Acute Skin Toxicities after Ultrahypofractionated Versus Hypofractionated Postoperative Radiotherapy in Patients with Early Breast Cancer—A Single-Institution Clinical Study

Background:Real-world safety data from Southeastern Europe are limited for ultrahypofractionated (UHF) whole-breast irradiation (WBI). We aimed to evaluate acute skin toxicity with UHF versus hypofractionated (HF) postoperative radiation therapy in early breast cancer, following implementation of this fractionation regimen. Methods:This combined prospective-retrospective study included women aged ≥50 years following breast-conserving surgery (pT1-2, pN0-1, M0). The UHF cohort (prospective) received 26 Gy in 5 fractions over one week between 2023 and 2024. The control group consisted of retrospective data obtained from institutional records of patients who received WBI using a HF schedule of 40.5-42.6 Gy in 15-16 fractions over 3 weeks between 2015 and 2020. All patients were treated with 3D-CRT WBI without regional nodal irradiation or boost. Acute skin toxicity was graded by CTCAE v5.0 at end of treatment and at 4 and 12 weeks. Results:This study included 80 patients, with 40 in each group, with a mean age of 61.1 ± 6.6 years. Baseline clinicopathological characteristics were comparable, except for a slightly larger median tumor size in the UHF group (p = 0.037). At the end of radiation therapy, acute radiodermatitis occurred in 36 of 40 (90%) patients receiving UHF and in 38 of 40 (95%) patients receiving HF (p = 0.396). The grade distribution was comparable across the two groups (p = 0.53), and no grade ≥3 events were recorded. At 4 weeks, no adverse skin reactions were observed in patients receiving UHF, and by twelve weeks, no active radiodermatitis persisted in either group. Conclusions:UHF WBI (26 Gy/5 fractions) demonstrated comparable acute skin toxicity to standard HF regimens, supporting its safety and clinical feasibility in routine practice.