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.

Fig. 1

Loess curves of the most severe symptoms and markers over time during concurrent chemoradiation: weekly assessment by MDASI. Loess curves illustrate a gradual increase in symptom severity (on a 0–10 scale) as the dose of concurrent chemoradiation therapy (CXRT) accumulated in patients with gastrointestinal cancer receiving CXRT. MDASI = M. D. Anderson Symptom Inventory; sTNF-R1 = soluble tumor necrosis factor receptor 1; IL-6 = interleukin 6.