Results of repeat proton beam radiotherapy in patients with locoregional recurrence or a second primary tumor in a previously irradiated area

Introduction. Re-irradiation for locoregional recurrence or second primary tumors in previously irradiated regions is constrained by cumulative organ-at-risk tolerance. Proton therapy may improve dose conformality and spare critical structures. Material and methods. We retrospectively reviewed 91 patients treated with repeat proton beam radiotherapy between 2017 and 2023. Patients (37 women, 54 men; age 28–90 years) were not eligible for salvage surgery, had histopathologically confirmed local failure, and had no distant metastases on PET. Recurrence was present in 67 patients (74%) and second primary tumors in 24 (23%). Re-irradiation was delivered with SIB IMPT at 1.8–2.0 Gy relative biological effectiveness (RBE)/fraction to 20–78 Gy(RBE) (mean 63.6). Treatment planning reconstructed the primary radiotherapy plan and applied cumulative dose limits to organs at risk using an ALARA-based approach. Results. Eighty-nine patients (98%) completed the planned course; two discontinued due to deterioration in general condition. Acute toxicity included grade 3 skin reactions in 7% and grade 2 in 74%, and grade 3 mucosal reactions in 12% and grade 2 in 59%. Two patients required packed red blood cell transfusions for grade 3 anemia during treatment. Three-month MRI demonstrated disease stabilization in 50%. Median overall survival (OS) was 16.9 months; OS was 48% at 1 year, 40% at 2 years, and 28% at 5 years. OS did not differ by sex, T or N category, or recurrence versus second primary tumor, but varied by primary tumor location (p = 0.008), with the most favorable survival in chordoma. Conclusions. Repeat proton beam therapy enabled radical re-irradiation in selected patients across diverse sites with acceptable acute toxicity and clinically meaningful survival. Longer follow-up and prospective validation are warranted to refine selection and cumulative dose constraints.