Abstract 4752: Inflammatory cytokines and hematopoietic stem cells are associated with fatigue and insomnia in breast cancer patients undergoing adjuvant radiation therapy
Authors: Shi Wei , Han Kathy , Li Madeline , Williams Justin , McCusker Megan , Su Jie , Xu Wei , Bratman Scott , Yip Kenneth , Liu Fei-Fei 
Published: July 2017

Abstract
Introduction: Breast cancer patients undergoing adjuvant radiation therapy (RT) commonly experience fatigue and insomnia. We previously reported that this fatigue is associated with a reduction in circulating hematopoetic stem cells (HSCs; CD34+); the role of inflammatory cytokines in mediating this process however, has not been clearly elucidated.
Materials and Methods: Breast cancer patients (n=147) undergoing adjuvant RT underwent phlebotomies for analysis of CD34+, CD45+, CBC, as well as 17 inflammatory cytokines using a multiplexed ELISA platform, during 5 time points: prior to RT (D1); after Days 2, 5, during final week of RT (D2, D5, and Df, respectively); as well as one month post RT-completion (M1). At the same time, patients also completed questionnaires for the multidimensional fatigue inventory (MFI-20), hospital anxiety and depression scale (HADS), and insomnia severity index (ISI).
Results: General fatigue worsened over the course of RT from D1 to Df, being most severe at the end of treatment (Df), but returned to baseline at M1. This trend was statistically significant (p&lt;0.001), after adjusting for anxiety, depression, and insomnia. The levels of CD34+, CD45+, white blood cell, as well as lymphocyte counts decreased over time, with the lowest levels observed at Df (p&lt;0.001 for all). General fatigue correlated inversely with CD34+ counts (adjusted for anxiety, depression, and ISI), and was also negatively associated with hemoglobin, RBC, and lymphocyte counts (p&lt;0.001 for all). There was also a significant correlation between increasing insomnia with lower CD34+, CD45+, white blood cell and lymphocyte counts (all p&lt;0.05). Serum concentrations of TGF-β1, MCP-1, MMP-2, IL-1ra and IFN-α2a changed significantly during RT (p&lt;0.01 for all), with either the highest or lowest levels observed at Df. Increasing levels of MCP-1, TNF-RII and TNF-a were associated with worsening general physical fatigue, reduced activity, decreased motivation, as well as increased insomnia (p&lt;0.001 for all). Furthermore, there appeared a trend between increasing MMP-2, as well as decreasing IL-1ra and TGF-β1, with reduced CD34+, CD45+, WBC and lymphocyte counts (p&lt;0.001). The 52 patients who received prior adjuvant chemotherapy demonstrated significantly higher fatigue, anxiety, and insomnia scores.
Conclusions: This study represents one of the most comprehensive longitudinal evaluations of the effects of RT on fatigue and insomnia, demonstrating that this process was associated with increased levels of the pro-inflammatory cytokines MCP-1, TNF-RII and TNF-a, and reductions in circulating HSCs and other hematologic parameters. Further understanding of the roles of these cytokines would provide important insights into both quality of life for patients undergoing cancer therapies, as well as the interactions between RT with immunotherapy.
Citation Format: Wei Shi, Kathy Han, Madeline Li, Justin Williams, Megan McCusker, Jie Su, Wei Xu, Scott Bratman, Kenneth Yip, Fei-Fei Liu. Inflammatory cytokines and hematopoietic stem cells are associated with fatigue and insomnia in breast cancer patients undergoing adjuvant radiation therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4752. doi:10.1158/1538-7445.AM2017-4752