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Background Recent comprehensive studies have revealed several molecular alterations that are frequently found in meningiomas. However, effective treatment reagents targeting specific molecular alterations have not yet been identified because of the limited number of representative research models of meningiomas. Methods We performed organoid cultures using meningioma cells and meningioma tumor tissues. Using immunohistochemistry and molecular analyses consisting of whole-exome sequencing, RNA-seq, and DNA methylation analyses, we compared the histological findings and molecular profiling of organoid models with those of parental tumors. Further, using these organoid models together with a public database of meningiomas, we explored molecular alterations, which are a potent treatment target for meningioma. Results We established 18 organoid models comprising of two malignant meningioma cells (HKBMM and IOMM-Lee), 10 benign meningiomas, four malignant meningiomas, and two solitary fibrous tumors (SFTs). The organoids exhibited consistent histological features and molecular profiles with those of the parental tumors. Using a public database, we identified that upregulated forkhead box M1 (FOXM1) was correlated with increased tumor proliferation. Overexpression of FOXM1 in benign meningioma organoids increased organoid proliferation; depletion of FOXM1 in malignant organoids decreased proliferation. Additionally, thiostrepton, a FOXM1 inhibitor combined with radiation therapy, significantly inhibited the proliferation of malignant meningioma organoid models. Conclusions An organoid model for meningioma enabled us to elucidate the tumor biology of meningioma along with potent treatment targets for meningioma.

Background Given concerns about risks associated with the growing use of mobile phones over recent decades, the authors analyzed temporal trends in incidence rates of nonmalignant meningioma and vestibular schwannoma in the United States. Methods The incidence of nonmalignant meningioma and vestibular schwannoma among adults in the Surveillance, Epidemiology, and End Results 18 registries during 2004 through 2017 was evaluated according to the method of diagnosis: microscopically (MC) or radiographically confirmed (RGC). Annual percent changes (APCs) and 95% CIs were estimated using log-linear models. Results Overall meningioma rates (n = 108,043) increased significantly from 2004 to 2009 (APC, 5.4%; 95% CI, 4.4%-6.4%) but subsequently rose at a slower pace through 2017 (APC, 1.0%; 95% CI, 0.6%-1.5%). Rates for MC meningiomas changed little from 2004 to 2017 (APC, -0.3%; 95% CI, -0.7%, 0.1%) but rose rapidly for RGC meningiomas until 2009 (APC, 9.5%; 95% CI, 7.8%-11.1%) and rose more modestly thereafter (APC, 2.3%; 95% CI, 1.5%-3.0%). Overall vestibular schwannoma rates (n = 17,475) were stable (APC, 0.4%; 95% CI, -0.2%, 1.0%), but MC vestibular schwannoma rates decreased (APC, -1.9%; 95% CI, -2.7%, -1.1%), whereas RGC vestibular schwannoma rates rose (2006-2017: APC, 1.7%; 95% CI, 0.5%-3.0%). For each tumor, the trends by diagnostic method were similar for each sex and each racial/ethnic group, but RGC diagnosis was more likely in older patients and for smaller tumors. Meningioma trends and the proportion of RGC diagnoses varied notably by registry. Conclusions Overall trends obscured differences by diagnostic method in this first large, detailed assessment, but the recent stable rates argue against an association with mobile phone use. Variation among registries requires evaluation to improve the registration of these nonmalignant tumors. Lay summary The etiology of most benign meningiomas and vestibular schwannomas is poorly understood, but concerns have been raised about whether mobile phone use contributes to risk of developing these tumors. Descriptive studies examining temporal trends could provide insight; however, globally, few registries collect these nonmalignant cases. In the United States, reporting benign meningiomas and vestibular schwannomas became required by law in 2004. This was the first large, systematic study to quantify and characterize incidence trends for meningioma and vestibular schwannoma according to whether the tumors were diagnosed microscopically or only radiographically. Differential trends across registries and by diagnostic method suggest that caution should be used when interpreting the patterns.

This study aimed to evaluate the long-term efficacy of proton beam therapy (PBT) for unresectable benign meningiomas at the University of Tsukuba, Japan. From 1986–1998, 10 patients were treated at the Particle Radiation Medical Science Center (PRMSC) with a relative biological effectiveness (RBE) value of 1.0 using an accelerator built for physics experiments. The total dose was compensated with an X-ray in three patients. Following that, from 2002–2017, 17 patients were treated with a RBE value of 1.1 at the Proton Medical Research Center (PMRC) which was built for medical use. At the PRMSC, the total dose ranged from 50.4–66 Gy (median: 54 Gy). During the follow-up, which lasted between 3.8 and 31.6 years (median: 25.1 years), the 5-, 10-, 15-, 20- and 30-year local control rates were 100%, and the 5-, 10-, 15-, 20- and 30-year survival rates were 90, 80, 70, 70 and 36%, respectively. One patient died of brainstem radiation necrosis 5.1 years after PBT. At PMRC, the total dose ranged from 45.0–61.2 GyE, with a median of 50.4 GyE. During the follow-up, which lasted between 3 and 17 years with a median of 10.5 years, the 5-, 10- and 15-year local control rates were 94.1%, and the 5-, 10- and 15-year survival rates were 100, 100 and 88.9%, respectively. Neither malignant transformation nor secondary malignancy was observed, indicating that fractionated PBT may be effective and safely control benign unresectable meningioma even for the lifelong period of time.

Introduction Spinal meningiomas constitute the majority of primary spinal neoplasms, yet their pathogenesis remains elusive. By investigating the distribution of these tumors across sociodemographic variables can provide direction in etiology elucidation and healthcare disparity identification. Methods To investigate benign and malignant spinal meningioma incidences (per 100,000) with respect to sex, age, income, residence, and race/ethnicity, we queried the largest American administrative dataset (1997–2016), the National (Nationwide) Inpatient Sample (NIS), which surveys 20% of United States (US) discharges. Results Annual national incidence was 0.62 for benign tumors and 0.056 for malignant. For benign meningiomas, females had an incidence of 0.81, larger (P = 0.000004) than males at 0.40; yet for malignant meningiomas, males had a larger (P = 0.006) incidence at 0.062 than females at 0.053. Amongst age groups, peak incidence was largest for those 65–84 years old (2.03) in the benign group, but 45–64 years old (0.083) for the malignant group. For benign and malignant meningiomas respectively, individuals with middle/high income had an incidence of 0.67 and 0.060, larger (P = 0.000008; P = 0.04) than the 0.48 and 0.046 of low income patients. Incidences were statistically similar (P = 0.2) across patient residence communities. Examining race/ethnicity (P = 0.000003) for benign meningiomas, incidences for Whites, Asian/Pacific Islanders, Hispanics, and Blacks were as follows, respectively: 0.83, 0.42, 0.28, 0.15. Conclusions Across sociodemographic strata, healthcare inequalities were identified with regards to spinal meningiomas. For benign spinal meningiomas, incidence was greatest for patients who were female, 65–84 years old, middle/high income, living in rural communities, White, and Asian/Pacific Islander. Meanwhile, for malignant spinal meningiomas incidence was greatest for males, those 45–65 years old, and middle/high income.

Anaplastic or malignant meningiomas that are classified as World Health Organization (WHO) grade III account for less than 1% of all meningiomas diagnosed. Despite the aggressive course, distant metastases are a rarity, occurring in only 0.1% to 0.2% of cases. We report the case of a 56-year-old woman who presented with parasagittal benign meningioma that underwent malignant transformation along with metastasis into the right orbitosphenoid region. The clinical, radiological, and histopathological aspects are highlighted, with an emphasis on the natural history of meningiomas.

