A large phase III clinical trial has demonstrated that hypofractionated (shortened) radiation therapy is safe and effective for breast cancer patients who undergo breast reconstruction after mastectomy. The RT CHARM trial (Alliance A221505) found that the shorter course of radiation was noninferior to conventional fractionation, potentially changing the standard of care for postmastectomy radiation therapy.
The findings, presented at the 2024 American Society for Radiation Oncology (ASTRO) Annual Meeting, represent a significant advancement in breast cancer treatment, allowing patients to complete radiation therapy in approximately three weeks rather than the conventional five weeks.
Trial Design and Patient Population
The RT CHARM trial enrolled 898 patients with unilateral invasive breast cancer across 209 academic and community-based cancer centers throughout the United States and Canada. Eligible participants included those with larger tumors (pT3N0) or smaller tumors with regional lymph node invasion (pT0–2 pN1–2). The median age of participants was 46 years.
Patients were randomly assigned to receive either:
- Conventional radiation: 25 fractions over 5 weeks (50 Gy total; n = 449)
- Hypofractionated radiation: 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, while 41% underwent autologous breast reconstruction (with or without implants). The median follow-up period was 5 years.
Key Findings
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 reconstructive surgery were 14% with hypofractionated radiation and 12% with conventional radiation, with the difference considered statistically noninferior (P = .0004).
"We expected a complication rate of 25% based on prior, single-institution studies of patients who received reconstructive surgery and radiation," said senior author Dr. Atif J. Khan, a radiation oncologist at Memorial Sloan Kettering Cancer Center. "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 low and statistically similar in both arms:
- Hypofractionated radiation: 1.5% recurrence rate
- Conventional radiation: 2.3% recurrence rate
Dr. Khan noted that without radiation therapy, typical local-regional recurrence rates after mastectomy in patients with high-risk disease are around 20%.
Treatment-related side effects were reported in less than 6% of patients in either treatment arm. Notably, regardless of the radiation schedule, patients experienced fewer complications after autologous breast reconstruction compared to implant-alone reconstruction (8.7% vs 15.5%; P = .0043).
Implications for Clinical Practice
Principal investigator Dr. Matthew M. Poppe, Professor of Radiation Oncology at the University of Utah, emphasized the significance of these findings: "Over the past 10 years, we've tried to move all patients who need breast radiation to a shorter, more convenient schedule. Now, the results of this trial show we can safely reduce treatment time for these patients to 3 weeks without compromising their reconstruction."
The study addresses a critical gap in breast cancer care. Approximately 40% of breast cancer patients undergo mastectomy, with the majority opting for reconstructive breast surgery. Many of these patients also require postmastectomy radiation therapy to prevent cancer recurrence. However, those seeking radiation therapy after mastectomy have typically been excluded from hypofractionation studies due to concerns about potential side effects on the reconstructive process.
Expert Perspectives
Dr. Rachel Jimenez, Associate Professor of Radiation Oncology at Harvard Medical School and Director of Breast Radiation Oncology at Mass General Cancer Center, called the RT CHARM a "tour de force clinical trial," highlighting its significant implications for patient care.
She emphasized two key points: first, the need to reconsider perceptions about radiation therapy's toxicity given the advances in technology that have improved treatment safety; and second, the growing focus on patient convenience and reducing the time and financial burden associated with radiation treatment.
Dr. Poppe hopes these findings will encourage more cancer centers to adopt shorter courses of radiation treatment for mastectomy patients. "We now have robust data, from hundreds of academic and community centers as well as from patients with any type of reconstruction, that clearly show the safety and effectiveness of short-course radiation," he said. "When I tell patients they can do 3 weeks of radiation instead of 6 weeks, you can see their relief."
Dr. Khan concluded: "Radiation therapy after mastectomy saves lives. Patients shouldn't have to choose between radiation or no radiation based on their desire for reconstruction or because they can't take 6 weeks out of their lives."
Additional Innovations in Radiation Therapy
This study builds on other innovative approaches to radiation therapy in breast cancer treatment. At RWJBarnabas Health and Rutgers Cancer Institute, researchers are exploring a different approach to shortened radiation therapy. As highlighted by Dr. M. Michele Blackwood, Director of Breast Surgery at RWJBarnabas Health, a trial led by Dr. Bruce Haffty is investigating a split radiation protocol for lumpectomy patients.
This approach delivers one week of radiation before surgery and two weeks afterward, considerably shortening the traditional course of post-lumpectomy radiation. The protocol is particularly beneficial for patients undergoing oncoplastic surgery or breast lifts during lumpectomy, as it allows radiation oncologists to target the exact location of the tumor before tissue is rearranged.
Together, these advances in radiation therapy protocols are making treatment more convenient and accessible for breast cancer patients while maintaining excellent clinical outcomes.
