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Acute adverse events of hypofractionated whole-breast radiotherapy with a simultaneous-integrated boost - Results from the randomized controlled HYPOSIB-trial (ARO 2013-05)

In brief

Simultaneous-integrated boost cuts moderate-dose skin toxicity from 39% to 25% of patients

In the HYPOSIB trial of 2,264 women after breast-conserving surgery, delivering the boost together with whole-breast hypofractionated radiotherapy reduced the proportion experiencing grade 2 or higher radiation dermatitis from 38.6% to 25.3% and led to faster resolution. Hot flashes were modestly more common but rarely linked to treatment, while pain and breast discomfort occurred later with standard schedules, suggesting the integrated approach improves early skin tolerance.

Journal
International journal of radiation oncology, biology, physics (Q1)
Published
31 July 2026
Study design
Randomized controlled trial
Evidence level
Level 1, High (CEBM 1b)
Authors
David Krug, Reinhard Vonthein, Andreas Schreiber, Alexander D Boicev, Jörg Zimmer, Dorit Uhlemann, et al.
PMID
42537852
DOI
10.1016/j.ijrobp.2026.07.022

Why clinicians should know about it

Abstract

BACKGROUND: Moderate hypofractionation (HF) is standard of care for adjuvant whole-breast irradiation after breast-conserving surgery (BCS). While boost irradiation has traditionally been administered sequentially (seq) after whole-breast irradiation, a growing amount of data suggests that delivery of a simultaneous integrated boost (SIB) may be equally effective and tolerable. METHODS: HYPOSIB is a randomized controlled non-inferiority trial enrolling patients with breast cancer after BCS. Patients were randomized 1:1 to HYPOSIB (40 Gy in 16 fractions to the breast with SIB of 48 Gy to the tumor bed) or to the standard arm (investigator's choice: conventionally fractionated radiotherapy (CF) with SIB (CFSIB) or CFseq or HFseq). The focus of this manuscript is the secondary endpoint of selected prespecified acute adverse events (radiation dermatitis, pain, feeling of pressure in the breast - further termed breast discomfort) according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 up to 3 months after treatment. RESULTS: From 06/2015 to 01/2019, 2310 patients were enrolled. The analysis set included 2264 consenting patients that received radiotherapy. HYPOSIB resulted in fewer cases with worst grade of radiation dermatitis (grade 2: 25.3% vs. 38.6%; grade 3: 2.3% vs. 3.1). Radiation dermatitis occurred earlier during HYPOSIB but resolved more rapidly. There were more worst grade hot flashes during the HYPOSIB (grade 2: 29.7% vs. 26.0%; grade 3: 8.6% vs. 6.8%). Only 3.3% of hot flashes were judged as radiotherapy-related. Pain and breast discomfort were more frequent during the standard treatment and at later time points after HYPOSIB, mirroring the temporal trends for radiation dermatitis. CONCLUSIONS: HYPOSIB in 16 fractions led to a clinically relevant reduction in worst grade radiation dermatitis. There were temporal differences between treatments in the occurrence of radiation dermatitis, pain, and breast discomfort with adverse events occurring and resolving earlier with HYPOSIB.

Abstract as published, via PubMed.

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For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.