Survival after meningioma surgery often is reported with inadequate allowance for competing causes of death.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.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, P0.001), 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, P0.001), spinal location (SHR 0.2, 95% CI 0.08-0.47, P0.001), cerebrospinal fluid shunt (SHR 3.13, 95% CI 1.9-5.16, P0.001), 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.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.

Background/aim Tumorigenesis and cancer progression might be driven by abnormal activation of growth factor receptors. Importantly, molecular changes in EGFR-dependent signaling is one of the most common characteristics of brain tumors. Patients and methods HER1 and EGFRvIII variants in meningiomas and glioblastomas were evaluated at the RNA level. Results EGFRvIII was found in 18.6% of glioblastomas (GBM), whereas 25% of EGFRvIII positive tumors express wild-type EGFR as well. HER1 was over-expressed in benign meningiomas compared to glioblastomas, whereas HER1 expression in meningiomas differed significantly between sub-types of meningiomas. EGFRvIII and HER1 where positively correlated in glioblastomas. Yet, the patient overall survival did not differ between high- and low-HER1 expressing glioblastomas or between EGFRvIII positive and negative GBMs. Conclusion HER1 may be considered as an independent factor for classification of benign meningiomas. The mRNA levels of HER1 or EGFRvIII should not be used as independent prognostic factors for patients with gliomas.

Patients with a benign meningioma often have a long survival following the treatment of their meningioma. Since radiotherapy is frequently part of the treatment, long-term side effects are of considerable concern. A controversial long-term side effect of radiotherapy is stroke. Due to its severity, it is important to know the frequency of this side effect. The aim of this study was to assess the stroke incidence and risk factors among patients receiving radiotherapy for their benign meningioma. We performed a retrospective database study of patients who underwent primary or adjuvant radiotherapy for their benign meningioma at University Hospitals Leuven from January 2003 to December 2017. We included 169 patients with a median age of 51 years (range 22–84). Every patient received fractionated radiotherapy using photons with a median dose of 56 Gy (range 54–56) in fractions of 2 Gy (range 1.8–2). The median follow-up was 5.3 years (range 0.1–14). The cumulative stroke incidence function showed an incidence of 11.6% after 9 years of follow-up, translating to a stroke incidence per year of 1.29%. We found two significant risk factors for stroke: medically treated arterial hypertension (p = 0.005) and history of previous stroke or transient ischemic attack (p

Secretory meningioma (SM) is a rare subtype of benign meningioma reported to cause significant peritumoral brain edema (PTBE). Therefore, patients with SM may have more severe presenting symptoms and possibly increased postoperative complications. Our aim was to perform a statistically rigorous comparison of patients with SM with other nonsecretory World Health Organization grade I meningiomas and examine PTBE, postsurgical outcomes, and recurrence in a large series of cases.A retrospective review of all patients at our institution with pathologically confirmed SM between 2000 and 2017 was performed. A control group of nonsecretory grade I meningiomas was matched 1:1 according to tumor location and size. Study groups were compared on clinical characteristics and outcomes using logistic, cumulative logit, and normal linear generalized estimating equations regression models.Fifty-five patients with SM met inclusion criteria and were matched with 55 control patients. After adjusting for size and location, the odds of a patient with SM having a more severe T2 edema grade were 8.9 (95% confidence interval, 3.8-21.1; P 0.001) times higher, and the odds of any T2 edema were 6.2 (95% confidence interval, 2.2-17.6; P 0.001) times higher. Significance remained even when adjusting for age. Postoperative complications, Simpson grade resection, neurologic outcome, and recurrence were not significantly different.Patients with SM have significantly greater odds of having PTBE compared with patients with nonsecretory World Health Organization grade I meningiomas of a similar size and location. Despite this situation, surgical outcome and recurrence rates are similar.

Meningiomas are the most common extra axial and non-glial primary neoplasms of the central nervous system. They account for nearly 15% of all intracranial neoplasms. The present study was planned to identify and describe the morphological and imaging characteristics of both typical and atypical meningiomas on CT and MRI, including Diffusion Weighted Imaging (DWI) and MR Spectroscopy (MRS). CT and MRI images of 43 patients histologically proven to have meningioma were retrospectively evaluated. The images were evaluated for- tumor location, imaging characteristics, atypical patterns of presentation and as well as advanced imaging features. Statistical analysis used included percentage and frequency. Institutional ethical committee clearance was obtained prior to commencement of the study. Our study population comprised of 23 females and 20 males. The bulk of our population belonged to 5th decade group (44%). The most common tumor site was the frontal lobe (40%). Features seen on imaging included- well defined margins (100%), broad dural base (67%), calcification-84% (n=36/43) and peritumoral edema (51%). On MRI, 84% and 67% of the lesions were T1 isointense and T2 mildly hyperintense respectively, when compared to the brain parenchyma, diffusion restriction was variable (benign meningiomas- 46% and atypical meningiomas-100%). Choline (100%) and Alanine peaks (28%) were observed on MRS. On post contrast imaging, homogeneous enhancement was seen in 95%, while a dural tail was seen in only 51% of the cases. Benign meningiomas present with typical extra-axial features (broad dural base, white matter buckling, CSF cleft, dural tail etc.), while atypical meningiomas have varied presentations which include-cystic/necrotic areas, significant vasogenic edema with mass effect and diffusion restriction on DWI. Keywords: Meningioma, Extra-axial lesion, Dural tail.

The systematic adoption of the histopathologic criteria provided by the 2016 update of the WHO classification of brain tumors has markedly increased the relative proportion of atypical and anaplastic meningiomas. These tumors exhibit a much greater recurrence rate compared to benign meningiomas, which negatively impacts survival. In recent years, the publication of numerous retrospective case series, yet no randomized controlled trials, on the impact of radiation therapy in non-benign meningioma, has yielded conflicting evidence. At present, maximum safe resection, including the dural attachment, is the preferred primary treatment modality for all types of meningiomas. Adjuvant radiotherapy is currently recommended for subtotally resected grade II and for all grade III meningiomas. However, in grade II meningiomas achieving complete resection, close radiologic and clinical observation is a feasible option. Despite the great amount of non-benign meningiomas available and eligible for trials, there is a striking lack of prospective studies testing adjuvant therapies against observation for this subset of patients. An updated and systematic literature review is provided on the effectiveness and indications of radiotherapy on grade II and III meningiomas.

The objective of this study was to more fully understand the optimal neurosurgical strategy for spinal benign meningiomas from a medium to long-term perspective. This retrospective study included a cohort of 35 patients with a diagnosis of spinal meningioma who were first operated at our institute over the past 10 years and followed-up for at least 2 years after surgery. The inclusion criterion for the study was the pathological diagnosis finally verified as benign meningioma of World Health Organization (WHO) grade 1. The average follow-up duration after surgery was 61.0 months. The location of the spinal meningioma was classified into ventral or dorsal type based on the operative video record and the preoperative MR images. The extent of resection of the spinal meningioma was carefully determined based on the Simpson grade. The average neurological condition was significantly improved at the final follow-up. Simpson grade I or II resection was achieved in 31 of 35 cases (88.6%). No Simpson grade I or II cases showed local recurrence during follow-up. Tumor recurrence was noted in 2 of 4 cases of Simpson grade IV resection. One case has been followed-up without any re-operation because of no neurological deterioration, and the other case underwent stereotactic radiosurgery. This study suggested that meticulous Simpson grade II resection of spinal benign meningiomas of WHO grade 1 may be good enough from a medium to long-term follow-up perspective, though longer follow-up is absolutely necessary.

