Hypofractionated Versus Conventional Fractionated Postmastectomy Radiotherapy for High-Risk Breast Cancer Patients: A Randomized, Phase III, Non-Inferiority, Open-Label Trial

Background: No randomized study has compared postmastectomy hypofractionated radiotherapy (HFRT) with conventional fractionated radiotherapy (CFRT) in breast cancer patients. This study aimed to determine whether a 3-week schedule of postmastectomy HFRT is as effective and safe as a 5-week schedule of CFRT. Methods: This randomized phase III non-inferiority open-label study was conducted in a single institution in China. We enrolled patients who had undergone mastectomy and had = 4 positive axillary lymph nodes or T3/4 disease. Patients were randomly assigned (1:1) using a random number generator to receive chest wall and nodal irradiation at a standard dose of 50 Gy in 25 fractions over 5 weeks (CFRT) or at a dose of 43.5 Gy in 15 fractions over 3 weeks (HFRT). The modified intention-to-treat population was used in primary and safety analyses. The primary endpoint was 5-year locoregional recurrence (LRR), and a 5% margin was used to establish non-inferiority. Findings: Between June 12, 2008 and June 16, 2016, 820 patients were recruited and randomly assigned to CFRT (n=411) or HFRT (n=409). Intention-to-treat analyses included 409 participants with CFRT and 401 with HFRT. At a median follow-up of 58.5 months (IQR 39.2-81.8), the 5-year cumulative incidence of LRR was 8.1% in the CFRT group and 8.3% in the HFRT group (absolute difference, 0.2%; 90% confidence interval [CI], -3.0-2.6; hazard ratio, 1.10; 90% CI, 0.72-1.69). The 5-year OS rate was 83.2% versus 85.6% (P=0.526). There were no significant differences in toxicities, except that the HFRT group had less acute skin toxicity than the CFRT group. Interpretation: Postmastectomy HFRT was non-inferior to and was as safe as CFRT in high-risk breast cancer patients. This option affords more convenient treatment and allows providers to treat more patients. Clinical Trial Number: The trial was registered at ClinicalTrials.gov, number NCT00793962. Funding Statement: This study was supported by the National Key Projects of Research and Development of China (2016YFC0904600); the Chinese Academy of Medical Science (CAMS) Innovation Fund for Medical Sciences (CIFMS, 2016-I2M-1-001); and Beijing Marathon of Hope, Cancer Foundation of China (LC2008A06). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This study is a randomized phase III non-inferiority, open-label trial, with patients recruited from a single academic hospital in China. The study protocol was approved by the local Ethics Committee.