Related mechanisms, current treatments, and new perspectives in meningioma.

Meningiomas are non-glial tumors that are the most common primary brain tumors in adults. Although meningioma can possibly be cured with surgical excision, variations in atypical/anaplastic meningioma have a high recurrence rate and a poor prognosis. As a result, it is critical to develop novel therapeutic options for high-grade meningiomas. This review highlights the current histology of meningiomas, prevalent genetic and molecular changes, and the most extensively researched signaling pathways and therapies in meningiomas. It also reviews current clinical studies and novel meningioma treatments, including immunotherapy, microRNAs, cancer stem cell methods, and targeted interventions within the glycolysis pathway. Through the examination of the complex landscape of meningioma biology and the highlighting of promising therapeutic pathways, this review opens the way for future research efforts aimed at improving patient outcomes in this prevalent intracranial tumor entity.

Relevance of the Foramen of Vesalius for Preoperative Tumor Embolization in Skull Base Meningioma.

OBJECTIVE: The objective of this study was to investigate the role of the foramen of Vesalius (FV) in the pathogenesis of skull base meningioma by analyzing data from various multi-image modalities. METHODS: For this single-center retrospective study, 39 consecutive patients with skull base meningioma who underwent tumor resection between January 2020 and March 2023 were enrolled. The anatomical and pathological characteristics of the FV were evaluated using computed tomography and 3-dimensional digital subtraction angiography. The clinical significance of the FV in tumor hemodynamics and treatment, such as preoperative tumor embolization, was investigated using the 3-dimensional digital subtraction angiography/computed tomography fusion images. RESULTS: We identified FV in 52% (17/27) of the finally included patients. In 10 (30%) patients, the FV was found bilaterally with no significant variation in appearance between the healthy and tumor-affected sides (P = 0.786). The mean FV diameter was significantly larger on the tumor-affected side (P = 0.010). No significant anatomical differences, like duplication and partial assimilation with the foramen ovale, were observed between the 2 sides. The FV was involved in venous skull base perfusion around the tumor in 9 cases. In 4 cases where it was the pathway for tumor feeders, preoperative tumor embolization via the FV resulted in disappearance of the tumor stain. No complications associated with endovascular treatment were observed. CONCLUSIONS: This study elucidated the anatomical asymmetry of the FV and its role in the hemodynamics of skull base meningioma. Our findings highlight the significance of performing anatomical and pathological evaluations of the FV in determining treatment strategies, including preoperative embolization, for skull base lesions.

A randomized control trial for evaluation of transfusion related immuno-modulation in patients with meningioma.

BACKGROUND: Blood transfusion necessity in neurosurgery varies based on surgical type, blood loss, and patient anemia. Leukocytes in red blood cells (RBCs) component release pro-inflammatory cytokines during storage, contributing to transfusion-related immunomodulation (TRIM). Our aim was to examine the impact of the leukocyte content in transfused PRBCs on patients undergoing neurosurgery for meningioma tumours. STUDY DESIGN AND METHODS: This prospective randomized controlled trial conducted from 2018 to 2020 by dividing patients randomly into non-leukoreduced (NLR) (n = 65) and leuko-reduced (LR) (n = 65) groups based on PRBCs received during surgery and hospital stay. Hospital and ICU stays, mechanical ventilation duration, and postoperative bacterial infections were observed. Hematological parameters and cytokine levels (IL-10, INF-gamma, and FAS-L) were assessed at pre-transfusion, 24 h, and 7 days post-transfusion. Data analysis included Mann-Whitney U test, Friedman test, Fisher's chi-square test, with statistical significance at p < 0.05. RESULTS: In our study, ICU and hospital stay duration showed no significant difference (p = 0.06) between groups. However, NLR group had longer mean mechanical ventilation (18 ± 40.1 h) than the LR group (12.8 ± 8.6 h). Both groups showed statistically significant increase in Fas-L level on days 1 and 7 (p < 0.05). The IL-10 levels rose 43% in the NLR group, while and decreased by 7% the LR group on day 1. On day 7, IL-10 increased by 75% in NLR and decreased by 40% in LR, with no significance (p > 0.05). CONCLUSION: In conclusion, leukoreduction appeared to offer some immune response protection in term of reducing mechanical ventilation timings and cytokine level changes.

