Longitudinal Analysis Of Quality Of Life As An Independent Predictor Of Neurocognitive Function In Brain Tumor Patients

Abstract

Primary brain tumor patients experience reduced health-related quality of life (hrQoL), which may be compounded by treatments including radiation therapy (RT). We conducted a prospective longitudinal study to examine the association between hrQoL (physical, social/family, emotional, functional, and brain cancer-specific) and domain-specific neurocognitive function in primary brain tumor patients. Primary brain tumor patients (n = 59) receiving fractionated brain RT underwent comprehensive hrQOL (Functional Assessment of Cancer Therapy-Brain [FACT-Br]) and neurocognitive evaluation at baseline and 3, 6, and 12 months post-RT. Neurocognitive assessments measured attention and processing speed (Delis-Kaplan Executive Function System Trail Making Test [DKEFS-TMT] Visual Scanning, Number Sequencing, and Letter Sequencing and Weschler-Adult Intelligence Scale-IV [WAIS-IV] Digit Span and Coding), memory (Hopkins Verbal Learning Test-Revised [HVLT-R] Total and Delayed Recall and Brief Visuospatial Memory Test [BVMT] Total and Delayed Recall), and executive function (DKEFS Verbal Fluency [DKEFS-VF] Letter Fluency and Category Switching and Wisconsin Card Sorting Test [WCST] Perseverative Errors). Cognitive scores were transformed to t-scores controlling for age and sex; higher cognitive t-scores and hrQOL scores reflect better function. Multivariable linear mixed-effects models assessed independent association between hrQOL scores and neurocognitive function over time, controlling for patient, tumor, and treatment characteristics as well as timepoint-specific patient-reported anxiety and depression symptoms. P-values were corrected for multiple comparisons using false discovery rate. Median age of the cohort was 47 years. Most were male (61%) and married (71%). Higher physical hrQoL showed significant independent association with better verbal memory (HVLT Total Recall p = 0.047), while higher functional hrQoL correlated with better executive function (DKEFS-VF Switching Total p = 0.009) and verbal memory (HVLT Delayed Recall p = 0.006). Higher brain cancer-specific hrQoL was associated with better performance on tests of verbal and non-verbal memory (HVLT Total p = 0.004 and Delayed Recall p = 0.030; BVMT Total p = 0.049 and Delayed Recall p = 0.049). There was no significant association between social/family or emotional hrQoL and neurocognitive scores. This is the first prospective study to assess the independent association of hrQOL and neurocognition in primary brain tumor patients. We found that reduced physical, functional, and brain cancer-specific hrQoL were independently associated with worse executive function and memory among primary brain tumor patients receiving RT. Physical and functional impairments may impact cognitive performance in this population after RT.