bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations between county-level general surgeon (GS) and gastroenterologist (GA) density and outcomes for hepatobiliary cancer (HBC).
Authors: Tsang Trevor C. , Cheung Winson Y. 
Published: February 2017

292 Background: Surgical resection is the mainstay of treatment for early, localized HBC. Prior studies consistently show an association between procedure volumes and cancer outcomes, but the impact of surgeon and physician density is unclear. Our aims were to 1) examine the effects of GS and GA density on HBC mortality and 2) compare the relative importance of GS versus GA density on HBC outcomes. Methods: Using county-level data from the Area Resource File, US Census, and National Cancer Institute, we developed both multivariate linear and logistic regression models to determine the effect of GS and GA density on overall HBC mortality between 2002 and 2006, while controlling for cancer incidence, county demographics and socioeconomic factors. Results: In total, 793 counties were analyzed: mean HBC incidence and mortality were 5.89 and 5.34 per 100,000 persons, respectively; 77% were metropolitan; mean GS and GA densities were 10.6 and 3.5 per 100,000 people, respectively. When compared to counties with no GS, those with at least one had a statistically significant decrease in HBC-specific mortality (beta coefficient -.115; p=.001). In contrast, when compared to counties with no GA, those with at least one showed a trend towards lower mortality (beta coefficient -.0677; p=.065). Increasing the county-level density of GS and GA improved outcomes, but increases beyond 10 GS or 4 GA per 100,000 people did not continue to result in significant reductions in HBC mortality; rather, these showed an increase in HBC mortality. Conclusions: Reductions in HBC mortality are more strongly influenced by increasing GS than GA density. There appears to be a ceiling effect at which point increasing GS and GA density does not appear to result in improvements in HBC outcomes. A strategy of allocating healthcare resources and distributing the workforce across counties will optimize outcomes at the population-level.
Association between skin toxicities and treatment outcomes in patients with pancreatic cancer (PC) receiving erlotinib (E): Memorial Sloan-Kettering Cancer Center (MSKCC) experience.
Authors: Alejandro Linh My , Adel Nelly G. , O'Reilly Eileen Mary , Riedel Elyn , Lacouture Mario E. 
Published: February 2017

294 Background: Rash is a common adverse event of E, an epidermal growth factor receptor (EGFR) inhibitor approved for advanced PC. Clinical trial results have shown that E-related rash grade 2 or higher is associated with a survival benefit in PC. We examined the correlation between all grades of rash and overall survival (OS) in PC patients receiving E at MSKCC. Methods: This was a retrospective single-institution study that included a review of all PC patients treated with E between March 1st 2005 and December 15th 2009 at MSKCC. The association of development of rash on OS was examined using a Cox proportional hazards model using development of rash as a time dependent covariate. The associations were examined univariately and after adjusting for gender, race, smoking history, prior lines of treatment for metastatic disease, and chemotherapy. An intervention was defined as a dose change, interruption, discontinuation or medical intervention for rash. Results: N=193 constituted the cohort of analysis. The median age was 64; 116 (60%) were male and 162 (84%) were Caucasian. Most patients (N=111, 58%) did not receive any prior medical treatment for pancreatic cancer. Skin rash occurred in 113 (59%) of patients. The median OS was 6.7 months (95% confidence interval, 5.7-7.9 months). In a univariate analysis, rash was protective compared to no skin rash (Grade 1 HR 0.71; 95% CI 0.50-1.00, Grade 2+ HR 0.57; 95% CI 0.40-0.82; P=0.007). In the multivariate model, rash appeared to have a protective effect on survival, but this was not statistically significant (Grade 1 HR 0.69; 95% CI 0.49-0.97, Grade 2+ HR 0.78; 95% CI 0.48-1.27). Non-medical interventions for rash included dose adjustment (5%), dose interruption (6%) and dose discontinuation (9%). 33 (29%) patients received medical intervention for rash. Conclusions: Our findings suggest that grade 1 or higher E-related rash may be a surrogate for survival. Appropriate symptom interventions are recommended to enhance patient comfort and avoid discontinuation of treatment.
Immediate versus delayed adjuvant chemoradiation for resected pancreatic cancer: An analysis of local control and survival.
Authors: Childs Stephanie Krejcarek , Mamon Harvey J. , Wo Jennifer Yon-Li , Blaszkowsky Lawrence Scott , Fernandez-del Castillo Carlos , Swanson Richard , Wolpin Brian M. , Kwak Eunice Lee , Allen Jill N. , Zhu Andrew X. , Clark Jeffrey W. , Wadlow Raymond Couric , Ryan David P. , Hong Theodore S. 
Published: February 2017

