Role of memantine to mitigate radiation-induced cognitive dysfunction in brain metastasis patient receiving whole brain radiotherapy: a systematic review

Abstract

Purpose: Identifying comprehensively the evidence of neuroprotective effects of memantine for preserving cognitive function in brain metastasis patients receiving whole brain radiotherapy (WBRT).

Methods: We searched randomized clinical trials (RCTs) analyzing the effects of memantine to preserve cognitive function in patients with brain metastasis treated with WBRT, performed in some databases, including PubMed, Embase, and Cochrane Library. The protocol was registered at PROSPERO (CRD42023476632). We reported the selection process according to the Preferred Reporting Items for Systematic Review and Meta-Analysis guideline. The studies were appraised by using the revised Cochrane Risk of Bias tool for randomized trials (RoB 2.0).

Results: We included three RCTs that met the eligibility criteria. No high risk of bias was found. Two articles compared WBRT + memantine to WBRT + placebo, and the other one compared hippocampal avoidance (HA)-WBRT + memantine to WBRT + memantine. There was no significant difference in characteristics among groups of treatment arms. The differences in cognitive function deterioration between treatment arms began to appear four months after initiated the treatment. The risk of cognitive failure was lower in patients receiving memantine compared to placebo. Moreover, combining HA-WBRT + memantine lowered the cognitive failure compared to standard WBRT + memantine. No article stated significant difference in quality of life (QoL) and survival outcomes in patients receiving memantine.

Conclusion: Although the evidence was still limited, memantine was reported to have the potential to mitigate radiation-induced cognitive dysfunction in patients with brain metastasis receiving WBRT. However, there was no evidence revealing the benefit of memantine for enhancing QoL and prolonging survival.

Keywords: Brain neoplasm; Cognition; Memantine; Radiotherapy.

Fig. 1.

The preferred reporting items for systematic reviews and meta-analyses flowchart of literature searching.

Fig. 2.

Estimation of cognitive function failure by treatment arms between two studies: (A) Brown et al. [22] and (B) Brown et al. [20]. Adapted from: Brown et al. Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial. Neuro Oncol 2013;15:1429-37 [22]. Brown et al. Hippocampal avoidance during whole-brain radiotherapy plus memantine for patients with brain metastases: phase III trial NRG oncology CC001. J Clin Oncol 2020;38:1019-29 [20]. WBRT, whole brain radiotherapy; HA, hippocampal avoidance.