Older patients have inferior outcomes for meningioma and experience more post-operative complications. The purpose of this study was to identify national treatment patterns and outcomes based on age for benign meningiomas using the National Cancer Database (NCDB).The NCDB was queried for patients with biopsy-proven World Health Organization Grade (WHO) grade I meningioma diagnosed between 2004 and 2015. Patients were stratified based on age: 18-50, 51-60, 61-70, 71-80, and 80 years of age. Clinicodemographic details were compared via the Chi Square test. Multivariable logistic regression was used to determine factors associated with receipt of treatment and post-operative complications. Multivariable Cox regression and the Kaplan-Meier method were used to examine survival.56,960 patients met inclusion criteria with a median follow-up of 48 months. Ages 61-70 (OR 0.73, 95% CI 0.62-0.85, p .001), ages 71-80 (OR 0.51, 95% CI 0.43-0.60, p .001), and age 80 (0.16, 95% CI 0.14-0.19, p .001) were less likely to receive treatment. Older age groups were associated with increased risk of post-operative complications and post-operative complications predicted for decreased survival. Treatment with surgery (HR 0.57, 95% CI 0.52-0.62, p .001) and surgery and radiation (HR 0.59, 95% CI 0.50-0.70, p .001) provided a survival benefit. Older age was associated with a survival decrement.Older patients are less likely to undergo treatment for benign meningioma and are more likely to have post-operative complications. Survival decreased with increasing age. Treatment improved survival among all patients. Risk-benefit ratio of treatment should be carefully considered when treating older patients with benign meningioma.

Background Meningioma is an intracranial tumor frequently encountered in the neurosurgical setting. Extracranial disease is a rare occurrence, with a reported incidence in 0.1% of cases. Metastasis is associated with previous craniotomy, venous sinus invasion, local recurrence, and World Health Organization (WHO) grade III tumor. Metastasis of a benign, grade I meningioma is extraordinarily rare. Case Description We report a case of a 41-year-old with a WHO grade I intracranial meningioma that had invaded and occluded the superior sagittal sinus. Chest computed tomography (CT) scan revealed pulmonary nodules, which were biopsied and confirmed benign meningioma. The metastatic meningiomas were found before resection of the primary tumor, suggesting direct seeding through the venous system versus iatrogenic seeding. Thirteen years later, an additional lung mass was found incidentally on abdominal CT scan for workup of a sarcoidosis. Biopsy and subsequent resection confirmed benign meningioma. A retrospective review of earlier chest CT scans revealed a small lesion that corresponded to the larger lesion found 13 years later. Conclusions This a rare case of a WHO grade I meningioma involving the sagittal sinus with direct seeding of the pulmonary vascular bed leading to multiple meningioma metastases. The report highlights an increased risk of distant metastases for a benign meningioma with invasion of dural sinuses.

Objective Meningiomas are among the most common primary intracranial tumors. Up to 20% of cases will show increased malignancy at histological examination (World Health Organization grade II or III). Effective pharmacotherapy, except for radiotherapy, is lacking. Therefore, it is necessary to study the pathogenesis of malignant meningioma to provide more treatment strategies. Methods RNA sequencing and micro-RNA (miRNA) microarray detection were applied to identify differentially expressed messenger RNAs (mRNAs) and miRNAs in benign and malignant meningioma. The miRDB and TargetScan databases were used to predict the potential interaction between miRNAs and mRNAs. A proliferation assay was used to evaluate the cell growth. A wound healing assay and Transwell assay were performed to assess the cell migration and invasion abilities, respectively. The interaction between miRNA and mRNA was identified using a luciferase reporter assay. Results We found fatty acid synthase (FASN) was significantly upregulated in malignant meningioma compared with benign meningioma. Knockdown of FASN significantly inhibited proliferation, migration, and invasion of IOMM-Lee cells. Moreover, miR-195 was verified to directly target FASN using a luciferase reporter assay. Upregulation of miR-195 also significantly inhibited proliferation, migration, and invasion of IOMM-Lee cells. Furthermore, we performed bioinformatics analysis to predict the competing endogenous RNAs (ceRNAs) and found that NUP210, SPIRE2, SLC7A1, and DMTN might function as ceRNAs of FASN by sponging miR-195 in meningioma. Conclusions Our results have suggested a tumor suppressive role for miR-195 in the tumorigenesis and progression of malignant meningioma by targeting FASN. In addition, NUP210, SPIRE2, SLC7A1, and DMTN might act as ceRNAs to regulate FASN expression by sponging miR-195.

Meningiomas are among the most common primary brain tumors. There is a growing need for novel ways of differentiating between benign (World Health Organization [WHO] grade I) and atypical (WHO grade II) meningiomas as well as for novel markers of the tumor's future behavior. A difference between glucose metabolism in atypical and benign meningiomas is well known. However, a significant correlation between the systemic metabolic status of the patient and the meningioma WHO grade has not yet been established. Our aim was to compare the WHO grades of intracranial meningiomas with the patient's HbA1c levels as a more reliable marker of the chronic systemic metabolic status than the fasting blood glucose value, which is usually looked at. We retrospectively analyzed 15 patients and compared their meningioma WHO grade with their preoperative HbA1c values. Our results show that patients with benign intracranial meningiomas have significantly lower HbA1c value. Conversely, patients with atypical intracranial meningiomas have higher HbA1c values. Furthermore, we showed that the proliferation factor Ki67 was statistically strongly correlated with the HbA1c value (p

The use of gamma knife radiosurgery (GKS) for meningiomas after cranial surgery has been extensively evaluated; however, studies on tumor progression, including recurrence out of the margin dose line, are scarce. Hence, we aimed to evaluate the meningioma recurrence after GKS within and out of the margin dose. We included 37 consecutive patients with World Health Organization (WHO) grade 1 meningiomas who were treated with GKS following cranial surgery. Radiologically indicated recurrences were classified into three patterns by their relationship to the margin dose and tumor. The median follow-up was 58.9 months; 2 (5.4%) patients died. Only 2 (5.4%) patients did not keep active daily lives because of tumor progression. Cumulative local control at 5 years was 85.2%. Local recurrence and recurrence out of the margin dose occurred in 5 (13.5%) and 13 (35.1%) patients, respectively. A larger preoperative maximum diameter was a risk factor for local recurrence (hazard ratio [HR]: 2.118; P = 0.033), adjacent progression (HR: 1.633; P = 0.015), and remote progression (HR: 2.016; P = 0.003). Symptomatic adverse radiation effects occurred in 1 patient. Salvage GKS and cranial surgery were performed in 9 (24.3%) and 8 (21.6%) patients, respectively. Progression to WHO grade 2–3 occurred in 5 (13.5%) patients. A larger preoperative maximum diameter was a risk factor for progression of WHO grade (HR: 2.016, P = 0.033). Progression out of the margin dose was associated with a larger preoperative tumor size.

Meningiomas rarely progress to malignant variants and there is no consensus regarding the period over which malignant transformation may occur. Here, we report a case of anaplastic meningioma that showed malignant transformation 18 years after gross total resection of benign meningioma in the primary surgery, which may be the longest duration reported to date. Although the recurrence rate is low following total resection of benign meningioma, malignant transformation can rarely occur after a long period as in our case. Long-term follow-up after total resection of benign meningioma is suggested considering the risk of malignant transformation.

