bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of outcomes in patients with locally advanced pancreatic adenocarcinoma treated with stereotactic body radiation therapy (SBRT) versus conventionally fractionated radiation: An analysis of the National Cancer Database.
Authors: Zhong Jim , Patel Kirtesh R. , Switchenko Jeffrey M. , Gillespie Theresa Wicklin , Cassidy Richard John , Kooby David A. , Landry Jerome Carl 
Published: March 2017

366 Background: As systemic therapy has improved for locally advanced pancreatic cancer (LAPC), efforts to improve local control have become critical. While conventionally fractionated radiation therapy (CFRT) has more recently shown a limited role in LAPC, stereotactic body irradiation (SBRT) is an emerging approach that delivers higher doses of radiation therapy, to small volumes, over a much shorter period of time. With no studies to date comparing SBRT to CFRT for LAPC, we utilized the National Cancer Database (NCDB) to evaluate these two modalities. Methods: Using the NCDB, patients with AJCC clinic cT2-4, N0-1, M0 adenocarcinoma of the pancreas diagnosed from 2004-2013 were analyzed. Radiation therapy delivered at 2 Gy per fraction or less was deemed CFRT, and 4 Gy or more per fraction was considered SBRT to allow inclusion of practice variations. Kaplan-Meier, log-rank test, and multivariable Cox proportional hazards regression were performed with overall survival (OS) as the primary outcome. Propensity score matching was employed to reduce treatment selection bias. Results: Among 8,450 patients, 7,819 (92.5%) were treated with CFRT, and 631 (7.5%) underwent SBRT. The median dose per fraction and number of fractions for CFRT and SBRT cohorts were 1.8 Gy per fraction in 28 fractions and 8 Gy per fraction in 5 fractions, respectively. Using propensity score matching, 988 patients were matched, with 494 patients in each cohort. Within the propensity-matched cohorts, the median OS was higher with SBRT (13.9 vs. 10.7 months), and 2-year OS of 21.5% and 15.9% for the SBRT and CFRT groups, respectively ( p = 0.0014). Multivariable analysis confirmed SBRT was a significant predictor for OS (Hazard ratio:0.84; 95% confidence interval: 0.75-0.93, p = 0.001). Additionally, pancreatoduodenectomy, low comorbidity index, chemotherapy use, and node negative disease also positively impacted survival. Conclusions: SBRT appears to be associated with an improved OS compared to CFRT for LAPC. Further prospective studies investigating these hypothesis-generating results are warranted.
Evaluating associations of diabetes, insulin use, and BMI with efficacy in patients with resected pancreatic cancer: An ancillary analysis of NRG Oncology/RTOG 9704.
Authors: Hong Theodore S. , Winter Kathryn A. , Fuchs Charles S. , Regine William , Abrams Ross A. , Safran Howard , Hoffman John Parker , Benson Al Bowen , Macdonald John S. , Kasunic Timothy , Strauss James Fredric , DiPetrillo Thomas A. , Stella Philip J. , Chen Yuhchyau , Plastaras John Peter , Crane Christopher H 
Published: March 2017

369 Background: Diabetes mellitus (DM) has been linked to poor prognosis in pancreatic cancer in numerous retrospective datasets, potentially due to higher levels of insulin and insulin-like growth factor increasing cellular proliferation. Additionally, the hyperglycemic state as well as obesity may lead to a pro-inflammatory state that may enhance tumor progression and metastases. In this analysis, the prognostic significances of diabetes, insulin use, and BMI are evaluated in a prospective, randomized trial of resectable pancreatic ductal adenocarcinoma. Methods: As previously