William C. Conway

Preoperative Modified FOLFIRINOX Treatment Followed by Capecitabine-Based Chemoradiation for Borderline Resectable Pancreatic Cancer: Alliance for Clinical Trials in Oncology Trial A021101

IMPORTANCE Although consensus statements support the preoperative treatment of borderline resectable pancreatic cancer, no prospective, quality-controlled, multicenter studies of this strategy have been conducted. Existing studies are retrospective and confounded by heterogeneity in patients studied, therapeutic algorithms used, and outcomes reported. OBJECTIVE To determine the feasibility of conducting studies of multimodality therapy for borderline resectable pancreatic cancer in the cooperative group setting. DESIGN, SETTING, AND PARTICIPANTS A prospective, multicenter, single-arm trial of a multimodality treatment regimen administered within a study framework using centralized quality control with the cooperation of 14 member institutions of the National Clinical Trials Network. Twenty-nine patients with biopsy-confirmed pancreatic cancer preregistered, and 23 patients with tumors who met centrally reviewed radiographic criteria registered. Twenty-two patients initiated therapy (median age, 64 years [range, 50-76 years]; 55% female). Patients registered between May 29, 2013, and February 7, 2014. INTERVENTIONS Patients received modified FOLFIRINOX treatment (85 mg/m2 of oxaliplatin, 180 mg/m2 of irinotecan hydrochloride, 400 mg/m2 of leucovorin calcium, and then 2400 mg/m2 of 5-fluorouracil for 4 cycles) followed by 5.5 weeks of external-beam radiation (50.4 Gy delivered in 28 daily fractions) with capecitabine (825 mg/m2 orally twice daily) prior to pancreatectomy. MAIN OUTCOMES AND MEASURES Feasibility, defined by the accrual rate, the safety of the preoperative regimen, and the pancreatectomy rate. RESULTS The accrual rate of 2.6 patients per month was superior to the anticipated rate. Although 14 of the 22 patients (64% [95% CI, 41%-83%]) had grade 3 or higher adverse events, 15 of the 22 patients (68% [95% CI, 49%-88%]) underwent pancreatectomy. Of these 15 patients, 12 (80%) required vascular resection, 14 (93%) had microscopically negative margins, 5 (33%) had specimens that had less than 5% residual cancer cells, and 2 (13%) had specimens that had pathologic complete responses. The median overall survival of all patients was 21.7 months (95% CI, 15.7 to not reached) from registration. CONCLUSIONS AND RELEVANCE The successful completion of this collaborative study demonstrates the feasibility of conducting quality-controlled trials for this disease stage in the multi-institutional setting. The data generated by this study and the logistical elements that facilitated the trials completion are currently being used to develop cooperative group trials with the goal of improving outcomes for this subset of patients. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01821612.

Evaluation of Rural vs Urban trauma patients served by 9-1-1 emergency medical services

Importance Despite a large rural US population, there are potential differences between rural and urban regions in the processes and outcomes following trauma. Objectives To describe and evaluate rural vs urban processes of care, injury severity, and mortality among injured patients served by 9-1-1 emergency medical services (EMS). Design, Setting, and Participants This was a preplanned secondary analysis of a prospective cohort enrolled from January 1 through December 31, 2011, and followed up through hospitalization. The study included 44 EMS agencies transporting to 28 hospitals in 2 rural and 5 urban counties in Oregon and Washington. A population-based, consecutive sample of 67 047 injured children and adults served by EMS (1971 rural and 65 076 urban) was enrolled. Among the 53 487 patients transported by EMS, a stratified probability sample of 17 633 patients (1438 rural and 16 195 urban) was created to track hospital outcomes (78.9% with in-hospital follow-up). Data analysis was performed from June 12, 2015, to May 20, 2016. Exposures Rural was defined at the county level by 60 minutes or more driving proximity to the nearest level I or II trauma center and/or rural designation in the Centers for Medicare & Medicaid Services ambulance fee schedule by zip code. Main Outcomes and Measures Mortality (out-of-hospital and in-hospital), need for early critical resources, and transfer rates. Results Of the 53 487 injured patients transported by EMS (17 633 patients in the probability sample), 27 535 were women (51.5%); mean (SD) age was 51.6 (26.1) years. Rural vs urban sensitivity of field triage for identifying patients requiring early critical resources was 65.2% vs 80.5%, and only 29.4% of rural patients needing critical resources were initially transported to major trauma centers vs 88.7% of urban patients. After accounting for transfers, 39.8% of rural patients requiring critical resources were cared for in major trauma centers vs 88.7% of urban patients. Overall mortality did not differ between rural and urban regions (1.44% vs 0.89%; P = .09); however, 89.6% of rural deaths occurred within 24 hours compared with 64% of urban deaths. Rural regions had higher transfer rates (3.2% vs 2.7%) and longer transfer distances (median, 97.4 km; interquartile range [IQR], 51.7-394.5 km; range, 47.8-398.6 km vs 22.5 km; IQR, 11.6-24.6 km; range, 3.5-97.4 km). Conclusions and Relevance Most high-risk trauma patients injured in rural areas were cared for outside of major trauma centers and most rural trauma deaths occurred early, although overall mortality did not differ between regions. There are opportunities for improved timeliness and access to major trauma care among patients injured in rural regions.

Su1660 Pre-Operative Lovenox Does Not Increase Blood Loss During Pancreaticoduodenectomy Compared to Heparin

S A T A b st ra ct s Six patients (5%) with conversion to OPD were included in LPD group based on intent-totreat. Daily opioid consumption of the LPD group was significantly less than that of OPD group from POD 2 through POD 5, and total opioid consumption of LPD group was also significantly less (LPD: 5.3 ± 6.4 mg/kg, OPD: 7.3 ± 9.4 mg/kg, P = 0.007). Multivariate analysis revealed that younger age (, 65 years old) (HR 1.89, 95% CI 1.29 2.79, P = 0.001), no preoperative diabetes mellitus (HR 1.74, 95% CI 1.10 2.80, P = 0.01), PD for chronic pancreatitis (HR 2.87, 95% CI 1.18 7.51, P = 0.02), OPD (HR 2.01, 95% CI 1.26 3.27, P = 0.003) and postoperative major complication (Grade III-V) (HR 2.30, 95% CI 1.36 3.91, P = 0.001) were independently associated with increased opioid consumption after PD (total opioid consumption . 6mg/kg). Conclusion: Patients undergoing TLPD have lless opioid consumption compared to those with the open approach. Younger age, absence of diabetes, chronic pancreatitis indication and major postoperative complications are independent predictors of increased opioid consumption. These findings warrant further evaluation as to the potential clinical impact of reduced pain and less opioid consumption on patient-specific advantages including early recovery and better quality of life after pancreaticoduodenectomy.