95 Individual Cognitive Trajectories Post-Radiotherapy for Brain Metastases negative changes are likely to have a significant impact on the daily lives of these patients. The heterogeneity in cognitive outcomes can likely be attributed to a range of factors, including the extent and location of metastases, individual variabilities in treatment response, and pre-existing cognitive or neural vulnerabilities. Future studies incorporating these different variables in large cohorts could advance our understanding of the complex interplay between treatment-related factors and patient-specific factors in shaping cognitive outcomes after radiotherapy. The current results present a snapshot of the currently available evidence on cognitive trajectories of individual patients with BMs after receiving radiotherapy. It is challenging to discern the effects of radiotherapy from those of other treatments and disease progression, as adjuvant systemic treatments during the study period may have contributed to declines in cognitive performance. Due to the inevitable deterioration in medical condition of this population, results are mainly representative of the group of patients fit enough 3 months post-radiotherapy. Nevertheless, both compliance rates and available patients for follow-up, especially in the long-term, were comparable to or higher than previous studies.13,14,20,49–51 Most importantly, these results can be used to design future studies to best capture the complexity of individual cognitive changes in patients with BMs. For example, as memory seems particularly vulnerable, multiple tests each capturing different aspects of this multifaceted cognitive function should be incorporated. CONCLUSION The increasing incidence of BMs and improved survival rates underscore the urgent need to investigate the effects of treatments on individuals, because group-level information alone is insufficient when conveying the potential treatment effects to patients and caregivers. Our study revealed a complex impact of radiotherapy on subjective and objective cognitive performance, involving both positive and negative changes across various cognitive domains. Particularly, memory showed vulnerability in the early post-radiotherapy period. The observed within-individual variation emphasizes the involvement of intricate underlying mechanisms, highlighting the need for further investigation. Despite current advancements in treatment patients remain at risk for intracranial progression, which was a clear risk factor for subjective cognitive decline in this study. These findings are specific to patients with BMs who have undergone radiotherapy and should be considered in light of the potential trade-off between cognitive difficulties and survival benefits. Our results show the heterogeneity of cognitive profiles post-radiotherapy, 4
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