Risk factors for brain metastasis in lung cancer: an umbrella review of systematic reviews and meta-analyses

Objectives To conduct an umbrella review to extensively evaluate and summarise the evidence regarding the relationship between risk factors and the occurrence of brain metastasis in lung cancer.Design Umbrella review of systematic reviews and meta-analyses.Data sources Four databases (PubMed, EMBASE, Web of Science and Cochrane Library) were searched from inception to 10 November 2024.Eligibility criteria Systematic reviews and meta-analyses that assessed the relationship between risk factors and brain metastasis in lung cancer were included. Only English language studies were considered.Data extraction and synthesis Two authors independently extracted data and assessed the methodological quality and risk of bias of the included studies. Certainty of evidence was evaluated and summarised for each identified risk factor.Results Six systematic reviews/meta-analyses were included. The quality of these studies varied, with most having low or critically low methodological quality. Epidermal growth factor receptor mutations, female gender, lung adenocarcinoma and advanced tumour stage were associated with an increased risk of brain metastasis. Prophylactic cranial irradiation and older age were associated with reduced risk.Conclusions This umbrella review suggests that several risk factors may be associated with brain metastasis in lung cancer, but the overall quality of evidence is low. Future studies with improved methodologies are needed to validate these findings.PROSPERO registration number CRD42023484563