groups study.
Authors: Silvia Stacchiotti, Stefano Ferrari, Andres Redondo, Emanuela Palmerini, Nadia Hindi, M. Angeles Vaz, Anna Maria Frezza, Antonio Gutierrez, Antonio Lopez-Pousa, Giovanni Grignani, Antoine Italiano, Sarah Dumont, Jean-Yves Blay, Nicolas Penel, Daniel Bernabeu, Enrique de Alava, Dominique Ranchère-Vince, Paola Collini, Josefina Cruz, Javier Martin Broto
Journal: Journal of Clinical Oncology (2017)

11062 Background: Extraskeletal myxoid chondrosarcoma (EMC) is an exceedingly rare sarcoma, marked by a specific translocation involving the gene NR4A3 that can be rearranged with different partners. Preliminary retrospective data suggest that sunitinib is active, but no formal prospective studies are available. We report on a multicentric European prospective, investigator-driven, Phase 2 study on pazopanib (P) in NR4A3+ advanced EMC patients (pts), carried out by the Spanish, Italian and French Sarcoma groups. Methods: From June 2014 to November 2016, 24 advanced EMC pts entered this study (median age: 64 yrs - disease extent: metastatic 77%, locally advanced 23% - prior medical treatment: 18 (86%) naive; 2 (9%) 1 line, 1 (5%) &gt; 1 line). Path diagnosis and NR4A3 rearrangement (FISH and/or real-time PCR analysis) were centrally confirmed. Pts received P 800 mg/day (relative dose intensity = 0,82%, 658 mg/day), until progression or toxicity. The primary study end-point was response rate as per RECIST 1.1. Secondary end-points were overall survival, progression-free survival (PFS), clinical benefit rate (CBR) (RECIST CR+PR+SD≥6mos). An exploratory evaluation of the correlation between the rearrangement subtype and the outcome is ongoing. Results: 20/24 pts were evaluable for response (1 early death; 3 too early). One patient (5%) had a partial response, 17 (75%) stable disease, 2 (10%) progression as their best RECIST responses. At the time of this analysis, 12 pts were still under treatment, while 12 interrupted P (10 progression, 1 toxicity, 1 other). At a 13-month median follow-up, the median PFS was 13 months (range 1.6-25.1), with 29% pts progression-free at 18 months and a 65% CBR. Median OS was not reached. Conclusions: This Phase 2 study is formally negative since the target of at least 3/21 RECIST responses was not reached. However, looking at PFS, P was associated with a prolonged disease stabilization in a significant proportion of pts. This suggests to further explore the use of P in EMC. Clinical trial information: NCT02066285.
Patterns of care and survival outcomes of stage IIIA endometrial cancer: An analysis of the National Cancer Database.
Authors: Sherry Yan, Shengyang Wu, Leslie R. Boyd, Ghadir Salame, Peter B. Schiff, Stella C. Lymberis
Journal: Journal of Clinical Oncology (2018)

