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Future Oncology (London, England) Sep 2018Meningiomas are the most common primary intracranial tumor. Important advances are occurring in meningioma research. These are expected to accelerate, potentially... (Review)
Review
Meningiomas are the most common primary intracranial tumor. Important advances are occurring in meningioma research. These are expected to accelerate, potentially leading to impactful changes on the management of meningiomas in the near and medium term. This review will cover the histo- and molecular pathology of meningiomas, including recent 2016 updates to the WHO classification of CNS tumors. We will discuss clinical and radiographic presentation and therapeutic management. Surgery and radiotherapy, the two longstanding primary therapeutic modalities, will be discussed at length. In addition, data from prior and ongoing investigations of other treatment modalities, including systemic and targeted therapies, will be covered. This review will quickly update the reader on the contemporary management and future directions in meningiomas. [Formula: see text].
Topics: Animals; Biopsy; Combined Modality Therapy; Humans; Meningeal Neoplasms; Meningioma; Multimodal Imaging; Neoplasm Staging; Prognosis; Symptom Assessment; Treatment Outcome
PubMed: 30084265
DOI: 10.2217/fon-2018-0006 -
Expert Review of Neurotherapeutics Mar 2018With an annual incidence of 5/100,000, meningioma is the most frequent primary tumor of the central nervous system. Risk factors are radiotherapy and hormone intake.... (Review)
Review
With an annual incidence of 5/100,000, meningioma is the most frequent primary tumor of the central nervous system. Risk factors are radiotherapy and hormone intake. Most meningiomas are grade I benign tumors, but up to 15% are atypical and 2% anaplastic according to the WHO 2016 histological criteria. Areas covered: This review details the current standard therapy based on international guidelines and recent literature, and describes new approaches developed to treat refractory cases. First-line treatments are observation and surgery, but adjuvant radiotherapy/radiosurgery is discussed for atypical and indicated for anaplastic meningiomas. The most problematic cases include skull base meningiomas that enclose vasculo-nervous structures and surgery- and radiation-refractory tumors that present with significant morbidity and mortality. The treatment of recurrent tumors is based on radiotherapy and repeated surgery. Systematic therapies are not effective in general but several clinical trials are ongoing. Expert commentary: Molecular characterization of the tumors, based on genetic mutations such as NF2, SMO, TERT, TRAF7, and on the methylation profile are developing, completing the histological classification and giving new insights into prognosis and treatment options.
Topics: Humans; Meningeal Neoplasms; Meningioma; Mutation; Neoplasm Grading; Neoplasm Recurrence, Local; Prognosis; Radiosurgery; Radiotherapy, Adjuvant; Risk Factors; Skull Base Neoplasms
PubMed: 29338455
DOI: 10.1080/14737175.2018.1429920 -
Journal of Neuro-oncology Nov 2022Meningiomas are the most common primary central nervous system neoplasm. Despite promising recent progress in elucidating the genomic landscape and underlying biology of... (Review)
Review
Meningiomas are the most common primary central nervous system neoplasm. Despite promising recent progress in elucidating the genomic landscape and underlying biology of these histologically, molecularly, and clinically diverse tumors, the mainstays of meningioma treatment remain maximal safe resection and radiation therapy. The aim of this review of meningioma radiotherapy is to provide a concise summary of the history, current evidence, and future for application of radiotherapy in meningioma treatment.
Topics: Humans; Meningioma; Meningeal Neoplasms; Radiotherapy, Adjuvant
PubMed: 36315366
DOI: 10.1007/s11060-022-04171-9 -
Nature Medicine Dec 2023Surgery is the mainstay of treatment for meningioma, the most common primary intracranial tumor, but improvements in meningioma risk stratification are needed and...
Surgery is the mainstay of treatment for meningioma, the most common primary intracranial tumor, but improvements in meningioma risk stratification are needed and indications for postoperative radiotherapy are controversial. Here we develop a targeted gene expression biomarker that predicts meningioma outcomes and radiotherapy responses. Using a discovery cohort of 173 meningiomas, we developed a 34-gene expression risk score and performed clinical and analytical validation of this biomarker on independent meningiomas from 12 institutions across 3 continents (N = 1,856), including 103 meningiomas from a prospective clinical trial. The gene expression biomarker improved discrimination of outcomes compared with all other systems tested (N = 9) in the clinical validation cohort for local recurrence (5-year area under the curve (AUC) 0.81) and overall survival (5-year AUC 0.80). The increase in AUC compared with the standard of care, World Health Organization 2021 grade, was 0.11 for local recurrence (95% confidence interval 0.07 to 0.17, P < 0.001). The gene expression biomarker identified meningiomas benefiting from postoperative radiotherapy (hazard ratio 0.54, 95% confidence interval 0.37 to 0.78, P = 0.0001) and suggested postoperative management could be refined for 29.8% of patients. In sum, our results identify a targeted gene expression biomarker that improves discrimination of meningioma outcomes, including prediction of postoperative radiotherapy responses.
