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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 -
Neuro-oncology Nov 2021Meningiomas are the most common intracranial tumors. Yet, only few controlled clinical trials have been conducted to guide clinical decision making, resulting in...
Meningiomas are the most common intracranial tumors. Yet, only few controlled clinical trials have been conducted to guide clinical decision making, resulting in variations of management approaches across countries and centers. However, recent advances in molecular genetics and clinical trial results help to refine the diagnostic and therapeutic approach to meningioma. Accordingly, the European Association of Neuro-Oncology (EANO) updated its recommendations for the diagnosis and treatment of meningiomas. A provisional diagnosis of meningioma is typically made by neuroimaging, mostly magnetic resonance imaging. Such provisional diagnoses may be made incidentally. Accordingly, a significant proportion of meningiomas, notably in patients that are asymptomatic or elderly or both, may be managed by a watch-and-scan strategy. A surgical intervention with tissue, commonly with the goal of gross total resection, is required for the definitive diagnosis according to the WHO classification. A role for molecular profiling including gene panel sequencing and genomic methylation profiling is emerging. A gross total surgical resection including the involved dura is often curative. Inoperable or recurrent tumors requiring treatment can be treated with radiosurgery, if the size or the vicinity of critical structures allows that, or with fractionated radiotherapy (RT). Treatment concepts combining surgery and radiosurgery or fractionated RT are increasingly used, although there remain controversies regard timing, type, and dosing of the various RT approaches. Radionuclide therapy targeting somatostatin receptors is an experimental approach, as are all approaches of systemic pharmacotherapy. The best albeit modest results with pharmacotherapy have been obtained with bevacizumab or multikinase inhibitors targeting vascular endothelial growth factor receptor, but no standard of care systemic treatment has been yet defined.
Topics: Aged; Humans; Magnetic Resonance Imaging; Meningeal Neoplasms; Meningioma; Radiosurgery; Vascular Endothelial Growth Factor A
PubMed: 34181733
DOI: 10.1093/neuonc/noab150 -
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 -
CNS Oncology Jun 2021Meningiomas are the most common primary intracranial tumors. The majority of meningiomas are benign, but they can present different grades of dedifferentiation from... (Review)
Review
Meningiomas are the most common primary intracranial tumors. The majority of meningiomas are benign, but they can present different grades of dedifferentiation from grade I to grade III (anaplastic/malignant) that are associated with different outcomes. Radiological surveillance is a valid option for low-grade asymptomatic meningiomas. In other cases, the treatment is usually surgical, aimed at achieving a complete resection. The use of adjuvant radiotherapy is the gold standard for grade III, is debated for grade II and is not generally indicated for radically resected grade I meningiomas. The use of systemic treatments is not standardized. Here we report a review of the literature on the clinical, radiological and molecular characteristics of meningiomas, available treatment strategies and ongoing clinical trials.
Topics: Brain Neoplasms; Child; Humans; Meningeal Neoplasms; Meningioma; Radiotherapy, Adjuvant
PubMed: 34015955
DOI: 10.2217/cns-2021-0003 -
Journal of Neuro-oncology Jan 2023Meningiomas are the most frequently diagnosed intracranial neoplasms. Usually, they are treated by surgical resection in curative intent. Radiotherapy and stereotactic... (Review)
Review
PURPOSE
Meningiomas are the most frequently diagnosed intracranial neoplasms. Usually, they are treated by surgical resection in curative intent. Radiotherapy and stereotactic radiosurgery are commonly applied in the adjuvant setting in newly diagnosed atypical (CNS WHO grade 2), and anaplastic (CNS WHO grade 3) meningioma, especially if gross total resection is not feasible, and in recurrent cases. Conversely, the evidence for pharmacotherapy in meningioma is scarce.
METHODS
The available literature of systemic treatment in meningioma was screened using PubMed, and ongoing clinical trials were explored using ClinicalTrials.gov.
RESULTS
Classical cytotoxic agents, somatostatin analogs, and antihormone treatments have shown only limited efficacy. In contrast, tyrosine kinase inhibitors and monoclonal antibodies, especially those targeting angiogenic signaling such as sunitinib and bevacizumab, have shown promising antitumoral activity in small phase 2 trials. Moreover, results of recent landmark studies on (epi-)genetic alterations in meningioma revealed potential therapeutic targets which are currently under investigation. These include inhibitors of mammalian target of rapamycin (mTOR), focal adhesion kinase (FAK), cyclin-dependent kinases (CDK), phosphoinositide-3-kinase (PI3K), sonic hedgehog signaling, and histone deacetylases. In addition, clinical trials evaluating immune checkpoint inhibitors such as ipilimumab, nivolumab, pembrolizumab and avelumab are currently being conducted and early results suggest clinically meaningful responses in a subset of patients.
CONCLUSIONS
There is a paucity of high-level evidence on systemic treatment options in meningioma. However, interesting novel treatment targets have been identified in the last decade. Positive signals of anti-angiogenic agents, genomically targeted agents and immunotherapy in early phase trials should be confirmed in large prospective controlled trials.
