205 Summary The findings presented in Chapter 2 demonstrate that cognitive deficits are prevalent in this population; in roughly one out of every two patients with BMs cognitive deficits can be observed prior to undergoing radiotherapy. Both these pre-treatment deficits and post-treatment declines were not limited to one cognitive domain, but rather span across multiple domains. Thus, in order to fully capture and comprehend the heterogeneity of cognitive functioning of this patient population, a comprehensive cognitive test battery should be used. Therefore, in Chapter 3 subjective cognitive complaints and neurocognitive functioning of 58 patients with BMs prior to radiotherapy were extensively investigated. Additionally, the added value of an elaborate cognitive test battery versus a core test battery in identifying cognitive deficits was assessed. We used data from the ongoing prospective Cohort for patient-reported Outcomes, Imaging and trial inclusion in Metastatic BRAin disease (COIMBRA) and Assessing and Predicting Radiation Influence on Cognitive Outcome using the cerebrovascular stress Test (APRICOT) study. Both studies include adult patients (≥18 years) with either radiographic and/ or histologic proof of BMs referred to the University Medical Center Utrecht (UMCU) for radiotherapy. Patients with BMs were able to make differentiated domainspecific judgements of their subjective cognitive functioning when using visual analogue scales (VAS). Moreover, nearly all BMs patients referred for radiotherapy experienced some degree of neurocognitive dysfunction. Both at the group and individual level, significant heterogeneity in cognitive functioning was observed, with a wide variety of cognitive domains affected. The pre-radiotherapy neurocognitive dysfunction could be clustered into four meaningful cognitive profiles, whereby the presence of memory deficits was a major determining factor. No clinical or patient characteristics were found to be related to cluster membership. Employing a 90 minute elaborate cognitive test battery was feasible in this group of cognitively vulnerable patients. When solely using the core battery, the extent of cognitive deficits may be underestimated, demonstrating the value of elaborate testing. In Chapter 4 we continued the investigation of neurocognitive dysfunction in patients with BMs at both the short (3 months) and long-term (≥11 months) after radiotherapy. Our focus was not solely on objective cognitive deficits, but also included an examination of subjective cognitive functioning. Reliable change indices were used to assess clinically meaningful individual changes. From the COIMBRA and APRICOT study, 36 patients completed short-term follow-up and 14 patients long-term. A considerable number of patients (50%) self-reported cognitive decline in at least one domain, commonly affecting memory and attention. Subjective cognitive decline was more commonly observed in patients with intracranial disease progression within three months post-radiotherapy. Almost all patients suffered from cognitive 8
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