reported, RTOG 9704 pts with resected pancreatic cancer were randomized to 5-fluorouracil (5-FU) or gemcitabine (Gem), given pre and post radiation (RT). Pts in both arms received RT to 50.4 Gy with 5-FU. DM and insulin use were collected on the RTOG 9704 CRFs. BMI was dichotomized as normal/underweight vs. overweight/obese. Overall survival (OS) and disease-free survival (DFS) were estimated by Kaplan-Meier method and variable levels were compared using log-rank test. Cox models were used for multivariable analyses. Results: 538 pts were enrolled from 1998-2002. 238 pts were eligible with analyzable diabetes and insulin use data, in addition to surgical pathology, and CA19-9 data. 32% and 35% of pts in the 5-FU and Gem arms, respectively, had DM. Of which, 24% and 19% used insulin in the 5-FU and Gem arms, respectively. 55% were overweight/obese. The 4 yr OS was 25% (95% CI: 18, 32) in pts with no diabetes, vs. 18% (10, 27) with DM (HR = 1.3 [0.9, 1.7]; p = 0.11). The 4-yr DFS was 14% (9, 20) in pts with no diabetes, vs. 9% (4, 16) with diabetes (HR = 1.2 [0.9, 1.5]; p = 0.31). Neither insulin use nor BMI was univariately associated with OS or DFS. On multivariate analysis, including nodal status, CA19-9, and other variables, DM, insulin use, and BMI were not associated with OS or DFS. Conclusions: DM, insulin use, and BMI were not associated with OS in pts with resected pancreatic cancer treated with adjuvant chemotherapy and chemoradiation. Node involvement and CA19-9 remain the most significant predictors of OS. Supported by NCI grants U10CA180868, U10CA180822, UG1CA189867 and Eli Lilly Clinical trial information: NCT00003216.
Liver resection for hepatocellular carcinoma associated with hepatic vein invasion: A Japanese nationwide survey.
Authors: Kokudo Takashi , Hasegawa Kiyoshi , Matsuyama Yutaka , Takayama Tadatoshi , Izumi Namiki , Kadoya Masumi , Kudo Masatoshi , Kubo Shoji , Sakamoto Michiie , Nakashima Osamu , Kumada Takashi , Kokudo Norihiro 
Published: March 2017

371 Background: Because of the rarity of hepatic vein tumor thrombus (HVTT), compared with portal vein tumor thrombus (PVTT), in patients with hepatocellular carcinoma (HCC), little is known about this disease entity. The aim of this study was to evaluate the prognosis of each treatment modality for HVTT through an analysis of data collected in a Japanese nationwide survey. Methods: We analyzed data for 1,021 Child-Pugh A HCC patients with HVTT without inferior vena cava invasion registered between 2000 and 2007. Of these patients, 540 patients who underwent liver resection (LR) and 481 patients who received other treatments were compared. The propensity scores were calculated and we successfully matched 244 patients (52.5% of the LR group). Results: The median survival time (MST) in the LR group was 2.89 years longer than that in the non-LR group (4.47 years vs 1.58 years; P < 0.001) and 1.17 years longer than that in the non-LR group (2.93 years vs 1.76 years; P = 0.009) in a propensity score-matched cohort. After curative resection, the MSTs were similar between patients with HVTT in the peripheral hepatic vein and those with HVTT in the major hepatic vein (4.85 years vs 4.67 years; P = 0.974). In the LR group, the postoperative 90-day mortality rate was 3.4% (16patients). In patients without PVTT, the MST was significantly better than that in patients with PVTT (5.67 years vs. 1.88 years; P < 0.001). Conclusions: LR is associated with a good prognosis in HCC patients with HVTT, especially in patients without PVTT.
Dose escalation in locally advanced pancreatic cancer patients receiving chemoradiotherapy.
