Search Results (26)

Meningiomas are the most common primary intracranial tumors, showing highly heterogeneous behavior and clinical outcomes. While the majority are benign, about one in five meningiomas are classified as higher grade (WHO Grade II–III), characterized by a more aggressive, treatment-resistant pathology. Although surgical resection remains the first-line therapy, peptide receptor radionuclide therapy is emerging as a novel and promising option for advanced, multifocal, or recurrent disease. The theranostic paradigm allows simultaneous detection and treatment of somatostatin receptor-expressing lesions using a single radiopharmaceutical. In this review, we explore the evolving role of PRRT in the management of meningiomas. We provide an integrated overview of preclinical findings—including radiosensitization mechanisms—and summarize the rapidly expanding clinical literature, which in recent years has grown both in patient numbers and in methodological sophistication. Particular emphasis is placed on advances in dosimetry, quantitative imaging, and radiomics, which are beginning to refine patient selection and improve response prediction. Together, current evidence highlights the therapeutic potential of radionuclide therapy in aggressive or refractory meningiomas and underscores the need for further prospective trials to define its optimal clinical application. Full article

Background: Meningiomas are common intracranial tumors in adults. Most are benign WHO grade I (GI) tumors, while approximately 20% are diagnosed as more aggressive WHO grade II (GII) and grade III (GIII) meningiomas. The study aimed to identify genes with tumor grade-related expression and to assess their functional relevance. Methods: RNA sequencing (RNA-seq) was performed to analyze transcriptomes of benign meningothelial (n = 19) and fibrous (n = 11), atypical (n = 18) and anaplastic (n = 12) meningiomas. The data were analyzed for differential genes expression and Gene Set Enrichment Analysis (GSEA). A deposited scRNA-seq dataset was used to define meningioma cellular composition and cell type-specific gene expression enabling deconvolution of RNA-seq data. Results: Unsupervised analysis revealed three tumor clusters corresponding to the histological subtypes of meningothelial (GI), fibrous (GI) and atypical/anaplastic (GII/GIII) meningiomas. Differential analysis identified 5518 protein-coding genes with grade-related changes in expression. GSEA showed that high-grade meningiomas were enriched for processes of cell proliferation, ribosome biogenesis, and metabolism, whereas benign tumors were enriched for cell morphogenesis, transmembrane ion transport, and immune regulation. PGK1 was the most significantly grade-related gene and increased expression of phosphoglycerate kinase 1 in GII and GIII tumors was confirmed by immunohistochemistry. Deconvolution of RNA-seq data revealed grade-related changes in the tumor microenvironment, notably a progressive decrease in border-associated macrophages from WHO GI to GIII tumors. Conclusions: In our study, we characterized key genes and processes dysregulated in high-grade meningiomas, including less understood mechanisms such as metabolic reprogramming, disrupted ion transport, altered immune regulation, and differences in the tumor microenvironment between benign and aggressive tumors. Full article

