bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discrepancies between two staging systems (European-ENETS versus. American-AJCC) of neuroendocrine neoplasms of the pancreas: A study of 77 cases.
Authors: Cienfuegos Javier A. , Salguero Joseba , Nuñez Jorge , Rotellar Fernando , Marti-Cruchaga Pablo , Zozaya Gabriel , Pardo Fernando 
Published: February 2017

318 Background: Pancreatic neuroendocrine tumors (pNETs) comprise a spectrum of neoplasm with variable biological behaviour and heterogeneous prognosis. The European Neuroendocrine Tumor Society (ENETS) and the American Joint Cancer Committee/Union for International Cancer Control (AJCC/UICC) TNM staging systems have been recently published. The aim of this study was to evaluate the consistency of both staging systems on outcomes for patients with pNETs. Methods: A retrospective clinico-pathological study of 77 consecutive patients with pNETs who were surgically treated from 1993 to 2014 was carried out. Results: The male to female ratio was 1.0 (38 men, 39 women); 56 tumors were non-functionating and 21 functionating. Most of the tumors were G1 (57) and 20 were classified as G2-G3. The AJCC/UICC stage was IA in 29 patients, IB in 14, IIA in 10, IIB in 7 and IV in 17. Meanwhile, according with the ENETS staging system was: stage I in 30, IIa in 14, IIb in 3, IIIa in 6, IIIb in 7 and IV in 17. We found 18 (23.3%) cases of ENETS - AJCC/UICC discrepancies regarding the primary tumor. They included 6 cases (33%) disagreement between IIA (T3 N0 M0) and IIIa (T4 N0 M0); and 7 cases (38.8%) between IIB (T1-T3 N1 M0) and IIIb (anyT N1 M0). Conclusions: The AJCC and ENETS TNM classification staging for pNETs provide meaninful prognostic value of long-term survival por patients with pNETs. The T staging discrepancies between AJCC/UICC and ENETS are relative frequent and should be strictly recognized.
A pilot study of molecularly tailored therapy for patients with metastatic pancreatic cancer (MPC).
Authors: Pishvaian Michael J. , Wang Hongkun , He Aiwu Ruth , Ley Lisa , Dorsch-Vogel Karen , Hartley Marion L. , Carney Erin , Weiner Louis M. , Smaglo Brandon George , Brody Jonathan Robert , Marshall John 
Published: February 2017

329 Background: We have entered an era where multiple chemotherapeutic (chemo) agents can be utilized in the treatment (Tx) of patients (pts) with MPC. However, there are no methods for selecting the optimal regimen for any individual pt, and pure empiricism has not proven to be an optimal strategy. Molecular profiling is now widely used, albeit without evidence-based studies linking molecular profiles to Tx choices. Methods: We initiated a pilot study to assess the feasibility of following a simple algorithm, basing Tx on 3 published predictive markers of response to chemo: RRM1 (for gemcitabine); ERCC1 (for platinums); and TS (for 5FU). Pts with untreated, biopsiable MPC were eligible. Tissue biopsies were analyzed by Caris, and the results used to assign pts to 1 of 7 doublet regimens. Our 1o objective was to provide preliminary data to inform a larger, randomized trial. Key 2o objectives included assessment of the response rate (RR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results: Between 12-2012 and 08-2014, 26 pts were enrolled. Eleven failed screening primarily due to inadequate tumor tissue availability (and pts not wanting to wait for a 2ndbiopsy). Of the 15 pts profiled, 6 different doublets were assigned, reflecting the breadth of profile results. Three pts were not evaluable for response by the date of this abstract. Of the 12 pts who received Tx, the RR was 9%, but the DCR rate was 82%. The median PFS and OS were 5.9 and 10.4 months, respectively. Conclusions: The incorporation of chemo biomarkers is feasible and resulted in a promising PFS and OS for pts with MPC. Our pilot experience suggests that there may be value to assessing a pt’s tumor molecular profile to select Tx. Expansion of this experience into a randomized trial of profile-directed Tx vs. Tx based on the physician’s discretion would not only be realistic, but could be critical to realizing the full, clinically meaningful benefit of molecular profiling. We do however caution that biomarker-directed Tx can be challenging in untreated pts, where initiation of Tx is time critical, and delays due to inadequate tumor samples may be untenable. Thus, a randomized trial in the second line setting may be more appropriate. Clinical trial information: NCT01888978.
Phase II randomized trial of MEK inhibitor pimasertib or placebo combined with gemcitabine in the first-line treatment of metastatic pancreatic cancer.
Authors: Van Cutsem Eric , Hidalgo Manuel , Bazin Igor , Canon Jean-Luc , Poddubskaya Elena , Manojlovic Nebojsa , Milella Michele , Radenkovic Dejan , Verslype Chris , Guo Wei , Damstrup Lars , Hammel Pascal 
Published: February 2017