Topics: Humans; Biomarkers; Gene Expression Profiling; Meningeal Neoplasms; Meningioma; Neoplasm Recurrence, Local; Prospective Studies
PubMed: 37944590
DOI: 10.1038/s41591-023-02586-z -
The Oncologist 2011Although meningiomas are the most common tumor in the central nervous system, their incidence, epidemiology, and clinical outcomes have historically been poorly defined.... (Review)
Review
Although meningiomas are the most common tumor in the central nervous system, their incidence, epidemiology, and clinical outcomes have historically been poorly defined. This has been attributed to their benign course, difficulty obtaining histologic diagnosis, and lack of uniform database registration. Their clinical behavior can range from a silent incidentaloma to a lethal tumor. Projections of an aging population should raise medical awareness of an expectant rise in the incidence of meningiomas. This disease increases with advancing age, has a female predilection, and exposure to ionizing radiation is associated with a higher risk for disease development. There have been minimal advances in treatment, except in radiation therapy. Although no U.S. Food and Drug Administration-approved systemic therapy exists, there are treatment options that include hydroxyurea and sandostatin. Currently, no molecularly targeted therapy has provided clinical benefit, although recurring molecular alterations are present and novel therapies are being investigated.
Topics: Humans; Meningeal Neoplasms; Meningioma; Neoplasm Grading; Risk Factors
PubMed: 22028341
DOI: 10.1634/theoncologist.2011-0193 -
Neuro-oncology Jan 2019Meningiomas are the most common primary intracranial neoplasm. The current World Health Organization (WHO) classification categorizes meningiomas based on... (Review)
Review
Meningiomas are the most common primary intracranial neoplasm. The current World Health Organization (WHO) classification categorizes meningiomas based on histopathological features, but emerging molecular data demonstrate the importance of genomic and epigenomic factors in the clinical behavior of these tumors. Treatment options for symptomatic meningiomas are limited to surgical resection where possible and adjuvant radiation therapy for tumors with concerning histopathological features or recurrent disease. At present, alternative adjuvant treatment options are not available in part due to limited historical biological analysis and clinical trial investigation on meningiomas. With advances in molecular and genomic techniques in the last decade, we have witnessed a surge of interest in understanding the genomic and epigenomic landscape of meningiomas. The field is now at the stage to adopt this molecular knowledge to refine meningioma classification and introduce molecular algorithms that can guide prediction and therapeutics for this tumor type. Animal models that recapitulate meningiomas faithfully are in critical need to test new therapeutics to facilitate rapid-cycle translation to clinical trials. Here we review the most up-to-date knowledge of molecular alterations that provide insight into meningioma behavior and are ready for application to clinical trial investigation, and highlight the landscape of available preclinical models in meningiomas.
Topics: Combined Modality Therapy; Genomics; Humans; Meningeal Neoplasms; Meningioma; Molecular Targeted Therapy; Prognosis; Translational Research, Biomedical
PubMed: 30649490
DOI: 10.1093/neuonc/noy178 -
Chinese Clinical Oncology Jul 2017Meningiomas are frequent intracranial and intraspinal tumors. They are tumors of the elderly, and meningioma growth at certain localizations, as well as recurrent tumors... (Review)
Review
Meningiomas are frequent intracranial and intraspinal tumors. They are tumors of the elderly, and meningioma growth at certain localizations, as well as recurrent tumors or primary aggressive biology may pose a therapeutic challenge. To understand the growth characteristics of meningiomas, animal models can provide insights both from a biological and therapeutical point of view. Using genetically-engineered mouse models (GEMM), it has been proven that alterations of the neurofibromatosis type 2 (NF2) gene are key steps for benign meningioma development. Aggressive meningiomas can be induced by simultaneous activation of Nf2 and the PDGF (platelet-derived growth factor)/-PDGF-Receptor (R) system, or inactivation of Tp53 and cdkn2ab in mice. However, mechanisms acting in NF2 wild-type meningiomas are poorly understood so far, because appropriate models are lacking. Xenograft models have been used either by implantation of primary cultures derived from human meningiomas, or immortalized human cell lines, respectively. While the value of primary cells is limited due to low rate of overall tumor growth and slow proliferation, xenograft approaches have been shown to be helpful for the evaluation of potential medical treatment options. Future studies must incorporate new molecular meningioma tumor drivers, as well as potential treatment options based on recurrent genetic alterations into the generation of meningioma models.
