Background
Randomized, non-inferiority phase 3 (Alliance A221505); N=898 enrolled 2018–2021, 825 evaluable. Women with unilateral invasive breast cancer, planned immediate or delayed reconstruction and PMRT. Fear of reconstruction complications has limited adoption of short-course PMRT. Stratified by immediate vs delayed and autologous vs implant-only reconstruction.
Results
Interventions and follow up: Arm A: Hypofractionated PMRT 42.56 Gy in 16 fractions over 3 weeks (n=422 evaluable)
Arm B: Conventional PMRT 50 Gy in 25 fractions over 5 weeks (n=403 evaluable)
Primary endpoint: 24-month reconstruction complication rate (composite of wound healing, readmission, capsular contracture, unplanned reoperation, reconstruction failure); non-inferiority margin 10%
mFollow up: 3.9 years
Results: 24-mo reconstruction complications: 12.3% (52/422) vs 10.2% (41/403); difference -2.1% (95% CI -6.5 to 2.2), non-inferiority met
Implant-only vs autologous (both arms): OR 1.65 for complications
36-mo locoregional recurrence: 1.5% (95% CI 0.7–3.2) vs 2.2% (95% CI 1.1–4.3), not significant
OS / DFS: NR
Arm B: Conventional PMRT 50 Gy in 25 fractions over 5 weeks (n=403 evaluable)
Primary endpoint: 24-month reconstruction complication rate (composite of wound healing, readmission, capsular contracture, unplanned reoperation, reconstruction failure); non-inferiority margin 10%
mFollow up: 3.9 years
Results: 24-mo reconstruction complications: 12.3% (52/422) vs 10.2% (41/403); difference -2.1% (95% CI -6.5 to 2.2), non-inferiority met
Implant-only vs autologous (both arms): OR 1.65 for complications
36-mo locoregional recurrence: 1.5% (95% CI 0.7–3.2) vs 2.2% (95% CI 1.1–4.3), not significant
OS / DFS: NR
Adverse events
Acute toxicity: not statistically different between arms
Late toxicity: not statistically different between arms
Grade ≥3 (any): NR
Late toxicity: not statistically different between arms
Grade ≥3 (any): NR
Conclusions
A 16-fraction hypofractionated PMRT course was safe and non-inferior to conventional PMRT for reconstruction complications in women undergoing breast reconstruction after mastectomy. Locoregional recurrence rates were low and similar.
Key Limitations
Open-label. Median follow-up 3.9 years, so late reconstruction outcomes and long-term locoregional control remain immature. Event rate in the control arm (10.2%) was lower than the 25% assumed, which affects the interpretation of the 10% margin. Complication composite is clinician-defined; patient-reported cosmesis and OS are NR in the abstract.
Clinical Context
Fills the main evidence gap left by earlier hypofractionation trials that largely excluded patients with reconstruction. Supports offering 3-week PMRT to patients with implant or autologous reconstruction. Implant-only reconstruction carried higher complication risk irrespective of fractionation. Guideline positioning not yet updated in this publication.
