Definitive hyperfractionated, accelerated proton reirradiation for patients with pelvic malignancies

Pelvic reirradiation (re-RT) presents challenges due to concerns for late toxicity to tissues-at-risk including pelvic bone marrow (PBM). We routinely utilize a hyperfractionated, accelerated re-RT for recurrent rectal or anal cancer in the setting of prior radiation. We hypothesized that proton beam radiation (PBR) is uniquely suited to limit doses to pelvic non-target tissues better than photon-based approaches.

All patients who received hyperfractionated, accelerated PBR re-RT to the pelvis from 2007 to 2017 were identified. Re-RT was delivered twice daily with a 6 h minimum interfraction interval at 1.5 Gray Relative Biological Effectiveness (Gy(RBE)) per fraction to a total dose of 39-45 Gy(RBE). Concurrent chemotherapy was given to all patients. Comparison photon plans were generated for dosimetric analysis. Dosimetric parameters compared using a matched-pair analysis and the Wilcoxon signed-rank test. Survival analysis was performed Kaplan Meier curves.

Fifteen patients were identified, with a median prior pelvic RT dose of 50.4 Gy (range 25-80 Gy). Median time between the initial RT and PBRT re-RT was 4.7 years (range 1.0-36.1 years). In comparison to corresponding photon re-RT plans, PBR re-RT plans had lower mean PBM dose, and lower volume of PBM getting 5 Gy, 10 Gy, 20 Gy, and 30 Gy (p < 0.001, p < 0.001, p < 0.001, and p = 0.033, respectively).With median 13.9 months follow-up after PBR re-RT, five patients had developed local recurrences, and four patients had developed distant metastases. One-year overall survival following PBR re-RT was 67.5% and one-year progression free survival was 58.7%. No patients developed acute or late Grade 4 toxicity.

PBR re-RT affords improved sparing of PBM compared with photon-based re-RT. Clinically, PBR re-RT is well-tolerated. However, given modest control rates with definitive re-RT without subsequent surgical resection, a multidisciplinary approach should be favored in this setting when feasible.