Topics: Humans; Meningioma; Meningeal Neoplasms; Prospective Studies; Hedgehog Proteins; Antineoplastic Agents
PubMed: 36181606
DOI: 10.1007/s11060-022-04148-8 -
The Lancet. Oncology Sep 2016Although meningiomas are the most common intracranial tumours, the level of evidence to provide recommendations for the diagnosis and treatment of meningiomas is low... (Review)
Review
Although meningiomas are the most common intracranial tumours, the level of evidence to provide recommendations for the diagnosis and treatment of meningiomas is low compared with other tumours such as high-grade gliomas. The meningioma task force of the European Association of Neuro-Oncology (EANO) assessed the scientific literature and composed a framework of the best possible evidence-based recommendations for health professionals. The provisional diagnosis of meningioma is mainly made by MRI. Definitive diagnosis, including histological classification, grading, and molecular profiling, requires a surgical procedure to obtain tumour tissue. Therefore, in many elderly patients, observation is the best therapeutic option. If therapy is deemed necessary, the standard treatment is gross total surgical resection including the involved dura. As an alternative, radiosurgery can be done for small tumours, or fractionated radiotherapy in large or previously treated tumours. Treatment concepts combining surgery and radiosurgery or fractionated radiotherapy, which enable treatment of the complete tumour volume with low morbidity, are being developed. Pharmacotherapy for meningiomas has remained largely experimental. However, antiangiogenic drugs, peptide receptor radionuclide therapy, and targeted agents are promising candidates for future pharmacological approaches to treat refractory meningiomas across all WHO grades.
Topics: Europe; Humans; Meningeal Neoplasms; Meningioma; Practice Guidelines as Topic
PubMed: 27599143
DOI: 10.1016/S1470-2045(16)30321-7 -
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 -
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 -
Journal of Neuro-oncology Jan 2023Meningiomas are associated with several gonadal steroid hormone-related risk factors and demonstrate a predominance in females. These associations led to investigations... (Review)
Review
INTRODUCTION
Meningiomas are associated with several gonadal steroid hormone-related risk factors and demonstrate a predominance in females. These associations led to investigations of the role that hormones may have on meningioma growth and development. While it is now accepted that most meningiomas express progesterone and somatostatin receptors, the conclusion for other receptors has been less definitive.
METHODS
We performed a review of what is known regarding the relationship between hormones and meningiomas in the published literature. Furthermore, we reviewed clinical trials related to hormonal agents in meningiomas using MEDLINE PubMed, Scopus, and the NIH clinical trials database.
RESULTS
We identify that all steroid-hormone trials lacked receptor identification or positive receptor status in the majority of patients. In contrast, four out of five studies involving somatostatin analogs used positive receptor status as part of the inclusion criteria.
CONCLUSIONS
Several clinical trials have recently been completed or are now underway using somatostatin analogs in combination with other therapies that appear promising, but a reevaluation of hormone-based monotherapy is warranted. Synthesizing this evidence, we clarify the remaining questions and present future directions for the study of the biological role and therapeutic potential of hormones in meningioma and discuss how the stratification of patients using features such as grade, receptor status, and somatic mutations, might be used for future trials to select patients most likely to benefit from specific therapies.
Topics: Female; Humans; Meningioma; Meningeal Neoplasms; Receptors, Progesterone; Receptors, Estrogen; Progesterone; Somatostatin
PubMed: 36418843
DOI: 10.1007/s11060-022-04187-1 -
Neuroendocrinology 2020Parasellar spaces remain particularly singular, comprising the most important neurovascular structures such as the internal carotid artery and optic, oculomotor, and... (Review)
Review
Parasellar spaces remain particularly singular, comprising the most important neurovascular structures such as the internal carotid artery and optic, oculomotor, and trigeminal nerves. Meningiomas are one of the most frequent tumors arising from parasellar spaces. In this location, meningiomas remain mostly benign tumors with WHO grade I and a meningothelial subtype. Progestin intake should be investigated and leads mostly to conservative strategies. In the case of benign nonsymptomatic tumors, observation should be proposed. Tumor growth will lead to the proposition of surgery or radiosurgery. In the case of an uncertain diagnosis and an aggressive pattern, a precise diagnosis is required. For cavernous sinus and Meckel's cave lesions, complete removal is rarely considered, leading to the proposition of an endoscopic endonasal or transcranial biopsy. Optic nerve decompression could also be proposed via these approaches. A case-by-case discussion about the best approach is recommended. A transcranial approach remains necessary for tumor removal in most cases. Vascular injury could lead to severe complications. Cerebrospinal fluid leakage, meningitis, venous sacrifice, visual impairment, and cranial nerve palsies are more frequent complications. Pituitary dysfunctions are rare in preoperative assessment and in postoperative follow-up but should be assessed in the case of meningiomas located close to the pituitary axis. Long-term follow-up is required given the frequent incomplete tumor removal and the risk of delayed recurrence. Radiosurgery is relevant for small and well-limited meningiomas or intra-cavernous sinus postoperative residue, whereas radiation therapy and proton beam therapy are indicated for large, extended, nonoperable meningiomas. The place of the peptide receptor radionuclide therapyneeds to be defined. Targeted therapy should be considered in rare, recurrent, and aggressive parasellar meningiomas.
Topics: Cavernous Sinus; Cranial Nerve Neoplasms; Humans; Meningeal Neoplasms; Meningioma; Skull Base Neoplasms
PubMed: 32492684
DOI: 10.1159/000509090