tbuckley/cabot-search huggingface dataset:
A randomized phase II trial of temozolomide (TMZ) and bevacizumab (BEV) or nab-paclitaxel (nab-P)/carboplatin (CBDCA) and bevacizumab (BEV) in patients with unresectable stage IV metastatic melanoma: A North Central Cancer Treatment Group Study (N0775).
Authors: L. A. Kottschade, V. Suman, D. G. Perez, R. R. McWilliams, J. S. Kaur, T. Amatruda, F. J. Geoffroy, H. M. Gross, P. A. Cohen, A. J. Jaslowski, M. L. Kosel, S. Markovic
Journal: Journal of Clinical Oncology (2011)

8532 Background: There is increasing evidence that chemotherapy in combination with VEGF inhibition is a clinically active treatment in metastatic melanoma (MM). Methods: A randomized phase II trial was conducted in chemotherapy naïve patients (pts) with unresectable stage IV MM treated with either TMZ (200 mg/m2 on days 1-5) and BEV (10mg/kg IV days 1 and 15 ) every 28 days (arm A); or CBDCA (AUC 6; day 1), nab-P (100mg/m2 days 1, 8 and 15), and BEV (10mg/kg on days 1 and 15) every 28 days (arm B). CBDCA and nab-P starting dose was reduced to AUC 5 and 80mg/m2 respectively, due to unexpected AE’s. The primary objective of this study was to independently assess progression-free survival at 6 months (PFS6) in each arm. With a sample size of 41 per arm, α=0.10 test of proportion will have a likelihood of 90% to detect the PFS6 rate is ≥ 60% when the PFS6 is ≥ 40%. A regimen is considered promising if >21 pts meet PFS6. Eligibility criteria included: ≥18 years of age, ECOG PS <2; adequate organ function; no prior exposure to VEGF inhibitors; no evidence of brain metastases; no contraindications for BEV use and no pregnant and/or nursing women. Results: Ninety-four pts (Arm A-43; Arm B-51) were enrolled between 8/15/2008-1/12/10. The majority of patients had M1c disease (46.5%-Arm A & 51%-Arm B) The PFS6 rate in Arm A was 31.2% (95% CI: 19.9-49.0%), with median PFS of 3.8 months and OS of 12.2 months. The PFS6 rate in Arm B was 54.9% (95% CI: 42.8-70.4%), with median PFS of 6.6 months and 0S of 15.4 months. The most common severe (≥ grade 3) toxicities in both groups (Arm A and B) were: neutropenia (9% & 49%); leukopenia (9% & 27%); fatigue (9% & 16%); vomiting (12% & 2%) and thrombosis (5% & 12%). Secondary endpoints and correlative studies will be presented. Conclusions: Both treatment arms exhibited tolerable toxicities with a suggestion of clinical benefit. over expected outcomes for chemotherapy alone. The regimen in Arm B is being considered for phase III clinical testing.
