Acute Skin Toxicity and Cosmetic Outcomes of Ultra-Hypofractionated Whole-Breast Radiotherapy Delivered with Intensity-Modulated Radiotherapy in Early-Stage Breast Cancer: A Phase II Single-Arm Trial

Background Ultra-hypofractionated whole-breast radiotherapy (UHWBRT) is an emerging strategy for shortening the duration and burden of adjuvant radiotherapy after breast-conserving surgery. We evaluated acute skin toxicity, cosmetic outcomes, and organ-at-risk (OAR) dosimetry in early-stage breast cancer patients treated with UHWBRT delivered by intensity-modulated radiotherapy (IMRT). Methods In this phase II, single-arm study, 46 women aged ≥ 55 years with early-stage breast cancer (pT1-3N0) who had undergone breast-conserving surgery received 26 Gy in 5 fractions to the whole breast using IMRT with volumetric-modulated arc therapy (VMAT); 3 patients with adverse risk features received an additional sequential boost of 10 Gy in 5 fractions to the tumor bed. Acute skin toxicity was graded with the RTOG scale, and cosmesis was assessed with the 12-item Breast Cancer Treatment Outcome Scale (BCTOS-12) at baseline and 1, 6, 12, and 24 months. Oncologic outcomes were recorded over a mean follow-up of 18.6 months. Trial registration: Iranian Registry of Clinical Trials (IRCT20240112060693N1), registered on 04/06/2025. Results Mean age was 64.15 ± 7.03 years; 71.7% of tumors were left-sided. No patient developed grade ≥ 2 acute dermatitis; 21.7% had grade 1 dermatitis at 2 weeks. At 6 months, all patients had excellent (69.6%) or good (30.4%) cosmetic outcomes, unaffected by prior chemotherapy (P = 0.276). Mean heart dose (MHD) was 1.99 Gy overall (2.52 Gy for left-sided vs 0.69 Gy for right-sided tumors, P < 0.001), and ipsilateral lung V20 was 8.52%. Non-dermatologic complications occurred in 15.2% of patients. No local recurrence occurred, and overall survival was 100%. Conclusions UHWBRT (26 Gy in 5 fractions) delivered with IMRT is a safe, well-tolerated, and effective regimen for older women with early-stage breast cancer, providing excellent OAR sparing, minimal acute skin toxicity, and durable early cosmesis, while compressing treatment into one week. Confirmation in randomized and longer-term studies is warranted. Trial registration Iranian Registry of Clinical Trials, IRCT20240112060693N1 date of registration 04/06/2025.