Atypical and anaplastic meningiomas in the later decades of life: A national cancer database analysis.

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

Impact of BrainLab VectorVision Infrared-Based Neuronavigation on Surgical Outcomes in Intracranial Meningioma Patients: A Retrospective Study.

BACKGROUND The BrainLab VectorVision neuronavigation system is an image-guided, frameless localization system used intraoperatively, which includes a computer workstation for viewing and analyzing operative microscopic images. This retrospective study aimed to evaluate the use of the BrainLab VectorVision infrared-based neuronavigation imaging system in 80 patients with intracranial meningioma removed surgically between 2013 and 2023. MATERIAL AND METHODS Data were retrospectively collected from 36 patients with convexity meningioma and 44 patients with parasagittal meningioma between 2013 and 2023. The surgical operation of 40 of these patients was performed with the help of neuronavigation, while the other 40 were performed without neuronavigation. Demographic data, preoperative and postoperative radiologic images, craniotomy measurements, surgical complications, and operative times of patients with and without neuronavigation were analyzed. RESULTS Using neuronavigation significantly increased surgery duration (P=0.023). In 6 patients without the use of neuronavigation, the craniotomy had to be enlarged and this resulted in superior sagittal sinus (SSS) damage (P=0.77, P=0.107). Patients for whom neuronavigation was used did not experience any sinus damage and did not require craniotomy enlargement. Postoperative epidural hematoma (EH) developed in 9 patients without navigation, whereas it developed in only 1 patient with navigation (P=0.104). Residual tumors were less common in patients using navigation (P=0.237). CONCLUSIONS The use of neuronavigation allows the incision and craniotomy to be reduced in size. Intraoperatively, it allows the surgeon to master the boundaries of the tumor and surrounding vascular structures, reducing the risk of complications. These results suggest that neuronavigation systems are an effective ancillary in meningioma surgery.

[Prediction of the Natural Course of Meningioma Using CT and MR Images].

The frequency of identification of asymptomatic meningiomas is increasing owing to the advancement and widespread use of CT and MRI. The first choice for asymptomatic meningiomas is observation. Approximately 70% of asymptomatic meningiomas increase in volume on long term follow-up. More than half of them reportedly exhibit a self-limiting pattern, in which growth eventually stops. Imaging findings related to increased meningioma volume include no calcification, large tumor size, high signal intensity inside the tumor on T2-weighted images, high brightness within the tumor on diffusion-weighted images, and perifocal edema. We also highlighted the presence of hypo-intensity of the surface layer on T2-weighted imaging, indicating growth arrest in a self-limiting growth pattern of meningioma. In this article, literature reports on image prediction using CT and MRI regarding the growth of asymptomatic meningiomas were reviewed, along with our report.

[Convexity Meningioma, Parasagittal Meningioma, Falx Meningioma].

During surgery for meningioma, basic surgical techniques and strategies required for the removal of the tumor are common, particularly for tumors located superficially, such as convexity, parasagittal, and falx meningiomas. Four basic surgical techniques, including detachment; devascularization; debulking; and dissection should be combined and repeated in appropriate sequence, tailored to the specific conditions of each tumor. This eventually enables the total circumferential dissection of the tumor from the surrounding tissues. It is essential to retract the tumor towards the space created at the tumor center through internal debulking, rather than retracting the normal brain, to avoid damage to the surrounding brain tissue. During surgery for parasagittal meningioma with venous sinus occlusion, it is crucial to preserve the cortical veins that have developed as collateral pathways to prevent venous complications. During surgery for falx meningioma, the selection of a surgical approach including a contralateral approach based on factors such as the development of bridging veins and significant peritumoral brain edema is required. In this article, detailed surgical procedures for convexity meningioma, parasagittal meningioma, and falx meningioma were described focusing on the application of fundamental surgical techniques tailored to each tumor type.

[Pathological Diagnosis and Genetic Alterations of Meningioma].

