45 Cognitive Impact of SRS vs. WBRT: Systematic Review & Meta-analysis longer period of time. This especially holds for those patients with shorter survival. Thereby, this review points towards SRS resulting in lowest risks for cognitive adverse side-effects in this already cognitively vulnerable patient population with limited survival. Since WBRT and SRS have resulted in comparable survival rates in selected groups of patients, it could even be suggested to totally abstain from WBRT in patients with a limited number of BMs.47 However, sometimes WBRT is inevitable due to high number of metastases and current technical capabilities. The information provided by this review can be used in communicating risks to patients and aid patients in making educated (shared) treatment decisions towards maintaining optimal QoL. A high percentage of patients already experience cognitive problems before starting radiotherapy treatment, with at least one out of every two patients with BMs demonstrating cognitive impairment on minimally one cognitive construct.18,29,30 Baseline cognitive impairment was only significantly predicted by larger baseline BMs volume, even when considering other factors such as the number of previous chemotherapy regimens.38 Thus, not only previous cancer treatments, but also the BMs themselves exert a significant burden on cognitive functioning. This indicates, once again, that patients with BMs represent a vulnerable patient group in which further cognitive decline should be minimized when possible. The majority of WBRT studies found a consistent decline in cognitive performance from baseline to short-term follow-up with a further decrease in performance at mid-term, with verbal L&M, EF and verbal fluency most often affected.18,25,26,28,33–40 However, in a subgroup of patients with a better outcome (lower baseline BMs volume, long-term BMs survivors) stable or improved cognitive performance was observed at mid-term.25,28 Additionally, patients receiving HA-WBRT showed less cognitive decline than those receiving conventional WBRT with even stable performance on some cognitive constructs.26,33,41 At long-term follow-up (9-15 months) cognitive performance either remained stable compared to mid-term follow-up or returned to baseline values for most cognitive constructs.18,25,40 Our meta-analysis confirmed these results; at short- and mid-term follow-up an increase in the incidence of WBRT patients with cognitive impairment was found, while a (relatively) stable or even lower incidence was found in the long-term. This suggests that while some patients show a decline in cognitive performance up until midterm follow-up after WBRT, a (relatively) good outcome is often accompanied by stable cognitive performance over time. To illustrate, stronger reduction in tumor volume four months after WBRT was related to better preservation of cognitive performance over time.18,36–38 It is unclear whether the observed decline in cognitive 2
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