bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of neoadjuvant chemoradiotherapy (nCRT) on survival in patients with borderline resectable (BR) pancreatic adenocarcinoma (PDA) with acceptable peri-operative morbidity.
Authors: Minter Rebecca Manget , Feng Mary Uan-Sian , Al-Hawary Mahmoud , Shen Jincheng , Schipper Matthew J , Bednar Filip , Proctor Erica , Warner Susanne Gray , Zalupski Mark M. , Simeone Diane M. 
Published: February 2017

288 Background: The impact of nCRT for patients (pts) with BR PDA has been debated, with wide variation in practice. Most studies in pts undergoing nCRT have no or historic controls, rather than a direct comparison of BR pts treated in the same era. We aimed to assess the effect of nCRT on operative, pathologic, and survival endpoints in pts with BR PDA. Methods: 241 pts underwent pancreatectomy (177 without and 64 with nCRT) for PDA (2001-2011). CT scans at dx were re-reviewed by a pancreatic radiologist using a standardized template. Pts were categorized as resectable, BR, or unresectable according to 2012 NCCN criteria. BR pts (n=74) were extracted for analysis. Survival was compared using log-rank tests; pathologic features and peri-op factors were compared using Wilcoxon rank sum tests (continuous variables) or Fisher's exact test (binary variables). Results: Median follow up was 26 ±21 months. nCRT was associated with higher 1 and 3 yr OS, lower margin and node positivity, decreased pre-op CA19-9, and lower post-op pancreatic fistula (POPF), with higher operative time, vascular reconstructions, and transfusion (PRBCs). On univariate analysis, POPF negatively impacted survival (HR 2.34, 1.16-4.75, p=0.02) as did pre-op CA19-9>150 U/mL (HR 2.11, 1.16-3.87, p=0.015). Conclusions: Pts receiving nCRT for BR PDA had higher 1 and 3 yr OS, more negative margins, and fewer positive nodes, with minimal additional peri-op co-morbidity, compared with pts going directly to surgery. These data support consideration of enrolling all pts with BR PDA into a neoadjuvant program prior to resection. [Table: see text]
Survival benefit of second-line chemotherapy in advanced pancreatic adenocarcinoma: A systematic review of the literature.
Authors: Nagrial Adnan , Chin Venessa T. , Sjoquist Katrin , Chantrill Lorraine A. , Yip Desmond 
Published: February 2017

296 Background: There is currently no standard of care for the second-line treatment of advanced pancreatic cancer. Very few randomised studies have been performed in this setting. The aim of this analysis was to compare the different therapeutic approaches in this setting, and the rate of second line treatment delivery and its influence on reported overall survival. Methods: We carried out a systematic analysis of studies in advanced pancreatic cancer. 1st and 2nd line chemotherapy trials were identified from MEDLINE, EMBASE & CENTRAL using the COCHRANE sensitive search strategy. Objective response rates (ORR) and survival (PFS & OS) were extracted and compared amongst groups using the Mann-Whitney U test. For 1st line studies, the percentage of patients who received 2nd line chemotherapy was also extracted and plotted against reported median overall survival (OS) and post-progression survival (PPS), defined as arithmetic difference between median OS and progression-free survival. Linear regression was used to explore the relationship between overall survival and second-line chemotherapy. Results: 20 first line clinical trials with 42 treatment arms met the inclusion criteria treating an aggregate total of 5,768 patients. Overall survival was positively correlated with use of second-line chemotherapy (r=0.65; p=0.012). 61 second-line studies were identified treating an aggregate total of 2,562 patients in 66 treatment arms. Combination treatment was associated with an improved response rate (p=0.045) and PFS (p=0.024) when compared to single agent therapy. Conclusions: In this exploratory analysis, these data suggest that there is a small benefit of second-line chemotherapy in pancreatic cancer. In first-line chemotherapy studies, the use of subsequent treatment correlates with improved overall survival. In second line studies, combination chemotherapy is associated with higher response rates and survival.
Effects of statin, aspirin, or metformin use on recurrence free and overall survival in patients with biliary tract cancer (BTC).
Authors: McNamara Mairead Geraldine , Aneja Priya , Le Lisa W , Horgan Anne M , McKeever Elizabeth , Knox Jennifer J. 
Published: February 2017

