Inflammatory biomarkers and fatigue during radiation therapy for breast and prostate cancer

Abstract

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 1beta (IL-1beta) 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 (Ps < 0.05), although serum levels of IL-1beta and IL-6 were not associated with fatigue. These effects remained significant (Ps < 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.

Figures

Fig. 1

Fatigue symptoms during radiation therapy. There was a significant increase in number of days fatigued in breast and prostate cancer patients during treatment, followed by a decrease in fatigue after treatment completion.

Fig. 2

Circulating inflammatory markers during radiation therapy. Box-and-whisker plots represent data with boxes ranging from the 25th to the 75th percentile of the observed distribution of values. Horizontal lines, the median value for serum levels of IL-1B (A), IL-6 (B), CRP (C), and IL-1 receptor antagonist (D). Whiskers span minimum to maximum observed values, with algorithm-defined outliers identified by open circles and stars.

Fig. 3

Association between CRP and fatigue symptoms. Representative data from two participants showing that, on weeks when serum levels of CRP were elevated, there was a corresponding elevation in the number of days fatigued.