Relationships between cognitive impairment and regional brain activity induced by central neurotoxicity of FOLFOX and FOLFIRI in colorectal cancer patients: a resting-state fMRI study.

[INTRODUCTION] Chemotherapy-induced neurologic dysfunction was experienced by colorectal cancer (CRC) survivors. However, the exact mechanism remains unclear.

[METHODS] We recruited CRC survivors who had undergone 2-3 month-long FOLFOX and FOLFIRI chemotherapy. Cognition was assessed at enrollment and after chemotherapy. FMRIdata were acquired and preprocessed. ReHowas calculated and compared to examine the differences of brain activities. ROCcurve was performed to evaluate the capacity of ReHo values in distinguishing patients after FOLFOX, FOLFIRI and HCs. Relationships between ReHo values, chemotherapy cycles and cognitive scores were evaluated. The mediating effects of ReHo values on the relationships between chemotherapy cycles and cognitive function were also evaluated.

[RESULTS] CRC patients exhibited decreased ReHo values in the left superior frontal gyrus (dorsolateral), inferior frontal gyrus (opercular part), right superior frontal gyrus (medial), inferior frontal gyrus (opercular part), middle temporal gyrus and increased ReHo values in the right rolandic operculum after FOLFIRI chemotherapy when compared with the group of FOLFOX. ROC analysis revealed that ReHo values might be helpful for distinguishing CRC patients after FOLFOX, FOLFIRI chemotherapy and HCs. Relationships were identified between cognitive scores, chemotherapy cycles and ReHo values of the prefrontal regions in CRC patients after chemotherapy. ReHo values of the left inferior frontal gyrus (opercular part) partially mediated the correlations between chemotherapy cycles and cognitive scores.

[CONCLUSION] The prefrontal cortex might be the preferred brain regions attacked by the central neurotoxicity of both FOLFOX and FOLFIRI, and the latter had wider implications on the regional brain activity.