303 Background: BTCs include intrahepatic (IHC), hilar, distal bile duct (DBD), and gallbladder carcinoma (GBC). Statins, aspirin and metformin may have antineoplastic properties. The impact of their use on overall survival and the recurrence free survival of patients who had curative resection of BTC has not been evaluated. Methods: Baseline demographics and use of statins, aspirin or metformin at diagnosis were evaluated in 913 patients with BTC from 01/87 - 07/13 treated at Princess Margaret Cancer Center, Toronto. Their prognostic significance for recurrence free and overall survival was determined using a Cox proportional hazards model. Results: The median age at diagnosis for the entire cohort was 65.7 years (range 23.7-93.7). 795 patients had a performance status < 2 and 461 (50.5%) were male. The primary site was GBC in 310 (34%) patients, DBD in 212 (23%), IHC in 200 (22%) and hilar in 191 (21%). Curative surgical resection was performed in 355 (39%) patients. Among the entire cohort of 913 patients, 151 (16.5%) reported statin use at diagnosis. Atorvastatin was the statin used in 55% of patients. 146 (16%) reported aspirin use and 81 (9%) reported metformin use at diagnosis. Age (p=0.05, p<0.01), and stage (p<0.001, p<0.001) were prognostic on multivariable analysis for recurrence free and overall survival respectively. GBC (p=0.01), DBD (p<0.01) primary and performance status ≥ 2 (p < 0.0001) were also prognostic for overall survival. Recurrence free and overall survival among statin users and nonusers was similar (Hazard Ratio (HR) 1.07, 95% confidence interval (CI) 0.78-1.48, p=0.68) and (HR 0.84 (95% CI 0.67-1.05, p=0.12) respectively. Recurrence free and overall survival among aspirin users and nonusers was similar (HR 0.91, 95% CI 0.64-1.29, P=0.58) and (HR 0.98 (95% CI 0.80-1.22, P=0.88) respectively. Recurrence free and overall survival among metformin users and nonusers was also similar (HR 0.71, 95% CI 0.43-1.17, p=0.18) and (HR 0.81 (95% CI 0.60-1.08, p=0.14) respectively. Conclusions: In this large retrospective cohort of BTC patients, statin, aspirin or metformin use was not associated with improved recurrence free or overall survival.
A prognostic examination of the chemotherapeutic selection for pancreatic cancer patients with peritoneal dissemination: A retrospective study from a single center.
Authors: Takada Ryoji , Ioka Tatsuya , Sueyoshi Hironari , Ishida Nobuko , Yamai Takuo , Fukutake Nobuyasu , Ashida Reiko , Katayama Kazuhiro 
Published: February 2017

331 Background: Pancreatic cancer(PC) patients(pts) with peritoneal dissemination are poor prognosis. This retrospective study evaluated the prognosis of Gemcitabine(GEM)-based current chemotherapy(G), GEM plus S-1 combination therapy(GS) and single agent of S-1 as 1st line chemotherapy regimen in PC pts with peritoneal dissemination. Methods: This is a retrospective study of PC pts with ascites or peritoneal nodules in the CT or US image who underwent chemotherapy between 2002 and 2011. We collected data on age, sex, Performance Status(PS), tumor location, other metastasis location, status of peritoneal dissemination, CA19-9, CEA, albumin, CRP. We classified 1st line chemotherapy regimen in G, GS and S-1, and we evaluated 1-year survival rate, progression free survival(PFS), overall survival(OS) for the 3 regimens. Results: A total of 81 pts were included. Median age were 64 (38-78), males 50%, PS 0-1 89%. The number of pts treated with G, GS, S-1 was 54, 14, 13. The 1-year survival rate of G, GS and S-1 were 20.3%, 28.5% and 53.8%. The median PFS were 106 days, 84 days and 88 days, respectively. The median OS were 196 days, 154 days, 359 days, respectively. The 1-year survival rate of S-1 was significantly better than that of G (p=0.01). Median PFS and median OS of S-1 didn’t demonstrate the superiority compared with that of G (p=0.40, p=0.08). Conclusions: We suggest the selection of S-1 as 1st line chemotherapy regimen in PC pts with peritoneal dissemination might be effective and we need further investigation.
A phase I/II study of capecitabine combined with peginterferon alfa-2a in sorafenib-refractory advanced hepatocellular carcinoma patients.
Authors: Ogasawara Sadahisa , Chiba Tetsuhiro , Ooka Yoshihiko , Kanogawa Naoya , Motoyama Tenyu , Suzuki Eiichiro , Tawada Akinobu , Kanai Fumihiko , Yokosuka Osamu 
Published: February 2017

