Whilst typically benign, a subset of meningiomas displays aggressive and recurrent behavior. There is a paucity of reliable treatment options for this subset of patients and a relative lack of consensus on how to best manage these patients. This clinical challenge reflects underlying molecular complexity, driven by NF2, TRAF7, and CDKN2A/B mutations alongside pervasive epigenetic dysregulation. High-throughput molecular profiling studies have proposed biologically distinct meningioma subgroups with varying clinical trajectories and therapeutic vulnerabilities. Distinct cell lineages of meningeal precursors are now appreciated to be essential in the establishment of the meninges. The numerous cellular lineages involved in meningeal development, the heterogeneity of meningioma location and (epi)genomic behavior, and the variability in its clinical and radiological manifestations raise the question of what critical insights can be gained by understanding meningeal development during embryogenesis to understand meningioma tumorigenicity. The current paper examines this paradigm by highlighting spatially linked mechanisms of anaplasia and treatment resistance, including the role of neural crest-derived convexity meninges in promoting dedifferentiation via YAP/TAZ signaling and mesoderm-derived skull base regions in maintaining TRAF7-mediated vulnerabilities. We further elucidate the emerging synthetic lethal paradigms, CRISPR-enabled target discovery, and PROTAC-mediated degradation strategies that may transform the therapeutic landscape of clinically challenging meningiomas driven by complex oncogenic circuitry. By bridging embryogenesis, spatial genomics, and molecular targeting, we propose a developmentally informed, lineage-stratified model for advancing precision therapeutics in high-grade and recurrent meningiomas.

BACKGROUND AND OBJECTIVES: Occipital condyle metastasis (OCM) is a rare condition characterized by severe occipital pain and neurological symptoms due to lower cranial nerve (CN) deficits, stemming from its anatomic location. Despite the widespread use of stereotactic radiosurgery (SRS) for cranial metastases, its specific impact on OCM remains underexplored. This study evaluates the efficacy and safety of CyberKnife SRS in treating OCM, focusing on occipital pain, dysfunctions of lower CNs, and local tumor control. METHODS: We retrospectively analyzed cases of OCM treated with SRS at our institute from 2012 to 2023, evaluating patient demographics, presenting symptoms, treatment parameters, and outcomes. RESULTS: Eighteen patients (10 females) with a mean age of 64 years (SD: 10.4) were treated. Common presentations included occipital pain (44.4%) and lower CN deficits (27.8%). The median target volume was 6.95 cc (IQR: 4.64-21.2). The mean single-fraction equivalent dose was 18.7 Gy₁₀ (SD: 1.9). Ten tumors received 15-20 Gy in 1 fraction (50%), 2 tumors received 20-28 Gy in 2 fractions (10%), 4 tumors received 27 Gy in 3 fractions (20%), and 4 tumors received 30-40 Gy in 5 fractions (20%). Based on Kaplan-Meier estimate, SRS achieved 93.8% local tumor control rate over 3 years, with a median overall survival of 13 months (95% CI: 0-32.2). Among patients presenting with symptoms, 87.5% reported occipital pain relief (P = .04), and 80% observed improvements in CN function (P = .003). Four patients experienced local recurrence. CONCLUSION: CyberKnife SRS is a promising treatment of OCM, offering significant pain relief and improvement in neurological symptoms, along with favorable local control rates. This noninvasive therapy provides a valuable alternative to surgery, potentially enhancing the quality of life for patients with limited treatment options due to this challenging condition.

BACKGROUND AND OBJECTIVES: CyberKnife (CK) is advanced stereotactic radiosurgery (SRS) technology indicated for brain metastases, arteriovenous malformations, functional disease, and a number of other neurosurgical conditions that combines a linear accelerator with a highly maneuverable robotic arm and real-time imaging, allowing for several advantages including the ability to deliver radiation from a wide variety of angles and frameless delivery of therapy. We seek to explore the current trend and evolution of publications related to CK SRS using bibliometric approach, with a particular focus on neurosurgical disease applications. METHODS: The Web of Science database was queried for data collection, using keyword “CyberKnife”. Network visualization figures representing exported Web of Science data were created using visualization of similarities viewer. Statistics were completed in R. RESULTS: In total, 3980 articles from 12 077 authors were identified for analysis. Annual publication number has expressed growth from 1 article in 1996 to 263 articles in 2023. Most frequently reported conditions were brain metastases, followed by vestibular schwannoma and meningiomas. The top 5 most prolific authors in the field are Alexander Muacevic, Steven D. Chang, Oliver Blanck, Christian Baues, and John R. Adler. The top 3 most prolific institutions are the University of Cologne, Stanford University, and the University of Munich. Institutional collaboration is strongest between institutions within countries. Through authorial key word analysis, we identified that articles related to pituitary adenoma, brain metastases, meningioma, hemangioma, and cavernous sinus have increased. Through the same analysis, we noticed an increase in key words potentially associated with interdisciplinary applications of CK, such as immunotherapy, machine learning, and deep learning. CONCLUSION: CK SRS is an emergent technology with increasingly more neurological conditions and diseases being researched for treatment options. The rise in academic focus on CK SRS has been spearheaded by international effort from the United States, Japan, and Italy. There remains significant potential for future international collaboration.