The significance of atypical histological features (AHF) as risk factors for recurrence in benign meningioma is not well understood. This study examined risk factors of World Health Organization (WHO) Grade I meningioma (GIM) recurrence, focusing on AHF. We investigated 150 consecutive newly diagnosed GIM patients who had more than one year of follow-up after resection in our hospital between January 2007 and March 2018. The following factors were reviewed retrospectively: age, sex, tumor location, extent of resection, MIB-1 index, mitotic figures, number and distribution of AHF, and recurrence. The patients were grouped according to the presence or absence of recurrence and comparatively examined. Recurrence was observed in 10 cases (6.7%). Univariate analysis showed that patients with recurrence had a significantly higher MIB-1 index (2.0 vs. 4.3; p = 0.006) and a significantly higher proportion of male patients (21.4% vs. 70.0%; p = 0.002) and patients with sheet-like growth (6.42% vs. 30.0%; p = 0.04). In multivariate analysis, skull base location (odds ratio [OR] 31.424; 95% confidence interval [CI] 1.74-569), gross total resection (OR 0.130; 95% CI 0.0189-0.897), and MIB-1 index (OR 1.939; 95% CI 1.19-3.15) were significantly associated with recurrence. Our study revealed that skull base location, subtotal resection, and high MIB-1 index were independent risk factors for recurrence. Only the presence of sheet-like growth had a significantly higher incidence in patients with recurrence in univariate analysis of AHF. Multivariate analysis found no significant association. Sheet-like growth may be involved in malignancy and recurrence of benign meningioma.

We report rapid recurrence and malignant transformation of a benign meningioma during pregnancy in a young woman. A 30-year-old female meeted an operation of benign meningioma (WHO Grade I) before her pregnancy. No signs of recurrence were found in MRI two months before her pregnancy. Subsequent MRI was performed 6 months after her giving birth. MRI results showed a recurrent meningioma with a size of 45 × 49 × 32 mm. Reoperation was performed later, histopathological workup showed an atypical meningothelial meningioma(WHO Grade II) with a Ki-67 level of about 10% and a PR expression above 70%; no ER was observed. To our best knowledge, this is the first report of the rapid malignant transformation of a benign meningioma during pregnancy.

Introduction: Meningiomas are most common primary intracranial neoplasm and predominantly benign tumors. Meningioma is characterised by increased number and growth of normal meningothelial cells. There was WHO grading, WHO I- Benign meningioma, WHO II -Atypical meningioma, WHO III- Malignant meningioma. Aims and objectives: To study the histomorphological variants of meningiomas, the incidence of age, gender & anatomical location of meningioma, and to grade meningiomas according to WHO grading system. Materials and methods: The study comprised of 50 cases received in department of surgical Pathology, B.J. Medical College, Ahmedabad during period of one year. Case history were studied in detail with respect to presenting symptoms, site, age and sex distribution. Results: In our study, a total 50 cases of meningiomas were studied, in which meningiomas were most common in the age group between 30-50yrs. In the study of 50 cases, male and female ratio were 1:4. So, meningiomas were more common in female patients. Among all other histological variants of meningiomas, 47 cases from intracranial origin, 3 cases from spinal origin. So intracranial (parietal lobe) meningiomas cases were more common which comprises 15 cases. Majority of cases presented with complains of headache. Most common histological subtype was found to be Meningothelial meningioma which consist of 16 cases. According to the World Health Organization (WHO) grading, WHO grade I consists of 45 cases, WHO grade II consists of 3 cases of meningioma, among them three cases were of atypical meningioma, WHO grade III consists of two cases. Most meningioma were benign in WHO grade I. Conclusion: Meningiomas are most common intracranial neoplasm comprises about one fourth of all primary tumors of the central nervous system. Meningiomas are predominantly benign tumors. The histological subtype of meningioma and grading determines management and patient’s prognosis. Grade I meningiomas are curable by surgical resection and prognosis depends on complete removal of tumor. Grade II meningiomas show aggressive clinical behaviour with increased rate of recurrence. Grade III meningiomas are capable of malignant clinical behaviour and distant metastasis.

Background It is difficult to prospectively differentiate between benign (World Health Organization [WHO] I) and nonbenign (WHO II and III) meningiomas. Purpose To evaluate the feasibility of preoperative differentiation between benign and nonbenign meningiomas by using texture analysis from multiparametric MR data. Study type Retrospective. Subjects In all, 184 patients with meningioma (139 benign and 45 nonbenign) were included as the training cohort and 79 patients with meningioma (60 benign and 19 nonbenign) were included as the external validation cohort. Field strength/sequence T1 -weighted, T2 -weighted, and contrast-enhanced T1 -weighted imaging were performed on 1.5 or 3.0T MR systems from two centers. Assessment Tumor segmentation and radiological characteristic (RC) evaluation were performed by experienced radiologists. The texture features were extracted from preprocessed images and combined with RCs, and then the combined features were reduced by using a two-step feature selection. Three single-sequence models and a multiparametric MRI (the combination of single sequences) model were constructed and then evaluated with the external validation cohort. Statistical tests Area under receiver operating characteristic curve (AUC), accuracy (Acc), f1-score (F1), sensitivity (Sen), and specificity (Spec), were calculated to quantify the performance of the models. Results Among the four texture models, the multiparametric MRI model demonstrated the best performance for differentiating between benign and nonbenign meningiomas in both the training and external validation cohorts (AUC 0.91, Acc 89%, F1 0.88, Sen 0.93, and Spec 0.87 in the training cohort; AUC 0.83, Acc 80%, F1 0.77, Sen 0.84, and Spec 0.78 in the validation cohort). Data conclusion Nonbenign meningiomas might be preoperatively differentiated from benign meningiomas by using texture analysis from multiparametric MR data. Level of evidence 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1810-1820.

Life expectancy continues to rise exponentially. The concept of frailty has emerged as a tool helping to gauge overall health status and risk of adverse events in aging patients, has shown to exhibit a linear relationship with poor survival in the elderly. Multiple pathologies have different genetic, radiographic, clinical and prognostic characteristics in the elderly, responding differently to various treatment modalities and thus present as unique clinical entities, not properly represented in large – guidelines generating studies. We present a two parts review discussing the unique features of the elderly patient harboring an intracranial neoplasm. In this Part-I, we review the management of benign meningioma in the elderly population. Meningioma is the second most common primary brain tumor. The risk of developing meningioma increases dramatically after 65 years of age. Predicting a specific meningioma’s growth pattern and clinical behavior is impossible. Clinicians must choose between GTR with associated morbidity/ mortality, SRS or a combined AHS approach, since progression rates after STR are high. Several scoring systems attempt to offer risk stratification in meningiomas (five systems presented). The most comprehensive and validated GSS (for both resection and SRS) offers the opportunity for intervention, with potentially modifiable parameters.

