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 = .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 < .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.

The impact of anti-inflammatory agents on the outcome of patients with colorectal cancer

“…In an interventional study of patients undergoing curative CRC resection, Malicki and co-workers found a significant reduction in pre-operative serum IL-6 in patients receiving statins (96). In contrast however, a recent study of the systemic inflammatory response to neoadjuvant chemoradiotherapy in patients with oesophageal and rectal cancer found that concomitant statin use did not attenuate the serum inflammatory response or treatment-associated symptoms (97). Further clarification of the effects of statins on cancer-related systemic inflammation is required, and such measures should be incorporated in to future studies of the chemotherapeutic benefits of statins.…”

High-Dose Asian Ginseng (Panax Ginseng) for Cancer-Related Fatigue

“…Most of the enrolled patients (Table 2) in the study were receiving cancer therapy. As CRF varies according to the cycle and duration of cancer therapy (ie, chemotherapy or targeted therapy or radiation therapy), 67,68 the cancer therapy can be a confounder in this study. Also because this study had no placebo arm, the efficacy of PG may have been due to a placebo effect.…”

Variation in fatigue among 6011 (long-term) cancer survivors and a normative population: a study from the population-based PROFILES registry

“…The pro-inflammatory cytokine, IL-4, was associated with the constellation of fatigue, pain, sleep disturbance, and depression symptoms in cancer survivors [41]. Overexpression of pro-inflammatory cytokines, sTNF-R1 and sIL-6, was associated with fatigue development over the course of chemoradiation treatment for gastrointestinal cancer [42]. To better understand the mechanisms underlying self-reported CRF, future research can include biological data such as inflammation markers.…”