Ultra-Hypofractionated Whole-Breast Irradiation: Real-World Data From a Prospective Single-Institution Cohort.

BACKGROUND: Ultra-hypofractionated (5-fraction) adjuvant whole-breast irradiation (WBI) is effective for early-stage breast cancer, as demonstrated by the FAST-Forward. We implemented a risk-adapted program, including 28 Gy/5-fractions when a boost was indicated but infeasible, and report real-world tolerability and early outcomes of this approach in a prospective cohort. PATIENTS AND METHODS: This prospective single-institution observational study included 718 patients with stage 0 to IIIA breast cancer treated after breast-conserving surgery (2020-2024). Patients received 26 Gy in 5 daily fractions (with or without a moderately hypofractionated sequential boost of 10-12.5 Gy in 4-5 fractions) or 28 Gy in 5 twice-weekly fractions (instead of a boost, n = 201). Acute and late toxicity, patient-reported outcomes, and cosmesis were prospectively assessed at regular follow-up visits. RESULTS: No grade ≥3 acute toxicities occurred; 13% developed grade 2 acute skin reactions. At 27 months median follow-up, late toxicity was low: 11% of patients had any grade ≥2 late effect (3% grade 3). The 3-year cumulative incidence of ipsilateral in-breast recurrence was 0.6%, and 3-year overall survival was 98.5%. Exploratory comparisons detected no significant toxicity differences among regimens. Larger breast volume was associated with acute and late toxicity. Cosmesis was good or excellent in 98% of patients. CONCLUSION: Risk-adapted 5-fraction WBI was well tolerated with excellent early tumor control. A 28 Gy twice-weekly regimen shortened treatment when a boost was infeasible without compromising early-to-intermediate outcomes. These findings support routine adoption of ultra-hypofractionated adjuvant radiotherapy in early breast cancer, pending long-term follow-up for safety confirmation.