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En la actualidad, no existe una indicación formal de profilaxis anticomicial en neurocirugía oncológica. Tampoco existen recomendaciones específicas sobre el uso de fármacos antiepilépticos (FAE) en pacientes portadores de meningiomas y libres de crisis que van a ser intervenidos. En general, se prescriben FAE de forma discrecional, teniendo en cuenta diversos factores de riesgo clínico-radiológicos. Presentamos una revisión sistemática y metaanálisis sobre la efectividad de la profilaxis anticomicial en meningiomas sin historia previa de crisis., No formal indication currently exists for seizure prophylaxis in neurosurgical oncology patients. Neither have specific recommendations been made on the use of antiepileptic drugs (AED) in seizure-free patients with meningiomas scheduled for surgery. AEDs are generally prescribed on a discretionary basis, taking into consideration a range of clinical and radiological risk factors. We present a systematic review and meta-analysis exploring the effectiveness of antiepileptic prophylaxis in patients with meningioma and no history of seizures.

PURPOSE: Conventional contrast-enhanced MRI is currently the primary imaging technique used to evaluate radiation treatment response in meningiomas. However, newer perfusion-weighted MRI techniques, such as 3D pseudocontinuous arterial spin labeling (3D pCASL) MRI, capture physiologic information beyond the structural information provided by conventional MRI and may provide additional complementary treatment response information. The purpose of this study is to assess 3D pCASL for the evaluation of radiation-treated meningiomas. METHODS: Twenty patients with meningioma treated with surgical resection followed by radiation, or by radiation alone, were included in this retrospective single-institution study. Patients were evaluated with 3D pCASL and conventional contrast-enhanced MRI before and after radiation (median follow up 6.5 months). Maximum pre- and post-radiation ASL normalized cerebral blood flow (ASL-nCBF) was measured within each meningioma and radiation-treated meningioma (or residual resected and radiated meningioma), and the contrast-enhancing area was measured for each meningioma. Wilcoxon signed-rank tests were used to compare pre- and post-radiation ASL-nCBF and pre- and post-radiation area. RESULTS: All treated meningiomas demonstrated decreased ASL-nCBF following radiation (p < 0.001). Meningioma contrast-enhancing area also decreased after radiation (p = 0.008) but only for approximately half of the meningiomas (9), while half (10) remained stable. A larger effect size (Wilcoxon signed-rank effect size) was seen for ASL-nCBF measurements (r = 0.877) compared to contrast-enhanced area measurements (r = 0.597). CONCLUSIONS: ASL perfusion may provide complementary treatment response information in radiation-treated meningiomas. This complementary information could aid clinical decision-making and provide an additional endpoint for clinical trials.

Introduction Meningiomas frequently occur within the field of neuro-oncology, but it is unclear whether exogenous or imbalanced endogenous hormones are involved in the pathophysiology. A previous case-control study found an almost 20-fold increase in the risk of developing meningioma among users of androgenic anabolic steroids. We, therefore, investigated this hypothesis. Methods We compared the incidence rate of meningioma in a cohort of males sanctioned for the use of androgenic anabolic steroids with age- and sex-matched controls with an identical enrollment date. Results We followed 1189 males sanctioned for using androgenic anabolic steroids for a total of 13,305 person-years and found 0 cases of meningioma. The control cohort of 59,450 males was followed for a total of 654,938 person-years, and 16 were diagnosed with meningioma. Thus, the incidence rate ratio was 0 (95% CI: 0–12.8). Conclusion We did not find any evidence supporting the hypothesis of an increased risk of meningioma development with the use of androgenic anabolic steroids. Due to the limited sample size, we cannot exclude androgenic anabolic steroids as a potential risk factor for meningioma development, despite the lack of apparent evidence in this study., Introduction: Meningiomas frequently occur within the field of neuro-oncology, but it is unclear whether exogenous or imbalanced endogenous hormones are involved in the pathophysiology. A previous case-control study found an almost 20-fold increase in the risk of developing meningioma among users of androgenic anabolic steroids. We, therefore, investigated this hypothesis. Methods: We compared the incidence rate of meningioma in a cohort of males sanctioned for the use of androgenic anabolic steroids with age- and sex-matched controls with an identical enrollment date. Results: We followed 1189 males sanctioned for using androgenic anabolic steroids for a total of 13,305 person-years and found 0 cases of meningioma. The control cohort of 59,450 males was followed for a total of 654,938 person-years, and 16 were diagnosed with meningioma. Thus, the incidence rate ratio was 0 (95% CI: 0–12.8). Conclusion: We did not find any evidence supporting the hypothesis of an increased risk of meningioma development with the use of androgenic anabolic steroids. Due to the limited sample size, we cannot exclude androgenic anabolic steroids as a potential risk factor for meningioma development, despite the lack of apparent evidence in this study.

Background The risk of recurrence is overestimated by the Kaplan–Meier method when competing events, such as death without recurrence, are present. Such overestimation can be avoided by using the Aalen-Johansen method, which is a direct extension of Kaplan–Meier that accounts for competing events. Meningiomas commonly occur in older individuals and have slow-growing properties, thereby warranting competing risk analysis. The extent to which competing events are considered in meningioma literature is unknown, and the consequences of using incorrect methodologies in meningioma recurrence risk analysis have not been investigated. Methods We surveyed articles indexed on PubMed since 2020 to assess the usage of competing risk analysis in recent meningioma literature. To compare recurrence risk estimates obtained through Kaplan–Meier and Aalen-Johansen methods, we applied our international database comprising ~ 8,000 patients with a primary meningioma collected from 42 institutions. Results Of 513 articles, 169 were eligible for full-text screening. There were 6,537 eligible cases from our PERNS database. The discrepancy between the results obtained by Kaplan–Meier and Aalen-Johansen was negligible among low-grade lesions and younger individuals. The discrepancy increased substantially in the patient groups associated with higher rates of competing events (older patients with high-grade lesions). Conclusion The importance of considering competing events in recurrence risk analysis is poorly recognized as only 6% of the studies we surveyed employed Aalen-Johansen analyses. Consequently, most of the previous literature has overestimated the risk of recurrence. The overestimation was negligible for studies involving low-grade lesions in younger individuals; however, overestimation might have been substantial for studies on high-grade lesions., Background: The risk of recurrence is overestimated by the Kaplan–Meier method when competing events, such as death without recurrence, are present. Such overestimation can be avoided by using the Aalen-Johansen method, which is a direct extension of Kaplan–Meier that accounts for competing events. Meningiomas commonly occur in older individuals and have slow-growing properties, thereby warranting competing risk analysis. The extent to which competing events are considered in meningioma literature is unknown, and the consequences of using incorrect methodologies in meningioma recurrence risk analysis have not been investigated. Methods: We surveyed articles indexed on PubMed since 2020 to assess the usage of competing risk analysis in recent meningioma literature. To compare recurrence risk estimates obtained through Kaplan–Meier and Aalen-Johansen methods, we applied our international database comprising ~ 8,000 patients with a primary meningioma collected from 42 institutions. Results: Of 513 articles, 169 were eligible for full-text screening. There were 6,537 eligible cases from our PERNS database. The discrepancy between the results obtained by Kaplan–Meier and Aalen-Johansen was negligible among low-grade lesions and younger individuals. The discrepancy increased substantially in the patient groups associated with higher rates of competing events (older patients with high-grade lesions). Conclusion: The importance of considering competing events in recurrence risk analysis is poorly recognized as only 6% of the studies we surveyed employed Aalen-Johansen analyses. Consequently, most of the previous literature has overestimated the risk of recurrence. The overestimation was negligible for studies involving low-grade lesions in younger individuals; however, overestimation might have been substantial for studies on high-grade lesions.