344 Background: In metastatic pancreatic cancer (mPaCa), KRAS mutations lead to constitutive activation of the MAPK pathway in the vast majority of cases. Pimasertib (Pim) is a selective, non-competitive MEK 1/2 inhibitor with potent antitumor activity in preclinical models with constitutive MAPK activation. Methods: Following a phase I, dose-finding part to the trial, 88 patients (pts) with mPaCa were randomized 1:1 to receive Pim 60 mg BID (A, 44 pts) or placebo (B, 44 pts) in combination with weekly gemcitabine (Gem) 1000 mg/m2(7 of 8 wks in cycle 1, then 3 of 4 wks in subsequent cycles), in a phase II setting (NCT01016483). The primary endpoint was progression-free survival (PFS). Response rate (RR), overall survival (OS) and safety were secondary endpoints. Biomarker analysis was an exploratory endpoint. Results: Pt characteristics were balanced (median age 63.5 yrs, males 56%, stage IV at initial diagnosis 75%) except for PS 0, which was more frequent in arm A (59 vs 41%). Time on treatment was longer in arm B (10.6 vs 8.0 wks). A higher proportion of pts in arm A discontinued treatment during the first 4 wks (31 vs 19%), predominantly due to adverse events (AEs) and PD. Median PFS was 3.7 mo in arm A and 2.8 mo in arm B (HR=0.883, 95% CI: 0.549–1.42; p=0.608). No statistically significant differences were observed between arms for OS (median 7.3 mo in arm A vs 8.3 mo in arm B) and RECIST 1.0 RR (9.1% in both arms). Grade ≥3 thrombocytopenia (20.0 vs 0%), vomiting (15.6 vs 4.8%), fatigue (15.6 vs 7.1%), stomatitis (13.3 vs 0%) and diarrhea (11.1 vs 2.4%) were more common in arm A. Typical allosteric MEK inhibitor-related AEs, such as all grade retinal detachment (24.4%) and creatine phosphokinase elevation (20.0%), were observed almost exclusively in arm A. KRAS mutational status did not influence PFS or OS. Conclusions: The primary study endpoint was not met; secondary endpoints did not suggest clinically meaningful differences between arms, except for selected toxicities observed more frequently with the combination of Gem and Pim. The outcome does not support further development of this combination in the first-line setting in mPaCa. Pim is currently in development in other solid tumors. Clinical trial information: NCT01016483.
Large-scale analysis for treatment strategy according to genetic alterations of KRAS and DPC4 (SMAD4) genes in pancreatic ductal adenocarcinoma.
Authors: Shin Sang Hyun , Kim Song Cheol , Song Ki Byung , Lee Jae Hoon , Hwang Dae Wook , Lee Dong Joo , Lee Jung Woo , Kim Hyoung Eun , Jun Eunsung , Park Kwang-Min , Lee Young-Joo 
Published: February 2017

361 Background: To investigate correlation of genetic alterations of pancreatic ductal adenocarcinoma (PDAC) with patients’ survival, recurrence patterns, and treatment for recurrent disease. Methods: We reviewed genetic alterations of major 4 genes (K-ras, DPC4, p53, and c-erbB-2) in 699 patients who underwent surgical resection, and correlated with clinical outcomes. Results: Median survival of all patients was 21.7 months, and 5-year survival rate was 20.4%. Alterational rates of each gene were as follows: K-ras, 48.3%; DPC4, 68.1%; p53, 40.8%; c-erbB-2, 14.0%. Mutation of K-ras and inactivation of DPC4 genes were associated with shorter patients’ survival in univariate analysis. In multivariate analysis, mutation of K-ras gene was independently correlated with patients’ survival (especially, GAT and TGT subtypes). Inactivated DPC4 gene had no independent correlation with overall survival, but it was strongly associated with distant metastasis following pancreatectomy. Survival after recurrence (SAR) was evaluated in subdivided groups according to DPC4 gene function (intact or loss)/recurrence patterns (locoregional or distant)/treatment options (local control or systemic therapy). In these 8 groups, patients in intact/locoregional/local control group showed the longest survival (24.2 months of median SAR), and intact/locoregional/systemic therapy and loss/distant/systemic therapy groups were associated with much shorter survival (9.5 and 9.2 months of median SAR, respectively). Conclusions: Assessment of genetic features of PDAC may assist in deciding targeted surveillance or treatment for primary as well as recurrent PDAC, and further studies for therapeutic strategies according to genetic analyses should be devised.
Comparative efficacy of sorafenib dose in patients with advanced hepatocellular carcinoma (HCC) with varying liver dysfunction.
Authors: Patel Sukeshi R. , Al-Rajabi Raed Moh'd Taiseer , Ketchum Norma , Lu Ting-Wei , Pollock Brad H. , Michalek Joel , Mahalingam Devalingam 
Published: February 2017

