Comparative efficacy and harms of adjuvant whole breast hypofractionation or external beam accelerated partial breast irradiation for treatment of breast cancer: a systematic review

BACKGROUND: Whole breast moderate hypofractionation is recommended for most breast cancer populations to improve survival and reduce recurrence. Whole breast ultra-hypofractionation and external beam accelerated partial breast irradiation (APBI) may reduce toxicity while maintaining benefits. METHODS: MEDLINE and Embase searches through March 2024 identified randomized controlled trials (RCTs) evaluating adjuvant external beam hypofractionated radiation therapy for breast cancer. Eligibility and risk of bias (RoB) were assessed by two reviewers and required consensus. For prioritized outcomes (e.g., overall survival, acute toxicity), certainty of evidence was assessed using GRADE. RESULTS: Thirty-nine RCTs compared whole breast moderate hypofractionation vs. conventional radiation (CFRT; k = 25); whole breast ultra-hypofractionation vs. moderate hypofractionation or CFRT (k = 8); or external beam APBI vs. whole breast radiation (k = 6). For all comparisons, there were low RoB, large trials (N > 2,000) with 5-10 year outcomes. Trials on ultra-hypofractionation and APBI focused on early stage cancer, some also including ductal carcinoma in situ (DCIS). High survival (> 90%) and low recurrence were found across all treatments. Moderate hypofractionation probably results in less overall acute toxicity, but makes little to no difference in specific adverse events. No trial on ultra-hypofractionation reported overall toxicity; evidence on acute skin toxicity is very uncertain. APBI probably results in less overall acute toxicity, but may result in more overall late toxicity; evidence was very uncertain or showed no difference for specific events. CONCLUSION: Radiation treatments had similar survival and recurrence. Moderate hypofractionation and APBI result in lower overall acute toxicity, but evidence is lacking for ultra-hypofractionation. For ultra-hypofractionation and APBI, future research is needed to better understand late toxicity outcomes, and whether effects may vary across settings and subgroups.