P19.09.A PATTERNS OF RECURRENCE OF MOLECULARLY HIGH-RISK MENINGIOMAS: AN IMAGING ATLAS AND SURGICAL SERIES
Authors: R Conger, A Choudhury, M P Nguyen, I Sethi, J Viner, N Oberheim Bush, R A Morshed, S E Braunstein, E Goldschmidt, D R Raleigh, W C Chen
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Molecular characterization of meningiomas has led to new WHO criteria and improved risk stratification. Molecularly high-risk meningiomas are at elevated risk of recurrence, but anatomic patterns of recurrence after resection, which could inform surgical planning or design of postoperative radiotherapy (RT), are poorly understood. MATERIAL AND METHODS This is a study of 23 patients (median age 61, interquartile range [IQR] 51-67, 61% female) who underwent primary resection of molecularly high-risk meningioma as defined by gene expression or DNA methylation profiling at a single institution (8/2005-6/2018) and recurred, out of a total of 61 such patients (5-year recurrence freedom 56.8%, overall survival 75.3%). Nineteen meningiomas (83%) underwent DNA methylation profiling, and 22 (96%) targeted gene expression profiling. Pre-, post-operative, and recurrence MRIs were analyzed to delineate recurrences with respect to resection cavity, surgical tracts, and anatomic structures. RESULTS Meningiomas were unfavorable by gene expression risk score (18 of 22 unfavorable, 81.8%; median score 0.59, IQR 0.51-0.70), and 3 had CDKN2A/B deletion (3 of 19, 15.8%, 2 of 3 homozygous). Nine of 19 (47.4%) were high-risk by DNA methylation profiling (Hypermetabolic or Proliferative). Aneuploidy was abundant (median % genome altered 18.1%, IQR 8.3-23.3%), 16 (84.2%) had 22q loss, and 13 (68.4%) had loss of both 22q and 1p. Tumors had a median of 7.5 mitoses/10hpf (IQR 4-20) and MIB1 index of 11.5% (IQR 6.3-20%). Five meningiomas (21.7%) had brain invasion. Tumor locations were sphenoid wing (11 of 23, 47.8%), parasagittal (4 of 23, 17.4%), peri-torcular (2 of 23, 8.7%), convexity (2 of 23, 8.7%), and para-clinoid (1 of 23, 4.3%). Nine underwent GTR (39.1%) and 12 (52.2%) received postoperative RT (10 external beam, median dose 55.8Gy). Local recurrence occurred a median of 2.9 years after surgery (IQR 1.3-3.9), leading to 7 disease related deaths (30.4%) after median 7.8 years of follow-up (IQR 3.6-9.1). After STR, recurrence at the residual was common (10 of 14, 78.6%), but recurrences could also be multifocal or regional (6 of 14, 42.9%). Common foci of recurrence were (1) near optic structures for sphenoid wing tumors, (2) adjacent to sagittal or torcular sinuses, and (3) arising from dura or sinus at the cut edge of the bone flap. No recurrences were observed within or clearly arising from brain parenchyma. CONCLUSION These qualitative data suggest that residual tumor, sinus or critical neurological structure interfaces, and unexposed adjacent dura beneath the cut edge of the bone flap may be at elevated risk of recurrence among molecularly high-risk meningiomas. Future work incorporating DOTATATE-PET to identify occult residual tumor foci, along with focal RT dose-escalation to regions at highest risk of recurrence, may improve local control of molecularly high-risk meningiomas.