Background: Inflammation is a putative mechanism of cognitive impairment in cancer patients.    As part of a prospective longitudinal study of cognitive function and fatigue in colorectal cancer (CRC) patients we evaluated cytokine levels. Methods: Serum levels of 10 cytokines were measured using a multiplex assay on patients with localized CRC at baseline (mean 7 weeks post-surgery or before neoadjuvant therapy), 6, 12 and 24 months, and in healthy controls (HC) at the first 3 time points. Group 1A (Stage III/high risk II) received chemotherapy (CT+) and group 1B (Stage I/II) received no CT (CTh-). Patients completed neuropsychological (NP) assessments and concurrent questionnaires for fatigue & QOL, anxiety/depression, and perception of cognitive function. Associations between cytokine levels, test results, demographic and disease-related factors were sought.

Results: In total, 299 localised CRC patients (173 CTh+, 116 CTh-), median age 58 (23-75), 63% male; and 72 HC were assessed. There was no difference in cognitive impairment between CTh+ and CTh- at any time point, but CRC patients had significantly higher rates of cognitive impairment than HC: baseline Group 1 45% vs HC 15%; 12 months (primary endpoint) Group 1 36% vs HC 10%.  Cancer patients had significantly higher cytokine levels at all time points compared to HC.  At baseline cytokine levels were associated with stage of disease.  There was no consistent association of cytokines with global cognitive impairment, but elevated cytokines were associated with impairment on some individual tests. Conclusions: Cytokine levels were elevated in most CRC patients. Cognitive impairment is present in 45% of CRC patients prior to chemotherapy and persists at 12 months in 36%, with no difference between CTh+ and CTh-.  Our study did not find convincing evidence for a relationship between cognitive impairment and cytokines, but indepth analysis is ongoing.