Poor prognosis associated with TERT gene alterations in meningioma is independent of the WHO classification: an individual patient data meta-analysis. Issue 4 (10th February 2020)

• Record Type: Journal Article
• Authors: Mirian, Christian; Duun-Henriksen, Anne Katrine; Juratli, Tareq; Sahm, Felix; Spiegl-Kreinecker, Sabine; Peyre, Matthieu; Biczok, Annamaria; Tonn, Jörg-Christian; Goutagny, Stéphane; Bertero, Luca; Maier, Andrea Daniela; Møller Pedersen, Maria; Law, Ian; Broholm, Helle; Cahill, Daniel P.; Brastianos, Priscilla; Poulsgaard, Lars; Fugleholm, Kåre; Ziebell, Morten; Munch, Tina; Mathiesen, Tiit
• Is Part Of: Journal of neurology, neurosurgery and psychiatry. Volume 91:Issue 4(2020)
• Page Start: 378
• Page End: 387
• Publication Date: 2020-02-10
• Subjects: TERT -- meningioma -- alteration -- meta-analysis -- brain tumors; Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Psychiatry -- Periodicals; 616.8
• DOI: 10.1136/jnnp-2019-322257
• Languages: English
• ISSNs: 0022-3050

Abstract

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 ( TERT p-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 TERT p-wt patients. The HR for TERT -alt was 3.74 in reference to TERT p-wt. For all TERT -alt patients versus all TERT p-wt patients, the median overall survival was 58 months and 160 months, respectively. The HR for TERT -alt was 2.77 compared with TERT p-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 TERT p-wt patients. The mortality rate was 2.7 times higher in the WHO-I and WHO-II TERT -alt patients compared with WHO-III TERT p-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.