title: Serum sTNF-R1, IL-6, and the development of fatigue in patients with gastrointestinal cancer undergoing chemoradiation therapy.
abstract: Although evidence of inflammation and fatigue has been noted in cancer survivors, whether inflammation is linked to the expression of fatigue and other symptoms arising from concurrent chemoradiation therapy (CXRT) has not been well studied. Patients undergoing CXRT for locally advanced colorectal or esophageal cancer (n=103) reported multiple symptoms weekly via the M. D. Anderson Symptom Inventory (MDASI) from start of therapy. Serum samples were collected weekly to examine changes in inflammatory markers (interleukin (IL)-6, IL-8, IL-10, IL-1 receptor antagonist (IL-1RA), vascular endothelial growth factor (VEGF), and soluble receptor 1 for tumor necrosis factor (sTNF-R1)) via enzyme-linked immunosorbent assay. Relationships between symptom severity and inflammatory-marker concentration levels were estimated using mixed-effect regression analysis, controlled for week of therapy, age, sex, body mass index, pre-CXRT tumor stage, pre-CXRT chemotherapy, pre-CXRT statin use, and type of cancer. Fatigue was the most severe symptom over time, its development profile shared with pain, distress, drowsiness, poor appetite, and disturbed sleep. sTNF-R1 and IL-6 shared a similar pattern of symptom development, with significant increase during CXRT and decrease after completion of CXRT. Serum concentrations of sTNF-R1 were positively associated over time with the severity of fatigue (p=0.00097), while sTNF-R1 and IL-6 were positively related to the severity of a component score of the six most severe symptoms (both p<0.0001). This longitudinal study suggests a role for over-expressed sTNF-R1 and IL-6 in the development of fatigue and other severe sickness symptoms during CXRT in patients with colorectal or esophageal cancer.
authors.affiliation: Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. xswang@mdanderson.org
authors.forename: Xin Shelley
authors.initials: XS
authors.lastname: Wang
authors.forename: Loretta A
authors.initials: LA
authors.lastname: Williams
authors.forename: Sunil
authors.initials: S
authors.lastname: Krishnan
authors.forename: Zhongxing
authors.initials: Z
authors.lastname: Liao
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Mao
authors.forename: Qiuling
authors.initials: Q
authors.lastname: Shi
authors.forename: Gary M
authors.initials: GM
authors.lastname: Mobley
authors.forename: Jeanie F
authors.initials: JF
authors.lastname: Woodruff
authors.forename: Charles S
authors.initials: CS
authors.lastname: Cleeland
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D015992:Body Mass Index; D015179:Colorectal Neoplasms / Q000150:complications; D003131:Combined Modality Therapy / Q000009:adverse effects*; D016207:Cytokines / Q000097:blood; D003627:Data Interpretation, Statistical; D004938:Esophageal Neoplasms / Q000150:complications; D005221:Fatigue / Q000097:blood* / Q000209:etiology / Q000523:psychology*; D001068:Feeding and Eating Disorders / Q000209:etiology; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000097:blood* / Q000523:psychology* / Q000628:therapy; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D015850:Interleukin-6 / Q000097:blood*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011878:Radiotherapy / Q000009:adverse effects; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood*; D012044:Regression Analysis; D012893:Sleep Wake Disorders / Q000209:etiology; D012959:Socioeconomic Factors; D013315:Stress, Psychological / Q000209:etiology
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D018836:Inflammation Mediators; D015850:Interleukin-6; D047888:Receptors, Tumor Necrosis Factor, Type I