KEY POINTS
- RT CHARM (Alliance A221505) was a randomized noninferiority trial enrolling 898 women with unilateral invasive breast cancer requiring postmastectomy radiotherapy (PMRT) and planning immediate or delayed breast reconstruction. Enrollment occurred between 2018 and 2021, and 825 patients were evaluable for the primary endpoint, with a median follow-up of 3.9 years.
- Patients were randomized 1:1 to conventional PMRT delivering 50 Gy in 25 fractions over five weeks, or hypofractionated PMRT delivering 42.56 Gy in 16 fractions over three weeks. Randomization was stratified by reconstruction timing (immediate versus delayed) and reconstruction type (autologous versus implant-only).
- The primary endpoint was the 24-month reconstruction complication rate, a composite of wound-healing complications, readmission, capsular contracture, unplanned reoperation and reconstruction failure. The trial prespecified a 10-percentage-point noninferiority margin, making reconstruction outcomes the primary basis for evaluating the shorter regimen.
- At 24 months, reconstruction complications occurred in 52/422 patients (12.3%) after hypofractionated PMRT versus 41/403 (10.2%) after conventional treatment. The absolute difference was approximately 2.1 percentage points, with confidence limits compatible with the trial's prespecified noninferiority criterion, establishing that the shorter schedule was noninferior for reconstruction complications.
- Reconstruction type influenced risk independently of treatment fractionation. Patients undergoing implant-only reconstruction had higher complication rates than those receiving autologous reconstruction, with a reported odds ratio of 1.65, emphasizing that surgical reconstruction strategy remains important even when RT fractionation is optimized.
- Locoregional recurrence at 36 months was 1.5% with hypofractionated PMRT versus 2.2% with conventional PMRT, without a statistically significant difference. These low event rates are reassuring, although the study's primary noninferiority conclusion concerns reconstruction complications rather than a formal demonstration of oncological noninferiority.
- Acute and late toxicity rates were not statistically different between treatment arms. The 16-fraction regimen shortened the radiation course from five to three weeks, reducing treatment visits without a demonstrated increase in reconstruction complications, local recurrence or reported toxicity during the available follow-up.
CLINICAL TAKEAWAY
RT CHARM provides randomized evidence that 42.56 Gy in 16 fractions is a reasonable alternative to 50 Gy in 25 fractions for women receiving PMRT with immediate or delayed breast reconstruction. The shorter regimen met its prespecified noninferiority criterion for reconstruction complications and reduces treatment burden, while longer-term oncological outcomes and individual reconstruction-related risks remain relevant to treatment selection.