Background/Objectives: Recurrent meningiomas remain difficult to manage due to the absence of effective systemic therapies and comparatively high treatment failure rates, particularly in high-grade tumors. Stereotactic radiosurgery (SRS) offers a minimally-invasive and precise option, particularly for tumors in surgically complex locations. However, the risks associated with re-irradiation, and recent changes in the WHO classification of CNS tumors highlight the need for more personalized and strategic treatment approaches. This systematic review evaluates the safety, efficacy, and clinical considerations for use of SRS for recurrent meningiomas. Methods: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic literature search was conducted using the PubMed, Scopus, and Web of Science databases for studies reporting outcomes of SRS in recurrent, pathologically confirmed intracranial meningiomas. Studies were excluded if they were commentaries, reviews, case reports with fewer than three cases, or had inaccessible full text. The quality and risk of bias of the included studies were assessed using the modified Newcastle-Ottawa Scale. Data on patient and tumor characteristics, SRS treatment parameters, clinical outcomes, adverse effects, and statistical analysis results were extracted. Results: Sixteen studies were included. For WHO Grade I tumors, 3- to 5-year progression-free survival (PFS) ranged from 85% to 100%. Grade II meningiomas demonstrated more variable outcomes, with 3-year PFS ranging from 23% to 100%. Grade III tumors had consistently poorer outcomes, with reported 1-year and 2-year PFS rates as low as 0% and 46%, respectively. SRS performed after surgery alone was associated with superior outcomes, with local control rates of 79% to 100% and 5-year PFS ranging from 40.4% to 91%. In contrast, tumors previously treated with radiotherapy, with or without surgery, showed substantially poorer outcomes, with 3- to 5-year PFS ranging from 26% to 41% and local control rates as low as 31%. Among patients with prior radiotherapy, outcomes were particularly poor in Grade II and III recurrent tumors. Toxicity rates ranged from 3.7% to 37%, and were generally higher for patients with prior radiation. Predictors of worse PFS included prior radiation, older age, and Grade III histology. Conclusions: SRS may represent a reasonable salvage option for carefully selected patients with recurrent meningioma, particularly following surgery alone. Outcomes were notably worse in high-grade recurrent meningiomas following prior radiotherapy, emphasizing the prognostic significance of both histological grade and treatment history. Notably, the lack of molecular and genetic data in most existing studies represents a key limitation in the current literature. Future prospective studies incorporating molecular profiling may improve risk stratification and support more personalized treatment strategies. Full article

Background: Although its validity has recently been questioned since its introduction, the Simpson grade has remained one of the most relevant factors in estimating the recurrence risk of intracranial meningiomas. This study aims to assess its role in spinal meningiomas through a retrospective analysis of a mono-institutional surgical series and literature meta-analysis. Methods: We conducted a systematic review and meta-analysis of the literature from 1980 to 2023, complemented by a mono-institutional series of 74 patients treated at “Santa Maria delle Grazie” hospital. Demographic, clinical, neuroradiological, pathological, surgical, and outcome data of case series were analyzed. For the meta-analysis, studies were selected based on predefined inclusion criteria, and a fixed-effects model was used to synthesize data due to assumed homogeneity among included studies. Statistical analyses included odds ratios (OR) for recurrence risk and assessment of publication bias using Peter’s test. Results: Mono-institutional sample included 74 patients, most of whom were women (85%) with a median age of 61.9 years. The thoracic spine was the most common tumor location (81%). Recurrences occurred in patients with Simpson grade II and III resections. The meta-analysis involved 2142 patients from 25 studies and revealed a significantly higher recurrence rate for Simpson grades III–V compared to grades I–II (OR 0.10; CI95 0.06–0.16). Additionally, Simpson grade II had a higher recurrence risk than grade I (OR 0.42; CI95 0.20–0.90). Conclusions: The Simpson grading remains a valid predictor of recurrence also for spinal meningiomas. Our findings revealed a significant increase in recurrence rate with higher Simpson grades. These results support the need to strive for Simpson grade I resection when feasible. Full article

In humans, tenascin-C (TN-C) expression has been detected in more aggressive neoplasms of the central nervous system, such as gliomas and meningiomas. No study has analyzed the immune expression of TN-C in canine meningioma. The current study aimed to investigate the immunohistochemical distribution of TN-C in different grades of canine meningiomas. Twenty-one cases of canine meningioma (12 grade I, 6 grade II, and 3 grade III) were analyzed. All samples were examined by immunohistochemistry with the following antibodies: TN-C, epithelial membrane antigen (EMA), Ki-67, pan-cytokeratin (Pan CK), and vimentin. The histopathological diagnosis of meningioma was reinforced with the positive labeling of vimentin (moderate to strong) and EMA (mild to moderate) in neoplastic cells in most cases, independently of its grade or subtype. The immunoreactivity of TN-C was irregular: mild in grade I, moderate in grade II, and moderate to severe in grade III neoplasms. Usually, immune positivity was observed in the stroma and perivascular space in all subtypes. In addition, the concentric whorls of neoplastic cells were labeled positive in some psammomatous and transitional meningiomas. The reaction to TN-C was more significant in grade II and III tumors. The immunohistochemical findings of the current study suggest that TN-C can act as a stromal marker, mainly in grade II or III meningiomas. Full article

