Prognosis of intracranial meningiomas with <i>TERTp</i> mutation: systematic review with meta-analysis

Abstract Background Telomerase reverse transcriptase promoter (TERTp; C228T/C250T) mutations are incorporated into the WHO 2021 classification of meningiomas (20–30% in Grade 3)1,5,6,7 as criteria for higher grade designation, despite heterogeneous evidence1,2,3,4 regarding their independent prognostic value. Objectives To evaluate the association between TERTp mutations and overall survival (OS) and progression-free survival (PFS) in patients with intracranial meningiomas. Methods A systematic review and meta-analysis of clinical-pathological cohort studies comparing TERTp-mutated and wild-type meningiomas was conducted. Studies were identified through searches of PubMed, Embase, and Web of Science. Survival outcomes were synthesized using hazard ratios (HRs) and median survival estimates. Results Thirteen studies were included. Meta-analyses comprised four studies for progression-free survival by hazard ratio, five for overall survival by hazard ratio, five for progression-free survival by mean difference (eight comparisons), and five for overall survival by mean difference. Sensitivity analyses excluded Maas et al. (2021), Spiegl-Kreineck et al. (2018), and Mellai et al. (2021) from the progression-free survival mean-difference, overall survival hazard-ratio, and overall survival mean-difference models, respectively; no study was excluded from the progression-free survival hazard-ratio model. Conclusions TERTp promoter mutations identify a biologically aggressive meningioma subgroup with markedly reduced survival, supporting their role as prognostic biomarkers. However, their isolated use for tumor reclassification should be interpreted cautiously and integrated with additional molecular features2. Funding No external funding was received. Registration PROSPERO platform (No. CRD420251135452).