Meningioma: International Consortium on Meningiomas (ICOM) consensus review on scientific advances & treatment paradigms for clinicians, researchers, and patients.

Meningiomas are the most common primary intracranial tumors in adults and are increasing in incidence due to the aging population and the rising availability of neuroimaging. While most exhibit non-malignant behaviour, a subset of meningiomas are biologically aggressive and lead to significant neurological morbidity and mortality. In recent years, meaningful advances in our understanding of the biology of these tumors have led to the incorporation of molecular biomarkers into their grading and prognostication. However, unlike other central nervous system tumors, a unified molecular taxonomy for meningiomas has not yet been established and remains an overarching goal of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy-Not Official WHO (cIMPACT-NOW) working group. There also remains clinical equipoise on how specific meningioma cases and patient populations should be optimally managed. To address these existing gaps, members of the International Consortium on Meningiomas (ICOM) including field-leading experts, have prepared a comprehensive consensus narrative review directed towards clinicians, researchers, and patients. Included in this manuscript are detailed overviews of proposed molecular classifications, novel biomarkers, contemporary treatment strategies, trials on systemic therapies, health-related quality of life studies, and management strategies for unique meningioma patient populations. In each section we discuss the current state of knowledge as well as ongoing clinical and research challenges to road map future directions for further investigation.

The experience of living with malignant meningioma.

OBJECTIVES: Meningiomas are the most common, primary intracranial tumor and most are benign. Little is known of the rare patient group living with a malignant meningioma, comprising 1-3% of all meningiomas. Our aim was to explore how patients perceived quality of daily life after a malignant meningioma diagnosis. METHODS: This qualitative explorative study was composed of individual semi-structured interviews. Eligible patients (n = 12) were selected based on ability to participate in an interview, from a background population of 23 patients diagnosed with malignant meningioma at Rigshospitalet from 2000 to 2021. We performed an inductive thematic analysis following Braun and Clarke's guidelines. RESULTS: Eight patients were interviewed. The analysis revealed 4 overarching themes: (1) perceived illness and cause of symptoms, (2) identity, roles, and interaction, (3) threat and uncertainty of the future, and (4) belief in authority. The perceived quality of daily life is negatively impacted by the disease. Patients experience a shift in self-concept and close interactions, and some struggle with accepting a new everyday life. Patients have a high risk of discordant prognostic awareness in relation to health-care professionals. SIGNIFICANCE OF RESULTS: We provide a much-needed patient-centered perspective of living with malignant meningioma: quality of life was affected by perception of threat and an uncertainty of the future. Perception of illness and the interpretation of the cause of symptoms varied between subjects, but a common trait was that patients' identity, roles, and interactions were affected. Shared decision-making and a strengthened continuity during follow-up could aid this rare patient group.

Translocator protein (TSPO) expression in neoplastic cells and tumor-associated macrophages in meningiomas.

Meningiomas are the most common primary intracranial tumors and show extensive infiltration of macrophages. The mitochondrial membrane protein translocator protein (TSPO) has been used as an in vivo marker of microglia and macrophage activation to visualize neuroinflammation. However, it is unknown which cell types express TSPO in meningiomas. Immunohistochemistry of 38 WHO grade 1-3 meningiomas was subjected to segmentation and deep learning classification of TSPO expression to either Iba1-positive tumor-associated macrophages (TAMs) or all other (mainly neoplastic) cells. A possible association between clinical data and TSPO expression intensities was also investigated. TAMs accounted for 15.9%-26% of all cells in the meningioma tissue. Mean fluorescence intensity of TSPO was significantly higher in TAMs (p < 0.0001), but the mass of neoplastic cells in the tumors exceeded that of TAMs. Thus, the summed fluorescence intensity of TSPO in meningioma cells was 64.1% higher than in TAMs (p = 0.0003). We observed no correlation between TSPO expression intensity and WHO grade. These results indicate that both macrophage-lineage and neoplastic cells in meningiomas express TSPO and that the SPECT-TSPO signal in meningiomas mainly reflects the latter; TSPO is expressed equally in parenchymal activated and resting macrophage/microglia lineage cells.

Meningioma animal models: a systematic review and meta-analysis.

