TERT Promoter Mutation, Possibly an Independent High-risk Prognostic Marker in Meningioma
Aman Bakhsh1, Hafiz Muhammad Moaaz Sajid2, FNU Prateek3, Akash Rawat4, Bavesh Siva5, Vansh Patel6, Romil Kukadiya7
1Netaji Subhash Chandra Bose Medical College Jabalpur, 2Punjab Medical College, Faisalabad Medical University, Faisalabad, Pakistan, 3AIIMS Rishikesh, 4Himalayan Institute of Medical Sciences, 5Davao medical school foundation, Philippines, 6BJMC Ahmedabad, 7Pramukhswami Medical College, Anand, India
Objective:
To evaluate the prognostic significance of the TERT promoter mutation (TERTp-m) in meningioma, quantifying its impact on overall survival and exploring the sources of heterogeneity through Bayesian meta-analysis methods.
Background:
The prognostic role of TERTp-m in meningioma remains controversial, with inconsistent findings across studies. Understanding the mutation’s influence on survival and its interplay with clinical and molecular factors is critical for risk stratification.
Design/Methods:
Nine studies including diverse meningioma cohorts were analyzed. Data on hazard ratios (HR) for survival were extracted and processed. A Bayesian random-effects meta-analysis was performed using weakly informative priors. Meta-regressions explored associations with WHO tumor grade and other covariates.
The primary outcome was the pooled HR for overall survival of TERTp-m versus wild-type. Secondary analyses assessed heterogeneity (I²), between-study variance (τ), and predictive probabilities of clinically relevant effect sizes. Language refinement was assisted by ChatGPT (OpenAI, GPT-5).
Results:
The pooled median HR was 2.09 (95% credible interval: 1.27–3.60), indicating that TERTp-m patients had approximately twice the risk of death compared to wild-type. The heterogeneity was moderate (τ = 0.48, I² ≈ 46%), suggesting variability among studies. Meta-regression showed that WHO Grade II tumor percentage significantly explained heterogeneity in effect sizes, while age and sex had no significant influence. The predictive probability that the true effect exceeds a 50% increase in hazard (HR>1.5) was high (~81%), confirming the clinical relevance of TERTp-m status.
Conclusions:
TERT promoter mutation is a significant independent adverse prognostic factor in meningioma, associated with a two-fold increased hazard of death. The mutation’s impact is largely moderated by the proportion of WHO Grade II tumors in the study populations. This evidence supports incorporating TERTp-m status into clinical prognostic models and highlights the importance of tumor grade in interpreting mutation effects.
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