A clinically applicable integrative molecular classification of meningiomas.

Meningiomas are the most common primary intracranial tumour in adults1. Patients with symptoms are generally treated with surgery as there are no effective medical therapies. The World Health Organization histopathological grade of the tumour and the extent of resection at surgery (Simpson grade) are associated with the recurrence of disease; however, they do not accurately reflect the clinical behaviour of all meningiomas2. Molecular classifications of meningioma that reliably reflect tumour behaviour and inform on therapies are required. Here we introduce four consensus molecular groups of meningioma by combining DNA somatic copy-number aberrations, DNA somatic point mutations, DNA methylation and messenger RNA abundance in a unified analysis. These molecular groups more accurately predicted clinical outcomes compared with existing classification schemes. Each molecular group showed distinctive and prototypical biology (immunogenic, benign NF2 wild-type, hypermetabolic and proliferative) that informed therapeutic options. Proteogenomic characterization reinforced the robustness of the newly defined molecular groups and uncovered highly abundant and group-specific protein targets that we validated using immunohistochemistry. Single-cell RNA sequencing revealed inter-individual variations in meningioma as well as variations in intrinsic expression programs in neoplastic cells that mirrored the biology of the molecular groups identified.

Drug target therapy and emerging clinical relevance of exosomes in meningeal tumors.

Meningioma is the most common central nervous system (CNS) tumor. In recent decades, several efforts have been made to eradicate this disease. Surgery and radiotherapy remain the standard treatment options for these tumors. Drug therapy comes to play its role when both surgery and radiotherapy fail to treat the tumor. This mostly happens when the tumors are close to vital brain structures and are nonbenign. Although a wide variety of chemotherapeutic drugs and molecular targeted drugs such as tyrosine kinase inhibitors, alkylating agents, endocrine drugs, interferon, and targeted molecular pathway inhibitors have been studied, the roles of numerous drugs remain unexplored. Recent interest is growing toward studying and engineering exosomes for the treatment of different types of cancer including meningioma. The latest studies have shown the involvement of exosomes in the theragnostic of various cancers such as the lung and pancreas in the form of biomarkers, drug delivery vehicles, and vaccines. Proper attention to this new emerging technology can be a boon in finding the consistent treatment of meningioma.

Comment on, "Expression of decitabine-targeted oncogenes in meningiomas in vivo".

The study by Canisius et al. (2022) explores the expression of decitabine-targeted oncogenes (TRIM58, FAM84B, ELOVL2, DIO3) in meningiomas, aiming to evaluate decitabine's therapeutic potential for high-grade tumors. Using immunohistochemical staining and RT-PCR in over 100 patient samples, the authors found significant correlations between oncogene expression and tumor grade, with elevated ELOVL2 levels being linked to tumor recurrence. This work highlights the role of decitabine in modulating oncogene expression and suggests its potential in treating refractory meningiomas. Despite the robust methodology, limitations such as the small sample size and the lack of comprehensive molecular data were noted. Future research should incorporate larger sample sizes and advanced genomic techniques like RNA sequencing to better understand oncogenic mechanisms. The study emphasizes the need for further in situ analyses of decitabine's efficacy, setting the foundation for future neuro-oncological treatments.

Application of bevacizumab in the management of meningiomas: a systematic review and meta-analysis.