Introduction Meningiomas frequently occur within the field of neuro-oncology, but it is unclear whether exogenous or imbalanced endogenous hormones are involved in the pathophysiology. A previous case-control study found an almost 20-fold increase in the risk of developing meningioma among users of androgenic anabolic steroids. We, therefore, investigated this hypothesis. Methods We compared the incidence rate of meningioma in a cohort of males sanctioned for the use of androgenic anabolic steroids with age- and sex-matched controls with an identical enrollment date. Results We followed 1189 males sanctioned for using androgenic anabolic steroids for a total of 13,305 person-years and found 0 cases of meningioma. The control cohort of 59,450 males was followed for a total of 654,938 person-years, and 16 were diagnosed with meningioma. Thus, the incidence rate ratio was 0 (95% CI: 0–12.8). Conclusion We did not find any evidence supporting the hypothesis of an increased risk of meningioma development with the use of androgenic anabolic steroids. Due to the limited sample size, we cannot exclude androgenic anabolic steroids as a potential risk factor for meningioma development, despite the lack of apparent evidence in this study., Introduction: Meningiomas frequently occur within the field of neuro-oncology, but it is unclear whether exogenous or imbalanced endogenous hormones are involved in the pathophysiology. A previous case-control study found an almost 20-fold increase in the risk of developing meningioma among users of androgenic anabolic steroids. We, therefore, investigated this hypothesis. Methods: We compared the incidence rate of meningioma in a cohort of males sanctioned for the use of androgenic anabolic steroids with age- and sex-matched controls with an identical enrollment date. Results: We followed 1189 males sanctioned for using androgenic anabolic steroids for a total of 13,305 person-years and found 0 cases of meningioma. The control cohort of 59,450 males was followed for a total of 654,938 person-years, and 16 were diagnosed with meningioma. Thus, the incidence rate ratio was 0 (95% CI: 0–12.8). Conclusion: We did not find any evidence supporting the hypothesis of an increased risk of meningioma development with the use of androgenic anabolic steroids. Due to the limited sample size, we cannot exclude androgenic anabolic steroids as a potential risk factor for meningioma development, despite the lack of apparent evidence in this study.

Patients with meningiomas frequently exhibit impairments in executive functioning. There are few studies specifically examining the role of frontal meningioma localization in executive functioning impairments. This study examines whether frontally located meningiomas are specifically associated with executive functioning impairments in a large sample of meningioma patients before treatment, using an axis-wise and lobe-based approach to meningioma localization. We retrospectively examined cognitive performances in 353 patients with frontal, frontally-involved and non-frontal meningiomas on a battery of tests including tests of executive functioning. We applied an axis-based approach to meningioma location, in addition to qualitative lobe-based localization. We examined the association between meningioma coordinates on an anterior-posterior axis and continuous cognitive performance scores in univariate correlations and linear regression analyses. We also examined the association between meningioma coordinates on an anterior-posterior axis with cognitive impairments in multivariable logistic regression analyses. Meningioma position on the anterior-posterior axis was only univariately associated with mean performance on the Stroop test Interference ratio and Symbol Digit Coding task. There was no (multivariable) association with impairments on tests of executive or non-executive domains. Increased odds of impairment on executive functioning tasks were associated with left-localization (Verbal Fluency) and larger meningioma volumes (Shifting Attention). We did not find a specific relation between a frontal meningioma location and executive functioning impairments, which may be explained by widespread organization of executive functioning throughout the brain, diffuse cognitive effects of the mass of meningiomas, functional reorganization due to neuroplasticity, or functional involvement of less-anteriorly located frontal areas.

Background The risk of recurrence is overestimated by the Kaplan–Meier method when competing events, such as death without recurrence, are present. Such overestimation can be avoided by using the Aalen-Johansen method, which is a direct extension of Kaplan–Meier that accounts for competing events. Meningiomas commonly occur in older individuals and have slow-growing properties, thereby warranting competing risk analysis. The extent to which competing events are considered in meningioma literature is unknown, and the consequences of using incorrect methodologies in meningioma recurrence risk analysis have not been investigated. Methods We surveyed articles indexed on PubMed since 2020 to assess the usage of competing risk analysis in recent meningioma literature. To compare recurrence risk estimates obtained through Kaplan–Meier and Aalen-Johansen methods, we applied our international database comprising ~ 8,000 patients with a primary meningioma collected from 42 institutions. Results Of 513 articles, 169 were eligible for full-text screening. There were 6,537 eligible cases from our PERNS database. The discrepancy between the results obtained by Kaplan–Meier and Aalen-Johansen was negligible among low-grade lesions and younger individuals. The discrepancy increased substantially in the patient groups associated with higher rates of competing events (older patients with high-grade lesions). Conclusion The importance of considering competing events in recurrence risk analysis is poorly recognized as only 6% of the studies we surveyed employed Aalen-Johansen analyses. Consequently, most of the previous literature has overestimated the risk of recurrence. The overestimation was negligible for studies involving low-grade lesions in younger individuals; however, overestimation might have been substantial for studies on high-grade lesions., Background: The risk of recurrence is overestimated by the Kaplan–Meier method when competing events, such as death without recurrence, are present. Such overestimation can be avoided by using the Aalen-Johansen method, which is a direct extension of Kaplan–Meier that accounts for competing events. Meningiomas commonly occur in older individuals and have slow-growing properties, thereby warranting competing risk analysis. The extent to which competing events are considered in meningioma literature is unknown, and the consequences of using incorrect methodologies in meningioma recurrence risk analysis have not been investigated. Methods: We surveyed articles indexed on PubMed since 2020 to assess the usage of competing risk analysis in recent meningioma literature. To compare recurrence risk estimates obtained through Kaplan–Meier and Aalen-Johansen methods, we applied our international database comprising ~ 8,000 patients with a primary meningioma collected from 42 institutions. Results: Of 513 articles, 169 were eligible for full-text screening. There were 6,537 eligible cases from our PERNS database. The discrepancy between the results obtained by Kaplan–Meier and Aalen-Johansen was negligible among low-grade lesions and younger individuals. The discrepancy increased substantially in the patient groups associated with higher rates of competing events (older patients with high-grade lesions). Conclusion: The importance of considering competing events in recurrence risk analysis is poorly recognized as only 6% of the studies we surveyed employed Aalen-Johansen analyses. Consequently, most of the previous literature has overestimated the risk of recurrence. The overestimation was negligible for studies involving low-grade lesions in younger individuals; however, overestimation might have been substantial for studies on high-grade lesions.

