bluuebunny/crossref_metadata_2025_split huggingface dataset:
FOLFIRI in advanced biliary tract cancers.
Authors: Mizrahi Jonathan , Gunchick Valerie , Mody Kabir , Xiao Lianchun , Surapaneni Phani Keerthi , Shroff Rachna T. , Sahai Vaibhav 
Published: January 2019

451 Background: Gemcitabine plus platinum (GP) is the standard of care first-line treatment for advanced biliary tract cancers (BTC). There is no established second-line therapy, and retrospective reviews report progression-free survival (PFS) for second-line treatment to be < 3 months. 5-Fluorouracil plus irinotecan (FOLFIRI) is a commonly used regimen in patients (pts) with BTC who have progressed on GP, though there is a paucity of data regarding its efficacy in this population. Methods: We retrospectively evaluated pts with advanced BTC who were treated with FOLFIRI at MD Anderson, University of Michigan and Mayo Clinic in Jacksonville. Data were obtained on pt demographics, type of BTC, PFS, and overall survival (OS). Results: Ninety-eight pts were included of which 74 (76%) had metastatic disease at the time of treatment with FOLFIRI. The median age was 59 (range, 22 to 86) years. The number of pts with extrahepatic cholangiocarcinoma (CCA)/gall bladder (GB)/intrahepatic CCA were 10, 17, and 71. FOLFIRI was used as 1st, 2nd, 3rd or 4th – Nth lines in 8, 50, 36, and 4 pts, respectively. Of the 65 pts whose best responses were documented, 23 (35%) had stable disease and 7 (11%) had a partial response per RECIST v1.1. Median duration on FOLFIRI was 2.2 months. The median PFS and OS were 2.4 (95% CI 1.7 to 3.1) and 6.6 (95% CI 4.7 to 8.4) months, respectively. Median PFS for pts treated with FOLFIRI in 1st, 2nd, 3rd or 4th – Nth lines were 3.1, 2.5, 2.3 and 1.5 months, respectively. Eighteen pts received concurrent bevacizumab (13) or EGFR-targeted therapy (5) with FOLFIRI, and both of groups exhibited a median PFS of 2.7 months. Eastern Cooperative Oncology Group performance status (PS) of 0-1 was associated with improved OS (P = 0.006) compared to PS of 2-3. Conclusions: In this multi-institution retrospective review of 98 pts with BTC treated with FOLFIRI, efficacy of this regimen appears to be modest. While PFS and OS outcomes were similar to what has been previously reported, the 46% disease control rate in this group of predominantly pretreated pts is encouraging. Given the lack of other standard therapies, FOLFIRI may still have a role in this pt population, but these results emphasize the need for more effective treatment options for pts with advanced, pretreated BTC.
Neoadjuvant multimodal treatment of borderline resectable (BRPC) and locally advanced unresectable pancreatic cancer (LAPC) in Mexico.
Authors: Camargo Vanessa Rosas , Martos Armedáriz Edgar Omar , Cisneros Cordero Miriam Heidi , NIETO GARCIA ZULEYMA , Flores Balcázar Christian Haydeé , Meneses Medina Mónica Isabel , Chan Nuñez Carlos , Gamboa Dominguez Armando , Huitzil Melendez Fidel David 
Published: January 2019

