Brain cortical structural differences between non-central nervous system cancer patients treated with and without chemotherapy compared to non-cancer controls: a cross-sectional pilot MRI study using clinically-indicated scans

Background: Cognitive deficit associated with cancer and its treatment is called cancer-related cognitive impairment (CRCI). Increases in cancer survival have made understanding the basis of CRCI more important. CRCI neuroimaging studies have traditionally used dedicated research brain MRIs in breast cancer survivors after chemotherapy with small sample sizes; little is known about other non-central nervous system (CNS) cancers after chemotherapy as well as those not exposed to chemotherapy. However, there may be a wealth of unused data from clinically-indicated MRIs that could be used to study CRCI.

Objective: Evaluate brain cortical structural differences in those with various non-CNS cancers using clinically-indicated MRIs.

Design: Cross-sectional.

Patients: Adult non-CNS cancer and non-cancer control (C) patients who underwent clinically-indicated MRIs.

Methods: Brain cortical surface area and thickness were measured using 3D T1-weighted images. An age-adjusted linear regression model was used and the Benjamini and Hochberg false discovery rate (FDR) corrected for multiple comparisons. Group comparisons were: cancer cases with chemotherapy (Ch+), cancer cases without chemotherapy (Ch-) and subgroup of lung cancer cases with and without chemotherapy vs C.

Results: Sixty-four subjects were analyzed: 22 Ch+, 23 Ch- and 19 C patients. Subgroup analysis of 16 lung cancer (LCa) patients was also performed. Statistically significant decreases in either cortical surface area or thickness were found in multiple regions of interest (ROIs) primarily within the frontal and temporal lobes for all comparisons. Effect sizes were variable with the greatest seen in the left middle temporal surface area ROI (Cohen's d -0.690) in the Ch- vs C group comparison.

Limitations: Several limitations were apparent including a small sample size that precluded adjustment for other covariates.

Conclusions: Our preliminary results suggest that, in addition to breast cancer, other types of non-CNS cancers treated with chemotherapy may result in brain structural abnormalities. Similar findings also appear to occur in those not exposed to chemotherapy. These results also suggest that there is potentially a wealth of untapped clinical MRIs that could be used for future CRCI studies.