Tesis por compendio, [ES] El cáncer constituye la segunda causa de muerte en España. El tromboembolismo venoso (TEV), una complicación del cáncer, conlleva gran gasto del presupuesto sanitario y representa la segunda causa de muerte en estos pacientes. Sin embargo, las herramientas actuales disponibles para la identificación de pacientes oncológicos con elevado riesgo trombótico son limitadas. Adicionalmente, no existen métodos simples, mínimamente invasivos y económicos de diagnóstico de cáncer vesical. Por este motivo, se utilizan técnicas dañinas como la tomografía computarizada la cual implica una elevada dosis de exposición a radiación y procedimientos invasivos como la cistoscopia. Además, un estado hipercoagulable parece tener una relación directa con una mayor carga tumoral y un peor pronóstico. El objetivo principal de la presente Tesis Doctoral es explorar la utilidad clínica de nuevos métodos diagnósticos y pronósticos para el cáncer y sus complicaciones trombóticas. En la primera parte de la Tesis, nos hemos centrado en el papel de miRNAs en orina como biomarcadores de cáncer vesical. Hemos identificado al miR-29c-3p como el miRNA más estable por lo que fue utilizado como normalizador. Hemos ajustado un modelo de regresión logística ordinal para el diagnóstico y estratificación de cáncer vesical utilizando la expresión de miRNAs en orina de pacientes y controles. Este modelo incluyó la expresión de 7 miRNAs: miR-221-3p, miR-93-5p, miR-362-3p, miR-191-5p, miR-200c-3p, miR-192-5p y miR-21-5p. En la segunda parte de la Tesis, nos centramos en el estudio de nuevos biomarcadores para la trombosis asociada a cáncer. Analizamos el potencial predictivo de los miRNAs y de marcadores de activación de neutrófilos en pacientes con cáncer pancreático y pacientes con glioma y meningioma. En cáncer pancreático, obtuvimos un perfil de 7 miRNAs (miR-486-5p, miR-106b-5p, let-7i-5p, let-7g-5p, miR-144-3p, miR-19a-3p y miR-103a-3p) capaz de estimar el riesgo de TEV al diagnóstico con dianas inc, [CA] El càncer constitueix la segona causa de mort a Espanya. El tromboembolisme venós (TEV), una complicació del càncer, representa la segona causa de mort en aquests pacients i comporta una gran despesa sanitària. No obstant això, les eines disponibles actualment per a la identificació de pacients oncològics amb elevat risc trombòtic són limitades. Actualment, no existeixen mètodes diagnòstics per al càncer de bufeta senzills, mínimament invasius i econòmics. Per aquest motiu, s'utilitzen tècniques nocives com la tomografia computada la qual implica una elevada dosi d'exposició a radiació i procediments invasius com la cistoscòpia. A més, un estat hipercoagulable sembla tindre una relació directa amb una major càrrega tumoral i un pitjor pronòstic. L'objectiu principal de la present Tesi Doctoral fou explorar la utilitat clínica de nous mètodes diagnòstics i pronòstics per al càncer i les seues complicacions trombòtiques. En la primera part de la Tesi, ens hem centrat en el paper dels microRNAs (miRNAs) en orina com biomarcadors de càncer de bufeta. Hem identificat al miR-29c-3p com el miRNA més estable per la qual cosa va ser utilitzat com a normalitzador. Hem ajustat un model de regressió logística ordinal per al diagnòstic i estratificació de càncer de bufeta utilitzant l'expressió de miRNAs en orina de pacients i controls. Aquest model va incloure l'expressió de 7 miRNAs: miR-221-3p, miR-93-5p, miR-362-3p, miR-191-5p, miR-200c-3p, miR-192-5p i miR-21-5p. En la segona part de la Tesi, ens centràrem en l'estudi de nous biomarcadors per a la trombosi associada a càncer. Analitzàrem el potencial predictiu dels miRNAs i de marcadors d'activació de neutròfils en pacients amb càncer pancreàtic i pacients amb glioma i meningioma. En càncer pancreàtic, vàrem obtindre un perfil de 7 miRNAs (miR-486-5p, miR-106b-5p, let-7i-5p, let-7g-5p, miR-144-3p, miR-19a-3p i miR-103a-3p) capaç d'estimar el risc de TEV al diagnostic dels pacients els quals tenen dianes incloses en les, [EN] Cancer is the second leading cause of death in Spain. Collaterally, venous thromboembolism (VTE), as a complication of cancer, consumes a great part of its healthcare budget and, more importantly, it is the second cause of death in these patients. However, limited tools are available to identify high risk patients. Additionally, a simple, minimally invasive and economical diagnostic methods for bladder cancer are also lacking. For that aim, harmful techniques are used like CT scan with high radiation exposure and invasive procedures like cystoscopy. Moreover, a hypercoagulable state seems directly related to a large tumor burden and poor prognosis. The overall aim of this Doctoral Thesis is to explore the clinical utility of novel diagnostic and prognostic methods for cancer and its thrombotic complications. In the first part of this Doctoral Thesis, we focused on the role of urine miRNAs as bladder cancer biomarkers. We identified miR-29c-3p as the most stable miRNA and was therefore used as normalizer. We adjusted an ordinal logistic regression model for the diagnosis and stratification of BC using the urine miRNA expression levels of patients and controls. This model included 7 miRNAs: miR-221-3p, miR-93-5p, miR-362-3p, miR-191-5p, miR-200c-3p, miR-192-5p and miR-21-5p. In the second part of this Doctoral Thesis, we focused on the study of novel biomarkers for cancer-associated thrombosis. We analyzed the predictive potential of miRNAs and neutrophil activation markers of thrombotic events in patients with pancreatic cancer and patients with glioma and meningioma. In pancreatic cancer, we obtained a profile of 7 miRNAs (miR-486-5p, miR-106b-5p, let-7i-5p, let-7g-5p, miR-144-3p, miR-19a-3p and miR-103a-3p) able to estimate the risk of potential VTE at diagnosis with targets involved in the pancreatic cancer and complement and coagulation cascades pathways. In the study of the neutrophil activation makers, we obtained a new predictive model of VTE with calprot

Tesis por compendio, [ES] El cáncer constituye la segunda causa de muerte en España. El tromboembolismo venoso (TEV), una complicación del cáncer, conlleva gran gasto del presupuesto sanitario y representa la segunda causa de muerte en estos pacientes. Sin embargo, las herramientas actuales disponibles para la identificación de pacientes oncológicos con elevado riesgo trombótico son limitadas. Adicionalmente, no existen métodos simples, mínimamente invasivos y económicos de diagnóstico de cáncer vesical. Por este motivo, se utilizan técnicas dañinas como la tomografía computarizada la cual implica una elevada dosis de exposición a radiación y procedimientos invasivos como la cistoscopia. Además, un estado hipercoagulable parece tener una relación directa con una mayor carga tumoral y un peor pronóstico. El objetivo principal de la presente Tesis Doctoral es explorar la utilidad clínica de nuevos métodos diagnósticos y pronósticos para el cáncer y sus complicaciones trombóticas. En la primera parte de la Tesis, nos hemos centrado en el papel de miRNAs en orina como biomarcadores de cáncer vesical. Hemos identificado al miR-29c-3p como el miRNA más estable por lo que fue utilizado como normalizador. Hemos ajustado un modelo de regresión logística ordinal para el diagnóstico y estratificación de cáncer vesical utilizando la expresión de miRNAs en orina de pacientes y controles. Este modelo incluyó la expresión de 7 miRNAs: miR-221-3p, miR-93-5p, miR-362-3p, miR-191-5p, miR-200c-3p, miR-192-5p y miR-21-5p. En la segunda parte de la Tesis, nos centramos en el estudio de nuevos biomarcadores para la trombosis asociada a cáncer. Analizamos el potencial predictivo de los miRNAs y de marcadores de activación de neutrófilos en pacientes con cáncer pancreático y pacientes con glioma y meningioma. En cáncer pancreático, obtuvimos un perfil de 7 miRNAs (miR-486-5p, miR-106b-5p, let-7i-5p, let-7g-5p, miR-144-3p, miR-19a-3p y miR-103a-3p) capaz de estimar el riesgo de TEV al diagnóstico con dianas inc, [CA] El càncer constitueix la segona causa de mort a Espanya. El tromboembolisme venós (TEV), una complicació del càncer, representa la segona causa de mort en aquests pacients i comporta una gran despesa sanitària. No obstant això, les eines disponibles actualment per a la identificació de pacients oncològics amb elevat risc trombòtic són limitades. Actualment, no existeixen mètodes diagnòstics per al càncer de bufeta senzills, mínimament invasius i econòmics. Per aquest motiu, s'utilitzen tècniques nocives com la tomografia computada la qual implica una elevada dosi d'exposició a radiació i procediments invasius com la cistoscòpia. A més, un estat hipercoagulable sembla tindre una relació directa amb una major càrrega tumoral i un pitjor pronòstic. L'objectiu principal de la present Tesi Doctoral fou explorar la utilitat clínica de nous mètodes diagnòstics i pronòstics per al càncer i les seues complicacions trombòtiques. En la primera part de la Tesi, ens hem centrat en el paper dels microRNAs (miRNAs) en orina com biomarcadors de càncer de bufeta. Hem identificat al miR-29c-3p com el miRNA més estable per la qual cosa va ser utilitzat com a normalitzador. Hem ajustat un model de regressió logística ordinal per al diagnòstic i estratificació de càncer de bufeta utilitzant l'expressió de miRNAs en orina de pacients i controls. Aquest model va incloure l'expressió de 7 miRNAs: miR-221-3p, miR-93-5p, miR-362-3p, miR-191-5p, miR-200c-3p, miR-192-5p i miR-21-5p. En la segona part de la Tesi, ens centràrem en l'estudi de nous biomarcadors per a la trombosi associada a càncer. Analitzàrem el potencial predictiu dels miRNAs i de marcadors d'activació de neutròfils en pacients amb càncer pancreàtic i pacients amb glioma i meningioma. En càncer pancreàtic, vàrem obtindre un perfil de 7 miRNAs (miR-486-5p, miR-106b-5p, let-7i-5p, let-7g-5p, miR-144-3p, miR-19a-3p i miR-103a-3p) capaç d'estimar el risc de TEV al diagnostic dels pacients els quals tenen dianes incloses en les, [EN] Cancer is the second leading cause of death in Spain. Collaterally, venous thromboembolism (VTE), as a complication of cancer, consumes a great part of its healthcare budget and, more importantly, it is the second cause of death in these patients. However, limited tools are available to identify high risk patients. Additionally, a simple, minimally invasive and economical diagnostic methods for bladder cancer are also lacking. For that aim, harmful techniques are used like CT scan with high radiation exposure and invasive procedures like cystoscopy. Moreover, a hypercoagulable state seems directly related to a large tumor burden and poor prognosis. The overall aim of this Doctoral Thesis is to explore the clinical utility of novel diagnostic and prognostic methods for cancer and its thrombotic complications. In the first part of this Doctoral Thesis, we focused on the role of urine miRNAs as bladder cancer biomarkers. We identified miR-29c-3p as the most stable miRNA and was therefore used as normalizer. We adjusted an ordinal logistic regression model for the diagnosis and stratification of BC using the urine miRNA expression levels of patients and controls. This model included 7 miRNAs: miR-221-3p, miR-93-5p, miR-362-3p, miR-191-5p, miR-200c-3p, miR-192-5p and miR-21-5p. In the second part of this Doctoral Thesis, we focused on the study of novel biomarkers for cancer-associated thrombosis. We analyzed the predictive potential of miRNAs and neutrophil activation markers of thrombotic events in patients with pancreatic cancer and patients with glioma and meningioma. In pancreatic cancer, we obtained a profile of 7 miRNAs (miR-486-5p, miR-106b-5p, let-7i-5p, let-7g-5p, miR-144-3p, miR-19a-3p and miR-103a-3p) able to estimate the risk of potential VTE at diagnosis with targets involved in the pancreatic cancer and complement and coagulation cascades pathways. In the study of the neutrophil activation makers, we obtained a new predictive model of VTE with calprot

