Hypofractionated postmastectomy radiotherapy (PMRT) has demonstrated non-inferiority to standard radiation in patients who underwent mastectomy and reconstruction, according to the phase 3 RT CHARM trial (NCT03414970). The findings, presented at the 2024 American Society for Radiation Oncology (ASTRO) Annual Meeting, suggest that a shorter course of radiation therapy may be as effective as the conventional, longer course, without increasing complications or compromising disease control.
The primary endpoint of the RT CHARM trial focused on reconstruction complications at 24 months. In the intent-to-treat analysis (n = 825), conventional PMRT resulted in complications in 12.2% of patients, while hypofractionated PMRT led to complications in 14.2% (estimated difference, –2.1%; 95% CI, –6.7% to 2.6%; P = .0004). This met the criteria for non-inferiority. An as-treated analysis (n = 650) showed complication rates of 13.1% and 16.6% for conventional and hypofractionated PMRT, respectively (estimated difference, –3.4%; 95% CI, –8.9% to 2.0%; P = .009).
Recurrence Rates
Local and local regional recurrence rates were similar between the two arms. In the conventional PMRT arm, 7 out of 403 patients experienced recurrence, compared to 9 out of 422 in the hypofractionated PMRT arm (HR, 0.85; 95% CI, 0.32-2.27). This indicates no significant difference in recurrence incidence between the two radiation approaches.
Clinical Implications
"Hypofractionated PMRT with reconstruction should become the new standard therapy," said lead study author Matthew M. Poppe, MD, FASTRO, professor in the Department of Radiation Oncology at the University of Utah Huntsman Cancer Institute. He emphasized that this shift could significantly improve the lives of breast cancer patients. Dr. Poppe also highlighted the novelty of the trial, noting the scarcity of prospective, randomized data on radiation and breast reconstruction complications, which have primarily been assessed retrospectively.
Trial Design
The RT CHARM trial enrolled 880 patients requiring PMRT with planned reconstruction. Participants were stratified based on immediate or delayed implant or autologous tissue reconstruction. They were then randomized to receive either conventional PMRT (50 Gy in 25 fractions over 5 to 6 weeks) or hypofractionated PMRT (42.56 Gy in 16 fractions over 3 to 4 weeks).
Secondary endpoints included the incidence of acute and late radiation complications based on Common Terminology Criteria for Adverse Events 4.0 toxicity, local and local regional recurrence-free survival, and reconstruction complication rates based on the reconstruction method.
