Inflammatory Biomarkers and Fatigue during Radiation Therapy for Breast and Prostate Cancer

Purpose: Biomarkers of radiation-induced behavioral symptoms, such as fatigue, have not been identified. Studies linking inflammatory processes to fatigue in cancer survivors led us to test the hypothesis that activation of the proinflammatory cytokine network is associated with fatigue symptoms during radiation therapy for breast and prostate cancer. Experimental Design: Individuals with early-stage breast (n = 28) and prostate cancer (n = 20) completed questionnaires and provided blood samples for determination of serum levels of interleukin 1 beta (IL-1 beta) and IL-6 at assessments conducted before, during, and after a course of radiation therapy. Serum markers of proinflammatory cytokine activity, including IL-1 receptor antagonist and C-reactive protein, were examined in a subset of participants. Random coefficient models were used to evaluate the association between changes in cytokine levels and fatigue. Results: As expected, there was a significant increase in fatigue during radiation treatment. Changes in serum levels of inflammatory markers C-reactive protein and IL-1 receptor antagonist were positively associated with increases in fatigue symptoms (P(S) < 0.05), although serum levels of IL-1 beta and IL-6 were not associated with fatigue. These effects remained significant (P(s) < 0.05) in analyses controlling for potential biobehavioral confounding factors, including age, body mass index, hormone therapy, depression, and sleep disturbance. Conclusions: Results suggest that activation of the proinflammatory cytokine network and associated increases in downstream biomarkers of proinflammatory cytokine activity are associated with fatigue during radiation therapy for breast and prostate cancer. (Clin Cancer Res 2009;15(17):5534-40)