Maximal Ablative Irradiation Because of Encasement for Patients With Locally Advanced Pancreatic Cancer

Importance: The best local therapy approach for patients with locally advanced pancreatic cancer (LAPC) remains undefined. Objective: To evaluate hypofractionated ablative radiation therapy (A-RT) followed by evaluation for surgery in patients with LAPC whose cancer remained unresectable after induction chemotherapy. Design, Setting, and Participants: This was a phase 2 single-arm nonrandomized clinical trial conducted at the Memorial Sloan Kettering Cancer Center, New York, New York, from June 2018 to April 2024. Participants with histologically confirmed pancreatic adenocarcinoma unresectable by multidisciplinary review after 3 or more months of modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX) or gemcitabine plus nab-paclitaxel were eligible. Intervention: Hypofractionated A-RT (67.5 Gy in 15 fractions or 75 Gy in 25 fractions) with capecitabine followed by evaluation for resection. Main Outcomes and Measures: Coprimary end points included resectability and 2-year overall survival. Secondary end points included 90-day surgical adverse events (AEs) and 2-year locoregional and distant metastasis rates. Results: Forty-eight participants underwent A-RT (25 [52.1%] male; median [range] age, 67 [50-80] years; median [range] tumor size 4.1 [2.4-8.3] cm; 47 (98%) with arterial and venous involvement; median [range] carbohydrate antigen 19-9, 88 [