Background
Randomized phase 3 noninferiority trial (Fudan University Shanghai Cancer Center). N=1,494 randomized (mITT 1,429) with high-risk operable breast cancer after mastectomy (pT1-4N2-3, pT3-4N1, or pT1-2N1 with additional high-risk factors) requiring PMRT with internal mammary node irradiation (IMNI). Question: is hypofractionation safe when IMN is covered?
Results
Interventions and follow up: Arm A: HypoRT 42.56 Gy in 16 fractions to chest wall + regional nodes incl. IMN
Arm B: ConvRT 50 Gy in 25 fractions, same volumes
Primary endpoint: locoregional recurrence (LRR)
mFollow up: 58.1 mo
Results: 5-y LRR: 1.7% (95% CI 0.9-2.9) vs 2.2% (95% CI 1.3-3.5); HR 0.69 (95% CI 0.32-1.51); noninferiority met (P=.017)
DMFS, BCRFS, DFS, OS (5-y): no significant differences; point estimates NR in abstract
Arm B: ConvRT 50 Gy in 25 fractions, same volumes
Primary endpoint: locoregional recurrence (LRR)
mFollow up: 58.1 mo
Results: 5-y LRR: 1.7% (95% CI 0.9-2.9) vs 2.2% (95% CI 1.3-3.5); HR 0.69 (95% CI 0.32-1.51); noninferiority met (P=.017)
DMFS, BCRFS, DFS, OS (5-y): no significant differences; point estimates NR in abstract
Adverse events
Grade 3 acute skin toxicity: 1.7% vs 12.2%, P<.001
Grade ≥2 radiation pneumonitis / pulmonary fibrosis: low, comparable between arms (rates NR in abstract)
Cardiac: no ischemic cardiac events
Grade ≥2 radiation pneumonitis / pulmonary fibrosis: low, comparable between arms (rates NR in abstract)
Cardiac: no ischemic cardiac events
Conclusions
16-fraction HypoRT was noninferior to 25-fraction ConvRT for locoregional control in high-risk patients needing PMRT with IMNI, with less acute skin toxicity and excellent cardiopulmonary safety. Supports hypofractionation including IMN coverage.
Key Limitations
Single-country (China) trial; median follow-up ~5 y, short for late cardiac/lymphedema/reconstruction outcomes. Very low event rate (LRR ~2%) means wide CI on HR (0.32-1.51). Open-label RT design; reconstruction and late toxicity details NR in abstract.
Clinical Context
Extends hypofractionated PMRT evidence (e.g., HypoG-01, FAST-Forward-type regimens, Chinese PMRT trials) to patients with IMN irradiation, an under-represented group. Guideline positioning (ASTRO/ESTRO) not verified here; confirm on review.