Authors: Chung Seung Yeun , Chang Jee Suk , Lee Byung Min , Lee Kyong Joo , Song Si Young , Seong Jinsil 
Published: March 2017

372 Background: In locally advanced pancreatic cancer, radiotherapy (RT) is an effective treatment modality, but challenged by conflicting results. Now, in the era of intensity-modulated radiation therapy (IMRT), dose escalation is possible without increasing the dose to organs-at-risk. We investigated whether RT dose escalation would improve treatment outcomes without increasing severe toxicity. Methods: From 2005 to 2015, a total of 497 locally advanced - including both borderline resectable and unresectable - pancreatic cancer patients who received neoadjuvant or definitive chemoradiotherapy were included. A total of 281 (56.5%) patients received 3D conformal RT and 216 (43.5%) patients received IMRT. Most common dose scheme for IMRT was 58.42 Gy in 23 fractions (EQD2 61.05 Gy). Patients were divided into two groups; < 61 Gy group (n = 345) and ≥ 61 Gy group (n = 152). Overall survival (OS), progression-free survival (PFS), local failure-free rate (LFFR), distant failure-free rate (DFFR) and toxicity rates were assessed. Results: At a median follow-up time of 14.1 months (range, 2.3-128.5 months), OS, PFS, LFFR, and DFFR rates were significantly higher in ≥ 61 Gy group. The 1-year OS rates were 74.7% and 60.6% (p = 0.001) and 1-year PFS rates were 46.2% and 30.9% (p < 0.001), for ≥ 61 Gy and < 61 Gy group, respectively. The 1-year LFFR was 86.9% and 70.9% (p = 0.001) and 1-year DFFR was 56.4% and 45.8% (p = 0.007), respectively. After multivariate analysis, ≥ 61 Gy group remained a favorable significant factor for OS (p = 0.019), PFS (p = 0.001), LFFR (p = 0.004), and DFFR (p = 0.008). When 152 patients in each group were matched by propensity score matching, ≥ 61 Gy group still showed higher OS (p = 0.011), PFS (p = 0.016), and LFFR (p = 0.002), but not DFFR (p = 0.205). There was no acute gastrointestinal toxicity higher than Grade 3 in both groups. Late toxicity rates were also similar, with RT-related duodenal and gastric hemorrhage ( ≥ Grade 3) in 19 patients (5.5%) in < 61 Gy group and 7 patients (4.6%) in ≥ 61 Gy group. Conclusions: Patients who received higher RT dose showed not only improved PFS and LFFR but improved OS without an increase in severe toxicity. Dose escalation via IMRT is recommended for RT in locally advanced pancreatic cancer patients.
Prognostic significance of chromogranin A in small pancreatic neuroendocrine tumors.
Authors: Raoof Mustafa , Jutric Zeljka , Melstrom Laleh Golkar , Warner Susanne , Woo Yanghee , Fong Yuman , Singh Gagandeep 
Published: March 2017

375 Background: Theincidence of non-functional pancreatic neuroendocrine tumors (PNETs) < 2 cm is rising. The biologic behavior of these tumors is variable and therefore their management remains controversial. We hypothesized that chromogranin A (CgA) levels are prognostic in these patients and may help guide management. Methods: Patients with PNETs measuring < 2 cm, without distant metastases were identified from the National Cancer Database (NCDB) over a ten-year period (2004-2014). Patients were categorized as CgA high (> 36.4 ng/ml) or CgA low (<36.4 ng/ml), and those lacking data on CgA levels were excluded from the study. Univariate and multivariate analyses were performed using Cox proportional hazards model. Results: Of the 445 eligible patients, 149 (33.5%) were CgA Low and 296 (66.5%) were CgA High. Median CgA level was 71 (Inter-quartile range, IQR 24-294) ng/ml. On multivariate analysis, CgA levels independently predicted overall survival after controlling for tumor size, grade, clinical nodal status and academic status of the facility (p = 0.001). At a median follow up of 26.5 months there were no deaths in the CgA Low group whereas 8% of the patients in CgA High group had died (p = 0.0068). Only CgA High patients benefited from surgical resection (HR 0.31, 95% CI 0.11-0.86, p = 0.025). Conclusions: Serum CgA levels can be incorporated in surgical decision making for patients with small PNETs. Patients with a high CgA should be strongly considered for resection.
A propensity-matched analysis of laparoscopic versus open distal pancreatectomy for pancreatic adenocarcinoma.
