Effects of Adjuvant Chemotherapy on Cognitive Function of Patients With Early-stage Colorectal Cancer

Clin Colorectal Cancer. 2019 Mar;18(1):19-27. doi: 10.1016/j.clcc.2018.09.002. Epub 2018 Sep 13.

Abstract

Purpose: Chemotherapy-related cognitive impairment can occur in cancer survivors after treatment, especially those patients who have undergone chemotherapy for breast cancer. The frequency and to what extent such toxicity develops in colorectal cancer (CRC) survivors is unknown. The present prospective study evaluated the effects of adjuvant chemotherapy on the cognitive performance of patients with localized CRC compared with a control group who had not undergone chemotherapy.

Patients and methods: Consecutive patients with localized stage II and III CRC completed neuropsychological assessments, self-reported cognitive complaint questionnaires, and depressive symptom evaluations before starting fluoropyrimidine-based adjuvant chemotherapy and after 12 months. Blood was collected for apolipoprotein E genotyping. Diffusion tensor imaging data were acquired from a subset of participants at both evaluation points.

Results: From December 2012 to December 2014, 137 patients were approached and 85 were included. Of these 85 patients, 49 had undergone chemotherapy and 26 had not, in accordance with the standard recommendations for adjuvant therapy for CRC. The mean age was 62.5 ± 9.4 years, 60% were men, and the mean educational attainment was 7.6 ± 3.7 years. No difference was found in the global composite score (P = .38), attention (P = .84), or memory (P = .97) between the 2 groups during the follow-up period (mean ± standard deviation, 375 ± 29 days). However, a statistically significant difference was found for executive function after adjustment for age, sex, education, and depressive symptoms at baseline (β -1.80; 95% confidence interval, -3.50 to -0.11; P = .04), suggesting worse performance for the chemotherapy group. For the 32 patients who had undergone magnetic resonance imaging, tract-based spatial statistics did not show voxelwise significant differences in structural brain connectivity at baseline or during follow-up. Apolipoprotein E polymorphisms were not predictive of cognitive dysfunction.

Conclusion: Patients with CRC who received adjuvant 5-fluorouracil with or without oxaliplatin presented with a decline in executive function after 12 months compared with patients with localized disease who had not received chemotherapy.

Keywords: Apolipoprotein; CRC; Cognition; Diffusion tensor imaging; Magnetic resonance imaging.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Case-Control Studies
  • Chemotherapy, Adjuvant
  • Cognition Disorders / diagnosis
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / etiology
  • Colorectal Neoplasms / complications*
  • Colorectal Neoplasms / pathology
  • Diffusion Tensor Imaging
  • Female
  • Fluorouracil / administration & dosage
  • Follow-Up Studies
  • Humans
  • Leucovorin / administration & dosage
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Oxaliplatin / administration & dosage
  • Prognosis
  • Prospective Studies
  • Surveys and Questionnaires

Substances

  • Oxaliplatin
  • Leucovorin
  • Fluorouracil