301 Background: Patients with resected pancreatic cancer have a significant risk of both local and distant failures. Because of the importance of chemotherapy (CT) highlighted by recent trials, the ongoing RTOG 0848 delays chemoradiation (CRT) randomization to after 5 cycles of chemotherapy (CT). However, the impact of delaying CRT on LR is unknown. We evaluated the patterns of failure and outcomes for patients treated with immediate vs. delayed CRT. Methods: 174 consecutive patients with resectable pancreas cancer who received post-operative CRT at the Massachusetts General Hospital and Brigham & Women’s Hospital/Dana-Farber Cancer Institute between 1998-2010 were retrospectively reviewed on an IRB approved protocol. CRT was delivered to 50.4 Gy with concurrent 5FU or capecitabine. Patient baseline characteristics, pathologic features, and CA19-9 were obtained. Patients were divided into immediate CRT vs. delayed CRT, defined as receiving any CT prior to CRT. LR was independently re-reviewed and confirmed. LR, PFS, and OS were calculated using the Kaplan-Meier method and groups compared using the log-rank test. Results: Median age was 62 (range, 34-83), 75 were male, and ECOG PS was 0-1 in 95% of patients. Median tumor size was 3 cm, 67% had positive nodes, and 33% had positive margins. Mean pre-operative and post-operative CA 19-9 was 813 U/mL and 19 U/mL, respectively. 123/174 (72%) patients received immediate CRT, of whom 101 received additional chemotherapy (5FU or gemcitabine (GEM)). 51/174 (28%) received delayed CRT, and received a median of 4 cycles of GEM prior to CRT. Median follow-up was 33 months (range, 3.6-67). 6/51 (12%) delayed CRT had LR prior to initiation of CRT. 25/51 in the delayed CRT group had a LR (49%) vs. 35/124 patients (28%) in the immediate CRT group. The 1-year LR rates in the immediate and delayed CRT groups were 18% and 40%, respectively (p=0.0093). There was no difference between immediate or delayed CRT, respectively, in mPFS (12.8 mo vs. 12.2 mo, p=0.6544) or mOS (24.8 mo vs. 26.7 mo, p=0.7163). Conclusions: Delayed radiation is associated with an increased risk of LR, though this did not appear to impact PFS or OS.
Effect of chemoradiation-related lymphopenia on survival in patients with unresectable, locally advanced pancreatic adenocarcinoma.
Authors: Wild Aaron Tyler , Balmanoukian Ani Sarkis , Laheru Dan , Zheng Lei , Tran Phuoc T. , Hacker-Prietz Amy , Yovino Susannah G. , Kumar Rachit , Ziegler Mark A. , Pawlik Timothy M. , Wolfgang Christopher Lee , Grossman Stuart A. , Herman Joseph M. 
Published: February 2017

307 Background: Pancreatic ductal adenocarcinoma (PDA) has been shown to elicit antitumor cell-mediated immune responses. In high grade gliomas, treatment-related lymphopenia has been associated with shorter survival. This study was performed to determine if patients with locally advanced PDA treated with definitive chemoradiation therapy (CRT) develop significant lymphopenia and if this affects overall survival (OS). Methods: A retrospective analysis of patients with locally advanced PDA treated at a single institution with CRT from 1997-2009 was performed. Serial lymphocyte counts were recorded and OS was analyzed as a function of lymphopenia and known prognostic factors. Results: 99 patients met eligibility criteria (≥18 years of age, ECOG performance status 0-2, and had baseline/follow-up lab values measured at our institution). Mean age was 61.6 years (SD, 11.6), 55% were male, mean tumor size 4.1 cm (SD, 1.6), and 97 had stage III disease. Median pre/post-CRT CA19-9 values were 241.5 and 105.2 U/mL, respectively. Total lymphocyte counts were normal in 87% of patients prior to RT. Mean RT dose was 47.3 Gy (SD, 8.2) and concurrent chemotherapy was 5-FU (67%), gemcitabine (20%), taxotere (7%), or none (6%). Chemotherapy dose reduction was necessary in 9%, and 39% required a RT break. Total lymphocyte counts fell to ≤500 cells/mm3 in 51% two months after initiating CRT with a median reduction of 66% from baseline (p<0.0001). Median OS of patients with lymphocyte counts ≤500 cells/mm3 at 2 months was 7.7 months (95% CI, 6.8-8.7) versus 15.4 (95% CI, 11.9-19.0) for patients with >500 cells/mm3 (p<0.001). Univariate analysis additionally revealed that among pre-treatment patient characteristics, only age ≥65 was significantly associated with OS (8.8 vs. 11.4 months; p=0.043). Type of concurrent chemotherapy was not significantly associated with OS. Multivariate analysis revealed a significant association between survival and lymphocyte count (<500 vs. ≥500 cells/mm3) at 2 months post-CRT (HR 3.8, p<0.001). Conclusions: Definitive CRT induced lymphopenia is frequent, severe, and appears to be an independent predictor for OS in patients with locally advanced PDA.
Is survival from resection of pancreatic adenocarcinoma with major arterial involvement any different than venous/minor arterial resection?
Authors: Miura John T. , Pappas Sam G , Gamblin T. Clark , Turaga Kiran 
Published: February 2017

