P13.01.B THE NATURAL HISTORY AND MOLECULAR ARCHITECTURE OF INCIDENTAL MENINGIOMAS

Abstract BACKGROUND The prevalence of incidentally discovered meningiomas is increasing, and there is an unmet clinical need to better understand the molecular architecture of incidental meningiomas to improve risk stratification and guide treatment planning for patients. MATERIAL AND METHODS This was a retrospective cohort study of consecutive incidental meningiomas from patients presenting from 1996 to 2020 to a single institution that were analyzed using serial magnetic resonance imaging (MRI) volumetrics, IMPACT model risk groups, targeted gene expression profiling to calculate a previously published 34-gene biomarker, DNA methylation profiling, and copy number alteration (CNA) profiling. Volumetric growth, treatment-free survival, and symptom-free survival from time of incidental meningioma detection were compared using the Kaplan-Meier method, Cox proportional hazards regression, and competing risks regression analyses. RESULTS The cohort was comprised of 238 consecutive meningiomas, 81% from women with a median age at detection of 59 years. Median meningioma volume at detection was 3.83 cm3, median annual and percent volumetric growth rate were 0.3 cm3 and 19.7%, respectively, and median volumetric doubling time was 4.3 years. The rate of symptomatic progression was 15.5%, and 93.7% of incidental meningiomas were treated during follow-up, with a median time-to-treatment of 1.06 years. IMPACT risk groups stratified treatment-free (p<0.0001) and symptom-free survival (p=0.0007), and only 5% of incidental meningiomas recurred after treatment. Targeted gene expression profiling and DNA methylation profiling revealed that most incidental meningiomas were low molecular risk, although incidental meningiomas from the Hypermitotic DNA methylation group were larger at the time of detection (p=0.0237). Cell cycle genes were suppressed in incidental meningiomas compared to 1434 previously-published non-incidental meningiomas, and incidental meningiomas showed lower CNA burden and distinct CNA patterns compared to non-incidental meningiomas. Molecular high-risk incidental meningiomas had favorable postoperative outcomes compared to propensity-matched non-incidental meningiomas from the same molecular groups. CONCLUSION Incidental meningiomas have excellent clinical outcomes after treatment but are overwhelmingly molecularly low risk and slow growing. These data indicate that the majority of incidental meningiomas can be safely followed with serial imaging surveillance. Molecular profiling of incidental meningiomas sheds light on early stages of meningeal tumorigenesis and suggests that early treatment of appropriately selected patients may improve long-term clinical outcomes for molecularly high-risk incidental meningiomas, which are rare.