The prognostic significance of TERT promoter mutations in meningioma: a systematic review and meta-analysis

Background: Mutations in the telomerase reverse transcriptase promoter (TERTp) region have been associated with worse prognosis in some cancers. Meningiomas are the most common type of primary central nervous tumors, and evaluation of the prognostic significance of TERTp mutations across the literature is lacking. The aim of this study was to pool all current evidence to assess for clinical relevance of TERTp mutations in meningioma and survival effect. Methods: Searches of seven electronic databases from inception to September 2018 were conducted following the appropriate guidelines. Two hundred and twenty seven articles were identified for screening. Hazard ratio (HR) and mean difference (MD) statistics were obtained and pooled utilizing both fixed- and random-effect (RE) models. Meta-regression was utilized to determine potential sources of heterogeneity and statistical influence. Results: A total of five retrospective observational cohort studies describing 532 meningioma patients satisfied selection criteria. The incidence of TERTp mutations was 8%, and was associated with significantly worse prognosis (HR 3.79; P = 0.005) and significantly shorter overall survival (MD 59.8 months; P = 0.037) by RE modelling. Meningioma grade was not significantly associated with a TERTp mutation effect, however, preliminary meta-regression trends indicated this may be significant once greater statistical power is achieved. Conclusion: The current evidence indicates the presence of a TERTp mutation in meningioma can be associated with worse prognosis, and shorter overall survival. Routine detection in greater numbers will allow for further validation, as well as delineate the effect across histological grades. By identifying this subgroup of meningioma patients early in management, it may support more frequent follow-up and aggressive management to optimize survival outcomes.