Patient Reported Outcomes Over 5 Years Following Whole or Partial Breast Radiotherapy: Longitudinal Analysis of the IMPORT LOW (CRUK/06/003) Phase III Randomised Controlled Trial

Abstract

Background: IMPORT LOW demonstrated non-inferiority of partial-breast and reduced-dose radiotherapy compared with whole-breast for local relapse, and similar or reduced toxicity at 5 years following radiotherapy. Comprehensive patient reported outcome measures (PROMs) collected at serial time-points are now reported. Methods: IMPORT LOW (ISRCTN12852634) recruited women aged ≥50 years after breast conserving surgery for low risk invasive breast cancer. Patients were randomly assigned to 40Gy whole-breast radiotherapy (control), 36Gy whole-breast and 40Gy to partial-breast (reduced-dose), or 40Gy to partial-breast only (partial-breast) in 15 daily fractions. EORTC QLQ-C30, QLQ-BR23, Body Image Scale, protocol-specific items and Hospital Anxiety and Depression Scales were administered at baseline, 6 months, 1, 2 and 5 years. Patterns of moderate/marked adverse effects (AE) were assessed using longitudinal regression models and baseline predictors investigated. Findings: Patients from 41/71 participating centres took part in the PROMs sub-study where 1265/1333 (95%) patients consented. 557/962 (58%) patients reported no moderate/marked AEs at 5 years. Breast appearance change was most prevalent and persisted over time (around 20% at each time-point). Prevalence of breast hardness, pain, oversensitivity, oedema and skin changes reduced over time (p<0.001 for each), whereas breast shrinkage increased (p<0.001). Analysis by treatment group showed average number of AEs per person at each time point was lower in the partial-breast (incidence rate ratio [IRR] 0.77, 95%CI 0.71-0.84, p<0.001) and reduced-dose (IRR 0.83, 95%CI 0.76-0.90, p<0.001) groups compared with the whole-breast group, and decreased over time in all groups. Younger age, larger breast size/surgical deficit, lymph node positivity, and higher levels of anxiety/depression were baseline predictors of subsequent AE reporting. Interpretation: The majority of AEs reduced over time. There were fewer AEs in the partial and reduced-dose groups and baseline predictors of AEs were identified. These findings will facilitate informed discussion and shared-decision making for future patients receiving moderately hypofractionated breast radiotherapy. Funding Statement: We acknowledge support from Cancer Research UK (grant number C1491/A6035), the National Institute for Health Research (NIHR) Cancer Research Network (CRN), National Health Service Research Scotland, Health and Care Research Wales and the National Institute of Health Research Royal Marsden/ Institute of Cancer Research Biomedical Research Centre. In addition Dr Charlotte Coles is supported by the Cambridge National Institute of Health Research Biomedical Research Centre. Dr Indrani Bhattacharya is supported by a Cancer Research UK clinical trial fellowship (C1491/A8895). Declaration of Interests: The authors declare they have no conflicts of interest. Ethics Approval Statement: This was approved by the Oxfordshire Research Ethics Committee B (06/Q1605/128) and conducted in accordance with the principles of Good Clinical Practice. Requests are reviewed by the TMG in terms of scientific merit and ethical considerations including patient consent. Data sharing is undertaken if proposed projects have a sound scientific or patient benefit rationale as agreed by the TMG and approved by the independent Trial Steering Committee with input from the Independent Data Monitoring Committee as required.