Authors: Raoof Mustafa , Dumitra Sinziana , Ituarte Philip HG , Woo Yanghee , Warner Susanne , Singh Gagandeep , Fong Yuman , Melstrom Laleh Golkar 
Published: March 2017

376 Background: Laparoscopic-assisted distal pancreatectomy (LDP) has improved perioperative outcomes over open distal pancreatectomy (ODP). Concerns regarding failure to achieve proper oncologic resection and compromised survival remain. Methods: Using the National Cancer Database (NCDB), we analyzed patients undergoing distal pancreatectomy for resectable pancreatic adenocarcinoma over a four-year period (2010-2014). Propensity score nearest-neighbor 1:1 matching (PSM) was performed between LDP and ODP patients based on age, sex, race, insurance, hospital volume, comorbidities, T-stage, N-stage, grade, neoadjuvant therapy, adjuvant therapy. Primary outcome was overall survival. Results: Of the 1,947 eligible patients, 605 (31%) underwent LDP. After PSM two well-balanced groups of 544 patients each were analyzed. There was a trend towards improved overall survival (OS) in patients undergoing LDP as compared to ODP (HR: 0.83, 95% CI 0.68-1.0; Median OS 29 vs. 23 months, p = 0.06). Patients undergoing ODP had a higher margin positive rate compared to those undergoing LDP (21.1% vs. 14.9%, p-value = 0.007). Overall conversion rate was 27%. Patients undergoing ODP had comparable outcomes to LDP in regards to median time to chemotherapy (50 vs. 48 days, p-value = 0.96); median nodes examined (12 vs. 12, p-value = 0.61); 30-day mortality (1.6% vs. 1.1%, p-value = 0.43); 90-day mortality (3.5% vs. 2.4%, p-value = 0.28); 30-day readmission rate (8.6% vs. 9.4%, p-value = 0.67). However, the median length of stay was shorter in the LDP group (6 vs. 7 days, p = 0.0001). Conclusions: In the absence of randomized trials, this is the largest comparative study demonstrating LDP as an acceptable alternative ODP, associated with a lower margin positive rate and shorter length of stay, and with no detriment in long term survival.
Propensity score matched analysis of neoadjuvant therapy for resectable pancreatic cancer.
Authors: Meredith Kenneth L , Huston Jamie , Patel Anjan Jayantilal , Brown Richard H. , Kayali Fadi , Koehler Kevin , Shridhar Ravi 
Published: March 2017

381 Background: Neoadjuvant therapy (NT) for resectable pancreatic cancer continues to be debated. There is little data to demonstrate survival benefit over patients who were treated with up front surgery (UFS) vs NT. We sought to examine the impact of neoadjuvant chemotherapy (NCT), neoadjuvant chemoradiation (NCRT), and UFS on survival in pancreatic cancer patients. Methods: The NCDB was accessed to identify patients with pancreatic adenocarcinoma. Propensity score matching (PSM) was performed against age, tumor size, margin status, and institutional surgery volume. Patient characteristics (continuous and categorical variables) were compared using Mann-Whitney U, Kruskal Wallis and Pearson’s Chi-square test as appropriate. Survival analyses were performed using the Kaplan-Meier method. Multivariable cox proportional hazard models (MVA) were developed to identify predictors of survival. All statistical tests were two-sided and α < 0.05 was considered significant. Results: After PSM, 5,034 patients (UFS 2,517; NT 2,517: 1,143 NCT and 1,374 NCRT) were included in the analysis. There was no difference in age, tumor size, or grade among cohorts. The mean nodes positive were 1.6 ± 2.6 in NT and 2 ± 3.3 in UFS, p = 0.02. In the pre-matched cohort R0 resections were performed in 75.9% UFS, 82.9% NCRT, and 79.6% NCT, p < 0.001. The median and 5 year survival for NCT, NCRT and UFS was 28.6 months and 25.2%, 25.7 months and 22.2%, and 21.3 months and 21.7%, p < 0.001. Adjuvant therapy (chemotherapy (CT) or CRT) in the UFS did demonstrate a survival benefit 22.5 months vs 18.6 months, p < 0.001, however this did not benefit NCT or NCRT, p = 0.8 and p = 0.8 respectively. Additionally survival in the UFS with adjuvant therapy either CT or CRT was still decreased compared to either NCT or NCRT, p < 0.001 and p = 0.001 respectively. MVA demonstrated that age, T-stage, lymph nodes positive, R0 resection, grade, NCT and NCRT were predictors of survival. Conclusions: Neoadjuvant therapy improves survival in resectable pancreatic cancer patients. NCT and NCRT demonstrated survival benefit compared to UFS even with adjuvant therapy. Patients with resectable pancreatic cancer should be considered for neoadjuvant therapy.
