In a phase II trial (MC1631) reported in The Lancet Oncology, Robert W. Mutter, MD, and colleagues found that the 24-month complication rate associated with hypofractionated proton postmastectomy radiotherapy (PMRT) was not noninferior to standard fractionated PMRT in patients undergoing mastectomy for breast cancer.
Robert W. Mutter, MD
Study Details
In the trial, 82 patients from Mayo Clinic, Rochester, and Mayo Clinic, Phoenix, were randomly assigned between June 2016 and August 2018 to receive hypofractionated proton PMRT at 40.05 Gy in 15 fractions of 2.67 Gy (n = 41) or conventional fractionation PMRT at 50 Gy in 25 fractions of 2 Gy (n = 41). A total of 30 patients (73%) in the hypofractionation group and 27 (66%) in the standard fractionation group underwent immediate breast reconstruction; of these, tissue expanders were used for reconstruction in 23 and 25 patients, and reconstruction was implant-based in 3 and 4 patients, respectively.
The primary endpoint was 24-month complication rate from date of first radiotherapy, defined as grade ≥ 3 adverse events occurring from 90 days after last radiotherapy or unplanned surgical interventions in patients with immediate reconstruction. Inferiority of hypofractionation would not be ruled out if the upper bound of the one-sided 95% confidence interval for the difference in 24-month complication rates between the two groups was greater than 10%.
Key Findings
As of data cutoff (end of January 2023), median follow-up was 39.3 months (interquartile range [IQR] = 37.5–61.2 months).
Median mean heart dose was 0.49 Gy (IQR = 0.25–0.64 Gy) in the hypofractionation group and 0.54 Gy (IQR = 0.30–0.72 Gy) in the standard fractionation group.
At 24 months, complications had occurred in eight patients (20%) in the hypofractionation group vs six (15%) in the standard fractionation group (absolute difference = 4.9%, one-sided 95% CI = 18.5%, P = .27).
Complications in the hypofractionated group consisted of eight infections, three of which were acute infections requiring surgical intervention and five of which were late infections, with four requiring surgical intervention. Complications in the conventionally fractionated group were contracture in five patients and fat necrosis in one patient, which required surgical intervention. All of the 14 total complications occurred in patients with immediate expander– or implant-based reconstruction.
In a post hoc analysis, the 24-month cumulative incidence of complications in patients who underwent immediate reconstruction was 26.7% in the hypofractionation group vs 23.1% in the conventional fractionation group (absolute difference = 3.6%, one-sided 95% CI = 21.1%).
The investigators concluded, “After a median follow-up of 39.3 months, noninferiority of the hypofractionation group could not be established. However, given similar tolerability, hypofractionated proton PMRT appears to be worthy of further study in patients with and without immediate reconstruction.”
Dr. Mutter, of the Department of Radiation Oncology, Mayo Clinic, Rochester, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by the National Cancer Institute and others. For full disclosures of the study authors, visit thelancet.com.