Topics: Animals; Disease Models, Animal; Genes, Neurofibromatosis 2; Heterografts; Humans; Meningeal Neoplasms; Meningioma; Mice; Neoplasm Recurrence, Local
PubMed: 28595424
DOI: 10.21037/cco.2017.05.03 -
Redox Biology Jun 2024The oncogene Aurora kinase A (AURKA) has been implicated in various tumor, yet its role in meningioma remains unexplored. Recent studies have suggested a potential link...
The oncogene Aurora kinase A (AURKA) has been implicated in various tumor, yet its role in meningioma remains unexplored. Recent studies have suggested a potential link between AURKA and ferroptosis, although the underlying mechanisms are unclear. This study presented evidence of AURKA upregulation in high grade meningioma and its ability to enhance malignant characteristics. We identified AURKA as a suppressor of erastin-induced ferroptosis in meningioma. Mechanistically, AURKA directly interacted with and phosphorylated kelch-like ECH-associated protein 1 (KEAP1), thereby activating nuclear factor erythroid 2 related factor 2 (NFE2L2/NRF2) and target genes transcription. Additionally, forkhead box protein M1 (FOXM1) facilitated the transcription of AURKA. Suppression of AURKA, in conjunction with erastin, yields significant enhancements in the prognosis of a murine model of meningioma. Our study elucidates an unidentified mechanism by which AURKA governs ferroptosis, and strongly suggests that the combination of AURKA inhibition and ferroptosis-inducing agents could potentially provide therapeutic benefits for meningioma treatment.
Topics: Ferroptosis; Forkhead Box Protein M1; Aurora Kinase A; Humans; NF-E2-Related Factor 2; Animals; Mice; Meningioma; Piperazines; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Signal Transduction; Kelch-Like ECH-Associated Protein 1; Meningeal Neoplasms; Drug Resistance, Neoplasm
PubMed: 38642502
DOI: 10.1016/j.redox.2024.103137 -
Ideggyogyaszati Szemle Sep 2015Meningiomas represent nearly one-third of all adult primary brain tumours. According to their clinical and histologic appearance, they can be divided into WHO grades... (Review)
Review
Meningiomas represent nearly one-third of all adult primary brain tumours. According to their clinical and histologic appearance, they can be divided into WHO grades I-III. Almost 90% of meningiomas are benign, showing favourable response to conventional therapies, however, patients diagnosed with grade 2 and 3 tumours may have a poor prognosis. In addition, high frequency of tumour recurrence renders treatments more challenging even in benign meningiomas. Molecular-pathological profiling of meningiomas could lead to development of more effective therapies. Although the cytogenetic background of these tumours are already well-characterised, the majority of related genes and mutations is still unknown. Recently, high-throughput techniques enabled better characterisation of mechanisms involved in meningioma development, progression and recurrence. Furthermore, epigenetic dysregulation could offer new opportunities for both diagnosis and treatment of meningiomas. We provide a comprehensive overview of cytogenetic and molecular genetic defects as well as epigenetic alterations in meningiomas. Many of these may serve as biomarker or therapeutic target in the near future.
Topics: Brain Neoplasms; CpG Islands; DNA Methylation; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; Genes, Neoplasm; Humans; Loss of Heterozygosity; Meningeal Neoplasms; Meningioma; MicroRNAs; Mutation; Neoplasm Grading; Neoplasm Recurrence, Local; Pathology, Molecular; Prognosis; Risk Factors
PubMed: 26665490
DOI: 10.18071/isz.68.0292 -
Neurosurgical Review Jul 2023Olfactory groove meningiomas (OGM) are a skull base neoplasm that represents between 8 and 13% of all intracranial meningiomas. Approach selection focuses on achieving... (Review)
Review
Olfactory groove meningiomas (OGM) are a skull base neoplasm that represents between 8 and 13% of all intracranial meningiomas. Approach selection focuses on achieving frontal lobe decompression, gross total resection and vision preservation. Recently, there has been a focus on olfaction and considering its preservation as a quality-of-life outcome measure. An electronic search of the databases Medline, Scopus, Embase, Web of Science and Cochrane library databases was performed and data extracted according 2020 Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) statement. Six articles were selected for inclusion mainly based due to reporting quantitative outcomes for olfaction assessed by a smell identification test (e.g. sniffin' sticks). Objective olfaction preservation can be achieved with a variety of surgical approaches. More research which includes objective assessment of olfactory function and ideally as well QoL outcome measures is needed to further optimize the treatment pathways in OGM patients.
Topics: Humans; Meningioma; Smell; Meningeal Neoplasms; Quality of Life; Olfaction Disorders
PubMed: 37500988
DOI: 10.1007/s10143-023-02096-z