Symptomatic Meningiomas Research Articles

Evolving concepts in meningioma management in the era of genomics.

Meningioma is the most common type of primary brain tumor. Surgical resection followed by surveillance is the first-line treatment for the majority of symptomatic meningiomas; however, recent advances in molecular sequencing, DNA methylation, proteomics, and single-cell sequencing provide insights into further characterizing this heterogeneous group of tumors with a wide range of prognoses. A subset of these tumors are highly aggressive and cause severe morbidity and mortality. Therefore, identifying those individuals with a poor prognosis and intervening are critical. This review aims to help readers interpret the molecular profiling of meningiomas to identify patients with worse prognoses and guide the management and strategy for surveillance.

Regression of all untreated lesions in multifocal low-grade meningioma following fractionated stereotactic radiotherapy-abscopal effect or spontaneous regression? : Case report and review of the literature.

Abscopal effects have been reported predominantly in metastatic cancers, indicating aradiographic response in alesion that has not been included in the radiotherapy target volume. The response is interpreted as ahumoral immune response to radiotherapy-generated tumour-specific antigens. In this case study, we present the first histologically confirmed multifocal low-grade meningioma with spontaneous regression of all other lesions after conventionally fractionated stereotactic radiotherapy (RT). Two localisations, right frontal and right spheno-orbital, were resected at the time of the initial diagnosis in a66-year-old woman. RT was performed 1year later to aprogressive occipital lesion at the cerebral falx. Regular magnetic resonance imaging (MRI) showed slightly decreasing tumour volume in untreated lesions 1year after RT and continued during further follow-up. Up to > 7years after treatment, MRI demonstrated an almost complete response of all initial lesions. Two prior reports withmeningioma were published in onepatient with an atypical meningioma after conventionally fractionated RT and anotherpatient with an intracranial meningiomatosis after radiosurgery. This case study supports the concepts of treating only progressive or symptomatic meningioma lesions locally and careful regular MRI surveillance for further assessment. Potential active interventions to trigger an abscopal effect are currently not known. Further research of this beneficial effect for our patients should be supported.

Abstract 2346: Meningioma molecular classification predict response to surgical resection and adjuvant radiotherapy: An integrated clinicomolecular analysis

Abstract Importance: Meningiomas are the most common primary brain tumor and a heterogeneous disease with a need to study response to surgery and adjuvant RT in the context of contemporary molecular classifications. Objective: The gold standard for treatment of symptomatic meningiomas has been surgical resection including complete removal of tumor and its surrounding dural margin, although the necessity of different degrees of marginal resection is controversial. Adjuvant radiotherapy (RT) is generally reserved for aggressive or subtotally resected (STR) meningiomas. However, uncertainty exists regarding optimal case selection for RT and response to treatment is variable. We aimed to examine the effects of treatment (surgery/RT), molecular, and clinical factors on meningiomas in the context of molecular classifications. Design, Setting, and Participants: In this retrospective analysis, a 20-year cohort of 2490 patients with meningiomas were assembled across 10 institutions. Molecular data (DNA methylation, RNA sequencing) was generated for 1645 cases. Propensity score matching (PSM) was performed for key baseline covariates including WHO grade and molecular classifications, mimicking a randomized, molecular pathology informed clinical trial. Main Outcome and Measures: Progression-free survival (PFS), and overall survival (OS) were assessed based on extent of resection (EOR), Simpson grade, and receipt of adjuvant RT. Results: Gross total resection (GTR) was associated with improved PFS across all molecular groups. The PFS benefit of GTR was lessened in molecularly-defined proliferative meningiomas (HR 0.69, 95%CI 0.50-0.95), but OS benefit was enhanced (HR 0.52, 95%CI 0.30-0.93). Surgically treating the dural margin (Simpson grade 1/2) was associated with improved PFS compared to removal of tumor alone (Simpson grade 3) particularly for immunogenic (HR 0.16, 95%CI 0.03-0.82) and NF2-wildtype meningiomas (HR 0.24, 95%CI 0.11-0.53). Adjuvant RT was associated with improved PFS across all molecular classifications. Molecular groups could reliably predict response to RT, even when controlling for WHO grade and EOR with immunogenic and NF2-wildtype meningiomas benefitting most while proliferative meningiomas are largely RT-resistant (HR 0.96, 95%CI 0.67-1.37). Conclusion: This study is the first to investigate interactions between contemporary molecular classifications and response to both surgical resection and adjuvant RT in a large, multi-institutional cohort of molecularly defined, clinically annotated meningioma cases. Citation Format: Justin Z. Wang, Alexander P. Landry, Vikas Patil, Andrew Ajisebutu, Christopher D. Wilson, Aaron Cohen-Gadol, Ghazaleh Tabatabai, Silky Chotai, Jill Barnholtz-Sloan, Rebecca Yakubov, Mark Wilson, Ramneet Kaloti, Alexander Rebchuk, Damian A. Almiron Bonnin, Eric C. Holland, Stephen Yip, Felix Sahm, Kenneth Aldape, The International Consortium on Meningiomas, Farshad Nassiri, Gelareh Zadeh. Meningioma molecular classification predict response to surgical resection and adjuvant radiotherapy: An integrated clinicomolecular analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2346.