Background: Meningiomas are the most prevalent benign intracranial tumors. When they are of the invasive subtypes, i.e., grades II and III, they can recur rapidly and present a real challenge for physicians. This study is focused on the use of stereotactic radiosurgery to manage high-grade meningiomas. Method: Medline via PubMed was searched from inception to December 2022 to retrieve studies on stereotactic radiation therapy for patients with grade II-III meningiomas. This study was conducted under PRISMA guidelines. Result: A total of 29 articles involving 1446 patients with grade II-III meningiomas treated with stereotactic radiation therapy were included in the present study. Of these studies, 11 were conducted exclusively on patients with atypical meningiomas (grade II), 1 targeted anaplastic meningiomas (grade III), and 17 articles were carried out on both grade II and III meningiomas. The pooled 1, 2, 3, 5, and 10-year overall survival (OS) of grade II meningiomas was 0.96 [p < 0.01], 0.89 [p = 0.01], 0.90 [p = 0.09], 0.81 [p < 0.01], and 0.66 [p = 0.55], respectively. The pooled 2, 5, and 10-year OS of grade III meningiomas was 0.64 [p = 0.01], 0.41 [p = 0.01], and 0.19 [p < 0.01], respectively. Conclusions: Although long-term prospective studies are still required, the outcomes of stereotactic radiation therapy appear promising regarding overall outcome and progression-free survival. Full article

Surgery stands as the primary treatment for spheno-orbital meningiomas, following a symptoms-oriented approach. We discussed the decision-making process behind surgical strategies through a review of medical records from 80 patients who underwent surgical resection at the University of Naples Federico II. Different surgical approaches were employed based on the tumor’s location relative to the optic nerve’s long axis, categorized into lateral (type I), medial (type II), and diffuse (type III). We examined clinical, neuroradiological, surgical, pathological, and outcome factors. Proptosis emerged as the most frequent symptom (97%), followed by visual impairment (59%) and ocular motility issues (35%). Type I represented 20%, type II 43%, and type III 17%. Growth primarily affected the optic canal (74%), superior orbital fissure (65%), anterior clinoid (60%), and orbital apex (59%). The resection outcomes varied, with Simpson grades I and II achieved in all type I cases, 67.5% of type II, and 18% of type III. Recurrence rates were highest in type II (41.8%) and type III (59%). Improvement was notable in proptosis (68%) and visual function (51%, predominantly type I). Surgery for spheno-orbital meningiomas should be tailored to each patient, considering individual characteristics and tumor features to improve quality of life by addressing primary symptoms like proptosis and visual deficits. Full article

Higher-grade meningiomas (WHO grade II and III) are characterized by aggressive invasiveness and high postoperative recurrence rates. The prognosis remains inadequate even with adjuvant radiotherapy and currently there is no definitive pharmacological treatment strategy and target for malignant meningiomas. This study aims to unveil the mechanisms driving the malignant progression of meningiomas and to identify potential inhibitory targets, with significant clinical implications. Implementing techniques such as protein immunoprecipitation, mass spectrometry, RNA interference, and transcriptome sequencing, we investigated the malignancy mechanisms in meningioma cell lines IOMM-LEE and CH157-MN. Additionally, in vivo experiments were carried out on nude mice. We discovered a positive correlation between meningioma malignancy and the levels of the receptor for activated C kinase 1 (RACK1), which interacts with CSNK2B, the β subunit of casein kinase 2 (CK2), inhibiting its ubiquitination and subsequent degradation. This inhibition allows CK2 to activate the NF-κb pathway, which increases the transcription of CDK4 and cyclin D3, resulting in the transition of the cell cycle into the G2/M phase. The RACK1 inhibitor, harringtonolide (HA), significantly suppressed the malignant tendencies of meningioma cells. Our study suggests that RACK1 may play a role in the malignant progression of meningiomas, and therefore, targeting RACK1 could emerge as an effective strategy for reducing the malignancy of these tumors. Full article