Meningiomas are the most common intracranial lesions and constitute one-third of diagnoses. Surgical resection is the gold-standard treatment option. In case of treatment failure, therapeutic options are limited. Bevacizumab is a vascular endothelial growth factor ligand-binding monoclonal antibody that prevents angiogenesis. This study aims to investigate the efficacy and feasibility of bevacizumab in meningiomas On December 30, 2023, a systematic search was conducted according to PRISMA guidelines using the PubMed, Scopus, Web of Science, and Embase databases. This study is conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart. Our study included 12 studies, comprising 243 individuals and 310 tumors. Most of the studies were retrospective (80%). Most of the patients were male (47.9%). The bevacizumab was mostly administered intravenously at 10 mg/kg every two weeks (77.8%). The mean progression-free survival (PFS) and overall survival (OS) were 19.1 ± 4.7 and 23.9 ± 8.4 months, respectively. The response rate was 0.33 (95%CI: 0.14-0.60). The PFS-6, PFS-12, and PFS-24 were 0.80 (95% CI: 0.64-0.89), 0.66 (95%CI: 0.46-0.82), and 25% (95%CI: 0.16-0.37), respectively. The OS-6, OS-12, and OS-24 were 0.89 (95% CI: 0.80-0.96), 0.86 (95%CI: 0.65-0.95), and 0.48 (95%CI: 0.16-0.82), respectively. The meta-regression identified the total number of individuals, number of tumors, gender, WHO II/III, and prior resection as a possible source of heterogeneity for outcomes. This study highlights the effectiveness of bevacizumab in meningiomas, especially in refractory, high-grade, or neurofibromatosis patients.

[Role of Pharmacotherapy in Treatment of Meningiomas].

Meningiomas constitute the most common primary tumors of the central nervous system. Despite maximum treatment, grade 2/3 meningiomas are associated with a high risk of recurrence. Stereotactic radiosurgery is the treatment of choice as adjuvant treatment for grade 2/3 meningiomas. Currently, pharmacotherapies, including molecular targeted therapy for various growth factors, their receptors, and the associated pathways, have shown limited effectiveness for management of refractory or recurrent meningiomas. Therefore, novel systemic treatment approaches are urgently required in such cases. Recent advances in genetics and epigenetics and the identification of specific genetic alterations have led to new classifications of these tumors and the development of therapeutic targets. Identification of targeted gene mutations may lead to precision-based medicine. Other therapeutic approaches such as immune checkpoint inhibitors rarely elicit a significant response in meningiomas with a high tumor mutation burden. Combination therapies that affect these multiple targets are also considered adjuvant therapeutic options. Comprehensive/in-depth research is warranted to investigate the safety and efficacy of other treatment strategies, including chimeric antigen receptor T-cells, oncolytic virus immunotherapy, and gene therapy. In this article, we review the current evidence regarding the efficacy of systemic treatments available in the literature and discuss recent and ongoing trials for meningiomas.

A systematic review and meta-analysis of the effects of tranexamic acid in surgical procedure for intracranial meningioma.

PURPOSE: During intracranial meningioma surgery, surgeons experience considerable blood loss. Tranexamic acid (TXA) is used to minimize blood loss in several neurosurgical settings. However, evidence and trials are lacking. Our objective is to establish the most recent evidence on TXA safety and efficacy in intracranial meningioma surgery. METHODOLOGY: Based upon Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), the authors collected fully published English literature on the administration of tranexamic acid for patients undergoing intracranial meningioma surgery using the keywords ["tranexamic acid" and "meningioma"] and its synonyms from Cochrane Central Database, the WHO International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov, and PubMed. The primary outcome of the current study was total blood loss. The secondary outcomes include individuals requiring blood transfusion, anesthesia duration, surgical duration, and complication rate. Each included studies' quality was assessed using the JADAD scale. RESULTS: For qualitative and quantitative data synthesis, we included five RCTs (n = 321) with the mean age was 47.5 ± 11.9 years for the intervention group and 47.2 ± 11.9 years for the control group. Our meta-analysis showed that the administration of TXA is associated with decreased total blood loss of standardized mean difference (SMD) of -1.40 (95% CI [-2.49, -0.31]), anesthetic time SMD -0.36 (95% CI [-0.63, -0.09]), and blood transfusion requirements RR 0.58 (95% CI [0.34, 0.99]). CONCLUSIONS: The current study showed that TXA was associated with reduced intraoperative blood loss and intra- and postoperative blood transfusion. However, the studies are small. More RCT studies with a greater sample size are favorable.

Hormone therapies in meningioma-where are we?

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.

Emerging systemic treatment options in meningioma.

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.

Molecular predictors for decitabine efficacy in meningiomas - a pilot study.