454 Background: Pancreatic cancer remains a highly lethal disease. There is no consensus on treatment sequences and chemotherapy (CT) regimen in BRPC and LAPC. Our aim was to describe the multimodal treatment and outcomes in our population. Methods: We retrospectively reviewed medical records of patients (pts) with BRPC/LAPC and histological diagnosis of adenocarcinoma evaluated at Instituto Nacional de Ciencias Médicas y Nutrición from January 2011-December 2016. Clinical and pathological variables at diagnosis and treatment were recorded. Overall survival (OS) was estimated using Kaplan-Meier method and compared by Log-rank test. Results: 69 pts were evaluated, 39% (27) did not receive treatment. We analyze 42 treated pts. BRPC 33%/LAPC 67%. Median age was 58.8 y/o, 54.8% were female. Symptoms at diagnosis: 79% abdominal pain, 76% weight loss, 55% jaundice. ECOG performance status (PS): 0 (17%), 1 (69%) and 2 (14%). Main location was pancreatic head (76%). Median laboratory values: total bilirubin 1.04 mg/dL (0.2-25), albumin 4.1 g/dL (2.4-5.1), CA 19.9 182.8 U/mL (0.8-4028). Laparotomy at diagnosis was performed in 21%. All pts received induction CT (iCT). FOLFIRINOX was the most common regimen (37%), followed by FOLFOX4 (34%). The best overall response with iCT was stable disease (62%), progressive disease was observed in 24%. iCT followed by chemoradiation (CRT) could be delivered to 48% (20/42). Capecitabine-based CRT was preferred (94%). Six pts (14%) underwent surgical resection after multimodal treatment (36% BRPC, 3.5% LAPC), 5 pts achieved R0 resection. The resection rate with single-agent iCT was 0% vs 20% with combination iCT. Median OS was 15.6 months (m): 14.4 m for BRPC and 15.5 m for LAPC. Median OS according iCT: gemcitabine 7.8 m, fluorouracil 13.7 m, FOLFOX4 15.5 m and FOLFIRINOX 24.6 m. Univariate analysis identified ECOG PS (0-1 vs 2, P = 0. 014) and age ( < 59 vs ³59, P = 0.002) as significantly associated with survival. Conclusions: Early administration of combination CT followed by CRT and/o surgical resection in selected pts improves oncological outcomes in pts with BRPC/LAPC. In pts with good PS, iCT with FOLFIRINOX is the preferred regimen given best results.
Retrospective, cohort study evaluating empiric dose-reduced nab-paclitaxel with gemcitabine in metastatic pancreatic adenocarcinoma: A single institution experience.
Authors: Olowokure Olugbenga Olanrele , Geraghty LeeAnn , Grate Lisa , Gesenhues Alicia , Lane Adam , Mueller Eric , Niu Alex , Yellu Mahender , Gupta Anumeha , Latif Tahir 
Published: January 2019

456 Background: The phase III MPACT trial was conducted to assess OS in patients with metastatic pancreatic adenocarcinoma (mPAC) receiving nab-paclitaxel (nab-P) 125 mg/m2 + gemcitabine (G) 1000 mg/m2 on days 1, 8, and 15 every 28 days. Due to reported increased incidence of adverse events (AEs) at this dose, practice at UC Health outside the setting of a clinical trial is to empirically dose reduce (EDR) nab-P to 100 mg/m2. This study is a review of the efficacy of EDR nab-P + G in patients with mPAC compared to MPACT data. Methods: This retrospective, single-center, cohort study included patients ≥18 years of age with mPAC (by biopsy) receiving first line therapy with EDR nab-P + G from January 1, 2012 to March 31, 2017. Primary outcome is OS. Secondary outcomes include PFS, CA19-9 percent reduction, incidence of grade ≥ 3 AEs. Results: See table. Conclusions: In patients with mPAC, EDR nab-P plus G demonstrated a median OS of 10 months and PFS of 5 months. 53% of patients had a 20% CA19-9 reduction from baseline with a 1 year OS rate of 45%. The incidence of grade ≥ 3 AEs appeared to be acceptable. [Table: see text]
Effect of surgical approach on node harvest in gastrectomy: Analysis of the National Cancer Database.
Authors: Watson Michael David , Trufan Sally J , Gower Nicole Lee , Hill Joshua S. , Salo Jonathan C. 
Published: January 2019

47 Background: Recent studies demonstrate significant surgical outcome advantages for patients undergoing minimally invasive versus open gastrectomy. Lymph node harvest at the time of gastrectomy is an indicator of adequate surgical resection and greater harvest is associated with improved staging and patient outcomes. Our aim is to evaluate lymph node harvest based on surgical approach. Our hypothesis is that a minimally invasive approach, particularly robot-assisted, will be associated with higher lymph node harvest. Methods: Patients undergoing gastrectomy for gastric adenocarcinoma in the period of 2010-2015 were identified using the National Cancer Database (NCDB). Data collected includes demographic data, institutional volume, approach, type of gastrectomy, tumor size, tumor location, pathologic T classification, year of diagnosis, Charlson-Deyo score and node harvest. Outcomes for patients undergoing open, laparoscopic, and robot-assisted gastrectomy were compared with univariate analysis and with a multivariate generalized linear mixed model (GLMM). Results: 19,555 patients were identified. There were 12,400 men (63.4%) and the mean age was 66.3 ± 12.5 years. 13,486 (69.0%) patients underwent open gastrectomy, 5,023 (25.7%) laparoscopic gastrectomy, and 1,046 (5.3%) robotic-assisted gastrectomy. Mean node harvest for open was 16.1 ± 11.5, laparoscopic was 15.1 ± 12.1, and robotic-assisted was 17.2 ± 13.3. Using a GLMM which controlled for the above listed covariates, robotic-assisted gastrectomy was associated with higher node harvest than both open (p = 0.041) and laparoscopic (p < 0.001) while open was associated with higher node harvest than laparoscopic (p < 0.001). There were 1582 operations with zero nodes harvested. In a sub-analysis of resections where at least one node was harvested (n = 17,973), the mean node harvest for open was 16.9 ± 11.1, laparoscopic was 17.5 ± 11.2, and robotic was 19.7 ± 12.3. Conclusions: This data suggests that a robot-assisted approach is associated with increased node harvest compared to laparoscopic and open approach in gastrectomy.
Lymphocyte-to-C-reactive protein ratio and score are clinically feasible biomarkers in gastric cancer patients.
Authors: Okugawa Yoshinaga , Toiyama Yuji , Yamamoto Akira , Shigemori Tsunehiko , Kusunoki Kurando , Kusunoki Yukina , Yin Chengzeng , Suzuki Akihiro , Fujikawa Hiroyuki , Yasuda Hiromi , Hiro Junichiro , Yoshiyama Shigeyuki , Ohi Masaki , Araki Toshimitsu , McMillan Donald C , Kusunoki Masato 
Published: January 2019

