• J Vardy, H M Dhillon, G R Pond, S B Rourke, W Xu, A Dodd, C Renton, A Park, T Bekele, J Ringash, H Zhang, R Burkes, S J Clarke, and I F Tannock.
• Sydney Medical School, University of Sydney, Sydney, Australia Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada Concord Cancer Centre, Concord Hospital, Concord, Australia janette.vardy@sydney.edu.au.
• Ann. Oncol. 2014 Dec 1; 25 (12): 2404-12.

BackgroundCognitive impairment and fatigue have been associated with cancer and its treatment. We present baseline data from a large longitudinal study that evaluates cognitive function, fatigue, and potential underlying mechanisms following diagnosis of colorectal cancer (CRC).Patients And MethodsWe evaluated CRC patients with stage I-III disease before or after surgery, participants with limited metastatic disease and healthy controls (HC). Neuropsychological evaluation included clinical and computerised tests. Participants completed questionnaires for fatigue and quality of life (QOL)-(FACT-F), anxiety/depression, and cognitive symptoms (FACT-Cog). Ten cytokines, clotting factors, sex hormones, carcinoembryonic antigen (CEA), and apolipoprotein E genotype were evaluated. Primary end points were cognitive function on clinical tests evaluated by a Global Deficit score (GDS) and fatigue. Associations between test results, demographic, and disease related factors were explored.ResultsWe assessed 291 participants with early-stage disease [median age 59 (23-75) years, 63% men], 72 with metastatic disease, and 72 HC. Using GDS, 45% (126/281) of participants with early-stage CRC had cognitive impairment versus 15% (11/72) of HC (odds ratio 4.51, 95% confidence interval 2.28-8.93; P < 0.001), with complex processing speed, attention/working memory, and verbal learning efficiency being most affected. Women with early-stage CRC had greater cognitive impairment than men [55/105 (52%) versus 71/176 (40%), P < 0.050]. Cognitive symptoms were self-reported by 21% (59/286) of early-stage patients versus 17% (12/72) of HC; fatigue by 52% (149/287) of early-stage patients and 26% (19/72) of HC (P < 0.0001). Women reported more fatigue than men (P = 0.003). Fatigue, QOL, anxiety/depression, and cognitive symptoms were associated with each other (r = 0.43-0.71), but not with neuropsychological performance. Most cytokines were elevated in cancer patients. Cognitive function was not associated with cytokines, sex hormones, clotting factors, CEA, or apolipoprotein E genotype.ConclusionsThe incidence of cognitive impairment was three to five times higher in CRC patients than HC, with women having higher impairment rates than men. The cognitive impairment profile suggests dysfunction primarily in fronto-subcortical brain systems.Trial RegistrationNCT00188331.© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

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