Are cancer families taking better care of themselves? A comparison of use of preventive care services between non-cancer individuals in cancer and non-cancer families
Authors: Y. T. Shih, I. Pan
Journal: Journal of Clinical Oncology (2008)

6516 Background: The estimated number of cancer survivors in the US was 10.8 million in 2004 (≈4% of the population). As the number of survivors increases, so will the number in cancer families, defined as survivors and their family members. We examined whether non-cancer individuals in cancer families were more likely to use preventive care than those in non-cancer families (i.e., positive spillover effect) because the former group may become more health conscious following the family experience with cancer. Methods: We used the 2005 Medical Expenditure Panel Survey and classified non-cancer adults (age ≥18) as those in cancer families (G1) and non-cancer families (G2). Preventive care included services related and unrelated to cancer (Table). For each service, we selected a study sample at appropriate age range and of relevant gender based on guidelines from professional societies to compare service use between G1 and G2. We conducted logistic regressions to control for confounding factors (e.g., demographics, socioeconomic status, and insurance), and applied appropriate weighting algorithms to account for the complex survey design. Results: 22,374 non-cancer adults were identified (949 in G1). Univariate analyses showed G1 had significantly higher utilization rate than G2 in dental care (73% vs 64%), routine check-up (66% vs 59%), blood cholesterol test (86% vs 76%), mammogram (64% vs 54%), and colorectal cancer (CRC) screening (55% vs 45%). However, after controlling for confounding factors, only dental care, mammogram, and CRC screening remained statistically significant (Table). Conclusions: Our study found positive spillover effect in the use of mammogram, CRC screening, and dental care. The low rate of flu shot (50.3%) observed in G1 raised a concern about the health of possibly immunocompromised cancer patients in these families and called for interventions to promote flu shots among non-cancer individuals in cancer families. Logistic Regression for Use of Preventive Care in Cancer and Non-Cancer Families OR (95% CI) Study Sample OR (95% CI) Study Sample Cancer-Related Non-Cancer Related Pap smear last year 1.21 (0.95-1.52) age ≥ 18, female One or more dental visit last year 1.37 (1.16-1.62) age ≥ 18 MMG last year 1.35 (1.06-1.73) age ≥ 40, female Routine check-up last year 1.03 (0.86-1.25) age ≥ 18 Even had CRC screening 1.26 (1.01-1.56) age ≥50 Blood cholesterol test last year 1.18 (0.88-1.57) age ≥ 20 PSA last year 1.20 (0.85-1.69) age ≥50, male Flu shot last year 1.004 (0.81-1.24) age ≥ 50 OR=odds ratio; CI=confidence interval; MMG=mammogram; CRC screening refers to sigmoidoscopy or colonoscopy. No significant financial relationships to disclose.
Induction treatment with FOLFOXIRI + bevacizumab (BV) followed by chemo-radiotherapy (CRT) + BV and surgery in locally advanced rectal carcinoma (LARC): The phase II TRUST trial.
Authors: Caterina Vivaldi, Aldo Sainato, Sara Lonardi, Piero Buccianti, Lorenzo Marcucci, Francesco Di Clemente, Gianna Musettini, Sabrina Montrone, Francesca Bergamo, Matteo Franceschi, Laura Ginocchi, Angelo Martignetti, Concetta Laliscia, Francesca Battaglin, Lucio Urbani, Bruno Manfredi, Laura Rumano', Francesco Sidoti, Alfredo Falcone, Gianluca Masi
Journal: Journal of Clinical Oncology (2016)

673 Background: Induction chemotherapy (CT) is a promising option in LARC. FOLFOXIRI + BV is an effective treatment in metastatic colorectal cancer. Methods: Patients (pts) with LARC at &lt; 12 cm from the anal verge, N+ or cT4 or high risk cT3 (MRI criteria) underwent 6 cycles of FOLFOXIRI + BV followed by CRT (50.4 Gy + 5FU 225 mg/m 2 /day or capecitabine 800 mg/m 2 /bid 5 days/week + BV 5 mg/kg on days 1, 15, 28). Surgery was planned 8 weeks after CRT. Primary endpoint is 2-year disease-free survival (DFS). Results: From April 2012 to April 2015 48 pts were enrolled. At now, 46 pts completed induction CT, 43 completed CRT and 39 underwent surgery (5 pts ongoing). Pts characteristics were: median age, 53 years (range 30-74); cT2/cT3/cT4, 4%/60%/36%; cN0/N+, 4%/96%. Main grade (G) 3/4 toxicities during induction were neutropenia (42%), febrile neutropenia (4.2%), diarrhea (12.5. Two pts did not complete induction: one died due to bowel perforation and sepsis and one discontinued CT after acute kidney injury. Response rate (RR) after induction was 77%. Forty-five pts started CRT (1 pts underwent surgery after induction because of SAE). After the first 13 patients, protocol was amended and schedule of capecitabine modified due to an excessive rate of G3 toxicities during CRT: hand-foot syndrome (23%), proctalgia (23%), proctitis (23%) and diarrhea (15%). After amendment all pts completed CRT with acceptable toxicity: G3 proctitis 6.7% and proctalgia 3.3%. One pts died due to early progressive disease (PD) after CRT. RR after CRT was 88%. Surgery was low anterior resection 87%, abdomino-perineal resection 8%, other 5%. Radical resection was achieved in 95% of pts. Early post-surgical complication rate was 31%. Pathologic complete response was reached in 33% and pathological downstaging in 44% of pts. At a median follow up of 17 months, 8 pts had PD and estimated 2y-DFS is 72%. Conclusions: Induction CT with FOLFOXIRI + BV is feasible and highly active. A protocol amendment was needed due to toxicities during CRT. The rate of early post-surgical complications is not negligible. A longer follow up is needed for DFS. Clinical trial information: 2011-003340-45.
