Researchers compared hypofractionated radiotherapy vs a conventional regimen to study outcomes and toxicity in breast cancer patients.
A regimen of hypofractionated radiotherapy (RT) was noninferior to conventional RT and had similar toxicity in patients with high-risk breast cancer following mastectomy, according to a new study. The shorter course of therapy may offer a convenient alternative to the conventional approach.
“There is growing interest in delivering postmastectomy radiotherapy with hypofractionated schedules, because shorter and more convenient hypofractionated dose schedules might help to treat more patients and reduce costs,” wrote study authors led by Shu-Lian Wang, MD, of the Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing. Before the new study, no randomized trial had compared hypofractionated and conventional approaches after mastectomy.
The study included 820 patients who had undergone mastectomy and had at least four positive axillary lymph nodes or a primary tumor stage of T3–4. They were randomized to receive either a hypofractionated RT regimen of 43.5 Gy in 15 fractions over 3 weeks (401 patients in modified intent-to-treat analysis) or a conventional regimen of 50 Gy in 25 fractions over 5 weeks (409 patients). They were followed for a median of 58.5 months; the results were published in Lancet Oncology.
In the hypofractionated group, 31 patients developed locoregional recurrence, compared with 29 in the conventional RT group. The 5-year cumulative incidence of locoregional recurrence was 8.3% with the hypofractionated regimen and 8.1% with the conventional regimen, for a hazard ratio (HR) of 1.10 (90% CI, 0.72–1.69; P < .0001 for noninferiority).
There were no differences between the groups with regard to survival outcomes. The 5-year overall survival rate was 86% with conventional RT and 84% with hypofractionated RT, for an HR of 1.13 (95% CI, 0.78–1.62; P = .526). For disease-free survival at 5 years, the rate was 70% with conventional RT and 74% with hypofractionated RT, for an HR of 0.88 (95% CI, 0.67–1.16; P = .429).
Toxicities were similar between the two groups, and there were no grade 4 toxicities or deaths due to adverse events seen in the study. Hypofractionated RT was associated with less frequent grade 3 acute skin toxicity compared with conventional RT, at 3% and 8%, respectively (P < .0001). There were no differences with regard to radiation pneumonitis, lymphedema, ischemic heart disease, and shoulder dysfunction.
The authors noted that longer follow-up is still needed to document any long-term toxicities associated with this therapy. “This study provides high-level evidence for the clinical use of hypofractionated postmastectomy radiotherapy for patients with high-risk breast cancer,” they concluded. “It can be recommended in clinical practice to patients who do not plan breast reconstruction and will not receive internal mammary node irradiation.”
In an accompanying editorial, Reshma Jagsi, MD, of the University of Michigan in Ann Arbor, wrote that hypofractionation is “an elegant approach that promises to help to contain the costs of cancer care and mitigate financial toxicity.” She noted that some differences in how patients are treated in China vs elsewhere in the world do make firm conclusions from this study difficult; for example, only 55% of patients with HER2-positive disease were treated with trastuzumab, which could have meaningful differences in terms of cardiac outcomes.
To address some of these gaps, she noted that several trials involving hypofractionation are underway in the United States. “Together with other ongoing trials, this research will hopefully advance our understanding in the near future, and one day, hypofractionated regional nodal irradiation might be considered a standard approach worldwide,” she wrote.