A shorter course of postmastectomy radiation therapy was noninferior to conventional radiation therapy in terms of breast reconstruction complications among women with breast cancer undergoing the procedure, according to findings from the randomized RT CHARM trial reported by Poppe et al in the Journal of Clinical Oncology. The investigators also found no significant differences in locoregional recurrence or overall radiation-related toxicity between the treatment approaches.
Study Details
The multicenter, open-label, noninferiority phase III RT CHARM trial (Alliance A221505) enrolled 898 women with unilateral invasive breast cancer who had undergone mastectomy and were planning or undergoing breast reconstruction. The trial was conducted at 209 academic and community sites in the United States and Canada between February 2018 and August 2021.
Patients were randomly assigned 1:1 to receive either hypofractionated radiation therapy (42.56 Gy in 16 fractions over approximately 3 weeks) or conventional radiation therapy (50 Gy in 25 fractions over approximately 5 weeks). Randomization was stratified by planned reconstruction timing (immediate vs delayed) and type (autologous vs implant-only).
The primary endpoint was the 24-month reconstruction complication rate, a composite measure including unplanned hospital readmission, reoperation, severe capsular contracture, and reconstruction failure. Secondary endpoints included locoregional recurrence and acute and late radiation-related toxicity. The prespecified noninferiority margin was 10%.
Key Results
Of the 898 enrolled patients, 825 were evaluable for the primary analysis, including 422 assigned to hypofractionated radiation therapy and 403 assigned to conventional radiation therapy. At a median follow-up of 3.9 years, the 24-month reconstruction complication rates were 12.3% (52 of 422 patients) and 10.2% (41 of 403 patients), respectively. The estimated difference, calculated as conventional minus hypofractionated therapy, was –2.1 percentage points (95% confidence interval [CI] = –6.5 to 2.2; P = .0001 for noninferiority), meeting the primary endpoint.
Among 631 patients who completed reconstruction within 18 months of radiation therapy, complication rates were 12.6% with hypofractionated therapy and 10.4% with conventional therapy (P = .001 for noninferiority). In multivariable analysis, delayed reconstruction was associated with significantly greater odds of complications than immediate reconstruction (odds ratio = 2.96, 95% CI = 1.42–6.17; P = .004), regardless of radiation schedule. Implant-only reconstruction was associated with numerically higher complication rates than autologous reconstruction, although the difference was not statistically significant.
At 3 years, locoregional recurrence–free survival was 97.0% with hypofractionated therapy vs 96.2% with conventional therapy (hazard ratio = 1.01, 95% CI = 0.53–1.96; P = .97). The corresponding cumulative incidences of locoregional recurrence were 1.5% and 2.2%, respectively.
Rates of grade 3 or higher acute toxicity were 5.0% with hypofractionated therapy and 7.7% with conventional therapy (P = .11). Acute grade 2 dermatitis occurred less frequently with hypofractionated therapy (20% vs 42%; P < .0001), as did grade 3 dermatitis (1% vs 3%; P = .048). Late toxicity rates did not differ significantly between groups.
The investigators concluded: “A 16-fraction course of hypofractionated [postmastectomy radiation therapy] is safe and noninferior to conventional [postmastectomy radiation therapy] in women undergoing breast reconstruction after mastectomy.”
Matthew Poppe, MD, of Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by the National Cancer Institute of the National Institutes of Health. For full disclosures of the study authors, visit ascopubs.org.
