Adult Meningioma Research Articles

Initial management of newly diagnosed WHO grade 2-3 adult meningioma following surgery: results from the Dutch Brain Tumour Registry (2016-2021).

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

ETMR-09. HEALTH-RELATED QUALITY OF LIFE OF CHILDREN, ADOLESCENTS AND ADULTS AFTER DIAGNOSIS OF CHILDHOOD-ONSET MENINGIOMA

Abstract BACKGROUND Meningiomas are rare intracranial tumors in childhood. Childhood-onset meningiomas differ from their adult counterparts in terms of frequency, molecular features and clinical presentation. There is limited data on health-related quality of life (HRQoL) of pediatric meningioma patients. The aim of this study was to analyze the HRQoL of pediatric or adult patients after completion of treatment for childhood-onset meningioma. Further, the influence of disease-specific characteristics on HRQoL, fatigue or functional capacity was analyzed. METHODS In this cross-sectional study, the HRQoL of 8 pediatric and 27 adult meningioma patients from the clinical trials HIT-ENDO, KRANIOPHARYNGEOM 2000/2007 and KRANIOPHARYNGEOM Registry 2019 was assessed. The validated questionnaires EQ-5D-Y, EQ-5D-3L, PedsQL Generic Core Scale, EORTC QLQ-C30 and QLQ-BN20 were used. Patients’ fatigue and functional capacity were scored using the EORTC QLQ-C30, the PedsQL Multidimensional Fatigue Scale and the FMH questionnaire. Exploratory data analysis was performed using univariate, bivariate and multivariate analyses (α=0.05). RESULTS The HRQoL was assessed in median 10 (IQR: 5-17) years after diagnosis. The mean HRQoL value was 86 (IQR: 79-92) for pediatric and 75 (IQR: 67-92) for adult patients using the PedsQL Generic Core Scale or EORTC QLQ-C30 questionnaire, respectively. Most limitations were reported in emotional function and fatigue. The median functional capacity of patients was at the 90th (IQR: 65-90) percentile. HRQoL was lower in adults with neurofibromatosis type 2 or at older age (p=0.009) and higher HRQoL after progressive disease. Age at diagnosis, WHO grade, residual tumor, use of radiotherapy, tumor location, tumor entity (meningioma vs. craniopharyngioma), degree of disability, or time since diagnosis did not affect HRQoL in adults. CONCLUSION The median HRQoL of childhood-onset meningioma patients indicates that it is comparable to the healthy normal population. Nevertheless, HRQoL is a construct that can be influenced in many ways. Further research on HRQoL is warranted.

Quality of Life Factors and Measurement in Adult Meningioma Patients: A Systematic Review.

Meningiomas are common brain neoplasms that can significantly influence health-related quality of life (HRQOL), yet the factors influencing HRQOL in adult patients remain unclear. We aimed to bridge this knowledge gap by determining these key factors. We conducted a systematic review, searching EMBASE, MEDLINE, CINAHL, Scopus and PsycINFO up to February 2024. We included original, peer-reviewed studies focusing on adult patients (>18 years) with current or past meningioma at any stage of treatment that measured HRQOL or its proxies in relation to patient-, tumour- and treatment-related factors. Two independent reviewers screened abstracts and full-texts, selecting studies with an acceptable risk of bias for data extraction and narrative synthesis. The protocol of this review was registered on PROSPERO (# CRD42023431097). Of N = 3002 studies identified, N = 31 studies were included. Key factors found to influence HRQOL in adult meningioma patients include surgery, radiotherapy, neurological function, functional status, comorbidities, sleep quality, psychological impairment, age and employment. Factors related to tumour characteristics yielded inconsistent findings. Heterogeneity and inconsistencies in HRQOL measurement across studies hindered definitive conclusions about the impact of factors on HRQOL. Our review elucidates the multifaceted influences on HRQOL in meningioma patients, with significant variability due to patient-, tumour- and treatment-related factors. We emphasize the need for standardized, disease-specific HRQOL assessments in meningioma patients. Collaborative efforts towards consistent, large-scale, prospective research are essential to comprehensively understand and improve HRQOL, thereby enhancing tailored care for this population.