The prognostic significance of prenephrectomy absolute lymphocyte count in clear cell renal cell carcinoma.
Authors: S. Saroha, R. Uzzo, G. R. Hudes, E. R. Plimack, K. Ruth, T. I. Al-Saleem
Journal: Journal of Clinical Oncology (2011)

4641 Background: We hypothesized that a low peripheral blood absolute lymphocyte count (ALC), a likely index of poor systemic immunity, may be associated with aggressive features and inferior outcome in clear cell renal cell carcinoma (RCC). Methods: We retrospectively analyzed preoperative blood cell counts in patients undergoing primary surgical resection for clear cell RCC at Fox Chase Cancer Center between 1994 and 2009. The patients from year 2009 were excluded from analysis of overall survival (OS) due to a short follow-up. ALC values as a continuous variable and at a level below 1,300/µl (below reference range in our laboratory) were correlated with tumor grade, pathologic tumor stage (pT), presence of distant metastases and a collaborative tumor-node-metastasis (TNM) stage. We used the Kaplan-Meier product-limit method to estimate the OS by low ALC status. Differences in the survival curves were assessed using the log rank test. We also performed Cox proportional hazards regression for inferences about the relationship of survival time with low ALC adjusting for age (<60 yrs versus 60+ yrs at surgery) and TNM stage as covariates. Results: 516 patients were eligible for analysis (32% female; median age= 60 yrs, range 25-89 yrs). 138 (27%) patients had ALC <1,300/µl. 430 patients were included for analysis of OS (median follow-up 33.5 months). As a continuous variable, low ALC was associated with higher nuclear grade (p 0.0044), higher pT (p 0.0088), presence of distant metastases (p <0.0001) and higher TNM stage (p <0.0001). Similarly, ALC at a level below 1300/µl was associated with high grade (p 0.0127), high pT (0.027), distant metastases (p <0.0001) and high TNM stage (p <0.0001). Low ALC was also associated with significantly worse OS (p <0.0001). The association with OS was independent of TNM stage and patient's age in multivariable analysis (p 0.018). Conclusions: Here we demonstrate for the first time that a low peripheral blood ALC is associated with higher nuclear grade, pathologic stage, presence of metastases and inferior overall survival in clear cell RCC patients.