Predicting histological grade in symptomatic meningioma by an objective estimation of the tumoral surface irregularity

IntroductionPredicting the histopathologic grade of meningioma is relevant because local recurrence is significantly greater in WHO grade II–III compared to WHO grade I tumours, which would ideally benefit from a more aggressive surgical strategy. It has been suggested that higher WHO grade tumours are more irregularly-shaped. However, irregularity is a subjective and observer-dependent feature. In this study, the tumour surface irregularity of a large series of meningiomas, measured upon preoperative MRI, is quantified and correlated with the WHO grade. MethodsUnicentric retrospective observational study of a cohort of symptomatic meningiomas surgically removed in the time period between January 2015 and December 2022. Using specific segmentation software, the Surface Factor (SF) was calculated for each meningioma. SF is an objective parameter that compares the surface of a sphere (minimum surface area for a given volume) with the same volume of the tumour against the actual surface of the tumour. This ratio varies from 0 to 1, being 1 the maximum sphericity. Since irregularly-shaped meningiomas present proportionally greater surface area, the SF tends to decrease as irregularity increases. SF was correlated with WHO grade and its predictive power was estimated with ROC curve analysis. ResultsA total of 176 patients (64.7% females) were included in the study; 120 WHO grade I (71.9%), 43 WHO grade II (25.7%) and 4 WHO grade III (2.4%). A statistically significant difference was found between the mean SF of WHO grade I and WHO grade II–III tumours (0.8651 ± 0.049 versus 0.7081 ± 0.105, p < 0.0001). Globally, the SF correctly classified more than 90% of cases (area under ROC curve 0.940) with 93.3% sensibility and 80.9% specificity. A cutoff value of 0.79 yielded the maximum precision, with positive and negative predictive powers of 82.6% and 92.6%, respectively. Multivariate analysis yielded SF as an independent prognostic factor of WHO grade. ConclusionThe Surface Factor is an objective and quantitative parameter that helps to identify aggressive meningiomas preoperatively. A cutoff value of 0.79 allowed differentiation between WHO grade I and WHO grade II–III with high precision.

NIMG-75. POSTOPERATIVE68GA-DOTATATE/PET-CT IMAGING IS PROGNOSTIC FOR PROGRESSION-FREE SURVIVAL IN MENINGIOMA WHO GRADE 1: A PROSPECTIVE SINGLE-CENTER STUDY

