213 Discussion Figure 1. Illustration showcasing the various challenges encountered in studying patients with BMs, including both patient-related and research-related obstacles. PATIENT-RELATED CHALLENGES Multifaceted treatment approaches The focus of the research presented in this thesis was on evaluating the effects of radiotherapy treatment. It is important to consider that treatment of patients with BMs most often requires a multifaceted treatment approach. While radiotherapy is the cornerstone of the medical treatment specifically for the BMs, the primary tumor and sometimes extracranial metastases often require additional systemic treatment and radiotherapy. Most patients with BMs (re)initialize systemic treatment in the weeks following brain radiotherapy, which can include chemotherapy, immunotherapy and targeted therapy or a combination. The significance of systemic treatments for patients with BMs is now underscored by the growing evidence that some systemic treatments also show intracranial efficacy, at least for patient with breast cancer, lung cancer or melanoma.6–8 It has become increasingly difficult to isolate the effect of a single factor, like radiotherapy, in observational studies where patients undergo a variety of treatment at different time points. Unfortunately, all these anti-cancer treatments can negatively impact cognitive functioning of patients.9–12 Cancer-related cognitive impairment is an increasingly recognized phenomena in patients with tumors outside the central nervous system12, and equally affects patients with BMs undergoing systemic treatment. 9
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