The significance of cognitive function assessment in treatment-naïve high-grade glioma patients on clinical outcomes using neuropsychological tests: A review of current research.

Abstract

e14022 Background: High-grade gliomas (HGGs), classified as WHO grades III and IV, represent over 50% of newly diagnosed malignant primary brain tumors, with median overall survival rates of 24–72 months (grade III) and 14–16 months (grade IV). Neurocognitive functioning (NCF) impairment, a common complication at diagnosis, often stems from tumor-related disruptions to brain networks, adversely affecting outcomes and survivorship. While post-treatment NCF assessment has shown benefits, there are limited comprehensive reviews on its role in treatment-naïve HGG patients. This review aims to investigate the significance of pre-treatment NCF assessment in prognosis prediction and monitoring disease progression for this population. Methods: A systematic review followed PRISMA guideline. PubMed was searched for studies (2015 – 2024) on NCF assessment in treatment-naïve high-grade glioma (HGG) patients (≥18 years) using MeSH terms and keywords related to ‘high-grade gliomas,’ ‘cognitive status,’ ‘neuropsychological tests,’ and ‘clinical outcomes.’ The search identified 87 studies. Eligible studies included pre-treatment neuropsychological assessments and reported outcomes on survival, progression, or treatment strategies. Three reviewers independently screened studies and assessed quality. Findings were synthesized narratively due to study heterogeneity. Results: Four observational studies met the inclusion criteria. Baseline NCF status emerged as a significant predictor of clinical outcomes. Impaired executive function was associated with reduced overall survival (OS) and early progression. Patients with unimpaired Trail Making Test-B (TMT-B) performance had a median OS of 26 months, compared to 10 months for those with impairments (P < .01). Decline in working memory was predictive of poorer survival (HR = 1.71, P = .018). Incorporating memory assessment into prognostic models improved model fit (P = .018) and discriminative ability, increasing AUC from 0.77 to 0.78. Baseline NCF assessment also provided diagnostic insights, regarding the association between cognitive performance and IDH mutation status. Patients with IDH mutations significantly outperformed IDH wild-type patients on TMT-B (P ≤ .01), Digit Span backward (P ≤ .01), and COWAT phonemic tests (P ≤ .01), reflecting distinct biological mechanisms beyond conventional tumor characteristics. Conclusions: Baseline cognitive function assessment offers critical prognostic and diagnostic insights for treatment-naïve HGG patients. It enhances the prediction of clinical outcomes and informed discussions with patients about treatment strategies. Future studies should focus on standardizing pre-treatment NCF assessment and exploring its broader application inclinical practice to guide personalized management for this population.