Prognostic factors in an open-label, nonrandomized study in chemonaive, malignant pleural mesothelioma (MPM) patients receiving pemetrexed plus cisplatin (P+Cis) or pemetrexed plus carboplatin (P+Cb)
Authors: R. A. Stahel, A. Santoro, M. O’Brien, K. Nackaerts, P. Baas, L. G. Paz-Ares, S. Sundstrom, J. Blatter, C. Visseren-Grul, C. Manegold
Journal: Journal of Clinical Oncology (2008)

8119 Background: This expanded access program provided access to Pemetrexed (P) alone or P plus a platinum (Cis or Cb) for 3311 MPM patients (pts) in 13 countries. In a subset analysis of chemonaive pts, this study confirmed the activity of P+Cis and P+Cb and demonstrated similar effectiveness of the two treatments (Santoro et al, ASCO 2007), while therapy assignment was based on the investigator’s clinical evaluation. Methods: In this post-hoc regression analysis, prognostic factors were built into a Cox regression model. Prognostic factors were then used to categorize pts into more homogenous subgroups and to compare clinical outcome - overall survival (OS) and time to progressive disease (TTPD) - between the two treatments. Results: A total of 1404 and 1405 pts were available for the OS and TTPD analyses, respectively, with about 700 pts in each treatment group. In the regression analysis, performance status (ECOG PS at baseline 0–1 vs. >1 or KPS 80–100 vs. 50–70) was identified as the only statistically significant factor for OS and TTPD in this study population. In the OS analysis, the HR for PS was 0.43 [95% CI 0.30, 0.63] and in the TTPD analysis, the HR was 0.57 [CI 0.43, 0.76]; (p <0.0001). Interestingly, neither gender nor age was identified as statistically significant factors (p>0.1). Patient subgroups based on PS were: Group 1 with ECOG PS 0–1 or KPS ≥80 (88% of pts), and group 2 with ECOG PS >1 or KPS 50–70 (12% of pts). Notably, approximately half of pts were treated with P+Cis and the other half with P+Cb; this ratio remained the same within each PS subgroup. Within the PS subgroups, a comparison between treatments did not reveal a statistically significant difference in OS and TTPD: In group 1, the logrank test p-value was 0.92 for OS and 0.46 for TTPD; in group 2, the logrank test p-value was 0.07 for OS and 0.67 for TTPD. Conclusions: PS was identified as the strongest prognostic factor in this patient population. Comparing P+Cis- and P+Cb-treated pts within the PS subgroups did not reveal a clinically relevant difference in either OS or TTPD. The investigator’s choice for P+Cis or P+Cb did not appear to be influenced by the baseline PS. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly Eli Lilly Eli Lilly Eli Lilly, Seminar presentations Eli Lilly Eli Lilly
Use of FoxP3+ and cytotoxic CD8+ T lymphocytes to identify a patient subgroup with a favorable prognosis similar to colon cancers with deficient DNA mismatch (dMMR) repair.
Authors: Harry H. Yoon, Jared M Orrock, Nathan R. Foster, Daniel J. Sargent, Thomas C. Smyrk, Frank Sinicrope
Journal: Journal of Clinical Oncology (2012)

460 Background: The immune response has emerged as a strong prognostic factor in colon cancer. Whereas CD8+ T cells mediate antitumor response, regulatory T cells expressing FoxP3+ can antagonize this effect, though prognostic data conflict. These markers have yet to be analyzed with MMR status, which is important since dMMR tumors show enhanced immune response. Methods: CD8 + and FoxP3 + density were analyzed by immunohistochemistry (IHC) in resected stage II and III colon carcinomas (N = 216) from participants in phase III adjuvant 5-fluorouracil-based trials. High vs low immune density was dichotomized at the median. MMR status, determined by IHC or analysis of microsatellite instability, was categorized as dMMR (12%) or proficient MMR (pMMR). Cox models, stratified by study, were adjusted for age, stage, grade and, where noted, MMR. Results: The association of FoxP3+ density with overall survival (OS) differed by CD8+ density (P for interaction = .040). By multivariable analysis, FoxP3+ high was significantly associated with improved OS in CD8+ low tumors (hazard ratio 0.43 [95% confidence interval 0.19 – 0.95]; P = .030], but not in CD8+ high tumors (P = .91). Results were consistent after MMR adjustment. We then determined their prognostic impact in the larger pMMR subset (N = 119). Tumors with high FoxP3+ were associated with improved OS in cases with low, but not high, CD8+ density ( Table ). These patients (FoxP3+ high , CD8+ low ) had similar 5-year OS rates as 107 dMMR cases from parent studies (89% vs 80%; P = .74), despite having distinct clinicopathologic features. Conclusions: The prognostic impact of FoxP3+ T cells depends on CD8+, indicating the importance of analyzing both in combination. High FoxP3+ exerts a paradoxically favorable survival impact, but only when CD8+ is low. Survival in pMMR tumors with high FoxP3 + and low CD8+ was similar to that of dMMR tumors, indicating that a favorable pMMR subset can be identified. [Table: see text]
Local effect and gastrointestinal toxicity for carbon-ion radiotherapy in patients with unresectable locally advanced pancreatic cancer.