PURPOSE: Effective chemotherapeutical agents for the treatment of meningiomas are still lacking. Previous in-vitro analyses revealed efficacy of decitabine (DCT), a DNA methyltransferase (DNMT) inhibitor established in the treatment of leukemia, in a yet undefined subgroup of meningiomas. METHODS: Effects of DCT on proliferation and viability was analyzed in primary meningioma cells by immunofluorescence and MTT assays, and cases were classified as drug responders and non-responders. Molecular preconditions for efficacy were analyzed using immunofluorescence for Ki67, DNMT1, and five oncogenes (TRIM58, FAM84B, ELOVL2, MAL2, LMO3) previously found to be differentially methylated after DCT exposition, as well as by genome-wide DNA methylation analyses. RESULTS: Efficacy of DCT (10µM) was found in eight (62%) of 13 meningioma cell lines 48 h after drug exposition (p < .05). DCT significantly reduced DNMT1 expression in all but two cell lines, and median ΔDNMT1 reduction 48 h after drug exposition was lower in DCT-resistant (-11.1%) than in DCT-sensitive (-50.5%, p = .030) cells. Rates of cell lines responsive to DCT exposition distinctly decreased to 25% after 72 h. No significant correlation of the patients´ age, sex, histological subtype, location of the paternal tumor, expression of Ki67, DNMT1 or the analyzed oncogenes with treatment response was found (p > .05, each). DCT efficacy was further independent of the methylation class and global DNA methylation of the paternal tumor. CONCLUSION: Early effects of DCT in meningiomas are strongly related with DNMT1 expression, while clinical, histological, and molecular predictors for efficacy are sparse. Kinetics of drug efficacy might indicate necessity of repeated exposition and encourage further analyses.

Malignant meningioma mTOR mutated and precision medicine.

BACKGROUND: WHO grade II and III meningiomas are more invasive than grade I malignancies and determine patients' shorter overall survival. Their tendency to recur after treatment has represented an important therapeutic challenge because of the limited treatment strategies at recurrence. Angiogenesis and mechanistic target of rapamycin (mTOR) activation are two of the main features of higher grade meningiomas, determining invasiveness and tendency to relapse. While these options prove promising, available clinical data on mTOR inhibitors' efficacy are somewhat limited. CASE STUDY: We report a case of a 25-year-old female patient diagnosed with a right parasagittal occipital anaplastic meningioma (grade III WHO) in 2013. The patient underwent multiple treatments and, in 2019, a further recurrence occurred. The patient reported an mTOR mutation, and it is for this reason that the MTB approved treatment with everolimus and bevacizumab. Therapy was administered in May 2019, and partial response and prolonged disease control was obtained in November 2021, when progression took place. The patient's death occurred in March 2022. CONCLUSIONS: This case report provides evidence on the efficacy of mTOR inhibitors as a treatment option in recurrent meningiomas. Furthermore, it highlights the importance of performing a molecular analysis as a preliminary step towards targeting the mTOR pathway.

Novel Medical Therapies in Meningiomas.

Meningiomas are the most common primary brain tumor in adults and have been historically managed with surgery and radiation therapy. However, in patients with inoperable, recurrent or high-grade tumors, medical therapy is often needed. Traditional chemotherapy and hormone therapy have been largely ineffective. However, with improved understanding of the molecular drivers in meningioma, there has been increasing interest in targeted molecular and immune therapies. In this chapter, we will discuss recent advances in meningioma genetics and biology and review current clinical trials with targeted molecular treatment and other novel therapies.

Uncovering the molecular landscape of meningiomas and the impact of perioperative steroids on patient survival.

