Determinants of fatigue and longitudinal changes up to 2 years post-radiotherapy for breast cancer

Abstract

Purpose or Objective The aims of this study were to assess fatigue levels over time in breast cancer patients receiving radiotherapy (RT), and to identify demographic and treatment factors associated with multiple dimensions of long-term fatigue. Materials and Methods Data from breast cancer patients undergoing adjuvant RT after breast-conserving surgery was collected in a prospective international multicentre cohort study (www.requite.eu), including treatment/disease factors, baseline sociodemographic data and patient-reported outcomes. 31% of patients also received chemotherapy. Fatigue was measured at four time points (pre-RT, end of RT, 12 months and 24 months after RT) using the Multidimensional Fatigue Inventory (MFI-20) to assess general fatigue, physical fatigue, mental fatigue, reduced activity, and reduced motivation. The prevalence of moderate-severe fatigue was calculated using a cut-point of >12 (scale range 4-20). The change in fatigue levels over time was analyzed using Friedman test followed by pairwise Wilcoxon signed-rank test. Multivariable logistic regression models (including chemotherapy) were used to identify factors associated with the occurrence of fatigue two years after RT for every MFI-20 dimension. Results A total of 1443, 1302, and 1098 patients completed the MFI-20 at baseline, end of RT and two years after RT. The prevalence of moderate-severe general fatigue in our sample was 37%, 50%, and 34%, respectively. Patients with chemotherapy had higher baseline fatigue levels (Fig. 1). From baseline to the end of RT, levels of fatigue significantly increased for all MFI 20 dimensions (p-values <0.05). Fatigue levels had their peak at the end of RT and returned to baseline levels after two years for mental fatigue. For the other four MFI-20 dimensions, there was a statistically significant decrease in fatigue levels when comparing the baseline and two-year measurements (p-values <0.05). Baseline fatigue, depression, sleeping disorders, and dyspnea were significantly associated with the occurrence of general fatigue 2 years after RT (e.g., depression OR = 1.75, 95% CI 1.04-2.92), whereas overall quality of life was inversely associated (OR = 0.85, 95% CI 0.77- 0.94). In addition to the previously mentioned variables, other factors such as obesity or pain were associated with other fatigue domains. Conclusion Fatigue is a prevalent symptom in long-term breast cancer survivors receiving RT. Fatigue levels peaked by the end of RT and declined to baseline levels afterwards. Despite this overall decline, still a third of patients reported moderate-severe fatigue two years after RT. Several patient demographic factors and quality of life at baseline were associated with different dimensions of long-term fatigue. Screening for fatigue should be implemented in routine care to identify patients at a higher risk of developing long-term fatigue so that tailored interventions (e.g., psychological, exercise) can be offered in early phases.