Abstract
A significant proportion of low-grade WHO grade I and higher-grade WHO grade II or III meningiomas are at risk to develop post-resection recurrence. Though recent studies investigated genomic alterations within histological subtypes of meningiomas, few have compared genomic profiles of primary meningiomas matched to their recurrences. The present study aimed to identify oncogenic driver mutations that may indicate risk of meningioma recurrence and aggressive clinical course. Seventeen patients treated for low-grade (n = 8) or high-grade (n = 9) meningioma and underwent both primary and recurrent resection between 2007–2017 were reviewed. Tumor specimens (n = 38) underwent genomic sequencing of known oncogenic driver mutations. Primary and recurrent tumors were compared using matched-pair analyses for mutational associations with clinical outcomes including functional status, progression-free survival (PFS) and overall survival (OS). Most common driver mutations included POLE and NF2. There was no enrichment for any driver mutation from primary to recurrent tumor specimen. NF2 mutant meningiomas were associated with larger tumor size (8-fold increase), presence of vasogenic edema, and higher mitotic proliferation on univariate and independently on multivariate regression (p’s < 0.05) after controlling for preoperative and tumor features. Tumors with POLE driver mutations were associated with decreased functional status at last postoperative follow-up (p = 0.022) relative to presentation. Mutation status was not associated with PFS or OS on multivariate Cox regression, but rather with grade of resection (p = 0.046) for PFS. While primary and recurrent tumors exhibited similar driver mutations within patients, the identification of driver mutations associated with clinical outcomes is crucial for guiding potential targeted treatments in recurrent meningiomas.
Highlights
Meningiomas are the most common primary brain tumor, accounting for approximately 34% of all primary intracranial neoplasms
Patients did not differ in their preoperative functional status from primary to recurrent tumor (p = 0.13)
A minority of primary and recurrent tumors presented with associated vasogenic edema (29 vs. 24%, p > 0.99)
Summary
Meningiomas are the most common primary brain tumor, accounting for approximately 34% of all primary intracranial neoplasms. While the majority of meningiomas are classified as WHO grade I and are benign, approximately 20% are grade II (atypical) and grade III (anaplastic). Grade II meningiomas are more likely to grow more rapidly than benign meningiomas and have a greater likelihood of recurring following gross total resection. Adjuvant radiation therapy (RT) is often prescribed in the case of subtotal resection of Grade II meningiomas. Grade III meningiomas comprise the smallest proportion of cases, about 1–3%, and have poor oncological outcomes. Grade III meningiomas grow at a faster rate than both benign and atypical tumors and are more likely to invade brain tissue, metastasize to other organs, and recur than the Grades I and II meningiomas [2, 3]
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