Background: Preoperative, noninvasive prediction of meningioma grade is important for therapeutic planning and decision making. In this study, we propose a dual-level augmentation strategy incorporating image-level augmentation (IA) and feature-level augmentation (FA) to tackle class imbalance and improve the predictive performance of radiomics for meningioma grading on Magnetic Resonance Imaging (MRI). Methods: This study recruited 160 consecutive patients with pathologically proven meningioma (129 low-grade (WHO grade I) tumors; 31 high-grade (WHO grade II and III) tumors) with preoperative multisequence MRI imaging. A dual-level augmentation strategy combining IA and FA was applied and evaluated in 100 repetitions in 3-, 5-, and 10-fold cross-validation. Results: The best area under the receiver operating characteristics curve of our method in 100 repetitions was ≥0.78 in all cross-validations. The corresponding cross-validation sensitivities (cross-validation specificity) were 0.72 (0.69), 0.76 (0.71), and 0.63 (0.82) in 3-, 5-, and 10-fold cross-validation, respectively. The proposed method achieved significantly better performance and distribution of results, outperforming single-level augmentation (IA or FA) or no augmentation in each cross-validation. Conclusions: The dual-level augmentation strategy using IA and FA significantly improves the performance of the radiomics model for meningioma grading on MRI, allowing better radiomics-based preoperative stratification and individualized treatment. Full article

Meningiomas are common intracranial tumors in adults. Abnormal microRNA (miRNA) expression plays a role in their pathogenesis. Change in miRNA expression level can be caused by impaired epigenetic regulation of miRNA-encoding genes. We found the genomic region covering the MIR193B gene to be DNA hypermethylated in meningiomas based on analysis of genome-wide methylation (HumanMethylation450K Illumina arrays). Hypermethylation of MIR193B was also confirmed via bisulfite pyrosequencing. Both hsa-miR-193b-3p and hsa-miR-193b-5p are downregulated in meningiomas. Lower expression of hsa-miR-193b-3p and higher MIR193B methylation was observed in World Health Organization (WHO) grade (G) II/III tumors as compared to GI meningiomas. CCND1 mRNA was identified as a target of hsa-miR-193b-3p as further validated using luciferase reporter assay in IOMM-Lee meningioma cells. IOMM-Lee cells transfected with hsa-miR-193b-3p mimic showed a decreased cyclin D1 level and lower cell viability and proliferation, confirming the suppressive nature of this miRNA. Cyclin D1 protein expression (immunoreactivity) was higher in atypical than in benign meningiomas, accordingly to observations of lower hsa-miR-193b-3p levels in GII tumors. The commonly observed hypermethylation of MIR193B in meningiomas apparently contributes to the downregulation of hsa-miR-193b-3p. Since hsa-miR-193b-3p regulates proliferation of meningioma cells through negative regulation of cyclin D1 expression, it seems to be an important tumor suppressor in meningiomas. Full article

