A targeted gene expression biomarker predicts clinic low-risk meningioma recurrence

Abstract Background Despite reassuring clinical and histological features, low grade meningiomas can recur after surgery. Targeted gene expression profiling improves risk stratification of meningiomas, but the utility of this approach for clinical low-risk meningiomas is incompletely understood. Methods This was a multicenter retrospective cohort study of meningiomas from patients who were treated at 4 institutions from 1992 to 2023. Adult patients with newly diagnosed or recurrent World Health Organization (WHO) grade 1 meningiomas that were treated with gross total resection (GTR) or subtotal resection (STR), or newly diagnosed WHO grade 2 meningiomas that were treated with GTR, were included. A 34-gene expression biomarker and gene expression risk score (continuous from 0 to 1) was evaluated in all samples. Results The study cohort was comprised of 723 patients, none of which were used for discovery or training of the gene expression biomarker and 265 of which were previously unreported. There were 626 WHO grade 1 meningiomas, 490 with GTR and 126 with STR, and 97 WHO grade 2 meningiomas with GTR. Targeted gene expression profiling classified 51.3% of clinical low-risk meningiomas as molecular intermediate-risk and 9.5% as molecular high-risk. Combining the gene expression biomarker with extent of resection revealed 19.8% of clinical low-risk meningiomas had unfavorable local freedom from recurrence (LFFR) and overall survival (OS), including 7.1% of newly diagnosed WHO grade 1 meningiomas with GTR. The risk score was prognostic for LFFR (HR per 0.1 increase in risk score 1.89, 95% CI 1.58-2.25) across all WHO grades, extents of resection, and newly diagnosed or recurrent presentations. Conclusions Targeted gene expression profiling can identify clinical low-risk meningiomas that are likely to recur after surgery