Moderately hypofractionated locoregional radiation therapy has been found to be non-inferior to standard normofractionated radiation therapy in terms of lymphedema risk for patients with early breast cancer. The phase 3 HypoG-01 trial, presented at the 2024 ESMO Congress, suggests a potential shift in practice towards shorter, 3-week radiotherapy regimens. This approach could reduce treatment burden for patients and decrease healthcare costs without compromising safety or survival outcomes.
Comparable Lymphedema Risk
With a median follow-up of 4.8 years, the HypoG-01 trial demonstrated that hypofractionated radiotherapy was non-inferior to normofractionated radiotherapy (P < .001). Among the 1113 patients with baseline and end-of-radiotherapy arm measurements, 275 events related to arm lymphedema occurred. The cumulative 5-year rate of arm lymphedema was 33.3% (95% CI, 28.7%-38.4%) in the hypofractionated arm versus 32.8% (95% CI, 27.9%-38.1%) in the normofractionated arm.
Sofia Rivera, MD, PhD, of the department of oncology at Institut Gustave Roussy in Villejuif, France, noted, "It's important to note that no detrimental effect of hypofractionated radiotherapy was seen regarding the safety profile, regarding all the criteria on survival... I think we should now privilege the 3 weeks regimen, even for nodal radiotherapy, in breast cancer."
Survival Outcomes
The study also found no sign of a detrimental effect of hypofractionated radiotherapy with regard to survival. The hazard ratio for breast cancer-specific survival was 0.53 (95% CI, 0.30-0.94), and the hazard ratio for overall survival was 0.59 (95% CI, 0.37-0.93). Additionally, there was no sign of detrimental effect of hypofractionated radiotherapy on local recurrent-free survival (HR = 0.62; 95% CI, 0.32-1.00) and distant disease-free survival (HR = 0.54; 95% CI, 0.31-0.96).
Shoulder Range of Motion and Adverse Events
Hypofractionated radiotherapy did not negatively impact patients' shoulder range of motion. The cumulative 5-year range of motion impairment rate was 19.6% (95% CI, 16.1%-23.7%) in the hypofractionated arm versus 20.7% (95% CI, 17.2%-24.8%) in the normofractionated arm. The hazard ratio for the cumulative range of shoulder motion impairment rate was 0.90 (95% CI, 0.81-1.00).
Adverse events were limited in both arms, with 12.7% (n = 80) of patients in the hypofractionated group experiencing a grade 3 or higher adverse event compared with 12.6% (n = 79) in the normofractionated group. No grade 5 events were reported. Cardiac disorders at 5 years were limited between patients assigned hypofractionated radiotherapy and those assigned normofractionated radiotherapy (2% vs 1%, respectively). Common adverse events, balanced between both arms, included fibrosis, fatigue, radiation skin injury, and pain.
Study Design and Patient Population
The HypoG-01 trial enrolled 1265 patients from 29 centers across France between September 2016 and March 2020. Eligible patients were women aged 18 years and older who underwent surgery for T1-3, N0-3, M0 breast cancer with an indication for regional nodes radiotherapy. Patients were randomized 1:1 to receive hypofractionated radiotherapy (40 Gy/15 fractions over 3 weeks) or normofractionated radiotherapy (50 Gy/25 fractions over 5 weeks). Both groups could receive a boost at the investigator’s discretion.
The primary endpoint was the 3-year cumulative incidence of arm lymphedema, defined as a 10% or more increase in arm circumference 15 cm proximal and/or 10 cm distal of the olecranon relative to baseline, compared with the contralateral circumference. Secondary endpoints included overall survival, locoregional-free survival, distant disease-free survival, breast cancer-specific survival, and shoulder range of motion.
Implications for Clinical Practice
The results of the HypoG-01 trial suggest that moderately hypofractionated radiotherapy is a safe and effective alternative to standard normofractionated radiotherapy for early breast cancer patients requiring nodal irradiation. The shorter treatment duration offers potential benefits for patients, including reduced treatment burden and improved convenience, as well as for healthcare systems through decreased costs and increased efficiency. As Dr. Rivera stated, "Because of the benefit for the patients and the shortening of the treatment, the benefit in terms of decreased burden and the benefits for healthcare in general, I think we should now privilege the 3 weeks regimen, even for nodal radiotherapy, in breast cancer."
