Patient selection and toxicity predictors in proton reirradiation for locoregional breast cancer recurrence.

Purpose: Patients with breast cancer isolated local-regional recurrence (iLRR) can benefit from salvage reirradiation (reRT) to provide durable control and prevent further progression. Conformal radiation techniques like pencil beam scanning (PBS) proton beam therapy (PBT) may improve the reRT therapeutic ratio by limiting cumulative dose and improving target region dose delivery. Materials and methods: Consecutive patients between 8/2019-9/2025 treated with PBS-PBT reRT for breast cancer iLRR with prior dose overlap were identified. Clinicopathologic, treatment, and outcomes details were collected. Associations between clinical/treatment factors and time to recurrence and grade (G) ≥2 adverse events (AEs) were evaluated with Fine-Gray models and logistic regression, respectively. Correlations between DVH metrics and late AEs were assessed using Kruskal-Wallis and Wilcoxon rank sum tests. Results: Seventy patients were identified with median first course (C1), reRT course (C2), and cumulative doses of 53, 50, and 106Gy(RBE), respectively. During C2, 82.2% received comprehensive nodal irradiation. Median follow-up was 30 months. Two- and three-year rates of any recurrence were 14% and 17%, and OS were 100% and 95%, respectively. Maximum acute G2 and G3 AEs occurred in 50% and 7%, and late G2 and G3 AEs in 34% and 10%, respectively. Rib fractures developed in 21.1% and were associated with C1 and C2 chest wall D200cc and C1 rib D10cc. Conclusion: In the largest experience of PBT reRT for breast cancer iLRR to date, we report promising disease control and limited severe AEs despite a high-risk patient cohort. We provide dose metrics that can serve as the foundation for reRT dose constraints and be further refined in future reRT investigations.