P.087 Factors affecting health-related quality of life among adult meningioma patients: a systematic review

Background: Meningiomas are common brain neoplasms that can significantly influence health-related quality of life (HRQOL), yet the factors influencing HRQOL in adult patients remain unclear. We aimed to bridge this knowledge gap by determining these key factors. Methods: We conducted a systematic review, searching EMBASE, MEDLINE, CINAHL, Scopus, and PsycINFO up to March 2023. We included original, peer-reviewed studies focusing on adult patients (&gt;18 years) with current or past meningioma at any stage of treatment that measured HRQOL or its proxies in relation to tumour-, treatment-, and patient-related factors. Two independent reviewers screened abstracts and full texts, selecting studies with acceptable risk of bias for data extraction and narrative synthesis. Results: Of N=2942 identified studies, N=30 were included. Key factors found to influence HRQOL in adult meningioma patients include surgery, radiotherapy, neurological function, functional status, comorbidities, sleep quality, psychological impairment, age, and employment. Factors related to tumour characteristics yielded inconsistent findings. Heterogeneity and inconsistencies in HRQOL measurement across studies hindered definitive conclusions about the impact of factors on HRQOL. Conclusions: Our review emphasizes the need for standardized, disease-specific HRQOL assessments in meningioma patients. More consistent, large-scale, prospective research is essential to comprehensively understand and improve HRQOL, and thereby ensure tailored care for this population.

Cystic meningioma of the brain

ABSTRACTMeningiomas with a cystic component are quite rare and account for 1.7–7.3 % of all intracranial meningiomas. The incidence of cystic meningioma in adults is 2–4 % of all meningiomas. Women have a higher incidence rate in comparison to men. Between 2014 and 2019, at the State Institution Romodanov Neurosurgery Institute of the National Academy of Medical Sciences of Ukraine, we collected data for a database of cystic meningioma cases. The data included preoperative imaging, surgery notes, and pathology reports. Over the course of 6 years, 1408 meningioma cases have been observed, and 1326 of those instances have undergone surgical treatment for intracranial meningioma. 73 (5.5 %) cases of cyst-associated meningiomas have been analyzed: 26 (2.0 %) of true cysts (primary), 47 (3.5 %) cases of pseudocysts (secondary). Nauta type IV was the most common cyst type accounting for 52.1 %, whereas atypical (27.4 %) and anaplastic (17.8 %) meningioma types were the most common histological subtypes. All patients were monitored for 24 months; only 73 patients had access to long-term monitoring, which lasted for an average of 49 months (range 36–96 months). The majority of atypical (2.7 %) and anaplastic (5.5 %) types of pseudocystic meningioma relapsed after radical tumor surgery removal. The preoperative diagnosis needs to be integrated with the examination performance, the surgical treatment is selected based on the Nauta classification, and most of the surgical operations can result in the complete resection of the tumor.

Epidemiology of adult meningioma: Report from the Dutch Brain Tumour Registry (2000-2019).

Meningiomas are the most common primary tumours of the central nervous system. This study aimed to provide comprehensive nationwide estimates on the incidence, prevalence and prognostic impact of meningioma diagnosis in the Netherlands. Adult patients diagnosed with meningioma in 2000-2019 were selected from the Dutch Brain Tumour Registry (DBTR), part of the Netherlands Cancer Registry (NCR). Time trends in age-adjusted incidence and prevalence rates were evaluated using the estimated annual percentage change (EAPC). Relative survival rates were calculated using the Pohar Perme estimator. Case completeness of the DBTR/NCR was estimated through record linkage with one of the Dutch neuro-oncology centres. From a total of 23,454 cases of meningioma, 11,306 (48.2%) were histologically confirmed and 12,148 (51.8%) were radiological diagnoses. Over time, the incidence of diagnosis increased from 46.9 per 1,000,000 inhabitants (European Standardized Rate [ESR]) to 107.3 (EAPC 4.7%, p < 0.01), with an increase in the incidence of radiological diagnoses from 14.0 to 70.2 per 1,000,000 ESR (EAPC 9.1%, p < 0.01). The prevalence of meningioma was estimated at 1012/1,000,000 on 1 January 2020, with almost 17,800 individuals having had a diagnosis of meningioma. Relative survival rate at 10 years for grade 1 meningiomas was 91.0% (95% confidence interval [CI] 89.4%-92.3%), 71.3% (95% CI 66.8%-75.2%) for grade 2 meningiomas and 36.4% (95% CI 27.3%-45.6%) for grade 3 meningiomas. Local case completeness was estimated at 97.6% for histologically confirmed meningiomas and 84.5% for radiological diagnoses. With a near-complete registry, meningioma prevalence was estimated at over 1000 per 1,000,000 inhabitants.