BackgroundThree- and five-year progression-free survival (PFS) for low-risk meningioma managed with surgery and observation reportedly exceeds 90%. Herewith we summarize outcomes for low-risk meningioma patients enrolled on NRG/RTOG 0539.MethodsThis phase II trial allocated patients to one of three groups per World Health Organization grade, recurrence status, and resection extent. Low-risk patients had either gross total (GTR) or subtotal resection (STR) for a newly diagnosed grade 1 meningioma and were observed after surgery. The primary endpoint was 3-year PFS. Adverse events (AEs) were scored using Common Terminology Criteria for Adverse Events (CTCAE) version 3.ResultsAmong 60 evaluable patients, the median follow-up was 9.1 years. The 3-, 5-, and 10-year rates were 91.4% (95% CI, 84.2 to 98.6), 89.4% (95% CI, 81.3 to 97.5), 85.0% (95% CI, 75.3 to 94.7) for PFS and 98.3% (95% CI, 94.9 to 100), 98.3%, (95% CI, 94.9 to 100), 93.8% (95% CI, 87.0 to 100) for overall survival (OS), respectively. With centrally confirmed GTR, 3/5/10y PFS and OS rates were 94.3/94.3/87.6% and 97.1/97.1/90.4%. With STR, 3/5/10y PFS rates were 83.1/72.7/72.7% and 10y OS 100%. Five patients reported one grade 3, four grade 2, and five grade 1 AEs. There were no grade 4 or 5 AEs.ConclusionsThese results prospectively validate high PFS and OS for low-risk meningioma managed surgically but raise questions regarding optimal management following STR, a subcohort that could potentially benefit from adjuvant therapy.

OBJECTIVE: Meningioma is the most common primary intracranial neoplasm. Only 1%-3% of meningiomas are malignant according to the 2016 WHO criteria (WHO grade III). High-grade meningiomas present specific gene expression signatures indicating aggressive growth or recurrence. However, changes in gene expression and in neuroinflammatory gene expression signatures in WHO grade III meningiomas and during progression from WHO grade I or II to grade III are unknown. METHODS: The authors used a NanoString targeted gene expression panel with focus on 787 genes relevant in meningioma pathology and neuroinflammatory pathways to investigate patients with grade III meningiomas treated at Rigshospitalet from 2000 to 2020 (n = 51). A temporal dimension was added to the investigation by including samples from patients earlier grade I and II meningiomas and grade III recurrences (n = 139 meningiomas). The authors investigated changes in neuroinflammatory gene expression signatures in 1) grade I meningiomas that later transformed into grade III meningiomas, and 2) grade III meningiomas compared with nonrecurrent grade I meningiomas. RESULTS: The authors data indicate that FOXM1, TOP2A, BIRC5, and MYBL2 were enriched and the HOTAIR regulatory pathway was enriched in grade III meningiomas compared with nonrecurrent grade I meningiomas. They discovered a separation of malignant and benign meningiomas based only on genes involved in microglia regulation with enrichment of P2RY12 in grade I compared with grade III meningiomas. Interestingly, FOXM1 was upregulated in premalignant grade I meningioma years before the grade III transformation. CONCLUSIONS: The authors found gene expression changes in low-grade meningiomas that predated histological transformation to grade III meningiomas. Neuroinflammation genes distinguished grade III from grade I meningiomas.

Meningiomas comprise a histologically and clinically diverse set of tumors arising from the meningothelial lining of the central nervous system. In the past decade, remarkable progress has been made in deciphering the biology of these common neoplasms. Nevertheless, effective systemic or molecular therapies for meningiomas remain elusive and are active areas of preclinical and clinical investigation. Thus, standard treatment modalities for meningiomas are limited to maximal safe resection, radiotherapy, or radiosurgery. This review examines the history, clinical rationale, and future directions of radiotherapy and radiosurgery as integral and effective treatments for meningiomas.

Patients with space-occupying lesions adjacent to the superior sagittal sinus (SSS) present several technical considerations. For craniotomies crossing the SSS, a two-part method allows for dissection of the epidural space and dura under direct vision after removing a more lateral parasagittal bone flap. However, when the inner table surface of the medial component of the two-part bone flap is irregular, this can be difficult. We describe a method for channel drilling of the diploic bone, which allows for the piecemeal removal of the inner table using an upbiting rongeur. This article presents the case of meningioma with documented growth and provides a technical note of this technique to facilitate safe dissection of the midline dura. A patient presented with headaches and an anterior one-third parasagittal meningioma with documented growth. She selected surgical removal for treatment. A right frontal two-part parasagittal craniotomy was recommended. The preoperative imaging showed that the frontal bone was thick, with irregularity of the inner table. Intraoperatively, a channel was drilled in the diploic space of the bone, leaving the outer table intact. This provided a thin lip of the inner table that could be dissected over a short distance and then removed with a 2-mm upbiting rongeur. This allowed for further dissection of the dura crossing the midline under direct vision and safe secondary bone piece removal. The dura was opened to the edge of the SSS, allowing full exposure of the parasagittal region and interhemispheric fissure, thus limiting retraction of the medial right frontal lobe. The bone flap was removed in two pieces without a dural tear over the midline in spite of inner table irregularities. A Simpson grade 1 removal was accomplished, including excision of the affected falx, and the postoperative course was uncomplicated. In conclusion, diploic bone channel drilling is a technique that can be used to create a thin lip of

Homozygous deletion of CDKN2A/B was recently incorporated into the World Health Organization classification for grade 3 meningiomas. While this marker is overall rare in meningiomas, its relationship to other CDKN2A alterations on a transcriptomic, epigenomic, and copy number level has not yet been determined. We therefore utilized multidimensional molecular data of 1577 meningioma samples from 6 independent cohorts enriched for clinically aggressive meningiomas to comprehensively interrogate the spectrum of CDKN2A alterations through DNA methylation, copy number variation, transcriptomics, and proteomics using an integrated molecular approach. Homozygous CDKN2A/B deletions were identified in only 7.1% of cases but were associated with significantly poorer outcomes compared to tumors without these deletions. Heterozygous CDKN2A/B deletions were identified in 2.6% of cases and had similarly poor outcomes as those with homozygous deletions. Among tumors with intact CDKN2A/B (without a homozygous or heterozygous deletion), we found a distinct difference in outcome based on mRNA expression of CDKN2A, with meningiomas that had elevated mRNA expression (CDKN2Ahigh) having a significantly shorter time to recurrence. The expression of CDKN2A was independently prognostic after accounting for copy number loss and consistently increased with WHO grade and more aggressive molecular and methylation groups irrespective of cohort. Despite the discordant and mutually exclusive status of the CDKN2A gene in these groups, both CDKN2Ahigh meningiomas and meningiomas with CDKN2A deletions were enriched for similar cell cycle pathways but at different checkpoints. High mRNA expression of CDKN2A was also associated with gene hypermethylation, Rb-deficiency, and lack of response to CDK inhibition. p16 immunohistochemistry could not reliably differentiate between meningiomas with and without CDKN2A deletions but appeared to correlate better with mRNA expression

A 6-year-old female spayed German Shepherd mixed-breed dog was presented for treatment of a frontal lobe mass diagnosed on MRI, after an acute onset of generalized seizures and behavior changes. Computed tomography of the head was performed for radiation therapy planning and revealed concurrent cribriform plate lysis without nasal sinus invasion, and focal lysis of the left ventrolateral cranial fossa. Histopathology of the mass obtained via surgical excision was consistent with a grade I fibrous meningioma. The dog had a good outcome following surgery and radiation therapy.

