tbuckley/cabot-search huggingface dataset:
First-line bevacizumab (BEV) and chemotherapy (CT) for metastatic colorectal cancer (mCRC): Results from a developing nation.
Authors: F. A. Franke, S. J. Azevedo, O. Gampel, J. Q. Guimarães, M. R. Schaum, A. Murad, A. K. Coutinho, J. A. Oliveira, J. N. Matos Neto, M. L. França
Journal: Journal of Clinical Oncology (2010)

e14082 Background: More than 2/3 of the 20 million new cases of cancer predicted to occur yearly by 2020 will be in developing nations. Access to cancer treatment is a major issue in the developing world and evidence-based programs should be used whenever possible. BEV significantly extends overall survival (OS) when added to standard first-line CT for mCRC and although previous observational studies showed that the efficacy and safety profile of BEV in routine practice was consistent with data from phase III trials, no separate results from developing nations were described until now. Here, we report the results of the Bevacizumab Expanded Access Trial (BEAT) in a cohort of Brazilian patients. Methods: Patients with unresectable and previously untreated mCRC received the physician's choice of a fluoropyrimidine-based CT in combination with BEV 5 mg/kg q2w (5- fluorouracil [5-FU] regimens) or 7.5 mg/kg q3w (capecitabine [cap] regimens). Primary objective was safety evaluation, particularly the incidence of adverse events (AEs) related to BEV. Secondary objective was efficacy assessment, including time to progression (TTP), progression free-survival (PFS) and OS. Results: This study enrolled 168 patients from 28 centers in Brazil, from May 2006 to March 2007. Final analysis included 162 patients who received ≥ 1 BEV dose (female 55%; median age 59 years; 30% ≥ 65 years; ECOG PS 0/1 75%/23%). CT regimens most commonly used with BEV included FOLFOX (44%), 5-FU/cap monotherapy (21%) and FOLFIRI (13%). Median follow-up was 17.7 months (range 0.4 to 36.5 months), and 155 patients (95.7%) were followed for > 60 days. Grade 3-4 AEs of special interest included hypertension (3.1%) and proteinuria (2.5%). There were no cases of grade 3-4 bleeding or thromboembolism. Median TTP, PFS and OS were respectively 11.4 months (95% CI: 9.5; 13.9), 11.0 months (95% CI: 9.5; 13.9) and 21.6 months (95% CI: 18.3; 25.5 months). Conclusions: The results observed with the use of BEV in a cohort of mCRC patients from a developing nation were consistent to those obtained in the United States and internationally. These data further support the addition of BEV to CT in the first-line treatment of mCRC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Roche Roche Roche
Association between abdominal adiposity, muscle mass, and metabolic syndrome in survivors of testicular germ cell cancer.
Authors: Kyaw Zin Thein, William Osai, Shi-Ming Tu, Lance C. Pagliaro, Jeri Kim, Sai-ching J. Yeung
Journal: Journal of Clinical Oncology (2016)

250 Background: Testicular germ cell tumor survivors (TGCTSs) contend with treatment side effects for decades after cure, and many have metabolic syndrome (MTS), a modifiable cardiometabolic risk factor. Because reliably predicting MTS could prompt interventionreducing risk, we analyzed clinical data and body composition in computed tomography (CT) scans to identify associations. Methods: In a retrospective review of 196 TGCTSs treated at a single institution from 1970 to 2007, we collected patient (pt) demographics, clinical data, body fat composition measures, and evidence from CT scans from baseline through posttreatment. NIH Image J was used to analyze cross-sectional CT images and measured subcutaneous adipose tissue, visceral adipose tissue, and skeletal muscle. Visceral fat-to-muscle ratio (VMR), visceral-to-subcutaneous fat ratio (VSR), and change in VMR and VSR from baseline to 3 to 5 years posttreatment (ΔVMR and ΔVSR) were calculated. We also gathered posttreatment glucose, blood pressure, lipid data, and body weight and height measured at time of scans. The 2001 U.S. National Cholesterol Education Program Adult Treatment Panel III guideline defined MTS. Univariate and multivariate logistic regression analyses identified associations. Results: Of the 167 pts included in the final analysis, 37.7% had MTS, 76.6% were white, and 68.9% had chemotherapy. Pts with MTS had significantly higher VMRs (p = .007) and VSRs (p = .021) than those without. Pts receiving chemotherapy and radiotherapy were significantly more likely to have MTS (p = .044 and p = .037). A multinomial logistic regression model including year of diagnosis, age, race, tumor histology, treatment, VSR, and VMR identified the association of high VMR and VSR with MTS; ΔVMR and ΔVSR were not statistically significant predictors. Conclusions: Body composition analyses identified VMR and VSR as significant predictors of MTS.
