Focal Radiation Therapy Dose Escalation Improves Overall Survival in Locally Advanced Pancreatic Cancer Patients Receiving Induction Chemotherapy and Consolidative Chemoradiation

Abstract

Toreviewoutcomes of locally advanced pancreatic cancer (LAPC) patients treated with dose-escalated intensity modulated radiation therapy (IMRT) with curative intent. A total of 200 patients with LAPC were treated with induction chemotherapy followed by chemoradiation between 2006 and 2014. Of these, 47 (24%) having tumors >1cm from the luminal organs were selected for dose-escalated IMRT (biologically effective dose [BED] >70Gy) using a simultaneous integrated boost technique, inspiration breath hold, and computed tomographic image guidance. Fractionation was optimized for coverage of gross tumor and luminal organ sparing. A 2- to 5-mm margin around the gross tumor volume was treated using a simultaneous integrated boost with a microscopic dose. Overall survival (OS), recurrence-free survival (RFS), local-regional and distant RFS, and time to local-regional and distant recurrence, calculated from start of chemoradiation, were the outcomes of interest. Median radiation dose was 50.4Gy (BED=59.47Gy) with a concurrent capecitabine-based (86%) regimen. Patients who received BED >70Gy had a superior OS (17.8 vs 15.0months, P=.03), which was preserved throughout the follow-up period, with estimated OS rates at 2years of 36% versus 19% and at 3years of 31% versus 9% along with improved local-regional RFS (10.2 vs 6.2months, P=.05) as compared with those receiving BED ≤70Gy. Degree of gross tumor volume coverage did not seem to affect outcomes. No additional toxicity was observed in the high-dose group. Higher dose (BED) was the only predictor of improved OS on multivariate analysis. Radiation dose escalation during consolidative chemoradiation therapy after induction chemotherapy for LAPC patients improves OS and local-regional RFS.