346 Background: Several studies have demonstrated the effectiveness of combining a pyrimidine fluoride drug with interferon. Therefore, this study examined the dose of capecitabine in combination with peginterferon alfa-2a (PEG-IFN α-2a) (Phase I part) and evaluated its safety and efficacy in sorafenib-refractory advanced hepatocellular carcinoma patients (Phase II part). Methods: Capecitabine was administrated daily on days 1–14 and PEG-IFN α-2a was given on days 1, 8, and 15. The cycles were repeated every 21 days. Patients were scheduled to received capecitabine (mg/m2/day) and PEG-IFN α-2a (μg/week) at one of three dose levels in phase I: 1200/90, 1600/90, and 2000/90 (levels 1–3, respectively). Results: Thirty patients were enrolled. The recommended dose was level 3. Of the 24 patients given the drug at the recommended dosage, two (8%) showed partial responses, nine (38%) had stable disease, ten (42%) had progressive disease, and three (13%) were not evaluated. The median time to progression was 3.0 months. The most common toxicities were decreased white blood cell, neutrophil, and platelet counts, palmar-plantar erythrodysesthesia syndrome, and fatigue. Dose modification was required in ten (42%) patients. Four (17%) patients discontinued treatment because of severe adverse events. Conclusions: Capecitabine at 2000 mg/m2/day combined with PEG-IFN α-2a 90 μg/week had moderate, but manageable toxicity. Further investigation is needed to refine the efficacy. Clinical trial information: UMIN000005697.
Cost-effectiveness of nab-paclitaxel plus gemcitabine versus erlotinib plus gemcitabine in metastatic pancreatic cancer.
Authors: Chiorean E. Gabriela , Whiting Scott , Binder Gary , Dranitsaris George , Manax Victoria 
Published: February 2017

353 Background: In a recent phase III trial nab-paclitaxel (albumin-bound paclitaxel) + gemcitabine (nab-P/G) demonstrated a 1.8 month, or 27%, improvement in median overall survival (OS) (HR = 0.72, P < 0.001) vs gemcitabine (G) in first-line metastatic pancreatic cancer (mPC). nab-P/G had higher 1 year OS (35% vs 22%) and improved PFS by 1.8 months (HR = 0.69, P < 0.01). nab-P/G is the first taxane based therapy to show a significant OS improvement in a phase III mPC trial. Erlotinib + gemcitabine (E/G) has also demonstrated activity in mPC, with a 0.3 month OS benefit vs G (HR = 0.82, P = 0.04), a 1 year OS of 23% vs 17%, and 0.2 months PFS benefit (HR = 0.77, P = 0.004) vs G. A cost-effectiveness analysis measuring the cost per life year (LY) gained for nab-P/G and E/G was conducted from the US payer perspective. Methods: Costs and clinical outcomes were evaluated fromnab-P/G vs G and E/G vs G trials of mPC. Health care resource use and the management of grade III/IV adverse events (AE) were collected from a large multisite US oncology clinic, expert opinion, and literature (2012 US dollars). Drug cost per cycle was multiplied by the median cycles delivered from the trials for nab-P/G and E/G. Results: Duration of therapy was 4 months for nab-P/G vs 3.9 months for E/G. Total cost for nab-P/G was $24,984 vs $23,044 for E/G, including drug, administration and AE management. AE costs were similar between the two therapies (Table). Differences of > 5% were noted in neutropenia (rates: nab-P/G = 33%; E/G = 24%), neuropathy (nab-P/G = 17%; E/G = 1%), and rash (nab-P/G = 0%; E/G = 6%). The net survival advantage for nab-P/G vs E/G was 1.5 incremental life months gained. Nab-P/G was cost-effective relative to E/G, at a cost of $15,522 per incremental life year gained. Conclusions: nab-P/G is a cost-effective alternative to E/G in mPC, bringing more months of OS at < $16,000 cost per incremental life year gained. [Table: see text]
Resection of isolated metastases to the pancreas: An institutional retrospective review.
Authors: Goldenberg Benjamin Adam , Gill Sharlene 
Published: February 2017