Sporadic and neurofibromatosis type 2-associated meningioma in children and adolescents.

Pediatric meningioma differs not only in its rare incidence from the adult meningioma, but also in its clinical characteristics. Many treatment approaches of pediatric meningioma are based on the study results of adult meningioma studies. The aim of this study was to explore the clinical and epidemiological characteristics of pediatric meningioma. Data on pediatric patients diagnosed between 1982 and 2021 with NF2-associated or sporadic meningioma and recruited in the trials/registries HIT-ENDO, KRANIOPHARYNGEOM 2000/2007 and KRANIOPHARYNGEOM Registry 2019 were retrospectively analyzed for clinical characteristics, etiology, histology, therapy, and outcome. One hundred fifteen study participants were diagnosed with sporadic or NF2-associated meningioma at a median age of 10.6 years. There was a 1:1 sex ratio, with 14% of study participants suffering from NF2. 46% of the meningiomas were located hemispherically, 17% at the optic nerve/ intraorbital and 10% ventricularly. Multiple meningiomas were detected in 69% of NF2 patients and in 9% of sporadic meningiomas. 50% of the meningiomas were WHO grade I, 37% WHO grade II and 6% WHO grade III. Progressions or recurrences occurred after a median interval of 1.9 years. Eight patients (7%) died, 3 of them due to disease. The event-free survival was higher for WHO grade I than for WHO grade II meningioma patients (p = 0.008). The major difference to the preceding literature could be found in the distribution of different WHO grades and their influence on event-free survival. Prospective studies are warranted to assess the impact of different therapeutic regimens. NCT00258453; NCT01272622; NCT04158284.

Hints for reclassification of meningiomas based on the fifth edition of WHO CNS.

e14059 Background: Meningioma is the most common primary neoplasm of the central nervous system (CNS) in adults. Genetic variants ( NF2, AKT1, TRAF7 etc.) are strongly related to the subtypes of meningioma. TERT promoter mutation or homozygous CDKN2A and/or CDKN2B deletion are independent evidence for diagnosing WHO grade 3 meningioma according to 5th CNS WHO. Our study reclassifies meningiomas using a clinical and molecular real-world dataset. Methods: This study retrospectively analyzed the genomic alteration of 347 Chinese meningioma patients during 2019-2022. Next-generation sequencing (NGS) was performed to detect gene mutations in tumor samples. Results: TERT promoter mutation or CDKN2A/B deletion were identified in 11% (n = 39) of patients ( TERT 5.2%, CDKN2A 8.1%, CDKN2B 8.6%). Of these cases, histologic grade information was available for 26 patients, 14(53.8%) of whom were reclassified as WHO grade 3 meningiomas, including four histologic grade 1 and ten histologic grade 2. There is a male preponderance in reclassified patients (56.4% vs. 40.0%, p &lt; 0.05), meanwhile the age showed no significant difference between them (average age: 54 vs 50, p = 0.11). The most frequently co-mutated gene was NF2. The proportion of TERT promoter mutation or CDKN2A/B deletion in NF2-mutant tumors was similar to NF2-wildtype tumors (10% vs. 11%, p &gt; 0.05). Conclusions: In our study, 11% of Chinese adult meningioma patients found TERT promoter mutation or CDKN2A/B deletion and showed a male preponderance, among 53.8% of whom were reclassified as meningiomas WHO grade 3. Overall, these data advance the understanding of the significance of molecular profiling in the classification of meningioma patients according to the 5th WHO CNS.

