title: Fatigue is associated with inflammation in patients with head and neck cancer before and after intensity-modulated radiation therapy.
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.
authors.affiliation: School of Nursing, Emory University, 1520 Clifton Road NE, Atlanta 30322, United States.
authors.forename: Canhua
authors.initials: C
authors.lastname: Xiao
authors.affiliation: School of Medicine, Emory University, 1520 Clifton Road NE, Atlanta 30322, United States.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Beitler
authors.affiliation: School of Medicine, Emory University, 1520 Clifton Road NE, Atlanta 30322, United States.
authors.forename: Kristin A
authors.initials: KA
authors.lastname: Higgins
authors.affiliation: Department of Human Genetics, School of Medicine, Emory University, 615 Michael Street, Atlanta, GA 30322, United States.
authors.forename: Karen
authors.initials: K
authors.lastname: Conneely
authors.affiliation: Biostatistics and Bioinformatics Shared Resource, 1365-B Clifton Road, Atlanta, GA 30322, United States.
authors.forename: Bhakti
authors.initials: B
authors.lastname: Dwivedi
authors.affiliation: Department of Psychiatry and Behavioral Sciences, School of Medicine, Emory University, 1365-B Clifton Road, Atlanta, GA 30322, United States.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Felger
authors.affiliation: Department of Psychiatry and Behavioral Sciences, School of Medicine, Emory University, 1365-B Clifton Road, Atlanta, GA 30322, United States.
authors.forename: Evanthia C
authors.initials: EC
authors.lastname: Wommack
authors.affiliation: School of Medicine, Emory University, 1520 Clifton Road NE, Atlanta 30322, United States.
authors.forename: Dong M
authors.initials: DM
authors.lastname: Shin
authors.affiliation: School of Medicine, Emory University, 1520 Clifton Road NE, Atlanta 30322, United States.
authors.forename: Nabil F
authors.initials: NF
authors.lastname: Saba
authors.affiliation: Emory University, 201 Dowman Dr, Atlanta, GA 30322, United States.
authors.forename: Luke Yeeloo
authors.initials: LY
authors.lastname: Ong
authors.affiliation: Biostatistics and Bioinformatics Shared Resource, 1365-B Clifton Road, Atlanta, GA 30322, United States.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Kowalski
authors.affiliation: School of Nursing, Emory University, 1520 Clifton Road NE, Atlanta 30322, United States.
authors.forename: Deborah W
authors.initials: DW
authors.lastname: Bruner
authors.affiliation: Department of Psychiatry and Behavioral Sciences, School of Medicine, Emory University, 1365-B Clifton Road, Atlanta, GA 30322, United States.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Miller
mesh_terms: D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D005221:Fatigue / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000532:radiotherapy*; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000097:blood; D011446:Prospective Studies; D011788:Quality of Life; D050397:Radiotherapy, Intensity-Modulated; D059467:Transcriptome; D016896:Treatment Outcome
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D016328:NF-kappa B; D002097:C-Reactive Protein
keywords: Fatigue; Head and neck cancer; Inflammation; Intensity-modulated radiation therapy