Background: There is currently no consensus in the field regarding whether a frontal or lateral approach is superior for microsurgical resection of olfactory groove meningiomas (OGM). Due to the lack of uniformity in classifying lesions and inherent differences in reporting outcomes after varying operative approaches, the best practice for approaching these lesions is yet to be determined. Objective: This study aimed to assess various surgical approaches undertaken for OGMs, investigate procedural aspects influencing the extent of resection, and analyze the respective complication rate associated with each approach. We performed a comprehensive literature review of presenting signs and symptoms in OGM patients, their surgical management, and the reported surgical outcomes. To address the lack of uniform data reporting across studies and to take more recent translational studies into account, we developed a new classification system for OGMs that can remedy the existing deficiencies in comparability of reporting. Methods: We conducted a PRISMA-guided literature search for surgical reports on OGMs published in the MRI era using broad search terms such as ‘olfactory groove meningioma’ and ‘surgery’, which yielded 20,672 results. After title screening and removal of duplicates, we assessed 871 studies on the specific surgical management of olfactory groove meningiomas. Following the application of exclusion criteria and abstract screening, a set of 27 studies was chosen for the final analysis of a pooled cohort of these reported patient outcomes. Results: The final twenty-seven studies included in our in-depth analysis identified a total of 1016 individual patients who underwent open microsurgical resection of OGMs. The approaches used included: pterional/unilateral, bifrontal with variations, and anterior interhemispheric approaches. Across all studies, gross total resection (Simpson Grades I or II) was achieved in 91.4% of cases, and subtotal resection (Grades III and IV) was reported in 8.6% of cases. A cumulative twenty-seven percent of surgical OGM patients sustained some form of complications. Minor issues accounted for 22.2% (CSF leak, seizures, infection, transient cranial nerve palsies, hydrocephalus), whereas major issues comprised 4.7% (hemorrhage, ischemic infarct, malignant cerebral edema). We then examined the correlation between these complications and the surgical approach chosen. Among pooled cohort of 426 patients who underwent unilateral approaches, 14% experienced minor complications, and 2.1% experienced major complications. For the mixed cohort of 410 patients who underwent bifrontal approaches, 24.6% experienced minor complications, and 7% experienced major complications. Conclusions: Unilateral approaches appear to have lower complication rates for the resection of OGMs compared to bilateral approaches. However, the extent of resection is not uniformly reported, making it difficult to identify differences. The use of an improved preoperative classification and scoring system can help establish a more coherent system to select the most suitable approach and to uniformly report surgical outcomes, such as EOR and complication rates specific to a given OGM and its surgical approach. Full article

Meningioma is the most common primary tumor of the central nervous system (CNS). Individualized treatment strategies should be formulated for the patients according to the WHO (World Health Organization) grade. Our aim was to investigate the effectiveness of various machine learning and traditional statistical models in predicting the WHO grade of preoperative patients with meningioma. Patients diagnosed with meningioma after surgery in West China Hospital and Shangjin Hospital of Sichuan University from 2009 to 2016 were included in the study cohort. As the training cohort (n = 1975), independent risk factors associated with high-grade meningioma were used to establish the Nomogram model. which was validated in a subsequent cohort (n = 1048) from 2017 to 2019 in our hospital. Logistic regression (LR), XGboost, Adaboost, Support Vector Machine (SVM), K-Nearest Neighbor (KNN), and Random Forest (RF) models were determined using F1 score, recall, accuracy, the area under the curve (ROC), calibration plot and decision curve analysis (DCA) were used to evaluate the different models. Logistic regression showed better predictive performance and interpretability than machine learning. Gender, recurrence history, T1 signal intensity, enhanced signal degree, peritumoral edema, tumor diameter, cystic, location, and NLR index were identified as independent risk factors and added to the nomogram. The AUC (Area Under Curve) value of RF was 0.812 in the training set, 0.807 in the internal validation set, and 0.842 in the external validation set. The calibration curve and DCA (Decision Curve Analysis) indicated that it had better prediction efficiency of LR than others. The Nomogram preoperative prediction model of meningioma of WHO II and III grades showed effective prediction ability. While machine learning exhibits strong fitting ability, it performs poorly in the validation set. Full article

Meningiomas (MGMs) are currently classified into grades I, II, and III. High-grade tumors are correlated with decreased survival rates and increased recurrence rates. The current grading classification is based on histological criteria and determined only after surgical tumor sampling. This study aimed to identify plasma metabolic alterations in meningiomas of different grades, which would aid surgeons in predefining the ideal surgical strategy. Plasma samples were collected from 51 patients with meningioma and classified into low-grade (LG) (grade I; n = 43), and high-grade (HG) samples (grade II, n = 5; grade III, n = 3). An untargeted metabolomic approach was used to analyze plasma metabolites. Statistical analyses were performed to select differential biomarkers among HG and LG groups. Metabolites were identified using tandem mass spectrometry along with database verification. Five and four differential biomarkers were identified for HG and LG meningiomas, respectively. To evaluate the potential of HG MGM metabolites to differentiate between HG and LG tumors, a receiving operating characteristic curve was constructed, which revealed an area under the curve of 95.7%. This indicates that the five HG MGM metabolites represent metabolic alterations that can differentiate between LG and HG meningiomas. These metabolites may indicate tumor grade even before the appearance of histological features. Full article