Rosai-Dorfman disease is an infrequent condition with no known etiology. The intracranial presentation is even rarer, and it resembles the appearance of a meningioma in image studies. We present the case of a 38-year-old male patient who was admitted because of an extra-axial supratentorial cranial tumor, associated to mild neurological deficit. The presumptive diagnosis was convexity meningioma. After surgery, the definitive histologic diagnosis was intracranial Rosai-Dorfman disease. This condition should be considered in the differential diagnosis of an extra-axial intracranial lesion suggesting meningioma, because of similar neuroimaging results and the similar clinical picture, La Enfermedad de Rosai-Dorfman es un trastorno infrecuente y de etiología desconocida. La presentación intracraneal es aún más rara y suele imitar la apariencia de un meningioma en las imágenes del encéfalo. Se presenta el caso de un paciente varón de 38 años que ingresa por una tumoración intracraneal, extra-axial y supratentorial asociada a déficit neurológico leve; con diagnóstico presuntivo de meningioma de la convexidad. Después de la intervención quirúrgica, el diagnóstico histológico definitivo fue de Enfermedad de Rosai-Dorfman intracraneal. Se debe considerar la Enfermedad de Rosai-Dorfman intracraneal dentro del diagnóstico diferencial de una lesión intracraneal extra-axial sugestiva de un meningioma debido a la similitud en las neuroimágenes y la presentación clínica entre ambas patologías

ObjectiveMeningiomas are the most common primary intracranial tumor, and resection is a mainstay of treatment. It is unclear what duration of imaging follow-up is reasonable for WHO grade I meningiomas undergoing complete resection. This study examined recurrence rates, timing of recurrence, and risk factors for recurrence in patients undergoing a complete resection (as defined by both postoperative MRI and intraoperative impression) of WHO grade I meningiomas.MethodsThe authors conducted a retrospective, single-center study examining recurrence risk for adult patients with a single intracranial meningioma that underwent complete resection. Uni- and multivariate nominal logistic regression and Cox proportional hazards analyses were performed to identify variables associated with recurrence and time to recurrence. Two supervised machine learning algorithms were then implemented to confirm factors within the cohort that were associated with recurrence.ResultsThe cohort consisted of 823 patients who met inclusion criteria, and 56 patients (6.8%) had recurrence on imaging follow-up. The median age of the cohort was 56 years, and 77.4% of patients were female. The median duration of head imaging follow-up for the entire cohort was 2.7 years, but for the subgroup of patients who had a recurrence, the median follow-up was 10.1 years. Estimated 1-, 5-, 10-, and 15-year recurrence-free survival rates were 99.8% (95% confidence interval [CI] 98.8%-99.9%), 91.0% (95% CI 87.7%-93.6%), 83.6% (95% CI 78.6%-87.6%), and 77.3% (95% CI 69.7%-83.4%), respectively, for the entire cohort. On multivariate analysis, MIB-1 index (odds ratio [OR] per 1% increase: 1.34, 95% CI 1.13-1.58, p = 0.0003) and follow-up duration (OR per year: 1.12, 95% CI 1.03-1.21, p = 0.012) were both associated with recurrence. Gradient-boosted decision tree and random forest analyses both identified MIB-1 index as the main factor associated with recurrence, aside from length of imaging follow-up. For tumors wit

Magnetic resonance spectroscopy (MRS) is an MR technique that provides informa-tion about the biochemistry of tissues in a noninvasive way. MRS has been widelyused for the study of brain tumors, both preoperatively and during follow-up. In thisstudy, we investigated the performance of a range of variants of unsupervised matrixfactorization methods of the non-negative matrix underapproximation (NMU) family,namely, sparse NMU, global NMU, and recursive NMU, and compared them withconvex non-negative matrix factorization (C-NMF), which has previously shown agood performance on brain tumor diagnostic support problems using MRS data. Thepurpose of the investigation was 2-fold: first, to ascertain the differences among thesources extracted by these methods; and second, to compare the influence of eachmethod in the diagnostic accuracy of the classification of brain tumors, using them asfeature extractors. We discovered that, first, NMU variants found meaningful sourcesin terms of biological interpretability, but representing parts of the spectrum, incontrast to C-NMF; and second, that NMU methods achieved better classificationaccuracy than C-NMF for the classification tasks when one class was notmeningioma., H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions, grant number H2020-MSCA-ITN-2018-813120. Proyectos de investigación en salud 2020, grant numbers PI20/00064 and PI20/00360. Spanish Ministerio de Economía y Competitividad SAF2014-52332-R. AEI Research Project PID2019-104551RB-I00. Centro de Investigacion Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN [http://www.ciber-bbn.es/en, accessed on September 12, 2022], CB06/01/0010), an initiative of the Instituto de Salud Carlos III (Spain) co-funded by EU Fondo Europeo de Desarrollo Regional (FEDER). Spanish AEI PID2019-104551RB-I00 grant. XartecSalut, 2018 XARDI 00016 and 2021 XARDI 00021., Peer Reviewed, Postprint (published version)

Introduction: Meningiomas account for nearly 40% of intracranial tumors. Recently, the immunohistochemistry (IHC) markers S100B, SCGN, ACADL and MCM2 have been shown to be associated with underlying biological subtypes of meningioma (MG1-MG4). We aimed to evaluate these IHC markers in a clinical setting. Research question: Are the new proposed IHC markers clinically useful? Methods: In total, 244 patients with meningiomas with tissue in TMAs were included and the IHC markers S100B, SCGN, ACADL and MCM2 were analyzed. Two sets of analyses were performed; the first included all samples with any staining considered positive, the second only samples with >10% immunopositivity. PFS and OS were analyzed in correlation to immunopositivity in the second analysis set. Results: In the first set of analyses only 26.2% of samples could be to allocate to one group. No further analyses were performed with this selection. In the second set of analyses 52.0% could be allocated to a group. There was an enrichment of WHO grade 2 and 3 tumors in MG3 and MG4 as compared to MG1 (24.1% and 25.7% vs. 12.1%). Both the molecular group (p 1/4 0.032) and WHO grade (p 1/4 0.005) had significant impact on PFS, but only WHO grade predicted OS (p 1/4 0.033). Conclusion: We studied the proposed new method of classifying meningiomas into groups MG1, MG2, MG3 and MG4 using IHC markers, but found difficulties applying the classification system in our material mainly due to lack of exclusivity of markers. Thus, in its present form the classification method lacks clinical applicability.

BACKGROUND: Meningiomas, the most common primary intracranial tumors, can be separated into 3 DNA methylation groups with distinct biological drivers, clinical outcomes, and therapeutic vulnerabilities. Alternative meningioma grouping schemes using copy number variants, gene expression profiles, somatic short variants, or integrated molecular models have been proposed. These data suggest meningioma DNA methylation groups may harbor subgroups unifying contrasting theories of meningioma biology. METHODS: A total of 565 meningioma DNA methylation profiles from patients with comprehensive clinical follow-up at independent discovery (n = 200) or validation (n = 365) institutions were reanalyzed and classified into Merlin-intact, Immune-enriched, or Hypermitotic DNA methylation groups. RNA sequencing from the discovery (n = 200) or validation (n = 302) cohort were analyzed in the context of DNA methylation groups to identify subgroups. Biological features and clinical outcomes were analyzed across meningioma grouping schemes. RESULTS: RNA sequencing revealed differential enrichment of FOXM1 target genes across two subgroups of Hypermitotic meningiomas. Differential expression and ontology analyses showed the subgroup of Hypermitotic meningiomas without FOXM1 target gene enrichment was distinguished by gene expression programs driving macromolecular metabolism. Analysis of genetic, epigenetic, gene expression, or cellular features revealed Hypermitotic meningioma subgroups were concordant with Proliferative or Hypermetabolic meningiomas, which were previously reported alongside Merlin-intact and Immune-enriched tumors using an integrated molecular model. The addition of DNA methylation subgroups to clinical models refined the prediction of postoperative outcomes compared to the addition of DNA methylation groups. CONCLUSIONS: Meningiomas can be separated into three DNA methylation groups and Hypermitotic meningiomas can be subdivided into Proliferative and Hypermetabolic s

Background: The coexistence of meningioma and dural arteriovenous fistula (dAVF) is a rare, but highly complex condition. Various pathophysiological mechanisms underlie intracranial meningiomas with continuous or distant dAVFs. We describe a case of coexisting meningioma and dAVF with a systematic review of the literature. Result: Including the present case, there are 21 reported cases of coexisting intracranial dAVF and meningioma. The patients’ ages ranged from 23 to 76 years, with a mean age of 61 years. The most common presenting symptom was headache. The dAVFs were commonly located at the transverse-sigmoid sinus (43%) and superior sagittal sinus (24%). The most common meningioma locations were the tentorium and parietal convexity. In 76% of the cases, the meningioma occluded the sinus. The most common dAVF treatment was transcatheter arterial embolization, followed by tumor resection (52%). Among the 20 cases with available outcome data, 90% reported favorable outcomes. Conclusion: This report highlights some of the features of coexisting dAVF and meningioma and presents a systematic review of other reports on this phenomenon. Through an in-depth analysis of the literature, we highlight some of the leading theories regarding the causes of concomitant dAVF and meningiomas. Our report supports one of the leading theories that impaired venous return, whether through the occlusion of sinuses or sinus manipulation during surgery, plays a role in the development of dAVF. Further understanding may help guide future clinical decision-making and surgical planning.

