5-year Update of a Multi Institution Prospective Phase II Hypofractionated Post-Mastectomy Radiation Therapy Trial.

Abstract Purpose/Objectives Hypofractionation in the setting of post mastectomy radiation (PMRT) is not currently the standard of care in most countries. Here we present a five-year update of our multi-institutional phase II prospective trial evaluating a novel 15 day hypofractionated PMRT regimen. Materials/Methods Patients were enrolled to receive 3.33 Gray (Gy) daily to the chest wall (or reconstructed breast) and regional lymphatics in 11 fractions with an optional 4 fraction mastectomy scar boost. The primary endpoint was freedom from grade 3 or higher late non-reconstruction related radiation toxicities. Toxicities were scored using Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Secondary endpoints included local and locoregional recurrence rates, cosmesis and reconstruction complications. Results After enrolling 69 patients with stage II-IIIa breast cancer, 67 women were eligible for analysis. At a median follow up of 54 months, there were no acute or late grade 3 and 4 non-reconstruction reported toxicities. The grade 2 or greater late toxicity rate was only 12.% which comprised grade 2 pain, fatigue and lymphedema that persisted beyond 6 months after completion of RT. Only 3 (4.6%) women experienced a chest wall or nodal recurrence, as a first site of relapse. Freedom from local failure, including local failure after distant relapse was 92% at 5 years and the 5-year overall survival was 90%. Conclusions This is the first prospective trial conducted in the United States to demonstrate the safe and effective use of hypofractionated PMRT. We have demonstrated a low complication rate while achieving excellent local control. Toxicity was better than anticipated based on previously published series of PMRT toxicities. Although our fractionation was novel, the radiobiological equivalent dose is similar to other hypofractionation schedules. This trial was the basis for the creation of Alliance Axxxxx (xxxxx), which is currently accruing patients in a phase 3 randomized design.