Five-Year Late Toxicity After Ultra-Hypofractionated Whole-Breast Radiotherapy With Simultaneous Integrated Boost: A...

Ultra-hypofractionated whole-breast radiotherapy has become an accepted option for early breast cancer, but evidence on the incorporation of a simultaneous integrated boost within a five-fraction schedule remains limited. The present study evaluated five-year late side effects after whole-breast irradiation with a simultaneous integrated boost delivered in five fractions in a prospective multicentre cohort.

This prospective, non-randomized, multicentre cohort included 242 patients with early breast cancer treated between April and December 2020. All patients underwent breast-conserving surgery with clear margins. Whole-breast irradiation was delivered at 26 Gy in five daily fractions, and 157 patients received a simultaneous integrated boost to 29 Gy in five fractions. The primary endpoint was late normal-tissue side effects in the simultaneous integrated boost subgroup, assessed prospectively with clinical examination, photographic documentation, and LENT-SOMA scoring. Comparisons with patients treated without a boost were exploratory.

Median follow-up was 64.7 months in both the overall cohort and the simultaneous integrated boost subgroup, and 221 of 242 patients completed the scheduled five-year visit. In the simultaneous integrated boost subgroup, cumulative any-grade pain was reported in 14.6% of patients at five years, and cumulative any-grade fibrosis in 8.9%. Other late side effects were uncommon, including breast oedema in 5.1%, arm oedema in 0.6%, atrophy in 1.9%, and telangiectasia in 0.6%; no ulceration was observed. In exploratory unadjusted analyses, pain was more frequent in the simultaneous integrated boost group than in the no-boost group, whereas no significant differences were observed for other late side effects. Chemotherapy receipt was also associated with persistent pain in exploratory analyses.

Whole-breast irradiation with a 29 Gy simultaneous integrated boost in five fractions achieved low rates of objective late side effects and reassuring oncological outcomes after more than five years, while shortening treatment to a single one-week course compared with sequential or moderately hypofractionated schedules. Persistent low-grade breast pain was more frequent with the boost, but non-randomized allocation and its association with chemotherapy preclude causal attribution, supporting continued, careful use in selected patients alongside further prospective, randomized studies with baseline symptom assessment.