A systematic review of extraneural meningioma metastasis: timing, evolution and outlook.

PURPOSE: Extraneural meningioma metastasis is a rare occurrence and may pose a clinical challenge due to its unclear prognosis. In this systematic review, we analyze patient demographics, clinical characteristics, management strategies, and outcomes. METHODS: PubMed, EMBASE, Scopus, Cochrane, and Web of Science databases were searched from inception to February 23, 2024 for cases of metastatic meningioma according to PRISMA guidelines. Descriptive statistics, Mann-Whitney U test, Fisher's exact tests, Kaplan-Meier curves, and log-rank tests were used for selected analyses. RESULTS: A total of 288 patients (52% male) were included with an average age of 49 years at meningioma diagnosis. Tumors were distributed across WHO grade 1 (38%), 2 (36%), and 3 (26%). Most patients experienced intracranial recurrence (79%) and mean time to first metastasis was approximately 8 years. No change in WHO grade between primary and metastasis was observed for most cases (65%). Treatment of the initial metastasis was most often with surgery (43%), chemotherapy (20%), or no treatment (14%). Half of the patients were alive (50%) with an average follow-up of 3 years following metastasis. Overall median survival was 36 months for the entire cohort. This differed significantly between WHO grade 1 versus 2/3 meningioma primaries (168 vs. 15 months, p < 0.005). CONCLUSION: Metastatic meningioma appears to be associated with more positive prognosis than other brain tumor types with extra-neural metastasis or metastasis in general. This is particularly true for cases arising from a WHO grade 1 meningioma.

Volumetric growth rate of incidentally found meningiomas on immunotherapy.

PURPOSE: The expression of PD-L1 in high-grade meningiomas made it a potential target for immunotherapy research in refractory cases. Several prospective studies in this field are still on going. We sought to retrospectively investigate the effects of check-point inhibitors (CI) on meningiomas that had been naïve to either surgical or radiation approaches by following incidental meningiomas found during treatment with CI for various primary metastatic cancers. METHODS: We used the NYU Perlmutter Cancer Center Data Hub to find patients treated by CI for various cancers, who also had serial computerized-tomography (CT) or magnetic-resonance imaging (MRI) reports of intracranial meningiomas. Meningioma volumetric measurements were compared between the beginning and end of the CI treatment period. Patients treated with chemotherapy during this period were excluded. RESULTS: Twenty-five patients were included in our study, of which 14 (56%) were on CI for melanoma, 5 (20%) for non-small-cell lung cancer and others. CI therapies included nivolumab (n = 15, 60%), ipilimumab (n = 11, 44%) and pembrolizumab (n = 9, %36), while 9 (36%) were on ipilimumab/nivolumab combination. We did not find any significant difference between tumor volumes before and after treatment with CI (1.31 ± 0.46 vs. 1.34 ± 0.46, p=0.8, respectively). Among patients beyond 1 year of follow-up (n = 13), annual growth was 0.011 ± 0.011 cm3/year. Five patients showed minor volume reduction of 0.12 ± 0.10 cm3 (21 ± 6% from baseline). We did not find significant predictors of tumor volume reduction. CONCLUSION: Check-point inhibitors may impact the natural history of meningiomas. Additional research is needed to define potential clinical indications and treatment goals.

The Natural History and Treatment of Meningiomas: An Update.

Meningiomas are the most frequent nonmalignant tumors of the central nervous system (CNS). Despite their benign nature and slow-growing pattern, if not diagnosed early, these tumors may reach relatively large sizes causing significant morbidity and mortality. Some variants are located in hard-to-access locations, compressing critical neurovascular structures, and making the surgical management even more challenging. Although most meningiomas have a good long-term prognosis after treatment, there are still controversies over their management in a subset of cases. While surgery is the first-line treatment, the use of fractionated radiotherapy or stereotactic radiosurgery is indicated for residual or recurrent tumors, small lesions, and tumors in challenging locations. Advances in molecular genetics and ongoing clinical trial results have recently helped both to refine the diagnosis and provide hope for effective biomolecular target-based medications for treatment. This article reviews the natural history and current therapeutic options for CNS meningiomas.