BACKGROUND: The current literature on meningioma reveals a gap in knowledge regarding the impact of genetic factors on patient survival. Furthermore, there is a lack of data on the relationship between the perioperative use of corticosteroids and patient survival in meningioma patients. Our study aims to overcome these gaps by investigating the correlation between genetic factors and overall survival and the effect of postoperative corticosteroids and other clinical characteristics on patient outcomes in meningioma patients. METHODS: A retrospective analysis of the medical records of 85 newly diagnosed meningioma patients treated from 2016 to 2017 with follow-up until December 2022 was performed. RESULTS: NF2 mutations occurred in 60% of tumors, AKT1 mutations in 8.2%, and TRAF7 mutations in 3.6%. Most tumors in the parasagittal region had the NF2 mutation. On the other hand, almost all tumors in the sphenoid ridge area did not have the NF2 mutation. AKT-1-mutated meningiomas had more frequent peritumoral edema. Patients who received steroids perioperatively had worse overall survival (OS) than those without steroids (p = 0.034). Moreover, preoperative peri-meningioma edema also was associated with worse OS (p < 0.003). Contrarily, NF2 mutations did not influence survival. CONCLUSIONS: The combination of clinical, pathomorphological, and genetic data allows us to characterize the tumor better and assess its prognosis. Corticosteroids perioperatively and peri-meningioma edema were associated with shorter OS, according to our study. Glucocorticoids should be used judiciously for the shortest time required to achieve symptomatic relief.

Drug Repositioning for Refractory Benign Tumors of the Central Nervous System.

Drug repositioning (DR) is the process of identifying novel therapeutic potentials for already-approved drugs and discovering new therapies for untreated diseases. DR can play an important role in optimizing the pre-clinical process of developing novel drugs by saving time and cost compared with the process of de novo drug discovery. Although the number of publications related to DR has rapidly increased, most therapeutic approaches were reported for malignant tumors. Surgical resection represents the definitive treatment for benign tumors of the central nervous system (BTCNS). However, treatment options remain limited for surgery-, chemotherapy- and radiation-refractory BTCNS, as well as malignant tumors. Meningioma, pituitary neuroendocrine tumor (PitNET), and schwannoma are the most common BTCNS. The treatment strategy using DR may be applied for refractory BTCNS, such as Grade 2 meningiomas, neurofibromatosis type 2-related schwannomatosis, and PitNETs with cavernous sinus invasion. In the setting of BTCNS, stable disease can provide significant benefit to the patient. DR may provide a longer duration of survival without disease progression for patients with refractory BTCNS. This article reviews the utility of DR for refractory BTCNS.

Eribulin prolongs survival in an orthotopic xenograft mouse model of malignant meningioma.

Meningioma is the most common intracranial tumor, with generally favorable patient prognosis. However, patients with malignant meningioma typically experience recurrence, undergo multiple surgical resections, and ultimately have a poor prognosis. Thus far, effective chemotherapy for malignant meningiomas has not been established. We recently reported the efficacy of eribulin (Halaven) for glioblastoma with a telomerase reverse transcriptase (TERT) promoter mutation. This study investigated the anti-tumor effect of eribulin against TERT promoter mutation-harboring human malignant meningioma cell lines in vitro and in vivo. Two meningioma cell lines, IOMM-Lee and HKBMM, were used in this study. The strong inhibition of cell proliferation by eribulin via cell cycle arrest was demonstrated through viability assay and flow cytometry. Apoptotic cell death in malignant meningioma cell lines was determined through vital dye assay and immunoblotting. Moreover, a wound healing assay revealed the suppression of tumor cell migration after eribulin exposure. Intraperitoneal administration of eribulin significantly prolonged the survival of orthotopic xenograft mouse models of both malignant meningioma cell lines implanted in the subdural space (P < .0001). Immunohistochemistry confirmed apoptosis in brain tumor tissue treated with eribulin. Overall, these results suggest that eribulin is a potential therapeutic agent for malignant meningiomas.

Concomitant Temozolomide plus radiotherapy for high-grade and recurrent meningioma: a retrospective chart review.

