Objective  Vestibular schwannoma (VS) are benign, often slow growing neoplasms. Some institutions opt for radiosurgery in symptomatic patients of advanced age versus surgical resection. The aim of the study is to analyze surgical outcomes of VS in patients over the age of 65 who were either not candidates for or refused radiosurgery. Methods  This includes retrospective analysis of VS patients between 1988 and 2020. Demographics, tumor characteristics, surgical records, and clinical outcomes were recorded. Patient preference for surgery over radiosurgery was recorded in the event that patients were offered both. Facial nerve outcomes were quantified using House-Brackmann (HB) scores. Tumor growth was defined by increase in size of >2 mm. Results  In total, 64 patients were included of average age 72.4 years (65-84 years). Average maximum tumor diameter was 29 mm (13-55 mm). Forty-five patients were offered surgery or GKRS, and chose surgery commonly due to radiation aversion (48.4%). Gross total resection was achieved in 39.1% ( n  = 25), near total 32.8% ( n  = 21), and subtotal 28.1% ( n  = 18). Average hospitalization was 5 days [2-17] with 75% ( n  = 48) discharged home. Postoperative HB scores were good (HB1-2) in 43.8%, moderate (HB3-4) in 32.8%, and poor (HB5-6) in 23.4%. HB scores improved to good in 51.6%, moderate in 31.3%, and remained poor in 17.1%, marking a rate of facial nerve improvement of 10.9%. Tumor control was achieved in 95.3% of cases at an average follow-up time of 37.8 months. Conclusion  VS resection can be safely performed in patients over the age of 65. Advanced age should not preclude a symptomatic VS patient from being considered for surgical resection.

Background

Meningiomas are the most common primary brain tumor. Though typically benign with a low mutational burden, tumors with benign histology may behave aggressively and there are no proven chemotherapies. Although DNA methylation patterns distinguish subgroups of meningiomas and have higher predictive value for tumor behavior than histologic classification, little is known about differences in DNA methylation between meningiomas and surrounding normal dura tissue.

Methods

Whole-exome sequencing and methylation array profiling were performed on 12 dura/meningioma pairs (11 WHO grade I and 1 WHO grade II). Single-nucleotide polymorphism (SNP) genotyping and methylation array profiling were performed on an additional 19 meningiomas (9 WHO grade I, 5 WHO grade II, 4 WHO grade III).

Results

Using multimodal studies of meningioma/dura pairs, we identified 4 distinct DNA methylation patterns. Diffuse DNA hypomethylation of malignant meningiomas readily facilitated their identification from lower-grade tumors by unsupervised clustering. All clusters and 12/12 meningioma-dura pairs exhibited hypomethylation of the gene promoters of a module associated with the craniofacial patterning transcription factor FOXC1 and its upstream lncRNA FOXCUT. Furthermore, we identified an epigenetic continuum of increasing hypermethylation of polycomb repressive complex target promoters with increasing histopathologic grade.

Conclusion

These findings support future investigations of the role of epigenetic dysregulation of FOXC1 and cranial patterning genes in meningioma formation as well as studies of the utility of polycomb inhibitors for the treatment of malignant meningiomas.

BACKGROUND: While it has been suspected that different primary cancers have varying predilections for metastasis in certain brain regions, recent advances in neuroimaging and spatial modeling analytics have facilitated further exploration into this field. METHODS: A systematic electronic database search for studies analyzing the distribution of brain metastases (BMs) from any primary systematic cancer published between January 1990 and July 2020 was conducted using PRISMA guidelines. RESULTS: Two authors independently reviewed 1957 abstracts, 46 of which underwent full-text analysis. A third author arbitrated both lists; 13 studies met inclusion/exclusion criteria. All were retrospective single- or multi-institution database reviews analyzing over 8227 BMs from 2599 patients with breast (8 studies), lung (7 studies), melanoma (5 studies), gastrointestinal (4 studies), renal (3 studies), and prostate (1 study) cancers. Breast, lung, and colorectal cancers tended to metastasize to more posterior/caudal topographic and vascular neuroanatomical regions, particularly the cerebellum, with notable differences based on subtype and receptor expression. HER-2-positive breast cancers were less likely to arise in the frontal lobes or subcortical region, while ER-positive and PR-positive breast metastases were less likely to arise in the occipital lobe or cerebellum. BM from lung adenocarcinoma tended to arise in the frontal lobes and squamous cell carcinoma in the cerebellum. Melanoma metastasized more to the frontal and temporal lobes. CONCLUSION: The observed topographical distribution of BM likely develops based on primary cancer type, molecular subtype, and genetic profile. Further studies analyzing this association and relationships to vascular distribution are merited to potentially improve patient treatment and outcomes.