The role of NCI-sponsored research in ASCO Clinical Cancer Advances 2005-2008.
Authors: B. Zuckerman, J. Corrigan
Journal: Journal of Clinical Oncology (2010)

6094 Background: Recent attention has been given to the return on investment to publicly-funded cancer research (e.g., Manton et al 2009, Sun et al 2009, which correlate changes in cancer mortality with R&D spending). Such approaches, however, cannot consider the likely future effect of current breakthroughs on clinical outcomes. The “Clinical Cancer Advances” special articles of the Journal of Clinical Oncology (published 2005-2009) identify “major advances” and “notable research advances” occurring in the past year. These advances, selected by a panel of experts, identify significant research studies, including those considered to have potential to decrease mortality from cancer (Petrelli et al 2009). Methods: A study of the 119 advances reported in the 2005-2008 issues used bibliometric techniques to assess: (1) the direct funding for the research, as identified through the funding sources acknowledged by the publications and presentations that form the basis for the advancements; and (2) upstream funding. The study identified the funders heavily represented in the acknowledgements, as a proxy for assessing the relative scientific return to funding. Results: The U.S. National Cancer Institute (NCI) was the most frequently cited funder; there was evidence of direct NCI support for at least one publication or presentation cited by JCO for 69 (58%) of the advances – 37 solely acknowledging NCI funding and 32 acknowledging a mix of NCI and non-NCI funding. 50 advances acknowledged industry funding. By comparison, Sun et al estimated that NCI funding represented approximately 25%-35% of total U.S. cancer research and development funding 1970- 2000. There was substantial variation in the extent to which NCI funding was acknowledged by type of advance. While nearly all of advances in pediatrics, prevention, and survivorship acknowledged NCI support (21 of 23), few advances in GU cancers (1 of 11) did. Cooperative Groups were the predominant performers of NCI-funded research acknowledged as underlying the advances (28 of 69). Conclusions: While the NCI is heavily represented in the support for the advances, there are differences both by disease area and mechanism of support that warrant future research. No significant financial relationships to disclose.
Could a biomarkers-based patients' selection help to plan a clinical trial with targeted agents (TA) for metastatic renal cell carcinoma (mRCC)? Interaction and power analysis of randomized trials (RCTs).