Meningiomas, renowned for their histological diversity, are one of the most prevalent brain tumors. Some meningiomas show unusual histomorphology, especially in intraoperative rapid diagnosis. Therefore, clinical and radiological information is crucial for pathological diagnosis. Before the 2021 World Health Organization Classification of Tumors of the Central Nervous System(5th edition), pathological diagnosis relied solely on histopathological features. However, this classification introduced new diagnostic criteria for anaplastic meningiomas, which now include TERT promoter mutations and the homozygous deletion of CDKN2A/B, indicating the necessity of genetic analysis. Some rhabdoid and papillary meningiomas have BAP1 alterations, which tend to demonstrate an aggressive clinical course and may represent a phenotype of BAP1-related tumor predisposition syndrome. Heterozygous deletion of CDKN2A/B and loss of H3 p.K28me3(K27me3)are also associated with poor prognosis. Although some immunohistochemical markers like MTAP may serve as surrogates for the homozygous deletion of CKKN2A/B, genetic analysis is required to confirm TERT promoter mutations. Therefore, in routine clinical practice, neurosurgeons and pathologists prioritize appropriate formalin fixation to facilitate genetic analysis using pathological specimens.

[Imaging Features and Differential Diagnosis of Meningiomas and Their Mimics].

Meningiomas are the most common brain tumors, often in the form of extra-axial masses adhering to the dura mater. Although there are typical imaging findings, meningiomas have a wide variety of imaging findings, owing to their different histological subtypes. Thus, it can be difficult to differentiate meningiomas from other diseases that present with similar imaging findings. This section outlines mimickers for monitoring meningiomas that present with imaging findings similar to those of meningiomas. Diseases that form masses and require differentiation from meningiomas include schwannomas, solitary fibrous tumors, dural metastases, and histiocytosis. Diseases that primarily present as dural thickening and require differentiation from meningiomas include hypertrophic duralitis, fungal infections, and IG4-related diseases. Notably, in addition to the various pathologies that can mimic meningiomas, such as those listed above, there are also cases in which the diagnosis of meningioma is difficult because of additional modifications, such as metastasis or meningioma infarction.

[Defining the Role of Radiotherapy in Meningioma Treatment].

The debate regarding the role and clinical impact of radiotherapy for meningiomas remains underdeveloped due to insufficient evidence. However, following recent revisions in the WHO classification and the integration of molecular diagnostics, there has been a substantial shift in the stratification of recurrence risks. Nevertheless, the specific circumstances under which radiotherapy proves crucial remain unclear. As risk stratification becomes more refined, the effectiveness of radiotherapy in treating high-risk meningiomas continues to be a contentious issue. Concurrently, there is vigorous discussion regarding the management of 'brain invasion in otherwise benign'(BIOB)meningiomas. The incorporation of PET imaging alongside MRI for defining radiation targets is increasingly acknowledged as advantageous. Boron neutron capture therapy(BNCT), which specifically targets the biological characteristics of tumor cells in invasive regions, is also gaining significant traction as a promising therapeutic approach for meningiomas with infiltrative components.

[Preoperative Embolization of Intracranial Meningioma].

Preoperative embolization(POE)of intracranial meningioma is performed worldwide. Although clear evidence of the effectiveness of POE has not been reported in the literature, the technique plays an important role in open surgery, especially for large or skull base meningiomas. The purposes of embolization include: 1)induction of tumor necrosis, resulting in a safer operation, 2)reduction in intraoperative bleeding, and 3)decrease in operative time. Knowledge of the functional vascular anatomy, embolic materials, and endovascular techniques is paramount to ensure safe embolization. Our standard procedure is as follows: 1)embolization is performed several days before open surgery; 2)in cases with strong peritumoral edema, steroid administration or embolization may be performed immediately prior to surgery; 3)patients undergo the procedure under local anesthesia; 4)the microcatheter is inserted as close as possible to the tumor; 5)particulate emboli are the first-line material; 6)embolization is occasionally performed with N-butyl cyanoacrylate(NBCA)glue; and 7)if possible, additional proximal feeder occlusion with coils is performed. The JR-NET study previous showed the situation regarding intracranial tumor embolization in Japan. Endovascular neurosurgeons should fully discuss the indications and strategies for POE with tumor neurosurgeons to ensure safe and effective procedures.

[Surgical Simulation of Meningioma Removal Using 3D Images].

The basics of meningioma surgery are represented in the '4Ds': Detachment, Devascularization, Debulking, and Dissection. When considering the 4Ds, surgical simulation using 3D images is useful, as it allows the surgeon to understand the 3D relationship between the tumor, feeding vessels, and surrounding tissues. However, the hardness of the tumor and the degree of adhesion between the tumor and surrounding tissue are difficult to determine based on 3D images, and must therefore be confirmed using MRI, such as T2-weighted images.

