bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of pathological response and tumor regression following neoadjuvant therapy in advanced gastric cancer patients.
Authors: Ribeiro Ulysses , Ramos Marcus Fernando Kodama Pertille , Pereira Marina Alessandra , Dias André Roncon , Yagi Osmar Kenji , Faraj Sheila , de Mello Evandro Sobroza , Charruf Amir Zeide , Pereira Guilherme Luiz Stelko , Zilberstein Bruno , Hoff Paulo Marcelo , Cecconello Ivan 
Published: March 2017

206 Background: Neoadjuvant chemotherapy (NACT) has became the standard approach for patients with advanced gastric cancer. Clinicopathological characteristics can be utilized to evaluate the effect of NACT, and may be a useful tool to identify responsive patients. Methods: We retrospectively reviewed all patients with GC treated with NACT and R0 resection between 2009 and 2015 from a prospective collected database. Histopathological response to the treatment was graded from 0% to 100% and the clinicopathological characteristics assessed to identify predictors of tumor response. A threshold of 50% histopathological response was used for the analysis. Results: NACT was performed in 45 patients. Cisplatin-irinotecan therapy was used in 64.4% of patients and 11 (24.4%) tumors were located in the proximal stomach. Ten (22.2%) patients demonstrated a tumor regression of at least 50% and one patient had complete response. The mean number of lymph node retrieved was 38.1 and 66.7% patients had lymph node metastasis (LNM). Factors associated with > 50% of response by univariate analyses included lower neutrophil-lymphocyte ratio (NLR) ( p = 0.035), diffuse/mixed Lauren type ( p = 0.007), lower depth of tumor invasion ( p = 0.043) and non cisplatin-irinotecan therapy (p = 0.01). A slight tendency of poorly differentiated tumors respond better to NACT than differentiated type was observed ( p = 0.05). There was no significant difference regarding the presence of mucin, calcification and/or necrosis and the tumor response. Multivariate analysis identified NLR and diffuse/mixed tumors as independent predictors of pathologic response. Median follow-up for all patients was 26.5 months and recurrence-free survival (RFS) rate was 74.3% and 60% for patients with > 50% and < 50% of response, respectively ( p= 0.08). RFS was significantly different in patients without LNM compared to patients who have LNM (100% vs. 55.2%, p = 0.01), and in patients with fibroinflammatory/inflammatory stroma infiltration compared to patients with only fibrotic stroma (80% vs. 53.3%, p = 0.015). Conclusions: Diffuse/mixed histopathological type and lower NLR are independently predictors of tumor response after NACT.
Clinical significance of p53 protein, beta-catenin, and HER2 in patients with Epstein-Barr virus-associated gastric cancer.
Authors: Baek Dong Won , Lee In Hee , Lee Soo Jung , Kang Byung Woog , Chae Yee Soo , Kim Jong Gwang 
Published: March 2017

22 Background: Epstein-Barr virus (EBV) infection can cause cancer tumorigenesis and malignant transformation of host cells through the activation of oncogenic pathways. Therefore, we assessed the expression of p53 protein, beta-catenin, and HER2 and their prognostic implication in patients with EBV-associated gastric cancer (EBVaGC). Methods: After reviewing 1318 consecutive cases of surgically resected or endoscopic submucosal dissected gastric cancers, 117 patients were identified as EBV-positive using EBV-encoded RNA in-situ hybridization. The results of immunohistochemistry were interpreted as follows: strong p53 nuclear expression in at least 50% of tumor nuclei was interpreted as a positive result; strong positive cytoplasmic-nuclear expression patterns for β-catenin ( ≥ 10%) were considered altered expression; moderate or strong complete or basolateral membrane staining in 10% of tumor cells for HER2 was reported as a positive results. Results: The median age of the patients was 62 years (32-80) and 93 (79.5%) were male. The pathologic stages were as follows : stage I (n = 74), stage II (n = 25), and stage III (n = 18). Among the 117 patients, immunohistochemical staining for p53 was performed in 105 patients and 25 patients (23.8%) were positive. Beta-catenin was positive in 10 patients (17.5%) and HER2 was positive in 8 patients (6.8%), respectively. The positive expression of p53 was significantly associated with a high T stage (p = 0.006). Conversely, more patients without lymph node metastasis were p53 positive (p = 0.013). In the univariate analysis, the patients with p53 positive tumors showed a significantly improved disease-free survival (DFS) compared to the patient with negative tumors (p = 0.022), although the p53 status was marginally associated with overall survival (OS)(p = 0.080). However, p53 expression showed no prognostic significance on DFS in the multivariate analysis. Meanwhile, beta-catenin and HER2 was not found to be associated with DFS and OS in the survival analysis. Conclusions: The current study found a significant correlation between p53 expression and tumor progression in patients with EBVaGC.
A randomized phase II study of individualized stereotactic body radiation therapy (SBRT) versus transarterial chemoembolization (TACE) with DEBDOX beads as a bridge to transplant in hepatocellular carcinoma (HCC).
Authors: Nugent Francis W. , Qamar Amir , Stuart Keith E. , Galuski Kari , Flacke Sebastian , Molgaard Chris , Gordon Frederick , Iqbal Shams , Hunter Klaudia Urbaniak , Hartnett Erin , Gunturu Krishna 
Published: March 2017