BACKGROUND: High-grade and recurrent meningiomas are often treatment resistant and pose a therapeutic challenge after surgical and radiation therapy (RT) failure. Temozolomide (TMZ) is a DNA alkylating agent that appears to have a radiosensitizing effect when used in combination with RT and may be worthwhile in meningioma treatment. Thus, we investigated the potential efficacy of concomitant RT plus TMZ compared to historical controls of just RT used in the treatment of high-grade and recurrent meningiomas. METHODS: We performed a retrospective analysis of patients with meningioma treated at the University of Colorado with TMZ chemoradiation. Progression free survival (PFS) and overall survival (OS) were calculated from the start of chemoradiation to local recurrence or death, respectively. RESULTS: Eleven patients (12 tumors) were treated with chemoradiation with a median follow-up of 41.5 months. There were two WHO grade 1, eight grade 2 and two grade 3 meningiomas. Three patients died during the follow-up period-one being disease related (11.1%). Two patients had meningioma recurrence-at 2.3 months (WHO grade 3), and 5.4 years (WHO grade 2). Three-year OS and PFS for grade 2 meningiomas were each 88%. Historical controls demonstrate a 3-year median OS and PFS of 83% and 75.8%, respectively. CONCLUSIONS: Treatment options are limited for meningiomas after local failure. In this study, TMZ chemoradiation demonstrated no significant difference in PFS and OS in the treatment of grade 2 meningiomas compared to historic controls. Further study is warranted to find novel methods for the treatment of malignant and recurrent meningiomas.

A rare case report of recurrent atypical meningioma with multiple metastases treated with anti-PD-1 and anti-VEGF therapy.

BACKGROUND: Meningioma is the most common type of primary intracranial tumor with 0.1-1% of all primary meningiomas have been reported to develop into metastases. However, there is no proven therapeutic strategy for multiple metastases of meningiomas. CASE PRESENTATION: A 60-year-old female accepted total tumor resection of a right frontal lobe meningioma in September 2018, In October 2021, the patient was admitted to hospital because of cough and shortness of breath and diagnosed with metastatic meningiomas. The computed tomography (CT) scan revealed the presence of large masses in the right thoracic and abdominal cavity. After two cycles of anti-PD-1 and anti-VEGF treatment, the symptoms were relieved and the tumor was necrotic. Follow up to June 21, 2022, the patient has been given eleven cycles of the treatment every 3 weeks without tumor progression. CONCLUSIONS: This case showed combined anti-PD-1 and anti-VEGF treatment stimulates peripheral blood immune cells to kill metastatic meningioma cells. Whether combined immunotherapy is more effective for metastatic meningioma needs further exploration.

Avenaciolide Induces Apoptosis in Human Malignant Meningioma Cells through the Production of Reactive Oxygen Species.

Malignant meningioma has a poor prognosis and there are currently no effective therapies. Avenaciolide is water-insoluble natural organic product produced by Aspergillus avenaceus G. Smith that can inhibit mitochondrial function. In the present study, we investigated the anti-cancer effects of avenaciolide in an isolated human malignant meningioma cell line, HKBMM. In addition, to assess the specificity of avenaciolide, its effects on normal human neonatal dermal fibroblast HDFn cells were also examined. Avenaciolide showed effective anti-cancer activity, and its cytotoxicity in HKBMM cells was greater than that in HDFn cells. The anti-cancer effects of avenaciolide were mediated by reactive oxygen species (ROS)-induced apoptosis, which may have been caused by mitochondrial disfunction. These results suggest that avenaciolide has potential as a therapeutic drug for malignant meningioma.

Somatostatin analogues in treatment-refractory meningioma: a systematic review with meta-analysis of individual patient data.