Authors: Francesco Massari, Francesca Maines, Sara Pilotto, Maria Bonomi, Diana Giannarelli, Matteo Brunelli, Guido Martignoni, Giampaolo Tortora, Emilio Bria
Journal: Journal of Clinical Oncology (2013)

399 Background: To predict the clinical benefit of TA in mRCC, several studies have analyzed some angiogenesis-related biomarkers including soluble VEGF and VEGF-Receptors, VEGF polymorphisms, IL-8 polymorphisms, and VHL mutations. We performed a power analysis to assess how much a biomarker-based approach can affect the sample size of a trial in mRCC. Methods: Hazard ratios (HR) for survival with 95% confidence intervals (CI) for overall survival were extracted and cumulated according to a random-effect model from RCTs. A sensitivity analysis according to ‘biomarker-selection’ approach and to ‘unselected’ fashion was accomplished in order to test for interaction. Testing for heterogeneity was performed as well. Results: A correlation between a featured biomarker and treatment effect was reported in three RCTs (1987 patients). The attrition rate for the survival analysis according to the molecular analysis was 45% (range 20 to 60%). In spite of the extremely different bio-markers’ profiles, demonstrated by the significant observed heterogeneity (p = 0.002), we found an Hazard Ratio (HR) for overall survival of 0.60 (95% CI 0.40-0.89; p = 0.013) and a significant interaction according to strategy (‘biomarker-selected’ vs.‘unselected’) (p = 0.025), supporting a differential effect of these drugs when administered according to a predictive phenotype. In the ‘unselected’ sample, considering the intention to treat analysis (all randomized patients) the HR was 0.90 (95% 0.80-1.00; p = 0.06). From a clinical trial design perspective, if targeting these expected survival differences, with a power 80%, and a alpha-error 0.05, the required events are described in the table. Conclusions: With the aim to avoid the attrition of the heterogeneity of biomarkers’ selection and drugs, we speculate that the sample size of a planned clinical trial design in mRCC according to a biomolecular classifier may help to shorten the gap between clinical research and practice. [Table: see text]
Gemcitabine and epirubicin in patients with malignant pleural mesothelioma (MPM): A North Central Cancer Treatment Group phase II study
Authors: S. H. Okuno, R. Delaune, J. Sloan, M.-C. Aubry, N. Foster, K. Rowland, J. Mailliard, D. Nikcevich, J. Jett, B. Bot
Journal: Journal of Clinical Oncology (2005)

7264 Background: MPM is a relentlessly progressive disease. Optimal chemotherapy for MPM is unknown, but there is preclinical evidence of cytotoxic synergy between gemcitabine (G) and epirubicin (E) that provides a rationale for studying this combination in MPM. Methods: Pts received 3-week cycles (for a max of 6 cycles) of GEMZAR 750 mg/m2 IV infusion (over 30 minutes) on d1, d8 and EPIRUB 70 mg/m2 (IV push into free flowing IV of NS) on d1. Planned accrual was 41 pts, where 8 of 41 with a confirmed tumor response was evidence of promising activity. Results: 45 eligible pts (35 M, 39/6 ECOG PS of 0–1/2) were enrolled in 20 months (mos) from 08/02–04/04. Median age was 67 years (range 38–85). 20% of pts had prior chemo; 69% had epitheliod histology; and 64% had IMIG stage 4 disease. 45 of 46 pts were evaluable for response and adverse events (AEs). Pts received a median of 4 cycles (range 1–6). 4 confirmed responses were observed (4 PR/0 CR), for a confirmed response rate of 9% (95% CI: 4%–30%). 34 pts have progressed and 33 have died, with a median follow-up of 5.2 mos (range 1.8–7.5). Median time to progression was 4.4 mos (95% CI: 2.7–5.6), and the median survival was 5.7 mos (95% CI: 4.7–8.6). 27 patients (60%) experienced at least one grade 4+ AE, with 4 pts having a grade 5 AE. Gr. 5 AEs included: pneumonitis (possibly related to Rx), hypoxia (possibly related to Rx), ischemia/infarction (not related to Rx), and cardiovascular (not related to Rx). Common Gr. 3–4 AEs included (pts): neutropenia (32), leukopenia (24), dyspnea (13), fatigue (10), and thrombocytopenia (9). Conclusions: Gemcitabine and epirubicin as given in this trial had limited activity and did not meet our predefined criteria for success. Supported by NCCTG Grant CA25224. No significant financial relationships to disclose.
Whole-breast hypofractionated IMRT and brachytherapy boost after conservative surgery for breast cancer: Early results of a prospective non-randomised trial.
