Multicenter randomized trial of hypofractionated postmastectomy radiation therapy in women with breast reconstruction

Patients with breast cancer requiring postmastectomy radiation therapy (PMRT) often desire breast reconstruction, which can be adversely affected by PMRT. A multicenter randomized noninferiority trial in USA compared hypofractionated versus conventional PMRT in patients undergoing breast reconstruction. The primary outcome was reconstruction complication rate, a composite of wound healing, readmission, capsular contracture, unplanned reoperation, and reconstruction failure. Women with unilateral invasive breast cancer with planned reconstruction and PMRT were randomized 1:1 to 50 Gy in 25 fractions over 5 weeks of 42.56 Gy in 16 fractions of 3 weeks. The noninferiority margin was 10%, assuming a 2-year reconstruction complication rate of 25% with conventional PMRT. Between 2018 and 2021, 898 patients enrolled with a median follow-up of 3.9 years. Among 825 patients evaluable for the primary endpoint, the 24 month reconstruction complication rates were 12.3% with hypofractionated PMRT and 10.2% with conventional PMRT (difference -2.1%; 95% CI -6.5 to 2.2). Regardless of arm, the complication rate was higher with implant-only versus autologous reconstruction (OR 1.65). There was no statistically significant difference in 36-month locoregional recurrence rates: 1.5% (95% CI 0.7-3.2) with hypofractionated PMRT and 2.2% (1.1-4.3) with conventional PMRT. Acute and late toxicity rates were not statistically different. The authors conclude that a 16-fraction course of hypofractionated PMRT is safe and noninferior to conventional PMRT in women undergoing breast reconstruction.