Healthcare utilization and costs among intracranial meningioma patients during long-term follow-up

PurposeFew studies have reported on healthcare utilization and costs for intracranial meningioma patients, while the tumor and its treatment profoundly affect patients’ functioning and well-being. Here we evaluated healthcare utilization and costs, including their determinants.MethodsA multicenter cross-sectional study of adult meningioma patients ≥ 5 years after intervention. Patients completed three validated patient-reported outcome measures (PROMs) assessing patients ‘functioning and wellbeing (SF-36, EORTC QLQ-BN20, and HADS) and a study-specific questionnaire assessing healthcare utilization over the previous twelve months. Healthcare costs of the twelve months prior were calculated using reported healthcare utilization ≥ 5 years after intervention by the Dutch Manual for Economic Evaluation in Healthcare. Determinants for healthcare utilization and costs were determined with regression analyses.ResultsWe included 190 patients with WHO grade I or II meningioma after a mean follow-up since intervention of 9.2 years (SD 4.0). The general practitioner (80.5%), physiotherapist (37.9%), and neurologist (25.4%) were visited most often by patients. Median annual healthcare costs were €871 (IQR €262–€1933). Main contributors to these costs were medication (45.8% of total costs, of which anti-seizure medication was utilized most [21.6%]), specialist care (17.7%), and physiotherapy (15.5%). Lower HRQoL was a significant determinant for higher healthcare utilization and costs.ConclusionIn patients with meningioma, medication costs constituted the largest expenditure of total healthcare costs, in particular anti-seizure medication. Particularly a lower HRQoL was a determinant for healthcare utilization and costs. A patient-specific approach aimed at improving patients’ HRQoL and needs could be beneficial in reducing disease burden and functional recovery.

KS04.6.A Epidemiology of adult meningioma in the Netherlands: a population-based study

Abstract Background Meningiomas are the most common primary tumours of the central nervous system. As the majority of meningiomas are benign, initial management often consists of observation only. Consequently, estimates on meningioma incidence are generally considered too low, with many registries mainly depending on pathology notifications. With additional notification sources, this study provides more complete population-based estimates on the incidence, prevalence, and prognostic impact of meningioma diagnosis in the Netherlands. Material and Methods Data on patients diagnosed with meningioma during 2000-2019 were obtained from the Netherlands Cancer Registry (NCR), which was expanded to the Dutch Brain Tumour Registry (DBTR) for meningiomas as of 2016. In addition to histological confirmations, the NCR/DBTR receives case notifications from hospital administrative registrations on cost reimbursement and outpatient care. In addition, a data linkage was performed with a clinical database maintained by one of the Dutch neuro-oncology centres to evaluate local completeness of the NCR/DBTR. Time trends of the age-adjusted incidence rates were evaluated by calculating the estimated annual percentage change (EAPC). Relative survival rates were calculated using the Pohar-Perme estimator. Results From 2000 to 2019, a total of 22,605 cases of meningioma were registered; 11,423 (50.5%) were histologically confirmed, while 11,182 (49.5%) had a radiological diagnosis. Over time, incidence increased from 4.7 per 100,000 inhabitants (European Standardized Rate, ESR) to 10.7 (EAPC 4.6%, p&amp;lt;0.01); the incidence of radiological diagnosis increased from 1.2 to 6.9 per 100,000 ESR (EAPC 9.6%, p&amp;lt;0.01). Local data completeness was estimated at 98% for histologically confirmed meningiomas and 87% for radiological diagnoses. On the basis of these incidence estimates, the prevalence of meningioma is estimated at 105/100,000 on January 1st of 2020, with over 17,500 individuals having had a diagnosis of meningioma at that moment. Relative survival rate at 5 years for grade I meningiomas was 94.8% (95%-confidence interval: 94.0%-95.4%), 84.0% (95%CI: 81.0%-86.5%) for grade II meningiomas, and 47.3% (95%CI: 38.2%-55.8%) for grade III meningiomas. Conclusion As the incidence estimates in this study may be considered most complete, the results obtained should approximate the true incidence, prevalence, and prognostic impact of meningioma diagnosis in the Netherlands.

