Fatigue is associated with inflammation in patients with head and neck cancer before and after intensity-modulated radiation therapy

• Type of Material: Article
• Authors: Canhua Xiao, Emory University; Jonathan Beitler, Emory University; Kristin Higgins, Emory University; Karen Conneely, Emory University; Bhakti Dwivedi, Emory University; Jennifer Felger, Emory University; Evanthia C. Wommack, Emory University; Dong Shin, Emory University; Nabil Saba, Emory University; Luke Yeeloo Ong, Emory University; Jeanne Kowalski, Emory University; Deborah Bruner, Emory University; Andrew Miller, Emory University
• Language: English
• Date: 2016-02-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.bbi.2015.10.016
• Title of Journal or Parent Work: Brain, Behavior, and Immunity
• ISSN: 0889-1591
• Volume: 52
• Start Page: 145
• End Page: 152
• Grant/Funding Information: The study was supported by NIH/NINR K99NR014587, NIH/NCI P30CA138292 and Oncology Nursing Society Foundation.
• Keywords: SYMPTOM CLUSTERS; SURVIVORS; QUALITY-OF-LIFE; ALPHA; Neurosciences & Neurology; CHEMORADIATION THERAPY; Life Sciences & Biomedicine; Head and neck cancer; FACTOR-KAPPA-B; Immunology; CONSECUTIVE PATIENTS; Fatigue; BASAL GANGLIA; Neurosciences; RADIOTHERAPY; MECHANISMS; Intensity-modulated radiation therapy; Science & Technology; Inflammation
• Research Categories: Psychology, Behavioral; Biology, Radiation; Health Sciences, Oncology

Abstract

Patients with head and neck cancer (HNC) receiving intensity-modulated radiation therapy (IMRT) have particularly high rates of fatigue, and pre- and post-radiotherapy fatigue are prognostic factors for pathologic tumor responses and poor survival. Although inflammation has been proposed as one of the potential mechanisms of fatigue in cancer patients, findings have not been consistent, and there is a dearth of longitudinal studies. Accordingly, we conducted a prospective study in 46 HNC patients pre- and one-month post-IMRT. Fatigue was measured by the Multidimensional Fatigue Inventory (MFI)-20 at both time points along with the assessment of peripheral blood inflammatory markers including interleukin (IL)-6, soluble tumor necrosis factor receptor 2, and C-reactive protein (CRP) and gene expression. Generalized estimating equations were used to examine the association between inflammatory markers and fatigue. Gene enrichment analysis using MetaCore software was performed using up-regulated genes that were significantly associated with IMRT and fatigue. Significant associations between fatigue and IL-6 as well as CRP, which were independent of time, were observed. In addition the change in fatigue from pre- to post-IMRT was positively associated with the change in IL-6 and CRP. Analysis of up-regulated gene transcripts as a function of IMRT and fatigue revealed overrepresentation of transcripts related to the defense response and nuclear factor kappa B. In conclusion, our findings support the hypotheses that inflammation is associated with fatigue over time in HNC patients. Future studies on how inflammation contributes to fatigue as well as strategies targeting inflammation to reduce fatigue are warranted.