Shorter Radiation Course Safe for Patients Undergoing Breast Reconstruction

Breast Reconstruction: Breast ReconstructionA shorter course of radiation therapy does not lead to increased complications among patients undergoing breast reconstruction after a mastectomy, according to data from the Phase III RT CHARM trial (Alliance A221505). These findings, presented during the 2024 ASTRO Annual Meeting, showed that hypofractionated radiation is non-inferior to standard radiation following mastectomy for reconstruction complications, toxicity, and local control (Abstract 1). “More than 100,000 mastectomies are performed in the U.S. each year for breast cancer and almost 50 percent of the women who undergo mastectomy will have breast reconstruction performed,” noted Matthew Poppe, MD, FASTRO, Professor of Radiation Oncology at the University of Utah in Salt Lake City. “Randomized trials tell us that radiation after mastectomy improves survival for a great many patients, such as those with larger tumors or involved lymph nodes,” he noted during a press conference. “Unfortunately, the standard-of-care radiation is not very convenient or cost-effective and takes 5-6 weeks. Many patients have to forgo this life-saving treatment given the time and expense involved.” Based on several randomized trials, hypofractionation, or short course, radiation has become standard practice in lumpectomy patients, according to Poppe. However, there is limited data on this approach in mastectomy and, particularly, breast reconstruction settings. Studying radiation effects in the reconstructed breast is difficult for a number of reasons, Poppe noted. There are a multitude of reconstruction methods, including implant, autologous tissue, and tissue expanders, and the timing of reconstruction can be immediate or delayed. Available data has shown that radiation after reconstruction can increase complication rates, with an estimated 20-30 percent of patients experiencing complications, such as wound healing, reoperation, infection, contracture, or even loss of the reconstructed breast. To address the lack of evidence regarding hypofractionated postmastectomy radiation therapy (PMRT) in this patient population, Poppe and colleagues initiated a non-inferiority, multi-institutional, prospective randomized trial. Research Methodology The Phase III RT CHARM study (Alliance A221505) compared hypofractionated radiation in 16 fractions to the standard 25 fractions in patients undergoing or having completed breast reconstruction. Composite reconstruction complication (i.e., wound healing, readmission, capsular contracture, unplanned reoperation, reconstruction failure) was the primary outcome of this analysis. Poppe and colleagues enrolled patients with unilateral invasive breast cancer, pT0-2 pN1-2 or pT3N0, or clinically staged before neoadjuvant chemotherapy who were planning delayed or immediate breast reconstruction and postmastectomy radiation therapy. Eligible patients were randomized 1:1 to receive either conventional radiation consisting of 25 fractions delivered across 5 weeks (50 Gy total) or hypofractionated radiation consisting of 16 fractions delivered across approximately 3 weeks (42.56 Gy total). “The study was designed to test non-inferiority of hypofractionated to conventional PMRT with non-inferiority margin of 10 percent, assuming a complication rate of 25 percent in the conventional arm,” Poppe and team explained. “Accounting for 10 percent ineligibility, a sample size of 880 patients provided 90 percent power at one-sided type I error of 0.025 with one interim analysis. Randomization was stratified by planned immediate versus delayed and autologous versus implant-only reconstruction.” Main Takeaways From 2018 to 2021, 898 patients were enrolled from 209 academic and community-based cancer centers in the U.S. and Canada with a median follow-up of 4.5 years. Seventy-three women left the study before the primary event could be analyzed, according to the researchers. Patient and tumor characteristics were well-balanced between both treatment arms. The median age was 49 years. Fifty-one percent of patients received neoadjuvant chemotherapy and 37 percent underwent chemotherapy following mastectomy. Among the 825 patients in the intention-to-treat analysis, Poppe and colleagues reported that the rate of complications at 2 years was .2 percent and 14.2 percent in the conventional PMRT and hypofractionated PMRT arms, respectively. This difference was considered statistically non-inferior, according to Poppe. Data showed that noninferiority was maintained irrespective of the timing or type of reconstruction surgery. During the study period, 650 patients completed reconstruction. Of those, 59 percent had implants alone and 41 percent underwent autologous reconstruction using their own tissue, with or without implants. The investigators observed that the rate of complications at 2 years was 13.1 percent among patients who received conventional PMRT compared with 16.6 percent in those who underwent hypofractionated treatment. Local and local-regional recurrence rates are low in both arms at 3 years, Poppe reported. “The conventional fractionation has a 1.9 percent recurrence and the short course radiation a 1.5 percent recurrence—both are low and not statistically different.” Results from the Phase III RT CHARM trial demonstrated that a 16-fraction course of hypofractionated postmastectomy radiation therapy appears safe and effective for patients undergoing breast reconstruction and is non-inferior to a traditional 25-fraction course of PMRT, according to Poppe. “Hypofractionated PMRT with reconstruction should become the new standard of therapy,” he said, while emphasizing that this change will improve the lives of breast cancer patients. “Over the past 10 years, we've tried to move all patients who need breast radiation to a shorter, more convenient schedule,” Poppe noted in a statement. “But patients after mastectomy who were planning breast reconstruction were the one group where we didn't have sufficient data to support shorter courses. Now, the results of this trial show we can safely reduce treatment time for these patients to 3 weeks without compromising their reconstruction. “There's been a slow start to moving to shorter treatment courses after mastectomy, even with no reconstruction,” he added. “But now we have robust data from hundreds of academic and community centers, and from patients with any type of reconstruction that clearly show the safety and effectiveness of short-course radiation.” Catlin Nalley is a contributing writer.

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