46 Chapter 2 performance is characteristic of the worse responders (i.e. patients with less tumor shrinkage), or that the good responders survive long enough to recover from this dip in performance. Nonetheless, the data suggest that for patients with a longer survival (at least 9-15 months) the benefits of WBRT radiotherapy outweigh the costs in the long-term. Currently the majority of patients do not (yet) survive long-term, despite improvements in life expectancy with the introduction of immunotherapies and targeted therapies.48–50 While early delayed effects (1-4 months after WBRT) are generally considered to be transient, the cognitive decline traditionally characterized as a late delayed effect (5-9 months after WBRT) is thought to be progressive and irreversible.51 Therefore, the cognitive decline found at short- and mid-term should not be discounted against the possible stable long-term cognitive performance in those with a good survival and should be discussed with BMs patients during shared decision making. However, better discernment of short and long survival should be included in evaluating this. Results regarding cognitive performance after SRS at short-term follow-up (1-4 months) were variable; approximately half of the included studies observed cognitive deterioration, most frequently for verbal L&M, fine motor coordination and EF.29,31,32,44 The other studies found no changes in cognition compared to baseline.25,30,45 At both mid-term (5-8 months) and long-term follow-up (9-12 months) all studies reported either stable or (slightly) improved cognitive performance compared to baseline.25,29–32,44,45 The meta-analysis largely confirms these results; a relatively stable incidence of patients with cognitive decline from baseline was observed up until long-term follow-up, albeit with large confidence intervals. The initial dip in cognitive performance in some of the patients could be attributed to an increase in peri-lesional edema which is sometimes observed shortly after SRS, but is often resolved six months later.52 Moreover, adjuvant systemic treatment will often be (re-)initialized shortly after SRS. The short-term side-effects of systemic treatments could therefore be the cause of this initial dip, rather than the radiotherapy treatment. Conclusively, after SRS an initial, transient dip in cognitive performance can occur, but at mid- and long-term the majority of patients will have returned to or remained at pre-radiotherapy cognitive levels. Looking in more detail at the affected cognitive constructs, not one is specifically affected by WBRT or SRS. Rather, change in cognitive performance was observed across several cognitive constructs, including, but not limited to verbal L&M, EF, information processing speed, and fine motor coordination, which have been linked to a wide range of neuroanatomical substrates involving both cortical areas and white matter networks.53–57 This is supported by previous research indicating
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