369 Background: Sorafenib (SOR) is the only FDA-approved systemic therapy for advanced hepatocellular carcinoma (HCC). In clinical practice, there are limited efficacy data related to dose modifications, which are often required. Given the high prevalence of HCC in South Texas, we assessed the efficacy and safety of SOR therapy in relation to dose and Child Pugh score (CP). Methods: Retrospective analysis of HCC patients (pts) receiving SOR from 2008-2013. Median progression-free survival (mPFS) and median overall survival (mOS) were estimated from Kaplan-Meier curves and groups were statistically compared with the log rank test. The magnitude of association between dichotomous factors and survival was estimated with the hazard ratio (HR). A proportional hazards regression model was used to assess the significance of SOR (low, high) by CP (A, B) interaction. Results: 107 pts were included. Median age 57 (41-93). Males 83%. Hispanic 72%, White 24%. ECOG PS 0–1 93%. Causes of cirrhosis: Hepatitis C 67%, Hepatitis B 5%, EtOH 60%. Portal vein thrombosis 33%, extrahepatic disease 39%. CP (available for 106 pts): A 57%, B 43%. mOS was 10.2 months (mo) (95% CI: 7.8-13.5); mPFS was 5.2 mo (95% Cl: 3.8-7.2). In subgroup analysis, mOS for 800 mg/day was 12.8 mo vs 6.6 mo for 400 mg/day (HR 0.59, p=0.04). mPFS for 800 mg/day was 5.9 mo vs 3.5 mo for 400 mg/day (HR 0.66, p=0.07). In CP A pts, higher SOR dose did not improve survival; however, in CP B pts, there were statistically significant improvements in mPFS and mOS (Table). The effect of dosage varied significantly with CP category (A, B) for both OS (p=0.002) and PFS (p=0.03). Conclusions: Historically, CP B advanced HCC pts have worse survival and tolerability to higher doses of SOR when compared to CP A. Our study suggests CP B pts should be considered for SOR 800 mg/day to improve survival with optimal management of toxicity but warrants further prospective studies. [Table: see text]
Predicting overall survival for patients with periampullary carcinoma.
Authors: Yeung Vincent , Gong Yutao , Yu Jialu , Yu Yan , Lu Bo , Palmer Joshua David , Burkhart Rick , Leiby Benjamin E , Siow vei Shaun , Lavu Harish , Rosato Ernest , Winter Jordan Michael , Lewis Nancy , Sama Ashwin Reddy , Mitchell Edith P. , Anne Pramila R. , Xiao Ying , Hurwitz Mark , Yeo Charles , Bar-Ad Voichita 
Published: February 2017

376 Background: The purpose of this study was to develop a model predicting the overall survival of patients with peri-ampullary cancer (PAC) following resection, with or without adjuvant therapy. This will help guide physicians in providing optimal post-operative care. Methods: Patients treated between 2006-2012 in our institutional pancreatic tumor registry were analyzed. All patients underwent pancreaticoduodenectomy for PAC. 334 patients had adequate records for analysis and were used to develop a multivariate model based on Cox regression. The variables used in our analysis were age, gender, T-stage, tumor differentiation, positive lymph node ratio (# positive/total), positive resection margins, chemotherapy, radiation therapy (RT), and tumor histology. Multivariate Cox hazards regression tested significance. Model performance was evaluated by the concordance index (c-index). Results: Median age of the cohort was 65 years. 54% of the patients were male. Median follow-up time was 16 months. Median overall survival was 19 months. T-stages were as follows: 7% T1, 9% T2, 77% T3, and 8% T4. 27% of the patients had a positive tumor margin, 68% of patients had positive lymph node spread. 81% of the patients had tubular adenocarcinoma, 9% ampullary adenocarcinoma, 5% cholangiocarcinoma, and 4% duodenal carcinoma. T-stage, tumor differentiation, tumor histology, positive lymph node (PLN) ratio, and adjuvant chemotherapy had a statistically significant association with overall survival (Table 1). The model performance c-index was evaluated as 0.630 with 95% CI as [0.571, 0.690], from a bootstrapping internal validation test on 3-year-survival. Conclusions: This model shows promise in predicting survival following resection for patients with PAC. More patient cases and further analysis of additional factors including specific RT related parameters and specific chemotherapy regimen are needed for development of a more robust model. [Table: see text]
Improvement in survival of advanced hepatocellular carcinoma patients: Results of an updated period analysis of SEER database.
Authors: Shah Binay Kumar , Bhandari Amit , Ghimire Krishna Bilas , Manandhar Sajani 
Published: February 2017