Abstract PURPOSE Microsurgical tumor resection represents the first-line treatment for symptomatic meningiomas, and extent of resection has been shown to be of prognostic importance. Assessment of tumor remnants with somatostatin receptor PET proves to be superior to intraoperative estimation with Simpson grading or MRI. However, prognostic relevance of postoperative PET for progression-free survival in meningiomas remains unclear. METHODS We conducted a prospective study including patients with surgically removed meningioma WHO grade 1 and collected clinical and imaging data. All patients received postoperative MRI and 68Gallium-DOTATATE/PET, and were followed regularly with MRI surveillance scans for detection of tumor recurrence/progression. RESULTS We included 46 patients with 49 tumors. Mean age at diagnosis was 57.8 ± 1.7 years with a male-to-female ratio of 1:1.7. Local tumor progression occurred in 7/49 patients (14%) after a median follow-up of 52 months. Positive PET was associated with an increased risk for progression (*p = 0.015) and a lower progression-free survival (*p = 0.029) whereas MRI was not. 20/20 patients (100%) with negative PET findings remained recurrence-free. Location of recurrence/progression on MRI was adjacent to regions where postoperative PET indicated tumor remnants in all cases. Gross tumor volumes were higher on PET compared to MRI (*p = 0.032). CONCLUSION Our data show that 68Ga-DOTATATE/PET is highly sensitive in revealing tumor remnants in patients with meningioma WHO grade 1. Negative PET findings were associated with a higher progression-free survival, thus improving surveillance. In patients with tumor remnants, additional PET can optimize adjuvant radiotherapy target planning of surgically resected meningiomas.

Predicción del grado histológico en meningiomas sintomáticos mediante una estimación objetiva de la irregularidad de su superficie

IntroductionPredicting the histopathologic grade of meningioma is relevant because local recurrence is significantly greater in WHO grade II–III compared to WHO grade I tumors, which would ideally benefit from a more aggressive surgical strategy. It has been suggested that higher WHO grade tumors are more irregularly-shaped. However, irregularity is a subjective and observer-dependent feature. In this study, the tumor surface irregularity of a large series of meningiomas, measured upon preoperative MRI, is quantified and correlated with the WHO grade. MethodsUnicentric retrospective observational study of a cohort of symptomatic meningiomas surgically removed in the time period between January 2015 and December 2022. Using specific segmentation software, the surface factor (SF) was calculated for each meningioma. SF is an objective parameter that compares the surface of a sphere (minimum surface area for a given volume) with the same volume of the tumor against the actual surface of the tumor. This ratio varies from 0 to 1, being 1 the maximum sphericity. Since irregularly-shaped meningiomas present proportionally greater surface area, the SF tends to decrease as irregularity increases. SF was correlated with WHO grade and its predictive power was estimated with ROC curve analysis. ResultsA total of 176 patients (64.7% females) were included in the study; 120 WHO grade I (71.9%), 43 WHO grade II (25.7%) and 4 WHO grade III (2.4%). A statistically significant difference was found between the mean SF of WHO grade I and WHO grade II–III tumors (0.8651±0.049 versus 0.7081±0.105, p<0.0001). Globally, the SF correctly classified more than 90% of cases (area under ROC curve 0.940) with 93.3% sensibility and 80.9% specificity. A cutoff value of 0.79 yielded the maximum precision, with positive and negative predictive powers of 82.6% and 92.6%, respectively. Multivariate analysis yielded SF as an independent prognostic factor of WHO grade. ConclusionThe surface factor is an objective and quantitative parameter that helps to identify aggressive meningiomas preoperatively. A cutoff value of 0.79 allowed differentiation between WHO grade I and WHO grade II–III with high precision.

P15.11.B POSTOPERATIVE68GA-DOTATATE/PET-CT IMAGING IS PROGNOSTIC FOR PROGRESSION-FREE SURVIVAL IN MENINGIOMA WHO GRADE 1: A PROSPECTIVE SINGLE-CENTER STUDY