Up-titration of sorafenib for hepatocellular carcinoma: Impact on duration of exposure and cost.
Authors: Kaplan David Edward , Yu Shun , Taddei Tamar H. , Reiss Kim Anna , Mehta Rajni , D'Addeo Kathryn , Aytaman Ayse , Hunt Kristel , Fox Rena , Baytarian Michelle , Valdarrama Adriana ,   VOCAL Study Group
Published: March 2017

385 Background: Few data exist how sorafenib starting dose impacts duration of exposure and cost of sorafenib therapy for patients with HCC. Methods: HCC patients exposed to sorafenib, initial doses, number of sorafenib fills, and medication exposure days were identified from the VA CDW using ICD9 codes and pharmacy records. ICD9 codes, CPT codes, AUDIT-C surveys and laboratory tests were utilized to characterize underlying liver disease, calculate Child-Turcotte-Pugh (CTP) and MELD scores. Two abstractors achieved 100% chart verification of tumor number, size, MVI/EHS on imaging proximate to sorafenib to quantify Barcelona Clinic Liver Cancer (BCLC) stage and to determine the provider specialty initiating sorafenib. Results: 2292 patients with BCLC B-C HCC, CTP A cirrhosis with ECOG PS ≤ 2 prescribed sorafenib for HCC between 2007 and 2015 were included in this interim analysis. Median age was 62; 98.8% were male, 61.8% white/26.0% black; Pre-sorafenib BCLC B-43%/C-57%. Prescription at full-dose became less common over 2007-2015, dropping from 80% to 48%. First-dose up-titration was more commonly done by hepatologists (21% vs. 4.5%, p < 0.0001), but oncologists were more likely to up-titrate at the second prescription (8.9% vs. 3.8%, p < 0.001). Overall, 38% of first sorafenib prescriptions were initiated at doses below 800mg/day; 43% were up-titrated whereas 57% never up-titrated. Patients starting at < 800 mg/d received fewer total pills (median 284 vs. 360, p = 0.008) but a greater number of prescription fills (median 4 vs. 3, p < 0.0001) and longer exposure duration (median 120 vs 90 days, p = 0.0012) at lower total cost (median $8,143 vs $9,685, p < 0.0001). Median overall survival for those starting < 800mg/d was not significantly different from full dose initiators (median 284 vs. 292 days, p = 0.33). Conclusions: Initiation of sorafenib < 800mg/d was associated with lower pill utilization, but longer exposure duration and equivalent survival at lower cost. Starting at a lower dose with uptitration may select patients with a higher likelihood of sustained benefit and improve cost-effective utilization of resources. This approach should be tested prospectively.
TGF-B1 inhibition with losartan in combination with FOLFIRINOX (F-NOX) in locally advanced pancreatic cancer (LAPC): Preliminary feasibility and R0 resection rates from a prospective phase II study.
Authors: Murphy Janet E. , Wo Jennifer Yon-Li , Ferrone Cristina , Jiang Wenqing , Yeap Beow Y. , Blaszkowsky Lawrence Scott , Kwak Eunice Lee , Allen Jill N. , Clark Jeffrey W. , Faris Jason Edward , Zhu Andrew X. , Goyal Lipika , Mamon Harvey J. , Lillemoe Keith D , Ryan David P. , DeLaney Thomas F. , Fernandez-del Castillo Carlos , Boucher Yves , Hong Theodore S. 
