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Background: Spheno-orbital meningiomas (SOM) are known to invaded critical skull base areas. The authors report a series of WHO I SOM, propose a subclassification of this tumor according to its extension to critical positions and analyze the impact of extent of resection and the role of stereotactic radiotherapy in tumor recurrence., Methods: A prospective maintained university medical center registry was utilized to undertake a retrospective review of patients operated with WHO I SOM. Details related to critical skull base region's extension (superior orbital fissure, cavernous sinus, orbital apex), extent of resection and adjuvant radiosurgery were collected. Statistical calculations were preformed using IBM SPSS Statistics version 25. A p value < 0.05 was considered significant. Survival analysis was performed using Kaplan-Meier survival analysis and the log rank test., Results: A total of 77 patients operated from 2002 to 2021 were included. There were 65 women (84.4 %) and 12 men (15.6 %). Mean age at surgery was 54.8 years (median 53 years, range 23 - 88). Tumors were defined as local in 28 (35.4 %) and with extension into the skull base critical structures in 51 (64.6 %). GTR was achieved in 35 (44.3 %), STR in 40 (50.6 %), and PR in four (5.1 %). Surgical morbidity was 10 %. There was no surgical mortality. 28 patients with STR or PR were treated with adjuvant radiotherapy. The total length of follow up was a mean of 172.3 months. There were 14 recurrences/progressive growth (17.7 %), 63 patients (79.7 %) had no recurrence/progressive growth, and two patients (2.5 %) were lost to follow-up. PFS was significant statistically different in patients with invasive tumors in whom the extent of resection was subtotal, with a longer PFS in patients that were treated with adjuvant radiotherapy. (P value < 0.001)., Conclusions: SOM could be divided in two groups according to its skull base extension facilitating decision management and outcome prediction. Patients with local WHO I SOM had higher rate of GTR and better PFS than tumors extending to involve critical regions. When STR or PR is achieved postoperative adjuvant radiotherapy is advised if there is evidence of previous tumor growth., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: The role of stereotactic radiosurgery (SRS) in the management of grade 2 and 3 meningiomas is not well elucidated. Unfortunately, local recurrence rates are high, and guidelines for management of recurrent disease are lacking. To address this knowledge gap, we conducted STORM (Salvage Stereotactic Radiosurgery for Recurrent WHO Grade 2 and 3 Meningiomas), a multicenter retrospective cohort study of patients treated with primary SRS for recurrent grade 2 and 3 meningiomas., Methods and Materials: Data on patients with recurrent grade 2 and 3 meningioma treated with SRS at first recurrence were retrospectively collected from 8 academic centers in the United States. Patients with multiple lesions at the time of initial diagnosis or more than 2 lesions at the time of first recurrence were excluded from this analysis. Patient demographics and treatment parameters were extracted at time of diagnosis, first recurrence, and second recurrence. Oncologic outcomes, including progression-free survival (PFS) and overall survival, as well as toxicity outcomes, were reported at the patient level., Results: From 2000 to 2022, 108 patients were identified (94% grade 2, 6.0% grade 3). A total of 106 patients (98%) had upfront surgical resection (60% gross-total resection) with 18% receiving adjuvant radiation therapy (RT). Median time to first progression was 2.5 years (IQR, 1.34-4.30). At first recurrence, patients were treated with single or fractionated SRS to a median marginal dose of 16 Gy to a maximum of 2 lesions (87% received single-fraction SRS). The median follow-up time after SRS was 2.6 years. The 1-, 2-, and 3-year PFS was 90%, 75%, and 57%, respectively, after treatment with SRS. The 1-, 2-, and 3-year overall survival was 97%, 94%, and 92%, respectively. In the multivariable analysis, grade 3 disease (HR, 6.80; 95% CI, 1.61-28.6), male gender (HR, 3.48; 95% CI, 1.47-8.26), and receipt of prior RT (HR, 2.69; 95% CI, 1.23-5.86) were associated with worse PFS. SRS dose and tumor volume were not correlated with progression. Treatment was well tolerated, with a 3.0% incidence of grade 2+ radiation necrosis., Conclusions: This is the largest multicenter study to evaluate salvage SRS in recurrent grade 2 and 3 meningiomas. In this select cohort of patients with primarily grade 2 meningioma with a potentially more favorable natural history of delayed, localized first recurrence amenable to salvage SRS, local control rates and toxicity profiles were favorable, warranting further prospective validation., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Anaplastic meningiomas, categorized as WHO grade 3 tumors, are rare and highly aggressive, accounting for 1-2% of all meningioma cases. Despite aggressive treatment, including surgery and Radiation, they exhibit a high recurrence rate and poor survival outcomes. The aggressive histopathological features emphasize the urgent need for effective management strategies., Methods: A retrospective multi-institutional analysis was conducted on patients with recurrent anaplastic meningioma who underwent re-irradiation between 2017 and 2023. Clinical, dosimetric, and outcome data were collected and analyzed, focusing on local control, progression free survival and treatment-related adverse events., Results: Thirty-four cases were analyzed, with a median follow-up 11 months after re-irradiation. Progression-free survival at 12 months was 61.9%, with higher doses correlating with better outcomes. Concomitant Bevacizumab improves progression-free survival and reduces the risk of radiation necrosis. CDKN2A homozygote deletion correlated with a higher risk of local failure. Symptomatic radiation necrosis occurred in 20.5% of cases, but its incidence was lower with concomitant Bevacizumab treatment., Conclusion: Re-irradiation presents a viable option for recurrent anaplastic meningioma despite the associated risk of radiation necrosis. Higher doses with concomitant Bevacizumab improve clinical outcomes and reduce toxicity. Individualized treatment approaches are necessary, emphasizing the importance of further research to refine management strategies for this challenging disease., (© 2024. The Author(s).)

Purpose: To assess whether the Modified 5 (mFI-5) and 11 (mFI-11) Factor Frailty Indices associate with postoperative mortality, complications, and functional benefit in supratentorial meningioma patients aged over 80 years., Methods: Baseline characteristics were collected from eight centers. Based on the patients' preoperative status and comorbidities, frailty was assessed by the mFI-5 and mFI-11. The collected scores were categorized as "robust (mFI=0)", "pre-frail (mFI=1)", "frail (mFI=2)", and "significantly frail (mFI≥3)". Outcome was assessed by the Karnofsky Performance Scale (KPS); functional benefit was defined as improved KPS score. Additionally, we evaluated the patients' functional independence (KPS≥70) after surgery., Results: The study population consisted of 262 patients (median age 83 years) with a median preoperative KPS of 70 (range 20 to 100). The 90-day and 1-year mortality were 9.0% and 13.2%; we recorded surgery-associated complications in 111 (42.4%) patients. At last follow-up within the postoperative first year, 101 (38.5%) patients showed an improved KPS, and 183 (69.8%) either gained or maintained functional independence. "Severely frail" patients were at an increased risk of death at 90 days (OR 16.3 (CI95% 1.7-158.7)) and one year (OR 11.7 (CI95% 1.9-71.7)); nine (42.9%) of severely frail patients died within the first year after surgery. The "severely frail" cohort had increased odds of suffering from surgery-associated complications (OR 3.9 (CI 95%) 1.3-11.3)), but also had a high chance for postoperative functional improvements by KPS≥20 (OR 6.6 (CI95% 1.2-36.2))., Conclusion: The mFI-5 and mFI-11 associate with postoperative mortality, complications, and functional benefit. Even though "severely frail" patients had the highest risk morbidity and mortality, they had the highest chance for functional improvement., (© 2024. The Author(s).)

Purpose: Meningiomas classified as grade 2-3 according to the World Health Organisation (WHO) require combined surgery and in most cases radiotherapy (RT). Their initial management was evaluated using the Dutch Brain Tumour Registry., Methods: The study included 393 patients aged ≥ 18 years with newly diagnosed meningioma WHO grade 2-3 between 2016 and 2021. Factors associated with adjuvant RT < 6 months following surgery were identified using logistic regression analyses, thereby accounting for variation between CNS regional tumour boards through mixed-effect modelling. This variation was further assessed by funnel plots for case-mix adjusted ratios of RT across tumour boards. The association with patients' survival at 5 years was evaluated with inverse probability-weighted accelerated failure (Weibull) models. Analyses were performed on multiple imputed datasets (m = 10) to account for missing data., Results: Adjuvant RT was administered to 22.2% (59/266) of patients with WHO grade 2 meningioma following a total resection, to 61.1% (58/95) following a partial resection, and to 68.8% (22/32) of patients with WHO grade 3 meningioma (61.5% after partial and 73.7% after total resection). RT was associated with grade 3, partial resection, bone invasion, and absence of multiple lesions. Management varied across tumour boards for grade 2 meningioma following total resection. Adjuvant RT was associated with survival benefit in case of grade 3 disease (hazard ratio: 0.40, 95%-confidence interval: 0.16-0.95, p = 0.04)., Conclusion: This national review revealed variation across CNS regional tumour boards in the management of grade 2 meningioma following total resection, and demonstrated survival benefit of adjuvant RT in grade 3 meningioma., (© 2024. The Author(s).)