Treatment-refractory meningiomas have a dismal prognosis and limited treatment options. Meningiomas express high-densities of somatostatin receptors (SSTR), thus potentially susceptible to antitumorigenic effects of somatostatin analogues (SSA). Evidence for SSA in meningiomas is scarce, and it is unclear if published literature would either (1) support wider use of SSA, if (2) more evidence is desirable, or if (3) available evidence is sufficient to discard SSA. We addressed the need for more evidence with a systematic review and meta-analysis. We performed an individual patient data (IPD) meta-analysis. Main outcomes were toxicity, best radiological response, progression-free survival, and overall survival. We applied multivariable logistic regression models to estimate the effect of SSA on the probability of obtaining radiological disease control. The predictive performance was evaluated using area under the curve and Brier scores. We included 16 studies and compiled IPD from 8/9 of all previous cohorts. Quality of evidence was overall ranked "very low." Stable disease was reported in 58% of patients as best radiological response. Per 100 mg increase in total SSA dosage, the odds ratios for obtaining radiological disease control was 1.42 (1.11 to 1.81, P = 0.005) and 1.44 (1.00 to 2.08, P = 0.05) for patients treated with SSA as monodrug therapy vs SSA in combination with everolimus, respectively. Low quality of evidence impeded exact quantification of treatment efficacy, and the association between response and treatment may represent reverse causality. Yet, the SSA treatment was well tolerated, and beneficial effect cannot be disqualified. A prospective trial without bias from inconsistent study designs is warranted to assess SSA therapy for well-defined meningioma subgroups.

Expression of decitabine-targeted oncogenes in meningiomas in vivo.

Treatment of meningiomas refractory to surgery and irradiation is challenging and effective chemotherapies are still lacking. Recently, in vitro analyses revealed decitabine (DCT, 5-aza-2'-deoxycytidine) to be effective in high-grade meningiomas and, moreover, to induce hypomethylation of distinct oncogenes only sparsely described in meningiomas in vivo yet.Expression of the corresponding onco- and tumor suppressor genes TRIM58, FAM84B, ELOVL2, MAL2, LMO3, and DIO3 were analyzed and scored by immunohistochemical staining and RT-PCR in samples of 111 meningioma patients. Correlations with clinical and histological variables and prognosis were analyzed in uni- and multivariate analyses.All analyzed oncogenes were highly expressed in meningiomas. Expression scores of TRIM58 tended to be higher in benign than in high-grade tumors 20 vs 16 (p = .002) and all 9 samples lacking TRIM58 expression displayed WHO grade II/III histology. In contrast, median expression scores for both FAM84B (6 vs 4, p ≤ .001) and ELOVL2 (9 vs 6, p < .001) were increased in high-grade as compared to benign meningiomas. DIO3 expression was distinctly higher in all analyzed samples as compared to the reference decitabine-resistant Ben-Men 1 cell line. Increased ELOVL2 expression (score ≥ 8) correlated with tumor relapse in both uni- (HR: 2.42, 95%CI 1.18-4.94; p = .015) and multivariate (HR: 2.09, 95%CI 1.01-4.44; p = .046) analyses.All oncogenes involved in DCT efficacy in vitro are also widely expressed in vivo, and expression is partially associated with histology and prognosis. These results strongly encourage further analyses of DCT efficiency in meningiomas in vitro and in situ.

Chemotherapy and targeted therapies for meningiomas: what is the evidence?

PURPOSE OF REVIEW: Although most meningiomas are slow growing tumors mainly controlled by surgery with or without radiotherapy, aggressive meningiomas that fail these conventional treatments constitute a rare situation, a therapeutic challenge and an unmet need in neuro-oncology. RECENT FINDING: Mutational landscape in recurrent high-grade meningiomas includes mainly NF2 mutation or 22q chromosomal deletion, whereas telomerase reverse transcriptase promoter, BAP-1 and CDK2NA mutations were also found in aggressive meningiomas. Pi3K-Akt-mTOR pathway is currently the most relevant intracellular signaling pathway target in meningiomas with preliminary clinical activity observed. Assessment of drug activity with progression free survival rate at 6 months is challenging in regard to meningioma growth rate heterogeneity, so that 3-dimensional growth rate before and during treatment could be considered in the future to selected new active drugs. SUMMARY: Despite a low evidence level, some systemic therapies may be considered for patients with recurrent meningioma not amenable to further surgery or radiotherapy. In recurrent high-grade meningioma, everolimus-octreotide combination, bevacizumab, sunitinib and peptide receptor radionuclide therapy exhibit a signal of activity that may justify their clinical use. Despite a lack of clear signal of activity to date, immunotherapy may offer new perspectives in the treatment of these refractory tumors.