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Oral Presentation

Tumor

Brainlab Neurosurgery Award: Multicentre prospective validation of integrated molecular classification of meningiomas and prediction of recurrence risk using DNA methylation

Saturday, May 4, 2024
4:36 PM – 4:40 PM CT
Location:  N427bc
Disclosure(s):
Justin Z. Wang, MD: No financial relationships to disclose
Aaron Cohen-Gadol, MD: No financial relationships to disclose
Alexander Landry, MD: No financial relationships to disclose
Gelareh Zadeh, MD PhD: No financial relationships to disclose
Introduction: Meningiomas have significant heterogeneity between patients and even within each WHO grade, making prognostication challenging. We previously developed and retrospectively validated a DNA methylation-based predictor of recurrence risk and integrated molecular groups (MG) of meningiomas. For this study we utilize prospectively collected cases to confirm the utility of these molecular tools in prognosticating meningioma patients and informing selection for adjuvant radiotherapy (RT) and compare these to WHO grade.

Methods: Genome-wide DNA methylation profiles were generated with the Illumina EPICArray. Clinical data elements including progression-free survival (PFS) were extracted from the medical records and corroborated with neuroimaging. The performance of our methylation-based predictor and MG were compared with WHO grade using generalized boosted regression modeling by generating time-dependent receiver operating characteristic (ROC) curves and computing area under the ROC curves (AUCs) along with their 95% confidence interval using bootstrap resampling with 10000 resamples.

Results: 173 meningiomas treated from 2018-2021 were included. Most patients were female (66%) and median age was 59. The cohort was enriched for WHO grade 2 (34%) and 3 (14%) meningiomas. Most cases received a gross total resection (56%). DKFZ classification confirmed the molecular diagnosis of meningioma for all cases. Meningiomas could be dichotomized into low-risk (Immunogenic, NF2-wildtype) or high-risk MG (Hypermetabolic, Proliferative). There was a significant increase in methylation-based risk scores and decrease in PFS with higher WHO grade and more aggressive MG. Using Cox proportional hazards modeling, increasing methylome recurrence risk was independently associated with a significantly increased hazard of recurrence (HR 4.16, 95% CI 2.14-8.09). Both the methylome-based predictor and MG had substantially improved performance in predicting 5-year PFS compared to WHO grade alone (ΔAUC = 0.10-0.23). Following results of methylation modeling, 59 cases (34%) were prescribed adjuvant RT prospectively following surgery.

Conclusion : DNA methylation modeling and molecular classification outperform conventional WHO classification in outcome prediction in an independent, prospectively collected cohort of meningiomas enriched for clinically aggressive cases and may be effectively used for real time prognostication, patient counseling, and referral for adjuvant RT.