Spinal Meningioma in Adults: Imaging Characteristics, Surgical Outcomes, and Risk Factors for Recurrence

Although spinal meningiomas (SMs) are associated with overall long tumor-free survival, SMs can recur. This study analyzed factors associated with complications, misdiagnosis, and recurrence of SMs. We reviewed patient demographics; radiographic characteristics of patients with SMs, including level, location within the canal, and size; surgical resection; pathology; and recurrence. The study included 64 women and 10 men (74 SMs). Of patients, 64 showed no recurrence after surgery with a median (range) follow-up of 17 (1-99) months. Recurrence was identified in 10 patients (13.5%) during a median (range) follow-up of 66 (25-230) months. There was no significant difference in sex between the recurrence and no recurrence cohorts. Patients in the recurrence cohort were significantly younger (median [range] age 58 [35-70] years) than patients in the no recurrence cohort (median [range] age 69 [18-93] years; P= 0.0091). There was significant predilection for foraminal locations in the recurrence cohort (P < 0.001) compared with the no recurrence cohort. SM was correctly identified on preoperative magnetic resonance imaging or computed tomography myelography in 62 of 64 tumors (96.9%) in the no recurrence cohort, but in only 6 of 10 tumors (60%) in the recurrence cohort (P < 0.001). In 74 patients with SMs, a preponderance of female patients and a predilection of tumors for the thoracic spine were shown. Recurrence was significantly more common in younger than older patients. Risk factors for recurrence included larger tumors, foraminal location, and en plaque lesions. Patients who developed recurrence were significantly more likely to have been misdiagnosed on preoperative imaging with nerve sheath tumors or lymphoma.

SURG-14. COMPARABLE SURVIVAL OUTCOMES BETWEEN THE ELDERLY AND THEIR YOUNGER COUNTERPARTS AFTER RESECTION OF BENIGN MENINGIOMAS

Abstract 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 &amp;gt; 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&amp;lt; 0.001), and 0.173 (95%CI=0.146-0.205, P&amp;lt; 0.001) for patients age 18-39, 60-79, and &amp;gt;= 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&amp;lt; 0.001) for patients age 18-39, 60-79, and &amp;gt;= 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 &amp;gt;= 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.

Wireless phone use and adult meningioma risk: a systematic review and Meta-analysis

Introduction: Several studies explored the effects of exposure to radiofrequency-electromagnetic field (RF-EMF) and extremely low frequency (ELF) EMF emitted from mobile phones on meningioma among adults. However, the results could not reach an agreement. This meta-analysis was conducted to confirm the relationship between adult meningioma risk and the use of a wireless phone. Methods: Pertinent studies were identified by searching PubMed and Embase up to August 2018. The random- or fixed-effects model was used to combine the results depending on the heterogeneity of the analysis. The publication bias was evaluated using Egger’s regression asymmetry test. The subgroup analysis was performed by time since the first use of wireless phone and laterality (ipsilateral/contralateral). Results: Eight studies were enrolled in this meta-analysis. The pooled results suggested that the ever use of wireless phone led to a borderline decreased adult meningioma risk [odds ratio (OR) 0.90; 95% confidence interval (CI) 0.83–0.99] with no heterogeneity (I 2 = 5.3%; p = 0.391). A decreased risk of meningioma was seen in short-term (OR = 0.85; 95% CI = 0.77–0.94) users. Neither decreased nor increased risk of meningioma was observed in mid-term (OR = 0.93, 95% CI = 0.75–1.16) and long-term (OR = 1.05, 95% CI = 0.93–1.19) users. Neither ipsilateral (OR = 1.05, 95% CI = 0.90–1.22) nor contralateral (OR = 0.86, 95% CI = 0.62–1.18) wireless phone use was associated with the risk of meningioma. Conclusions: This meta-analysis suggested a relationship between decreased meningioma risk and wireless phone use. However, the findings need further validation.