Purpose: Grade II meningiomas are rarer than Grade I, and when operated on, bear a higher risk of local recurrence, with a 5-year progression free survival (PFS) ranging from 59 to 90%. Radiotherapy (RT) or radiosurgery, such as Gamma Knife radiosurgery (GKRS) can reduce the risk of relapse in patients with residual disease, even if their role, particularly after gross total resection (GTR), is still under debate. Main goal of this study was to compare the outcomes of different post-surgical management of grade II meningiomas, grouped by degree of surgical removal (Simpson Grade); next in order we wanted to define the role of GKRS for the treatment of residual disease or relapse. Methods: from November 2016 to November 2020 all patients harboring grade II meningiomas, were divided into three groups, based on post-surgical management: (1) wait and see, (2) conventional adjuvant radiotherapy and (3) stereotactic GKRS radiosurgery. Relapse rate and PFS were registered at the time of last follow up and results were classified as stable, recurrence next to or distant from the surgical cavity. In the second part of the study we collected data of all patients who underwent GKRS in our Centers from November 2017 to November 2020. Results: A total of 37 patients were recruited, including seven patients with multiple meningiomas. Out of 47 meningiomas, 33 (70.2%) were followed with a wait and see strategy, six (12.7%) were treated with adjuvant radiotherapy, and 8 patients (17.0%) with adjuvant GKRS. Follow up data were available for 43 (91.4%) meningiomas. Within the wait and see group, recurrence rates differed based on Simpson grades, lower recurrence rates being observed in three Simpson I cases (30%) compared to twelve relapses (60%) in patients with Simpson grade II/III. Finally, out of the 24 meningiomas undergoing GKRS (8 residual and 16 recurrence), 21 remained stable at follow up. Conclusions: Gross total resection (GTR) Simpson II and III have a significantly worse outcome as compared to Simpson I. The absence of adjuvant treatment leads to significant worsening of the disease progression curve. Adjuvant radiotherapy, especially GKRS, provides good local control of the disease and should be considered as an adjuvant treatment in all cases where Simpson I resection is not possible. Full article

Somatostatin receptor (SSTR)-targeted peptide receptor radionuclide therapy (PRRT) represents a promising approach for treatment-refractory meningiomas progressing after surgery and radiotherapy. The aim of this study was to provide outcomes of patients harboring refractory meningiomas treated by 177Lu-DOTATATE and an overall analysis of progression-free survival at 6 months (PFS-6) of the same relevant studies in the literature. Eight patients with recurrent and progressive WHO grade II meningiomas were treated after multimodal pretreatment with 177Lu-DOTATATE between 2019 and 2022. Primary and secondarily endpoints were progression-free survival at 6-months (PFS-6) and toxicity, respectively. PFS-6 analysis of our case series was compared with other similar relevant studies that included 86 patients treated with either 177Lu-DOTATATE or 90Y-DOTATOC. Our retrospective study showed a PFS-6 of 85.7% for WHO grade II progressive refractory meningiomas. Treatment was clinically and biologically well tolerated. The overall analysis of the previous relevant studies showed a PFS-6 of 89.7% for WHO grade I meningiomas (n = 29); 57.1% for WHO grade II (n = 21); and 0 % for WHO grade III (n = 12). For all grades (n = 86), including unknown grades, PFS-6 was 58.1%. SSTR-targeted PRRT allowed us to achieve prolonged PFS-6 in patients with WHO grade I and II progressive refractory meningiomas, except the most aggressive WHO grade II tumors. Large scale randomized trials are warranted for the better integration of PRRT in the treatment of refractory meningioma into clinical practice guidelines. Full article