Introduction: WHO Grade 2 meningiomas present diagnostic and management challenges. Surgery, particularly gross total resection (GTR), is crucial, often followed by adjuvant radiotherapy (RT); however, there are clinical equipoise and ongoing randomized trials of RT after GTR., Methods: This systematic review evaluates the efficacy of gross total resection (GTR) and GTR plus adjuvant radiotherapy (RT) for WHO grade 2 meningiomas, adhering to PRISMA guidelines. It excludes irrelevant studies, conducts a thorough search until January 2024, and specifically analyzes overall survival (OS) and progression-free survival (PFS) outcomes for WHO grade 2 meningiomas. Statistical analysis adopts a two-stage approach with the R package "IPDfromKM," and quality assessment is conducted using the ROBINS-I tool., Results: In our analysis of 23 studies involving 3822 WHO grade 2 meningioma patients, GTR + RT resulted in a significantly longer PFS (HR: 0.849, 95% CI: 0.730 to 0.988, p = 0.035) compared to GTR alone. Although OS trended better with GTR + RT (HR: 0.79, 95% CI: 0.57 to 1.11, p = 0.173), the difference was not statistically significant, suggesting the need for further investigation., Conclusion: Our study reveals a benefit to adjuvant RT for improving PFS for WHO grade 2 meningiomas. Integrating molecular characteristics into treatment strategies will refine the management of these tumors in the future., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: This study aimed to examine the effect of postoperative radiotherapy on survival outcomes in patients with malignant meningiomas., Methods: We identified patients with malignant meningioma diagnosed between 2007 and 2018 using the Taiwan Cancer Registry and followed them up using the death registry. Survival was compared between patients with and without adjuvant radiotherapy. The potential confounding factors evaluated in this study included age, sex, comorbidities, and the Charlson Comorbidity Index (CCI)., Results: The analysis included 204 patients; 94 (46%) received adjuvant radiotherapy. The two groups had similar sex distributions (p = 0.53), mean age (p = 0.33), histologic subtype (p = 0.13), and CCI (p = 0.62). The prognosis of malignant meningioma was poor, with a median overall survival (OS) of 2.4 years. The median OS was 3.0 years (interquartile range (IQR) [1.4-6.1], and 2.0 years (IQR [0.5-3.9]) in the radiotherapy and non-radiotherapy groups, respectively (p = 0.001). However, Kaplan-Meier curves with the log-rank test showed no significant difference in OS between the two groups (p = 0.999). Controlling for age group, sex, histologic subtype, treatment, comorbidities, and CCI, adjuvant radiotherapy did not impart a survival benefit (hazard ratio [HR] = 0.87; 95% confidence interval [CI]: 0.6‒1.26); however, only factor of higher comorbidity score (HR = 2.03, 95%CI: 1.04‒3.94) was associated with unfavorable survival., Conclusion: This population-based retrospective analysis suggests that the role of radiotherapy remains unclear and underscores the need for randomized clinical trials to assess the usefulness of adjuvant radiotherapy in malignant meningioma., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To report the outcomes of a large series of intracranial meningiomas (IMs) submitted to proton therapy (PT) with curative intent., Methods: We conducted a retrospective analysis on all consecutive IM patients treated between 2014 and 2021. The median PT prescription dose was 55.8 Gy relative biological effectiveness (RBE) and 66 GyRBE for benign/radiologically diagnosed and atypical/anaplastic IMs, respectively. Local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), overall survival (OS), and radionecrosis-free survival (RNFS) were evaluated with the Kaplan-Meier method. Univariable analysis was performed to identify potential prognostic factors for clinical outcomes. Toxicity was reported according to the latest Common Terminology Criteria for Adverse Events (CTCAE) version 5.0., Results: Overall, 167 patients were included. With a median follow-up of 41 months (range, 6-99), twelve patients (7%) developed tumor local recurrence after a median time of 39 months. The 5-year LRFS was 88% for the entire cohort, with a significant difference between benign/radiologically diagnosed and atypical/anaplastic IMs (98% vs. 47%, p < 0.001); this significant difference was maintained also for the 5-year OS and the 5-year DRFS rates. Patients aged ≤ 56 years reported significantly better outcomes, whereas lower prescription doses and skull base location were associated with better RNFS rates. Two patients experienced G3 acute toxicities (1.2%), and three patients G3 late toxicities (1.8%). There were no G4-G5 adverse events., Conclusion: PT proved to be effective with an acceptable toxicity profile. To the best of our knowledge this is one of the largest series including IM patients submitted to PT., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: WHO Grade 3 (G3) meningiomas are rare tumours with limited data to guide management. This retrospective study documents UK management approaches across 14 centres over 11 years., Materials and Methods: Patients with WHO G3 meningioma between 01/01/2008 and 31/12/2018 were identified. Data were collected on demographics, management strategy, adjuvant radiotherapy, approach in recurrence setting and survival., Results: 84 patients were identified. 21.4% transformed from lower-grade disease. 96.4% underwent primary surgical resection, with 20.8% having evidence of residual disease on their post-op MRI. 59.3% of patients underwent adjuvant radiotherapy (RT) following surgical resection. Overall median PFS and OS were 12.6 months and 28.2 months, respectively. Median OS in the group who underwent complete surgical resection was 34.9 months, compared to 27.5 months for those who had incomplete resection (HR 0.58, 95% CI 0.27-1.23, p = 0.15). Median OS was 33.1 months for those who underwent adjuvant RT and 14.0 months for those who did not (HR 0.48, 95% CI 0.27-0.84, p = 0.004). Median adjuvant RT dose delivered was 60Gy (range 12Gy-60Gy), 45.8% of adjuvant RT was delivered using IMRT. At disease relapse, 31% underwent salvage surgery and 29.3% underwent salvage RT. Of those treated with salvage RT, 64.7% were re-treats and all were treated with hypofractionated RT., Conclusion: Surgery continues to be the preferred primary management strategy. Post-operative MRI within 48 hours is indicated to assess presence of residual disease and guide further surgical options. Adjuvant radiotherapy plays an important part of the management paradigm in these patients with the data supporting an attached survival advantage. Further surgery and re-irradiation is an option in the disease recurrence setting with radiosurgery frequently utilised in this context., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Purpose: To examine demographic and clinical characteristics and their association with survival in grade 2 and 3 pediatric meningiomas in a large cohort using the National Cancer Database (NCDB)., Methods: We conducted a comprehensive analysis using data from NCDB between 2004 to 2018. Tumor-specific data included tumor grade and size. Treatment details, including surgical resection, extent of resection, and radiotherapy, were gathered. Our analytic approach incorporated logistic and Poisson regression, Kaplan-Meier survival estimates, and Cox proportional hazards models., Results: Among the included 239 patients aged 0-21 years, age category distribution was significantly different between grade 2 and grade 3 tumors (p = 0.018). For grade 2 meningiomas, 51.5% of patients were female, and 76.7% were white. 85.3% of patients with grade 2 meningiomas underwent surgical resection, of which 67% underwent gross total resection. Overall survival (OS) was significantly different between resected and non-resected patients (p = 0.048). Uninsured patients were over seven times as likely to have prolonged length of stay (LOS) versus those with private insurance (OR = 7.663, p = 0.014). For grade 3 meningiomas, 51.4% of patients were male, and 82.9% were white. 91.4% of patients with grade 3 meningiomas underwent surgical resection, of which 53.3% underwent subtotal resection. OS was not significantly different between resected and non-resected patients (p = 0.659)., Conclusion: In summary, there were significant differences in age, maximum tumor dimension, unplanned readmission, radiotherapy, and treatment combinations between grade 2 and 3 meningiomas. These findings highlight the intricacies of managing pediatric meningiomas and emphasize the necessity for tailored therapeutic approaches to enhance outcomes in the future., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Frailty is an independent risk factor for adverse postoperative outcomes following intracranial meningioma resection (IMR). The role of the Risk Analysis Index (RAI) in predicting postoperative outcomes following IMR is nascent but may inform preoperative patient selection and surgical planning., Methods: IMR patients from the Nationwide Inpatient Sample were identified using diagnostic and procedural codes (2019-2020). The relationship between preoperative RAI-measured frailty and primary outcomes (non-home discharge (NHD), in-hospital mortality) and secondary outcomes (extended length of stay (eLOS), complication rates) was assessed via multivariate analyses. The discriminatory accuracy of the RAI for primary outcomes was measured in area under the receiver operating characteristic (AUROC) curve analysis., Results: A total of 23,230 IMR patients (mean age = 59) were identified, with frailty statuses stratified by RAI score: 0-20 "robust" (R)(N = 10,665, 45.9%), 21-30 "normal" (N)(N = 8,895, 38.3%), 31-40 "frail" (F)(N = 2,605, 11.2%), and 41+ "very frail" (VF)(N = 1,065, 4.6%). Rates of NHD (R 11.5%, N 29.7%, F 60.8%, VF 61.5%), in-hospital mortality (R 0.5%, N 1.8%, F 3.8%, VF 7.0%), eLOS (R 13.2%, N 21.5%, F 40.9%, VF 46.0%), and complications (R 7.5%, N 11.6%, F 15.7%, VF 16.0%) significantly increased with increasing frailty thresholds (p < 0.001). The RAI demonstrated strong discrimination for NHD (C-statistic: 0.755) and in-hospital mortality (C-statistic: 0.754) in AUROC curve analysis., Conclusion: Increasing RAI-measured frailty is significantly associated with increased complication rates, eLOS, NHD, and in-hospital mortality following IMR. The RAI demonstrates strong discrimination for predicting NHD and in-hospital mortality following IMR, and may aid in preoperative risk stratification., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: We conducted a National Cancer Database (NCDB) study to investigate the epidemiological characteristics and identify predictors of outcomes associated with geriatric meningiomas., Methods: The NCDB was queried for adults aged 60-89 years diagnosed between 2010 and 2017 with grade 2 and 3 meningiomas. The patients were classified into three age groups based on their age: 60-69 (hexagenarians), 70-79 (septuagenarians), and 80-89 (octogenarians). The log-rank test was utilized to compare the differences in overall survival (OS). Univariate and multivariate Cox proportional hazards regressions were used to evaluate the mortality risk associated with various patient and disease parameters., Results: A total of 6585 patients were identified. Hexagenerians were the most common age group (49.8%), with the majority of meningiomas being classified as grade 2 (89.5%). The incidence of high-grade meningiomas increased in all age groups during the study period. Advanced age, male sex, black race, lower socioeconomic status, Charlson-Deyo score ≥ 2, and higher tumor grade were independent factors of poor survival. Among the modes of treatment, the extent of surgical resection, adjuvant radiotherapy, and treatment at a noncommunity cancer program were linked with better outcomes., Conclusion: In geriatric patients with high-grade meningiomas, the greater extent of surgical resection and radiotherapy are associated with improved survival. However, the management and outcome of geriatric patients with higher-grade meningiomas are also associated with several socioeconomic factors., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Objectives: To find predictive biomarkers for recurrence and progression of meningioma., Background: Despite great advances in meningioma treatment, the prognosis remained unfavorable due to the high recurrence rate., Methods: In this study, we evaluated the immunohistochemical expression of FOXM1, MMP-9, and Ki67 in 50 cases of intracranial meningioma to detect its potential role in meningioma progression, recurrence, and patients' survival., Results: Strong FOXM1 expression was detected in 20% of the cases and was significantly associated with meningioma grade ( P = 0.002) and peritumoral brain edema (PTBE; P <0.001). Strong MMP-9 expression was noted in 32% of the cases and was significantly associated with meningioma grade and PTBE ( P <0.001, P <0.001, respectively). High Ki67 was noted in 50% and significantly associated with tumor grade and PTBE ( P <0.001, P = 0.002, respectively). The follow-up period revealed that meningiomas with strong FOXM1, strong MMP-9, and high Ki67 expression were associated with tumor recurrence, shorter OS, and recurrence-free survival. Furthermore, up-regulation of FOXM1 and MMP-9 expression had a significant relation with poor clinical response to the therapy ( P = 0.010, P = 0. 001, respectively). However, high Ki67 cases were more sensitive to clinical therapy ( P = 0.005)., Conclusion: Strong FOXM1, strong MMP-9, and high Ki67 in meningiomas indicate highly aggressive tumors with a shortened survival rate, dismal outcome, and high risk of recurrence after the standard protocol of therapy., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Meningiomas are the most frequent primary intracranial tumor. While histological grade and grade of excision are established predictors of recurrence, the predictive ability of other clinical features, such as the role of radical excision of dural attachment and postoperative radiation therapy in intermediate-risk groups, remains unknown., Methods: Clinical and radiological features and surgical details were analyzed in 451 World Health Organization (WHO) grade 1 intracranial meningiomas and 248 WHO grade 2 meningiomas operated on between 2010 and 2015. Outcomes were assessed in 352 WHO grade 1 and 208 WHO grade 2 meningiomas, studying the effect of extent of resection and use of radiation therapy. Kaplan-Meier analysis was used to determine differences in survival by extent of resection and use of postoperative radiation therapy in the treatment of the meningiomas., Results: The mean age of the cohort was 46.3 years, with a female predominance. On univariate analysis, sex, WHO grade, and Simpson grade were significant predictors of recurrence. On multivariate analysis, WHO grade and Simpson grade remained significant predictors of recurrence. Recurrence was significantly associated with poor performance status and mortality. Postoperative radiation significantly improved progression-free survival among patients with grade 2 meningiomas who underwent gross total resection, but not among patients with grade 1 and grade 2 meningiomas who underwent subtotal resection., Conclusions: WHO grade and Simpson grade are independent predictors of recurrence in meningiomas. Regardless of WHO grade, gross total resection must be performed when possible, and postoperative radiation therapy may be recommended in grade 2 meningiomas., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Giant meningiomas may show special features in terms of biological behavior and management. We aimed to research recurrence and mortality of giant meningiomas., Methods: Medical files of patients with meningioma with at least 1 dimension of ≥5 cm in any plane in radiological investigations between December 2012 and January 2022 were retrospectively reviewed. Tumor dimensions were measured on magnetic resonance images except 1. All patients except two underwent clinical follow-up at a mean of 27.19 ± 29.87 (range, 4-112) months., Results: There were 42 patients, 26 (61.9%) women and 16 (38.1%) men who ranged in age from 31 to 85 (mean, 60.31 ± 14.86) years. Headache (57.1%) was the most common symptom. The mean tumor size was 70.14 ± 19.03 (range, 50-152) mm. Tumors were most located at the frontal convexity (40.5%). Simpson grade I resection was achieved in 19% of the cases. The tumors were World Health Organization grade 1 in 74% and grade 2 in 26% of the cases. Major complications developed in 26.1% of the patients. Recurrence happened in 5 (11.9%) cases. The number of World Health Organization grade 2 tumors (P = 0.013; P < 0.05) and tumor size (P = 0.006; P < 0.01) were significantly higher in the recurrent cases. Mortality was % 11.9 and statistically significantly higher in the recurrence group (P = 0.025; P < 0.05)., Conclusions: Giant intracranial meningiomas are challenging because of surgical experience, tumor size, peritumoral edema, blood supply, anatomical changes, and limited visibility. They have a high risk of recurrence and mortality., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Re-irradiation (re-RT) for recurrent intracranial meningiomas is hindered by the limited radiation tolerance of surrounding tissue and the risk of side effects. This study aimed at assessing outcomes, toxicities and prognostic factors in a cohort of patients with recurrent meningiomas re-treated with different RT modalities., Materials and Methods: A multi-institutional database from 8 Italian centers including intracranial recurrent meningioma (RM) patients who underwent re-RT with different modalities (SRS, SRT, PT, EBRT) was collected. Biologically Equivalent Dose in 2 Gy-fractions (EQD2) and Biological Effective Dose (BED) for normal tissue and tumor were estimated for each RT course (α/β = 2 for brain tissue and α/β = 4 for meningioma). Primary outcome was second progression-free survival (s-PFS). Secondary outcomes were overall survival (OS) and treatment-related toxicity. Kaplan-Meier curves and Cox regression models were used for analysis., Results: Between 2003 and 2021 181 patients (pts) were included. Median age at re-irradiation was 62 (range 20-89) and median Karnofsky Performance Status (KPS) was 90 (range 60-100). 78 pts were identified with WHO grade 1 disease, 65 pts had grade 2 disease and 10 pts had grade 3 disease. 28 pts who had no histologic sampling were grouped with grade 1 patients for further analysis. Seventy-five (41.4 %) patients received SRS, 63 (34.8 %) patients SRT, 31 (17.1 %) PT and 12 (6.7 %) EBRT. With a median follow-up of 4.6 years (interquartile range 1.7-6.8), 3-year s-PFS was 51.6 % and 3-year OS 72.5 %. At univariate analysis, SRT (HR 0.32, 95 % CI 0.19-0.55, p < 0.001), longer interval between the two courses of irradiation (HR 0.37, 95 % CI 0.21-0.67, p = 0.001), and higher tumor BED (HR 0.45 95 % CI 0.27-0.76, p = 0.003) were associated with longer s-PFS; in contrast, Ki67 > 5 % (HR 2.81, 95 % CI 1.48-5.34, p = 0.002) and WHO grade > 2 (HR 3.08, 95 % CI 1.80-5.28, p < 0.001) were negatively correlated with s-PFS. At multivariate analysis, SRT, time to re-RT and tumor BED maintained their statistically significant prognostic impact on s-PFS (HR 0.36, 95 % CI 0.21-0.64, p < 0.001; HR 0.38, 95 % CI 0.20-0.72, p = 0.003 and HR 0.31 95 % CI 0.13-0.76, p = 0.01, respectively). Acute and late adverse events (AEs) were reported in 38 (20.9 %) and 29 (16 %) patients. Larger tumor GTV (≥10 cc) was significantly associated with acute and late toxicity (p < 0.001 and p = 0.009, respectively)., Conclusions: In patients with recurrent meningiomas, reirradiation is a feasible treatment option associated with acceptable toxicity profile. Prognostic factors in the decision-making process have been identified and should be incorporated in daily practice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Meningioma is the most common primary brain tumor and many studies have evaluated numerous biomarkers for their prognostic value, often with inconsistent results. Currently, no reliable biomarkers are available to predict the survival, recurrence, and progression of meningioma patients in clinical practice. This study aims to evaluate the prognostic value of immunohistochemistry-based (IHC) biomarkers of meningioma patients. A systematic literature search was conducted up to November 2023 on PubMed, CENTRAL, CINAHL Plus, and Scopus databases. Two authors independently reviewed the identified relevant studies, extracted data, and assessed the risk of bias of the studies included. Meta-analyses were performed with the hazard ratio (HR) and 95% confidence interval (CI) of overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS). The risk of bias in the included studies was evaluated using the Quality in Prognosis Studies (QUIPS) tool. A total of 100 studies with 16,745 patients were included in this review. As the promising markers to predict OS of meningioma patients, Ki-67/MIB-1 (HR = 1.03, 95%CI 1.02 to 1.05) was identified to associate with poor prognosis of the patients. Overexpression of cyclin A (HR = 4.91, 95%CI 1.38 to 17.44), topoisomerase II α (TOP2A) (HR = 4.90, 95%CI 2.96 to 8.12), p53 (HR = 2.40, 95%CI 1.73 to 3.34), vascular endothelial growth factor (VEGF) (HR = 1.61, 95%CI 1.36 to 1.90), and Ki-67 (HR = 1.33, 95%CI 1.21 to 1.46), were identified also as unfavorable prognostic biomarkers for poor RFS of meningioma patients. Conversely, positive progesterone receptor (PR) and p21 staining were associated with longer RFS and are considered biomarkers of favorable prognosis of meningioma patients (HR = 0.60, 95% CI 0.41 to 0.88 and HR = 1.89, 95%CI 1.11 to 3.20). Additionally, high expression of Ki-67 was identified as a prognosis biomarker for poor PFS of meningioma patients (HR = 1.02, 95%CI 1.00 to 1.04). Although only in single studies, KPNA2, CDK6, Cox-2, MCM7 and PCNA are proposed as additional markers with high expression that are related with poor prognosis of meningioma patients. In conclusion, the results of the meta-analysis demonstrated that PR, cyclin A, TOP2A, p21, p53, VEGF and Ki-67 are either positively or negatively associated with survival of meningioma patients and might be useful biomarkers to assess the prognosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Aung et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Psammomatous meningiomas (PMs) are a rare histological subtype of meningioma but are rather frequent in spinal meningiomas. The authors aimed to analyze the incidence, clinical features, molecular alterations, long-term outcomes, and prognostic factors of PMs., Methods: In total, 151 patients with PMs were included in this study. Clinical characteristics, molecular alterations, and progression-free survival (PFS) were analyzed in PMs. Clinical characteristics were compared between PMs and other WHO grade 1 meningiomas. Targeted sequencing of meningioma-relevant genes was performed to determine the molecular alterations in PMs., Results: PMs accounted for 1.34% of all meningiomas. Clinically, spinal location (p < 0.001) and female predominance (p < 0.001) were statistically significant in PMs when compared with the other grade 1 subtypes. Radiologically, calcification was frequently found in PMs (88.24%). Genetically, NF2 was the most frequently mutated gene in PMs (59.7%), followed by TRAF7 and AKT1. Ten patients experienced recurrence during the long-term follow-up. Multivariate analysis demonstrated that age (p = 0.009), extent of resection (p < 0.001), Ki-67 index (p = 0.007), and NF2 status (p < 0.001) were independent prognostic factors in the cohort of PMs. Interestingly, NF2 mutation was detected in all (48/48) spinal PMs (SPMs) but in only 38.46% (35/91) of cranial PMs (CPMs), revealing a significant difference (p < 0.001). The mean Ki-67 index (p = 0.044) and proportion of PMs with PR-positive expression (p = 0.048) were significantly higher in SPMs than in CPMs. The frequent NF2 mutations are associated with spinal location predominance and worse PFS in PMs., Conclusions: Female sex and spinal location predominance were statistically significant in PMs. NF2 mutation was an independent predictor for worse PFS of PMs. Of note, NF2 mutation was detected in all SPMs but in only 38.46% of CPMs, revealing a significant difference.