Lifestyle and subsequent meningioma in childhood cancer survivors: A report from the St. Jude Lifetime Cohort study.

BACKGROUND: Lifestyle is associated with meningioma risk in the general population. AIMS: We assessed longitudinal associations between lifestyle-associated factors and subsequent meningiomas in childhood cancer survivors. METHODS AND RESULTS: Childhood cancer survivors age ≥18 years in the St. Jude Lifetime Cohort Study were evaluated for body composition, self-reported physical activity, cardiopulmonary fitness, muscle strength, smoking, and alcohol consumption at baseline. Time to first meningioma analyses were performed, adjusted for sex, age at diagnosis and baseline assessment, treatment decade, and childhood cancer treatment exposures. The study included 4,072 survivors (47% female; [mean (SD)] 9 (6) years at diagnosis; 30 (8.5) years at the start of follow-up, with 7.0 (3.3) years of follow-up). 30% of the participants were survivors of acute lymphoblastic leukemia and 29% of the participants had received cranial radiation. During follow-up, 90 participants developed ≥1 meningioma, of whom 73% were survivors of acute lymphoblastic leukemia, with cranial radiation being the strongest risk factor (relative risk [RR] 29.7, 95% confidence interval [CI] 10.6-83.2). Muscle strength assessed by knee extension was associated with a lower risk of developing a meningioma in the adjusted analyses (RR 0.5, 95% CI 0.2-1.0, p = 0.04 for quartiles 3-4 vs. 1). No other lifestyle-associated variable was associated with subsequent meningioma. CONCLUSION: Independent of cranial radiation, muscle strength was associated with a lower risk of developing a subsequent meningioma in childhood cancer survivors.

Pediatric Meningiomas: Current Insights on Pathogenesis and Management.

Meningiomas are rare tumors in children, ranging from 0.4 to 4% of intracranial tumors. Differently from their adult counterpart, pediatric meningiomas (PMs) often show peculiar aspects such as the development of tumoral cysts, the involvement of the intraventricular space, and missing attachment to the dura mater. The most important difference with adults is represented by the high incidence of WHO grade II and III variants, which can account for more than 70% of cases. The prognosis of PMs mainly depends on the initial surgical resection because radiotherapy, which is the main treatment option in the case of tumor recurrence or progression, does not seem to increase the relapse free survival and the overall survival, and chemotherapy still misses specific and effective protocols.On these grounds, the need to better understand these tumors, to favor an appropriate multidisciplinary management, is particularly felt. The present review is focused on the advances on the pathogenesis, the molecular aspects, and the managements of PMs, with the goal to improve the knowledge of these challenging neoplasms.

Incidence, management, and outcome of incidental meningioma: what has happened in 10 years?

PURPOSE: The aim of this study was to study the use of brain scanning, and the subsequent findings of presumed incidental meningioma in two time periods, and to study differences in follow-up, treatment, and outcome. METHODS: Records of all performed CT and MRI of the brain during two time periods were retrospectively reviewed in search of patients with presumed incidental meningioma. These patients were further analyzed using medical health records, with the purpose to study clinical handling and outcome during a 3 year follow up. RESULTS: An identical number of unique patients underwent brain imaging during the two time periods (n = 22 259 vs. 22 013). In 2018-2019, 25% more incidental meningiomas were diagnosed compared to 2008-2009 (n = 161 vs. 129, p = 0.052). MRI was used more often in 2018-2019 (26.1 vs. 12.4%, p = 0.004), and the use of contrast enhancement, irrespective of modality, also increased (26.8 vs. 12.2%, p < 0.001). In the most recent cohort, patients were older (median 79 years vs. 73 years, p = 0.03). Indications showed a significant increase of cancer without known metastases among scanned patients. 29.5 and 35.4% of patients in the cohorts were deceased 3 years after diagnosis for causes unrelated to their meningioma. CONCLUSIONS: Despite the same number of unique patients undergoing brain scans in the time periods, there was a trend towards more patients diagnosed with an incidental asymptomatic meningioma in the more recent years. This difference may be attributed to more contrast enhanced scans and more scans among the elderly but needs to be further studied. Patients in the cohort from 2018 to 2019 more often had non-metastatic cancer, with their cause of scan screening for metastases. There was no significant difference in management decision at diagnosis, but within 3 years of follow up significantly more patients in the latter cohort had been re-scanned. Almost a third of all patients were deceased within 3 years after diagnosis, due to causes other than their meningioma.