BACKGROUND: Animal models are widely used to study pathological processes and drug (side) effects in a controlled environment. There is a wide variety of methods available for establishing animal models depending on the research question. Commonly used methods in tumor research include xenografting cells (established/commercially available or primary patient-derived) or whole tumor pieces either orthotopically or heterotopically and the more recent genetically engineered models-each type with their own advantages and disadvantages. The current systematic review aimed to investigate the meningioma model types used, perform a meta-analysis on tumor take rate (TTR), and perform critical appraisal of the included studies. The study also aimed to assess reproducibility, reliability, means of validation and verification of models, alongside pros and cons and uses of the model types. METHODS: We searched Medline, Embase, and Web of Science for all in vivo meningioma models. The primary outcome was tumor take rate. Meta-analysis was performed on tumor take rate followed by subgroup analyses on the number of cells and duration of incubation. The validity of the tumor models was assessed qualitatively. We performed critical appraisal of the methodological quality and quality of reporting for all included studies. RESULTS: We included 114 unique records (78 using established cell line models (ECLM), 21 using primary patient-derived tumor models (PTM), 10 using genetically engineered models (GEM), and 11 using uncategorized models). TTRs for ECLM were 94% (95% CI 92-96) for orthotopic and 95% (93-96) for heterotopic. PTM showed lower TTRs [orthotopic 53% (33-72) and heterotopic 82% (73-89)] and finally GEM revealed a TTR of 34% (26-43). CONCLUSION: This systematic review shows high consistent TTRs in established cell line models and varying TTRs in primary patient-derived models and genetically engineered models. However, we identified several issues regarding the quality of reporting and the methodological approach that reduce the validity, transparency, and reproducibility of studies and suggest a high risk of publication bias. Finally, each tumor model type has specific roles in research based on their advantages (and disadvantages). SYSTEMATIC REVIEW REGISTRATION: PROSPERO-ID CRD42022308833.

DNA methylation profile of human dura and leptomeninges.

Healthy meninges are used as control tissue in meningioma studies usually without specification of the exact meningeal layer or macroanatomical origin but the DNA methylation profile of human meninges has not been investigated on a macroanatomical level. We undertook a proof-of-principle analysis to determine whether (1) meningeal tissues show sufficiently homogenous DNA methylation profiles to function as normal control tissue without further specification and (2) if previously described location-specific molecular signatures of meningiomas correspond to region-specific DNA methylation patterns. Dura mater and arachnoid membrane specimens were dissected from 5 anatomical locations in 2 fresh human cadavers and analyzed with the Illumina Infinium MethylationEPIC array. Dura and leptomeninges showed marked differences in global DNA methylation patterns and between rostral and caudal anatomical locations. These differences did not reflect known anatomical predilection of meningioma molecular signatures. The highest numbers of differentially methylated probes were annotated to DIPC2 and FOXP1. Samples from foramen magnum showed hypomethylation of TFAP2B compared to those from remaining locations. Thus, the DNA methylation profiles of human meninges are heterogenous in terms of meningeal layer and anatomical location. The potential variability of DNA methylation data from meningiomas should be considered in studies using meningeal controls.

Gene expression analysis during progression of malignant meningioma compared to benign meningioma.

OBJECTIVE: Meningioma is the most common primary intracranial neoplasm. Only 1%-3% of meningiomas are malignant according to the 2016 WHO criteria (WHO grade III). High-grade meningiomas present specific gene expression signatures indicating aggressive growth or recurrence. However, changes in gene expression and in neuroinflammatory gene expression signatures in WHO grade III meningiomas and during progression from WHO grade I or II to grade III are unknown. METHODS: The authors used a NanoString targeted gene expression panel with focus on 787 genes relevant in meningioma pathology and neuroinflammatory pathways to investigate patients with grade III meningiomas treated at Rigshospitalet from 2000 to 2020 (n = 51). A temporal dimension was added to the investigation by including samples from patients' earlier grade I and II meningiomas and grade III recurrences (n = 139 meningiomas). The authors investigated changes in neuroinflammatory gene expression signatures in 1) grade I meningiomas that later transformed into grade III meningiomas, and 2) grade III meningiomas compared with nonrecurrent grade I meningiomas. RESULTS: The authors' data indicate that FOXM1, TOP2A, BIRC5, and MYBL2 were enriched and the HOTAIR regulatory pathway was enriched in grade III meningiomas compared with nonrecurrent grade I meningiomas. They discovered a separation of malignant and benign meningiomas based only on genes involved in microglia regulation with enrichment of P2RY12 in grade I compared with grade III meningiomas. Interestingly, FOXM1 was upregulated in premalignant grade I meningioma years before the grade III transformation. CONCLUSIONS: The authors found gene expression changes in low-grade meningiomas that predated histological transformation to grade III meningiomas. Neuroinflammation genes distinguished grade III from grade I meningiomas.

