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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 -
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 -
Neuro-oncology May 2022Meningiomas are the most common primary intracranial tumor in adults. Clinical care is currently guided by the World Health Organization (WHO) grade assigned to...
BACKGROUND
Meningiomas are the most common primary intracranial tumor in adults. Clinical care is currently guided by the World Health Organization (WHO) grade assigned to meningiomas, a 3-tiered grading system based on histopathology features, as well as extent of surgical resection. Clinical behavior, however, often fails to conform to the WHO grade. Additional prognostic information is needed to optimize patient management.
METHODS
We evaluated whether chromosomal copy-number data improved prediction of time-to-recurrence for patients with meningioma who were treated with surgery, relative to the WHO schema. The models were developed using Cox proportional hazards, random survival forest, and gradient boosting in a discovery cohort of 527 meningioma patients and validated in 2 independent cohorts of 172 meningioma patients characterized by orthogonal genomic platforms.
RESULTS
We developed a 3-tiered grading scheme (Integrated Grades 1-3), which incorporated mitotic count and loss of chromosome 1p, 3p, 4, 6, 10, 14q, 18, 19, or CDKN2A. 32% of meningiomas reclassified to either a lower-risk or higher-risk Integrated Grade compared to their assigned WHO grade. The Integrated Grade more accurately identified meningioma patients at risk for recurrence, relative to the WHO grade, as determined by time-dependent area under the curve, average precision, and the Brier score.
CONCLUSION
We propose a molecularly integrated grading scheme for meningiomas that significantly improves upon the current WHO grading system in prediction of progression-free survival. This framework can be broadly adopted by clinicians with relative ease using widely available genomic technologies and presents an advance in the care of meningioma patients.
Topics: Adult; Cohort Studies; Humans; Meningeal Neoplasms; Meningioma; Neoplasm Grading; Neoplasm Recurrence, Local; Prognosis; Retrospective Studies; World Health Organization
PubMed: 34508644
DOI: 10.1093/neuonc/noab213 -
Science (New York, N.Y.) Jul 2020The tumor microenvironment plays a critical regulatory role in cancer progression, especially in central nervous system metastases. Cancer cells within the cerebrospinal...
The tumor microenvironment plays a critical regulatory role in cancer progression, especially in central nervous system metastases. Cancer cells within the cerebrospinal fluid (CSF)-filled leptomeninges face substantial microenvironmental challenges, including inflammation and sparse micronutrients. To investigate the mechanism by which cancer cells in these leptomeningeal metastases (LM) overcome these constraints, we subjected CSF from five patients with LM to single-cell RNA sequencing. We found that cancer cells, but not macrophages, within the CSF express the iron-binding protein lipocalin-2 (LCN2) and its receptor SCL22A17. These macrophages generate inflammatory cytokines that induce cancer cell LCN2 expression but do not generate LCN2 themselves. In mouse models of LM, cancer cell growth is supported by the LCN2/SLC22A17 system and is inhibited by iron chelation therapy. Thus, cancer cells appear to survive in the CSF by outcompeting macrophages for iron.
Topics: Animals; Humans; Iron; Lipocalin-2; Macrophages; Meningeal Neoplasms; Mice; Tumor Microenvironment
PubMed: 32675368
DOI: 10.1126/science.aaz2193 -
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 -
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 -
Acta Bio-medica : Atenei Parmensis Mar 2022The far lateral approach is an inferolateral extension of the lateral suboccipital approach. Designed for clipping of the aneurysms of the vertebrobasilar junction and...
The far lateral approach is an inferolateral extension of the lateral suboccipital approach. Designed for clipping of the aneurysms of the vertebrobasilar junction and proximal segments of the posterior inferior cerebellar artery, it became over the years a workhorse approach for ventral foramen magnum meningiomas and other intradural lesions located anterior to the dentate ligament. This article summarizes the technical key aspects of the far lateral approach and transcondylar, supracondylar, and paracondylar extension.
Topics: Foramen Magnum; Humans; Meningeal Neoplasms; Meningioma; Neurosurgical Procedures; Vertebral Artery
PubMed: 35441601
DOI: 10.23750/abm.v92iS4.12823 -
Neuro-oncology Nov 2021
Topics: Humans; Immunologic Factors; Immunotherapy; Meningeal Neoplasms; Meningioma
PubMed: 34244788
DOI: 10.1093/neuonc/noab168 -
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