223 Background: For HCC pts undergoing LT, local regional treatment as a "bridge" is standard to decrease tumor progression. The most common treatment is TACE, but the best bridging modality is unclear. Recently, SBRT has been shown to be both safe and effective when used in pts with locally advanced HCC. We prospectively compare SBRT to TACE as a bridge for HCC pts undergoing LT. Methods: 60 pts planned for accrual. From 9/2014-9/2016, 29 pts within Milan Criteria with C-P Class A/B cirrhosis were randomized to TACE vs. SBRT. TACE pts received 2 treatments one month apart utilizing DEBDOX beads (n = 15). TACE pts were hospitalized after each TACE. Pts receiving SBRT (n = 12) received a median total dose of 45Gy delivered over 5 fractions using fiducials. Mean liver dose, Veff, and NTCP were utilized to determine the prescription dose. Pts were assessed by imaging using mRECIST criteria at 2 months and every 3 months thereafter until LT or death. Toxicity and quality of life were assessed before treatment, during treatment, two weeks post-treatment, and then every three months using the PIQ-6 Pain Impact Questionnaire and the SF-36v2 Health Survey. Primary endpoint was time to retreatment of treated lesion(s). Secondary endpoints include toxicity, pathologic response, radiologic response, number of subsequent treatments, cost, and QOL. Results: A. Demographics/Toxicity. Conclusions: For HCC patients with C-P Class A/B liver cirrhosis, SBRT appears equally effective to TACE as a bridge to liver transplantation, may engender less toxicity, and eliminates hospitalizations. Clinical trial information: NCT02182687. [Table: see text][Table: see text]
Gemox versus surveillance following surgery of localized biliary tract cancer: Results of the PRODIGE 12-ACCORD 18 (UNICANCER GI) phase III trial.
Authors: Edeline Julien , Bonnetain Franck , Phelip Jean Marc , Watelet Jérôme , Hammel Pascal , Joly Jean-Paul , Ben Abdelghani Meher , Rosmorduc Olivier , Bouhier-Leporrier Karine , Jouve Jean-Louis , Faroux Roger , Guerin Meyer Véronique , Assenat Eric , Seitz Jean Francois , Malka David , Louvet Christophe , Bertaut Aurelie , Juzyna Beata , Stanbury Trevor , Boucher Eveline 
Published: March 2017