Abstract BACKGROUND Microsurgical tumor resection represents the first-line treatment for symptomatic meningiomas, and extent of resection has been shown to be of prognostic importance. Assessment of tumor remnants with somatostatin receptor PET proves to be superior to intraoperative estimation with Simpson grading or MRI. However, prognostic relevance of postoperative PET for progression-free survival in meningiomas remains unclear. METHODS We conducted a prospective study including patients with surgically removed meningioma WHO grade 1 and collected clinical and imaging data. All patients received postoperative MRI and 68Gallium-DOTATATE/PET, and were followed regularly with MRI surveillance scans for detection of tumor recurrence/progression. RESULTS We included 46 patients with 49 tumors. Mean age at diagnosis was 57.8 ± 1.7 years with a male-to-female ratio of 1:1.7. Local tumor progression occurred in 7/49 patients (14%) after a median follow-up of 52 months. Positive PET was associated with an increased risk for progression (*p = 0.015) and a lower progression-free survival (*p = 0.029) whereas MRI was not. 20/20 patients (100%) with negative PET findings remained recurrence-free. Location of recurrence/progression on MRI was adjacent to regions where postoperative PET indicated tumor remnants in all cases. Gross tumor volumes were higher on PET compared to MRI (*p = 0.032). CONCLUSION Our data show that 68Ga-DOTATATE/PET is highly sensitive in revealing tumor remnants in patients with meningioma WHO grade 1. Negative PET findings were associated with a higher progression-free survival, thus improving surveillance. In patients with tumor remnants, additional PET can optimize adjuvant radiotherapy target planning of surgically resected meningiomas.

Postoperative [68Ga]Ga-DOTA-TATE PET/CT imaging is prognostic for progression-free survival in meningioma WHO grade 1

PurposeTumor resection represents the first-line treatment for symptomatic meningiomas, and the extent of resection has been shown to be of prognostic importance. Assessment of tumor remnants with somatostatin receptor PET proves to be superior to intraoperative estimation with Simpson grading or MRI. In this preliminary study, we evaluate the prognostic relevance of postoperative PET for progression-free survival in meningiomas.MethodsWe conducted a post hoc analysis on a prospective patient cohort with resected meningioma WHO grade 1. Patients received postoperative MRI and [68Ga]Ga-DOTA-TATE PET/CT and were followed regularly with MRI surveillance scans for detection of tumor recurrence/progression.ResultsWe included 46 patients with 49 tumors. The mean age at diagnosis was 57.8 ± 1.7 years with a male-to-female ratio of 1:1.7. Local tumor progression occurred in 7/49 patients (14%) after a median follow-up of 52 months. Positive PET was associated with an increased risk for progression (*p = 0.015) and a lower progression-free survival (*p = 0.029), whereas MRI was not. 20 out of 20 patients (100%) with negative PET findings remained recurrence-free. The location of recurrence/progression on MRI was adjacent to regions where postoperative PET indicated tumor remnants in all cases. Gross tumor volumes were higher on PET compared to MRI (*p = 0.032).ConclusionOur data show that [68Ga]Ga-DOTA-TATE PET/CT is highly sensitive in revealing tumor remnants in patients with meningioma WHO grade 1. Negative PET findings were associated with a higher progression-free survival, thus improving surveillance. In patients with tumor remnants, additional PET can optimize adjuvant radiotherapy target planning of surgically resected meningiomas.

Clinical management of seizures in patients with meningiomas: Efficacy of surgical resection for seizure control and patient-tailored postoperative anti-epileptic drug management.

Meningiomas are the most common primary intracranial tumor. They are slow growing and often incidentally found tumors that arise from the arachnoid villi. As they grow, they have a greater likelihood of becoming symptomatic with seizures being one of the most clinically significant symptoms. Seizures are more likely to present as a symptom of larger meningiomas and meningiomas that compress cortical areas particularly those in non-skull base locations. These seizures are often managed medically, utilizing the same anti-seizure medications that are used to treat other causes of epilepsy. We discuss common anti-seizure medications used including valproate, phenobarbital, carbamazepine, phenytoin, lacosamide, lamotrigine, levetiracetam and topiramate and their common adverse effects. The goal of pharmacotherapy for seizure control is to maximize seizure control while minimizing the adverse effects of the medication. The decision to provide medical management is dependent on individual seizure history and plans for surgical treatment. Patients who did not require seizure prophylaxis before surgery are commonly prescribed seizure prophylaxis postoperatively. Symptomatic meningiomas not controlled by medical management alone are commonly evaluated for surgical resection. The efficacy of surgical resection in providing seizure freedom is dependent on several features of the tumor including tumor size, the extent of the peritumoral edema, the number of tumors, sinus infiltration and the degree of resection.

