The ENIGMA Cancer and Chemotherapy Working Group and Cancer-Related Cognitive Impairment

Objective: Study brain morphometric abnormalities that might underlie cancer-related cognitive impairment Background: By 2026 there will be 20.3 million cancer survivors. Given this, it is important to address cancer-related cognitive impairment (CRCI). CRCI is very common, but its neural substrates remain unclear. Most CRCI neuroimaging studies have evaluated small cohorts and have focused almost entirely on breast cancer after chemotherapy. While these studies have found morphometric differences between cancer survivors compared to controls, results have been variable. Furthermore, little is known about other cancers or the effects in the absence of chemotherapy. Design/Methods: In two independent cohorts, we conducted cross-sectional studies using clinical brain MRI scans of survivors of various non-central nervous system (CNS) cancers. FreeSurfer (version 5.3) was used to measure brain morphometry. Multivariate linear regression was used to assess predictors of brain metrics, while adjusting for multiple comparisons. Results: In our first cohort (n = 104), we found statistically significant decreases in subcortical volumes in the caudate and amygdala after chemotherapy (Ch+) compared to non-cancer controls. Without chemotherapy (Ch-), similar findings were seen in the caudate. In our second cohort (n = 64), we found 5 regions of either lower cortical thickness or surface area for Ch+; for Ch-, 21 such regions were found. Many of these effects were in frontal and temporal regions. Conclusions: Our preliminary data suggest that cancers other than breast cancer may result in brain morphometric abnormalities. To boost statistical power to detect subtle effects, larger multicohort studies are valuable. Our lab is home to the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium, an international neuroimaging effort that studies over 20 brain disorders. To validate our preliminary results, we formed an ENIGMA Cancer and Chemotherapy Working Group whose goal is to perform the highly-powered CRCI neuroimaging studies and assess how well findings generalize across cohorts. Study Supported by: Supported in part by the following grants: NIH KL2TR000131, NIH 1L30CA209248-01, NIH Big Data to Knowledge (BD2K) Initiative under U54EB020403, Wright Foundation Pilot Award and American Cancer Society IRG-16-181-57. Disclosure: Dr. Shiroishi has nothing to disclose. Dr. Gupta has nothing to disclose. Dr. Faskowitz has nothing to disclose. Dr. Bigjahan has nothing to disclose. Dr. Cen has nothing to disclose. Dr. Rashid has nothing to disclose. Dr. Hwang has nothing to disclose. Dr. Lerner has nothing to disclose. Dr. Boyko has nothing to disclose. Dr. Liu has nothing to disclose. Dr. Law has nothing to disclose. Dr. Thompson has nothing to disclose. Dr. Jahanshad has nothing to disclose.