Long-Term Follow-Up, Treatment Strategies, Functional Outcome, and Health-Related Quality of Life after Surgery for WHO Grade 2 and 3 Intracranial Meningiomas.

Progression-free survival (PFS) and overall survival (OS) for WHO grade 2 and 3 intracranial meningiomas are poorly described, and long-term results and data evaluating the routine use of supplementary fractionated radiotherapy (RT) or stereotactic radiosurgery (SRS) has been inconclusive. The aim of this study was to determine the long-term PFS and OS at a center that does not employ routine adjuvant RT. For this purpose, a retrospective population-based cohort study was conducted of all WHO grade 2 and 3 meningiomas surgically treated between 2005 and 2013. The cohort was uniformly defined according to the WHO 2007 criteria to allow comparisons to previously published reports. Patient records were reviewed, and patients were then prospectively contacted for structured quality-of-life assessments. In total, 51 consecutive patients were included, of whom 43 were WHO grade 2 and 8 were grade 3. A Simpson grade 1-2 resection was achieved in 62%. The median PFS was 31 months for grade 2 tumors, and 3.4 months for grade 3. The median OS was 13 years for grade 2, and 1.4 years for grade 3. The MIB-1-index was significantly associated with an increased risk for recurrence (p = 0.018, OR 1.12). The median PFS was significantly shorter for high-risk tumors compared to the low-risk group (10 vs. 46 months; p = 0.018). The surviving meningioma patients showed HRQoL measures comparable to that of the general population, with the exception of significantly more anxiety and depression. All patients who worked before surgery returned to work after their treatment. In conclusion, we confirm dismal prognoses in patients with grade 2 and 3 meningiomas, with tumor-related deaths resulting in severely reduced OS. However, the cohort was heterogenous, and a large subgroup of both grade 2 and 3 meningiomas was alive at 10 years follow-up, suggesting that a cure is possible. In addition, fractionated radiotherapy and chemotherapy had little benefit when introduced for recurrent and progressive diseases.

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.

Loss of H3K27me3 in WHO grade 3 meningioma.

Immunohistochemical quantification of H3K27me3 was reported to distinguish meningioma patients with an unfavorable prognosis but is not yet established as a prognostic biomarker within WHO grade 3 meningiomas. We studied H3K27me3 loss in a series of biopsies from primary and secondary malignant meningioma to validate its prognostic performance and describe if loss of H3K27me3 occurs during malignant transformation. Two observers quantified H3K27me3 status as "complete loss", < 50% and > 50% stained cells in 110 tumor samples from a population-based consecutive cohort of 40 WHO grade 3 meningioma patients. We found no difference in overall survival (OS) in patients with > 50% H3K27me3 retention compared to < 50% in the cohort of patients with WHO grade 3 meningioma (Wald test p = 0.5). H3K27me3 staining showed heterogeneity in full section tumor slides while staining of the Barr body and peri-necrotic cells complicated quantification further. H3K27me3 expression differed without a discernible pattern between biopsies from repeated surgeries of meningioma recurrences. In conclusion, our results were not compatible with a systematic pattern of immunohistochemical H3K27me3 loss being associated with OS or malignant transformation of meningiomas and did not support H3K27me3 loss as a useful immunohistochemical biomarker within grade 3 meningiomas due to staining-specific challenges in quantification.

Adjuvant radiotherapy and stereotactic radiosurgery in grade 3 meningiomas - a systematic review and meta-analysis.