Prospective phase II trial of the dual mTORC1/2 inhibitor vistusertib for progressive or symptomatic meningiomas in persons with neurofibromatosis 2.

Meningiomas occur in 80% of persons with neurofibromatosis 2 (NF2) and cause significant mortality and morbidity, yet there are no effective medical treatments. NF2-deficient tumors have constitutive activation of mammalian/mechanistic target of rapamycin (mTOR), and treatment with mTORC1 inhibitors results in growth arrest in a minority of tumors, with paradoxical activation of the mTORC2/AKT pathway. We studied the effect of vistusertib, a dual mTORC1/mTORC2 inhibitor, in NF2 patients with progressive or symptomatic meningiomas. Vistusertib was administered orally at 125 mg twice daily for 2 consecutive days each week. The primary endpoint was the imaging response in the target meningioma, defined as a volume decrease of 20% compared with the baseline. Secondary endpoints included toxicity, imaging response of nontarget tumors, quality of life, and genetic biomarkers. Eighteen participants (13 female), median age of 41 (range, 18-61) years, were enrolled. In target meningiomas, the best response was partial response (PR) in 1/18 tumors (6%) and stable disease (SD) in 17/18 tumors (94%). For all measured intracranial meningiomas and vestibular schwannomas, the best imaging response was PR in 6/59 tumors (10%) and SD in 53 (90%). Treatment-related grade 3/4 adverse events occurred in 14 (78%) participants, and 9 participants discontinued treatment due to side effects. Although the study did not meet the primary endpoint, vistusertib treatment was associated with high rates of SD in progressive NF2-related tumors. However, this dosing regimen for vistusertib was poorly tolerated. Future studies of dual mTORC inhibitors for NF2 should focus on optimizing tolerability and evaluating the relevance of tumor stability in participants.

EVALUATION OF MICROSURGERY ON SUPRATENTORIAL MENINGIOMA UNDER SELECTIVE EMBOLIZATION PREOPERATION

Objectives: To evaluate clinical and preclinical characteristics and results of microsurgery of meningioma under preoperative selective embolization. Subjects and methods: A descriptive research on 9 patients with meningioma who experienced selective embolization preoperation and microsurgery in Military Hospital 103 from January 2016 to July 2021. Evaluating the tumor extent of resection by Simpson, surgery result by Ojemann. Results: Clinical characteristics include consciousness disorder 11.1%, increased intracranial pressure 88.9%, epilepsy 33.3%, movement disorder 33.3% often in the parietial-temporal lobe, psychosis 11.1% often in the frontal lobe. 100% of patients under total resection, medium duration was 155.56 ± 33.58 minutes. Blood transfusion was 0.33 ± 0.5 units. None of the patients had surgery complications postoperation. The good result was 100%. Conclusion: Symptomatic meningioma depends on the situation. Preoperative selective embolization enables to decline the surgery duration, blood transfusion, to remove tumor totally, and to have good results post-operation.

Sporadic multiple intracranial meningioma does not infer worse patient outcomes: results from a case control study.

