Hypofractionated Conformal Radiotherapy with Concurrent Full-Dose Gemcitabine Versus Standard Fractionation Radiotherapy with Concurrent Fluorouracil for Unresectable Pancreatic Cancer: a Multi-Institution Experience.

PURPOSE/OBJECTIVE(S): The purpose of this study was to compare oncologic outcomes and toxicity profile of hypofractionated conformal radiotherapy (RT) with concurrent full-dose gemcitabine versus standard fractionation RT with concurrent 5-fluorouracil (5-FU) in the treatment of unresectable non-metastatic pancreatic cancer. MATERIALS/METHODS: Patients with unresectable non-metastatic adenocarcinoma of the pancreas treated at three institutions were included. All patients were treated with chemoradiotherapy (CRT) consisting of either hypofractionated RT to the gross disease concurrent with a full-dose gemcitabine-based regimen versus standard fractionation RT to the tumor and elective nodes concurrent with 5-FU. End points included rates of gastrointestinal (GI) toxicities, overall survival (OS), and distant metastasis free survival (DMFS). RESULTS: From January 1999 to December 2009, 170 patients were identified (118 RT/gemcitabine, 52 RT/5-FU). There were no differences in demographic or clinical factors. Acute GI toxicities (grades≥3) were 82.2 and 17.8 %, respectively, for patients treated with RT/gemcitabine and 78.9 and 21.2 % for those treated with RT/5-FU (p = 0.67). Late GI toxicities (grades≥3) were 88.1 and 11.9 %, respectively, for RT/gemcitabine and 80.8 and 19.2 % for RT/5-FU (p = 0.23). OS for RT/gemcitabine and RT/5-FU were 52 versus 36 % at 1 year and 14 versus 6 % at 2 years favoring the RT/gemcitabine group (p = 0.02). DMFS at 1 and 2 years for RT/gemcitabine were 41 and 11 % versus 24 and 4 % for RT/5-FU (p = 0.02). CONCLUSIONS: RT/gemcitabine was equivalent in toxicity to RT/5-FU but was associated with superior OS and DMFS. When RT is used in the treatment of unresectable pancreatic cancer, hypofractionated conformal RT with concurrent full-dose gemcitabine may be the preferred approach