365 Background: Resection of isolated metastases in good performance status patient (pts) has increasingly become an accepted standard of care. While resection of hepatic and pulmonary metastases from selected cancers such as CRC and RCC have supportive evidence, the safety and effectiveness of pancreatic resections for metastases from these same tumour sites is not as well established. We aim to identify the optimal assessment and selection criteria which would best predict a favourable outcome from pancreatic metastatectomy. Methods: A prospective pathology database was used to identify pts who underwent partial or total pancreatectomy for solid tumour metastases to the pancreas between Sept 2000 to May 2013. Demographic, histologic, surgical and survival data was collected and analyzed using descriptive statistics. Results: 19 pts were identified and included. Follow-up time ranged from 5 months to 8 years. Most common primary sites were RCC (42%,) CRC (11%) and GIST (11%). Favourable outcome, defined as an event-free survival greater than 12 mos from pancreatectomy, was observed in 63% (12/19) and was associated with a higher proportion of RCC (50% vs 14%), pancreas as M1 presentation (58% vs 43%), longer time from presentation to resection (median 5mos vs 2mos), multidisciplinary conference (MDC) review (33% vs 14%) and preop PET (42% vs 14%). No differences were observed by age or gender. Median postoperative length of stay was 22.1 days. Conclusions: Resection of pancreatic metastases remains a rare indication. Given the morbidity and extended LOS associated with pancreatectomy, careful patient selection is required. In this small retrospective series, favourable outcomes were more frequently associated with RCC primary, delayed resection, pre-op MDC and PET staging. Multicentre surgical registries would enhance future analysis and better guide patient selection.
Validation of hepatectomy for elderly patients with hepatocellular carcinoma.
Authors: Kishida Norihiro , Hibi Taizo , Itano Osamu , Shinoda Masahiro , Kitago Minoru , Yagi Hiroshi , Abe Yuta , Kitagawa Yuko 
Published: February 2017

380 Background: Hepatectomy for hepatocellular carcinoma (HCC) and its outcomes in the elderly population have yet to be defined. We aimed to validate our current strategy to determine surgical indication regardless of age. Methods: A single-center, retrospective cohort study was conducted for 104 patients who underwent hepatectomy for HCC from 2005 to 2010. The patients were divided into 2 groups according to age; i.e. <75 years (non-elderly cohort; n=82) and ≥75 years (elderly cohort; n=22), and short-/long-term results were compared. Results: In the elderly cohort, the prevalence of ECOG performance status 1 preoperatively (p<0.001) and HCV or non-HBV/non-HCV were higher than in the non-elderly cohort (p=0.04). Otherwise, patient/tumor characteristics were comparable between the 2 groups. The elderly cohort suffered postoperative complications more frequently (42% vs. non-elderly, 16%, p=0.01) but the length of hospital stay was equivalent. Ninety-day mortality occurred in 1 case each (elderly, respiratory failure; non-elderly, liver failure; p=0.38). During a median follow-up period of 47 months, unadjusted 5-year disease-free and overall survivals were comparable per log-rank comparison (elderly, 25% and 80% vs. non-elderly, 33% and 79%, p=0.96 and 1.00, respectively). Cox univariate analyses on recurrent HCC showed hypertension, Child-Pugh grade B, tumor size, recurrent/multiple tumors, preoperative alpha-fetoprotein level, moderate/poor differentiation, portal invasion, intrahepatic metastases, and positive margins to have p values <0.20. After adjustment, the hazard ratio of recurrent HCC at 5 years in the elderly cohort was 0.87 (95% CI, 0.40-1.91; p=0.74). Tumor size, alpha-fetoprotein level, and intrahepatic metastases emerged as independent predictors of diminished 5-year disease-free survival in the entire cohort. Conclusions: Although postoperative complications develop more frequently, hepatectomy in the elderly patients affords comparable short- and long-term prognoses to the non-elderly patients. Surgical strategy for HCC should be based on tumor factors and hepatic reserve and not by age alone. Perioperative management needs to be individualized according to coexisting disorders.
Reinitiating nab-paclitaxel plus gemcitabine in patients with advanced pancreatic cancer.
Authors: Borazanci Erkut , Schroeder Katy , Jameson Gayle S. , Ramanathan Ramesh K. , Von Hoff Daniel D. 
Published: February 2017

