15 General introduction and thesis outline To provide a thorough overview of the current knowledge in the field, Chapter 2 summarizes and compares the available literature on the effect of either SRS or WBRT on neurocognitive performance in patients with BMs. Since SRS is increasingly being favored over WBRT in current practice, this review aimed to gain insight on whether current evidence regarding cognitive side-effects substantiate contemporary shifts in treatment preference. Moreover, this chapter offers insights into potential gaps in knowledge, which can serve as a foundation for future studies. Chapter 3 offers a detailed description of the cognitive performance, both subjectively and objectively, of patients with BMs before they begin radiotherapy. Examination of clusters of cognitive deficits enabled a deeper understanding of how different aspects of cognitive function may relate to one another. This chapter provides a thorough understanding of the patients who will be the topic of investigation in this thesis and their presentation to the radiotherapy clinic. It thereby provides important context within which the post-radiotherapy cognitive changes should be evaluated. Chapter 4 evaluates the short- and long-term changes in both subjective and objective cognitive performance in patients with BMs after radiotherapy. It provides insight into the multifaceted nature of changes and highlights opportunities for interventions (e.g. patient-tailored psycho-education, cognitive strategy training) in this specific group of patients. Individual trajectories of cognitive function are assessed to gain a clearer understanding of the cognitive impact of radiotherapy on the individuals comprising this patient group. Part II: Using imaging techniques to understand neurocognitive functioning To aid in understanding of the pathophysiology underlying the cognitive difficulties described in part I, the second part of this thesis focuses on the use of various imaging techniques. The aim is two-fold. First, I determined the generalizability of insights from other imaging studies to different patient populations. Next, the use of physiological MRI biomarkers within the BMs population was assessed. As researching lesion-behavior patterns in large populations of patients with BMs is challenging due to their limited life expectancy and diversity of lesion locations, we sought to gain insights from other diseases affecting the central nervous system, like ischemic stroke. In Chapter 5 we examined whether damage to the same brain regions cause by either a stroke or primary brain tumor resulted in similar or different sets of cognitive outcomes. This aids in understanding the generalizability of findings from one patient population to others. 1
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