bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of estrogen receptor beta isoforms in pancreatic adenocarcinoma.
Authors: Younes Mamoun , Ly Charles J , Singh Kanchan , Ertan Atilla , Guha Sushovan , Younes Pamela S , Biley Jennifer M 
Published: March 2017

337 Background: There have been several limited trials in which tamoxifen efficacy was tested in patients with pancreatic adenocarcinoma (PAC). Most of these studies were small series of patients with unresectable PAC and reported mixed results. In these studies, patients were not stratified by estrogen receptor status because estrogen receptor beta (ER-b) had not yet been identified, and PAC did not express the traditional ER-alpha. Recent studies showed that the effects of estrogens, phytoestrogens and tamoxifen on PAC cell lines depended on ER-b expression. The aim of this study was to investigate ER-b expression in human PAC and whether such expression correlates with any clinicopathologic parameters. Methods: Sections of tissue microarray containing 18 formalin fixed and paraffin embedded human PAC were stained by immunohistochemistry (IHC) using monoclonal antibodies to ER-b isoforms 1, 2, and 5 (ER-b1, ER-b2, and ER-b5, respectively), and for Cyclin A. The levels of ER-b isoform expression in tumor cells and the S-phase fraction (SPF) were determined using a quantitative digital image analysis solution (OTMIAS). Results: All isoforms were expressed in PAC, although at different levels. Higher mean ER-b2 levels correlated with male sex (p = 0.057), older age (p = 0.005), and lower pT stage (p = 0.008), but not with grade, pN stage, or SPF. Mean ER-b5 levels correlated negatively with SPF (p = 0.021), but not with sex, age, grade, pT or pN. Mean ER-b1 expression did not correlate with any of the above mentioned clinicopathologic factors. Conclusions: ER-b1, ER-b2, and ER-b5 are expressed in PAC. Higher ER-b2 and ER-b5 levels of expression are significantly correlated with lower tumor pT stage and with lower SPF, respectively, suggesting that they may play a tumor suppressive role in PAC. The association between ER-b2 levels and patient sex and age suggest that it could be influenced by endogenous/exogenous hormonal exposure.
Two randomized, placebo-controlled phase 3 studies of ruxolitinib (Rux) + capecitabine (C) in patients (pts) with advanced/metastatic pancreatic cancer (mPC) after failure/intolerance of first-line chemotherapy: JANUS 1 (J1) and JANUS 2 (J2).
Authors: Hurwitz Herbert , Van Cutsem Eric , Bendell Johanna C. , Hidalgo Manuel , Li Chung-Pin , Garrido Marcelo , Macarulla Teresa Mercade , Sahai Vaibhav , Sama Ashwin Reddy , Greeno Edward , Yu Kenneth H. , Verslype Chris , Dawkins Fitzroy W. , Walker Christopher , Clark Jason , O'Reilly Eileen Mary 
Published: March 2017

343 Background: The JAK-STAT pathway plays a role in the pathogenesis of PC. In a phase 2 study, the JAK1/2 inhibitor Rux + C improved OS vs C alone in mPC pts with evidence of systemic inflammation. Methods: In two phase 3 studies, advanced/mPC pts with only 1 prior chemotherapy regimen and C-reactive protein > 10mg/L were randomized to 21-day cycles of Rux 15 mg BID + C 2000 mg/m2/d (day 1-14) vs placebo (Pb) BID + C 2000 mg/m2/d (day 1-14). The primary endpoint was OS. The studies were terminated early based on efficacy findings of a planned interim analysis for J1, with J2 enrollment incomplete. Results: 321 pts were randomized in J1 and 86 in J2. The median age was similar between groups (Rux + C vs Pb + C): J1, 68 vs 67 yrs; J2, 68 vs 69 yrs. The most common prior chemotherapy regimens were gemcitabine (gem) + nab-paclitaxel (J1: 50% vs 51%, J2: 42% vs 37%), gem alone (J1: 24% vs 21%, J2: 28% vs 33%). Median study treatment durations were 42 d for both Rux and Pb in J1; 40 d for Rux and 43 d for Pb in J2. Discontinuations were mainly due to disease progression (J1: 62% vs 65%, J2: 51% vs 58%), AEs (J1: 4% vs 10%, J2: 12% vs 12%) or death (J1: 8% vs 5%, J2: 7% vs 5%). Rux + C did not show a benefit over C alone in OS or PFS (see Table). Overall response rates were < 5% in each treatment group (NS).The most common grade 3/4 non-hematologic AEs were abdominal pain (J1: 7% vs 14%; J2: 14% vs 5%), palmar-plantar erythrodysesthesia syndrome (J1: 7% vs 4%; J2: 0% vs 12%), pulmonary embolism (J1: 4% vs 3%; J2: 10% vs 5%), dyspnea (J1: 2% vs 2%; J2: 10% vs 2%) and vomiting (J1: 5% vs 5%; J2: 2% vs 12%). The most common new/worsening hematologic labs abnormalities of grade 3/4 included: anemia (J1: 20% vs 6%; J2: 11% vs 8%) and lymphopenia (J1: 17% vs 9%; J2: 16% vs 8%). Conclusions: When added to C, Rux was well tolerated but did not improve clinical outcomes in the second-line treatment of mPC pts. Clinical trial information: NCT02117479 and NCT02119663. [Table: see text]
Significant upstaging of patients with stage I pancreatic cancer from clinical to pathologic staging.
Authors: Stuart Heather , Ripat Caroline , Azab Basem , Yakoub Danny , Franceschi Dido , Livingstone Alan S , Dudeja Vikas , Merchant Nipun B. 
Published: March 2017

349 Background: Clinical staging of patients with pancreatic cancer is essential to determine if neo-adjuvant treatment, surgery or palliative treatment is required. Patients with early stage disease often receive upfront surgery, where as patients with more advanced disease often receive neo-adjuvant therapy. Therefore the accuracy of clinical staging significantly influences management decisions. This study investigates the correlation between clinical and pathologic staging for patients with stage I pancreatic cancer. Methods: A retrospective review of patients with pancreatic cancer in National Cancer Data Base from 1998-2006 was preformed. The clinical stage of patients with presumed stage I disease was compared to the postoperative pathologic stage. Cox proportional hazard ratio model and regression analysis were used to determine factors associated with mortality and upstaging, respectively. Results: 1697 patients with clinical stage I pancreatic cancer were divided into two groups. Group 1 was comprised of patients who were stage I postoperatively and Group 2 was comprised of patients that were upstaged to either stage II, III or IV postoperatively. There were 704 (41%) in group 1 and 993 (59%) in group 2. Within group 2, 595 (60%) were stage II, 321 (32%) were stage III and 77 (8%) were stage IV. Patients that were upstaged after surgery had an increased risk of mortality (HR 1.414, p < 0.001), whereas patients that received adjuvant chemotherapy had a decreased risk of mortality (HR 0.799, p < 0.001). Compared to Grade 1 tumors, Grade 2 and 3 tumors on biopsy were most likely to be upstaged on final pathology (p < 0.001). Conclusions: Patients with stage I pancreatic cancer are often candidates for upfront surgery, however this study demonstrates that a large number are upstaged on postoperative staging. Recognizing this may lead clinicians to administer neo-adjuvant treatment in a greater number of patients with early stage disease in order to optimize survival.
Development and validation of a prognostic nomogram and score to predict overall survival and usefulness of second-line chemotherapy in advanced pancreatic adenocarcinoma.
