Memory preservation in whole brain radiotherapy with and without hippocampal sparing: a systematic review

Background: Whole brain radiotherapy (WBRT) is the mainstay therapy for metastatic brain tumor. Cognitive dysfunction, particularly memory, is a common side effect of WBRT. Memory preservation has become increasingly popular, as memory is inter-related with other cognitive domains as well as with quality of life. Previous studies showed that WBRT with hippocampal sparing has shown some protective effects in memory preservation. We conducted systematic review to determine whether WBRT with hippocampal sparing is beneficial in preserving memory compared to conventional WBRT. To our knowledge, this is the first study in Indonesia exploring hippocampal sparing WBRT and memory. Methods: We systematically searched for clinical trials and observational studies with hippocampal sparing WBRT as the intervention and memory as one of the outcomes. Major databases, clinical trial registries, as well as local databases and gray literature were searched. Risk of bias assessment was performed using Risk of Bias-2 (RoB-2), Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I), and Newcastle-Ottawa Scale (NOS) tools, according to study type. Data were presented using Harvest plot and focused narrative synthesis. Results: We identified 8 studies, which consisted of randomized and non-randomized studies. Most studies assessed memory using Hopkins Verbal Learning Test-Delayed Recall (HVLT-DR). All randomized clinical trials showed overall low risk of bias, whereas nonrandomized trials and cohort studies showed moderate risk of bias. In all studies, no information of previous comorbidities at baseline were stated. Harvest plot distribution showed a positive gradient. i.e., protective effect of hippocampal sparing WBRT. In comparison to previous systematic review of the same topic, our current review included a larger number of studies with a robust risk of bias assessment. Conclusion: WBRT with hippocampal sparing showed protective effect towards memory preservation in patients with metastatic brain tumor. We recommend performing WBRT with hippocampal sparing and routine cognitive monitoring post-radiotherapy for our patients.