Conventional versus hypofractionated postmastectomy proton radiotherapy in the USA (MC1631): a randomised phase 2 trial

• Published in: The lancet oncology 2023-10, Vol.24 (10), p.1083-1093
• Main Authors: Mutter, Robert W, Giri, Sharmila, Fruth, Briant F, Remmes, Nicholas B, Boughey, Judy C, Harless, Christin A, Ruddy, Kathryn J, McGee, Lisa A, Afzal, Arslan, Gao, Robert W, Shumway, Dean A, Vern-Gross, Tamara Z, Villarraga, Hector R, Kenison, Stephanie L, Kang, Yixiu, Wong, William W, Stish, Bradley J, Merrell, Kenneth W, Yan, Elizabeth S, Park, Sean S, Corbin, Kimberly S, Vargas, Carlos E
• Format: Article
• Language: English
• Subjects: Adult; Aged; Breast cancer; Breast Neoplasms - pathology; Breast Neoplasms - radiotherapy; Breast Neoplasms - surgery; Cancer therapies; Chemotherapy; Clinical trials; Dose Fractionation, Radiation; Endocrine therapy; Female; Humans; Lumpectomy; Lymphatic system; Mastectomy; Middle Aged; Oncology; Physical properties; Proton Therapy; Protons; Radiation Dose Hypofractionation; Radiation therapy; Radiotherapy, Adjuvant; Reconstructive surgery; Surgery; Treatment Outcome; United States
• ISSN: 1470-2045; 1474-5488; 1474-5488
• DOI: 10.1016/S1470-2045(23)00388-1

Proton therapy is under investigation in breast cancer as a strategy to reduce radiation exposure to the heart and lungs. So far, studies investigating proton postmastectomy radiotherapy (PMRT) have used conventional fractionation over 25–28 days, but whether hypofractionated proton PMRT is feasible is unclear. We aimed to compare conventional fractionation and hypofractionation in patients with indications for PMRT, including those with immediate breast reconstruction. We did a randomised phase 2 trial (MC1631) at Mayo Clinic in Rochester (MN, USA) and Mayo Clinic in Arizona (Phoenix, AZ, USA) comparing conventional fractionated (50 Gy in 25 fractions of 2 Gy [relative biological effectiveness of 1·1]) and hypofractionated (40·05 Gy in 15 fractions of 2·67 Gy [relative biological effectiveness of 1·1]) proton PMRT. All patients were treated with pencil-beam scanning. Eligibility criteria included age 18 years or older, an Eastern Cooperative Oncology Group performance status of 0–2, and breast cancer resected by mastectomy with or without immediate reconstruction with indications for PMRT. Patients were randomly assigned (1:1) to either conventional fractionation or hypofractionation, with presence of immediate reconstruction (yes vs no) as a stratification factor, using a biased-coin minimisation algorithm. Any patient who received at least one fraction of protocol treatment was evaluable for the primary endpoint and safety analyses. The primary endpoint was 24-month complication rate from the date of first radiotherapy, defined as grade 3 or worse adverse events occurring from 90 days after last radiotherapy or unplanned surgical interventions in patients with immediate reconstruction. The inferiority of hypofractionation would not be ruled out if the upper bound of the one-sided 95% CI for the difference in 24-month complication rate between the two groups was greater than 10%. This trial is registered with ClinicalTrials.gov, NCT02783690, and is closed to accrual. Between June 2, 2016, and Aug 23, 2018, 88 patients were randomly assigned (44 to each group), of whom 82 received protocol treatment (41 in the conventional fractionation group and 41 in the hypofractionation group; median age of 52 years [IQR 44−64], 79 [96%] patients were White, two [2%] were Black or African American, one [1%] was Asian, and 79 [96%] were not of Hispanic ethnicity). As of data cutoff (Jan 30, 2023), the median follow-up was 39·3 months (IQR 37·5–61·2). The median mean he