Authors: Vienot Angélique , Beinse Guillaume , Louvet Christophe , de Mestier Louis , Meurisse Aurelia , Fein Francine , Heyd Bruno , Cleau Denis , d'Engremont Christelle , Dupont-Gossard Anne Claire , Lakkis Zaher , Tournigand Christophe , Bouche Olivier , Rousseau Benoit , Neuzillet Cindy , Bonnetain Franck , Borg Christophe , Vernerey Dewi 
Published: March 2017

354 Background: In advanced pancreatic ductal adenocarcinoma (aPDAC), there is no consensual strategy for second-line chemotherapy (L2). Better discrimination of overall survival (OS) may help clinical decision-making in this setting. We aimed to predict OS from the beginning of L2 and to assess the benefit from chemotherapy among the identified risk groups. Methods: Analyses were derived from all consecutive aPDAC patients treated at Besancon hospital, France, during 11 years. The association of 50 parameters with OS was evaluated using univariate and multivariate Cox analyses. Based on the final model, a prognostic nomogram and score were developed, and externally validated in patients receiving L2 in three other French centers, between 2010 and 2016. Results: The development cohort included 462 patients. 395 patients (85%) were eligible for L2, of which 261 (66%) were treated. Age, smoking status, liver metastases, Eastern Cooperative Oncology Group performance status, pain, jaundice, ascites, duration of first-line chemotherapy, and type of L2 regimen were identified as independent prognostic factors for OS in L2. The final model exhibited excellent calibration and discrimination (C-index = 0.75, 95% confidence interval 0.72 to 0.78), and robust internal validity. Based on the final model, a prognostic nomogram was built. The nomogram total points were input into a prognostic score that delineated three risk groups with median OS of 11.3, 3.6 and 1.4 months (P < 0.0001). By applying the score in the population eligible for L2 but untreated, the chemotherapy benefit was significant across all groups but with a magnitude of the effect decreased significantly from low to high-risk groups (P = 0.0123 for treatment and risk groups interaction term). The clinical benefit centered accuracy of the final model was confirmed by a decision curve analysis. The score ability to discriminate OS was externally confirmed in 162 patients, by identifying the same risk groups. Conclusions: These prognostic tools in patients with aPDAC can accurately predict OS before administration of L2 and strengthen the prognosis-based decision making for clinicians.
Impact of timing of adjuvant chemotherapy initiation on survival in pancreatic adenocarcinoma.
Authors: Palacio Sofia , Ripat Caroline , Stuart Heather , Yakoub Danny , Merchant Nipun B. 
Published: March 2017

355 Background: Pancreatic adenocarcinoma (PDAC) is now the third leading cause of cancer death. Surgical resection followed by adjuvant chemotherapy has been the standard of care. Due to the significant risk of morbidity following pancreatic surgery, initiation of adjuvant chemotherapy is often delayed. Prior prospective adjuvant trials have suggested that adjuvant therapy can be initiated as late as 12 weeks without detriment, but data regarding the effectiveness of beginning adjuvant therapy beyond that time remains unknown. Methods: We retrospectivelyreviewed data from the National Cancer Data Base (2004-2014) and included adult patients (pts) with PDAC with pathologic stage I-IIB who underwent surgical resection with curative intent. The primary outcome was overall survival (OS) based on time to adjuvant chemotherapy post-surgery as defined by postoperative weeks. Data were analyzed using Cox proportional hazard model and Kaplan-Meier survival curves. Results: 5279 pts. had surgery alone and 4,537 pts. received adjuvant chemotherapy. The median age was 64 years. 52% were male, 88% were white, 46% were treated at comprehensive community cancer centers. The primary surgical approach was whipple procedure in 61% of pts. 63% pts. received single agent chemotherapy and the mean time from surgery to chemotherapy was 61 days. Adjuvant chemotherapy was associated with improved OS irrespective of disease stage compared to those undergoing surgery alone (median OS for surgery alone 14 months vs adjuvant chemotherapy 21 months, p < 0.001). Cox proportional hazard model controlling for stage, surgical technique, lymph node dissection and margin status revealed improved OS in pts. receiving adjuvant chemotherapy. No significant differences in OS were seen for pts. starting adjuvant chemotherapy at 3, 6, 9, 12, 16, 20 or 24 weeks after surgical resection. Conclusions: Current guidelines recommend initiation of adjuvant chemotherapy prior to 12 weeks after pancreatic resection. Initiating adjuvant chemotherapy even up to six months post-operatively improves OS compared to those undergoing surgery alone. Our data supports the use of adjuvant chemotherapy if indicated regardless of time of surgery.
