Proton Beam Therapy Reirradiation for Recurrent Breast Cancer: Multi-Institutional Prospective PCG Registry Analysis

Abstract

To investigate the adverse events (AEs) and clinical outcomes in patients receiving proton beam therapy (PBT) reirradiation (reRT) for recurrent breast cancer. Between 2011 and 2016, 50 patients were treated with reRT for breast cancer with PBT in the prospective Proton Collaborative Group (PCG) registry. Prior radiation (RT) was for breast cancer (43 patients), Hodgkin lymphoma (5 patients), thymoma (1 patient), and non-small cell lung cancer (1 patient). AEs were considered acute if it occurred within 180 days from the start of reRT and late if it began or persisted after 180 days from the start of reRT. AEs were graded based on the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Differences between groups were tested using Fisher’s exact test for categorical variables and Mann-Whitney rank-sum test for continuous variables. Kaplan Meier curves were used to measure clinical outcomes. Statistical analysis was performed using SAS v 9.4 (SAS Institute Inc.). Median follow-up was 12.7 months (range, 0-41.8). Median dose of prior RT was 60 Gy (RBE) (range, 10-96.7). Median dose of reRT was 55.1 Gy (RBE) (range, 45.1-76.3). Median cumulative dose was 110.6 Gy (RBE) (range, 70.6-156.8). Median interval between RT courses was 103.8 months (range, 5.5-430.8). Local targets for reRT with PBT included the following: unilateral chest wall in 58%, bilateral chest wall in 12%, whole breast in 8%, and partial breast in 2%, with 20% receiving nodal RT only. Nodal targets included: axilla + supraclavicular + internal mammary (AX+SCV+IMN) in 42%, AX+SCV in 6%, AX alone in 4%, SCV+IMN in 6%, IMN alone in 18%, and nonspecific “regional nodes” in 8%, with 16% not receiving nodal RT. Surgery included: mastectomy in 44%, wide local excision in 22%, biopsy only in 22%, lumpectomy in 6%, and reduction mammoplasty in 2%, with 4% having no surgery. Overall, 16% of patients experienced any grade 3 AE, with 10% acute grade 3 AEs and 8% late grade 3 AEs. Development of grade 3 AE was associated with body mass index (BMI) > 30 kg/m2 (p=0.02), bilateral recurrence (p=0.02), and bilateral reRT (p=0.004). All 8 grade 3 AEs occurred in patients receiving IMN RT (p=0.08). Patients with gross disease at the time of PBT trended toward worse 1-year local recurrence free survival (100% without gross disease vs. 84% with gross disease, p=0.06). For the entire cohort, 1-year local recurrence free survival was 93%, and 1-year OS was 97%. Proton beam reRT is well tolerated with favorable local control. BMI > 30, bilateral disease, and IMN RT may increase risk for grade 3 AEs. Despite median cumulative dose > 110 Gy (RBE), we demonstrate acceptable toxicity.