310 Background: Major arterial involvement is considered a contraindication to surgical resection for pancreatic adenocarcinoma (PA). We hypothesized that survival for patients (pts) with T3 or T4 disease with major arterial involvement (SMA/Celiac Axis) undergoing pancreatic resection was worse than those undergoing venous resections. Methods: We included all pts with T3 or T4 PA in the SEER database from 2004-2007. Patients were divided into those involving the portal vein/SMV/GDA/hepatic artery and those involving the SMA and celiac axis. Non-surgical control arm (CA) included pts who were recommended surgery but did not undergo it. Multivariate survival analyses were performed using the cox-proportional hazards model. Results: We identified 571 pts, of whom 323(56%) underwent resection. Median disease specific survival of pts undergoing surgery with SMA, Celiac involvement was 12, 8 vs. 7, 6 months respectively in the CA(p=0.01). Pts undergoing venous resection had a longer survival than those undergoing arterial resection in multivariate models (18 vs. 12 months, p=0.001) Conclusions: Resection for pancreatic adenocarcinoma with major arterial involvement is associated with a poorer survival as compared to those with venous/minor arterial involvement. This study validates the current practice of considering major arterial involvement as a contraindication to resection. [Table: see text]
Meta-analysis of randomized phase II and phase III trials of gemcitabine with/without S-1 in Asian patients with advanced pancreatic cancer.
Authors: Ku Geoffrey Yuyat , Haaland Benjamin , Ioka Tatsuya , Isayama Hiroyuki , Nakai Yousuke , Cheng Ann-Lii , Okusaka Takuji , Lopes Gilberto de Lima 
Published: February 2017

311 Background: Advanced pancreatic cancer (PC) is a virulent disease, where gemcitabine is considered the standard-of-care. A recent phase III evaluation demonstrated superiority of FOLFIRINOX (bolus and infusional 5-fluorouracil (FU), irinotecan, oxaliplatin) in patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) of ≤1. Recently, three studies were presented in abstract form, comparing gemcitabine/S-1 (GS) to gemcitabine. S-1 is a mixture of tegafur (an oral 5-FU prodrug), a dihydropyrimidine dehydrogenase inhibitor and an agent designed to reduce the gastrointestinal toxicity of 5-FU. All three trials demonstrated significant improvements in progression-free survival (PFS) while one study also showed a statistically significant improvement in overall survival (OS). Methods: We performed a meta-analysis of the three trials. Results: Seven hundred and seventy patients were randomized to receive GS vs. gemcitabine; 75% had metastatic disease and 65% had an ECOG PS of 0. GS was associated with superior RR (hazard ratio (HR) 0.348, p=3.06×10-7), PFS (HR 0.64, p=7.26×10-9) and OS (HR 0.79, p=2.47×10-2) compared to gemcitabine. Patients receiving GS were more likely to experience nausea, diarrhea, rash and stomatitis (mostly grade 1/2); neutropenic fever occurred in <2% of patients. One study demonstrated superior quality-of-life for GS. Conclusions: GS should be considered a first-line option for the treatment of advanced PC in Asian patients. This regimen should serve as the reference for future trials and comparison with FOLFIRINOX in patients with ECOG PS ≤1 is warranted.
Dosimetic parameter predicting the hepatic complication after helical tomotherapy for patients with unresectable primary hepatocellular carcinoma.
Authors: Jang HongSeok 
Published: February 2017