Hepatocellular carcinoma (HCC): Resection with adjuvant hepatic artery infusion chemotherapy (HAIC) versus resection alone—A systematic review and meta-analysis.
Authors: Moran Alexandra , Flor Ramos Lorena , Picado Omar , Stuart Heather , Dudeja Vikas , Pendola Fiorella , Sleeman Danny , Merchant Nipun B. , Yakoub Danny 
Published: March 2017

357 Background: HCC have a recurrence rate of up to 70% in 5 years after resection detrimentally lowering survival. The role of adjuvant HAIC in management of HCC in patients who are not candidates for transplantation is controversial. We aimed to evaluate overall and disease free survival in these patients. Methods: A comprehensive online search of MEDLINE, EMBASE, PubMed, SCOPUS and the Cochrane database was conducted (Jan 1994 - August 2016). Comparative studies including patients with HCC, who are not transplant candidates, undergoing surgical resection and adjuvant HAIC vs surgical resection alone were reviewed. Study quality was assessed using STROBE checklist. Pooled risk ratios and 95% confidence intervals (CI) for overall and disease-free survival at 1, 3 and 5 years were calculated. Results: Overall, 10 studies with 595 HCC patients were included; 283 underwent resection followed by HAIC and 312 underwent resection alone. Mean age was 61 ± 10.1 years with a male/female ratio of 6/1. Meta-analysis of all included studies showed better overall survival in patients undergoing resection followed by HAIC compared with resection alone at 1-YR (Average 90.1% vs 79.5%, RR:1.15, CI:1.07 – 1.24, p=0.095, NS), 3-YR (Average 72.1% vs 49.4%, RR:1.57, CI:1.34 – 1.77, p<0.01) and 5-YR (Average 51% vs 30.2%, RR:1.71, CI:1.33 – 2.20, p<0.01). Median survival time for the resection with HAIC group was 54.94 months compared to 31.5 months for the resection alone group. In addition, disease-free survival was better with HAIC at 1-YR (RR:1.36, CI:1.21 – 1.54, p<0.01), 3-YR (RR:1.59, CI:1.27 – 1.98, p<0.01) and 5-YR (RR:1.85, CI:132. – 2.61, p=0.011). The median disease-free survival time for the resection with HAIC group was 17.5 months compared to 7.35 months for the resection alone group. Subgroup analysis showed that this survival advantage was more significant in patients with tumors ≥7cm (p<0.05). Conclusions: Combination of HCC resection with HAIC improve overall and disease-free survival of patients with HCC who are not candidates for transplantation, especially in tumors ≥ 7cm.
Analysis of the effect of adjuvant therapy on overall survival for resected gallbladder adenocarcinoma using the National Cancer Database.
Authors: Brauer David G. , Lim Kian-Huat , Doyle Maria Majella , Hawkins William G. , Chapman William C. , Fields Ryan C 
Published: March 2017

360 Background: The effect of adjuvant chemotherapy on survival after resection for gallbladder adenocarcinoma (GBC) is based on limited evidence. Since prospective trials are not generally practical for GBC, we sought to evaluate current best evidence to evaluate the role of adjuvant chemotherapy in multiple clinical scenarios by analyzing data from the U.S. National Cancer Database (NCDB). Methods: Patients who underwent resection for GBC diagnosed between 2004 and 2012 were identified in the NCDB. The effect of adjuvant therapy on overall survival (OS) was assessed using Kaplan-Meier analysis and Cox proportional hazards regression modeling. Results: 10,402 patients met inclusion criteria. Median follow-up was 14 months. Median survival was 16 months. One- and five-year OS were 57% and 23%, respectively. 3,509 patients (34%) received any modality of adjuvant therapy. Receipt of adjuvant therapy improved one-year OS (63% vs 55%, p < 0.01), but median OS was minimally changed (17 vs 15 months, NS). Adjuvant therapy was associated with improved one-year OS in T3 and T4N1 disease (Table 1). Only chemoradiation therapy was associated with improved one-year OS for T2 disease. Adjuvant chemotherapy was associated with worse one-year OS in T1N0 disease. Conclusions: Using data from the US NCDB, adjuvant therapy for resected gallbladder adenocarcinoma is associated with improved one-year overall survival with the exception of T1N0 disease. In the absence of prospective studies in this rare disease, retrospective data can provide insights into successful treatment strategies and guidelines for GBC. [Table: see text]
Prognostic value of immunohistochemical factors in esophageal small cell carcinoma (ESCC): Analysis of clinicopathologic features of 73 patients.
