A 3-week moderately hypofractionated radiotherapy regimen has been found to be noninferior to the 5-week fractionation when irradiating nodal areas in patients with breast cancer, according to data presented at the European Society for Medical Oncology (ESMO) Congress 2024.1 The 5-year results of the phase III HypoG-01 trial demonstrated a cumulative incidence of arm lymphedema of approximately 33% with both regimens, potentially changing the standard of care for patients with breast cancer requiring nodal irradiation.
Sofia Rivera, MD, PhD
“Nodal radiotherapy for breast cancer no longer needs 5 weeks,” said lead investigator Sofia Rivera, MD, PhD, of the Department of Oncology at Institut Gustave Roussy in Villejuif, France. “Because of the benefit for patients and the shortening of the treatment, we should now adopt the 3-week regimen even for nodal radiotherapy in breast cancer.”
Although hypofractionated radiotherapy has become standard for breast-alone irradiation, said Dr. Rivera, concerns about possible increased toxicity have limited its use in nodal irradiation. The HypoG-01 trial addressed this gap, focusing on patients requiring nodal irradiation using modern radiotherapy techniques.
Study Design
The HypoG-01 trial enrolled 1,265 patients across 29 centers in France between September 2016 and March 2020. Eligible patients had T1–3, N0–3, M0 breast cancer requiring nodal irradiation. Participants were randomly assigned 1:1 to receive either moderately hypofractionated radiotherapy over 3 weeks or standard fractionated radiotherapy over 5 weeks, with or without a boost in both arms.
The study design included the primary endpoint of 3-year cumulative incidence of arm lymphedema. Secondary endpoints encompassed overall survival, locoregional-free survival, distant disease–free survival, breast cancer–specific survival, and shoulder range-of-motion impairments. The per-protocol population consisted of 562 patients in the hypofractionated arm and 551 in the standard fractionated arm.
Equivalent Efficacy, Reduced Treatment Time
As Dr. Rivera reported, results showed noninferiority of hypofractionated radiotherapy in terms of arm lymphedema, with a 5-year cumulative incidence of approximately 33% in both trial arms. Of note, there were no detrimental effects on survival outcomes observed, said Dr. Rivera, with a potential trend toward improved breast cancer–specific and overall survival (hazard ratios = 0.53 and 0.59, respectively).
KEY POINTS
- Results of the phase III HypoG-01 trial have shown that moderately hypofractionated radiotherapy (3 weeks) is noninferior to standard fractionation (5 weeks) for nodal irradiation in breast cancer.
- The 5-year cumulative incidence of arm lymphedema was approximately 33% in both treatment arms.
- No detrimental effects were observed in the safety profile or survival outcomes with the hypofractionated regimen.
Toxicity rates were also found to be similar between the treatment arms, with about 12.6% grade 3 or higher adverse events. The shoulder range-of-motion impairment was comparable, occurring in approximately 20% of patients in both trial arms.
“The cumulative rate of arm lymphedema and shoulder range-of-motion impairment remains significant in both arms, highlighting the need for continued focus on reducing these side effects in future strategies,” said Dr. Rivera.
What’s Next?
Looking ahead, Dr. Rivera noted that trials investigating five-fraction regimens for nodal irradiation are beginning, with results expected in 5 to 10 years. However, the HypoG-01 results, along with the anticipated publication of the parallel Skagen 1 trial, are set to reshape radiotherapy practices in breast cancer treatment.
“This study offers a more sustainable radiotherapy approach, potentially increasing access for patients who need it while reducing treatment burden,” Dr. Rivera concluded. “We eagerly await the combined publication with the Skagen 1 trial to further solidify these practice-changing results.”
EXPERT POINT OF VIEW
Charlotte E. Coles, MD, FRCR
Invited discussant of the HypoG-01 trial, Charlotte E. Coles, MD, FRCR, Professor of Breast Cancer Clinical Oncology, University of Cambridge, United Kingdom, emphasized the robust evidence now available supporting hypofractionated radiotherapy for breast cancer, including nodal irradiation.
“We now have data from more than 5,800 participants in really high-quality randomized trials,” said Dr. Coles. “We have not seen any statistical differences in late normal tissue effects, including lymphedema, and other cancer endpoints are no different compared with 5-week radiotherapy.”
Based on this accumulating evidence, Dr. Coles concurred with the HypoG-01 investigators, asserting that “5-week nodal radiotherapy is no longer indicated, and 3-week nodal radiotherapy is the international standard of care.”
Advantages of Hypofractionated Radiotherapy
According to Dr. Coles, this shift represents a significant change in practice, potentially benefiting patients worldwide. Here she highlighted several advantages of hypofractionated radiotherapy:
- Efficacy: Equivalent tumor control to conventional fractionation
- Safety: Reduced or similar toxicity compared with longer regimens
- Patient-centric: Reduces treatment burden, allowing patients to resume normal life sooner
- Health system benefits: Lowers costs and increases treatment capacity
- Global equity: Improves access to radiotherapy, particularly in resource-limited settings. According to Dr. Coles, shorter treatment regimens may help to address this inequity.
On the Horizon
Looking to the future, Dr. Coles mentioned ongoing trials investigating ultra-hypofractionation (1-week regimens) for nodal irradiation, including the FAST-Forward boost study and the HYPORT adjuvant trial. She called for continued collaboration in designing and recruiting for high-quality studies to further improve patient outcomes.
“Hypofractionation is efficacious, has reduced or similar toxicity, reduces patient burden, reduces health-system costs, and increases equity of access globally,” Dr. Coles concluded. “If ultra-hypofractionation is proven to be safe and effective, I hope that adoption of 1-week regimens is faster than the relatively slow uptake of 3-week regimens.”
DISCLOSURE: Dr. Rivera reported no conflicts of interest. Dr. Coles was a member of the independent data monitoring committee for HypoG-01 trial (last meeting: February 20, 2019, no involvement since then).
REFERENCE
1. Rivera S, Ghodssighassemabadi R, Brion T, et al: Locoregional hypo vs normofractionated RT in early breast cancer: 5 years results of the HypoG-01 phase III UNICANCER trial. ESMO Congress 2024. Abstract 231O. Presented September 15, 2024.