Disease-Based Prognostication: Neuro-Oncology.

Primary malignant and non-malignant brain and other central nervous system (CNS) tumors, while relatively rare, are a disproportionate source of morbidity and mortality. Here we provide a brief overview of approaches to modeling important clinical outcomes, such as overall survival, that are critical for clinical care. Because there are a large number of histologically distinct types of primary malignant and non-malignant brain and other CNS tumors, this chapter will provide an overview of prognostication considerations on the most common primary non-malignant brain tumor, meningioma, and the most common primary malignant brain tumor, glioblastoma. In addition, information on nomograms and how they can be used as individualized prognostication tools by clinicians to counsel patients and their families regarding treatment, follow-up, and prognosis is described. The current state of nomograms for meningiomas and glioblastomas are also provided.

[Molecular genetic features of meningiomas]. / Molekulyarno-geneticheskie osobennosti meningiom.

Meningioma is the most common primary tumor of the central nervous system. Traditional classification is based on histological properties of tumors and distinguishes different grades of meningioma malignancy. However, knowledge about different molecular mechanisms of tumor provided new data on genetic features of meningiomas. The authors analyze current available data on the main driver mutations, new classifications based on molecular genetic characteristics and potential targets for therapy.

Paradigm Shift in the Treatment of Meningiomas.

Meningiomas are the most common brain tumor in adults with rising incidence rates due to an aging population globally, increased availability of neuroimaging, and increased awareness of this condition by treating clinicians and primary care physicians. Surgical resection remains the mainstay of treatment, with adjuvant radiotherapy reserved for higher grade meningiomas or tumors that undergo incomplete resections. Whereas these tumors were classically defined by their histopathological features and subtypes, recent work has uncovered the molecular alterations that may lead to tumor development and have important prognostic implications. However, there remain important clinical questions regarding the management of meningiomas and current clinical guidelines continue to evolve as additional studies add onto the growing body of work that enables us to better understand these tumors.

Clinical Presentation and Prognosis.

Over the past three decades, the care for patients with meningioma has steadily improved as a result of a better understanding of the natural history, molecular biology, and classification of these tumors. Surgical frameworks for management have been established and validated with more options for adjuvant and salvage treatment available for patients with residual or recurrent disease. Overall these advances have improved clinical outcomes and prognosis.Alongside the improved clinical management has come an increase in biological understanding of these tumors. The number of publications within the field of meningioma research continues to expand and biological studies identifying molecular factors at the cytogenic and genomic level offer exciting potential for more personalized management strategies. As survival and understanding have increased, treatment outcomes are moving from traditional metrics, which describe the morbidity and mortality to more patient-centered measures. The subjective experiences of patients with meningioma are gaining interest among clinical researchers and it is recognized that even supposedly mild symptoms arising from meningioma can have a significant effect on a patient's quality of life.This chapter reviews the varied clinical presentations of meningioma, which in the modern era of widespread brain imaging must include a discussion of incidental meningioma. The second part examines prognosis and the clinical, pathological, and molecular factors that can be used to predict outcomes.

Immune Profiling of Meningiomas.

Though meningiomas are generally regarded as benign tumors, there is increasing awareness of a large group of meningiomas that are biologically aggressive and refractory to the current standards of care treatment modalities. Coinciding with this has been increasing recognition of the important that the immune system plays in mediating tumor growth and response to therapy. To address this point, immunotherapy has been leveraged for several other cancers such as lung, melanoma, and recently glioblastoma in the context of clinical trials. However, first deciphering the immune composition of meningiomas is essential in order to determine the feasibility of similar therapies for these tumors. Here in this chapter, we review recent updates on characterizing the immune microenvironment of meningiomas and identify potential immunological targets that hold promise for future immunotherapy trials.

Preclinical Models of Meningioma.