Sporadic multiple meningioma are uncommon. Population-based data suggests that these patients have a reduced overall survival when compared to patients with solitary meningioma. The aim of this study was to investigate the clinical outcomes in multiple and solitary meningioma. A single-center matched cohort study (2008-2018) was performed. Patients with synchronous multiple meningioma at presentation, with no history of prior intracranial radiation, concurrent hormone replacement therapy or features of NF2-schwannomatosis were included. Eligible patients were matched 1:1 to patients with solitary meningioma. Outcomes of interest were occurrence of an intervention, recurrence, new meningioma development and mortality. Thirty-four patients harboring 76 meningioma at presentation were included. Mean age was 59.3years (SD = 13.5). Thirty-one (91.2%) were female. The median number of meningioma per patient was 2 (range 2-6). Eighteen patients (52.9%) were symptomatic at presentation. Median overall follow-up was 80.6months (IQR 44.1-99.6). Compared to patients with a sporadic meningioma, there was no difference in intervention rates (67.6% vs 70.6%, P = 0.792). Eight patients (34.8%) with a multiple meningioma had a WHO grade 2 meningioma compared to 7 (29.2%) with a solitary meningioma (P = 0.679). Median recurrence-free survival was 89months (95% CI 76-104) with no difference between the two groups (P = 0.209). Mean overall survival was 132months (95% CI 127-138) with no difference between the two groups (P = 0.860). One patient with multiple meningioma developed two further new meningioma 36months following diagnosis. Sporadic multiple meningioma may not have worse clinical outcomes. Management of patients with sporadic multiple meningioma should be tailored towards the symptomatic meningioma or high-risk asymptomatic meningioma.

Matched case-control analysis of outcomes following surgical resection of incidental meningioma.

The management of incidentally discovered meningioma remains controversial. We sought to compare outcomes following surgical resection of incidental meningioma to a matched cohort of symptomatic meningiomas. A retrospective single-center case-control study was conducted for patients undergoing resection of incidental meningioma from 2000 to 2019. A 1:1 case-control matching for incidental and symptomatic meningioma was performed using the following variables: age at initial visit, gender, tumor location/size, and presence of peritumoral edema. Primary outcomes included (1) WHO grading/histopathological subtype/MIB-1 index, (2) extent of resection (gross total resection or subtotal resection), and (3) recurrence. Outcomes were compared between groups using descriptive/bivariate analyses. A total of 91 incidental meningiomas were analyzed. Trauma was the most common reason (n = 19, 21%) to obtain imaging, and tumor size the leading reason to operate (n = 37, 41%). Median time-to-surgery from initial clinical encounter was 5-months (Q1:3, Q3:16.5). More incidental meningioma patients (n = 47, 52%) were privately insured compared to their matched symptomatic cohort (n = 30, 33%) (P = 0.006). Patients with incidental meningioma had significantly higher mean Karnofsky Performance Scale at time-of-surgery (93.2, SD:11.1 vs. 81.4, SD:12.7) (P < 0.001). There were no significant differences in primary/secondary outcomes between the groups. Incidental meningioma was not associated with recurrence on Cox proportional hazards analysis (HR: 0.795, 95%CI: 0.3-2.1, P = 0.637). Matched case-control analysis demonstrated no significant differences in clinical, histopathological, and functional outcomes following resection of incidental and symptomatic meningioma. While non-operative management with close follow-up and serial imaging is preferred for incidental meningiomas, those undergoing resection when indicated can anticipate similar safety and efficacy as symptomatic meningiomas.

Molecular determinants of outcomes in meningiomas.

Meningiomas are the most common intracranial primary tumor in adults. Surgery is the predominant therapeutic modality for symptomatic meningiomas. Although the majority of meningiomas are benign, there exists a subset of meningiomas that are clinically aggressive. Recent advances in genetics and epigenetics have uncovered molecular alterations that drive tumor meningioma biology with prognostic and therapeutic implications. In this review, we will discuss the advances on molecular determinants of therapeutic response in meningiomas to date and discuss findings of targeted therapies in meningiomas.