383 Background: Sorafenib was approved by FDA for treatment of advanced unresectable hepatocellular carcinoma (HCC) patients in November 2007. In this study, we update survival trends in advanced HCC using Surveillance, Epidemiology, and End Results (SEER) data. Methods: We selected patients with advanced HCC diagnosed from January 2001 to December 2010 from SEER 18 registries. We excluded diagnosed at autopsy, from death certificate only, or those without survival date. We calculated 1- and 2- year relative survival rates in pre-sorafenib (2001-2007) and post-sorafenib (2008-2010) era by age, sex and ethnicity among using SEER*stat software. Results: The total number of advanced HCC patients during 2001-2010, 2001-2007 and 2008-2010 were 5,092, 2,747 and 2,345 respectively. The 1- and 2- year survival rates of patients improved significantly from pre-sorafenib era to post-sorafenib era (1 year RS: 17.20±0.7% to 19.90±0.80%, Z=2.63; 2 year RS: 8.00±0.5% to 8.7±0.60%, Z=2.31). Survival rates of male patients improved significantly in post-sorafenib era (1 year RS: 16.4±0.80 to 19.4±0.90%, Z=2.18; 1 year RS: 7.4±0.60% to 8.6±0.70%, Z=2.18). There was no improvement in survival rates of female patients. Similarly, younger patients had improvement in survival rates in post-sorafenib era compared to pre-sorafenib era (1 year Z value 2.46; 2 year Z value 2.23). There was no improvement in survival rates of older patients. Conclusions: Since FDA approval of sorafenib, survival rates of patients with advanced hepatocellular carcinoma have improved. The improvement in survival rates is limited to males and younger patients
Radiosensensitivity index prognostic for survival with adjuvant radiation in resectable pancreatic cancer.
Authors: Strom Tobin Joel Crill , Hoffe Sarah E. , Coppala Domenico , Springett Gregory M. , Malafa Mokenge Peter , Eschrich Steven A. , Torres-Roca Javier , Shridhar Ravi 
Published: February 2017

398 Background: Adjuvant radiation therapy (RT) for resectable pancreatic cancer remains controversial. We evaluated whether a previously validated molecular signature of tumor radiosensitivity (RSI) is prognostic for survival in pancreatic cancer. Methods: We identified patients treated with upfront surgery between 2006 and 2012. Briefly, RSI score is derived from the expression of 10 specific genes and a linear regression algorithm modeled on SF2 of 48 cancer cells (RSI, high index = radioresistant). We assessed the relative radiosensitivity of pancreatic cancers compared with other common cancers and then tested the association of RSI with overall survival (OS). Results: Compared with other common cancers such as lung, breast, and prostate, pancreatic cancers were more radioresistant as a group (p<0.0001). We identified 80 patients who underwent upfront surgery with both RSI and clinical outcome available (49 RT, 31 no RT). Median follow-up among surviving patients was 4.1 years. Median OS for radiosensitive tumors (RS), defined by lower ½ RSI, was 2.7 years compared with 1.5 years for radioresistant (RR) tumors (p=0.35). Among the high-risk pancreatic cohort, (positive margins, positive lymph nodes, or a post-operative CA 19-9 >90), irradiated patients with RS tumors had a trend toward improved OS (3y OS: 38% vs. 8%; p=0.07), while there was no difference in OS between RS and RR patients who weren’t treated with RT (p=0.79). When RSI was integrated, high-risk-RS patients had similar OS compared with low-risk-RR patients (3y OS: 38% vs. 50%; p=0.29). When low-risk-RR and high-risk-RS were combined into a single intermediate-risk group, RSI score added substantial prognostic value to OS outcomes on univariate (3 y OS: 78%, 42%, and 8%, for low-risk-RS, intermediate-risk group, and high-risk-RR, respectively; p=0.001) and multivariate analysis (intermediate-risk HR: 4.3, 1.0-18.6; p=0.053; high-risk HR: 9.9, 2.2-45.1; p=0.003). Conclusions: Patients with pancreatic tumors have relatively radioresistant tumors. Integrating RSI with standard prognostic variables refines the classification of resected pancreatic cancer patients.
Effect of body mass index on outcomes in biliary tract cancer.
Authors: Doherty Mark , McNamara Mairead Geraldine , Aneja Priya , Le Lisa W , Cleary Sean P. , Horgan Anne M. , Knox Jennifer J. 
Published: February 2017

