94 Chapter 4 compared to pre-radiotherapy. After excluding the two patients who received WBRT, these percentages remained unchanged, highlighting the notable prevalence of memory decline within our SRS patient sample. The negative impact of radiotherapy on learning and memory performance has received widespread recognition. As the hippocampus is the primary brain region responsible for learning and memory, a great deal of interest has now been put into hippocampal avoidance WBRT (HAWBRT)e.g. 32–34 and now even HA-SRS35 for the possible preservation of neurocognition. While damage the hippocampus has indeed been implicated in cognitive decline following brain radiotherapy, recent findings underscore concomitant shrinkage in other subcortical brain structures, as well as damage to both white matter and other cortical territories.36–42 Moreover, contemporary perspectives on cognitive functioning emphasize its network-based nature, moving beyond mere localization.43,44 This recognition complicates the straightforward attribution of cognitive side-effects exclusively to specific radiotherapy-vulnerable brain regions. Further research is needed to better understand the complex interplay between radiotherapy, brain structures, and cognitive functioning in order to optimize treatment outcomes in clinical settings. In the long-term, slowing of both processing and psychomotor speed was most prominent, while this was not reflected accordingly in self-reported cognitive changes. Multiple factors could have contributed to the observed slowing as processing and psychomotor speed both rely on a widespread neural network.45,46 As most patients with BMs receive systemic treatment after brain radiotherapy, the long-term psychomotor slowing could also be a consequence of chemotherapyinduced neuropathy rather than long-term radiotherapy effects.47,48 In our sample, a decline in objective cognitive performance was observed in nearly all patients. Interestingly, for the majority, this decline was accompanied by improvement in another cognitive domain. This pattern of mixed responses persisted in the long-term and was irrespective of patients’ pre-radiotherapy cognitive impairment. While not statistically significant, a higher number of BMs and metasynchronous BMs diagnosis appeared more common among patients with cognitive decline 3 months post-radiotherapy, suggesting potential areas for future investigation. As mixed responses were predominant, no other clear risk factors for post-radiotherapy cognitive changes were found. It is important to acknowledge that cognitive improvement does not necessarily indicate the absence of cognitive impairment, as demonstrated by the small percentage of patients without any cognitive impairment at both follow-up times (3-21%). Nonetheless, the RCI enabled us to identify meaningful changes, indicating that both the observed positive and
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