In an analysis reported in The Lancet Oncology by Gui et al in the International Consortium on Meningiomas, TERT expression in meningiomas was found to be associated with poorer progression-free survival.
Study Details
The multi-institutional cohort study involved retrospectively collected data from 1,241 meningiomas surgically resected in adult patients between January 2000 and December 2024 at Toronto Western Hospital, Canada (n = 380; discovery cohort) and external institutions in Canada, Germany, and the United States (n = 861; validation cohort). The primary outcome measures were TERT expression in meningiomas with and without TERT promoter mutations, and the difference in progression-free survival between patients with tumors expressing vs not expressing TERT.
Key Findings
Median follow-up was 6.2 years (interquartile range [IQR] = 1.7–12.5 years) in the discovery cohort and 3.3 years (IQR = 1.3–3.8 years) in the validation cohort.
TERT expression was found in 157 (28.7%) of 547 wild-type TERT promoter meningiomas and in 193 (32.0%) of 604 with RNA data.
In the discovery cohort, median progression-free survival was 3.2 years (95% confidence interval [CI] = 1.7–6.5 years) in patients with wild-type TERT promoter tumors expressing TERT, 16.0 years (95% CI = 7.1 years to not reached) in patients with TERT-negative wild-type TERT promoter tumors (P = .0021), and 1.6 years (95% CI = 0.9 years to not reached) in patients with TERT promoter mutations (P = .039). Findings were confirmed in the validation cohort.
Within each WHO grade, patients with TERT expression had progression-free survival similar to that in patients with TERT-negative meningiomas of one grade higher. Grade 1 tumors with TERT expression had progression-free survival similar to TERT-negative grade 2 tumors—ie, median = not reached (95% CI = 16.0 years to not reached) vs 8.2 years (95% CI = 4.5 years to not reached); P = .59. Similarly, grade 2 tumors with TERT expression had progression-free survival similar to TERT-negative grade 3 tumors—ie, median = 3.6 years (95% CI = 2.4–5.3 years) vs 3.8 years (95% CI = 2.3 years to not reached); P = .42.
On multivariate regression analysis, TERT expression remained significantly associated with shorter progression-free survival after adjusting for TERT promoter mutations, CDKN2A/B loss, chromosome 1p/22q status, and WHO grade (hazard ratio = 1.85, 95% CI = 1.33–2.57, P = .0002).
The investigators concluded: “TERT expression in meningiomas predicted earlier disease progression, independent of TERT promoter mutation and other markers, and might warrant reclassification of meningiomas that express TERT to a higher WHO grade.”
Gelareh Zadeh, MD, PhD, of the Division of Neurosurgery, Department of Surgery, University of Toronto, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by the Canadian Institutes of Health Research, Brain Tumour Charity UK, and others. For full disclosures of all study authors, visit thelancet.com.
