TOPLINE

A 16-fraction radiotherapy regimen achieved locoregional control comparable to conventional 25-fraction radiotherapy in patients with high-risk breast cancer requiring internal mammary node irradiation (IMNI), with 5-year locoregional recurrence rates of 1.7% vs 2.2%. The hypofractionated course also reduced acute skin toxicity while maintaining low rates of cardiopulmonary complications.

METHODOLOGY

• It's unclear whether hypofractionated regimens are safe and effective for patients with high-risk breast cancer requiring IMNI. To investigate, researchers conducted a phase 3 noninferiority trial, enrolling 1494 women with high-risk disease (pathologic stage T1-4N2-3, T3-4N1, or T1-2N1 with additional high-risk factors) after mastectomy with negative margins and axillary lymph node dissection.
• Participants were randomly assigned 1:1 to receive either hypofractionated radiotherapy (HypoRT; 42.56 Gy in 16 fractions) or a conventional course (ConvRT; 50 Gy in 25 fractions), both targeting the chest wall and regional lymph nodes including the internal mammary nodes.
• Radiotherapy was delivered using contemporary techniques including simplified intensity-modulated radiotherapy or volumetric modulated arc therapy, with deep inspiration breath hold used selectively for left-sided cases.
• The primary outcome was locoregional recurrence. Secondary outcomes included distant metastasis-free survival (DMFS), breast cancer recurrence-free survival (BCRFS), disease-free survival (DFS), overall survival, and treatment-related toxicity.

TAKEAWAY

• Over a median follow-up of 58.1 months, HypoRT met the prespecified noninferiority criterion for locoregional recurrence, with a hazard ratio (HR) of 0.69 (P = .017 for noninferiority); the 5-year recurrence rate was 1.7% vs 2.2% with ConvRT. 
• No significant differences were observed between arms in 5-year DMFS (92.3% vs 92.7%; HR, 1.00), BCRFS (91.8% vs 92.3%; HR, 0.99), DFS (88.5% vs 89.4%; HR, 1.05), or overall survival (95.1% vs 96.1%; HR, 1.21).
• Grade 3 acute skin toxicity occurred significantly less often with HypoRT (1.7% vs 12.2%, P < .001), as did grade 1-2 skin pruritus (26.7% vs 35.2%, P = .001) and skin pain (7.7% vs 23.3%, P < .001).
• Both treatment groups had low and comparable rates of grade 2 or higher radiation pneumonitis (about 2% in both arms) and pulmonary fibrosis (1.3% in both). There were no ischemic cardiac events recorded.

IN PRACTICE

"For patients with high-risk, operable breast cancer requiring [post-mastectomy radiotherapy] 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," the study authors wrote. “These findings establish HypoRT as a safe and effective treatment option for this patient population.”

SOURCE

The study was led by Xiaofang Wang, MD, PhD, of Fudan University Shanghai Cancer Center in Shanghai, China. It was published online in the Journal of Clinical Oncology.

LIMITATIONS

The trial was conducted at a single center in China, which may affect generalizability. Exclusion of patients receiving neoadjuvant chemotherapy limits applicability to contemporary practice using newer systemic therapies and de-escalation strategies. All patients underwent axillary lymph node dissection, which may not reflect current practices. Longer follow-up is needed to track late toxicities, particularly cardiac effects.

DISCLOSURES

The study was supported by grants from the Noncommunicable Chronic Diseases-National Science and Technology Major Project, the National Key Research and Develop Program of China, and the National Natural Science Foundation of China. One author reported consulting fees from Lilly and holding a patent for a vascular support dilator used in microsurgery. The remaining authors reported no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.