Malignant meningioma is a rare, aggressive form of meningioma. Radiation is commonly included in treatment guidelines either as adjuvant radiotherapy (RT) or stereotactic radiosurgery (SRS). Nevertheless, the treatment recommendations are not supported by prospective comparative trials and systematical, critical evaluation of supportive evidence is lacking. For this systematic review, studies analyzing the effectiveness of adjuvant RT and SRS in grade 3 (gr. 3) meningioma were reviewed. Thirty studies met the inclusion criteria for qualitative synthesis, and 6 studies were assessed in quantitative analysis. In quantitative analysis, the weighted average of hazard ratios for adjuvant RT in univariate analyses of overall survival (OS) was 0.55 (CI: 0.41; 0.69). The median 5-year OS after adjuvant RT in gr. 3 meningiomas was 56.3%, and the median OS ranged from 24 to 80 months for patients treated with adjuvant RT versus 13 to 41.2 months in patients not treated. For SRS, the 3-year progression free survival was 0% in one study and 57% in another. The 2-year OS ranged from 25 to 75% in 2 studies. The quality of evidence was rated as "very low" in 14 studies analyzed, and considerable allocation bias was detected. Treatment toxicity was reported in 47% of the studies. The severity, according to the CTCAE, ranged from grades I-V and 5.3 to 100% of patients experienced complications. Adjuvant RT is usually considered standard of care for WHO grade 3 meningiomas, although supporting evidence was of low quality. Better evidence from registries and prospective trials can improve the evidence base for adjuvant fractionated RT in malignant meningiomas.

The prognostic significance of biomarkers in cerebrospinal fluid following severe traumatic brain injury: a systematic review and meta-analysis.

After severe traumatic brain injury (sTBI) proteins, neurotrophic factors and inflammatory markers are released into the biofluids. This review and meta-analysis searched the literature for prognostic candidate cerebrospinal fluid markers and their relation to sTBI patient outcome. A systematic search of the literature was carried out across PubMed, EMBASE, PubMed Central (PMC), and Cochrane Central Library. Biomarker concentrations were related to the Glasgow Outcome Scale dichotomized into favorable and unfavorable outcomes. When a biomarker was reported in ≥ 3 studies, it was included in meta-analysis. The search returned 1527 articles. After full-text analysis, 54 articles were included, 34 from the search, and 20 from the reference lists. Of 9 biomarkers, 8 were significantly different compared to controls (IL-4, IL-6, IL-8, IL-10, TNFα, sFas, BDNF, and cortisol). Of these, 5 were significantly increased in sTBI patients with unfavorable outcome (IL-6, IL-8, IL-10, TNFα, and cortisol), compared to patients with favorable outcome. This review demonstrated a correlation between 5 biomarkers and clinical outcome in sTBI patients. The paucity of included studies, however, makes it difficult to extrapolate further on this finding.

Granular clinical history and outcome in 51 patients with primary and secondary malignant meningioma.

OBJECTIVE: WHO grade III meningiomas, also known as malignant meningiomas (MMs), are rare, and the heterogenous clinical course in patients with MM is not well described. To characterize the clinical course of patients with MM, granular clinical data were gathered from 51 patients treated at the Department of Neurosurgery and Radiation Oncology, Rigshospitalet, in Copenhagen, Denmark, between 2000 and 2020. METHODS: The authors investigated outcome and timing in terms of 1) tumor progression and grade transformation in patients previously diagnosed with WHO grade I or II meningiomas (patients with a secondary MM [sMM]); 2) performance status and complications following surgery; and 3) transition to noncurative treatment and ultimately death. Complications, time between recurrences, and outcome (modified Rankin Scale [mRS] score) for every surgery were analyzed, both malignant and premalignant. RESULTS: Of the 51 patients, 24 (47%) had an sMM. The time to WHO grade III transformation in the sMM group varied widely (median 5.5 years, range 0.5-22 years), but after transformation to a WHO grade III tumor, patients with an sMM and those with a primary MM (pMM) did not differ significantly in overall survival and cumulative risk of progression. Median overall survival for all 51 patients was 4.2 years (95% CI 2.6-7.2 years). Time from the decision to shift from curative to noncurative treatment until death was 3.8 months and the 30-day mortality rate following surgery was 11.8%. From a cumulative number of 151 surgeries, 10 surgeries were followed by improvement on the mRS, mRS score was unchanged in 70, and it worsened in 71. The MM was the underlying cause of death in 30 of 31 patients who had died at the end of follow-up. CONCLUSIONS: Together, these findings clearly show a significant morbidity and mortality from the disease itself and from the treatment. These findings warrant studies of prognostic factors for earlier support and adjuvant measures in MM and identify a need for better palliative strategies in this patient group.

[Arachnoid cysts can be associated with cognitive and affective symptoms].