48 Background: Systemic inflammation arising from complex host-tumor interactions is considered the seventh hallmark of cancer. The aim of this retrospective study was to assess the clinical feasibility of our newly developed ‘lymphocyte-to-C-reactive protein (CRP) ratio’ (LCR) and ‘lymphocyte CRP score’ (LCS) for predicting short- and long-term outcomes in patients with gastric cancer. Methods: In total, 551 patients who underwent gastrectomy for primary gastric cancer at our institution were enrolled in this study. Preoperative LCR was calculated as follows: lymphocyte count (number/µL)/CRP level (mg/dL), and scoring system (LCS) was devised based on the cut-off value of both lymphocytes (1 × 109/L) and CRP (0.3 mg/dL) from previous evidences. Results: Reduced pre-operative LCRs significantly correlated with all of the well-established clinicopathological factors for disease development, including advanced T stage, venous invasion, lymphatic vessel invasion, lymph node metastasis hepatic metastasis, peritoneal metastasis, distant metastasis, and advanced tumor-node-metastasis stage. In the short-term outcome, low pre-operative LCR was an independent predictive factor for post-operative surgical site infection (SSI: OR:1.82, 95.0% CI:1.06–3.12, P = 0.03). In the long-term outcome, low pre-operative LCR was an independent prognostic factor for disease-free survival (DFS: HR:1.53, 95.0% CI:1.01–2.32, P = 0.04) and overall survival (OS: HR:2.03, 95.0% CI:1.42–2.90, P < 0.001), and prognostic impact of pre-operative LCR were verified in patients with metastatic and non-metastatic gastric cancer using the same cut-off value. Furthermore, our developed scoring system using lymphocyte and CRP could also demonstrated all of clinical significance using same difinite cut-off value in GC patients (SSI: OR: 4.43, 95.0% CI:1.75–11.2, P = 0.002; DFS: HR: 3.82, 95.0% CI:1.81–8.06, P < 0.001; OS: HR:2.88, 95.0% CI:1.48–5.61, P = 0.002). Conclusions: Assessment of lymphocytes and CRP could aid physicians in determining surgical risk, and oncological risk, thus faciliating appropriate peri-operative and post-operative management of patients with gastric cancer.
A randomized, double-blinded, placebo-controlled multicenter phase II trial of adjuvant immunotherapy with tecemotide (L-BLP25) after R0/R1 hepatic colorectal cancer metastasectomy (LICC): Final results.
Authors: Schimanski Carl Christoph , Kasper Stefan , Hegewisch-Becker Susanna , Schroeder Jan , Overkamp Friedrich , Kullmann Frank , Bechstein Wolf Otto , Vöhringer Matthias , Oellinger Robert , Lordick Florian , Heinemann Volker , Geissler Michael , Schulz-Abelius Armin , Linz Bernhard , Bernhard Helga , Schoen Michael R. , Greil Richard , Smith-Machnow Victoria , Schmidtmann Irene , Moehler Markus Hermann 
Published: January 2019