Application of computer-aided image reconstruction and image guide in parasagittal meningioma resection

BackgroundIn recent years, smaller-sized (diameter < 2.5 cm) meningiomas are diagnosed due to increased cranial imaging. Symptomatic meningiomas need to be removed surgically. Therefore, it is extremely important to locate the lesion exactly to tailor the craniotomy especially if the neuro-navigation system is not available. Many hospitals located in the underdeveloped countries cannot afford the high costs of neuro-navigation equipment. Hence, it is relevant to discover low-cost associated and effective methods for lesion localization for surgery.MethodsThe use of localization markers in advance can help to acquire preoperative CT images of the patients to create and calculate a three-dimensional (3D) virtual graph using a computer. With the 3D graph, spatial distance of the tumor from the markers is calculated and the tumor location projected on the scalp by the Triangle Pythagorean theorem. This enables precise localization of intracranial microlesions preoperatively.ResultsThe location of the tumor was consistent with that of the pre-operative virtual image, and the craniotomy was exact. The patient was discharged 3 days later without any neurological deficits.ConclusionsThis method is simple and reliable, inexpensive, and accurate in the location of small-sized lesions, which can partially compensate for the lack of neuro-navigation and is suitable for widespread application in hospitals in developing countries.

OTHR-31. The molecular profile of secondary meningiomas in survivors of childhood non-central nervous system (CNS) cancers

Abstract INTRODUCTION: Secondary meningiomas are a late effect in children who received cranial irradiation, frequently with a long latency. The molecular genetic profile of primary meningiomas is well studied; however, few studies describe the genomic landscape of radiation-induced meningiomas (RIM). METHODS: Patients followed at the Stollery Children’s Hospital (Edmonton, Canada) with a history of non-CNS malignancies who received cranial irradiation and then developed meningiomas between 1971 and 2013 were identified. Whole exome sequencing (WES), RNA sequencing as well as DNA methylation profiling were performed for patients with available tumor tissue and germline DNA. RESULTS: Of 96 patients who received cranial irradiation for non-CNS tumors, 16 (16.7%) developed symptomatic meningiomas. This patient cohort is unique; all 16 patients identified received 2000-2400 cGy of cranial irradiation, suggesting a threshold dose. 9/16 (56%) had WHO Grade 2 meningiomas or greater and 7/16 (44%) of meningiomas infiltrated other tissues. Post-surgical recurrences occurred in 43%. Patients experienced considerable morbidities directly attributable to the meningiomas or their treatment. 14 patients had samples suitable for further analysis. NF2 mutations were identified in 50% (8; 4 DNA,4 fusion). Other meningioma related genes with mutations identified in other cohorts were not identified. Copy number alternations were noted in all 16 patients in chromosomes 1p and 22q. 850k methylation analysis with PCA as well as UMAP and tSNE did not demonstrate clustering. Ongoing additional studies include examining tumor mutation burden and the radiation mutational profile. CONCLUSIONS: This study examined the RIM in a cohort of patients having received similar doses of radiation for their childhood cancer. There is increased risk of radiation-induced meningioma in survivors of non-CNS cancers given ≥ 2000 cGy during childhood. To date, our findings are consistent with previously described primary and RIM mutations. Enhanced knowledge in secondary meningiomas is crucial for accurate patient counselling, prognostication, and treatment.

Development of ‘Core Outcome Sets’ for Meningioma in Clinical Studies (The COSMIC Project): protocol for two systematic literature reviews, eDelphi surveys and online consensus meetings

IntroductionMeningioma is the most common primary intracranial tumour in adults. The majority are non-malignant, but a proportion behave more aggressively. Incidental/minimally symptomatic meningioma are often managed by serial imaging. Symptomatic...

Introduction. Petroclival meningiomas

INTRODUCTIONThe petroclival region of the posterolateral skull base continues to be an anatomic challenge for neurosurgeons. This is particularly true when addressing symptomatic meningiomas, as they are heterogeneous in their nature and clinical behavior, with distinct biologies that we are just beginning to understand. The early surgical history was marked by attempts at understanding how to approach this region, with difficult outcomes; the development of transtemporal approaches was a turning point. Radiosurgery, endonasal and endoscopic techniques, and the concept of the tailored management paradigm are a part of the evolving approach to what remains one of the

COT-18 Trends in Primary Brain Tumors in Kumamoto Prefecture with Declining Birthrate and Aging Population - Kumamoto Prefecture Brain Tumor Epidemiological Survey