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., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Pro-tumorigenic electrochemical synapses between neurons and brain tumour cells in preclinical studies suggest unfavourable effects of epilepsy on patient survival. We investigated associations of epilepsy and survival in three cohorts of brain tumour patients (meningioma, glioblastoma and brain metastases). Cohorts were segregated into three groups for comparative analyses: (i) no epilepsy; (ii) epilepsy without status epilepticus; and (iii) status epilepticus. Status epilepticus was considered a surrogate of extensive neuronal hyperexcitability. The main outcome was progression-free survival (meningioma) and overall survival (glioblastoma and brain metastases), adjusted for established prognostic factors and onset of epilepsy by time-dependent multivariate Cox modelling. The primary analysis population comprised 1792 patients (742 meningioma, 249 glioblastoma, 801 brain metastases). Epilepsy was associated with favourable prognostic factors. However, on multivariate analyses, status epilepticus was associated with inferior overall survival of patients with glioblastoma [status epilepticus versus no epilepsy multivariate hazard ratio (HR) 3.72, confidence interval (CI) 1.78-7.76, P < 0.001] and brain metastases (status epilepticus versus no epilepsy HR 2.30, CI 1.10-4.79, P = 0.026). Among brain metastases patients, but not among patients with meningioma or glioblastoma, epilepsy was similarly associated with inferior overall survival (epilepsy versus no epilepsy HR 2.16, CI 1.60-2.93, P < 0.001). We conclude that epilepsy may convey inferior survival of patients with malignant brain tumours., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The objective of this study is to determine the population-based estimates of the epidemiology, incidence, and outcomes of spinal meningiomas., Methods: The data of patients with spinal meningiomas diagnosed between 2004 and 2016 were extracted from the SEER database. Descriptive analyses were conducted to evaluate the distribution and tumor-related characteristics of patients with spinal meningiomas. Multivariate logistic regression analysis was performed to predict which patients were inclined to be diagnosed with borderline or malignant spinal meningiomas. Possible prognostic indicators were analyzed by Kaplan-Meier curves and the Cox proportional hazards model., Results: The age-adjusted incidence rate was 0.37 cases per 1,000,000 person-years between 2004 and 2016. Spinal meningiomas represented 4.25% of all meningiomas. A total of 4204 patients with spinal meningiomas were included in our study. Most of the patients were white and diagnosed at 60-69 years of age, and the female:male ratio was 4:1. Most of the tumors were benign and less than 3 cm in size. The most common pathological type was psammomatous meningioma. Surgery was the first choice of treatment for patients with spinal meningiomas. Male and pediatric patients were more vulnerable to borderline or malignant spinal meningiomas. Survival analysis showed that married, female, and younger patients with benign meningiomas had better overall survival than their counterparts., Conclusion: Spinal meningiomas are relatively rare lesions with a favorable prognosis. Psammomatous meningioma is the most common subtype. Male and pediatric patients are more frequently diagnosed with borderline or malignant spinal meningiomas. Surgery is the primary choice of treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier Ltd.)