399 Background: Biliary Tract Cancer (BTC) is associated with poor outcomes, and prognostic factors are not well documented. Body Mass Index (BMI) has been shown to correlate with survival in colon, breast, lung and prostate cancer. The effect of BMI on survival in patients with BTC is unclear. Greater understanding of prognostic markers in BTC can help with treatment decisions. Methods: Patients treated for BTC in Princess Margaret Cancer Centre between 06/1987 and 08/2014 were included for analysis. Data were collected on clinicopathologic features, BMI, and survival. Patients were separated into two groups by resectability: definitive surgery (DS) or no definitive surgery (NDS). Multivariable proportional hazards regression was used to investigate the association between variables and overall survival (OS) for DS and NDS groups. Results: 902 patients (461 DS, 441 NDS) were included, with median BMI 25.7 (range 15.5-48.7). Median OS was 48.1 months in DS patients and 11 months in NDS patients. 244 NDS patients received palliative chemotherapy (55%). BMI was prognostic for OS in DS patients. In univariate analysis, DS patients with BMI <25 had poorer outcomes than those with BMI ≥25 [HR 1.40, 95% CI 1.08-1.82, p=0.01]. In multivariable analysis, the effect of BMI in DS patients remained significant: BMI <25 was associated with poorer OS [HR 1.36, 95%CI 1.03-1.81, p=0.03]. No significant differences were found in OS in NDS patients according to BMI by univariate [HR 1.04, 95%CI 0.83-1.29, p=0.74] or multivariable analysis. Prognostic factors by multivariable analysis are summarized in the Table. Conclusions: For patients undergoing definitive surgery for BTC, BMI <25 was a poor prognostic marker independent of other known prognostic variables. Other prognostic variables from our dataset match reported literature. This study is limited by its retrospective nature, however BMI may aid patient risk stratification after DS for BTC. [Table: see text]
Surgery and adjuvant therapy in gallbladder cancer: A single-institution experience.
Authors: Kothari Nishi , Kim Richard D. , Springett Gregory M. , Hoffe Sarah E. , Almhanna Khaldoun , Hodul Pamela Joy , Pimiento Jose Mario , Malafa Mokenge Peter , Fulp William J. , Zhao Xiuhua , Shridhar Ravi 
Published: February 2017

405 Background: Gallbladder cancer is a highly fatal disease with a high rate of recurrence even when diagnosed at an early stage. Because of its relative rarity, there are currently no established algorithms to guide therapy after cholecystectomy. To explore the value of adjuvant therapy with chemotherapy and radiation, we evaluated patients with resected gallbladder cancer treated at our institution. Methods: Patients diagnosed with gallbladder cancer who underwent cholecystectomy (simple or radical) between 2000 and 2010 were identified using our cancer registry. Retrospective chart review was performed for clinicopathologic data, including age, stage, grade, type of surgery, margin status, and type and duration of adjuvant therapy. The primary endpoint was overall survival (OS). Univariate (UVA) and multivariate (MVA) analysis was performed with Cox logistic regression analyses. Results: We identified 73 patients with a median followup for all patients of 28.2 months. The majority of patients were female (74%) and underwent radical cholecystectomy (64%). Positive margins and adjuvant radiation therapy were documented in 21% and 37%, respectively. The majority of patients did not receive any adjuvant therapy (53.4%). Median OS for all patients was 41.3 months. There was a survival benefit associated with patients undergoing radical cholecystectomy followed by adjuvant radiation (median OS 48.4 months vs. 22.3 months; HR 0.35; 95% CI: 0.13–0.98; p=0.0448) compared to simple cholecystectomy alone. On UVA, increasing age and positive margins were significantly associated with worse OS, while radical cholecystectomy was associated with improved OS. On MVA, increasing age, male gender, poorly differentiated tumor, and positive margins were associated with worse OS, while adjuvant radiation was associated with improved OS (p=0.0113). Conclusions: Our analysis supports the role for adjuvant radiation therapy in resected gallbladder cancer. Multi-institutional prospective studies should be performed to evaluate the optimal treatment strategy. Biomarker analysis might also help determine the subset of patients who would benefit from combined chemoradiation.