Longitudinal Associations Between Inflammatory Biomarkers and Fatigue in Patients With Colorectal Cancer: A Multicenter Study

PURPOSE: Fatigue affects up to 90% of patients with cancer during chemotherapy and persists in approximately 30% after treatment completion. This study examined the longitudinal associations between fatigue and 16 inflammatory markers in patients with colorectal cancer (CRC) up to 3 years after surgery. METHODS: Patients with Stage I-IV CRC who participated in the prospective ColoCare cohort study were included. Fatigue was measured using the 3-item fatigue subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) at baseline and each subsequent time point (score range: 0-100). Inflammatory markers were measured using blood specimens from each time point (T0: baseline/surgery; T1: 3-9 months; T2: 10-19 months; T3: 20-36 months post-baseline). Linear mixed-effects models were used to examine associations between inflammatory markers and fatigue scores over time. Linear regression was used to analyze the relationships between T0/T1 markers and fatigue at T3. RESULTS: There were 271 patients with Stage I-III CRC and 30 patients with Stage IV CRC. Among patients with Stage I-III CRC, mean fatigue peaked at T1 (36.9), with higher fatigue among women than men (44.8 vs. 30.9). In longitudinal mixed-effects models, twofold higher mean levels of IL-6 and IL-17A were associated with higher fatigue over time (3.51 (p = 0.01) and 3.91 (p = 0.01), respectively). IL-4, IL-17A, and TNF-α at T1 were nominally associated with higher levels of fatigue at T3. CONCLUSION: Higher levels of selected inflammatory biomarkers were associated with fatigue up to 3 years after CRC diagnosis. These markers may help identify patients at risk for persistent fatigue and warrant further study as potential therapeutic targets.