Arachnoid cysts are frequent incidental findings on brain scans. Traditionally, they are regarded as harmless, congenital structures which do not require surgical treatment. In the rare cases where surgery is indicated it can be due to haemorrhage, hydrocephalus or cranial nerve affection caused by the cyst. However, recent literature suggests a correlation between arachnoid cysts and cognitive and affective symptoms. The hypothesised pathomechanisms include pressure, affected neuronal or glial metabolism and inflammation. If this is correct a more active approach might benefit the patients as suggested in this review.

The role of systemic inflammatory cells in meningiomas.

The aim of this review is to describe the inflammatory systemic cell infiltrate and its role in pathophysiology and prognostic implications of meningiomas. Articles from PubMed describing inflammation and immune cells in meningioma were systematically selected and reviewed. Infiltrating inflammatory cells are common in meningiomas and correlate with tumor behavior and peritumoral edema. The immune cell infiltrate mainly comprised macrophages, CD4 + T cells of the Th1 and Th2 subtype, CD8 + cytotoxic T cells, mast cells, and to a lesser degree B cells. The polarization of macrophages to M1 or M2 states, as well as the differentiation of T-helper cells to Th1 or Th2 subsets, is of prognostic value, but whether or not the presence of macrophages is associated with the degree of malignancy of the tumor is controversial. The best documented immunosuppressive and tumor-promoting mechanism is the expression of programmed cell death protein 1 (PD-1/PD-1L) which is found on both tumor cells and tumor-infiltrating immune cells. The immune cell infiltration varies between different meningiomas. It contributes to a microenvironment with potential contradictory effects on tumor growth and edema. The immune mechanisms are potential therapeutic targets provided that their effects can be comprehensively understood.

Implementation of TERT promoter mutations improve prognostication of the WHO classification in meningioma.

TERT promoter mutations have been associated with increased risk of recurrence in meningioma cohorts, thus a potential biomarker for aggressive phenotypes. A main purpose of refining tumour classification is better predictions on the patient level. We compiled data from previous published cohorts to investigate patient-level predictions of recurrence based on TERTp-mut status. Implementation of TERTp-mut into the WHO grading led to better patient prognostication by improved prediction of recurrence. Our results support implementation of TERTp-mut into diagnostics and classification of meningiomas.

Proposal of a new grading system for meningioma resection: the Copenhagen Protocol.

INTRODUCTION: The extent of meningioma resection is the most fundamental risk factor for recurrence, and exact knowledge of extent of resection is necessary for prognostication and for planning of adjuvant treatment. Currently used classifications are the EANO-grading and the Simpson grading. The former comprises radiological imaging with contrast-enhanced MRI and differentiation between "gross total removal" and "subtotal removal," while the latter comprises a five-tiered differentiation of the surgeon's impression of the extent of resection. The extent of resection of tumors is usually defined via analyses of resection margins but has until now not been implemented for meningiomas. PET/MRI imaging with 68Ga-DOTATOC allows more sensitive and specific imaging than MRI following surgery of meningiomas. OBJECTIVE: To develop an objective grading system based on microscopic analyses of resection margins and sensitive radiological analyses to improve management of follow-up, adjuvant therapy, and prognostication of meningiomas. Based on the rationale of resection-margin analyses as gold standard and superior imaging performance of 68Ga DOTATOC PET, we propose "Copenhagen Grading" for meningiomas. RESULTS: Copenhagen Grading was described for six pilot patients with examples of positive and negative findings on histopathology and DOTATOC PET scanning. The grading could be traceably implemented and parameters of grading appeared complementary. Copenhagen Grading is prospectively implemented as a clinical standard at Rigshospitalet, Copenhagen. CONCLUSION: Copenhagen Grading provided a comprehensive, logical, and reproducible definition of the extent of resection. It offers promise to be the most sensitive and specific imaging modality available for meningiomas. Clinical and cost-efficacy remain to be established during prospective implementation.

Long-term postoperative health-related quality of life in patients with subfrontal meningiomas.

