Longitudinal Analysis of Patient-Reported Outcomes and Cosmesis in a Randomized Trial of Conventionally Fractionated Versus Hypofractionated Whole-Breast Irradiation

Abstract

PURPOSE There are few prospective data on predictors of patient-reported outcomes (PROs) after whole breast irradiation (WBI) plus a boost. We sought to characterize longitudinal PROs and cosmesis in a randomized trial comparing conventionally fractionated (CF) vs hypofractionated (HF) WBI. METHODS From 2011 to 2014, women age ≥40 years with Tis-T2 N0-N1a M0 breast cancer who underwent lumpectomy with negative margins were randomized to CF-WBI (50Gy/25 fractions plus boost) vs HF-WBI (42.56Gy/16 fractions plus boost). At baseline (pre-radiation), 6 months, and yearly thereafter through 5 years, PROs included the Breast Cancer Treatment Outcome Scale (BCTOS), Functional Assessment of Cancer Therapy-Breast (FACT-B), and Body Image Scale; cosmesis was reported by the treating physician using Radiation Therapy Oncology Group cosmesis. Multivariable mixed effects growth curve models evaluated associations of treatment arm and patient factors with outcomes and tested for relevant interactions with treatment arm. RESULTS A total of 287 patients were randomized, completing a total of 14,801 PRO assessments. Median age was 60 years, 37% had bra cup size ≥D, 44% were obese, and 30% received chemotherapy. Through 5-years, there were no significant differences in PROs or cosmesis by treatment arm. Bra cup size ≥D was associated with worse BCTOS cosmesis (P<0.001), BCTOS pain (P=0.001), FACT-B Trial Outcome Index (P=0.03), FACT-B Emotional Well-being (P=0.03), and Body Image Scale (P=0.003). Physician-rated cosmesis was worse in patients who were overweight (P=0.02) or obese (P<0.001). No patient subsets experienced better PROs or cosmesis with CF-WBI. CONCLUSIONS Both CF-WBI and HF-WBI confer similar longitudinal PROs and physician-rated cosmesis through five years follow up, with no relevant subsets that fared better with CF-WBI. This evidence supports broad adoption of hypofractionation with boost including in patients receiving chemotherapy and in a population with high prevalence of obesity. The associations of large breast size and obesity with adverse outcomes across multiple domains highlights the opportunity to engage at-risk patients in lifestyle intervention strategies as well as consideration of alternative radiation treatment regimens.