Objective: Subtotal meningioma resection (STR) is often performed to minimize surgical morbidity. Nevertheless, only a few studies have reported on patient outcome after STR. We studied the long-term outcome of SIV (Simpson grade IV) resection and identified predictive factors of overall survival (OS), progression-free survival (PFS) and time to progression (TTP)., Methods: A retrospective analysis was performed on 68 patients who underwent SIV resection of meningioma (grade I) from 2004 to 2010. Data were collected from clinical, surgical and pathology records and radiological imaging. Long-term outcomes were evaluated at least 10 years after surgery., Results: Permanent morbidity was 11.8%, 30-day mortality 2.9% and progression rate 50.0% for a median follow-up duration of 126.6 months. Median TTP was 86.2 months. Adjuvant SRS was the only significant factor associated with longer PFS (p = 0.0052) and TTP (p = 0.0079). Higher age (p = 0.0022), KPS (p = 0.0182), postoperative ECOG score (p = 0.0182) were reliable predictors of shortened OS and aSRS (p = 0.0445) was reliable predictor of longer OS., Conclusion: STR in intracranial meningioma is still viable and often the only treatment option available in high-risk patients or high-risk tumors. Although surgical morbidity and mortality are high, the OS rate was 85.3% at 5 years and 79.4% at 10 years. Because of the considerable progression rate and rather a long term OS the adjuvant SRS should be considered following SIV resection., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Rhabdoid Meningiomas (RM) are rare malignant type of meningiomas, classified as grade III in the WHO classification. Only a few case series have been reported, and factors affecting prognosis are still unclear., Methods: We did a retrospective chart review of all the RMs diagnosed in our institute between 2007 and 2019. Demographic profile, clinical status, imaging, surgical procedures used, post-operative course, adjuvant therapy and follow-ups were reviewed. Histopathological slides were also reviewed., Results: There were 11 patients with RM who underwent 17 surgical procedures between them. Median age was 26 years. On imaging, four had lesions in skull base, three in convexity and four in parasagittal region. Five patients had lesions which had bled and two had leptomeningeal dissemination. Two patients underwent Simpson's grade 1 excision, seven underwent grade 2 and one patient each underwent grade 3 and 5 excisions. One patient presented with poor sensorium and underwent surgery but ultimately succumbed. All reported patients had Rhabdoid features (>50%). Features of anaplasia were seen in four cases and atypical meningioma in others. The median progression-free-survival and overall survival was 6 months and 9 months, respectively. Female gender (n = 5; p = 0.032) and patients who received radiotherapy (p = 0.030) had a survival advantage. Location of the tumor (p = 0.43), presence of hemorrhage in the lesion (p = 0.49), grade of excision (p = 0.40) and WHO pathological grade (p = 0.11) did not have a statistically significant survival benefit., Conclusion: Female gender and adjuvant radiotherapy were associated with survival advantage in our sample. Large studies are required to establish the factors associated with survival., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Meningiomas are the most commonly diagnosed benign intracranial adult tumors. Subsets of meningiomas that present with extensive invasion into surrounding brain areas have high recurrence rates, resulting in difficulties for complete resection, substantially increased mortality of patients, and are therapeutically challenging for neurosurgeons. Exciting new data have provided insights into the understanding of the molecular machinery of invasion. Moreover, clinical trials for several novel approaches have been launched. Here, we will highlight the mechanisms which govern brain invasion and new promising therapeutic approaches for brain-invasive meningiomas, including pharmacological approaches targeting three major aspects of tumor cell invasion: extracellular matrix degradation, cell adhesion, and growth factors, as well as other innovative treatments such as immunotherapy, hormone therapy, Tumor Treating Fields, and biodegradable copolymers (wafers), impregnated chemotherapy. Those ongoing studies can offer more diversified possibilities of potential treatments for brain-invasive meningiomas, and help to increase the survival benefits for patients., (© 2021. The Japan Society of Brain Tumor Pathology.)