OBJECTIVE: Subfrontal meningiomas grow insidiously in areas with high cerebral compliance and a relative scarcity of eloquent function. Symptoms develop progressively, are nonspecific, and include anosmia, changes in personality and cognition, depressive symptoms, headaches, visual disturbances, and seizures. Patients with subfrontal meningiomas carry the highest risk of developing psychological symptoms, which makes patient-reported outcome in terms of long-term health-related quality of life (HRQOL), anxiety, and depression of particular importance. This observational study aimed to investigate long-term HRQOL, anxiety, and depression in patients with subfrontal meningiomas who underwent a bifrontal craniotomy (subfrontal) approach between 2008 and 2017 at a single tertiary center. Correlations between preoperative, perioperative, and postoperative factors and HRQOL, anxiety, and depression were analyzed to detect prognostic factors. METHODS: Seventy-seven consecutive patients who underwent operations at Rigshospitalet, Copenhagen, Denmark, between 2008 and 2017 were retrospectively analyzed. Patients were prospectively invited to respond to the Functional Assessment of Cancer Therapy-General, Functional Assessment of Cancer Therapy-Brain, and Hospital Anxiety and Depression Scale. Information regarding preoperative, perioperative, and postoperative factors were collected from the patients' medical records and scans. RESULTS: Patients with subfrontal meningiomas exhibited better HRQOL and lower levels of anxiety and depression than general populations and other meningioma and glioblastoma cohorts. The only statistically significant prognostic factors for long-term HRQOL were number of symptoms at diagnosis and whether patients were discharged home or to a local hospital postoperatively. Tumor and peritumoral brain edema volumes were not prognostic factors. CONCLUSIONS: Patients with subfrontal meningiomas exhibited better long-term postoperative HRQOL and were less likely to have anxiety or depression than the reference populations. This information on long-term prognosis is very valuable for patients, next of kin, and neurosurgeons and has not been previously studied in detail.

Health-Related Quality of Life and Return to Work after Surgery for Spinal Meningioma: A Population-Based Cohort Study.

Spinal meningiomas are the most common primary spinal intradural tumor. This study aimed to assess Health-related quality of life (HRQoL) and the frequency of return to work in patients surgically treated for spinal meningiomas, in comparison to the general population. Variables were collected from patient charts, EQ-5D-3L, and study specific questionnaires. Patients who had been operated between 2005-2017 were identified in a previous study and those alive in 2020 (104 of 129) were asked to participate. Eighty-four patients (80.8%) with a mean follow-up of 8.7 years, responded and were included. Data was compared to the Stockholm Public Health Survey 2006, a cross-sectional survey of a representative sample of the general population. Analysis for potential non-response bias showed no significant differences. Women in the meningioma sample scored more problems than men with regards to mobility (p = 0.048). There were no significant differences concerning EQ-5Dindex (p = 0.325) or EQVAS (p = 0.116). The correlation between follow-up time and EQ-5Dindex was low (r = 0.167). When comparing HRQoL to the general population sample, no significant differences were found within the EQ-5D-3L dimensions, EQ-5Dindex or EQVAS. Those who postoperatively scored 3-5 on mMCs scored significantly more problems in the EQ-5D-3L dimension mobility (p = 0.023). Before surgery, 41 (48.8%) of the spinal meningioma patients were working and after surgery all returned to work, the majority within three months. Seventy-eight (96%) of the patients would accept surgery for the same diagnosis if asked today. We conclude that surgery for spinal meningiomas is associated with good long-term HRQoL and a high frequency of return to work.

Meningioma-Brain Crosstalk: A Scoping Review.

Background: In recent years, it has become evident that the tumoral microenvironment (TME) plays a key role in the pathogenesis of various cancers. In meningiomas, however, the TME is poorly understood, and it is unknown if glia cells contribute to meningioma growth and behaviour. Objective: This scoping review investigates if the literature describes and substantiates tumour-brain crosstalk in meningiomas and summarises the current evidence regarding the role of the brain parenchyma in the pathogenesis of meningiomas. Methods: We identified studies through the electronic database PubMed. Articles describing glia cells and cytokines/chemokines in meningiomas were selected and reviewed. Results: Monocytes were detected as the most abundant infiltrating immune cells in meningiomas. Only brain-invasive meningiomas elicited a monocytic response at the tumour-brain interface. The expression of cytokines/chemokines in meningiomas has been studied to some extent, and some of them form autocrine loops in the tumour cells. Paracrine interactions between tumour cells and glia cells have not been explored. Conclusion: It is unknown to what extent meningiomas elicit an immune response in the brain parenchyma. We speculate that tumour-brain crosstalk might only be relevant in cases of invasive meningiomas that disrupt the pial-glial basement membrane.