Impact of radiation dose on complications among women with breast cancer who underwent breast reconstruction and post-mastectomy radiotherapy: a multi-institutional validation study

Abstract Purpose Emerging data suggest that higher radiation doses in post-mastectomy radiotherapy may be associated with an increased risk of reconstruction complications. This study aimed to validate previous findings regarding the impact of radiation dose on complications among women with breast cancer using a multi-center dataset. Methods Fifteen institutions participated, and women with breast cancer who received radiotherapy after either autologous or prosthetic breast reconstruction were included. The primary endpoint was major post-radiotherapy complications requiring re-operation for explantation, flap failure, or bleeding control. Results In total, 314 patients were included. Radiotherapy was performed using both conventional fractionation and hypofractionation in various schedules. The range of the radiotherapy dose in Equivalent Dose in 2 Gy fractions (EQD2; α/β=3.5) varied from 43.4 to 71.0 Gy (median dose: 48.6 Gy). Boost radiotherapy was administered to 49 patients. Major post-radiotherapy complications were observed in 24 (7.6%) patients. In multivariate analysis, an increasing EQD2 per Gy (odds ratio [OR]: 1.58, 95% confidence interval [CI]: 1.26–1.98; p Conclusion A dose-response relationship between radiation dose and the risk of complications was validated in this multi-center dataset. In this context, we hypothesize that the use of hypofractionated radiotherapy (40 Gy in 15 fractions) may improve breast reconstruction outcomes. Our multi-center prospective observational study (NCT03523078) is underway to further validate this hypothesis.