Published: March 2017

386 Background: F-NOX is utilized in LAPC due to improved response over gemcitabine, with theoretical potential for curative resection. However the response rate remains well below 50%. Preclinical data suggest that inhibition of the renin-angiotensin system with losartan reduces the activity of TGF-B1, enhancing intratumoral penetration of chemotherapy by remodeling desmoplastic stroma and improving vascular perfusion. In this study, we evaluate the feasibility of adding losartan to F-NOX in LAPC. Methods: Pts ECOG PS 0-1 with LAPC (NCCN criteria) were enrolled in a single institution, NCI-sponsored phase II study (NCT01821729). Pts received F-NOX/losartan for 8 cycles. If the tumor was radiographically resectable after chemotherapy, pts received short-course chemoradiation (CRT) in 5 fractions (protons 25 GyE, capecitabine 825 mg/m2 bid). If it was still abutting vasculature, pts received CRT to 50.4 Gy with a vascular boost to 58.8 Gy. The primary endpoint was proportion of pts remaining progression-free after 8 cycles of F-NOX/losartan. Results: 32 pts were enrolled from 8/2013 to 6/2016. One pt withdrew prior to treatment, 6 pts are still receiving F-NOX/losartan or CRT. 25 were included in this analysis. Median age was 62y (46-75). Median tumor size was 42mm (22-68). Tumor was in the head of the pancreas in 16 (64%) pts. Of evaluable pts, 18 (72%) completed F-NOX/losartan followed by CRT. Reasons for discontinuation included losartan intolerance (3), failure to thrive (2), investigator discretion (1), and progression (1). Grade 3 or greater toxicity occurred in 11 (40%) pts, including diarrhea (4, 16%), thrombocytopenia (3, 12%), nausea (3, 12%), neutropenia (2, 8%), and febrile neutropenia (1, 4%). Two pts (8%) had short course CRT, 16 (64%) had long course CRT. In evaluable pts, 4 remained unresectable while one pt had R1 resection. R0 resection was achieved in 13 (52%). Conclusions: Based on the low discontinuation rate of the F-NOX/losartan combination, it met criteria for feasibility. The high R0 resection rate in the feasibility cohort has prompted expansion as a phase II study with an R0 resection endpoint. Clinical trial information: NCT01821729.
Proton beam therapy for liver cancer is well tolerated: Outcomes from the Proton Collaborative Group REG001-09 trial.
Authors: Chuong Michael David , Apisarnthanarax Smith , Hartsell William F. , Larson Gary L. , Tsai Henry K. , Rossi Carl , Vargas Carlos E. 
Published: March 2017

389 Background: The liver is one of the most radiosensitive organs, making radiation therapy (RT) for liver tumors extremely challenging. RT is appropriate only for a minority of liver patients with limited tumor burden; a reduction in the prescribed radiation dose may be needed to lower the probability of radiation-induced liver disease especially in the presence of cirrhosis. Proton beam therapy (PBT) delivers less dose to the liver than photon therapy and is expected to reduce toxicity while also permitting safe dose escalation for some patients with liver tumors. Methods: The Proton Collaborative Group REG001-09 trial (NCT01255748) prospectively collects data for PBT patients with a variety of cancer types. To better understand treatment details and outcomes associated with liver PBT, patients enrolled on the PCG registry trial from 5 institutions who received liver PBT for any cancer between 2012 and 2016 were analyzed. Results: A total of 43 liver cancer patients were included, most with hepatocellular carcinoma (48.8%) or cholangiocarcinoma (25.6%). The vast majority did not have surgery at any time (86%). Most were treatment naive prior to PBT; 2 previously had RT and 8 had prior chemotherapy (mostly cholangiocarcinoma patients). The median total prescribed PBT dose was 58.05 Gy(RBE) (range 21.7-67.5). The median number of prescribed fractions was 15 (range 12-37). PBT was delivered to only the liver in 90.7% of patients; inclusion of lymph nodes was rare. Uniform scanning was used in 26 (72.1%) and pencil beam scanning in 2 patients (4.7%); the delivery technique used for the remaining patients was unknown (23.2%). With median follow up of 4.4 months (range 1.3-17.9), 3 patients (7%) had an intrahepatic recurrence, 2 patients (4.6%) developed distant metastasis, and 10 patients (23.3%) died. No grade 3 or higher toxicity was reported although 17 patients (39.5%) had grade 2 toxicity predominantly fatigue, anorexia, nausea, or vomiting. Conclusions: Although longer follow up is needed to assess late toxicities as well as disease control, early outcomes from the PCG registry trial for liver cancer patients shows that predominantly hypofractionated PBT has a very favorable acute toxicity profile.