Authors: Benjamin Guix, Ivan Garcia, Ines Guix, Juan Antonio Lejarcegui, Jose Ignacio Tello, Miquel Prats, Luis Quinzaños, Joel Mases, Manel Algara, Josep Maria Sole Monne, Teresa Guix
Journal: Journal of Clinical Oncology (2015)

46 Background: To report early results obtained in a prospective group of patients (pts) treated with whole breast IMRT radiotherapy plus a brachytherapy boost to the tumor bed after conservative surgery, given either with hypofractionated or normofractionated radiotherapy. Methods: Between 12/2008 and 06/2014, 829 pts with &lt;4cm, N0-2 breast cancers treated with conservative surgery were assigned to enter the study. Pts were offered to be treated either with IMRT hypofrationated whole breast and lymphnode areas (if needed) radiotherapy 42.6 Gy (266cGyx16 fractions) plus a 7 Gy boost to the tumor bed, (hypofractionated group) or IMRT normofractionated 50 Gy (200cGyx25) to the whole breast and lymphatic areas (when needed) plus 16 Gy brachytherapy boost (200cGyx8 fractions) (normofractionated group). Treatment assignation was done according to the patients preference or, if none, were randomly assigned to have both groups uniformly balanced. During treatment and follow-up special attention was taken to early and late side-effects, breast fibrosis, arm lymphedema, skin reaction, patient satisfaction and local, regional and distant disease control. Results: A total of 309 pts were included in the hypofractionated group and 520 in the normofractionated group. All patients completed treatment. Pts were evaluated weekly during treatment and every 3 months for the first 2 years of follow-up and in a yearly basis after. Photographs were taken at each visit. SOMA-LENT scales were used in every visit. For quality of life EORTC QLQ-C30 plus the BR-15 module were used. No pts had adverse side-effect that required treatment ending in any group. In the hypofractionated group, there were 1 LR, 1 M1 and 1 death due to the disease. In the normofractionated group there were 12 LR, 7 M1 and 4 patients died due to the disease. Conclusions: Hypofractionated IMRT to the whole breast followed by a 1 fraction HDR breast implant was a safe and effective method of treatment for early breast cancer treated with conservative surgery, even in those patients N+ in which the supraclavicular fossa was included in the treatment fields. Pts satisfaction was greater in the hypofractionated group.
Phase Ib trial of gemcitabine with yttrium-90 in patients with hepatic tumors of pancreatobiliary origin.
Authors: Hyun S Kim, Juan C. Camacho, Bassel F. El-Rayes
Journal: Journal of Clinical Oncology (2016)

460 Background: The rationale for combining Gemcitabine (G) with Yttrium-90 (Y90) is based on G being a potent radio sensitizer and activity of Y90 against liver tumors of pancreatobiliary histology. Therefore, a safety and efficacy trial of adding G to Y90 is required. Methods: Eligibility: Chemo-naïve patients with histologic diagnosis of unresectable PC or CC with liver predominant disease. Design: Open label phase I design with 3+3 G dose escalation. Induction G on Day 1 followed by Y90 on Day 2 and subsequent pre-assigned dose levels of G until week 12. Primary objective: To determine the maximal tolerated dose of G that can be used in combination with Y90. Secondary objectives: To characterize the toxicity, evaluate hepatic progression free survival (HPFS); determine tumor response rate using RECIST and PERCIST criteria; determine the progression free survival (PFS) and overall survival (OS). Correlative Imaging: 18-FDG PET/CT with contrast at baseline and 12 weeks. Results: 14 patients were recruited and 8 met the inclusion criteria. Seven out of eight patients tolerated the dose escalation regime of G (dose level 1-400 and dose level 2-600mg/m 2 ). All the patients developed grade 1 toxicities (Hepatobiliary 25%, Bone marrow 25%, Fatigue 100%). Three patients (37.5 %) had grade 2 hepatobiliary toxicity and one patient (12.5 %) had grade 3 hepatobiliary toxicity, which required short-term hospitalization. No radiation pneumonitis, gastrointestinal ulceration, or procedure-related mortality occurred. Six patients (75%) developed grade 1 toxicity (fatigue). All of the patients had SD in the liver by RECIST; the objective response rate was 62.5% by PERCIST (CR12.5%, PR50%, SD25% PD12.5%). Overall objective response rate was 0% by RECIST (SD62.5%, PD37.5%); and 50% for PERCIST (CR12.5%, PR37.5%, SD12.5%, PD37.5%). The median OS from diagnosis was 13.8 months (95% CI, 9.65 to 26.29 months) and from Y90 therapy 10.9 months (95% CI, 6.47 to 22.39 months). PFS was 6.92 months (95%CI, 4.37-16.5 months) and HPFS of 8.72 months (95%CI, 4.48-19.36 months). Conclusions: In patients with hepatic tumors of pancreatobiliary origin, Gemcitabine at 600mg/m 2 with Y90 therapy appears to be a viable and safe therapy. Clinical trial information: NCT01434459.