Aim This pilot study made a preliminary attempt to distinguish different metabolic phenotypes of primary human brain tumors with dual tracer 13N-ammonia and 18F-FDG. Methods 74 patients were included in this study including 12 benign meningiomas (B-MEN), 4 malignant meningiomas (M-MEN), 15 low-grade gliomas (LGG), 32 high-grade gliomas (HGG) and 11 primary central nervous system lymphomas (PCNSL). All patients underwent 13N-ammonia and 18F-FDG PET imaging. Semi-quantification analysis by tumor-to-gray matter (T/G) ratios was used for the evaluation of tracer uptakes. After the calculation of canonical discriminant functions, cross validation was done for all cases to evaluate the differential efficacy of dual tracers. Results According to the visual analysis, B-MEN were characterized by lower uptake of 18F-FDG and higher uptake of 13N-ammonia, while PCNSLs displayed contrary results. Both M-MEN and HGG had higher uptake of 18F-FDG and 13N-ammonia, while LGG displayed negative results for both tracers. According to the T/G ratios analysis, the accuracy of predicted tumor classification by means of canonical discriminant analysis for B-MEN, LGG, HGG and PCNSL was 91.7 %, 100 %, 84.4 % and 93.3 % respectively; the overall accuracy was 90.5 %. Conclusion The combination of dual tracer 13N-ammonia and 18F-FDG has a certain potential in distinguishing different types of brain tumors (meningiomas, gliomas and PCNSL). However, an advantage of the additional use of 13N-ammonia PET compared to a combined diagnosis with MRI and 18F-FDG PET could not be demonstrated and requires further studies.

ObjectiveThe purpose of this systematic review and meta-analysis is to evaluate the efficacy and safety of carbon ion radiotherapy (CI-RT) in improving meningioma by comparing photon and protons radiotherapy.MethodsA comprehensive search for relevant studies published until March 17, 2021, was conducted in PubMed, the Cochrane Library, Chinese Biomedical Literature Database and EMBASE. Statistical analyses were performed with R 4.0.3.ResultsWe identified 396 studies, of which 18 studies involving 985 participants were included. Except for one low quality study, the quality of the included studies was found to be either moderate or high quality. The analyses conducted according random effects model indicated that the 1-year overall survival rate (OS) of benign and non-benign meningiomas after the CI-RT treatment was 99% (95%CL=.91-1.00, I2 = 0%). The overall average 5-year OS for meningiomas was 72% (95%CL=0.52-0.86, I2 = 35%), not as effective as proton radiotherapy (PR-RT) 85% (95%CL=.72-.93, I2 = 73, Q=4.17, df=2, p=.12). Additionally, 5-year OS of atypical meningiomas (81%) was found to be significantly higher than anaplastic meningiomas (52%). The 10-year OS after CI-RT of patients with mixed grade meningioma was 91% (95%CL=.75-.97, I2 = 73%). The 15-year OS after CI-RT 87% (95%CL=.11-1.00) or PR-RT 87% (95%CL=.23-.99, I2 = 79%) were the same (Q=0, df=1, p=.99). After undergoing CI-RT for 3 and 5 years, the LC for benign meningioma was 100% and 88%, respectively, while the 2-year LC of non-benign meningiomas (atypical/anaplastic) was 33%. Headache, sensory impairment, cognitive impairment, and hearing impairment were found to be the most common adverse reactions, with individual incidences of 19.4%, 23.7%, 9.1%, and 9.1%, respectively.ConclusionCI-RT is a rapidly developing technique that has been proven to be an effective treatment against meningioma. The efficacy and safety of CI-RT for meningiomas were similar to those of PR-RT, better than photon radiotherapy (PH-RT). However, there is a need for more prospective trials in the future that can help provide more supportive evidence.

Background Benign meningiomas are the most frequently reported central nervous system tumors in the United States, with increasing incidence in past decades. However, the future trajectory of this neoplasm remains unclear. Methods We analyzed benign meningioma incidence of cases identified by any means (eg, radiographically with or without microscopic confirmation) in US Surveillance, Epidemiology, and End Results cancer registries among groups aged 35 to 84 years during 2004-2017 by sex and race and ethnicity using age-period-cohort models. We employed age-period-cohort forecasting models to glean insights regarding the etiology, distribution, and anticipated future (2018-2027) public health impact of this neoplasm. Results In all groups, meningioma incidence overall increased through 2010, then stabilized. Temporal declines were statistically significant overall and in most groups. JoinPoint analysis of cohort rate-ratios identified substantial acceleration in White men born after 1963 (from 1.1% to 3.2% per birth year); cohort rate-ratios were stable or increasing in all groups and all birth cohorts. We forecast that meningioma incidence through 2027 will remain stable or decrease among groups aged 55-84 years but remain similar to current levels among groups aged 35-54 years. The case count of total meningioma burden in 2027 is expected to be approximately 30 470, similar to the expected case count of 27 830 in 2018. Conclusions Between 2004 and 2017, overall incidence of benign meningioma increased and then stabilized or declined. For 2018-2027, our forecast is incidence will remain generally stable in younger age groups but decrease in older age groups. Nonetheless, the total future burden will remain similar to current levels because the population is aging.

Novel data report a “cross-talk” between Heat-Shock Factor 1 (HSF1) and the transient receptor potential vanilloid 1 cation channel (TRPV1) located in the cell membrane, introducing these channels as possible drug targets for the regulation of HSF1 activation. This study aims to investigate the co-expression of TRPV1 and HSF1 in human brain tumors. Additionally, the expression of the transient receptor potential ankyrin 1 channel (TRPA1), which is co-operated with TRPV1 in a plethora of cells, was studied. Immunohistochemical staining for HSF1, TRPV1 and TRPA1 expression was quantitatively analyzed in paraffin-embedded semi-serial tissue sections from 74 gliomas and 71 meningiomas. mRNA levels of HSF1, TRPV1 and TRPA1 were evaluated using real-time PCR. Although HSF1 was significantly increased compared with TRPV1/TRPA1 (p ≤ 0.001) in both gliomas and meningiomas, high co-expression levels for HSF1, TRPV1 and TRPA1 were found in 62.50% of diffuse fibrillary astrocytomas (WHO, grade II), 37.50% of anaplastic astrocytomas (WHO, grade III), 16.32% of glioblastomas multiforme (WHO, grade IV), and 42.25% of meningiomas (WHO, grade I and II). Correlation analysis revealed a relationship of HSF1 with TRPV1/TRPA1 in diffuse fibrillary astrocytomas (WHO, grade II) and benign meningiomas (WHO, grade I) contrary to glioblastomas multiforme (WHO, grade IV) and high grade meningiomas (WHO, grade II). Importantly, TRPA1 and TRPV1 expression levels were significantly increased in meningiomas compared with astrocytic tumors (p

Aims Brain invasion (BI) was firstly defined as a single criterion of atypia in otherwise benign meningiomas in the revised fourth edition of 2016 WHO classification of brain tumours after being previously inconsistently addressed. However, recent studies have raised doubts about the prognostic significance of BI in otherwise benign meningiomas. In our study, we investigate the reproducibility of such a prognostic effect. Methods We identified two cohorts one consisting of 483 patients with meningioma WHO grade I (M°I) or atypical meningioma WHO grade II (M°II) from Hannover Medical School and the other including atypical meningiomas defined according to the classical WHO criteria (M°IIb) from University Hospital Heidelberg. Follow-up data with a median observation time of 38.2 months were available from 308 cases. These included 243 M°I and 65 M°II patients with the latter group consisting of 25 patients with otherwise benign meningiomas with BI (M°IIa) and 40 with M°IIb. Results A significant difference of progression-free interval (PFI) was found between patients with M°I and M°II, M°I and M°IIa and those with M°I and M°IIb of both cohorts and each separately. However, PFI of M°IIa and M°IIb patients showed no significant difference. In the multivariate regression analysis adjusted for M°I/M°IIa versus M°IIb, sex, age, extent of resection and tumour location, BI exhibited the strongest risk of relapse (Hazard ratio: 4.95) serving as an independent predictor of PFI (p = 0.002). Conclusions Our results clearly support the definition of BI as a single criterion of atypia in WHO classification of 2016.