TMOD-21. TARGETING ANAPLASTIC MENINGIOMA WITH PANOBINOSTAT IN PATIENT-DERIVED ORTHOTOPIC XENOGRAFT (PDOX) MODELS DERIVED FROM A MATCHING PAIR OF PRIMARY AND RECURRENT TUMORS

Abstract BACKGROUND Meningioma is the most common brain tumor in adults. Despite the overall benign nature of meningioma, skull base tumors can be difficult to completely resect while others exhibit progression and aggressive profiles. The lack of clinically relevant animal models is blocking the development of novel therapies. MATERIAL AND METHODS Twelve surgical specimens (1 × 105) from 11 adult meningioma patients were implanted into the frontal cranial-base of the brain of SCID mice. Mice were then followed and assessed for tumor formation. Tumor growth was confirmed by small animal MRI. Pathologic features of the PDOX models and the matched patient tumors were compared with standard H&amp;E and immunohistochemical staining. RNAseq was performed to examine the molecular fidelity of PDOX tumors and to identify new therapeutic targets. A panel of 60 clinically-relevant drugs was developed for screening drug sensitivity. In vivo examination of therapeutic efficacy of Panobinostat was performed in two models by treating preformed PDOX tumors with i.p. injection (10 mg/kg), 5 days on, 5 days off for 2 cycles. RESULTS Intracranial xenograft formation was confirmed in two samples derived from the same patient, the first an atypical meningioma (K029MEN-P) and the second, which progressed to anaplastic meningioma at recurrence (K029MEN-R). MRI scanning revealed that the PDOX tumors grew from the skull base. These patient tumor cells can be cryopreserved for long-term maintenance of tumorigenicity. The xenograft tumors replicated histopathological features of parental tumors. Overall gene expression profiles of PDOX were similar to the original patient tumors. Using MEN primary culture cells, we screened 60 drugs and identified 12 (20%) active compounds. Panobinostat also significantly prolonged survival of mice bearing orthotopic meningiomas. CONCLUSION A set of meningioma PDOX models derived from primary and recurrent tumor was established. Our data further demonstrate that panobinostat exerts potent antitumor activity against high-grade meningioma.

EPID-02. HEIGHT AND THE RISK OF MENINGIOMA

Abstract BACKGROUND Meningiomas are the most common primary central nervous system tumors. Risk factors for meningiomas including obesity, height, history of allergy/atopy or autoimmune diseases, have been previously assessed with conflicting results. We reviewed a large cohort of Israeli adolescents in order to assess potential risk factors for the development of meningiomas. METHODS This study analyzed a cohort of 2,035,915 Jewish men and women who underwent obligatory physical examination when aged 16 to 19 years, from 1967 to 2011. Meningioma incidence was identified by linkage to the national cancer registry. Cox proportional hazard models were used to estimate the hazard ratios for meningioma according to sex, body mass index (BMI), height, history of allergic and autoimmune disease. RESULTS Linkage of the adolescent military database with the Israeli cancer registry identified 480 cases (152 males and 328 females) of meningioma during a follow up of 40,304,078-person years. The median age at diagnosis of meningioma was 42.1 ± 9.4 (range 17.4–62.6). On univariate analysis, only female gender (p&lt; 0.01) and height (p&lt; 0.01) were associated with risk for meningioma in the total study population. When stratified by gender, height remained a significant risk factor only in men. Spline analysis in the men group showed the minimum risk at a height of 1.62 meters and a statistically significant increase in the risk for meningioma at heights taller than 1.85 meters. BMI, past medical history including asthma, diabetes, and atopic and autoimmune diseases, were not associated with meningioma risk. CONCLUSION in this large population study, we found that sex and taller height in adolescent males was associated with an increased risk of adult meningioma.

Allergic conditions and risk of glioma and meningioma in the CERENAT case-control study.

