Single-center phase 2 trial of maximal ablative irradiation for locally advanced pancreatic cancer with extensive vascular encasement

A phase 2 study at Memorial Sloan Kettering Cancer Center (New York, NY) evaluated hypofractionated ablative radiation therapy (A-RT) followed by evaluation for surgery in patients with locally advanced pancreatic cancer (LAPC) whose cancer remained unresectable after induction chemotherapy. Between June 2018 and April 2024, the trial included participants with histologically confirmed pancreatic adenocarcinoma unresectable by multidisciplinary review after 3 or more months of mFOLFIRINOX or gemcitabine plus nab-paclitaxel. The patients underwent hypofractionated A-RT (67.5 Gy in 15 fractions or 75 Gy in 25 fractions). Co primary endpoints were resectablity and 2-year overall survival (OS) rate. Forty-eight participants underwent A-RT (52.1% male, median tumor size 4.1 cm; 98% with arterial and venous involvement). Seventeen participants (34%) underwent a laparoscopy, with resection performed in 13 (27%). At a median follow-up of 3 years, 2-year OS rate from A-RT was 38% (95% CI 26-54) among all participants, 31% (19-51) among participants with unresected disease, and 54% (33-89) among participants with resected disease. A-RT was not associated with an increase in postsurgical morbidity when surgery was performed. The authors conclude that for patients with LAPC with extensive vascular encasement after induction chemotherapy, hyperfractionated A-RT prior to possible surgery was associated with promising OS for both ultimately resected and unresected groups.