Meningiomas are benign tumors that are treated surgically. Local recurrence is likely if the dura is preserved, and en bloc tumor and dura resection (Simpson grade I) is recommended. In some cases the dura is cauterized and preserved after tumor resection (Simpson grade II). The purpose of this study was performed to analyze clinical features and prognostic factors associated with spinal meningioma, and to identify the most effective surgical treatment. The subjects were 116 patients (22 males, 94 females) with spinal meningioma who underwent surgery at seven NSG centers between 1998 and 2018. Clinical data were collected from the NSG database. Pre- and postoperative neurological status was defined using the modified McCormick scale. The patients had a mean age of 61.2 ± 14.8 years (range 19-91 years) and mean symptom duration of 11.3 ± 14.7 months (range 1-93 months). Complete resection was achieved in 108 cases (94%), including 29 Simpson grade I and 79 Simpson grade II resections. The mean follow-up period was 84.8 ± 52.7 months. At the last follow-up, neurological function had improved in 73 patients (63%), was stable in 34 (29%), and had worsened in 9 (8%). Eight patients had recurrence, and recurrence rates did not differ significantly between Simpson grades I and II in initial surgery. Kaplan-Meier analysis of recurrence-free survival showed that Simpson grade III or IV, male, and dural tail sign were significant factors associated with recurrence (P < 0.05). In conclusion, Simpson I resection is anatomically favorable for spinal meningiomas. Younger male patients with a dural tail and a high-grade tumor require close follow-up. The tumor location and feasibility of surgery can affect the surgical morbidity in Simpson I or II resection. All patients should be carefully monitored for long-term outcomes, and we recommend lifelong surveillance after surgery.

Background: Decision about treatment of incidentally found intracranial meningiomas is controversial and conditioned by the growth potential of these tumors. We aimed to evaluate the growth rate of a cohort of incidentally found asymptomatic meningiomas and to analyze their natural course and the need for eventual treatment., Methods: A total of 193 patients harboring intracranial meningiomas (85 with 109 incidental and 108 with 112 symptomatic) were included between 2015 and 2019. In the prospective cohort of incidental meningiomas, we measured size at diagnosis, volumetric growth rate (by segmentation software), appearance of symptoms, and need for surgery or radiotherapy. Progression-free survival and risk factors for growth were assessed with Kaplan-Meier survival and Cox regression analyses., Results: Among incidental meningiomas, 94/109 (86.2%) remained untreated during a median follow-up of 49.3 months. Tumor growth was observed in 91 (83.5%) and > 15% growth in 40 (36.7%). Neurological symptoms developed in 1 patient (1.2%). Volume increased an average of 0.51 cm 3 /year (95% CI, 0.20-0.82). Nine patients were operated (9.2%) and 4 underwent radiotherapy (4.7%). Treatment-related complication rates of incidental and symptomatic meningiomas were 0% and 35.4%, respectively. Persistent neurological defects occurred in 46 (40.7%) of symptomatic versus 2 (2.3%) of incidental meningiomas. Among covariates, only brain edema resulted in an increased risk of significant tumor growth in the female subgroup (Cox regression HR 2.96, 95% CI 1.02-8.61, p = 0.046). Size at diagnosis was significantly greater in the symptomatic meningioma group (37.33 cm 3 versus 4.74 cm 3 , p < 0.001)., Conclusions: Overall, 86% of incidentally found meningiomas remained untreated over the first 4 years of follow-up. The majority grew within the 20% range, yet very few developed symptoms. Treatment-related morbidity was absent in the incidental meningioma group.

Background: Meningiomas are the most frequent brain tumours occurring after pediatric cranial radiotherapy (CrRT). Data on course of disease, to inform clinical management of meningiomas, are sparse. This study reports the clinical characteristics of histologically confirmed meningiomas in childhood cancer survivors (CCS) in the Netherlands., Methods: In total, 6015 CCS from the Dutch Long-Term Effects After Childhood Cancer (LATER) cohort were eligible, including 1551 with prior CrRT. These CCS were diagnosed with cancer age <18 y (between 1963 and 2002) and are not subject to brain tumour screening. We identified histologically confirmed meningiomas by record linkage with the Dutch Pathology Registry (PALGA; 1991-2018), and in the Dutch LATER registry. We extracted details regarding diagnosis, treatment, and follow-up from medical records., Results: We described 93 CCS with meningioma, of whom 89 (95.7%) were treated with CrRT (5.7% of 1551 with prior CrRT; OR = 68). Median age at diagnosis was 31.8 y (range: 13.2-50.5). Thirty survivors (32.3%) had synchronous meningiomas; 84 (90.3%) presented with symptoms. Only 16.1% of meningioma was detected at late effects clinics. Over time, all survivors had surgery; one-third also received radiotherapy. During follow-up 38 (40.9%), survivors developed new meningiomas, 22(23.7%) recurrences and at least four died due to the meningioma., Conclusions: Histologically confirmed meningiomas after childhood cancer are mostly diagnosed with symptoms and not during routine follow-up at late effects clinics. The meningiomas occur at a median of 20-25 y younger age than incidental meningiomas, are frequently multiple and recurrence after treatment is high. It is crucial to inform CCS and healthcare providers about risk and symptoms of subsequent meningiomas., Competing Interests: Conflict of interest statement The authors have no conflicts of interest to disclose., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The use of stereotactic radiosurgery for the treatment of intracranial meningiomas has been established as an effective and safe treatment modality. Larger meningiomas typically are managed by surgery followed by radiosurgery. Treatment of large meningiomas (usually defined as >10 cc) by stereotactic radiosurgery has been investigated in some recent reports, either by single-session, volume-staged, or the hypofractionation technique. We sought to assess the long-term efficacy and safety of single-session stereotactic radiosurgery for large (10 cc or more) intracranial benign meningiomas., Patients and Methods: In this retrospective study, we included 273 patients with large benign meningiomas (≥10 cc) who were treated by single-session SRS and followed up for more than 2 years. Tumors were in a basal location in 228 patients (84%). There were 161 tumors (59%) in the perioptic location. The median tumor volume was 15.5 (10-57.3 cc [interquartile range {IQR} 12.3 cc]). The median prescription dose was 12 Gy (9-15 Gy [IQR 1 Gy])., Results: The median follow-up period was 6.1 years (2-18 years [IQR 5.5 years]). The tumor control rate was 90%. The progression-free survival at 5 and 10 years was 96% and 81%, respectively, for the whole cohort. Among 161 patients with perioptic meningiomas, favorable (better/stable) visual outcome was reported in 155 patients (96%) and unfavorable (worse) outcome in 6 patients (4%). Temporary adverse radiation effects were observed in 41 patients (15%) but only 16 (6%) were symptomatic., Conclusions: Stereotactic radiosurgery provides an effective and safe treatment option for large meningiomas., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Population aging is likely increasing the number of surgically treated very old (≥ 80-year-old) intracranial meningioma (IM) patients. Since there is little data on mortality in this patient group, we studied whether survival of surgically treated very old IM patients differs from survival of a matched general population. We retrospectively identified 83 consecutive very old IM patients (median age 83 years; 69% women) operated between 2010 and 2018. During the first postoperative year, operated IM patients suffered 2.5 times higher mortality as compared to age- and sex-matched general population but no annual survival difference occurred thereafter. Regarding cumulative estimates, no excess mortality was detected after the second postoperative year. Of the patient who were and who were not able to live at home preoperatively, 78% and 42% lived at home within 3 months, respectively. Preoperative loss of capability to live at home associated with a less frequent return to home [odds ratio (95% confidence interval) 0.21 (0.06-0.67)]. Operated very old IM patients had short-term excess mortality but similar cumulative survival as the matched general population. Moreover, most patients returned home soon after surgery.

Background: Atypical meningiomas (AMs) are meningiomas that have a higher rate of recurrence than grade I meningioma. Due to the higher risk of recurrence, adjuvant radiotherapy (RT) after resection of AM has been employed. At our institution, some neurosurgeons employ adjuvant RT on all primarily resected AMs, while others employ watchful waiting with serial imaging., Objective: To study the effect of adjuvant RT on newly resected AMs., Methods: A retrospective review of all AMs primarily resected at our institution from 1996 to 2018 was completed. Data on patient demographics, radiographic findings, use of adjuvant RT, time of follow-up, and recurrences were collected. Adjuvant RT was defined as RT that occurred within 6 mo of initial resection., Results: A total of 162 patients met the inclusion criteria. Gross total resection was achieved in 73% of cases. Average time until recurrence in the cohort was 37 mo. A total of 108 patients had adjuvant RT, while 54 patients did not. On multivariate survival analysis, sex, Simpson grade resection, and use of adjuvant RT were independent predictors of recurrence. Mean time to recurrence in patients who received adjuvant RT was 43.7 mo versus 34.7 mo for those who did not receive adjuvant RT., Conclusion: This study includes the largest retrospective cohort of patients who have received adjuvant RT after primary resection of AM. Our results suggest that the use of adjuvant RT is independently associated with a lower chance of recurrence. These data suggest that practitioners can consider the use of adjuvant RT for newly resected AMs, regardless of Simpson grade resection., (© Congress of Neurological Surgeons 2021.)