[Current Status of Genetic/Molecular Abnormality Analysis and Prognosis Prediction of Meningioma].

Biological molecular studies of meningiomas have also developed with the development of molecular biological methods. In 2013, Clark et al. reported that driver genetic mutations other than NF2, including TRAF7, KLF4, AKT1, and SMO, were associated with meningioma development. In 2017, Sahm et al. proposed a classification of meningiomas based on global methylation status, which was more accurate in predicting prognosis than conventional WHO grading. In 2022, based on this classification, various groups reported an integrated classification that comprehensively included some biological molecular abnormalities, such as DNA mutations, copy number alterations, and RNA sequences. This field is expected to elucidate the mechanism of meningioma development and further research is expected to lead to the development of effective molecularly targeted therapeutics and biomarkers of radiosensitivity in the future. In this article, we summarize the current status and prospects of these biological molecular studies.

[Benefits and Pitfalls of Re-Operation for Recurrent Meningioma].

Malignant forms of meningioma, such as atypical and anaplastic meningiomas, commonly relapse. Recently, there have been many reports elucidating the molecular biological mechanisms underlying meningioma recurrence. Tumors with loss of CDKN(cyclin dependent kinase)2A and 2B or lack of the tri-methylation of lysine 27 on histone H3 protein have a particularly high recurrence rate. In general, primary treatment for recurrent meningiomas comprises stereotactic radiosurgery(SRS)or stereotactic radiotherapy(SRT). However, re-operation is recommended for SRS-, SRT-refractory tumors. One of the benefits of reoperation is that it allows tumor control while decompressing the normal tissue, and changing the tumor microenvironment. Another is that it facilitates the acquisition of pathological and molecular genetic information, which can enable clinicians to recommend precision medicine. However, during reoperation, it is often difficult to detach the tumor from the surrounding brain tissue and cranial nerves because of severe adhesion. In cases of malignant meningiomas with multiple relapses, it is important to share the purpose and goal of the surgery with the patients and their families. In other words, which is being prioritized more, a high resection rate or functional outcomes? Furthermore, salvage surgery should also be a consideration.

[Meningiomas in the Central Skull Base:From the Perspective of Endoscopic Transnasal Surgery].

Recent advancements in endoscopic transnasal surgery(ETS)have expanded the application of this technique to meningiomas in the central skull base area, offering a less invasive alternative with a potentially lower physical burden on patients than conventional microscopic skull base surgery. Notably, while ETS allows surgeons to reach tumors without traversing the brain and nerves, thus theoretically reducing the risk of cranial nerve damage, it requires a high level of proficiency to avoid inadequate resection and tumor recurrence. In this article, we discuss the various surgical considerations, including preoperative imaging, surgical setting, nasal cavity expansion, skull base opening, tumor removal, and skull base reconstruction, as general procedures for specific meningiomas. We further describe the concept and details of our multi-layer fascial closure technique for dural repair in ETS, underlining the importance of skilled dural reconstruction in preventing postoperative complications. In conclusion, while ETS for skull base meningiomas presents a promising and less invasive treatment option, its success relies heavily on the surgeon's experience and understanding of the skull base anatomy, stressing the need for careful approach selection.

[Jugular Foramen, Foramen Magnum Meningiomas].

The jugular foramen, also known as the foramen magnum, is a highly intricate region of the skull base through which numerous critical blood vessels and nerves traverse. Meningiomas, the most common tumors in neurosurgical pathology, can arise at any location where the meninges are present, posing significant challenges. Meningiomas involving the jugular foramen and sublingual neural tube are particularly notable for their potential to extend from intracranial to extracranial sites, necessitating familiarity with extracranial anatomy, which is not typically encountered in clinical practice. A comprehensive understanding of anatomical characteristics, along with an ample field of view and working space, is crucial for handling the cerebellum, brainstem, and nerves meticulously. The use of surgical support tools such as neuromonitoring and navigation is essential for enhancing the safety of the procedure. Furthermore, preparedness for treatment options, rehabilitation, and adjunctive therapies is vital in the event of neurological symptoms such as those affecting the glossopharyngeal, vagal, or hypoglossal nerves.

