Breast Brain Metastases Are Associated with Increased Risk of Leptomeningeal Disease After Stereotactic Radiosurgery: a Systematic Review and Meta-analysis

Brain metastases are the most common malignant tumors of the brain. Leptomeningeal dissemination is a late-stage complication of intracranial metastasis and portends an extremely poor prognosis. An increased risk of leptomeningeal disease (LMD) from metastatic breast cancer compared to other cancer types after stereotactic radiosurgery (SRS) has been reported. Validation of this observation has significant public health ramifications. The aim of this study was to determine the consistency of this association in the available literature via formal meta-analysis and systematic review of the literature. Searches of seven electronic databases from inception to August 2019 were conducted following PRISMA guidelines and appropriate selection criteria. Prognostic hazard ratios (HRs) for LMD in breast cancer brain metastases derived from multivariate regression analysis were analyzed using meta-analysis of proportions. Our search strategy identified 8 studies meeting inclusion criteria which provided data on 2555 unique brain metastases patients treated with SRS. The risk of LMD in the setting of breast cancer brain metastasis was significantly greater compared to other histologic cancer types (pooled HR = 2.22; 95% CI 1.69-2.93; P < 0.001). Statistical assessment of small studies bias and heterogeneity were negative. Outcome certainty was low. Breast cancer brain metastases are associated with an increased risk of LMD compared to other cancer types after SRS. The certainty of this outcome will be improved with future prospective studies. Providers should factor this increased susceptibility for LMD in breast cancer brain metastasis to allow for appropriate risk stratification and the development of appropriate surveillance paradigms.