Introduction: Meningiomas account for nearly 40% of intracranial tumors. Recently, the immunohistochemistry (IHC) markers S100B, SCGN, ACADL and MCM2 have been shown to be associated with underlying biological subtypes of meningioma (MG1-MG4). We aimed to evaluate these IHC markers in a clinical setting. Research question: Are the new proposed IHC markers clinically useful? Methods: In total, 244 patients with meningiomas with tissue in TMAs were included and the IHC markers S100B, SCGN, ACADL and MCM2 were analyzed. Two sets of analyses were performed; the first included all samples with any staining considered positive, the second only samples with >10% immunopositivity. PFS and OS were analyzed in correlation to immunopositivity in the second analysis set. Results: In the first set of analyses only 26.2% of samples could be to allocate to one group. No further analyses were performed with this selection. In the second set of analyses 52.0% could be allocated to a group. There was an enrichment of WHO grade 2 and 3 tumors in MG3 and MG4 as compared to MG1 (24.1% and 25.7% vs. 12.1%). Both the molecular group (p 1/4 0.032) and WHO grade (p 1/4 0.005) had significant impact on PFS, but only WHO grade predicted OS (p 1/4 0.033). Conclusion: We studied the proposed new method of classifying meningiomas into groups MG1, MG2, MG3 and MG4 using IHC markers, but found difficulties applying the classification system in our material mainly due to lack of exclusivity of markers. Thus, in its present form the classification method lacks clinical applicability.

Background: The present narrative review aims to discuss cognitive–emotional–behavioral symptoms in adults with brain tumors at the time of diagnosis. Methods: The PubMed database was searched considering glioma, pituitary adenoma, and meningioma in adulthood as pathologies, together with cognitive, neuropsychological, or behavioral aspects. Results: Although a significant number of studies describe cognitive impairment after surgery or treatment in adults with brain tumors, only few focus on cognitive–emotional–behavioral symptoms at diagnosis. Furthermore, the importance of an effective communication and its impact on patients’ quality of life and compliance with treatment are seldom discussed. Conclusions: Adults with brain tumors have needs in terms of cognitive–emotional–behavioral features that are detectable at the time of diagnosis; more research is needed to identify effective communication protocols in order to allow a higher perceived quality of life in these patients.

Meningiomas are the most common primary intracranial tumors and show extensive infiltration of macrophages. The mitochondrial membrane protein translocator protein (TSPO) has been used as an in vivo marker of microglia and macrophage activation to visualize neuroinflammation. However, it is unknown which cell types express TSPO in meningiomas. Immunohistochemistry of 38 WHO grade 1–3 meningiomas was subjected to segmentation and deep learning classification of TSPO expression to either Iba1-positive tumor-associated macrophages (TAMs) or all other (mainly neoplastic) cells. A possible association between clinical data and TSPO expression intensities was also investigated. TAMs accounted for 15.9%–26% of all cells in the meningioma tissue. Mean fluorescence intensity of TSPO was significantly higher in TAMs (p < 0.0001), but the mass of neoplastic cells in the tumors exceeded that of TAMs. Thus, the summed fluorescence intensity of TSPO in meningioma cells was 64.1% higher than in TAMs (p = 0.0003). We observed no correlation between TSPO expression intensity and WHO grade. These results indicate that both macrophage-lineage and neoplastic cells in meningiomas express TSPO and that the SPECT-TSPO signal in meningiomas mainly reflects the latter; TSPO is expressed equally in parenchymal activated and resting macrophage/microglia lineage cells., Meningiomas are the most common primary intracranial tumors and show extensive infiltration of macrophages. The mitochondrial membrane protein translocator protein (TSPO) has been used as an in vivo marker of microglia and macrophage activation to visualize neuroinflammation. However, it is unknown which cell types express TSPO in meningiomas. Immunohistochemistry of 38 WHO grade 1-3 meningiomas was subjected to segmentation and deep learning classification of TSPO expression to either Iba1-positive tumor-associated macrophages (TAMs) or all other (mainly neoplastic) cells. A possible association between clinical data and TSPO expression intensities was also investigated. TAMs accounted for 15.9%-26% of all cells in the meningioma tissue. Mean fluorescence intensity of TSPO was significantly higher in TAMs (p < 0.0001), but the mass of neoplastic cells in the tumors exceeded that of TAMs. Thus, the summed fluorescence intensity of TSPO in meningioma cells was 64.1% higher than in TAMs (p = 0.0003). We observed no correlation between TSPO expression intensity and WHO grade. These results indicate that both macrophage-lineage and neoplastic cells in meningiomas express TSPO and that the SPECT-TSPO signal in meningiomas mainly reflects the latter; TSPO is expressed equally in parenchymal activated and resting macrophage/microglia lineage cells.

Grade 3 meningiomas are rare malignant tumors that can originate de novo or from the progression of lower grade meningiomas. The molecular bases of anaplasia and progression are poorly known. We aimed to report an institutional series of grade 3 anaplastic meningiomas and to investigate the evolution of molecular profile in progressive cases. Clinical data and pathologic samples were retrospectively collected. VEGF, EGFR, EGFRvIII, PD-L1; and Sox2 expression; MGMT methylation status; and TERT promoter mutation were assessed in paired meningioma samples collected from the same patient before and after progression using immunohistochemistry and PCR. Young age, de novo cases, origin from grade 2 in progressive cases, good clinical status, and unilateral side, were associated with more favorable outcomes. In ten progressive meningiomas, by comparing molecular profile before and after progression, we identified two subgroups of patients, one defined by Sox2 increase, suggesting a stem-like, mesenchymal phenotype, and another defined by EGFRvIII gain, suggesting a committed progenitor, epithelial phenotype. Interestingly, cases with Sox2 increase had a significantly shortened survival compared to those with EGFRvIII gain. PD-L1 increase at progression was also associated with worse prognosis, portending immune escape. We thus identified the key drivers of meningioma progression, which can be exploited for personalized treatments.

Purpose: The management of brain tumors during pregnancy is challenging. The clinical rarity and prognostic heterogeneity of such condition makes it difficult to develop standardized guidelines of treatment. The aim of this study was to assess the treatment options used in pregnant women with brain tumors that are currently used in Italy, considering the management of these patients reported in current literature in this field. Methods: A survey addressing the treatments options and management of brain tumors during pregnancy was designed on behalf of an ad-hoc task-force Neuro-Oncology committee of the Società Italiana di Neurochirurgia (SINch) to analyze the management of pregnant patients with brain tumors. We conducted a search of the literature published between January 2011 and September 2021, using MEDLINE (PubMed) in accordance to PRISMA guidelines. Data were discussed to obtain recommendations after evaluation of the selected articles and discussion among the experts. Results: A total of 18 Neurosurgical centers participated in the survey. A total of 31 pregnant women were included in this retrospective study. Meningiomas and gliomas were the two most common types of brain tumors diagnosed during pregnancy. An emergency surgical procedure was required in 12.9% of cases. Conclusion: A multidisciplinary and tailored approach is fundamental. In women showing clinical stability, neurosurgical options should preferably be delayed if possible, and considered during the second trimester or after delivery. In patients with acute neurological symptoms or tumor progression, medical abortion in the first trimester or a C-section in the second and third trimester need to be considered.

