Eva van Grinsven

84 Chapter 4 involvement. Additionally, for those patients who completed follow-up NCAs, the clinical MRI follow-up scans were evaluated to determine intracranial progression during follow-up and new radiotherapy treatments were registered. Statistical analyses For this study the subjective and objective cognitive data acquired from October 2020 to May 2023 was used. Analyses were performed using SPSS (IBM SPSS Statistics, 25.0.0). Statistical significance was set at p<0.05, adjusted for multiple comparisons when necessary. We anticipated that the assumption of normally distributed data would be violated due to the sample size and selected non-parametric alternatives for all statistical tests. Differences between patient completing and not completing the follow-up NCAs were assessed using chi-square test for categorical data and Mann-Whitney U-tests for continuous data. At each time point, the percentage of patients with a cognitive performance below the impairment threshold (Z≤-1.5) was calculated for each task as well as for each domain. Additionally, individual changes in both subjective and objective cognitive performance were calculated for (1) each domain (“domain-level”) and (2) across all domains (“overall-level”). Above-described cut-off scores were used to determine an improvement, deterioration, mixed or stable score. Changes in scores were calculated for baseline versus 3 months, and 3 versus ≥11 months. For the overall-level, patients were categorized into four categories for subjective and objective cognitive performance separately: (1) decline, (2) improvement, (3) mixed, and (4) stable performance. Decline and improvement were defined as either a decrease or increase on at least one cognitive domain, respectively. The category “mixed” included patients who showed both declined and improved performance across the domain and/or, for objective cognitive performance only, within one domain. Patients were categorized into “stable” if performance across all domains remained unchanged. Subsequently, age, baseline KPS, primary tumor, presence of extracranial metastases, number of BMs, symptomatic BMs, synchronous diagnosis of BMs, intracranial progression at 3 months as determined by clinical follow-up scans and baseline cognitive impairment were assessed for the four categories, separately for the two time periods and for subjective and objective cognitive performance. As this analysis aimed to explore possible risk factors for cognitive decline, no corrections for multiple comparisons were performed.

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