[Role of Pharmacotherapy in Treatment of Meningiomas].

Meningiomas constitute the most common primary tumors of the central nervous system. Despite maximum treatment, grade 2/3 meningiomas are associated with a high risk of recurrence. Stereotactic radiosurgery is the treatment of choice as adjuvant treatment for grade 2/3 meningiomas. Currently, pharmacotherapies, including molecular targeted therapy for various growth factors, their receptors, and the associated pathways, have shown limited effectiveness for management of refractory or recurrent meningiomas. Therefore, novel systemic treatment approaches are urgently required in such cases. Recent advances in genetics and epigenetics and the identification of specific genetic alterations have led to new classifications of these tumors and the development of therapeutic targets. Identification of targeted gene mutations may lead to precision-based medicine. Other therapeutic approaches such as immune checkpoint inhibitors rarely elicit a significant response in meningiomas with a high tumor mutation burden. Combination therapies that affect these multiple targets are also considered adjuvant therapeutic options. Comprehensive/in-depth research is warranted to investigate the safety and efficacy of other treatment strategies, including chimeric antigen receptor T-cells, oncolytic virus immunotherapy, and gene therapy. In this article, we review the current evidence regarding the efficacy of systemic treatments available in the literature and discuss recent and ongoing trials for meningiomas.

[Preoperative Embolization Performed Before Meningioma Resection Might Inhibit Tumor Recurrence].

Recent advances in endovascular treatment have improved the safety and efficacy of this procedure, and the number of cases in which preoperative embolization is performed is likely to increase. Preoperative tumor embolization is still a controversial treatment, and as long as it carries a risk of complications, its primary benefit of reducing blood loss during surgery may not be sufficient to justify treatment. We recently reported that preoperative embolization does not significantly increase complications, but may prolong recurrence-free survival. However, currently, tumor embolization is only a preoperative adjunctive therapy, and there is no evidence that it is a stand-alone option for meningioma treatment. Nevertheless, the possibility that tumor embolization alone can promote tumor shrinkage and reduce peripheral oedema has been reported, although the number of cases is small. Further research is needed, but in the future, tumor embolization may become an in-office treatment under certain conditions, such as in cases of poor general condition, multiple meningiomas, recurrent and refractory cases, difficult surgery and cases where re-irradiation is difficult after post-radiation therapy.

[Challenges to Overcome in Clinical Research on Meningiomas].

In contrast to other cancer research areas, the development of chemotherapy and radiotherapy for meningiomas has been challenging, lacking standardized criteria for assessing treatment response and progression. Although efforts by RANO have proposed evaluation criteria, a consensus on effective evaluation parameters for meningiomas remains elusive. This paper underscores the importance of establishing efficacy endpoints in clinical trials, compares efficacy assessment in meningioma research with other solid tumor areas, and outlines the challenges ahead in meningioma research. Recent analyses revealed the absence of consensus on efficacy endpoints in meningioma trials, complicating trial design and hindering cross-trial comparisons. The unique anatomical constraints and histological variability of meningiomas pose challenges in determining appropriate efficacy measures. To address these challenges, future research must focus on accumulating prognostic data, standardizing evaluation criteria, and considering multiple endpoints in trial designs. Akin to other cancer areas, investigating targeted therapies and establishing international consensus on efficacy endpoints are crucial steps forward.

NF2 regulates IP3R-mediated Ca2+ signal and apoptosis in meningiomas.

Meningiomas are the most common primary intracranial tumors and account for nearly 30% of all nervous system tumors. Approximately half of meningioma patients exhibit neurofibromin 2 (NF2) gene inactivation. Here, NF2 was shown to interact with the endoplasmic reticulum (ER) calcium (Ca2+) channel inositol 1,4,5-trisphosphate receptor 1 (IP3R1) in IOMM-Lee, a high-grade malignant meningioma cell line, and the F1 subdomain of NF2 plays a critical role in this interaction. Functional assays indicated that NF2 promotes the phosphorylation of IP3R (Ser 1756) and IP3R-mediated endoplasmic reticulum (ER) Ca2+ release by binding to IP3R1, which results in Ca2+-dependent apoptosis. Knockout of NF2 decreased Ca2+ release and promoted resistance to apoptosis, which was rescued by wild-type NF2 overexpression but not by F1 subdomain deletion truncation overexpression. The effects of NF2 defects on the development of tumors were further studied in mouse models. The decreased expression level of NF2 caused by NF2 gene knockout or mutation affects the activity of the IP3R channel, which reduces Ca2+-dependent apoptosis, thereby promoting the development of tumors. We elucidated the interaction patterns of NF2 and IP3R1, revealed the molecular mechanism through which NF2 regulates IP3R1-mediated Ca2+ release, and elucidated the new pathogenic mechanism of meningioma-related NF2 variants. Our study broadens the current understanding of the biological function of NF2 and provides ideas for drug screening of NF2-associated meningioma.

