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

Abstract

PurposeIMPORT LOW demonstrated noninferiority of partial-breast and reduced-dose radiotherapy versus whole-breast radiotherapy for local relapse and similar or reduced toxicity at 5 years. Comprehensive patient-reported outcome measures collected at serial time points are now reported.Patients and MethodsIMPORT LOW recruited women with low-risk breast cancer after breast-conserving surgery. Patients were randomly assigned to 40 Gy whole-breast radiotherapy (control), 36 Gy whole-breast and 40 Gy partial-breast radiotherapy (reduced-dose), or 40 Gy partial-breast radiotherapy only (partial-breast) in 15 fractions. European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires Core 30 and Breast Cancer–Specific Module, Body Image Scale, protocol-specific items, and the Hospital Anxiety and Depression Scale were administered at baseline, 6 months, and 1, 2, and 5 years. Patterns of moderate/marked adverse effects (AEs) were assessed using longitudinal regression models, and baseline predictors were investigated.ResultsA total of 41 of 71 centers participated in the patient-reported outcome measures substudy; 1,265 (95%) of 1,333 patients consented, and 557 (58%) of 962 reported no moderate/marked AEs at 5 years. Breast appearance change was most prevalent and persisted over time (approximately 20% at each time point). Prevalence of breast hardness, pain, oversensitivity, edema, and skin changes reduced over time (P < .001 for each), whereas breast shrinkage increased (P < .001). Analysis by treatment group showed average number of AEs per person was lower in partial-breast (incidence rate ratio, 0.77; 95% CI, 0.71 to 0.84; P < .001) and reduced-dose (incidence rate ratio, 0.83; 95% CI, 0.76 to 0.90; P < .001) versus 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.ConclusionMost AEs reduced over time, with fewer AEs in the partial-breast and reduced-dose groups. Baseline predictors for AE reporting were identified. These findings will facilitate informed discussion and shared decision making for future patients receiving moderately hypofractionated breast radiotherapy.

Can patient-reported outcomes be used instead of clinician-reported outcomes and photographs as primary endpoints of late normal tissue effects in breast radiotherapy trials? Results from the IMPORT LOW trial

“…Thirdly, there is a risk of bias related to questionnaire return as patients who return questionnaires may have different characteristics to those who don’t and may report either more or fewer side-effects. In IMPORT LOW, women who declined participation in the PROMs sub-study were slightly older than those who did consent [13]. There were no significant differences in the majority of baseline characteristics in those who did or did not return questionnaires at 5 years, with the exception of higher baseline HADS anxiety and depression subscale scores in patients who did not return their year-5 questionnaire [13].…”

“…Separate analyses were conducted in patients with PROMs and CRO, and PROMs and photographs, at year-2 and year-5. Data regarding baseline characteristics [1] and PROMs questionnaire return rates [13] have been published.…”

“…In IMPORT LOW, women who declined participation in the PROMs sub-study were slightly older than those who did consent [13]. There were no significant differences in the majority of baseline characteristics in those who did or did not return questionnaires at 5 years, with the exception of higher baseline HADS anxiety and depression subscale scores in patients who did not return their year-5 questionnaire [13]. Also, patients who reported more adverse effects at year-2 were more likely to return questionnaires at year-5 [13].…”

“…The low overall prevalence of moderate/marked NTE, irrespective of the data ascertainment method used, has been reported in a number of adjuvant breast radiotherapy trials [1], [2], [13]. It is therefore increasingly important, in an era of improving radiotherapy techniques to monitor NTE using sufficiently sensitive methods.…”

Optimizing MR-Guided Radiotherapy for Breast Cancer Patients

“…In recent decades, this has led to prioritization of treatment de-escalation aiming to reduce treatment-related toxicity without impeding survival (4). Studies comparing adjuvant whole breast irradiation (WBI) vs. adjuvant partial breast irradiation (PBI) in women with lower-risk breast cancers have demonstrated that PBI is as effective as WBI in terms of 5-years local recurrence rates and survival but with lower rates of late patient-reported and clinician-reported toxicity (5)(6)(7)(8). Nonetheless, late treatment-related toxicity remains an issue in a significant proportion of patients (6,8).…”