Poor prognosis associated with TERT gene alterations in meningioma is independent of the WHO classification: an individual patient data meta-analysis

Christian Mirian, Anne Katrine Duun-Henriksen, Tareq Juratli, Felix Sahm, Sabine Spiegl-Kreinecker, Matthieu Peyre, Annamaria Biczok, Jörg-Christian Tonn, Stéphane Goutagny, Luca Bertero, Andrea Daniela Maier, Maria Møller Pedersen, Ian Law, Helle Broholm, Daniel P Cahill, Priscilla Brastianos, Lars Poulsgaard, Kåre Fugleholm, Morten Ziebell, Tina MunchTiit Mathiesen

76 Citations (Scopus)

Abstract

BACKGROUND: TERT gene alterations (TERT-alt) have been linked to increased risk of recurrence in meningiomas, whereas the association to mortality largely remain incompletely investigated. As incongruence between clinical course and WHO grade exists, reliable biomarkers have been sought.

METHODS: We applied the Preferred Reporting Items for Systematic Review and Meta-Analyses of individual participant data Statement. We compiled data from eight studies and allocated patients to TERT-alt (n=59) or TERT promoter wild-type (TERTp-wt; n=618). We compared the two groups stratified for WHO grades as: incidence rates, survival probabilities and cumulative recurrences. We estimated the effects of WHO grade, age at diagnosis and sex as HRs.

RESULTS: TERT-alt occurred in 4.7%, 7.9% and 15.4% of WHO-I/WHO-II/WHO-III meningiomas, respectively. The median recurrence-free survival was 14 months for all TERT-alt patients versus 101 months for all TERTp-wt patients. The HR for TERT-alt was 3.74 in reference to TERTp-wt. For all TERT-alt patients versus all TERTp-wt patients, the median overall survival was 58 months and 160 months, respectively. The HR for TERT-alt was 2.77 compared with TERTp-wt. TERT-alt affected prognosis independent of WHO grades. Particularly, the recurrence rate was 4.8 times higher in WHO-I/-II TERT-alt patients compared with WHO-III TERTp-wt patients. The mortality rate was 2.7 times higher in the WHO-I and WHO-II TERT-alt patients compared with WHO-III TERTp-wt patients.

CONCLUSIONS: TERT-alt is an important biomarker for significantly higher risk of recurrence and death in meningiomas. TERT-alt should be managed and surveilled aggressively. We propose that TERT-alt analysis should be implemented as a routine diagnostic test in meningioma and integrated into the WHO classification.

TRIAL REGISTRATION NUMBER: PROSPERO: CRD42018110566.

Original languageEnglish
JournalJournal of neurology, neurosurgery, and psychiatry
Volume91
Issue number4
Pages (from-to)378-387
Number of pages10
ISSN0022-3050
DOIs
Publication statusPublished - Apr 2020

Keywords

  • Humans
  • Meningeal Neoplasms/genetics
  • Meningioma/genetics
  • Mutation
  • Prognosis
  • Promoter Regions, Genetic
  • Survival Rate
  • Telomerase/genetics
  • World Health Organization
  • meningioma
  • meta-analysis
  • brain tumors
  • TERT
  • alteration

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