218 Chapter 9 These findings also highlight an important opportunity for healthcare. That is, patients with BMs may benefit from an elaborate NCA three to four months after radiotherapy, which could provide them with insights into their individual cognitive strengths and weaknesses. Such assessments could help patients and their caregivers understand their cognitive abilities, which in itself could be of great value. Moreover, these individual cognitive profiles could potentially identify specific avenues for cognitive rehabilitation (e.g. memory strategy training), ultimately improving the QoL for these patients. RESEARCH CHALLENGES Dynamics of healthcare As illustrated above, the complexities of the BMs population necessitate careful consideration of multiple factors and influences in research. This research is subsequently conducted within the ever-evolving context of contemporary healthcare. A perfect example of this is the shift in treatment preference from WBRT to SRS, where (Dutch) guidelines advise up to 10 BMs to be treated with SRS.35–38 However, unlike WBRT, SRS lacks the ability to sterilize not-yet visible BMS. This has likely led to the increase in retreatments with SRS whereby patients return for subsequent courses of SRS for new BMs in different locations. In 2018 retreatment constituted 12.5% of SRS treatment, which increased to approximately 33% in 2022 in the UMC Utrecht. A wealth of research has demonstrated the feasibility, tolerability and efficacy of multiple courses of SRS for recurrent BMs.e.g. 39–44 This research shows that while rates of radiation necrosis are significant, repeated SRS may be indicated for a selected group of patients with local disease recurrence. Consequently, repeated SRS may serve as a means to delay or even avoid WBRT, which would align with the favorable cognitive outcomes after SRS compared to WBRT (Chapter 2). However, the impact of these multiple rounds of treatment on the brain in the long-term requires further exploration. It is plausible to speculate that there exists a threshold for brain damage that can be sustained from SRS beyond which clinical manifestations arise, akin to the concept of brain reserve.45 This may also explain the absence of apparent changes in vascular or metabolic reserve capacity in patients with BMs after one round of SRS (Chapter 7). Future research endeavors should investigate whether the notion of brain reserve extends to repeated rounds of SRS. Understanding the context of changes An important part of this thesis has centered around identifying and understanding changes in either cognitive functioning or brain physiology after radiotherapy. To
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