Postmastectomy radiation therapy may be significantly shortened for many patients planning breast reconstruction, according to data from a large phase III trial (RT CHARM, Alliance A221505).¹ Investigators reported that hypofractionated (short-course) radiation therapy was found to be noninferior to conventional fractionation in patients with breast cancer who underwent breast reconstruction after mastectomy. According to the study authors, these findings may potentially change the standard of care for postmastectomy radiation therapy and represent a “significant step forward” for this patient population. These findings were presented at the 2024 American Society for Radiation Oncology (ASTRO) Annual Meeting.¹

“Over the past 10 years, we’ve tried to move all patients who need breast radiation to a shorter, more convenient schedule,” said principal investigator of the trial, Matthew M. Poppe, MD, FASTRO, Professor of Radiation Oncology at the University of Utah in Salt Lake City. “Now, the results of this trial show we can safely reduce treatment time for these patients to 3 weeks without compromising their [breast] reconstruction.”

“The results of this trial show we can safely reduce treatment time for these patients to 3 weeks without compromising their [breast] reconstruction.”

— MATTHEW M. POPPE, MD, FASTRO

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As Dr. Poppe reported, breast cancer is the second most frequently diagnosed cancer for women in the United States. Approximately 40% of patients with breast cancer undergo mastectomy, with the majority opting for reconstructive breast surgery. Many of these patients also require postmastectomy radiation therapy to prevent cancer recurrence.

Recent research has shown that shorter courses of radiation therapy may be effective for some patients with breast cancer, noted Dr. Poppe. However, those seeking radiation therapy after mastectomy have been typically excluded from these studies because of concerns about potential side effects on the reconstructive process.

Study Design

The RT CHARM trial enrolled 898 patients with unilateral invasive breast cancer at 209 academic and community-based cancer centers across the United States and Canada. Eligible patients included those with larger tumors (pT3N0) or smaller tumors as well as invasion of the regional lymph nodes (pT0–2 pN1–2). The median patient age was 46 years.

Patients were randomly assigned to receive either conventional radiation consisting of 25 fractions over 5 weeks (50 Gy total; n = 449) or hypofractionated radiation consisting of 16 fractions over approximately 3 weeks (42.56 Gy total; n = 449). Among the 650 patients who completed breast reconstruction during the study period, 59% had implants alone, and 41% had autologous breast reconstruction (with or without implants). The median follow-up period was 5 years.

Hypofractionation Did Not Increase Complications

The primary analysis, based on patients with a minimum of 2 years of follow-up, demonstrated noninferiority between conventional fractionation and hypofractionation in terms of breast reconstruction complications. Complication rates at 2 years after breast reconstructive surgery were 14% with hypofractionated radiation and 12% with conventional radiation, and the difference was considered to be statistically noninferior (P = .0004).

“It was very exciting to see a complication rate that was nearly half what we anticipated.”

— ATIF J. KHAN, MD, MS

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“We expected a complication rate of 25% based on prior, single-institution studies of patients who received [breast] reconstructive surgery and radiation,” said senior author of the study, Atif J. Khan, MD, MS, a radiation oncologist at Memorial Sloan Kettering Cancer Center in New York. “It was very exciting to see a complication rate that was nearly half what we anticipated.”

Local and regional recurrence rates at 3 years were considered to be low and statistically similar in both arms, with a 1.5% recurrence rate with hypofractionated radiation and a 2.3% rate with conventional radiation. Dr. Khan noted that without radiation therapy, typical local-regional recurrence rates after mastectomy in patients with high-risk disease are in the range of 20%.

The use of hypofractionation was considered to be noninferior in terms of toxicity compared with conventional fractionation. Treatment-related side effects were reported in less than 6% of patients on either treatment arm. Of note, regardless of the treatment schedule, patients experienced fewer complications after autologous breast reconstruction vs implant-alone breast reconstruction (8.7% vs 15.5%; P = .0043).

Future Outlook

Dr. Poppe hopes these findings will encourage more cancer centers to adopt a shorter course of radiation treatment for any patient who has a mastectomy. And he underscored the potential impact on patients’ lives.

“We now have robust data, from hundreds of academic and community centers as well as from patients with any type of [breast] reconstruction, that clearly show the safety and effectiveness of short-course radiation,” said Dr. Poppe. “When I tell patients they can do 3 weeks of radiation instead of 6 weeks, you can see their relief.”

Dr. Khan shared these concluding comments: “Radiation therapy after mastectomy saves lives. Patients shouldn’t have to choose between radiation or no radiation based on their desire for [breast] reconstruction or because they can’t take 6 weeks out of their lives.” 

DISCLOSURE: Dr. Poppe reported no conflicts of interest. Dr. Khan owns stock or other ownership interests in Novavax and Xtrava; has received research funding from Clovis Oncology, Merck KGaA, and Varian Medical Systems; has a patent for the drug riluzole awarded to Rutgers University for which he is the inventor; and has an uncompensated relationship with AI MindSystems Foundation.

REFERENCE

1. Poppe MM, Le-Rademacher J, Haffty Jr BG, et al: A randomized trial of hypofractionated post-mastectomy radiation therapy in women with breast reconstruction (RT CHARM, Alliance A221505). 2024 ASTRO Annual Meeting. Abstract 1. Presented September 30, 2024.

EXPERT POINT OF VIEW 

Invited discussant Rachel Jimenez, MD, called the RT CHARAM a “tour de force clinical trial,” acknowledging its significant implications for patient care and underscoring two key takeaway points. Dr. Jimenez is Associate Professor of Radiation Oncology, Harvard Medical School, and Director of Breast Radiation Oncology at Mass General Cancer Center.

First, Dr. Jimenez highlighted the importance of reconsidering the perception of radiation therapy. “Radiation often receives undeserved negative press or concerns around toxicity,” she said. “Although it’s true that all cancer therapy has associated morbidity, the advances in radiation technology over the past several decades have markedly and meaningfully improved the quality and safety of treatment for all our patients.”

According to Dr. Jimenez, the complication rates for breast reconstruction in this study were significantly lower than expected based on historical controls, regardless of whether patients received longer or shorter courses of radiation treatment. This finding underscores the safety of modern radiation therapy techniques.

Second, Dr. Jimenez emphasized the growing focus on patient convenience and reducing the time and financial burden associated with radiation treatment. “As we move forward with hypofractionation, this study provides valuable data to support this transition,” she stated. “Other smaller studies have shown similar results, suggesting a critical mass of data now supports the use of hypofractionated schedules for patients who undergo breast reconstruction and require postmastectomy radiation.” 

DISCLOSURE: Dr. Jimenez reported no conflicts of interest.