Acute Adverse Events of Hypofractionated Whole-Breast Radiation Therapy With a Simultaneous Integrated Boost—Results From the Randomized Controlled HYPOSIB-Trial (ARO 2013-05)

PURPOSE: Moderate hypofractionation is standard of care for adjuvant whole-breast irradiation after breast-conserving surgery. Although boost irradiation has traditionally been administered sequentially 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 AND MATERIALS: HYPOSIB is a randomized controlled noninferiority trial enrolling patients with breast cancer after breast-conserving surgery. 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 radiation therapy with SIB or sequentially fractionated radiation therapy or sequential hypofractionation). 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 version 4.0 up to 3 months after treatment. RESULTS: From June 2015 to January 2019, 2310 patients were enrolled. The analysis set included 2264 consenting patients that received radiation therapy. 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 radiation therapy-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.