Background: Atypical and anaplastic meningiomas have reduced progression-free/overall survival (PFS/OS) compared to benign meningiomas. Stereotactic radiosurgery (SRS) for atypical meningiomas (AMs) and anaplastic meningiomas (malignant meningiomas, MMs) has not been adequately described., Objective: To define clinical/radiographic outcomes for patients undergoing SRS for AM/MMs., Methods: An international, multicenter, retrospective cohort study was performed to define clinical/imaging outcomes for patients receiving SRS for AM/MMs. Tumor progression was assessed with response assessment in neuro-oncology (RANO) criteria. Factors associated with PFS/OS were assessed using Kaplan-Meier analysis and a Cox proportional hazards model., Results: A total of 271 patients received SRS for AMs (n = 233, 85.9%) or MMs (n = 38, 14.0%). Single-fraction SRS was most commonly employed (n = 264, 97.4%) with a mean target dose of 14.8 Gy. SRS was used as adjuvant treatment (n = 85, 31.4%), salvage therapy (n = 182, 67.2%), or primary therapy (1.5%). The 5-yr PFS/OS rate was 33.6% and 77.0%, respectively. Increasing age (hazard ratio (HR) = 1.01, P < .05) and a Ki-67 index > 15% (HR = 1.66, P < .03) negatively correlated with PFS. MMs (HR = 3.21, P < .05), increased age (HR = 1.04, P = .04), and reduced KPS (HR = 0.95, P = .04) were associated with shortened OS. Adjuvant versus salvage SRS did not impact PFS/OS. A shortened interval between surgery and SRS improved PFS for AMs (HR = 0.99, P = .02) on subgroup analysis. Radiation necrosis occurred in 34 (12.5%) patients. Five-year rates of repeat surgery/radiation were 33.8% and 60.4%, respectively., Conclusion: AM/MMs remain challenging tumors to treat. Elevated proliferative indices are associated with tumor recurrence, while MMs have worse survival. SRS can control AM/MMs in the short term, but the 5-yr PFS rates are low, underscoring the need for improved treatment options for these patients., (© Congress of Neurological Surgeons 2021.)

The WHO 2016 classification introduced brain invasion as a standalone criterion for grade II meningioma (GIIM). We systematically reviewed studies published after 2000 and performed a PRISMA-compliant meta-analysis of the hazard ratios (HRs) for progression-free survival (PFS) between brain-invasive and noninvasive meningiomas. In five studies that included both benign and higher-grade meningiomas, brain invasion was a significant risk factor for recurrence (HR = 2.45, p = 0.0004). However, in 3 studies comparing "brain-invasive meningioma with otherwise benign histology (BIOB)" with grade I meningioma, brain invasion was not a significant predictor of PFS (HR = 1.49, p = 0.23). Among GIIM per the WHO 2000 criteria, brain invasion was a significant predictor of shorter PFS than noninvasive GIIM (HR = 3.40, p = 0.001) but not per the WHO 2016 criteria (HR 1.13, p = 0.54), as the latter includes BIOB. Meta-regression analysis of seven studies of grade II meningioma showed that more frequent BIOB was associated with lower HRs (p < 0.0001). Hence, there is no rationale for brain invasion as a standalone criterion for grade II meningioma, although almost all studies were retrospective and exhibited highly heterogeneous HRs due to differences in brain-tumor interface data availability.

Background: Meningiomas are common brain tumours that are usually defined by benign clinical course. However, some meningiomas undergo a malignant transformation and recur within a short time period regardless of their World Health Organization (WHO) grade. The current study aimed to identify potential markers that can discriminate between benign and malignant meningioma courses., Methods: We profiled the metabolites from 43 patients with low- and high-grade meningiomas. Tumour specimens were analyzed by nuclear magnetic resonance analysis; 270 metabolites were identified and clustered with the AutoPipe algorithm., Results: We observed two distinct clusters marked by alterations in glycine/serine and choline/tryptophan metabolism. Glycine/serine cluster showed significantly lower WHO grades and proliferation rates. Also progression-free survival was significantly longer in the glycine/serine cluster., Conclusion: Our findings suggest that alterations in glycine/serine metabolism are associated with lower proliferation and more recurrent tumours. Altered choline/tryptophan metabolism was associated with increases proliferation, and recurrence. Our results suggest that tumour malignancy can be reflected by metabolic alterations, which may support histological classifications to predict the clinical outcome of patients with meningiomas.

Background: The impact of adjuvant radiotherapy (RT) on atypical meningioma (AM) underwent a gross total resection (GTR) remains unclear, showing conflicting results from various studies. The objective of this study was to perform an updated meta-analysis for observational studies to determine the effect of adjuvant RT after GTR on local recurrence and survival outcomes compared to observation after GTR., Methods: PubMed, Embase, and Web of Science were searched to identify comparative studies that reported outcomes of adjuvant RT versus observation for AM patients after GTR. Local recurrence rate, progression-free survival (PFS), overall survival (OS), and toxicities related to RT were considered as outcomes of interest. Differences between two cohorts were estimated by calculating odds ratios (OR) for LR rate and hazard ratios (HR) for survival outcomes with 95% confidence intervals (CIs) for meta-analysis, using R version 4.0.3 software. Included studies were appraised with the Risk of Bias Assessment tool for Non-Randomized Studies. Outcome ratios were combined with the Mantel-Haenszel method and the inverse variance-weighted method, appropriately., Results: Data from 30 studies involving 2904 patients (adjuvant RT: n = 737; observation: n = 2167) were eventually included. Significant reduction of local recurrence rate was seen in the adjuvant RT cohort compare to that in the observation cohort (OR 0.50; 95% CI 0.36-0.68; p < 0.0001). Pooled HRs of PFS at 1-year, 3-year, 5-year, and > 5-year revealed that adjuvant RT was superior to observation. There was no significant difference in OS between the two cohorts during any period. Most toxicities were tolerable with grade 1 or 2. There was no documented grade 5 toxicity., Conclusions: For AM patients who underwent GTR, evidence suggested that adjuvant RT could potentially decrease local recurrence and improve PFS better than observation.