Authors: Li Cong , Zhang Yigong 
Published: March 2017

37 Background: Esophageal small cell carcinoma (ESCC) is a very rare but aggressive disease with poor prognosis. The objective of this study was to describe immunohistochemical and clinicopathological features of patients with ESCC in Chinese population, and to clarify how the utilization of different marker combinations affects prognostic outcome. Methods: We retrospectively reviewed a total of 73 patients with ESCC. The tumor samples obtained were immunohistochemically analysed of neuron specific enolase enolase (NSE), synaptophysin (Syn), chromogranin A (CgA), and Thyroid Transcriptional Factor-1 (TTF-1). The positivity of these four factors and their correlation with clinical characteristics was described. The relation between positive expression of them and survival was also analysed. Results: The median age at the time of diagnosis was 57 (ranging from 36 to 77 years). 55 patients were male (75.3%) and 18 patients (24.7%) were female. Immunological reactivity of the samples was Syn 68.5%, TTF-1 46.6%, NSE 90.4%, CgA 43.8%. There were sixteen cases with four biomarkers positive (21.9%), twenty-six cases with three biomarkers positive (35.6%), fourteen cases with two biomarkers positive (19.2%), and twelve cases with only one biomarker positive (16.4%). Five cases (6.8%) were all negative. The expression of NSE was insignificantly associated with primary tumor location (P = 0.01). The 2-year and 3-year cancer-specific survivals were 24.8% and 19.9%, respectively. The median OS was 13.5 months. Although not statistically significant, expression of any factor was tended to positively affect survival. And the median OS of patients without expression of four factors was significant worse than those with at least one factor of positive expression (6.1 months vs 15.3 months, P = 0.002). Conclusions: Chinese ESCC patients have a poor prognosis even after local or systemic treatment. Relatively high percentages of positive labeling of Syn, CgA, NSE and TTF-1 implicated their diagnostic value in ESCC. More important, these four biomarkers might be probable favourable prognostic factors for ESCC.
Necuparanib combined with nab-paclitaxel + gemcitabine in patients with metastatic pancreatic cancer: Phase 2 results.
Authors: O'Reilly Eileen Mary , Mahalingam Devalingam , Roach James M. , Miller Paul Justin , Rosano Molly E. , Krause Silva , Avery William , Bekaii-Saab Tanios S. , Shao Spencer H. , Richards Donald A. , Vaickus Louis , Wolf Julie , Flaherty Keith , Ryan David P. 
