Efficacy and safety of ultra-hypofractionated post-operative radiation therapy for breast cancer: a systematic review and meta-analysis.

purposeTo evaluate the efficacy and safety of ultra-hypofractionated post-operative radiation therapy (UHF-RT) compared with moderately hypofractionated radiotherapy (MHF-RT) in patients with breast cancer. MATERIALS AND

methodsA comprehensive search of PubMed, Embase, Cochrane Library, and Web of Science databases was conducted up to June 30, 2025. Both randomized controlled trials (RCTs) comparing UHF-RT to MHF-RT and non-randomized observational studies (prospective or retrospective cohort studies) containing only UHF-RT were included. The primary outcomes were grade ≥ 2 acute radiation dermatitis and late radiation therapy-related toxicities. Secondary outcomes included cosmetic outcomes and survival metrics.

resultsA total of 35 studies were included, comprising 7 RCTs and 28 non-randomized cohort studies, with 4,926 patients in the RCTs and 4,548 patients in the cohort studies. Meta-analysis of RCTs revealed no significant differences between UHF-RT and MHF-RT for grade ≥ 2 acute radiation dermatitis (RR = 0.84, 95% CI 0.48–1.47), late breast edema (RR = 1.37, 95% CI 0.50–3.75), breast shrinkage (RR = 1.02, 95% CI 0.55–1.92), or telangiectasia (RR = 0.79, 95% CI 0.20–3.02). Analysis of non-randomized cohort studies revealed that the most common grade ≥ 2 acute toxicities were radiation dermatitis (10.23%, 95% CI 9.26–11.30%). Subgroup analysis revealed a dose-dependent relationship for toxicity: regimens with total doses ≥ 30 Gy showed significantly higher rates of acute radiation dermatitis (28.85% vs. 2.73%, p < 0.01) and late breast fibrosis (12.94% vs. 1.90%, p < 0.01) compared to regimens with total doses < 30 Gy. Late toxicity rates were generally low in regimens with total doses < 30 Gy, with breast fibrosis (1.90%, 95% CI 1.30–2.78%) and breast edema (1.65%, 95% CI 1.23–2.20%) being the most frequent. Cosmetic outcomes were rated as excellent or good in over 90% of patients receiving UHF-RT in most trials, although a few trials reported lower rates. Patients receiving UHF-RT or MHF-RT showed similar survival outcomes, although fewer RCTs reported these metrics.

conclusionsUHF-RT is a safe and effective alternative to MHF-RT for breast cancer in the short-to-mid term, with comparable acute toxicity outcomes. The reduced treatment time and improved patient convenience make UHF-RT an attractive option for clinical practice. However, further large-scale randomized controlled trials with long-term follow-up are needed to confirm these findings and to guide the optimal implementation of UHF-RT in breast cancer treatment.