Factors associated with fatigue in breast cancer patients undergoing external beam radiation therapy

Purpose: Cancer-related fatigue (CRF), a prevalent symptom among cancer patients, is a side effect of external beam radiotherapy (EBRT). Even when targeting organs unrelated to caloric intake or the CNS, radiotherapy can increase CRF, a poorly understood toxicity resulting from patient-specific, systemic therapy-related, and radiation-specific factors. We sought to determine factors associated with fatigue among patients receiving EBRT for breast cancer.

Methods and materials: To determine the variables associated with fatigue among nonmetastatic breast cancer patients, we retrospectively analyzed prospectively collected toxicity data for a cohort of 1,286 adult female breast cancer patients who began curative-intent EBRT between 4/2010-10/2017. We hypothesized certain variables are associated with provider-reported Common Terminology Criteria for Adverse Events (CTCAE) version 4 fatigue, graded 0-3, at baseline and over the course of radiation treatment.

Results: All patients were women, with a median age of 57 (range 24-90). Mean fatigue was low (0.35 [95% confidence interval 0.32-0.38]) at the start of radiation, increasing weekly and peaking at week 6 (0.85 [0.81-0.90]). Baseline fatigue was associated with higher AJCC stage (p<0.001), N-stage (p<0.001), anxiolytics (p<0.001), anticonvulsants (p=0.002), antidepressants (p=0.006), antihistamines (p<0.001), and antipsychotics (p<0.001). Chemotherapy was not associated with baseline fatigue. Over the course of treatment, on multivariable analysis, only lower dose per fraction (p<0.001) was significantly associated with increasing fatigue. In a subgroup analysis, heart and lung mean, V5, and V20 doses were not found to be associated with increasing fatigue.

Conclusions: This work informs clinicians which factors are associated with CRF at the start of radiotherapy (more advanced disease and prescription of anxiolytics, anticonvulsants, antidepressants, antihistamines, and antipsychotics), and increase CRF over the course of radiation (smaller fraction size). This extensive analysis of factors associated with fatigue provides further evidence that hypofractionated radiotherapy for breast cancer is associated with less acute toxicity than conventionally fractionated treatment.

Keywords: Breast Cancer; Fatigue; Hypofractionation; Neoplasms; Patient-reported Outcomes; Quality of Life; Radiotherapy Fatigue; Toxicity.