Stereotactic radiosurgery for intraventricular meningioma: a systematic review and meta-analysis.

BACKGROUND: Intraventricular meningioma (IVM) is a rare subtype of intracranial meningioma, accounting for 9.8 to 14% of all intraventricular tumors. Currently, there is no clear consensus on which patients with IVM should receive conservative treatment, surgery, or stereotactic radiosurgery (SRS). This research aims to analyze the outcomes, including survival and recurrence rates of patients who undergo SRS for IVM as a primary or adjuvant treatment. METHODS: A systematic search was conducted in Scopus, Web of Science, PubMed, and Embase till June 5th 2023. Screening and data extraction were performed by two independent authors. Random-effect meta-analysis was performed to determine the tumor control proportion of IVM cases treated with SRS. Individual patient data (IPD) meta-analysis was performed for the progression-free survival (PFS) of the patients in the follow-up time. All analyses were performed using the R programming language. RESULTS: Out of the overall 132 records, 14 were included in our study, of which only 7 had enough data for the meta-analysis. The tumor control proportion was 0.92 (95% CI, 0.69-0.98) in patients who underwent SRS for primary IVM. The overall tumor control in both primary and adjuvant cases was 0.87 (95% CI, 0.34-0.99). the heterogeneity was not significant in both meta-analyses (P = 0.73 and P = 0.92, respectively). Post-SRS perifocal edema occurred in 16 out of 71 cases (0.16; 95% CI, 0.03-0.56), with no significant heterogeneity (P = 0.32). IPD meta-analysis showed a PFS of 94.70% in a 2-year follow-up. Log-rank test showed better PFS in primary SRS compared to adjuvant SRS (P < 0.01). CONCLUSIONS: According to this study, patients with IVM can achieve high rates of tumor control with a low risk of complications when treated with SRS, regardless of whether they have received prior treatment. Although SRS could be a promising first-line treatment option for asymptomatic IVM, its efficacy in symptomatic patients and its comparison with resection require further investigation.

[The Transcranial Approach for Parasellar Meningiomas].

Patients with parasellar meningiomas often initially present with visual impairment. Understanding the surrounding anatomy is essential when preparing for surgery of parasellar meningiomas, as this region includes various crucial neurovascular structures. Historically, invasive craniotomy, such as the orthozygomatic approach or zygotomy, has often been attempted to access the region; however, the use of these invasive approaches has become less common, because of the accumulation of anatomical knowledge, as well as the development of surgical techniques and devices, including the endonasal endoscopic approach. Herein, we summarize how we perform surgery for parasellar meningiomas, and outline tips and pitfalls that could be useful for young residents and trainees who are new to the skull base field.

[Surgical Approaches for Cerebellopontine Angle/Petroclival Meningiomas].

Considering that most meningiomas are pathologically benign, tumors located in the cerebellopontine angle and petroclival area should be reduced as much as possible, and radiation therapy should be administered if necessary. Consequently, relatively good preservation of cranial nerve function and local lesion control can be expected. However, because the lesions are generally located deep, and are surrounded by various important structures, performing surgical procedures is difficult, and careful management of the surgical strategy is important to avoid complications. Surgical outcomes have dramatically improved with the development of skull base and microsurgical techniques. The main surgical approaches for cerebellopontine angle meningiomas and petroclival meningiomas currently include the anterior and posterior combined transpetrosal, anterior transpetrosal, and lateral suboccipital approaches. Furthermore, with the recent developments in endoscopic surgery, minimally invasive surgery for skull base meningiomas has gradually been introduced. In this article, we explain the preoperative checkpoints, selection of the surgical approach, and surgical techniques for the resection of cerebellopontine angle meningiomas and petroclival meningiomas.