Ultra-Hypofractionated Palliative Radiotherapy for Symptomatic Locoregionally Advanced Breast Cancer: A Prospective, Single-Arm Phase II Trial of Toxicity and Quality-of-Life Outcomes

Introduction: To report the safety, efficacy, and patient-reported outcomes of a prospective trial of weekly hypofractionated radiotherapy (RT) for symptomatic locoregionally advanced breast cancer (SLABC). Methods and Materials: In this single-arm, prospective phase II trial, 24 patients received a palliative RT course of 40 Gy delivered in five weekly 8 Gy fractions. The primary endpoint was dose-limiting toxicity (DLT), defined as grade ≥3 acute radiation dermatitis. Secondary endpoints included objective response rate (ORR) and health-related quality of life (HRQoL), assessed longitudinally using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30/BR23 and Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaires. Results: All 24 enrolled patients completed the prescribed treatment. The regimen led to profound and statistically significant improvements in EORTC Global Health/QoL scores (+44.1 points; 95% Confidence Interval (CI): 34.6 to 53.7; p<0.001) and pain scores (-33.3; 95% CI: -39.0 to -27.7; p<0.001) at 3 months, which were sustained at 6 months. At 3 months, the objective response rate was 40.9% (95% CI: 20.7%–63.6%). The primary DLT was Grade ≥3 acute dermatitis, occurring in 29.2% of patients; however, this toxicity was transient, with all events occurring at treatment completion and the rate decreasing to 8.3% by the one-month follow-up. Conclusion: This signal-seeking study demonstrates the feasibility of a 40 Gy in five fractions palliative regimen. It presents a manageable, transient acute toxicity profile and offers promising signals of symptom palliation, locoregional disease control, and associated improvements in patient-reported quality of life.