Inverse association between allergic conditions and glioma risk has been consistently reported in epidemiological studies with little attention paid to potential environmental confounders; the association with meningioma risk is less consistent. We examined the association between allergy history and risk of glioma and meningioma in adults using data from the CERENAT (CEREbral tumors: a NATional study) multicenter case-control study carried out in 4 areas in France in 2004-2010. Participants' histories of doctor-diagnosed allergic asthma, eczema, rhinitis/hay fever and other allergic conditions were collected at onset through a detailed questionnaire delivered in a face-to-face interview. Conditional logistic regression for matched sets was adjusted for participants' educational level and mobile phone use. A total of 273 glioma cases, 218 meningioma cases and 982 matched controls selected from the local electoral rolls were analyzed. A significant inverse association was found between glioma and a history of any allergy (OR 0.52, 95% CI 0.36-0.75), with a dose-effect relationship with the number of allergic conditions reported (p-trend = 0.001) and a particularly strong association with hay fever/allergic rhinitis (OR 0.46, 95% CI 0.30-0.72). Interestingly, associations with glioma risk were more pronounced in women. For meningioma, no association was observed with overall or specific allergic conditions. Our findings confirmed the inverse association between allergic conditions and glioma risk but questioned the role of allergy in meningioma risk. Future research is needed to clarify the biological mechanism of overall allergy and allergic rhinitis on glioma and to confirm the different effect by gender.

Association of Genetic Predisposition With Solitary Schwannoma or Meningioma in Children and Young Adults

Meningiomas and schwannomas are usually sporadic, isolated tumors occurring in adults older than 60 years and are rare in children and young adults. Multiple schwannomas and/or meningiomas are more frequently associated with a tumor suppressor syndrome and, accordingly, trigger genetic testing, whereas solitary tumors do not. Nevertheless, apparently sporadic tumors in young patients may herald a genetic syndrome. To determine the frequency of the known heritable meningioma- or schwannoma-predisposing mutations in children and young adults presenting with a solitary meningioma or schwannoma. Using the database of the Manchester Centre for Genomic Medicine, this cohort study analyzed lymphocyte DNA from young individuals prospectively referred to the clinic for genetic testing between January 1, 1990, and December 31, 2016, on presentation with a single meningioma (n = 42) or schwannoma (n = 135) before age 25 years. Sequencing data were also examined from an additional 39 patients with neurofibromatosis type 2 who were retrospectively identified as having a solitary tumor before age 25 years. Patients with schwannoma were screened for NF2, SMARCB1, and LZTR1 gene mutations, while patients with meningioma were screened for NF2, SMARCB1, SMARCE1, and SUFU. The type of underlying genetic mutation, or lack of a predisposing mutation, was associated with the presenting tumor type and subsequent development of additional tumors or other features of known schwannoma- and meningioma-predisposing syndromes. In 2 cohorts of patients who presented with an isolated meningioma (n = 42; median [range] age, 11 [1-24] years; 22 female) or schwannoma (n = 135; median [range] age, 18 [0.2-24] years; 60 female) before age 25 years, 16 of 42 patients (38%) had a predisposing mutation to meningioma and 27 of 135 patients (20%) to schwannoma, respectively. In the solitary meningioma cohort, 34 of 63 patients (54%) had a constitutional mutation in a known meningioma predisposition gene. Twenty-five of 63 patients (40%) had a constitutional NF2 mutation, and 9 (14%) had a constitutional SMARCE1 mutation. In the cohort of those who developed a solitary schwannoma before age 25 years, 44 of 153 patients (29%) had an identifiable genetic predisposition. Twenty-four patients (55%) with a spinal schwannoma had a constitutional mutation, while only 20 (18%) with a cranial schwannoma had a constitutional predisposition (P < .001). Of 109 cranial schwannomas, 106 (97.2%) were vestibular. Four of 106 people (3.8%) with a cranial schwannoma had an LZTR1 mutation (3 were vestibular schwannomas and 1 was a nonvestibular schwannoma), and 9 (8.5%) had an NF2 mutation. A significant proportion of young people with an apparently sporadic solitary meningioma or schwannoma had a causative predisposition mutation. This finding has important clinical implications because of the risk of additional tumors and the possibility of familial disease. Young patients presenting with a solitary meningioma or schwannoma should be referred for genetic testing.

Folate metabolism genetic polymorphisms and meningioma and glioma susceptibility in adults.