225 Background: No standard post-surgery adjuvant treatment is currently recommended in localized biliary tract cancer (BTC). Gemcitabine combined with platinum is the standard chemotherapy for advanced BTC. The aim of this phase III randomized trial was to assess whether GEMOX would increase relapse-free survival (RFS) while maintaining health-related quality of life (HrQoL). Methods: We performed a multicenter randomized phase III trial. Patients were randomized, within 3 months of R0 or R1 resection of a localized BTC (intra-hepatic, perihilar, extra-hepatic cholangiocarcinoma or gallbladder cancer), to receive either GEMOX 85 for 12 cycles (Experimental Arm A) or surveillance (Standard Arm B). Co-primary objectives were RFS and HrQoL. 190 patients and 126 RFS events were required to show an increase of median RFS from 18 to 30 months. Results: Between July 2009 and February 2014, 196 patients were included in 33 French centers. Baseline characteristics were balanced, with similar primary sites, R0 resection rates were 86.2% (Arm A) vs 87.9% (Arm B), lymph node invasion present in 37.2% vs 36.4%. In Arm A, a median of 12 cycles was delivered (mean: 9.3, range: 0-12). Maximal grade of adverse events were grade 3 in 57.5% vs 22.2%, and grade 4 in 17.0% vs 9.1%. During treatment one patient died in each arm. The main grade ≥ 3 adverse events in the year following inclusion were peripheral neuropathy (50.0% vs 1.1%), and neutropenia (22.3% vs 0%). Median follow-up was 44.3 months, with 54 and 64 RFS events in arms A vs B. There was no significant difference in RFS between the arms (log-rank p = 0.31), with a hazard ratio of 0.83 [95% CI: 0.58-1.19], p = 0.31 (futility boundaries were crossed). Median RFS was 30.4 [95% CI: 15.4-45.8] vs 22.0 months [95%CI: 13.6-38.3] in arms A & B respectively, and 4-years RFS was 39.3% [95%CI: 28.4%-50.0%] vs 33.2% [95%CI: 23.1-43.7%]. Global Health HrQoL scores were not different at 12 months (70.8 vs 83.3, p = 0.18) and at 24 months (75.0 vs 83.3, p = 0.50). Conclusions: Adjuvant chemotherapy in BTC with GEMOX was feasible and associated with expected toxicities and no deterioration of HrQoL. There was no significant difference in RFS between GEMOX and surveillance. Clinical trial information: NCT01313377.
Nivolumab dose escalation and expansion in patients with advanced hepatocellular carcinoma (HCC): The CheckMate 040 study.
Authors: Melero Ignacio , Sangro Bruno , Yau Thomas Cheung , Hsu Chiun , Kudo Masatoshi , Crocenzi Todd S. , Kim Tae-You , Choo SuPin , Trojan Jorg , Meyer Tim , Welling Theodore Hobart , Yeo Winnie , Chopra Akhil , Anderson Jeffrey , Dela Cruz Christine Marie , Lang Lixin , Neely Jaclyn , Tang Hao , El-Khoueiry Anthony 
Published: March 2017

226 Background: HCC diagnosed at advanced stages has a poor prognosis. Patients who progress on sorafenib have few options. Nivolumab, a fully human IgG4 monoclonal antibody inhibitor of programmed death-1 (PD-1), has demonstrated clinical and survival benefit in a number of tumor types. Here we report updated interim analyses of safety, efficacy, and exploratory biomarkers in patients with advanced HCC treated with nivolumab in the CheckMate 040 study (NCT01658878). Methods: Patients enrolled had advanced HCC with or without hepatitis C or B virus (HCV or HBV) infection. Prior sorafenib was allowed. Phase 1 dose-escalation evaluated nivolumab (0.1–10 mg/kg) Q2W. Phase 2 dose-expansion was initiated in 4 cohorts: sorafenib naïve/intolerant, sorafenib progressors, HCV infected, and HBV infected. All cohorts received nivolumab 3 mg/kg Q2W. The primary endpoint in the dose-escalation phase was safety/tolerability, and the primary endpoint in the dose-expansion phase was objective response rate (ORR) by RECIST v1.1 (central review). Secondary endpoints included duration of response (DOR), disease control rate (DCR), and overall survival (OS). Biomarkers within pre-treatment tumors were assessed. Results: Across dose escalation and expansion phases, 262 patients have been treated. Grade 3/4 treatment-related adverse events occurred in 20%. No maximum tolerated dose was reached during dose escalation (n = 48). The ORR (investigator-assessed) was 20% (95% CI 15–26) in 214 patients treated in the dose expansion phase with a median DoR of 9.9 months; DCR was 64% (95% CI 58–71). Responses were observed across etiologies and regardless of tumor PD-L1 expression. ORRs of 23% (95% CI 13–36) and 21% (95% CI 11–34) were observed in the uninfected sorafenib-naive and -treated patients, respectively. The 9-month overall survival rate in the expansion phase was 74% (95% CI 67–79). Association between immune-cell biomarkers and clinical outcomes will be presented. Conclusions: In this heavily pretreated population, responses to nivolumab were durable with encouraging overall survival. Safety was manageable and consistent with that observed in other solid tumors with no new safety signals. Clinical trial information: NCT01658878.
Survival by pattern of tumor progression during prior sorafenib (SOR) treatment in patients with hepatocellular carcinoma (HCC) in the phase III RESORCE trial comparing second-line treatment with regorafenib (REG) or placebo.
Authors: Bruix Jordi , Merle Philippe , Granito Alessandro , Huang Yi-Hsiang , Bodoky Gyorgy , Pracht Marc , Yokosuka Osamu , Gerolami René , Masi Gianluca , Ross Paul J. , Qin Shukui , Song Tianqiang , Bronowicki Jean-Pierre , Ollivier-Hourmand Isabelle , Kudo Masatoshi , Le Berre Marie-Aude , Meinhardt Gerold , Han Guohong ,   On Behalf of RESORCE Investigators
Published: March 2017

