Association of sTNF-R1 and the development of treatment-related symptoms in patients undergoing concurrent chemoradiation therapy for colorectal or esophageal cancer

Abstract

3041 Background: Cancer-treatment-induced dysregulation of proinflammatory cytokines may be a common mechanism underlying the development of symptom burden (e.g., pain, fatigue, distress, and disturbed sleep) during concurrent chemoradiation therapy (CXRT). Methods: Patients undergoing CXRT for locally advanced colorectal or esophageal cancer (N=97) reported symptoms weekly via the M. D. Anderson Symptom Inventory (MDASI). Serum samples were tested weekly during therapy for changes in concentration levels of inflammatory cytokines (interleukin [IL]-6, IL-8, IL-10, IL-1 receptor antagonist [IL-1RA], vascular endothelial growth factor [VEGF], and soluble tumor necrosis factor receptor type 1 [sTNF-R1]) via enzyme-linked immunosorbent assay (ELISA). Symptom responses were modeled using longitudinal ordinal probit regression functions that included these serum cytokine values, along with age, cancer type, prechemotherapy status, and race (non-Hispanic white vs. others), as explanatory variables. Results: The severity of multiple symptoms significantly increased at week 4 and peaked around the end of CXRT (weeks 5–7). We found that an increase in the serum level of sTNF-R1 was significantly associated with an increase in the severity of 14 of the 16 MDASI symptoms individually over the course of CXRT, as well as with each of the 6 interference items (all p<.001). Even when week of observation was added as a variable to account for concurrent systematic trends in symptom reports and cytokine levels, sTNF-R1 retained a significant positive association with 14 of 16 symptoms, and IL-6 also showed a significant positive association with 6 of 16 symptoms. Conclusions: Longitudinal analysis identified temporal associations between increases in level of serum sTNF-R1 (and, to a lesser degree, IL-6) and the development of multiple symptoms in patients undergoing CXRT for colorectal and esophageal cancer. The results may be indicative of these cytokines as potential intervention targets of reducing aggressive chemoradiation-induced symptom burden. No significant financial relationships to disclose.