Purpose/Objective(s): To assess toxicities and disease specific outcomes after proton beam therapy (PBT) for isolated locoregional recurrence (LRR) of breast cancer after mastectomy without prior radiotherapy (RT).

Materials/Methods: In the prospective multi-institutional Proton Collaborative Group (PCG) registry, 19 patients with isolated LRR of breast cancer after mastectomy without prior RT were identified from 2013 to 2016. Adverse events (AEs) were prospectively graded using CTCAE v4.0. Acute AE was defined as any AE within 6 months after start of PBT. Late AE was defined as any AE beginning or persisting beyond 6 months after start of PBT. Additional clinical data was extracted from patient records. Disease specific outcomes were measured from date of RT completion. Clinical and treatment characteristics were tested for association with AE grade using Fisher’s exact test for categorical and Kruskal-Wallis test for continuous variables. Spearman correlation coefficients were calculated to assess strength of associations. Kaplan Meier curves were used to determine clinical outcome rates. Statistical analysis was performed using SAS v 9.4 (SAS Institute Inc.).

Results: Median interval from mastectomy to isolated LRR was 67.2 months (range 68.8-139.2). Recurrences involved chest wall in 79%, internal mammary lymph nodes (LNs) in 16%, axillary LNs in 5%, infraclavicular LNs in 5%, and supraclavicular LNs in 5%. Recurrences were resected in 79% (resection status R0 in 58%, R1 in 11%, R2 in 11%). Most patients had grade 3 (63%) ductal carcinoma (79%), ER-positive (67%), PR-positive (56%), and HER2-negative (83%). At time of PBT, median age was 48.7 years old (range 32-84). Most patients were treated with uniform scanning PBT (84%) to chest wall and regional lymphatics (90%). Total median dose was 60.4 Gy (RBE) (range 47.2-70.4). Median follow-up after PBT was 13.4 months (range 0.0-36.6), with 74% having > 6 months follow-up and 53% having > 12 months follow-up. At last follow-up, 89% of patients were alive with no locoregional or distant recurrence, 5% were alive with metastatic disease, and 5% had died of metastatic disease. Maximum grade AE was grade 2 in 68% and grade 3 in 21%. Acute AEs were as follows: dermatitis (63% grade 2, 11% grade 3), pain (21% grade 2, 5% grade 3), fatigue (11% grade 2), and neuropathy (5% grade 2). Late AEs were as follows: dermatitis (11% grade 2, 5% grade 3) and lymphedema (5% grade 3). All grade 3 AEs occurred in patients receiving > 60 Gy (RBE) (p = 0.04, rho = 0.50) and with body mass index (BMI) > 25 kg/m² (p=0.09, rho = 0.50).

Conclusion: To our knowledge, this is the first report of PBT in the treatment of isolated LRR of breast cancer after mastectomy without prior RT. All grade 3 AEs occurred in patients receiving > 60 Gy (RBE) and with BMI > 25. Overall, there were no locoregional recurrences and low rates of late grade 3 AEs.