Background: Survival after meningioma surgery often is reported with inadequate allowance for competing causes of death., Methods: We processed the French Système National des Données de Santé database using an algorithm combining the type of surgical procedure and the International Classification of Diseases to retrieve appropriate cases of meningiomas. The cumulative incidence of meningioma-related death was the primary end point. A competing risk analysis was performed to identify factors associated with meningioma-specific death of patients who underwent meningioma surgery., Results: The risk of meningioma-related death at 1, 2, and 3 years respectively was 2.4%, 95% confidence interval [CI] 2-2.7; 3%, 95% CI 2.6-3.4; and 3.1%, 95% CI 2.7-3.6. In the adjusted Fine-Gray competing risk regression for meningioma cause-specific survival, age at surgery (subdistribution hazard ratio [SHR] 1.07, 95% CI 1.05-1.09, P < 0.001), mortality-related morbidity index (SHR 1.68, 95% CI 1.07-2.63, P = 0.025), expenditure-related morbidity index (SHR 1.06, 95% CI 1.03-1.09, P < 0.001), spinal location (SHR 0.2, 95% CI 0.08-0.47, P < 0.001), cerebrospinal fluid shunt (SHR 3.13, 95% CI 1.9-5.16, P < 0.001), grade (SHR 1.88, 95% CI 1.13-3.14, P = 0.015) redo surgery for recurrence (SHR 1.6, 95% CI 1.01-2.51, P = 0.043), and progressing meningioma (SHR 2.87, 95% CI 1.23-6.68, P = 0.015) were established as independent prognostic factors of meningioma-related death., Conclusions: Cause-specific survival after meningioma surgery is greater in younger, low-comorbidity adults with spinal and benign meningioma. Those with an intracranial, progressing malignant tumor requiring cerebrospinal fluid shunting and having a severe global health-state have a significant increased risk of meningioma-related death. Redo surgery failed to improve the outcome. We recommend the use of competing risk model in meningioma studies in which unrelated mortality may be substantial, as this approach results in more accurate estimates of disease risk and associated predictors., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: There are very few nationwide studies on meningioma outcome, the most common primary intracranial tumour., Methods: We processed the French Système National des Données de Santé (SNDS) database using an algorithm combining the type of surgical procedure and the International Classification of Diseases to retrieve all cases of meningiomas operated between 2007 and 2017. A survival analysis was performed., Results: This nationwide study found 28 773 patients of which 75 % were female. Median age at surgery was 59 years, IQR[49-68]. Cranial convexity (24.4 %) and middle skull base (21.7 %) were the most common locations. 91.3 % of the tumours were benign and 2.6 % malignant.7.5 % of the patients underwent redo surgery, 9.1 % radiotherapy (RT) and 3.2 % stereotactic radiosurgery for recurrence. Median follow-up was 5.3 years 95 % CI [5.24-5.35]. 0.64 % of the patients died within a month of surgery and 2.1 % within a year. Overall survival (OS) rates at 5 and 10 years respectively were: 92.6 %, 95 %CI[92.3, 93] and 85 %, 95 %CI[84.3, 85.8]. In the multivariable analysis, female gender (HR = 0.64, 95 %CI[0.59, 0.69], p < 0.001), older age at surgery (HR= 1.07, 95 %CI[1.06, 1.07], p < 0.001), type 2 neurofibromatosis (HR= 3.89, 95 %CI[2.62, 5.76], p < 0.001), parasagittal (HR= 1.2, 95 %CI[1.05, 1.37], p = 0.00944) or falx cerebri location (HR= 1.18, 95 %CI[1.01, 1.37], p = 0.0343), atypical or (HR= 1.34, 95 %CI[1.15, 1.56], p < 0.001) malignant histology (HR= 2.34, 95 %CI[2.01, 2.73], p < 0.001), redo surgery (HR=1.81, 95 %CI[1.6, 2.04], p < 0.001), progressing meningioma (HR=1.34, 95 %CI[1.05, 1.71], p = 0.0175) or RT for recurrence (HR=2.17, 95 %CI[1.95, 2.4], p < 0.001) were established as independent prognostic factors of the OS., Conclusion: In this registry-based study, OS after meningioma surgery is good and is even better in women, younger adults and those with convexity and benign tumour. We also found that NF2 patients and those required redo surgery or additional treatment for uncontrolled meningioma disease are further at risk of death., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: No large-scale study evaluating the usefulness of tamoxifen after meningioma surgery has been undertaken., Methods: We processed the French Système National des Données de Santé (SNDS) database using an algorithm combining the type of surgical procedure and the International Classification of Diseases to retrieve cases of meningiomas operated between 2007 and 2017. Survival analyses were performed using a matched cohort study., Results: 251 patients treated by tamoxifen were extracted from a nationwide population-based cohort of 28 924 patients operated on for a meningioma over a 10-year period. 94% were female and median age at meningioma first surgery was 57 years IQR[47-67]. Tamoxifen treatment median duration was 1.4 years IQR[0.4-3.2]. Tamoxifen treatment median cumulative given dose was 11.4 gs, IQR[3.6-24.9]. There was a strong positive correlation between treatment duration and cumulative dose (τ=0.81, p<0.001). 6% of the patient had to be reoperated for a meningioma recurrence and 26.3% had radiotherapy. OS rates at 5 and 10 years were: 92.3%, 95% CI[90.3-94.3] and 81.3%, 95% CI[75.2-88] respectively. These 251 patients were matched by gender, age at surgery and grade with the same number of subjects within the nationwide cohort. Nor overall (HR=1.46, 95% CI[0.86- 2.49], p=0.163) or progression-free survival (HR=1.2, 95% CI[0.89- 1.62], p=0.239) were significantly improved by the tamoxifen treatment., Conclusion: Using this unique database, in the setting of breast cancer, we could not conclude on a favourable effect of tamoxifen to prevent recurrence after meningioma surgery or to increase meningioma-related survival even in case of prolonged treatment duration or high cumulative given dose., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Clear cell meningioma (CCM) is a rare WHO grade II meningioma variant, characterized by aggressive features and a high tumor recurrence rate. In this study, we compared overall and progression-free survivals between CCMs and other WHO grade II meningiomas., Methods: A retrospective institutional database review was performed to identify all patients who underwent surgical resection of a WHO grade II meningioma between 1997 and 2019. Overall survival and progression-free survival were compared between patients with clear cell meningiomas and patients with other WHO grade II meningiomas. Multivariable Cox proportional-hazards analysis was used to identify independent predictors of tumor recurrence and survival., Results: We included a total of 214 patients in this study (43 CCMs, 171 other WHO grade II meningiomas). Patients with CCMs had significantly shorter progression-free (p = 0.001) and overall (p = 0.026) survivals than patients with other grade II meningiomas. In multivariable analysis, clear cell histology was a significant and powerful independent predictor of tumor recurrence (HR 1.93; 95% CI 1.14-3.26) when controlling for tumor location, extent of resection, and adjuvant radiation. In multivariable analysis, clear cell histology correlated with increased mortality (HR 1.96, 95% CI 0.97-3.94), though this was not statistically significant., Conclusion: This is the first study to compare overall and progression-free survivals between CCMs and other WHO grade II meningiomas. Clear cell histology predicts a higher risk of tumor recurrence and mortality than other grade II histologies. Future studies may help to understand the impact of these findings and the treatment implications.

Background: Meningioma is a common intracranial tumor originating from arachnoid cap cells. Meningiomas are generally benign tumors curable by one-time resection. However, some meningiomas regrow and invade into the dura mater, and thus frequently require additional treatment. A useful marker to predict the regrowth of meningioma is desired. This study aimed to clarify the significance of p53 and Ki67 for postoperative recurrence of meningioma., Materials and Methods: The expression of p53 and Ki67 in 215 intracranial or intraspinal meningiomas was investigated by immunohistochemistry., Results: Of the 215 meningiomas, 35 cases (16.3%) were p53-positive and 49 cases (22.8%) were Ki67-positive. Multivariate analysis revealed Ki67 and p53 status as being significantly correlated with recurrence. Positivity for either Ki67- or p53 was significantly associated with poor recurrence-free survival., Conclusion: Combined p53 and Ki67 status might represent a useful independent predictive marker for recurrence of meningioma., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: WHO grade II meningiomas behave aggressively, with recurrence rates as high as 60%. Although complete resection in low-grade meningiomas is associated with a relatively low recurrence rate, the impact of complete resection for WHO grade II meningiomas is less clear. We studied the association of extent of resection with overall and progression-free survivals in patients with WHO grade II meningiomas., Methods: A retrospective database review was performed to identify all patients who underwent surgical resection for intracranial WHO grade II meningiomas at our institution between 1995 and 2019. Kaplan-Meier analysis was used to compare overall and progression-free survivals between patients who underwent gross total resection (GTR) and those who underwent subtotal resection (STR). Multivariable Cox proportional-hazards analysis was used to identify independent predictors of tumor recurrence and mortality., Results: Of 214 patients who underwent surgical resection for WHO grade II meningiomas (median follow-up 53.4 months), 158 had GTR and 56 had STR. In Kaplan-Meier analysis, patients who underwent GTR had significantly longer progression-free (p = 0.002) and overall (p = 0.006) survivals than those who underwent STR. In multivariable Cox proportional-hazards analysis, GTR independently predicted prolonged progression-free (HR 0.57, p = 0.038) and overall (HR 0.44, p = 0.017) survivals when controlling for age, tumor location, and adjuvant radiation., Conclusions: Extent of resection independently predicts progression-free and overall survivals in patients with WHO grade II meningiomas. In an era of increasing support for adjuvant treatment modalities in the management of meningiomas, our data support maximal safe resection as the primary goal in treatment of these patients.

Purpose: In view of the risk associated with the surgical treatment of intracranial meningiomas in the elderly population due to the physiology of aging and multiple comorbidities, an attempt was made to identify factors influencing outcomes and to define the subgroup of patients who should not be operated on due to poor results., Patients and Methods: A retrospective analysis of 58 patients over 70 years old with assessment of short-term and long-term outcomes. Scores by previously described CRGS, SKALE, and GSS grading systems were also calculated for our patients., Results: Neurological morbidity was only associated with a critical location according to the SKALE grading system ( P =0.02). Six patients (10.3%) died. Mortality was associated with the Karnofsky Performance Scale score (KPS ≤60 vs KPS ≥70; P =0.0162), the American Society of Anesthesiologists scale status (ASA 1 or 2 vs ASA 3; P =0.0022) and the WHO grade of meningiomas ( P =0.012). Risk factors for tumor recurrence (six patients) were WHO grade ( P =0.00048) and Simpson grade of resection ( P =0.0437). At follow-up, excluding patients who died due to surgery or recurrence (15.5%), most patients improved (50%) or remained unchanged (25.9%) in relation to the preoperative KPS status., Conclusion: Postoperative neurological deterioration was only associated with a critical tumor location (skull base, eloquent area, large vessels involvement by the tumor). Due to a significantly higher risk of death, careful consideration should be taken for surgery in patients in a poor functional condition (KPS ≤60) or in a poor physical condition (ASA 3 status). An improvement or at least nonworsening of the neurological status in relation to the preoperative condition was observed in the majority of patients during follow-up., Competing Interests: The author reports no conflicts of interest in this work., (© 2020 Czernicki.)

Sphenoid wing meningiomas are generally considered as skull base meningiomas (SBMs). However, given their surgical similarities with non-skull base meningiomas (NSBMs), we hypothesized that lateral sphenoid wing meningiomas (LSWMs) without bone invasion (BI) should be considered as NSBMs. N = 65 LSWMs without BI operated between 1990 to 2010 at a single-center were compared to N = 352 NSBMs, represented by convexity meningiomas (CMs), and to N = 23 SBMs, represented by spheno-orbital meningiomas (SOMs), with respect to baseline demographics, clinical presentations, Simpson grades, complications, adjuvant therapies, as well as overall survival (OS) and progression-free survival (PFS). Only WHO grade I meningiomas were included. No significant differences in baseline demographics, clinical presentation, or pre-operative KPS were found between the three groups. Simpson grade 1-3 was achieved in 90.1% of LSWMs, 97.1% in CMs (p = 0.05), and 82.6% in SOMs (p = 0.23). There were no significant differences in postoperative infection, hematoma, neurological worsening, 30-day mortality, or OS between the three groups. Lower re-treatment rates were observed in LSWMs and CMs compared to SOMs (p = 0.06). With respect to PFS, there was no significant difference between LSWMs and CMs (89.1% and 88.5% at 5 years, respectively), whereas PFS was significantly higher in LSWMs than in SOMs (79% at 5 years) (p = 0.05). LSWMs without BI should be considered as an intermediate entity between NSBMs and SBMs. LSWMs are similar to SOMs with respect to extent of resection, but more similar to CMs with respect to re-treatment rates and PFS.