324 Background: We evaluated the parameters of radiation-induced liver disease (RILD) and deterioration of the hepatic function in patients with advanced hepatocellular carcinoma (HCC), who were treated with helical tomotherapy. Methods: From April 2009 to October 2010, 32 patients with unresectable primary HCC received hypofractionated radiation therapy using the TomoTherapy Hi-Art (TomoTherapy, Madison, WI, USA) at Seoul St. Mary's Hospital, the Catholic University of Korea. To assess the deterioration of hepatic function, we evaluated the Child-Pugh class (CP class). The gross tumor volume (GTV) were 178.7 ± 216.1 cm3 and the planning target volume (PTV) were 423.1 ± 399.7 cm3. The total dose administered were 50 Gy (range: 32.5-60 Gy) in 10 or 20 fractions (range: 10-24 fractions). We evaluated the clinical parameters for predicting the RILD and the deterioration of the hepatic function (gender, age, ECOG performance saretatus, pretreatment CP class, AJCC stage, pretreatment level of AFP and hepatitis, liver cirrhosis, PVTT and previous treatments) and the dosimetric parameters (GTV, PTV, the non-target liver volume (NTLV). Results: Of 32 patients, we observed that 4 patients (13%) developed RILD after helical tomotherapy. Classical RILD was diagnosed in one patient and non-classical RILD in three patients. In the analysis evaluating the associations between the clinical/dosimetric parameters and the RILD, there was no statistically significant parameter. Of 32 patients, five patients (16%) developed the progression of CP class. In the multivariate logistic regression analysis evaluating the associations between the clinical/dosimetric parameters and the progression of CP class, The NTLV receiving <35 Gy (VBED35) was the only significant parameter associated with the risk of progression of CP class (p = 0.039). Conclusions: The progression of CP class is a dose-limiting toxicity. VBED35 was a significant parameter predicting the risk of the progression of CP class.
Dose-escalated radiotherapy with helical tomotherapy to spine oligometastasis from intrahepatic malignancies.
Authors: Seong Jinsil , Choi Younsun , Kim Jun Won 
Published: February 2017

325 Background: Traditional palliative radiotherapy of 30 Gy in 10 fractions to spine metastases often results in poor local control. This study evaluated the role of high dose helical tomotherapy (HT) to improve local control of spine oligometastasis from intrahepatic malignancies Methods: From 2006 to 2010, 11 hepatocellular carcinoma (HCC) patients and 3 intrahepatic cholangiocellular carcinoma patients were treated with HT for oligometastsis to spine. The gross tumor volume (GTV) was the tumor evident from MRI images fused with simulation CT images. Planning target volume (PTV) encompassed involved vertebral body or 1cm margin to GTV. The spinal cord contour represented a small area within the intradural space. To the adjacent spinal cord volume, 20 Gy dose constraint was used. Mega-voltage computed tomography (MVCT) images were used to maintain setup error within 1 mm. We assessed local control rate after HT for spine metastasis in this retrospective study. Pain response was scored by using a numerical rating scale (from 0 to 10). Results: Spine metastatic lesions were treated with median dose of 40 Gy (range 31-51 Gy) and median 5 Gy per fraction (range 3-6 Gy) to GTV and median dose of 29 Gy (range 22.5-42.5 Gy) and median 3.75 Gy per fraction( range 2.5-5 Gy) to PTV. Median biologically equivalent dose (BED, α/β=10 Gy) was 55.2 Gy (range 45.6-76.8) to GTV. Infield failure rate was 35.7% and outfield failure rate was 78.6%. Ten patients initially accompanied pain with spine metastasis (median NPIS 7.5), and all patients showed pain relief after tomotherapy. Complete relief was shown in 20% of patients and partial relief in 80 % of patients, with median NPIS reduction of 5. The patients treated with BED (α/β=10 Gy) over 56 Gy had no local failure. Median local recurrence free survival (LRFS) was 3 months. In the univariate analysis, BED (α/β=10 Gy) over 56 Gy was a prognostic factor associated with improved LRFS (p=0.008). Conclusions: HT was capable of delivering higher BED to metastatic lesions in close proximity of the spinal cord. Spine metastases from intrahepatic tumors were sensitive to high dose radiation, and BED (α/β=10Gy) higher than 56 Gy could improve local control.
An interim evaluation of efficacy and safety of the combination of panitumumab, gemcitabine, and irinotecan in patients with advanced or metastatic cholangiocarcinoma: A phase II study.
Authors: Sun Weijing , Sohal Davendra , Mykulowycz Kristine , Teitelbaum Ursina R. , Damjanov Nevena , Giantonio Bruce J. , Carberry Mary , Wissel Paul Stephen , Jacobs-Small Mona , O'Dwyer Peter James 
Published: February 2017