480 Background: Hepatic metastasectomy is the only potential curative treatment option for stage IV colorectal cancer (CRC) limited to liver metastases (LM). After R0 resection of LM the high recurrence rate remains a major challenge. L-BLP25 is an antigen-specific cancer vaccine targeting mucin 1 (MUC1). The LICC trial aimed to improve survival outcome in mCRC patients (pts) after R0/R1 LM resection. Methods: This LICC trial, a binational, multicenter, double-blinded, placebo controlled phase II trial, included pts with stage IV LM limited CRC after resection of primary tumor and LM (R0/R1) within the last 8 weeks, ECOG 0/1 and adequate organ function. Pts were 2:1 randomized to receive L-BLP25 or placebo. L-BLP25 930 µg was administered as 8 weekly subcutaneous doses followed by 6 week maintenance intervals until recurrence or a maximum of 2 years. Cyclophosphamide 300 mg/m2 (CP) or matching saline (NS) was given intravenously 3 days prior to first L-BLP25/placebo. Co-primary endpoints were recurrence-free survival (RFS) and 3-year overall survival (OS), secondary endpoints were RFS and OS in subgroups with different MUC1 expression and safety. Differences in RFS and OS were analyzed with exploratory log-rank tests on the intention-to-treat population. Results: Of 121 pts enrolled between Oct 2011 and Dec 2014, 79 pts received L-BLP25+CP, 42 placebo+NS. Baseline characteristics were well balanced. Median age was 60 years. Median RFS was 6.1 (90% CI: 5.8-8.8) vs. 11.4 months (90% CI: 5.0-20.3) and estimated 3-year OS rate 69.1% vs. 79.1% for L-BLP25 and placebo, respectively. Two-factorial Cox regression models showed no impact of MUC1 expression or treatment on RFS or OS. The most common L-BLP25-related grade 3/4 adverse events were diarrhea, anemia and back pain. There was one death in the L-BLP25 arm due to Merkel cell carcinoma assessed by the investigator as being potentially related to vaccination. Conclusions: The LICC trial failed to meet its primary endpoint of significantly improving RFS and OS with L-BLP25. MUC1 expression was not associated with outcome. Clinical trial information: NCT01462513 . Clinical trial information: NCT01462513.
CCTG CO.26 trial: A phase II randomized study of durvalumab (D) plus tremelimumab (T) and best supportive care (BSC) versus BSC alone in patients (pts) with advanced refractory colorectal carcinoma (rCRC).
Authors: Chen Eric Xueyu , Jonker Derek J. , Kennecke Hagen F. , Berry Scott R. , Couture Felix , Ahmad Chaudhary E. , Goffin John R. , Kavan Petr , Harb Mohammed , Colwell Bruce , Samimi Setareh , Samson Benoit , Abbas Tahir , Aucoin Nathalie , Aubin Francine , Koski Sheryl L. , Wei Alice Chia-chi , Magoski Nadine M , Tu Dongsheng , O'Callaghan Christopher J. 
Published: January 2019

481 Background: D is a human monoclonal antibody (mAb) that inhibits binding of programmed cell death ligand 1 (PD-L1) to its receptor. T is a mAb against the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Targeting both PD-L1 and CTLA-4 may have additive/synergistic activity as the mechanisms of action of CTLA-4 and PD-L1 inhibition are non-redundant. This study evaluated whether combining PD-L1 and CTLA-4 inhibition would lead to improved pt survival vs BSC alone in rCRC. Methods: Pts with rCRC were randomized 2:1 to D+T vs BSC . Pts were eligible if they failed all standard regimens; containing a fluoropyrimidine, irinotecan and oxaliplatin (and an EGFR inhibitor if Ras wild type). Prior treatment (Tx) with anti-VEGF agents or TAS-102 was permitted but not mandatory. Tx consisted of D (1500 mg) D1 q 28 days and T (75 mg) D1 for first 4 cycles, and all appropriate supportive measures. Primary endpoint was overall survival (OS) and a two-sided p-value < 0.10 was considered statistically significant. Results: Between August 2016 and June 2017, 180 pts were enrolled and 179 treated as randomized. Pt baseline characteristics were balanced. 85% of pts received ≥ 90% of planned doses of D and T. No pts with known defective mismatch repair (dMMR) tumors were enrolled. With a median (med) follow-up of 15.2 months (mo), the med OS was 6.6 mo for D+T and 4.1 mo for BSC (p = 0.07; Hazard ratio (HR): 0.72, 90% confidence interval (CI): 0.54–0.97). Med progression free survival was 1.8 mo and 1.9 mo respectively (HR 1.01, 90% CI 0.76–1.34; p=0.97). Disease control rate was 22.7% for D+T and 6.6% for BSC (p = 0.006). Grade 3/4 abdominal pain, fatigue, lymphocytosis and eosinophilia were significantly higher in D+T. At 16 weeks, there was significantly less deterioration on EORTC QLQ-C30 physical function for D+T. Confirmation of MMR status is ongoing. Conclusions: D+T significantly prolonged OS in pts with rCRC and preserved quality of life. Adverse events were more frequent with D+T. This is the first study showing that combined PD-L1 and CTLA-4 inhibition prolongs survival in pts with advanced refractory CRC not selected for dMMR. Clinical trial information: NCT02870920.
Circulating tumor cell count from a blood sample for colorectal cancer (CRC) prevention: A 627-patient prospective study.
Authors: Tsai Wen-Sy , Watson Drew , Chang Ying , Hsieh Ben , Shao Hung-Jen , Wu Jen-chia , Lai Jr-Ming , Chang Shih-En , Javey Mana , Mei Rui , Nimgaonkar Ashish 
Published: January 2019