Treatment of aggressive meningiomas remains challenging due to a high rate of recurrence in higher-grade meningiomas, frequent subtotal resections, and the lack of effective systemic treatments. Substantial overexpression associated with a poor prognosis has been demonstrated for kinesin family member 11 (KIF11) in high-grade meningiomas. Due to anti-tumor activity for KIF11 inhibitors (KIF11i) filanesib and ispinesib in other cancer types, we sought to investigate their mode of action and efficacy for the treatment of aggressive meningiomas. Dose curve analysis of both KIF11i revealed IC50 values of less than 1 nM in anaplastic and benign meningioma cell lines. Both compounds induced G2/M arrest and subsequent subG1 increase in all cell lines. Profound induction of apoptosis was detected in the anaplastic cell lines determined by annexin V staining. KIF11i significantly inhibited meningioma growth in xenotransplanted mice by up to 83%. Furthermore, both drugs induced minor hematological side effects, which were less pronounced for filanesib. We identified substantial in vitro and in vivo anti-tumor effects of the KIF11 inhibitors filanesib and ispinesib, with filanesib demonstrating better tolerability, suggesting future use of filanesib for the treatment of aggressive meningioma.

Meningioma-like dermal tumor with diffuse coexpression of CD34 and hcaldesmon is rarely reported. Herein, we report a case of a 58-years-old woman who complained of a solitary dome-shaped papule on the left hand. An ellipse of skin measuring 1 x 0.5 x 0.5 cm was excised and sent for histopathological evaluation. Upon sectioning, the specimen showed a whitish firm dermal nodule measuring 3 mm in its greatest dimension. Microscopic examination revealed a well-circumscribed barely encapsulated dermal lesion showing compact round whorled sheets formed of round to ovoid uniform cells with abundant pink cytoplasm. Occasional intranuclear vacuoles were seen. A minor capillary-sized vascular component was seen in the background. Immunohistochemical (IHC) study revealed a diffuse positivity of tumor cells to CD34 and h-caldesmon along with faint reaction to Smooth Muscle Actin (SMA) and ER. However, Desmin, S100, HMB45, EMA, Pan Cytokeratin, and Chromogranin were all negative. Ki67 was very low (1%). The main differential diagnoses of the current lesion are meningioma and glomus family tumors. While the current lesion is morphologically reminiscent of cutaneous meningioma; neither the location nor the IHC stains support that diagnosis. The glomus family is highly suggestive. However, the location, the compact nature of the proliferation, and the positivity of CD34, all are unusual in such entities.

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.

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.

While hemorrhage is commonly encountered in various intracranial tumors, it is relatively rare in benign meningiomas. We present an interesting case report of a 75-year-old male who fell during intoxication, sustaining right frontal cranial trauma, coincidentally directly overlying a previously undiagnosed right frontal meningioma. He experienced an acute neurological decline and was found to have an intracranial hematoma, causing significant mass effect and herniation. Based on the radiographic appearance, an underlying neoplasm with significant edema was suspected. Intraoperatively, the hematoma and mass were successfully evacuated, and post-operative pathology confirmed the presence of a World Health Organization Grade I meningioma with a microcystic and angiomatous pattern. We speculate on the mechanism of injury and hemorrhage in this patient through review of the literature and discussion of medical and pathological risk factors.

Purpose Radiosurgery and fractionated intensity modulated radiation therapy (IMRT) are effective treatment modalities for meningiomas and schwannomas. Although fractionated IMRT yields favorable tumor control, daily treatments for 5 to 6 weeks can be burdensome for patients and health care systems. Thus, hypofractionated radiation may be a reasonable alternative. The purpose of this study was to review the results of patients with benign meningiomas or schwannomas treated at our institution with moderately hypofractionated IMRT. Methods and Materials After institutional review board approval, patients treated at a single academic institution between 2008 and 2018 with a primary diagnosis of either meningioma or schwannoma and who received 30 Gy at 3 Gy per fraction were identified. Patient and tumor characteristics, as well as follow-up documentation, were reviewed. Tumor progression was determined by reviewing patient imaging and provider notations. Results From 2008 to 2018, 70 patients with either meningioma or schwannoma were treated to 30 Gy. The median patient age was 73 years (range, 43-92 years). At the median follow up of 3.2 years, the local control was 92.9%. Two patients (2.9%) had disease progression, which occurred at 9.6 and 6.6 years after treatment. One patient developed asymptomatic radiographic changes consistent with radiation necrosis, which resolved without intervention. All patients completed the prescribed course without interruption. The mean tumor volume was 18.9 cm3, median volume was 36.6 cm3 (range, 3.4-245.5 cm3), and tumor volume was not associated with recurrence risk. Both tumors with progression were schwannomas. Conclusions Hypofractionated radiation with 30 Gy at 3 Gy per fraction is an effective, convenient, and well-tolerated alternative for patients with benign meningiomas or schwannomas. Modest hypofractionation provided durable control for a wide range of tumor volumes and should be considered for patients with a limited life expectancy or those unable to receive a more extended fractionated radiation therapy course.

Meningiomas are the most frequent primary brain tumor. Usually, they are curable by surgery, but even after seemingly complete resection, some low-grade lesions recur. Despite recent improvements, signatures having prognostic value in grade I tumors remain poorly characterized. The frequency and delicate location of these tumors suggest that the risk of recurrence might be more accurately predicted. Herein, we show an easy way to evaluate the methylation status of meningiomas and its correlation with the prognosis of the disease. A series of 120 meningiomas, including primary tumors and recurrences, were analyzed histopathologically, and 24 tumor suppressor genes (TSGs) were studied by methylation-specific multiple ligation probe amplification. Long-term follow-up was conducted to classify patients with grade I primary tumors according to their outcomes. We found that hypermethylation in at least one TSG is frequent. The number of hypermethylated TSG per case was significantly higher in recurrences than in primary tumors and in primary benign meningiomas that recurred than in tumors from patients who showed no evidence of disease during follow-up. Finally, hypermethylation in RASSF1A, MLH1, and CDKN2B was an independent prognostic factor associated with the time to recurrence of these benign tumors that were biologically aggressive. To our knowledge, this is one of the widest studies of primary grade I tumors of patients who developed a tumor recurrence. The frequency of epigenetic changes suggests that hypermethylation is an early event in meningiomas, whereas the accumulation of epigenetic changes is related to greater biological aggressiveness and may be a signature of potential clinical relevance.

BACKGROUND Stereotactic radiosurgery (SRS) for benign intracranial meningiomas is an established treatment. OBJECTIVE To summarize the literature and provide evidence-based practice guidelines on behalf of the International Stereotactic Radiosurgery Society (ISRS). METHODS Articles in English specific to SRS for benign intracranial meningioma, published from January 1964 to April 2018, were systematically reviewed. Three electronic databases, PubMed, EMBASE, and the Cochrane Central Register, were searched. RESULTS Out of the 2844 studies identified, 305 had a full text evaluation and 27 studies met the criteria to be included in this analysis. All but one were retrospective studies. The 10-yr local control (LC) rate ranged from 71% to 100%. The 10-yr progression-free-survival rate ranged from 55% to 97%. The prescription dose ranged typically between 12 and 15 Gy, delivered in a single fraction. Toxicity rate was generally low. CONCLUSION The current literature supporting SRS for benign intracranial meningioma lacks level I and II evidence. However, when summarizing the large number of level III studies, it is clear that SRS can be recommended as an effective evidence-based treatment option (recommendation level II) for grade 1 meningioma.