Polymorphic variants of genes involved in folate metabolism are implicated in the susceptibility to meningioma and glioma, but the results from published articles are controversial and inconclusive. Therefore, we performed this meta-analysis including all studies available to evaluate the relationship between folate metabolism genetic polymorphisms and the susceptibility to meningioma and glioma in adults. We searched the literature in PubMed, EMBASE and Cochrane Central Library for relevant articles published up to August 2016. The odds ratios (ORs) and the corresponding 95% confidence intervals (95%Cls) were used to evaluate the associations of two folate metabolism genetic variants MTRR A66G (rs1801394) and MTHFR A1298C (rs1801131) with the risk of meningioma and glioma in adults. We found significant association of MTHFR A1298C (rs1801131) variant genotypes with increased incidence of meningioma and glioma in this study population (CA vs. AA: OR=1.22, P<0.001; CA+CC vs. AA: OR=1.18, P=0.002). Moreover, we found that MTRR A66G (rs1801394) variant genotypes was associated with increased risk of meningioma and glioma (G vs. A: OR=1.11, P=0.020; GG vs. AA+AG: OR=1.17, P=0.043; GG vs. AA: OR=1.22, P=0.023). In conclusion, our meta-analysis suggests that two folate metabolism genetic variants MTRR A66G (rs1801394) and MTHFR A1298C (rs1801131) contribute to genetic susceptibility to meningioma and glioma in adults.

Occupational exposure to metals and risk of meningioma: a multinational case-control study.

The aim of the study was to examine associations between occupational exposure to metals and meningioma risk in the international INTEROCC study. INTEROCC is a seven-country population-based case-control study including 1906 adult meningioma cases and 5565 population controls. Incident cases were recruited between 2000 and 2004. A detailed occupational history was completed and job titles were coded into standard international occupational classifications. Estimates of mean workday exposure to individual metals and to welding fumes were assigned based on a job-exposure-matrix. Adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated using conditional logistic regression. Although more controls than cases were ever exposed to metals (14 vs. 11 %, respectively), cases had higher median cumulative exposure levels. The ORs for ever vs. never exposure to any metal and to individual metals were mostly greater than 1.0, with the strongest association for exposure to iron (OR 1.26, 95 % CI 1.0-1.58). In women, an increased OR of 1.70 (95 % CI 1.0-2.89) was seen for ever vs never exposure to iron (OR in men 1.19, 95 % CI 0.91-1.54), with positive trends in relation with both cumulative and duration of exposure. These results remained after consideration of other occupational metal or chemical co-exposures. In conclusion, an apparent positive association between occupational exposure to iron and meningioma risk was observed, particularly among women. Considering the fact that meningioma is a hormone dependent tumor, the hypothesis that an interaction between iron and estrogen metabolism may be a potential mechanism for a carcinogenic effect of iron should be further investigated.

Body mass index, physical activity, and risk of adult meningioma and glioma

Whether adiposity and lack of physical activity affect the risk for developing meningioma and glioma is poorly understood. Our objective was to characterize these associations in detail. We conducted a systematic review and meta-analysis of adiposity and physical activity in relation to meningioma and glioma using cohort and case-control studies published through February 2015. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We identified 12 eligible studies of body mass index (BMI) and 6 studies of physical activity, comprising up to 2,982 meningioma cases and 3,057 glioma cases. Using normal weight as the reference group, overweight (summary relative risk [RR] = 1.21, 95% confidence interval [CI] = 1.01-1.43) and obesity (RR = 1.54, 95% CI = 1.32-1.79) were associated with increased risk of meningioma. In contrast, overweight (RR = 1.06, 95% CI = 0.94-1.20) and obesity (RR = 1.11, 95% CI = 0.98-1.27) were unrelated to glioma. Similarly, dose-response meta-analyses revealed a statistically significant positive association of BMI with meningioma, but not glioma. High vs low physical activity levels showed a modest inverse relation to meningioma (RR = 0.73, 95% CI = 0.61-0.88) and a weak inverse association with glioma (RR = 0.86, 95% CI = 0.76-0.97). Relations persisted when the data were restricted to prospective studies, except for the association between physical activity and glioma, which was rendered statistically nonsignificant (RR = 0.91, 95% CI = 0.77-1.07). Adiposity is related to enhanced risk for meningioma but is unassociated with risk for glioma. Based on a limited body of evidence, physical activity is related to decreased risk of meningioma but shows little association with risk of glioma.