229 Background: HCC progression may be due to tumor growth or new intrahepatic or extrahepatic lesions. RECIST does not discriminate between progression patterns even though the prognosis may differ (Reig, Hepatology 2013). REG improves overall survival (OS) in patients with HCC who progress during SOR treatment (HR 0.63; 95% CI 0.50, 0.79; P < 0.001). This exploratory analysis aimed to validate the pattern of progression concept in a global cohort treated with prior SOR and to assess the impact of REG on survival by prior progression. Methods: Adults with HCC who tolerated SOR and had radiologic progression during SOR, Child–Pugh A liver function, and ECOG PS 0–1 were randomized 2:1 to REG 160 mg/day or placebo during weeks 1–3 of each 4-week cycle. Progression during SOR was due to tumor growth or new lesions. Post-progression survival (PPS) was the time from progression on SOR until death. Results: Baseline characteristics of the 573 randomized patients (REG = 379; placebo = 194) were balanced; median age was 63 years, 88% were male, 87% were BCLC stage C, 29% had macrovascular invasion, and 72% had extrahepatic disease. Hazard ratios favored REG irrespective of pattern of progression during prior SOR, but differed according to progression pattern (Table). Conclusions: The development of new extrahepatic lesions is associated with worse survival irrespective of treatment. REG provided an OS benefit, regardless of progression pattern. Progression pattern may be a key prognostic parameter and should be considered in future trial design and analysis. Clinical trial information: NCT01774344. [Table: see text]
Multi-agent and single-agent chemotherapy in stage IV pancreatic cancer: An NCDB analysis.
Authors: Ahmed Aabra , Walters Ryan W , Malouff Timothy Dean , Chintalacheruvu Lakshmi Manogna , Silberstein Peter T. 
Published: March 2017

231 Background: Cartright et al (2014) examined 2,422 patients in the iKnowMed database and found that patients with advanced pancreatic cancer lived longer with multi-agent chemotherapy compared to single-agent chemotherapy (11.2 months vs 7.2 months). Our goal was to compare survival of patients with stage IV pancreatic cancer receiving multi-agent, single-agent, or no chemotherapy using a significantly larger sample of patients identified in the National Cancer Database (NCDB). Methods: We identified 86,048 patients with stage IV pancreatic cancer. Between-chemotherapy survival differences were estimated by the Kaplan-Meier method and associated log-rank tests; Tukey-Kramer adjusted p < .05 indicated statistical significance. Results: Patients receivingmulti-agent chemotherapy were more likely to have private insurance than single-agent and no chemotherapy patients (49.9% vs. 33.0% vs. 22.9%, respectively), live in an area with a median income of $63,000+ (36.9% vs. 30.2% vs. 28.4%, respectively), receive treatment at an academic center (43.3% vs. 34.5% vs. 32.8%, respectively), and have no comorbidities (72.9% vs. 66.9% vs. 61.1%, respectively). Statistically significant survival differences were indicated between all chemotherapy groups (all adjusted p < 0.05), such that patients receiving multi-agent chemotherapy had the longest survival followed by patients receiving single-agent chemotherapy and patients receiving no chemotherapy (median survival = 7.4, 4.9, and 1.4 months, respectively). A larger proportion of patients receiving multi-agent chemotherapy were alive at 6, 12, and 24 months relative to patients receiving single-agent or no chemotherapy. Conclusions: Our study is the largest to show the benefit of multi-agent chemotherapy over single-agent chemotherapy for stage IV pancreatic cancer, as well as analyze the demographics of patients receiving differing chemotherapy treatments. [Table: see text]
Short and long-term survival in metastatic pancreatic adenocarcinoma, 1993-2013.
Authors: Golan Talia , Sela Tal , Margalit Ofer , Amit Uri , Halpern Naama , Aderka Dan , Shmueli Einat Shacham , Urban Damian , Lawrence Yaacov Richard 
Published: March 2017