Meningiomas are the most common non-metastatic brain tumors, and although the majority are relatively slow-growing and histologically benign, a subset of meningiomas are aggressive and remain challenging to treat. Despite a standard of care that includes surgical resection and radiotherapy, and recent advances in meningioma molecular grouping, there are no systemic medical options for patients with meningiomas that are resistant to standard interventions. Misactivation of the cell cycle at the level of CDK4/6 is common in high-grade or molecularly aggressive meningiomas, and CDK4/6 has emerged as a potential target for systemic meningioma treatments. In this review, we describe the preclinical evidence for CDK4/6 inhibitors as a treatment for high-grade meningiomas and summarize evolving clinical experience with these agents. Further, we highlight upcoming clinical trials for patients meningiomas, and discuss future directions aimed at optimizing the efficacy of these therapies and selecting patients most likely to benefit from their use.

Core Outcome Sets (COS) define minimum outcomes to be measured and reported in clinical effectiveness trials for a particular health condition/health area. Despite recognition as critical to clinical research design for other health areas, none have been developed for neuro-oncology. COS development projects should carefully consider: scope (how the COS should be used), stakeholders involved in development (including patients as both research partners and participants), and consensus methodologies used (typically a Delphi survey and consensus meeting), as well as dissemination plans. Developing COS for neuro-oncology is potentially challenging due to extensive tumor subclassification (including molecular stratification), different symptoms related to anatomical tumor location, and variation in treatment options. Development of a COS specific to tumor subtype, in a specific location, for a particular intervention may be too narrow and would be unlikely to be used. Equally, a COS that is applicable across a wider area of neuro-oncology may be too broad and therefore lack specificity. This review describes why and how a COS may be developed, and discusses challenges for their development, specific to neuro-oncology. The COS under development are briefly described, including: adult glioma, incidental/untreated meningioma, meningioma requiring intervention, and adverse events from surgical intervention for pediatric brain tumors.

BackgroundMeningiomas are the most common primary brain tumor. Though typically benign with a low mutational burden, tumors with benign histology may behave aggressively and there are no proven chemotherapies. Although DNA methylation patterns distinguish subgroups of meningiomas and have higher predictive value for tumor behavior than histologic classification, little is known about differences in DNA methylation between meningiomas and surrounding normal dura tissue.MethodsWhole-exome sequencing and methylation array profiling were performed on 12 dura/meningioma pairs (11 WHO grade I and 1 WHO grade II). Single-nucleotide polymorphism (SNP) genotyping and methylation array profiling were performed on an additional 19 meningiomas (9 WHO grade I, 5 WHO grade II, 4 WHO grade III).ResultsUsing multimodal studies of meningioma/dura pairs, we identified 4 distinct DNA methylation patterns. Diffuse DNA hypomethylation of malignant meningiomas readily facilitated their identification from lower-grade tumors by unsupervised clustering. All clusters and 12/12 meningioma-dura pairs exhibited hypomethylation of the gene promoters of a module associated with the craniofacial patterning transcription factor FOXC1 and its upstream lncRNA FOXCUT. Furthermore, we identified an epigenetic continuum of increasing hypermethylation of polycomb repressive complex target promoters with increasing histopathologic grade.ConclusionThese findings support future investigations of the role of epigenetic dysregulation of FOXC1 and cranial patterning genes in meningioma formation as well as studies of the utility of polycomb inhibitors for the treatment of malignant meningiomas.

'Intracranial mesenchymal tumor, FET-CREB fusion-positive' occurs primarily in children and young adults and has previously been termed intracranial angiomatoid fibrous histiocytoma (AFH) or intracranial myxoid mesenchymal tumor (IMMT). Here we performed genome-wide DNA methylation array profiling of 20 primary intracranial mesenchymal tumors with FET-CREB fusion to further study their ontology. These tumors resolved into two distinct epigenetic subgroups that were both divergent from all other analyzed intracranial neoplasms and soft tissue sarcomas, including meningioma, clear cell sarcoma of soft tissue (CCS), and AFH of extracranial soft tissue. The first subgroup (Group A, 16 tumors) clustered nearest to but independent of solitary fibrous tumor and AFH of extracranial soft tissue, whereas the second epigenetic subgroup (Group B, 4 tumors) clustered nearest to but independent of CCS and also lacked expression of melanocytic markers (HMB45, Melan A, or MITF) characteristic of CCS. Group A tumors most often occurred in adolescence or early adulthood, arose throughout the neuroaxis, and contained mostly EWSR1-ATF1 and EWSR1-CREB1 fusions. Group B tumors arose most often in early childhood, were located along the cerebral convexities or spinal cord, and demonstrated an enrichment for tumors with CREM as the fusion partner (either EWSR1-CREM or FUS-CREM). Group A tumors more often demonstrated stellate/spindle cell morphology and hemangioma-like vasculature, whereas Group B tumors more often demonstrated round cell or epithelioid/rhabdoid morphology without hemangioma-like vasculature, although robust comparison of these clinical and histologic features requires future study. Patients with Group B tumors had inferior progression-free survival relative to Group A tumors (median 4.5 vs. 49 months, p = 0.001). Together, these findings confirm that intracranial AFH-like neoplasms and IMMT represent histologic variants of a single tumor type ('intracranial

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 meningioma, those that threaten neurovascular structures, or demonstrate radiological growth, are usually resected as first-line management strategy. For patients in poor clinical condition, or with inoperable, residual or recurrent disease, radiotherapy is often used as primary or adjuvant treatment. Effective pharmacotherapy treatments do not currently exist. There is heterogeneity in the outcomes measured and reported in meningioma clinical studies. Two 'Core Outcome Sets' (COS) will be developed: (COSMIC: Intervention) for use in meningioma clinical effectiveness trials and (COSMIC: Observation) for use in clinical studies of incidental/untreated meningioma.Methods and analysisTwo systematic literature reviews and trial registry searches will identify outcomes measured and reported in published and ongoing (1) meningioma clinical effectiveness trials, and (2) clinical studies of incidental/untreated meningioma. Outcomes include those that are clinician reported, patient reported, caregiver reported and based on objective tests (eg, neurocognitive tests), as well as measures of progression and survival. Outcomes will be deduplicated and categorised to generate two long lists. The two long lists will be prioritised through two, two-round, international, modified eDelphi surveys including patients with meningioma, healthcare professionals, researchers and those in caring/supporting roles. The two final COS will be ratified through two 1-day online consensus meetings, with representation from all stakeholder groups.Ethics and disseminationInstitutional review board (University of Liverpool) approval was obtained for the conduct of this study. Participant eConsent will be obtained prior to participation in the eDelphi surv

BackgroundMeningiomas are the most common primary brain tumor. Though typically benign with a low mutational burden, tumors with benign histology may behave aggressively and there are no proven chemotherapies. Although DNA methylation patterns distinguish subgroups of meningiomas and have higher predictive value for tumor behavior than histologic classification, little is known about differences in DNA methylation between meningiomas and surrounding normal dura tissue.MethodsWhole-exome sequencing and methylation array profiling were performed on 12 dura/meningioma pairs (11 WHO grade I and 1 WHO grade II). Single-nucleotide polymorphism (SNP) genotyping and methylation array profiling were performed on an additional 19 meningiomas (9 WHO grade I, 5 WHO grade II, 4 WHO grade III).ResultsUsing multimodal studies of meningioma/dura pairs, we identified 4 distinct DNA methylation patterns. Diffuse DNA hypomethylation of malignant meningiomas readily facilitated their identification from lower-grade tumors by unsupervised clustering. All clusters and 12/12 meningioma-dura pairs exhibited hypomethylation of the gene promoters of a module associated with the craniofacial patterning transcription factor FOXC1 and its upstream lncRNA FOXCUT. Furthermore, we identified an epigenetic continuum of increasing hypermethylation of polycomb repressive complex target promoters with increasing histopathologic grade.ConclusionThese findings support future investigations of the role of epigenetic dysregulation of FOXC1 and cranial patterning genes in meningioma formation as well as studies of the utility of polycomb inhibitors for the treatment of malignant meningiomas.