485 Background: Up to 25% of patients with adenomas progress to having colorectal cancer. If detected early, adenomas can be removed with a diagnostic colonoscopy procedure, preventing cancer. Invasive colonoscopy is the only screening method with the sensitivity to accurately detect adenomas, but has a low compliance rate of 38% for screening. Available non-invasive tests (including stool-based multi-analyte tests) have very limited sensitivity for adenomas. Hence, there is an unmet need for a non-invasive test for adenoma detection. Methods: IRB-approved prospective study was conducted in 627 subjects 50 years or older- recommended for routine CRC screening- 405 subjects had adenoma or CRC, confirmed by colonoscopy with tumor biopsy. Two mL peripheral blood was processed using the CellMax biomimetic platform (CMx), which uses a microfluidic biochip to enumerate circulating tumor cells (CTCs). Nominal logistic regression was used to assess performance while proportional odds logistic regression and Cuzick’s trend test were used to determine association of CTC counts with cancer stage. Results: An increase in CTC count was significantly correlated with an increase in disease burden (Cuzick’s Test p-value < 0.0001). Furthermore, there was a significant association between CTC counts and stages of adenoma-carcinoma progression (Likelihood ratio p-value < 0.0001). The CTC enumeration was able to differentiate between healthy and diseased patients (adenoma + cancer). Conclusions: To the best of our knowledge, these are the first reported results for a blood test that has high accuracy for adenoma detection, and truly enables colorectal cancer prevention. This test can be administered in the primary care setting and drive high compliance.[Table: see text]
Immunoscore clinical utility to identify good prognostic colon cancer stage II patients with high-risk clinico-pathological features for whom adjuvant treatment may be avoided.
Authors: Galon Jerome , Hermitte Fabienne , Mlecnik Bernhard , Marliot Florence , Bifulco Carlo Bruno , Lugli Alessandro , Nagtegaal Iris D. , Hartmann Arndt , Van Den Eynde Marc , Roehrl Michael H. A. , Ohashi Pamela S , Zavadova Eva , Torigoe Toshihiko , Patel Prabhudas S. , Wang Yili , Kawakami Yutaka , Marincola Francesco , Ascierto Paolo Antonio , Fox Bernard A. , Pages Franck 
Published: January 2019

487 Background: Immunoscore Colon is an IVD test predicting the risk of relapse in early-stage colon cancer (CC) patients, by measuring the host immune response at the tumor site. It is a risk-assessment tool providing independent and superior prognostic value than the usual tumor risk parameters and is intended to be used as an adjunct to the TNM classification. Risk assessment is particularly important to decide when to propose an adjuvant (adj.) treatment for stage (St) II CC patients. High-risk stage II patients defined as those with poor prognostic features including T4, lymph nodes < 12, poor differentiation, VELIPI, bowel obstruction/perforation can be considered for adj. chemotherapy (CT). However, additional risk factors are needed to guide treatment decisions. Methods: A subgroup analysis was performed on the St II untreated patients (n = 1130) from the Immunoscore international validation study (Pagès The Lancet 2018). The high-risk patients (with at least 1 clinico-pathological high-risk feature) were classified in 2 categories using pre-defined cutoffs: Low Immunoscore versus High Immunoscore and their five-year time to recurrence (5Y TTR) was compared to the TTR of the low-risk patients (without any clinico-pathological high-risk feature). Results: Among the patients with high-risk features (n = 630), 438 (69.5%) had a High Immunoscore with a corresponding 5Y TTR of 87.4 (95% CI 83.9-91.0), statistically similar (logrank pv not stratified p > 0.42, wald pv stratified by center p > 0.20) to the TTR 89.1 (95% CI 86.1-92.1) observed for the 500 low-risk patients (with no clinico-pathological feature). Furthermore, 5Y TTR for these patients were statistically similar to those of St II patients with high-risk features and a High Immunoscore (n = 438), who received adj. CT (n = 162) (5Y TTR of 83.4 (95% CI 77.6-89.9). Conclusions: These data show that despite the presence of high-risk features that usually trigger adj. treatment, when not treated with CT, a significant part of these patients (69.5%) have a recurrence risk similar to the low risk patients. Therefore, the Immunoscore test could be a good tool for adj. treatment decision in St II patients.