31 Cognitive Impact of SRS vs. WBRT: Systematic Review & Meta-analysis Data on the incidence of baseline cognitive impairment before SRS was explicitly reported for the pilot-study by Chang et al. (N = 15) and by Habets et al. (N = 77).29,30 Pre-radiotherapy 53-67% of patients had cognitive impairment (Z-score <1.5 SD) on ≥1 neuropsychological test. At baseline, EF was impaired in 47% of the patients, fine motor coordination in 40%, L&M in 31%, visual memory and visuoconstruction in 22%, information processing speed in 10% and verbal fluency in 7%. Before SRS the mean z-scores of both the Chang et al. (N = 30) and the Brown et al. cohort (N = 111) were impaired.31,32 Worst group performance was observed on tasks for EF and information processing speed. Patients with a baseline BMs volume of >3 cc performed worse on attention than those with smaller lesion volumes.29 Similarly, Onodera et al. reported higher total lesion volume, but not number of BMs at baseline corresponded with worse cognitive performance, while Habets et al. reported no significant association with BMs volume.25,30 Post-radiotherapy cognitive performance At short-term follow-up (1-4 months) the majority of the WBRT studies (N = 455 patients) found consistent declines in cognitive performance on most cognitive constructs.18,25,26,28,33–40 Overall, between 19-37% of the patients deteriorated regarding L&M performance. Gondi et al. found that patients treated with hippocampal avoidance WBRT (HA-WBRT) had significantly less mean relative decline in L&M performance compared to the patients of Mehta et al. who received conventional WBRT (7% vs 30%, respectively).18,26 The change in L&M performance was correlated to pre-treatment BMs volume, age and the volume of white matter injuries.27 Other impaired cognitive constructs in the WBRT studies were EF (29-38%), fine motor coordination (31%), information processing speed (28%) and verbal fluency (7-32%). Even though Westover et al. observed a decline in 17% of their patients (N = 18) regarding L&M performance, on the group level no significant changes from baseline were found for the other cognitive constructs.41 Nevertheless, large variations in mean relative change were found for all cognitive constructs (L&M, information processing speed, EF, verbal fluency). At mid-term follow-up (5-8 months) the results were more variable. The 29 patients who received HA-WBRT had a mere relative decline of 0-3% on multiple tests for L&M at mid-term follow-up compared to baseline.26,33 Similarly, patients who survived more than 6 months after HA-WBRT with simultaneous integrated boost recovered to baseline scores regarding L&M performance.42 On the contrary, performance on most cognitive tasks declined in at least 114 patients who received conventional WBRT.35,39,40 L&M performance was most often affect, with 53% of the patients showing decline.35 Moreover, the percentage of patients with declined performance 2
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