Background: Atypical meningiomas are characterized by a high rate of recurrence and shorter overall survival (OS) compared with grade I meningioma. Predictive parameters for OS and recurrence-free survival (RFS) are controversial., Methods: Patient age, sex, preoperative symptoms, tumor localization, size, Simpson grade, postoperative complications, extent of resection, number of mitoses, MIB1 proliferation index, brain invasion, postoperative radiotherapy, and clinical outcome (Karnofsky performance scale [KPS] postoperatively and at long-term follow-up) were evaluated. Data regarding recurrence rate, mortality, OS, and RFS at 1-, 3-, and 5-year follow-up were also collected. Median follow-up was 76 months; all patients had at least 3 years of follow-up., Results: Between 2007 and 2017, 73 patients underwent surgery for atypical meningiomas (World Health Organization grade II) at 2 centers. Preoperative KPS score >80 as well as 1-month, 6-month, and 1-year follow-up KPS scores were related to better OS. Postoperative complications did not modify OS and RFS. Gross total removal (Simpson grade I, II) was achieved in 80.8% of patients. RFS was statistically influenced by extent of resection (P = 0.002). MIB1 proliferation index >8 was a negative predictive factor for recurrence at univariate and multivariate analysis (P = 0.001 and P = 0.021). Radiotherapy was statistically related to a worse outcome. The incidence of recurrence was 38%. RFS was 98.6% at 1-year follow-up, 81.1% at 3 years, and 57.5% at 5 years. All patients were alive at 1-year follow-up. OS was 90.5% at 3-year follow-up and 78.8% at 5-year follow-up., Conclusions: Despite some limitations, our study demonstrates that aggressive surgical treatment achieving a gross total removal is a positive predictive parameter for RFS as well as a good clinical outcome (KPS score >80) and is related to a longer OS., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: There is no dedicated study on outcome after meningioma surgery in neurofibromatosis type 2 (NF2) patients., Methods: We processed the French Système National des Données de Santé (SNDS) database using an algorithm combining the type of surgical procedure and the International Classification of Diseases to retrieve cases of meningioma operated in NF2 patients between 2007 and 2017. Descriptive and survival analyses were performed., Results: This nationwide study found 184 patients who were operated on for 315 meningiomas over a 10-year period. 57.6 % were female, median age at first surgery was 40 years IQR[24.8-50.2] and 10.9 % were under 18 years. Cranial convexity (23.4 %) and posterior skull base (16.8 %) were the most common locations. 89.7 % of the tumours were benign and 3.3 % malignant. 16.3 % of the patient received radiotherapy and 13.6 % stereotactic radiosurgery. Median follow-up was 6.3 years, IQR[5.3-7]. At data collection, 28 patients were dead (15.2 %) and median age at death was 41.7 years, IQR [32.7-50.4]. 5 patients died within the year of meningioma surgery. OS rates at 5 and 10 years were: 87.8 %, 95 %CI[82.6-93.3] and 73.2 %, 95 %CI[63.7-84.1] respectively. In univariable Cox regression analysis, Mortality-Related Morbidity Index (MRMI) (HR = 1.57, 95 %CI[1.3-1.9], p < 0.001) Expenditure-Related Morbidity Index (HR1.16, 95 %CI[1.09-1.24], p < 0.001), a malignant meningioma (HR=8.15, 95 %CI[2.78-23.85], p < 0.001), and a diagnosis of deafness or vestibular schwannoma (HR=2.52, 95 %CI[1.02-6.23], p = 0.0447), were associated to the outcome. In multivariable analysis, solely the MRMI and a malignant meningioma remained significant predictors of reduce OS., Conclusion: Using this unique database, we found that outcome of NF2 patients after meningioma surgery is impaired, especially for those with significant co-morbidities and affected by a malignant meningioma., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Meningiomas are common in adults (~35% of brain tumors) but rare in children, where they exhibit unique clinical, pathological and molecular features compared to adult counterparts. Thus, data generated from adult cohorts may be imperfectly suited to guiding diagnostic, prognostic and treatment decisions for children. We studied 50 meningioma patients ≤18 years with available clinical and pathological data to address the need for data obtained in the pediatric setting. As previously described, we noted a slight bias toward male patients and a higher proportion of spinal tumors compared to adults. Thirty-eight of 50 specimens were further analyzed by next generation sequencing. Loss-of-function mutations in NF2 and chromosome 22 losses were common, but pathogenic variants in other genes (SMARCB1, FUBP1, BRAF, TERT promoter, CHEK2, SMAD and GATA3) were identified in a minority of cases. Copy number variants outside of chromosomes 22 and 1 were infrequent. H3K27 hypomethylation, a useful biomarker in adult tumors, was not found in our cohort. In exploring the correlation between mitotic count and recurrence-free survival, we found a threshold of six mitoses per 10 high powered fields as the optimal cutoff in predicting recurrence-free survival. If independently validated in larger studies, adjusted grading thresholds could enhance the clinical management of pediatric meningiomas., (© 2020 International Society of Neuropathology.)

Incidental meningiomas (IMs) are the most common intracranial neoplasms, especially in perimenopausal women. There is ongoing debate on whether their incidence is increased by hormone replacement therapy. Meningiomas often express estrogen receptors, which were linked to higher proliferative activity according to some reports. Consequently, there is a theoretical risk of estrogen-based HRT (e-HRT) leading to an increase in tumor growth and thus altering the natural history of IMs. However, clinical data is lacking to support this notion. To identify differences in the natural history of IM after e-HRT exposure. We queried the NorthShore Meningioma Database for patients with ≥ 6 months of e-HRT. They were compared with age-matched IM controls. Forty patients were included in the e-HRT group (mean age 62.1 ± 12.0 years; mean duration of HRT 5.3 ± 4.5 years) and 80 in the no-HRT group (mean age 62.2 ± 12 years). Radiographic appearance was similar between groups. The average 2D tumor diameter was 35% lower in the e-HRT group (p = 0.02), with an absolute growth-rate of half of the no-HRT group (p = 0.02). Radiographic and clinical progression-free survival were 1.2 years and 3.3 years longer in the e-HRT group, respectively. These preliminary results suggest that e-HRT may be safe in incidental meningiomas.

Background: Falcine meningiomas have unique characteristics including their high rates of recurrence, association with high grade pathology, increased male prevalence, and potential for diffuse involvement of the falx., Objective: To address these issues in a substantial series of falcine meningiomas and report on the impact of extent of resection for this distinct meningioma entity., Methods: Retrospective analysis of characteristics and outcomes of 59 falcine meningioma patients who underwent surgery with the senior author. A "Grade Zero" category was used when an additional resection margin of 2 to 3 cm from the tumor insertion was achieved., Results: For de novo falcine meningiomas, gross total resection (GTR) was associated with significantly decreased recurrence incidence compared with subtotal resection (P ≤ .0001). For recurrent falcine meningiomas, median progression-free survival (PFS) was significantly improved for GTR cases (37 mo vs 12 mo; P = .017, hazard ratio (HR) .243 (.077-.774)). "Grade Zero" resection demonstrated excellent durability for both de novo and recurrent cases, and PFS was significantly improved with "Grade Zero" resection for recurrent cases (P = .003, HR 1.544 (1.156-2.062)). The PFS benefit of "Grade Zero" resection did not achieve statistical significance over Simpson grade 1 during the limited follow-up period (mean 2.8 yr) for these groups., Conclusion: The recurrence of falcine meningiomas is related to the diffuse presence of tumor between the leaflets of the falx. Increased extent of resection including, when possible, a clear margin of falx surrounding the tumor base was associated with the best long-term outcomes in our series, particularly for recurrent tumors., (Copyright © 2020 by the Congress of Neurological Surgeons.)

Objective: Grade 2 meningioma is more likely to recur than grade 1 meningioma. Recurrence decreases overall survival in patients with grade 2 meningioma. However, the clinical course of grade 2 meningioma with several repeated recurrences is poorly understood. The purpose of this study was to clarify the clinical characteristics of grade 2 meningioma with repeated recurrences., Methods: This study included 28 patients with grade 2 meningioma treated at our institution from January 1994 to December 2017. The relationship between survival and factors including age, sex, number of recurrences, malignant transformation, radiation therapy, tumor location, MIB-1 labeling index, Simpson grade, Karnofsky Performance Status, and surgical interval were analyzed., Results: The average age at the initial operation was 53.4 years. The number of recurrences was 3.7 times on average during the follow-up of 113.9 months after the initial operation. An increasing number of recurrences resulted in shortening of the surgical interval, increase in the MIB-1 labeling index, and decrease in Karnofsky Performance Status. In fatal cases, the average surgical interval before death was approximately 1 year. Three factors were related to poor prognosis: number of recurrences (odds ratio, 1.620; P = 0.030), malignant transformation (odds ratio, 10.625; P = 0.019), and high MIB-1 labeling index (odds ratio, 1.089; P = 0.044)., Conclusions: Shortening of the surgical interval within 1 year because of multiple recurrences led to death in patients with grade 2 meningioma. Malignant transformation was the most potent among the poor prognostic factors., (Copyright © 2020. Published by Elsevier Inc.)