Abstract PS9-29: Factors influencing fatigue in breast cancer patients undergoing breast irradiation
Authors: Perry Edward , Mulay Sudhanshu , Kamath Jayesh , Dowsett Robert , Wu Rong , Wang Xiaoyan , Greenwood Matthew , Neuwirth Jacob , Grady James , Liang Bruce , Tannenbaum Susan 
Published: February 2021

Abstract
Background: Fatigue is one of the most common acute complications of radiation therapy (RT). It can have a serious impact on a patient’s quality of life and ability to engage in treatment, and has been associated with lower recurrence-free and overall survival in patients with breast cancer. The pathogenesis of radiation-induced fatigue remains elusive, and factors implicated include biological (low hemoglobin and elevated pro-inflammatory cytokines and chemokines) and psychological (pain, depression and anxiety). Although it is a common clinical issue, optimal treatment strategies are lacking, and a better understanding of the mechanisms involved is needed to devise effective interventions. The purpose of this exploratory, non-randomized, prospective study was to examine a number of possible biological and psychological factors influencing fatigue in patients undergoing breast irradiation for early stage breast cancer.
Methods: All subjects were assessed at five time points: immediately before RT, mid-point of RT, end of RT, and 6 months and 1 year after completion of RT. Clinical evaluation of skin toxicity and cosmetic outcome and laboratory measures evaluating anemia and hepatic toxicity were performed. Laboratory markers of systemic inflammatory/stress response included salivary cortisol, CRP and cytokines. Caspase-1 and caspase-3, novel markers of apoptosis, were also collected. Fatigue, distress, depression, anxiety, sleep, energy level and pain were assessed at each time point using validated measures. A two-sample student t-test or a non-parametric Wilcoxon rank sum test was used to identify significant associations between fatigued and non-fatigued subjects at each time point.
Results: Fifty-three subjects completed the study. Subjects were predominantly white and non-Hispanic, middle to upper-middle class, with a mean age of 59. Fatigued subjects were more likely than non-fatigued subjects to have a history of anxiety and/or depression. Across all subjects, fatigue increased during treatment and returned to or near baseline by 6 months after treatment. Fatigue was significantly associated with overall distress, energy level, and some measures of physical and functional well-being during treatment; these associations were not present at baseline and resolved by 6 months. Fatigued subjects were more likely to have increases in depression scores by the end of treatment, although mean depression scores did not reach clinical significance. Fatigue was significantly associated with breast-specific pain by the end of treatment, and this resolved by 6 months. Fatigue was significantly associated with some measures of sleep at baseline, and this persisted during treatment and resolved by 6 months to 1 year. Fatigue was not associated with measures of skin toxicity and cosmetic outcome and laboratory measures of anemia, hepatic toxicity, salivary cortisol, caspase-1, caspase-3, and IL-10; most other cytokines were undetectable.
Conclusions: This was a comprehensive, longitudinal study evaluating the association of biological and psychological factors with the development of fatigue in patients undergoing breast irradiation. As expected, in patients experiencing heightened fatigue during breast irradiation, fatigue was greatest at the end of treatment and returned to or near baseline by 6 months after treatment. Important associations with the development of fatigue included physical and functional parameters, and of particular significance were patients with a prior history of mental health diagnoses. In contrast to previous studies, we did not find an increase in pro-inflammatory or in novel biomarkers including caspase-1 and caspase-3. Identification of and interventions directed at those patients at risk could impact positively on the experience associated with fatigue and radiation.
Citation Format: Edward Perry, Sudhanshu Mulay, Jayesh Kamath, Robert Dowsett, Rong Wu, Xiaoyan Wang, Matthew Greenwood, Jacob Neuwirth, James Grady, Bruce Liang, Susan Tannenbaum. Factors influencing fatigue in breast cancer patients undergoing breast irradiation [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-29.