381 Background: The recent results of the phase III trial MPACT (Metastatic Pancreatic Adenocarcinoma Clinical Trial) demonstrated an improvement in progression free survival, overall response rate, and overall survival for the combination of nab-paclitaxel plus gemcitabine compared to gemcitabine alone. Methods: A retrospective analysis of patients with advanced pancreatic adenocarcinoma was undertaken to determine the disease control rate (CR+PR+SD ≥ 16 weeks) in patients who had received prior nab-paclitaxel plus gemcitabine and were retreated with nab-paclitaxel plus gemcitabine again after receiving other interval therapies. Results: Nine patients were identified. The median time between treatments of nab-paclitaxel plus gemcitabine was 7.67 months (range 2.53 to 54.03 months). The regimens used in between treatments of nab-paclitaxel plus gemcitabine were 5FU-based in 8 of the 9 patients, with the other patient undergoing temozolomide, cetuximab, and sorafenib sequential treatment. Five of the nine patients received repeat nab-paclitaxel plus gemcitabine > 6 months after their initial nab-paclitaxel/gemcitabine regimen and four of the nine received repeat nab-paclitaxel plus gemcitabine < 6 months after their initial nab-paclitaxel/gemcitabine regimen. The disease control rate seen for the second treatment with nab-paclitaxel plus gemcitabine was 44% (four of nine patients). Two of these patients received repeat nab-paclitaxel plus gemcitabine < 6 months after their first nab-paclitaxel plus gemcitabine regimen and two of these patients received repeat nab-paclitaxel plus gemcitabine > 6 months after their first nab-paclitaxel plus gemcitabine regimen. Three of nine patients (33%) had treatment a third time with nab-paclitaxel plus gemcitabine, with 2 of 3 of these patients having disease control. As of September 1st, 2013, two of nine patients are still undergoing repeat nab-paclitaxel plus gemcitabine therapy. Conclusions: Nab-paclitaxel plus gemcitabine can be an effective repeat regimen in patients with advanced pancreatic adenocarcinoma. In this very small series, the time between reinitiation of nab-paclitaxel plus gemcitabine appears to not play a role in disease control rate.
Chemoradiation (CRT) followed by surgery and adjuvant capecitabine plus oxaliplatin (CAPOX) compared with induction CAPOX followed by concomitant CRT and surgery for locally advanced rectal cancer: Results of the Spanish GCR-3 randomized phase II trial after a median follow-up of 5 years.
Authors: Fernandez-Martos Carlos , Pericay Carles , Aparicio Jorge , Safont Maria Jose , Salud Antonia , Massuti Bartomeu , Alonso Vicente , Vera Ruth , Escudero Pilar , Martin-Richard Marta , Bosch Carlos , Maurel Juan 
Published: February 2017

383 Background: In locally advanced rectal cancer in contrast with the conventional approach the administration of chemotherapy prior to chemoradiation (CRT) and surgery allow most patients receive planned treatment with better toxicity profile without compromising the pCR and complete resection rates, as we previously demonstrated. (J Clin Oncol 28:859-865, 2010). We now report on the 5-year outcomes of this randomized trial. Methods: Patients with distal or middle third, T3-T4 and/or N+ rectal adenocarcinoma selected by Magnetic Resonance +/- endorectal ultrasound, were randomly assigned to arm A—preoperative CRT followed by surgery and four cycles of postoperative adjuvant capecitabine and oxaliplatin (CAPOX)—or arm B— four cycles of CAPOX followed by CRT and surgery. The following five-year outcomes were assessed: the cumulative incidence of local-regional (LRF) and distance failure (DF), disease-free (DFS) and overall (OS) using the Kaplan-Meier method. Results: Of 108 patients accrued, 52 were randomly assigned to arm A and 56 to arm B. According to intention-to-treat analysis with a median follow-up time of 69.5 months, the 5-years DFS rates were 64.3% (95% CI, 49% to 76%) in arm A and 60.7% (95 CI, 46% to 72%) in arm B (P=0.73). The 5-year cumulative incidences of local relapse were 1.9 % and 7.1% in A and B arms respectively (P= 0.36). No significant differences were detected for 5-year cumulative incidence of distant metastases (21.1% and 23.2%; P = 0.80) and 5-years overall survival (77.9% and 74.7%; P= 0.64). Conclusions: Both approaches yield similar 5-y outcomes. Because of the associated acute toxicity sparing and better compliance with induction CT compared with adjuvant CT, integrating effective systemic therapy prior to CRT and surgery may well be the next step in phase III testing versus the standard strategy to capture meaningful differences in DFS.