Published: March 2017

370 Background: The Phase 1 portion of a Phase 1/2 trial of Necuparanib (“Necu”) combined with nab-paclitaxel (nabP) + gemcitabine (gem) in patients with metastatic pancreatic cancer (ClinicalTrials.gov Identifier NCT01621243) showed acceptable safety and tolerability and encouraging signals of activity and established a dose for the randomized, placebo (PBO)-controlled Phase 2 portion. Methods: In Phase 2, patients received daily s.c. injections of either 5 mg/kg Necu daily or PBO, combined with i.v. 125 mg/m2 nabP and 1000 mg/m2 gem (Days 1, 8, 15 of each 28-day cycle). The primary endpoint was overall survival (OS); other endpoints included progression-free survival (PFS), response rates, safety, and CA19.9 levels. An interim futility analysis was conducted in July 2016 once 57 deaths (50% of the target number of 114 events required for trial completion) had occurred. Results: The analysis was conducted on data from 120 randomized patients (62 Necu, 58 PBO). The Z-score for futility was -0.42 (prespecified boundary of -0.148 was crossed as actual score was lower). Median OS was Necu = 10.71 and PBO = 9.99 months; hazard ratio (HR) = 1.12 (favoring PBO); OS curves were intertwined. PFS was Necu = 5.52 and PBO = 6.93 months; HR = 0.97. RECIST response rates were comparable between arms: complete response, Necu = 0%, PBO = 3%; partial response, Necu = 26%, PBO = 26%; stable disease, Necu = 31%, PBO = 34%; disease control rate, Necu = 56%, PBO = 64%. The most common Grade 3+ adverse events (AEs) were neutropenia (Necu = 33%, PBO = 33%), thrombocytopenia (Necu = 27%, PBO = 5%), and anemia (Necu = 22%, PBO = 11%). There were lower rate of serious AEs with Necu (48%) vs. PBO (60%). Modest increases in APTT, AST, and ALT were noted following Necu relative to PBO. 23% of Necu and 5% of PBO patients were IgG positive with an anti-heparin/PF4 antibody titer of ≥ 0.4 at any time. There were no treatment differences for decreases in CA19.9. Conclusions: No new safety signals were observed and the toxicity profile was considered manageable; however, Necu in combination with nabP and gem did not show a sufficient level of efficacy in metastatic pancreatic cancer to warrant continued enrollment. Clinical trial information: NCT01621243.
Adjuvant therapy (AT) following resection of pancreatic ductal adenocarcinoma (PDAC): Are patients from rural, remote areas disadvantaged?
Authors: Bertens Kimberly A , Massman John , Garbus Samuel , Mandelson Margaret T , Lin Bruce , Picozzi Vincent J. , Alseidi Adnan , Biehl Thomas , Helton William Scott , Rocha Flavio G 
Published: March 2017

373 Background: AT with chemotherapy (CT) + radiation (RT) has been shown to improve PDAC survival over surgery alone. Although race and socioeconomic status can affect outcomes in PDAC, the impact of rural or remote residence on the delivery and effect of AT has not been studied. Methods: Patients undergoing pancreatectomy for PDAC were identified from the National Cancer Data Base between 2006 and 2013. Individuals were classified as living in a metro area, urban/rural adjacent to metro area (URA), and urban/rural remote area (URR). Patients with less than 6 months follow-up were excluded. Logistic regression was performed to assess residence as a predictor of receiving AT. Overall survival (OS) as a function of inhabitance was estimated by the method of Kaplan and Meier and prognostic factors were identified by Cox regression. Results: A total of 32,521 individuals underwent pancreatectomy for PDAC. The majority of AT was delivered in academic research facilities in 56% of patients while only 29% of patients received both CT and RT. Univariate analysis demonstrated individuals in URR were less likely to receive CT (55% vs 58%, p < 0.01) but not RT (30% vs 31%, p < 0.261) and had a longer interval to AT (82 vs 75 days, p < 0.009) than those in metro areas. However on multivariate analysis URR inhabitance was no longer predictive of any form of AT (OR = 0.892, 95% CI: 0.792-1.006, p = 0.062). Hispanic ethnicity, Medicaid insurance, uninsured status, and lower education were all predictive of decreased likelihood of receiving AT. Median OS was inferior for URR dwellers with pathologic T2 and T3 tumors compared to those in metro areas (19.8 vs. 24.4 months, p = 0.044 and 17.5 vs. 19.4 months, p < 0.001). Cox regression revealed URR location remained independently associated with poorer OS (HR 1.076, 95% CI: 1.008-1.149, p < 0.029). Conclusions: While living in a URR does not lead to reduced access to AT, it is associated with a worse OS in resected PDAC. This may be due to inadequate AT or other socioeconomic factors present in URR patients. Attention must be focused on improving oncologic care for groups susceptible to treatment disparities.