232 Background: Over the previous two decades several new agents have been approved for the treatment of metastatic pancreatic cancer (mPDAC). Their efficacy was demonstrated amongst highly selected patients that participate in randomized phase III trials, hence it is not clear to what extent these advances are reflected within the broader mPDAC population. We performed a population-based survival analysis of newly diagnosed patients who presented with mPDAC. Methods: Survival statistics were extracted from the Survival, Epidemiology and End Results (SEER) Database for patients diagnosed with mPDAC between 1993-2013. Demographic variables collected included age, gender, race, and marital status. Tumor characteristics collected included location and grade. Survival was analyzed using the Kaplan-Meier method and proportional hazard models as appropriate. Exclusion criteria included diagnosis at autopsy, unknown histology and pancreatic neuroendocrine tumors. Results: The study population consisted of 57,263 patients diagnosed with mPDAC from 1993-2013, 52% male, median age 69 years (range 15-104). Prognosis correlated with age, gender, race, marital status, tumor location, grade and year of diagnosis. Median overall survival (OS) stayed stable at 2 months between 1993 and 2013. Improvements in OS were seen for all patients, but especially for younger patients ( < 50 years of age) and more recent year of diagnosis group (2009-2013). The percentage of patients who died within two months of initial diagnosis decreased between 1993 and 2013 (from 63.5% to 50.6%, p < 0.0001). The subgroup of patients achieving longer-term survival has increased, with 12-month survival improving from 4.9 % to 12.7% (p < 0.0001) between 1993 and 2013. Conclusions: There has been a continuous but modest improvement in OS of patients diagnosed with mPDAC between 1993 and 2013. The percentage of patients living beyond one year has significantly increased over time; however the percentage of patients dying within 2 months has only slightly decreased.
Larger size extracellular vesicle as early biomarker in patients with metastatic pancreatic cancer.
Authors: Kim Dong Uk , San Lucas Francis A , Cagley Matthew , Stephens Bret , Mulu Feven C , Castillo Jonathan , Bernard Vincent , Varadhachary Gauri R. , Katz Matthew H. G. , Alvarez Hector A , Maitra Anirban 
Published: March 2017

234 Background: Current research suggests that tumor-derived extracellular vesicles (EVs) play an important role in tumor progression especially with regard to metastasis. Atypically large EVs have been reported to have the ability to transport bioactive molecules through the blood stream. Therefore, EV physical properties such as diameters and concentrations may have a biological impact on tumor progression. However, it has not been described which characteristics are clinically relevant in the longitudinal assessment of tumor progression and chemo-response. Methods: Plasma from 19 metastatic PDAC patients was collected at treatment-naïve baseline and in more than 2 consecutive assessments during chemotherapy between May 2015 and July 2016. EVs from plasma were isolated using a sequential centrifugation protocol, confirmed as described previously and analyzed using the Particle Metrix (Zetaview, Diessen, Germany) and proprietary software. The clinical variables along with concentration and size distribution of EVs were analyzed to identify prognostic factors associated with chemo-response. Results: Mean EV size and concentration were 122.85 nm and 4.13x109/mL plasma at treatment naïve baseline, 123.62 nm and 4.39x109/mL plasma at first response assessment during chemotherapy. Median overall and progression-free survivals were 256 and 165 days, respectively. The change of CA 19-9 (hazard ratio 17.477, p = 0.001, 95% CI 0.995-1.045) and proportion of EVs larger than 150nm (hazard ratio 11.022, p = 0.017, 95% CI 3.183-95.964) was a significant independent predictor of progression-free survival at first response assessment during chemotherapy. In addition, we observed a dramatic increase in the proportion of larger EVs earlier than the increases in CA 19-9. Conclusions: Our data suggests that increases in the amounts of larger EVs are independent predictors of tumor progression and chemo-response in metastatic pancreatic cancer patients. Furthermore, the increases in the amounts of larger EVs may potentially be more clinically useful than CA19-9 in the earlier stages of progression. Concentrations of larger-sized EVs could be a valuable component of more sophisticated diagnostics in liquid biopsies.