Novel BET Protein Proteolysis Targeting Chimeras (BETP-PROTACs) Exert Potent Single Agent and Synergistic Activity with Ibrutinib and Venetoclax Against Human Mantle Cell Lymphoma Cells
Authors: Baohua Sun, Warren Fiskus, Liang Zhang, Kanak Raina, Kevin Coleman, Jim Winkler, Yimin Qian, Andrew Crew, Angela Shen, Dyana T Saenz, Christopher P Mill, Michael Wang, Craig Crews, Kapil N. Bhalla
Journal: Blood (2016)
<i>Methylated glutathione s-transferase 1 (mGSTP1)</i> as a potential plasma epigenetic marker of prognosis and response to chemotherapy in castrate-resistant prostate cancer (CRPC).
Authors: Kate Lynette Mahon, Wenjia Qu, James Devaney, Cheryl Paul, Lesley Castillo, Richard Wykes, Mark D Chatfield, Michael J. Boyer, Martin R. Stockler, Gavin M. Marx, Howard Gurney, Girish Mallesara Hiriyanna Gowda, Peter Molloy, Lisa Horvath, Susan J. Clark
Journal: Journal of Clinical Oncology (2014)

11 Background: GSTP1 is inactivated and displays aberrant CpG island promoter methylation in the majority of prostate cancers (PCs). The aim of this study was to assess whether changes in methylated glutathione s-transferase 1 (mGSTP1) levels are predictive of response to chemotherapy and overall survival (OS). Methods: Plasma samples were collected prospectively from a phase I exploratory cohort of 75 men with castration-resistant prostate cancer (CRPC) (40 treated with chemotherapy) and a phase II independent validation cohort (n=51). Plasma samples were collected at presentation with CRPC and pre- and post-cycle one of chemotherapy (90% Docetaxel). mGSTP1 levels were measured using a methylation-specific head-loop PCR assay from DNA isolated from either (1) immunomagnetic separation of circulating tumor cells (CTCs) or (2) free plasma DNA. The associations between plasma mGSTP1 levels, PSA response (defined by PCWG1 criteria), and OS were tested using non-parametric tests and survival analyses. Results: The ability to detect mGSTP1 was significantly higher for the plasma free DNA assay compared to DNA from CTCs (p&lt;0.0001), so for the remainder of the study the plasma free DNA assay was used. The phase I exploratory cohort identified that detectable mGSTP1 at CRPC presentation predicted for poorer OS (HR 4.2, 95% CI 2.1-8.2; p&lt;0.0001). In the 40 men treated with chemotherapy, a decrease in mGSTP1 levels after cycle one predicted a subsequent more than 50% decrease in PSA prior to cycle 4 (p=0.008). The phase II validation cohort demonstrated that undetectable plasma mGSTP1 after one cycle of chemotherapy predicted for a clinical benefit from treatment (PR+SD vs. PD) (p=0.007). Furthermore, an undetectable plasma mGSTP1after one cycle of chemotherapy was a better predictor of death within 12 months than change in PSA after three months (AUC 0.87, 95% CI 0.77-0.98; p=0.006). Conclusions: We have identified plasma mGSTP1 levels as a potential prognostic marker in men with CRPC as well as a potential surrogate therapeutic efficacy marker for cytotoxic chemotherapy and validated these findings in an independent phase II cohort. Prospective phase III assessment of mGSTP1 as a biomarker of therapeutic response is now warranted.