5592 Background: Stage IIIA endometrial cancer with serosal or adnexal involvement has a better prognosis than other advanced uterine cancers and likely behaves differently compared to those with vaginal, parametrial or lymph node involvement. We performed a population-based analysis of Stage IIIA endometrial cancer from the National Cancer Database (NCDB) to evaluate survival outcomes by treatment regimens. Methods: Patients with FIGO stage IIIA endometrioid endometrial cancer treated with hysterectomy and bilateral oophorectomy and receiving adjuvant treatment between 2004 and 2014 were identified. Treatments evaluated include chemotherapy alone (CT), pelvic radiation ± brachytherapy (RT±BT), chemotherapy with brachytherapy (CT+BT), chemotherapy with pelvic radiation (CT+RT), or chemotherapy with pelvic radiation and brachytherapy (CT+RT+BT). Treatment trends over time were analyzed. Multivariate Cox proportional hazard models were developed to examine treatment outcomes. Results: Of 6,760 patients who met study criteria, 1842 (27.2%) received adjuvant CT; 2,732 (40.4%) received RT±BT; 702 (10.4%) received CT+BT; 871 (12.9%) received CT+RT; and 613 (9.1%) received CT+RT+BT. The practice of RT±BT declined from 56% to 16%, while CT alone rose from 18% to 36% and CT+BT rose from 4% to 14% over the study period (p < 0.001). Median follow-up was 69.0 months. Five-year overall survival was 83.7%, 69.7%, 73.6%, 63.6% and 78.0% for CT+BT, CT, CT+RT, RT±BT, and CT+RT+BT, respectively. Older age, black race, higher Charlson-Deyo comorbidity score, higher tumor grade, lymphovascular invasion, and having Medicare/uninsured were negative predictors of survival on multivariate analysis. CT+BT was significantly associated with improved survival over CT (HR 1.89, 95% CI 1.53-2.33; p < 0.001), CT+RT (HR 1.72, 95% CI 1.36-2.18; p < 0.001), RT±BT (HR 2.46, 95% CI 2.01-3.01; p < 0.001), and CT+RT+BT (HR 1.38, 95% CI 1.07-1.79; p < 0.001). Conclusions: While pattern of care shows an increase in use of adjuvant chemotherapy alone in Stage IIIA endometrial cancer, our findings demonstrate that chemotherapy should be combined with vaginal cuff brachytherapy to decrease mortality.
Feasibility of real-time cell-of-origin subtype identification by gene expression profile in the phase 3 trial of lenalidomide plus R-CHOP vs placebo plus R-CHOP in patients with untreated ABC-type diffuse large B-cell lymphoma (ROBUST).
Authors: Grzegorz S. Nowakowski, Annalisa Chiappella, Thomas E. Witzig, Michele Spina, Randy D. Gascoyne, Lei Zhang, Jocelyne Flament, Jacqueline Repici, Erin Conlin, Krista Delissio, Umberto Vitolo
Journal: Journal of Clinical Oncology (2016)

7538 Background: Gene expression profiling (GEP) represents a gold standard in identifying patients (pts) with activated B-cell–like (ABC) DLBCL, a subtype associated with inferior outcomes. Until recently, real-time identification of pts with ABC DLBCL as an integrated biomarker and inclusion criterion was not feasible due to technology limitations. The randomized, double-blind, phase 3 ROBUST study (NCT02285062) compares lenalidomide + R-CHOP (R2-CHOP) with placebo + R-CHOP in pts with previously untreated ABC-type DLBCL. Methods: ROBUST methods have been described (Nowakowski, ASCO 2015). A key entry criterion is previously untreated, histologically confirmed ABC-type CD20+ DLBCL. Formalin-fixed paraffin-embedded excisional/surgical or core needle biopsy samples (Storhoff, Blood 2015) are analyzed by central pathology using the NanoString Lymphoma Subtyping Test (LST; Wallden, JCO 2015), based on the Lymph2Cx GEP assay (Scott, Blood 2014). Turnaround time is defined as number of days between central pathology sample receipt and results being provided to the study site. Results: As of 11 Jan 2016, 357 pts were screened for ROBUST using the LST. Samples were analyzed in 2 central pathology labs in the US and UK. Cell of origin (COO) was ABC and non-ABC in 118 (33%) and 212 (59%), respectively. 27 pts (8%) had samples that could not be processed for technical reasons (incorrect/insufficient slides or blocks, or low tissue RNA concentration and/or purity). Mean turnaround time was 2.25 days (range, 0-9). 86 pts have met all inclusion criteria and were enrolled in ROBUST. Conclusions: Real-time COO assessment is feasible in a multi-center, global phase 3 DLBCL study with short turnaround time. The percentage of pts with ABC-type DLBCL was similar to that reported in the literature. Our findings have important implications for the design and size estimation of both current and future studies in newly diagnosed DLBCL utilizing COO as a biomarker, promising a significant step forward in precision medicine. Updated results will be presented. Clinical trial information: NCT02285062.