Backgrounds: The demographic characteristics of Kumamoto Prefecture are that there is little population movement and the total population remains constant at about 1.8 million, but in recent years the birthrate is declining and the population is aging. We have been conducting the Kumamoto Prefecture Brain Tumor Epidemiological Survey since 1989 in cooperation with neurosurgical institutions in the prefecture. In this study, we examined whether recent demographic changes have affected the incidence of primary brain tumors (BT). Methods: Patients with primary BT were collected annually from 44 institutions in Kumamoto Prefecture (as of 2020), and the number of incidences per 100,000 population was calculated for each BT for each year, excluding patients living outside the prefecture and duplicate cases. Results: The total number of primary BT was 11441 (top 3: meningioma 40%, pituitary adenoma 17%, glioma 17%). Of 4261 men with primary BT, the top 3 were meningioma (27%), glioma (23.7%), and pituitary adenoma (18.4%)), and 7180 women (top 3: meningioma (47.7%), pituitary adenoma (16.2%), and glioma (12.9%)). The number of primary BT increased every year, and the incidence increased significantly when comparing 1989–2004 and 2005–2020 (13.6 vs. 25.0/100,000, p<0.000001). Typical brain tumors (meningioma, pituitary adenoma, glioma, schwannoma, malignant lymphoma) also increased year by year, especially asymptomatic meningioma. The median age of asymptomatic meningiomas was significantly higher than that of symptomatic meningiomas (69 vs. 65 years, p<0.0001). Gliomas increased significantly in the later stages compared with the early stages in children (0–14 years) and the elderly (65 years and older). Conclusion: Our results suggest that an increase in the number of BT such as glioblastoma, which are more common in the elderly, as well as an increase in the number of opportunities for intracranial examinations in the aging of the population may be responsible for the increased incidence of primary BT.

RARE-15. THE MOLECULAR PROFILE OF SECONDARY MENINGIOMAS IN SURVIVORS OF CHILDHOOD NON-CENTRAL NERVOUS SYSTEM CANCERS

IntroductionCranial irradiation remains part of childhood cancer therapy and secondary meningiomas are a late effect. Secondary meningiomas are reported in patients who received low and high dose cranial irradiation and arise ~ 20 years post exposure. The molecular and genetic profile of primary meningiomas has been well studied; however, only a few studies describe these in radiation-induced meningiomas (RIM). MethodsWe identified patients followed at the Childhood Cancer Survivor Clinic, Stollery Children’s Hospital who had a history of non-central nervous system malignancies and received cranial irradiation who developed meningiomas between clinic inception in 1971 and June 2013. Whole exome sequencing (WES) as well as DNA methylation profiling were performed for patients where tumor and germline DNA were available. ResultsOf 96 patients who received cranial irradiation, 16 (16.7%) developed symptomatic meningiomas. This patient cohort is unique; all 16 patients received 2000–2400 cGy, suggesting a threshold dose. 9/16 (56%) had WHO Grade 2 meningiomas or greater and 7/16 (44%) were infiltrative. Post-surgical recurrences occurred in 43%. Patients experienced considerable morbidities directly attributable to the meningiomas or their treatment. 14 patients had samples suitable for further analysis. Preliminary results revealed that NF2 mutations were the most common (5). Other meningioma related genes with mutations identified in our patient cohort include TRAF7, AKT3, MSH4 (2), KMT2C (2), TET1 (2), KDM6A, and MLH3. Copy number alternations were noted with increased frequency on chromosomes 1p, 22q, 19q. 850k methylation analysis did not conclusively show any clustering. Ongoing studies include assessment of tumor mutation burden, RNAseq, and the mutational profile. ConclusionsThis study examined RIM in patients who received similar doses of radiation for their childhood cancer. To date, our findings are consistent with previously described primary and RIM mutations. Enhanced knowledge in secondary meningiomas is crucial for accurate patient counseling, prognostication, and treatment.