INTRODUCTION: Surgical outcomes and healthcare utilization have been shown to vary based on patient insurance status. We analyzed whether patients’ insurance affects case urgency for and readmission after craniotomy for meningioma resection, using benign meningioma as a model system to minimize confounding from the disease-related characteristics of other neurosurgical pathologies. METHODS: We analyzed 90-day readmission for patients who underwent resection of a benign meningioma in the Nationwide Readmission Database from 2014–2015. RESULTS: A total of 9783 meningioma patients with private insurance (46%), Medicare (39%), Medicaid (10%), self-pay (2%), or another scheme (3%) were analyzed. 72% of all cases were elective; with 78% of cases in privately insured patients being elective compared to 71% of Medicare (p>0.05), 59% of Medicaid patients (OR 2.3, p

BACKGROUND In contrast to benign meningiomas, malignant meningiomas (MM) are rare and associated with an unfavourable prognosis. Reports on MM concern fairly small cohorts, often comprising less than 30 cases. OBJECTIVE To describe the outcome MM and identify factors that may influence survival. METHODS Pathology reports and clinical data of 178 patients treated between 1989 and 2017 for a MM at 6 different international institutions were retrospectively reviewed. Seventy-six patients (42.7%) had a previous history of grade I or grade II meningioma. The patients underwent a total of 380 surgical resections and 72.5% received radiotherapy. Median follow-up was 4.5 yr. RESULTS At data collection, 111 patients were deceased (63.4%) and only 23 patients (13.7%) were alive without any residual tumor on the most recent scan. Median overall survival was 2.9 yr, 95% confidence interval [CI; 2.4, 4.5]. Overall survival rates at 1, 5, and 10 yr, respectively, were: 77.7%, 95% CI [71.6, 84.3], 40%, 95% CI [32.7, 49], and 27.9%, 95% CI [20.9, 37.3]. In the multivariable analysis, age at MM surgery

Preoperative, noninvasive prediction of the meningioma grade is important because it influences the treatment strategy. The purpose of this study was to evaluate the role of radiomics features of postcontrast T1-weighted images (T1C), apparent diffusion coefficient (ADC), and fractional anisotropy (FA) maps, based on the entire tumor volume, in the differentiation of grades and histological subtypes of meningiomas. One hundred thirty-six patients with pathologically diagnosed meningiomas (108 low-grade [benign], 28 high-grade [atypical and anaplastic]), who underwent T1C and diffusion tensor imaging, were included in the discovery set. The T1C image, ADC, and FA maps were analyzed to derive volume-based data of the entire tumor. Radiomics features were correlated with meningioma grades and histological subtypes. Various machine learning classifiers were trained to build classification models to predict meningioma grades. We tested the model in a validation set (58 patients; 46 low-grade; 12 high-grade). The machine learning classifiers showed variable performances depending on the machine learning algorithms. The best classification system for the prediction of meningioma grades had an area under the curve of 0.86 (95% confidence interval [CI], 0.74–0.98) in the validation set. The accuracy, sensitivity, and specificity of the best classifier were 89.7, 75.0, and 93.5% in the validation set, respectively. Various texture parameters differed significantly between fibroblastic and non-fibroblastic subtypes. Radiomics feature-based machine learning classifiers of T1C images, ADC, and FA maps are useful for differentiating meningioma grades. • Preoperative, noninvasive differentiation of the meningioma grade is important because it influences the treatment strategy. • Radiomics feature-based machine learning classifiers of T1C images, ADC, and FA maps are useful for differentiating meningioma grades. • In benign meningiomas, there were significant differences in the various texture parameters between fibroblastic and non-fibroblastic meningioma subtypes.

Background Benign meningiomas constitute 80%–90% of all meningiomas and represent the most common type of central nervous system tumor in adults. The vast majority of meningiomas are minimally symptomatic or asymptomatic early in their onset and thereby can often result in delayed diagnosis. Early diagnosis of meningioma is critical, as it can maximize treatment options and improve outcomes and survival. Although seizures and focal neurologic deficits are considered to be the most prevalent symptoms, depression also may be an important and significant sign. A subtle neurologic depression may be an even early presenting sign of meningioma and may precede more traditional presenting symptoms. Methods We performed a comprehensive literature review that analyzes the results of prospective studies and case reports on this topic. Results Our findings show evidence to suggest that depression may be correlated with meningioma presentation. Its prevalence is possibly increased with an anterior location of the tumor. Conclusions For patients who exhibit nuances of depression without a history of psychiatric illness, an index of suspicion for meningioma may be warranted.

A late complication following cranial irradiation is the induction of tumors, most of which are intracranial meningiomas. The latency period between radiation exposure and diagnosis of radiation- induced meningioma varies with the timing of the initial radiation exposure and total radiation dose. The authors report two cases of meningiomas as a result of highdose irradiation received for a PNET. Both patients underwent surgical removal of the tumor and immunohistochemical examination revealed a benign meningioma. These cases illustrate the importance of continued follow up after cranial irradiation in the pediatric population.

Atypical and anaplastic meningiomas (WHO grade II and III) are uncommon tumors with poorer prognosis than benign meningiomas. They represent a small and heterogeneous subgroup of meningiomas that has more aggressive biological nature and higher frequency of recurrence. Treatment of these tumors remains challenging and recurrence is common even after gross total resection. We report five year experience of an experienced neurosurgical center (INC) reviewing treatment options and predictor of treatment outcomes for malignant meningiomas.

To treat or not to treat an asymptomatic or pauci-symptomatic benign meningioma, that is the question. And if treatment is necessary, what is the best technique: radical resection, sub-total resection or radiotherapy? This question is also pertinent for meningiomas of the skull base, posterior part of the sagittal sinus, anterior part of the foramen magnum and cerebellopontine angle. When the results of the treatment are good, the patient and the surgeon are satisfied. But when a new neurological deficit appears after the treatment, the patient is entitled to obtain compensation. What should be the position of the specialist medical assessor in this situation when the prognosis of these benign tumors is unknown? Is the preoperative information that is due to the patient complete, objective and sufficient? Is the therapeutic indication unquestionable? Is the technique irreproachable? For meningiomas, there is no "evidence-based medicine"; the therapeutic option is often based on the personal experience and/or the education of the surgeon and thus is, in fact, highly subjective.