The management of clinically aggressive meningiomas remains challenging due to limited treatment options aside from surgical removal and radiotherapy. High recurrence rates and lack of effective systemic therapies contribute to the unfavorable prognosis of these patients. Accurate in vitro and in vivo models are critical for understanding meningioma pathogenesis and to identify and test novel therapeutics. In this chapter, we review cell models, genetically engineered mouse models, and xenograft mouse models, with special emphasis on the field of application. Finally, promising preclinical 3D models such as organotypic tumor slices and patient-derived tumor organoids are discussed.

Immunotherapy for Meningiomas.

Systemic treatment approaches are urgently needed for a subset of meningioma patients who do not achieve local tumor control with surgery and radiotherapy. Classical chemotherapy or anti-angiogenic agents exert only very limited activity in these tumors. Long-term survival of patients with advanced metastatic cancer following treatment with immune checkpoint inhibitors, i.e., monoclonal antibodies designed to unleash suppressed anticancer immune responses, has fostered hopes for benefit from similar approaches in patients with meningiomas that recur after standard local therapy. Moreover, a plethora of immunotherapy approaches beyond these drugs have entered clinical development or clinical practice for other cancer entities, including (i) novel immune checkpoint inhibitors that may act independently of T cell activity, (ii) cancer peptide or dendritic cell vaccines to induce anticancer immunity utilizing cancer-associated antigens, (iii) cellular therapies utilizing genetically modified peripheral blood cells to directly target cancer cells, (iv) T cell engaging recombinant proteins that link tumor antigen-binding sites to effector cell activating or recognition domains, or to immunogenic cytokines, and (v) oncolytic virotherapy utilizing attenuated viral vectors designed to specifically infect cancer cells, seeking to elicit systemic anticancer immunity. This chapter provides an overview of the principles of immunotherapy, summarizes ongoing immunotherapy clinical trials in meningioma patients, and discusses the applicability of established and emerging immunotherapy concepts to meningioma patients.

Health-Related Quality of Life in Intracranial Meningioma: Current Evidence and Future Directions.

Historically, largely due to the good prognosis for survival, there has been little attention paid to the possible impact of meningiomas and their treatment on health-related quality of life (HRQoL). However, in the last decade there has been increasing evidence that patients with intracranial meningiomas suffer from long-term decreases in their HRQoL. Compared with controls and normative data, meningioma patients have worse HRQoL scores both before and after intervention and continuing long term (even after >4 years of follow-up). Overall, surgery results in improvements in many aspects of HRQoL. The limited available studies investigating the impact of radiotherapy suggest that this type of treatment decreases HRQoL scores, especially in the long term. There is however only limited evidence on additional determinants of HRQoL. Patients with anatomically complex skull base meningiomas and severe comorbidities, including epilepsy, report the lowest HRQoL scores. Other tumor and sociodemographic characteristics have shown weak associations with HRQoL. Furthermore, about one-third of caregivers of meningioma patients report caregiver burden, warranting interventions to improve caregiver HRQoL. As antitumor interventions may not improve HRQoL scores to be comparable to those of the general population, more attention should be paid to the development of integrative rehabilitation and supportive care programs for meningioma patients.

Metastatic meningioma: a case series and systematic review.

BACKGROUND: Meningiomas are the most common primary intracranial tumor. While the majority of meningiomas are benign, rarely they can metastasize extracranially. There is a need for a more comprehensive review of these patients to improve our understanding of this rare phenomenon and its prevalence globally. Here we describe our institution's experience of patients presenting with metastatic meningiomas. We further perform a systematic review of the existing literature to explore common features of this rare manifestation of meningioma and review the efficacy of current treatments. METHODS: We performed a retrospective clinical review of all adult patients with metastatic meningioma managed at our institution over the past 20 years, identifying 6 patients. We then performed a systematic review of cases of metastatic meningioma in the literature ranging from the years 1886 to 2022. A descriptive analysis was then conducted on the available data from 1979 onward, focusing on the grade and location of the primary tumor as well as the latency period to, and location of, the metastasis. RESULTS: In total, we analyzed 155 cases. Fifty-four percent of patients initially presented with a primary meningioma located in the convexity. The most common site of metastasis was the lung. Risk factors associated with a shorter time to metastasis were male sex and a high initial grade of the tumor. Regarding treatment, the addition of chemotherapy was the most common adjunct to the standard management of surgery and radiotherapy. Despite an exhaustive review we were unable to identify effective treatments. The majority of published cases came from centers situated in high-income countries (84%) while only 16% came from lower- and middle-income countries. CONCLUSIONS: Metastatic meningiomas pose a pertinent, and likely underestimated, clinical challenge within modern neurosurgery. To optimize management, timely identification of these patients is important. More research is needed to explore the mechanisms underlying these tumors to better guide the development of effective screening and management protocols. However, screening of each meningioma patient is not feasible, and at the heart of this challenge is the inability to control the primary disease. Ultimately, a consensus is needed as to how to correctly screen for and manage these patients; genomic and epigenomic approaches could hold the answer to finding druggable targets.

