| Abstract: |
Key Points: Question: What are the outcomes of hypofractionated (16 treatments) postmastectomy radiation therapy in the setting of implant-based reconstruction compared with conventionally fractionated (25 treatments) radiation therapy? Findings: In this multi-institutional randomized clinical trial of 400 patients, there was no statistically significant increase in change in physical well-being at 6 months (primary study outcome) with hypofractionation. However, among younger patients (aged <45 years), the hypofractionation group had higher physical well-being scores and were less bothered by treatment-related adverse effects compared with those randomized to conventional fractionation at 6 months. Meaning: This study's finding that hypofractionation did not result in significantly improved physical well-being at 6 months adds to the growing body of data on hypofractionated postmastectomy radiation therapy. This randomized clinical trial compares the outcomes of hypofractionation vs conventional fractionation postmastectomy radiation therapy regimens in patients undergoing implant-based breast reconstruction. Importance: Postmastectomy radiation therapy (PMRT) improves local-regional disease control and patient survival. Hypofractionation (HF) regimens have comparable efficacy and complication rates with improved quality of life compared with conventional fractionation (CF) schedules. However, the use of HF after mastectomy in patients undergoing breast reconstruction has not been prospectively examined. Objective: To compare HF and CF PMRT outcomes after implant-based reconstruction. Design, Setting, and Participants: This randomized clinical trial assessed patients 18 years or older undergoing mastectomy and immediate expander or implant reconstruction for breast cancer (Tis, TX, or T1-3) and unilateral PMRT from March 8, 2018, to November 3, 2021 (median [range] follow-up, 40.4 [15.4-63.0] months), at 16 US cancer centers or hospitals. Analyses were conducted between September and December 2023. Interventions: Patients were randomized 1:1 to HF or CF PMRT. Chest wall doses were 4256 cGy for 16 fractions for HF and 5000 cGy for 25 fractions for CF. Chest wall toxic effects were defined as a grade 3 or higher adverse event. Main Outcomes and Measures: The primary outcome was the change in physical well-being (PWB) domain of the Functional Assessment of Cancer Therapy–Breast (FACT-B) quality-of-life assessment tool at 6 months after starting PMRT, controlling for age. Secondary outcomes included toxic effects and cancer recurrence. Results: Of 400 women (201 in the CF arm and 199 in the HF arm; median [range] age, 47 [23-79] years), 330 patients had PWB scores at baseline and at 6 months. There was no difference in the change in PWB between the study arms (estimate, 0.13; 95% CI, −0.86 to 1.11; P =.80), but there was a significant interaction between age group and study arm (P =.03 for interaction). Patients younger than 45 years had higher 6-month absolute PWB scores if treated with HF rather than CF regimens (23.6 [95% CI, 22.7-24.6] vs 22.0 [95% CI, 20.7-23.3]; P =.047) and reported being less bothered by adverse effects (mean [SD], 3.0 [0.9] in the HF arm and 2.6 [1.2] in the CF arm; P =.02) or nausea (mean [SD], 3.8 [0.4] in the HF arm and 3.6 [0.8] in the CF arm; P =.04). In the as-treated cohort, there were 23 distant (11 in the HF arm and 12 in the CF arm) and 2 local-regional (1 in the HF arm and 1 in the CF arm) recurrences. Chest wall toxic effects occurred in 39 patients (20 in the HF arm and 19 in the CF arm) at a median (IQR) of 7.2 (1.8-12.9) months. Fractionation was not associated with chest wall toxic effects on multivariate analysis (HF arm: hazard ratio, 1.02; 95% CI, 0.52-2.00; P =.95). Fewer patients undergoing HF vs CF regimens had a treatment break (5 [2.7%] vs 15 [7.7%]; P =.03) or required unpaid time off from work (17 [8.5%] vs 34 [16.9%]; P =.02). Conclusions and Relevance: In this randomized clinical trial, the HF regimen did not significantly improve change in PWB compared with th CF regimen. These data add to the increasing experience with HF PMRT in patients with implant-based reconstruction. Trial Registration: ClinicalTrials.gov Identifier: NCT03422003 |
