Effect of dose-escalation of IMRT for unresectable pancreatic cancer 1 cm away from the luminal mucosa on long-term survival

354 Background: The use of chemoradiation (CXRT) for locally advanced pancreatic cancer (LAPC) is controversial. Delivery of high doses of RT capable of leading to local tumor control is challenging. We reviewed outcomes of treatement with dose-escalated IMRT with curative intent. Methods: Of 211 patients treated from 5/2006 to 8/2014 with CXRT for LAPC, 49(23%) had tumors > 1 cm from the luminal organs ere selected for dose-escalated IMRT using integrated boost (SIB) technique, inspiration breath hold, and computed tomographic (CT) image guidance. Fractionation was optimized for coverage of gross tumor (GTV,Table 1). A 2-5mm margin on the GTV, was treated as an SIB within a microscopic dose. Forty-seven (96%) patients received a median of 4.0 months of induction chemotherapy and 45 (92%) received concurrent capecitabine or gemcitabine. Results: Mean GTV coverage was 86% (95% CI 78% to 94%). Median FU was 32 mo. Median OS and 1, 2, 3 and 5 year OS rates were 22.6mo (95% CI 16.4 to 43.9mo), 83%, 49%,38%, and 18% from the date of diagnosis and 17.8mo, 63%, 38%, 33%, and 18% from the start of RT. Degree of GTV coverage and Biological Equivalent Dose (BED) did not appear to affect outcome. Freedom from progression at 3 y were 40.6% (local) and 37.1% (distant). Acute toxicity was uncommon: grade 2 pain, diarrhea, anorexia, nausea or fatigue in 18 (37%), and grade 3 diarrhea in one patient (2%). Four patients (13%) required transfusion for anemia. One patient had a GI bleed possibly related to treatment. Conclusions: Dose-escalated IMRT across a BED range of 70-100Gy for inoperable patients selected with induction chemotherapy appears well tolerated and may improve the likelihood of long term survival. These results are similar to the best outcomes reported for patients after surgical resection. Incomplete high-dose GTV coverage does not appear to be detrimental. A randomized phase II trial is testing IMRT (RTOG 1201, 63Gy/28fx, with stratification by SMAD4 expression). [Table: see text]