1284 - Large-Scale Real-World Implementation of Risk-Adapted Ultra-Hypofractionated Whole-Breast Irradiation in Early-Stage Breast Cancer

Purpose/Objective(s): In light of evidence supporting ultrahypofractionated whole-breast irradiation (uhWBI) for early-stage breast cancer, we implemented a risk-adapted 5-fraction uhWBI program in routine practice. This program included a standard 26 Gy in 5 daily fractions regimen, with an optional moderately hypofractionated (10-12.5 Gy in 4-5 fractions) sequential tumor bed boost when indicated, and a modified 28 Gy in 5 fractions delivered twice weekly as a pragmatic alternative when a tumor bed boost was indicated but infeasible. We assessed treatment tolerability, patient-reported outcomes, and early tumor control in this prospective cohort.

Materials/Methods: A prospective single-institution cohort of 718 patients with stage 0–IIIA breast cancer was treated from 2020–2024 with adjuvant 5-fraction WBI after breast-conserving surgery. Patients received either 26 Gy in 5 daily fractions to the whole breast (with a sequential boost for high-risk cases) or 28 Gy in 5 fractions delivered twice weekly (~2.5 weeks) to the whole breast when a boost was indicated but not feasible. Acute and late toxicities were prospectively graded (CTCAE for acute events; LENT-SOMA for late effects) at baseline, end of treatment, and scheduled follow-ups (median follow-up 27 months). Patient-reported outcomes, including cosmetic results and symptoms, were collected via standardized questionnaires. Descriptive statistics and multivariable analyses were used to evaluate toxicity and recurrence outcomes.

Results: All patients completed therapy without unplanned breaks. No grade =3 acute adverse events occurred; 13% of patients had grade 2 acute skin reactions. Late treatment-related effects were uncommon: 11% of patients developed any grade =2 late toxicity (3% grade 3). Patient-reported cosmetic outcomes were highly favorable, with 98% of patients rating breast cosmesis as good or excellent at 2 years. With median follow-up of 27 months, only 4 patients (0.6%) experienced ipsilateral breast tumor recurrence, corresponding to a 3-year in-breast recurrence-free rate of 99.3%; 3-year overall survival was 98.5%. No significant differences in adverse events, cosmetic outcomes, or recurrence rates were observed between the 26 Gy daily and 28 Gy twice-weekly regimens, nor between patients treated with versus without a boost. Larger breast volume was the only significant predictor of increased acute and late toxicity.

Conclusion: A personalized, risk-adapted five-fraction uhWBI strategy was feasible in a real-world setting, demonstrating low toxicity and excellent early tumor control. Incorporating a twice-weekly 28 Gy schedule as an alternative to a boost enabled completion of therapy in five fractions even for higher-risk patients, without compromising tolerability or cancer control. These findings support broader adoption of ultra-hypofractionated WBI in early-stage breast cancer, while longer follow-up is needed to confirm enduring safety and efficacy.