Outcomes of Preoperative Transophthalmic Artery Embolization of Meningiomas: A Systematic Review with a Focus on Embolization Agent.

BACKGROUND: Transophthalmic artery embolization of intracranial meningiomas is thought to be associated with a high complication risk. PURPOSE: With advances in endovascular techniques, we systematically reviewed the current literature to improve our understanding of the safety and efficacy of transophthalmic artery embolization of intracranial meningiomas. DATA SOURCES: We performed a systematic search using PubMed from inception until August 3, 2022. STUDY SELECTION: Twelve studies with 28 patients with intracranial meningiomas embolized through the transophthalmic artery were included. DATA ANALYSIS: Baseline and technical characteristics and clinical and safety outcomes were collected. No statistical analysis was conducted. DATA SYNTHESIS: The average age of 27 patients was 49.5 (SD, 13) years. Eighteen (69%) meningiomas were located in the anterior cranial fossa, and 8 (31%), in the sphenoid ridge/wing. Polyvinyl alcohol particles were most commonly (n = 8, 31%) used to preoperatively embolize meningiomas, followed by n-BCA in 6 (23%), Onyx in 6 (23%), Gelfoam in 5 (19%), and coils in 1 patient (4%). Complete embolization of the target meningioma feeders was reported in 8 (47%) of 17 patients; partial embolization, in 6 (32%); and suboptimal embolization, in 3 (18%). The endovascular complication rate was 16% (4 of 25), which included visual impairment in 3 (12%) patients. LIMITATIONS: Selection and publication biases were limitations. CONCLUSIONS: Transophthalmic artery embolization of intracranial meningiomas is feasible but is associated with a non-negligible complication rate.

Sporadic and neurofibromatosis type 2-associated meningioma in children and adolescents.

PURPOSE: Pediatric meningioma differs not only in its rare incidence from the adult meningioma, but also in its clinical characteristics. Many treatment approaches of pediatric meningioma are based on the study results of adult meningioma studies. The aim of this study was to explore the clinical and epidemiological characteristics of pediatric meningioma. METHODS: Data on pediatric patients diagnosed between 1982 and 2021 with NF2-associated or sporadic meningioma and recruited in the trials/registries HIT-ENDO, KRANIOPHARYNGEOM 2000/2007 and KRANIOPHARYNGEOM Registry 2019 were retrospectively analyzed for clinical characteristics, etiology, histology, therapy, and outcome. RESULTS: One hundred fifteen study participants were diagnosed with sporadic or NF2-associated meningioma at a median age of 10.6 years. There was a 1:1 sex ratio, with 14% of study participants suffering from NF2. 46% of the meningiomas were located hemispherically, 17% at the optic nerve/ intraorbital and 10% ventricularly. Multiple meningiomas were detected in 69% of NF2 patients and in 9% of sporadic meningiomas. 50% of the meningiomas were WHO grade I, 37% WHO grade II and 6% WHO grade III. Progressions or recurrences occurred after a median interval of 1.9 years. Eight patients (7%) died, 3 of them due to disease. The event-free survival was higher for WHO grade I than for WHO grade II meningioma patients (p = 0.008). CONCLUSIONS: The major difference to the preceding literature could be found in the distribution of different WHO grades and their influence on event-free survival. Prospective studies are warranted to assess the impact of different therapeutic regimens. CLINICAL TRIAL REGISTRATION NUMBERS: NCT00258453; NCT01272622; NCT04158284.