Authors: Makoto Shinoto, Yoshiyuki Shioyama, Hiroaki Suefuji, Akira Matsunobu, Shingo Toyama, Sho Kudo
Journal: Journal of Clinical Oncology (2016)

410 Background: Carbon-ion radiotherapy (CIRT) is a unique external radiotherapy that has an excellent dose conformity and higher biological effectiveness compared to conventional radiotherapy. The sensitivity of the organs in upper abdomen has limited the radiation dose to levels that are ineffective against pancreatic cancer, which has extreme radioresisnatnce. We investigated effectiveness and gastrointestinal (GI) toxicity of CIRT. Methods: From April 2014 to June 2015, 41 patients with pancreatic cancer were treated with definitive CIRT. 26 patients who were confirmed as unresectable locally advanced pancreatic cancer pathologically and by imaging techniques were included in this retrospective analysis. 15 patients were excluded because of resectable disease (n = 3), borderline disease (n = 4), no cell evidence (n = 11). CIRT was performed with 55.2 Gy (RBE) at 12 fractions. The maximal absolute dose with covered 2cm 3 of the organ (D2) was restricted under 46 Gy (RBE). All patients were followed up using CT, FDG-PET and upper gastrointestinal endoscopy at least every six months. Anti-tumor effect was evaluated using CT and FDG-PET according to RECIST. If FDG accumulation was negative or equal to normal pancreatic tissue after CIRT, it was defined CR even no decreasing in seize on CT. GI toxicity was evaluated using CTCAE. Results: Tumor location were head in 7, head-body in 2, body-tail in 16. Median tumor size was 35mm (range 21-50). In all patients, sequential and/or concurrent chemotherapy was performed. The median follow-up period was 7.7 months. Local effect using CT criteria was CR in 0, PR in 2, SD in 22, and PD in 2. The evaluation adding FDG-PET criteria was CR in 12, PR in 4, SD in 8, and PD in 2. Two patients who were SD by CT and CR by FDG-PET performed tumor resection and were revealed pCR. The actual incidence of gastric ulcer/bleeding was 15% (n = 4). Only one patient (4%) received blood transfusion because of grade 3 gastric ulcer. The other patients experienced grade 1/2 gastric ulcer. There was no duodenal ulcer. Conclusions: CIRT were effective and well tolerated under the restriction of D2 &lt; 46 Gy (RBE). FDG-PET was useful for the evaluation of local effect after CIRT.
Metabolome analyses in human gastric cancer tissue using capillary electrophoresis time-of-flight mass spectrometry.
