PurposeReirradiation for rectal cancer (RC) after prior pelvic radiation therapy (RT) has been shown to be safe and effective. However, limited data exist for proton therapy (PT), including pencil beam scanning proton therapy (PBS-PT). We hypothesize that PT is safe and feasible for re-treatment and may allow for decreased toxicity and treatment escalation. Methods and materialsA single-institution, retrospective, institutional review board–approved analysis of all patients with RC and prior pelvic RT receiving PBS-PT reirradiation was performed. Data on patient and treatment characteristics and outcomes were collected. Local progression, progression-free survival, overall survival, and late grade >3 toxicity were estimated using the Kaplan-Meier method. ResultsTwenty-eight patients (median follow-up: 28.6 months) received PBS-PT reirradiation between 2016 and 2019, including 18 patients with recurrent RC (median prior dose: 54.0 Gy) and 10 patients with de novo RC and variable prior RT. The median reirradiation dose was 44.4 Gy (range, 16.0-60.0 Gy; 21 of 28 twice daily), and 24 of 28 patients received concurrent chemotherapy. Six underwent surgical resection. Three (10.7%) experienced grade 3 acute toxicities, and 1 did not complete RT owing to toxicity. Four (14.2%) had late grade <3 toxicity, including 1 grade 5 toxicity in a patient with a prior RT-related injury. The 1-year local progression, progression-free survival, and overall survival rates were 33.7% (95% confidence interval [CI], 14.5%-52.9%), 45.0% (95% CI, 26.2%-63.8%), and 81.8% (95% CI, 67.3%-96.3%), respectively. ConclusionsThis is the largest series using PT for reirradiation for RC and the first study using PBS-PT. Low acute toxicity rates and acceptable late toxicity support PBS-PT as an option for this high-risk patient population, with a need for continued follow-up.