NCOG-09. ASSOCIATIONS OF COGNITIVE FUNCTION WITH BRAIN STRUCTURE, COMT GENOTYPE, AND PSYCHOLOGICAL FACTORS IN MELANOMA PATIENTS PRIOR TO ADJUVANT IMMUNE CHECKPOINT INHIBITOR THERAPY

Abstract BACKGROUND Cancer-related cognitive impairment (CRCI) presents a significant concern in cancer patients. Yet, limited research addresses its prevalence and potential underlying risk factors in melanoma patients, including neurobiological, genetic, and psychological factors. METHODS We assessed cognitive functioning, cognitive complaints, brain gray matter (GM) properties, COMT genotype, and psychological factors (fatigue, anxiety, depression, insomnia severity, sleep difficulties, quality of life) in malignant melanoma patients (MMPs) before treatment with immune checkpoint inhibitors (ICIs) and compared with matched healthy controls (HCs). A total of 47 MMPs and 53 HCs were enrolled. Between-group differences were tested, and statistical associations between cognitive function and brain GM properties, COMT polymorphisms, and psychological factors were explored. RESULTS MMPs exhibited significantly lower levels of cognitive functioning compared with HCs across multiple cognitive tests (all p’s<.05), with a high prevalence of clinically significant CRCI (68.1% VS 26.4%). Analysis of GM properties revealed volumetric differences in the left cuneus between MMPs and HCs with MMPs having smaller volume compared to HCs. In MMPs but not in HCs, statistically significant associations were found between WAIS-IV Coding and right precentral cortical thickness, TMT-A and left inferior parietal cortical thickness, and BVMT-R Delayed Recall and right postcentral GM volume (all p’s<.01). COMT polymorphisms were associated with self-reported cognitive complaints but not with objective cognitive performance. Compared with HCs, MMPs reported higher levels of fatigue, anxiety, insomnia severity, and sleep difficulties, and lower levels of quality of life (all p’s ≤.009). Additionally, self-reported cognitive complaints in MMPs were associated with different cognitive test performances (all p’s<.05), fatigue (p<.001) and anxiety (p<.045). CONCLUSIONS These findings underscore the importance of comprehensive cognitive and psychological assessments in MMPs referred for adjuvant ICI therapy. Understanding the complex array of symptoms including CRCI in this population can inform tailored interventions to improve quality of life and treatment outcomes.