Authors: Masanori Terashima, Masatoshi Kusuhara, Junya Kondo, Masanori Tokunaga, Yutaka Tanizawa, Etsuro Bando, Taiichi Kawamura, Tamaki Fujimori, Hiroyuki Yamamoto, Yoshiaki Ohashi
Journal: Journal of Clinical Oncology (2012)

61 Background: In order to explore carcinogenic and prognostic biomarkers for gastric cancer, genomic, transcriptomic and proteomic approach had been extensively investigated. However, little information is possible for metabolomics profiles in gastric cancer. As cancer cells demonstrates distinguishable growth pattern from normal cells, presence of specific metabolic pathway in cancer cells is expected. Therefore, we investigated the metabolme profiles of gastric cancer tissue by capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). Methods: Twenty seven patients with gastric cancer underwent gastrectomy were enrolled in this study. Cancer tissue and adjacent non-cancerous tissue were obtained from surgically resected sample and immediately frozen. Frozen tissues were homogenized and then applied to CF-TOFMS.The metabolomics data by CE-TOFMS were analyzed using principal component analysis (PCA) in order to compare the metabolic profiling of the non cancerous and the cancer tissues. Correlation between metabolic profile and clinicopathologic factors were also investigated. Results: A total of 245 metabolites were detected and quantified. In PCA, the first component separated the cancer tissue data from the non-cancerous tissue data. Metabolic data from cancer tissues showed severe heterogeneity. PCA based on the difference between cancer tissue and non-cancerous tissue revealed that metabolic profile of gastric cancer was classified into two groups. One cancer group (group 1) accumulated lactate and most amino acids excessively, and another group (group 2) didn’t. In group 1, the adenylate energy charge of the cancer tissues was maintained compared to that of the non-cancerous tissues.In comparison with clinicopathologic factors, only histological type demonstrated significant correlation with metabolic classification. Undifferentiated type was significantly predominant in group 2. Conclusions: Gastric cancer was classified into two groups by quantitative metabolome profiling. As this classification significantly correlated with histological type, existence of specific metabolic pathway related to histological type is suggested.
Peri-operative modified FOLFIRINOX (mFOLFIRINOX) in resectable pancreatic cancer (PDAC): A pilot study.
Authors: Robert de Wilton Marsh, Marshall Baker, Daniel V.T. Catenacci, Mark Kozloff, Blase N. Polite, Mitchell C. Posner, Kevin K. Roggin, Mark S. Talamonti, Hedy Lee Kindler
Journal: Journal of Clinical Oncology (2016)

312 Background: Surgical resection plus adjuvant gemcitabine or 5-FU is standard therapy for resectable PDAC. Infusional 5-FU, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) has substantial activity in metastatic PDAC. Efficacy and tolerability of peri-operative FOLFIRINOX in resectable PDAC is unknown. Methods: Patients (pts) with ECOG PS 0/1 and resectable PDAC confirmed by multidisciplinary review received 4 cycles of mFOLFIRINOX (mFFX)(oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2 day 1, 5-FU 2400 mg/m2 x 48 hours, peg-filgrastim 6 mg SQ day 3) pre- and 4 cycles post- surgery. Results: 21/21 enrolled pts started therapy (median age: 63 (47-78), 81% ECOG 0). 20/21 pts completed 4 cycles of preoperative mFFX (1 withdrew for toxicity), 17/21 pts had successful surgical resection (3 had disease noted in the liver at surgery) and 14/21 completed 4 cycles of postoperative mFFX (2 pts expired prior to postoperative mFFX within 90 days of surgery -1 from an M.I. and 1 from a GI bleed; 1 pt had excessive toxicity after cycle 5). Radiographic response by RECIST following preoperative therapy was 1 CR, 3 PR, 16 SD, 0 PD. Of the 17 (81%) patients undergoing curative-intent surgery, 16/17 (94%) had R0 resections. Treatment effect was seen in 10/17 specimens with 1 pathologic CR. Doses were modified per protocol in 30% pts preoperatively (neuropathy 1; thrombocytopenia 2; neutropenia 3; diarrhea 2) and 26% postoperatively (neuropathy 3; diarrhea 3; allergic reaction 1). Grade III and IV adverse events were observed in 23% and 14% pts (overlapping) in the preoperative, and 26% and 0.06% pts in the postoperative phases. 18 pts are alive with a median follow up of 17.3 months. Conclusions: 17/21 (81%) pts completed neoadjuvant mFFX and surgical resection. 14/21 (66%) pts completed all planned therapy. Radiographic responses were rare but efficacy is suggested by the high R0 resection rate: 16/17 (94%) in pts undergoing resection, and 16/21 (76%) pts overall. Toxicity was manageable and within the expected range. 8 cycles of mFFX is a feasible and tolerable peri-operative regimen in pts with resectable PDAC and ECOG PS 0/1. Definitive assessment of efficacy will require longer follow up and larger studies. Clinical trial information: NCT01660711.