OBJECTIVE Using the Surveillance, Epidemiology and End Results (SEER) database, we characterized the patterns of surgical recommendations and outcomes after benign meningioma resection in the elderly population. METHODS 27,839 adult meningioma patients were identified in SEER between 1973- 2015 and 6,967 patients were identified between 2016-18. Patients were stratified into four age groups:18-39, 40-59, 60-79, and > 80 years old. The likelihood for recommendation to proceed with resection, extent of resection, and survival outcome were determined using logistic regression models. RESULTS In a multi-variate model that accounted for gender, race, marital status, tumor size, and tumor location, the likelihood of recommendation to proceed with benign meningiomas resection decreased with advancing age. Relative to patients age 40-59, the likelihood of recommendation for surgery were 1.130 (95%CI=0.925-1.380, P=0.230), 0.593 (95%CI=0.531-0.662, P< 0.001), and 0.173 (95%CI=0.146-0.205, P< 0.001) for patients age 18-39, 60-79, and >= 80, respectively. A similar trend in the likelihood of gross total resection (GTR) was observed. Relative to patients age 40-59, the likelihood of gross total resection were 1.009 (95%CI=0.913-1.114, P=0.867), 0.903 (95%CI=0.849-0.961, P=0.001), and 0.580 (95%CI=0.512-0.657, P< 0.001) for patients age 18-39, 60-79, and >= 80, respectively. However, survival after meningioma resection did not vary significantly as a function of patient age. Relative to patients age 40-59, the hazard of death after GTR of meningioma resection were 1.324 (95%CI=0.795-2/203, P=0.280), 0.813 (95%CI=0.639-1.035, P=0.092), and 0.913 (95%CI=0.618-1.350, P=0.649) for patients age 60-79, and >= 80, respectively. These results were validated using SEER data from 2016-2018. CONCLUSION This analysis provide evidence that surgeons exert caution in surgical resection of benign meningioma in the elderly, with decreased likelihood for recommending surgery in this population. In patients selected for and underwent gross resection, survival outcome in the elderly was comparable to their younger counterparts, suggesting safety of procedure in appropriately selected elderly.

Background In cases of meningioma surrounding the optical apparatus, this study sought to reduce the incidence of radiation-induced optical neuropathy resulting from gamma knife surgery (GKS) by dividing the treatment volume into 2 or 3 fractions. Methods Four patients with a large skull base meningioma (1 male and 3 females; median age: 42 years; range: 33–43 yrs) were treated using volume-staged GKS. In stage I, the large basal part of the tumor (13.2 mL; range: 3.9–54.7 mL) was treated with a marginal dose of 13.5 Gy (range: 12–15 Gy). In stage II, treatment focused on the smaller upper portion of the tumor located close to the optical apparatus (4.3 mL; range: 1.5–16.2 mL), and the marginal dose was 9 Gy (range: 8–10 Gy). Results All patients tolerated the treatments well, and tumors regressed over a median follow-up period of 100.5 months (range: 42–122 mos). Specifically, a 34–46% reduction in tumor volume was observed. All four patients presented improvements in the neurological deficits observed prior to GKS treatment, albeit to varying degrees. No adverse effects of radiation or new visual deterioration were observed during the follow-up period. Furthermore, no evidence of new endocrine dysfunction or new cranial nerve neuropathy was observed within a follow-up period of 100.5 months. Conclusion The application of volume-staged GKS using snowman-shape design appears to be an effective approach to control tumor growth when treating benign meningiomas surrounding the optical apparatus. This approach enables the application of higher radiation dosages to facilitate tumor control while still preserving optic nerve function.

Purpose To assess the outcomes of benign meningiomas (BM) treated to two radiation dose levels. Methods and Materials We randomly assigned patients (1:1) with incompletely resected or recurrent BM to 2 radiation doses: 55.8 Gy(relative biological effectiveness [RBE]) and 63.0 Gy(RBE) of fractionated combined proton–photon radiation therapy. The primary endpoint was local control with hypothesis of improved tumor control with higher dose. Secondary endpoints included progression-free survival, overall survival, and rates of treatment-related toxicities. Results Between 1991 and 2000, 47 patients were randomized. Three patients were excluded for nonbenign histology; therefore, 44 patients were analyzed: 22 who received 55.8 Gy(RBE) and 22 who received 63.0 Gy(RBE). The median follow-up was 17.1 years. Local control for the entire cohort was 98% at 10 years and 90% at 15 years. Of the 5 patients with local recurrence, 4 occurred after 10 years of follow-up, and 3 were in the lower dose group (P=.322). In the modified intention to treat analysis, there was no difference in progression-free survival (P=.234) and overall survival (P=.271) between arms. A total of 26 patients (59%) experienced a grade 2 or higher late toxicity, including 9 patients (20%) incurring a cerebrovascular accident (CVA), 7 of which were deemed at least possibly attributable to irradiation. The median time between completion of radiation therapy and CVA was 5.6 years (range, 1.4-14.0 years). Conclusions Fractionated combined proton–photon radiation therapy is effective for BM, with no apparent benefit in dose escalation. Further investigation is needed to better define the risk of late toxicities, including CVA after cranial radiation therapy.

Objective Atypical meningioma has a higher recurrence rate than benign meningioma. The mainstay of treatment is surgery with or without radiation therapy (RT). The objective of this study was to investigate progression-free survival (PFS) and factors associated with postoperative recurrence in patients with atypical meningioma. Methods Patients with diagnoses of atypical menigioma who underwent surgery at Siriraj Hospital during the 2004 to 2014 study period were included. Features potentially associated with PFS and tumor recurrence from clinical records, operative records, and neuroimaging studies were evaluated and analyzed. Results One hundred twenty-six patients (mean age, 55 years) were included. The median PFS was 55 months. The 5-year and 10-year PFS rates were 72.5% and 32%, respectively. The median follow-up duration was 52 months. In multivariate analysis, tumor location (convexity, parasagittal/falcine, intraventricular, skull base) (P = 0.003), and pial invasion (hazard ratio [HR]: 2.02; P = 0.045) were significantly associated with tumor recurrence. Postoperative RT was associated with reduction in tumor recurrence in both univariate (odds ratio: 0.48; P = 0.039) and multivariate analysis (HR: 0.42; P = 0.005). Conclusions Tumor location and pial invasion were significantly correlated with increased incidence of tumor recurrence, and postoperative RT was found to be significantly associated with decreased tumor progression and recurrence.

Benign meningioma undergoing a malignant transformation (to a chondrosarcoma) in intraventricular location is very rare and this is first case report to best of our knowledge. Herein, we report a rare case of malignant transformation of a benign intraventricular meningioma with relevant literature.

To investigate the difference in amide proton transfer (APT)-weighted signals between benign and atypical meningiomas and determine the value of APT imaging for differentiating the two. Fifty-seven patients with pathologically diagnosed meningiomas (benign, 44; atypical, 13), who underwent preoperative MRI with APT imaging between December 2014 and August 2016 were included. We compared normalised magnetisation transfer ratio asymmetry (nMTR asym ) values between benign and atypical meningiomas on APT-weighted images. Conventional MRI features were qualitatively assessed. Both imaging features were evaluated by multivariable logistic regression analysis. The discriminative value of MRI with and without nMTR asym was evaluated. The nMTR asym of atypical meningiomas was significantly greater than that of benign meningiomas (2.46% vs. 1.67%; P

There is a small part of the pathological type of the meningioma has a malignant tendency and patients have the poor prognosis. Looking for effective biomarkers to predict the degree of malignancy of the tumors, will help us to better manage the patient and guide the treatment. The present study aims at investigating the prognostic value of the expression of Stathmin in a series of meningiomas of different grade. We integrated eight published microarray datasets of meningiomas to screen grade biomarkers in meningiomas patients using the WebArrayDB platform. We focused on Stathmin, Using formalin-fixed paraffin-embedded (FFPE) tumor samples, we corroborated the relationship between Stathmin and patient outcomes using qRT-PCR for gene expression. We also found expression of Stathmin that atypical/anaplastic meningiomas have higher expression than benign meningiomas (p0.01). No correlation between Stathmin expression and age, gender and tumor extent of resection was found (p0.05). Moreover, increased Stathmin expression was correlated to higher meningioma grade and shorter disease-free survival (DFS) of meningioma patients with Simpson I resection. Stathmin might be promising targets to improve the cure rates in meningiomas.