Hypofractionated Versus Conventionally Fractionated Postmastectomy Radiotherapy With Internal Mammary Node Irradiation for High-Risk Breast Cancer (HypoMast-IMNI): A Randomized Phase III Trial
In brief
16-session breast radiotherapy matches 25 sessions, with less severe skin toxicity
In this randomized trial of 1,429 patients with high-risk breast cancer, recurrence near the treated area at 5 years was 1.7% with 16 radiotherapy sessions and 2.2% with 25, meeting the study's noninferiority criterion. Severe acute skin reactions were less frequent with the shorter course, while other cancer outcomes and lung and heart safety were similar; longer follow-up will clarify durability.
- Journal
- Journal of clinical oncology : official journal of the American Society of Clinical Oncology (Q1)
- Published
- 19 October 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Xiaofang Wang, Xiaomeng Zhang, Xingxing Chen, Zhaozhi Yang, Xin Mei, Li Zhang, et al.
- PMID
- 42896129
- DOI
- 10.1200/JCO-25-02843
Why clinicians should know about it
- Picked for Radiation Oncology (paper of the day, 20 October 2026): Phase III hypofractionated postmastectomy RT trial
- Picked for Oncology and Radiation Oncology (paper of the day, 20 October 2026): Phase III non‑inferiority hypofractionated PMRT with IMNI
Abstract
PURPOSE: When coverage of internal mammary nodes (IMN) is required, the efficacy and safety of hypofractionated regimens within postmastectomy radiotherapy (PMRT) remain to be established. This study evaluated hypofractionated radiotherapy (HypoRT) in patients with high-risk, operable breast cancer undergoing PMRT with IMN irradiation (IMNI). METHODS: In this phase III noninferiority trial, eligible patients with high-risk disease after mastectomy (including pT1-4N2-3, pT3-4N1, or pT1-2N1 disease with additional high-risk factors) were randomly assigned (1:1) to HypoRT (42.56 Gy in 16 fractions) or conventionally fractionated radiotherapy (ConvRT; 50 Gy in 25 fractions), both targeting the chest wall and regional lymph nodes, including the IMN. The primary end point was locoregional recurrence (LRR). Secondary end points were distant metastasis-free survival (DMFS), breast cancer recurrence-free survival (BCRFS), disease-free survival (DFS), overall survival (OS), and treatment-related toxicity. The trial is registered with ClinicalTrial.gov (identifier: NCT03856372). RESULTS: Between September 2018 and July 2022, 1,494 patients were randomly assigned. After a median follow-up of 58.1 months in the modified intention-to-treat population (n = 1,429), the 5-year cumulative incidence of LRR was 1.7% (95% CI, 0.9 to 2.9) with HypoRT and 2.2% (95% CI, 1.3 to 3.5) with ConvRT (hazard ratio, 0.69 [95% CI, 0.32 to 1.51]), meeting the noninferiority criterion (P = .017). No significant differences were observed in 5-year DMFS, BCRFS, DFS, or OS. Grade 3 acute skin toxicity was significantly lower with HypoRT (1.7% v 12.2%, P < .001). The incidence of grade ≥2 radiation pneumonitis and pulmonary fibrosis was low and comparable between arms, with no ischemic cardiac events recorded. CONCLUSION: For patients with high-risk, operable breast cancer requiring PMRT with IMNI, the 16-fraction HypoRT regimen is noninferior to ConvRT for locoregional control, offers a superior acute toxicity profile, and demonstrates excellent cardiopulmonary safety.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.