Prospective Comparison of Hypofractionated Versus Normofractionated Intensity-Modulated Radiotherapy in Breast Cancer: Late Toxicity Results of the Non-Inferiority KOSIMA Trial (ARO2010-3)

Gustavo R Sarria, Grit Welzel, Martin Polednik, Frederik Wenz, Yasser Abo-Madyan, Gustavo R Sarria, Grit Welzel, Martin Polednik, Frederik Wenz, Yasser Abo-Madyan

Abstract

Purpose: To compare the late toxicity profile of hypofractionation and normofractionation for whole-breast radiotherapy in breast cancer (BC) patients after conserving surgery.

Methods: Sixty-year-old or older patients with pTis-pT3, pN0-pN1a, M0 BC were recruited and stratified to hypofractionated (arm R-HF) or normofractionated (arm L-NF) intensity-modulated radiotherapy (IMRT), for right- and left-sided BC, respectively, in this single-center, non-randomized, non-inferiority trial. A boost was allowed if indicated. The primary outcome was the cumulative percentage of patients developing grade III fibrosis, grade I telangiectasia, and/or grade II hyperpigmentation after 2 years, with a pre-specified non-inferiority margin of 15% increase from an expected 2-year toxicity rate of 20%.

Results: The Median follow-up was 4.93 (0.57-8.65) years for R-HF and 5.02 (0.65-8.72) years for L-NF (p=0.236). The median age was 68 (60-83 and 60-80) years, respectively. In total, 226 patients were recruited (107 for R-HF and 119 for L-NF), with 100 and 117 patients suitable for assessment, respectively. A boost was delivered in 51% and 53% of each arm, respectively. Median PTV volumes were 1013.6 (273-2805) cm3 (R-HF) and 1058.28 (315-2709) cm3 (L-NF, p=0.591). The 2-year primary endpoint rate was 6.1% (95% CI 1.3-11.7, n=5 of 82) and 13.3% (95% CI 7-20.2, n=14 of 105), respectively (absolute difference -7.2%, one-sided 95% CI ∞ to -0.26, favoring R-HF). No local recurrence-free- or overall-survival differences were found.

Conclusion: In this prospective non-randomized study, hypofractionation did not have higher toxicity than normofractionated whole-breast IMRT.

Keywords: breast cancer; breast-conserving surgery; hypofractionation; normofractionation; toxicity; whole-breast IMRT.

Conflict of interest statement

GS: Personal fees and travel expenses from Carl Zeiss Meditec AG, personal fees from Roche Pharma AG, personal fees from MedWave Clinical Trials, travel costs from Guerbet SA, not related to this work. FW: Personal fees from Roche Pharma AG and Eli Lilly and Company, grants and others from Carl Zeiss Meditec AG and Elekta AB, a patent by Carl Zeiss Meditec AG, outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a declared a past co-authorship with one of the authors FW.

Copyright © 2022 Sarria, Welzel, Polednik, Wenz and Abo-Madyan.

Figures

Figure 1
Figure 1
Incidence of secondary events. The cumulative incidence of patients developing secondary events (GI-III) is displayed in a cross-sectional fashion for each treatment arm and time point.
Figure 2
Figure 2
Cumulative local recurrence rate. Longitudinal local control displayed according to the Kaplan-Meier method.
Figure 3
Figure 3
Overall survival. Kaplan-Meier curves for the estimated overall survival.

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