Pathogenic Variants and Prognosis in Meningiomas: A Systematic Review and Meta-Analysis.

Background: Intracranial meningiomas are the most common primary tumors of the central nervous system. Although generally benign, some genetic alterations can induce aggressive behavior characterized by higher recurrence rates and reduced survival.

Methods: A systematic review and meta-analysis were conducted following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, using PubMed, EMBASE, Web of Science, and Scopus databases to identify studies published until November 2024. Studies investigating genetic alterations in meningiomas with prognostic data (recurrence or survival) and a minimum sample size of five patients were included. Data were extracted and analyzed independently by two reviewers.

Results: Of 3032 studies identified, 20 met the inclusion criteria. The most frequently studied pathogenic variants were telomerase reverse transcriptase promoter (TERTp) and neurofibromatosis type 2 (NF2), both associated with shorter recurrence-free survival (RFS) and overall survival (OS), respectively TERTp RFS (hazard ratio [HR] 4.35, 95% confidence interval [CI] 2.87-6.60) and OS (HR 2.55, 95%CI 1.25-5.22), and NF2 RFS (HR 1.49, 95%CI 1.04-2.14) and OS (HR 2.98, 95% CI 1.37-6.49). Subgroup analysis suggested that the TERTp variant may be more predictive of lower survival for overall meningiomas (instead of World Health Organization III only), similar to NF2 variants. Additionally, Krüppel-like factor 4 was identified as a protective factor, while cyclin-dependent kinase inhibitor 2A/B was identified as a risk factor.

Conclusions: This systematic review highlights the importance of pathogenic variants, particularly TERTp and NF2, as prognostic markers in intracranial meningiomas. These findings underscore the potential of integrating genetic profiling into clinical practice to refine risk stratification and guide personalized therapeutic strategies, ultimately improving patient outcomes and quality of life.