328 Background: Cholangiocarcinoma is an aggressive neoplasm. Current chemotherapy approaches suggest that combinations may be superior to single agents in this disease. Over-expression of epidermal growth factor receptor (EGFR) is associated with tumor stage and prognosis. This study was designed to evaluate the efficacy and tolerability of the combination of panitumumab, a monoclonal anti-EGFR antibody, with gemcitabine and irinotecan in patients with advanced and metastatic cholangiocarcinoma. Methods: Pts with advanced unresectable or metastatic cholangiocarcinoma, ECOG PS 0-2, and adequate liver, kidney and bone marrow function were treated with panitumumab (9 mg/kg) on day 1, gemcitabine (1000 mg/m2/100 min) iv and irinotecan (100 mg/m2) iv on days 1 and 8 of a 21-day cycle. Tissue specimens were collected based on availability for future biomarker analyses. The primary objective was to evaluate the 5-month progression-free survival (PFS) rate. The secondary objectives include overall response rate (ORR), overall survival rate (OS) and toxicity of the combination. Results: There have been 24 (of planned 42) pts recruited to the study. Toxicity of the combination was assessed in all enrolled pts. There were no treatment related deaths. The most common gr 3 or higher toxicity was were neutropenia (10 pts [40%]), thrombocytopenia (6 pts, [25%]), skin rash (4 pts [17%]) and diarrhea (3 pts, [12%]). One pt developed a gr 2 infusion reaction, which was considered related to panitumumab. Efficacy was evaluated in 20 pts. Among them, there were 2 CR, 6 PR, and 10 SD (with disease control rate of 90%), and 2 PD (assessed by RECIST criteria). Two pts went on to have surgical resection. Eight pts had ≥ 10 cycles of the therapy, and dose modification/interruption were needed for some of these pts. Conclusions: The data of this on-going study showed encouraging results of the combination of panitumumab with gemcitabine and irinotecan in both tolerability and efficacy. The pre-specified efficacy criteria to continue enrollment were met. Further analysis by biomarker status (KRAS/BRAF/EGFR) is forthcoming.
Single-institution experience with FOLFIRINOX in advanced pancreatic cancer (PC).
Authors: Gunturu Krishna Soujanya , Thumar Jaykumar Ranchodbhai , Hochster Howard S. , Stein Stacey , Yao Xiaopan , Cong Xiangyu , Hahn Carol , Kaley Kristin , Lacy Jill 
Published: February 2017

330 Background: FOLFIRINOX provides clinically significant benefit in advanced PC compared to gemcitabine (Conroy et al. New Engl J Med 2011;364:1817). Despite superior efficacy, toxicities have tempered enthusiasm for FOLFIRINOX and limited its use in full doses. To assess the impact of dose attenuations on toxicity and efficacy, we reviewed our experience with FOLFIRINOX in pts with advanced PC. Methods: We performed a retrospective review of dose, toxicity, efficacy of FOLFIRINOX in all pts with locally advanced unresectable PC (LAPC) and metastatic PC (MPC) treated with FOLFIRINOX at Yale Cancer Center between 06/10 and 06/11. Dose attenuations were at the treating physician’s discretion. All pts received prophylactic pegfilgrastim. Pts were treated until progression, unacceptable toxicity, or surgical resection. Toxicities and efficacy were compared to historical data reported by Conroy. Results: 31 pts with ECOG PS 0 or 1 were treated. Pt characteristics: LAPC 15; MPC 16; median (med) age 60 yrs (range 48-78); male 11; prior chemotherapy 5 (adjuvant 3). Med number of cycles received was 6 (range 1-18). Only 5 pts received full doses of all drugs with cycle 1. Dose reductions with cycle 1 were: IRI 26 pts, OX 10 pts, bFU 10 pts, infusional FU 1 pt. b5FU was omitted in 6 pts. Med relative dose intensities were: OX 88%, IRI 64%, b-FU 57%, infusional FU 100% (compared to OX 78%, IRI 81%, and FU 82% [Conroy]). The % of pts with grade 3 or 4 toxicities was: fatigue or mucositis, 9.6%; dehydration or neutropenia 6.4%; vomiting, thromboembolism, febrile neutropenia, thrombopenia or anemia, 3.2%. Neutropenia (p<0.0001), diarrhea (p<0.03), fatigue (p<0.02) were significantly decreased compared to historical data (Conroy). Response (CR+PR) in 30 evaluable pts was 33% (1 CR, 9 PR, 14 SD, 6 PD) and similar to historical data (31.6%; p 0.21). 2 pts with LAPC underwent resection. Evaluation for OS and PFS is ongoing. Conclusions: Our findings suggest that dose attentuation of FOLFIRINOX, esp IRI and bFU, with prophylactic pegfilgrastim is associated with improved tolerability and equivalent response rate compared to full dose FOLFIRINOX in advanced PC. The impact of dose attenuations on toxicity and efficacy warrants further evaluation in both LAPC and MPC.