Primary Mediastinal B Cell Lymphoma Treated with CHOP-Like Chemotherapy with or without Rituximab: 5-Year Results of the Mabthera International Trial Group (MInT) Study
Authors: Mathias Witzens-Harig, Anthony D Ho, Evelyn Kuhnt, Marek Trneny, Michael Rieger, Anders Österborg, Ruth Pettengell, Robert Stevens, Devinder S Gill, Jan Walewski, Markus Loeffler, Michael Pfreundschuh
Journal: Blood (2012)
Neoadjuvant chemotherapy with concomitant hypofractionated accelerated radiotherapy in the treatment of advanced head and neck cancer
Authors: S. Hameed, A. Jamshed, R. Hussain, M. A. Shah, U. Majeed, K. Rehman, M. Adeel, Z. S. Faruqui, A. A. Syed, Q. Ahmed
Journal: Journal of Clinical Oncology (2008)

17021 Background: Recent evidence suggests that addition of induction chemotherapy may improve outcome by enhancing both locoregional and distant control. Data on the use of concomitant hypofractionated radiotherapy (CHOART) is sparse. The purpose of this retrospective study was to analyse toxicity and response to neoadjuvant gemcitabine and cisplatin (GC) followed by CHOART in advanced HAN cancer. Methods: Between 1/9/2005 - 1/10/2006, 20 patients with untreated AJCC stage 4 (T4N0 40%, T4N1 25%, T4N2 30% and T4N3 5%) HAN squamous cell carcinoma underwent treatment in our institution. M:F ratio was 55%:45% with a median age was 50 years. Site of disease was oral cavity 16 (80%), oropharynx 1 (5%), paranasal sinuses 3 (15%). All patients received 2 cycles of neoadjuvant chemotherapy cisplatin 75 mg/m2 day 1 and gemcitabine 1000 mg/m2 day 1, 8 followed 4 weeks later by CHOART. Primary tumour and nodal metastases were irradiated with 2.75 Gy once a day, 5 days a week to a median tumour dose of 55 Gy with concurrent cisplatin 75 mg/m2 on day 1 and 22. Spinal cord dose was limited to 30.2 Gy. Percutaneous endoscopic gastrostomy was placed in 16 patients (80%). Results: Neoadjuvant GC induced grade 3–4 neutropenia in 1/20 patients (5%) and no grade 3–4 gastrointestinal, renal or hepatic toxicity was observed. CHOART induced grade 2–3 oral mucositis in 19/20 patients (95%) and grade 4 in 1/20 patient (5%). Neoadjuvant GC complete responses were 3/20 patients (15%), partial responses in 15/20 patients (75%), no response/progression 2/20 patients (10%) and an overall response rate of 90%. With CHOART complete response was seen in 12/20 (60%), partial response in 6/20 (30%), no response/progression in 2/20 (10%) and overall response in 90%. In patients with PR following induction GC, CHOART achieved CR in 9 out of 15 patients (60%). Two patients with no response/progression on induction GC also did not respond to CHORT. The median disease free survival was 12 months (95% CI: 5.21-20.12) Conclusions: CHOART is feasible and has a high CR rate with acceptable acute toxicity. Induction GC with CHOART should be evaluated in controlled clinical trials to define its role in the management of advanced HAN cancer. No significant financial relationships to disclose.