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

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Abstract
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.
Funding Information
  • National Cancer Institute (U01CA206110)
  • National Institute of Nursing Research (R01NR018762)

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