Treatment-refractory meningiomas have a dismal prognosis and limited treatment options. Meningiomas express high-densities of somatostatin receptors (SSTR), thus potentially susceptible to antitumorigenic effects of somatostatin analogues (SSA). Evidence for SSA in meningiomas is scarce, and it is unclear if published literature would either (1) support wider use of SSA, if (2) more evidence is desirable, or if (3) available evidence is sufficient to discard SSA. We addressed the need for more evidence with a systematic review and meta-analysis. We performed an individual patient data (IPD) meta-analysis. Main outcomes were toxicity, best radiological response, progression-free survival, and overall survival. We applied multivariable logistic regression models to estimate the effect of SSA on the probability of obtaining radiological disease control. The predictive performance was evaluated using area under the curve and Brier scores. We included 16 studies and compiled IPD from 8/9 of all previous cohorts. Quality of evidence was overall ranked "very low." Stable disease was reported in 58% of patients as best radiological response. Per 100 mg increase in total SSA dosage, the odds ratios for obtaining radiological disease control was 1.42 (1.11 to 1.81, P = 0.005) and 1.44 (1.00 to 2.08, P = 0.05) for patients treated with SSA as monodrug therapy vs SSA in combination with everolimus, respectively. Low quality of evidence impeded exact quantification of treatment efficacy, and the association between response and treatment may represent reverse causality. Yet, the SSA treatment was well tolerated, and beneficial effect cannot be disqualified. A prospective trial without bias from inconsistent study designs is warranted to assess SSA therapy for well-defined meningioma subgroups.

BackgroundMeningiomas are the most common primary intracranial tumor in adults. Clinical care is currently guided by the World Health Organization (WHO) grade assigned to meningiomas, a 3-tiered grading system based on histopathology features, as well as extent of surgical resection. Clinical behavior, however, often fails to conform to the WHO grade. Additional prognostic information is needed to optimize patient management.MethodsWe evaluated whether chromosomal copy-number data improved prediction of time-to-recurrence for patients with meningioma who were treated with surgery, relative to the WHO schema. The models were developed using Cox proportional hazards, random survival forest, and gradient boosting in a discovery cohort of 527 meningioma patients and validated in 2 independent cohorts of 172 meningioma patients characterized by orthogonal genomic platforms.ResultsWe developed a 3-tiered grading scheme (Integrated Grades 1-3), which incorporated mitotic count and loss of chromosome 1p, 3p, 4, 6, 10, 14q, 18, 19, or CDKN2A. 32% of meningiomas reclassified to either a lower-risk or higher-risk Integrated Grade compared to their assigned WHO grade. The Integrated Grade more accurately identified meningioma patients at risk for recurrence, relative to the WHO grade, as determined by time-dependent area under the curve, average precision, and the Brier score.ConclusionWe propose a molecularly integrated grading scheme for meningiomas that significantly improves upon the current WHO grading system in prediction of progression-free survival. This framework can be broadly adopted by clinicians with relative ease using widely available genomic technologies and presents an advance in the care of meningioma patients.

Core Outcome Sets (COS) define minimum outcomes to be measured and reported in clinical effectiveness trials for a particular health condition/health area. Despite recognition as critical to clinical research design for other health areas, none have been developed for neuro-oncology. COS development projects should carefully consider: scope (how the COS should be used), stakeholders involved in development (including patients as both research partners and participants), and consensus methodologies used (typically a Delphi survey and consensus meeting), as well as dissemination plans. Developing COS for neuro-oncology is potentially challenging due to extensive tumor subclassification (including molecular stratification), different symptoms related to anatomical tumor location, and variation in treatment options. Development of a COS specific to tumor subtype, in a specific location, for a particular intervention may be too narrow and would be unlikely to be used. Equally, a COS that is applicable across a wider area of neuro-oncology may be too broad and therefore lack specificity. This review describes why and how a COS may be developed, and discusses challenges for their development, specific to neuro-oncology. The COS under development are briefly described, including: adult glioma, incidental/untreated meningioma, meningioma requiring intervention, and adverse events from surgical intervention for pediatric brain tumors.

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 meningioma, those that threaten neurovascular structures, or demonstrate radiological growth, are usually resected as first-line management strategy. For patients in poor clinical condition, or with inoperable, residual or recurrent disease, radiotherapy is often used as primary or adjuvant treatment. Effective pharmacotherapy treatments do not currently exist. There is heterogeneity in the outcomes measured and reported in meningioma clinical studies. Two 'Core Outcome Sets' (COS) will be developed: (COSMIC: Intervention) for use in meningioma clinical effectiveness trials and (COSMIC: Observation) for use in clinical studies of incidental/untreated meningioma.Methods and analysisTwo systematic literature reviews and trial registry searches will identify outcomes measured and reported in published and ongoing (1) meningioma clinical effectiveness trials, and (2) clinical studies of incidental/untreated meningioma. Outcomes include those that are clinician reported, patient reported, caregiver reported and based on objective tests (eg, neurocognitive tests), as well as measures of progression and survival. Outcomes will be deduplicated and categorised to generate two long lists. The two long lists will be prioritised through two, two-round, international, modified eDelphi surveys including patients with meningioma, healthcare professionals, researchers and those in caring/supporting roles. The two final COS will be ratified through two 1-day online consensus meetings, with representation from all stakeholder groups.Ethics and disseminationInstitutional review board (University of Liverpool) approval was obtained for the conduct of this study. Participant eConsent will be obtained prior to participation in the eDelphi surv

Meningiomas are the most common non-metastatic brain tumors, and although the majority are relatively slow-growing and histologically benign, a subset of meningiomas are aggressive and remain challenging to treat. Despite a standard of care that includes surgical resection and radiotherapy, and recent advances in meningioma molecular grouping, there are no systemic medical options for patients with meningiomas that are resistant to standard interventions. Misactivation of the cell cycle at the level of CDK4/6 is common in high-grade or molecularly aggressive meningiomas, and CDK4/6 has emerged as a potential target for systemic meningioma treatments. In this review, we describe the preclinical evidence for CDK4/6 inhibitors as a treatment for high-grade meningiomas and summarize evolving clinical experience with these agents. Further, we highlight upcoming clinical trials for patients meningiomas, and discuss future directions aimed at optimizing the efficacy of these therapies and selecting patients most likely to benefit from their use.

'Intracranial mesenchymal tumor, FET-CREB fusion-positive' occurs primarily in children and young adults and has previously been termed intracranial angiomatoid fibrous histiocytoma (AFH) or intracranial myxoid mesenchymal tumor (IMMT). Here we performed genome-wide DNA methylation array profiling of 20 primary intracranial mesenchymal tumors with FET-CREB fusion to further study their ontology. These tumors resolved into two distinct epigenetic subgroups that were both divergent from all other analyzed intracranial neoplasms and soft tissue sarcomas, including meningioma, clear cell sarcoma of soft tissue (CCS), and AFH of extracranial soft tissue. The first subgroup (Group A, 16 tumors) clustered nearest to but independent of solitary fibrous tumor and AFH of extracranial soft tissue, whereas the second epigenetic subgroup (Group B, 4 tumors) clustered nearest to but independent of CCS and also lacked expression of melanocytic markers (HMB45, Melan A, or MITF) characteristic of CCS. Group A tumors most often occurred in adolescence or early adulthood, arose throughout the neuroaxis, and contained mostly EWSR1-ATF1 and EWSR1-CREB1 fusions. Group B tumors arose most often in early childhood, were located along the cerebral convexities or spinal cord, and demonstrated an enrichment for tumors with CREM as the fusion partner (either EWSR1-CREM or FUS-CREM). Group A tumors more often demonstrated stellate/spindle cell morphology and hemangioma-like vasculature, whereas Group B tumors more often demonstrated round cell or epithelioid/rhabdoid morphology without hemangioma-like vasculature, although robust comparison of these clinical and histologic features requires future study. Patients with Group B tumors had inferior progression-free survival relative to Group A tumors (median 4.5 vs. 49 months, p = 0.001). Together, these findings confirm that intracranial AFH-like neoplasms and IMMT represent histologic variants of a single tumor type ('intracranial

Invasion of brain tissue by meningiomas has been identified as one key factor for meningioma recurrence. The identification of meningioma tumor tissue surrounded by brain tissue in neurosurgical samples has been touted as a criterion for atypical meningioma (CNS WHO grade 2), but is only rarely seen in the absence of other high-grade features, with brain-invasive otherwise benign (BIOB) meningiomas remaining controversial. While post-surgery irradiation therapy might be initiated in brain-invasive meningiomas to prevent recurrences, specific treatment approaches targeting key molecules involved in the invasive process are not established. Here we have compiled the current knowledge about mechanisms supporting brain tissue invasion by meningiomas and summarize preclinical models studying targeted therapies with potential inhibitory effects.

Meningiomas are the most common primary intracranial tumors. There are no effective medical therapies for meningioma patients, and new treatments have been encumbered by limited understanding of meningioma biology. Here, we use DNA methylation profiling on 565 meningiomas integrated with genetic, transcriptomic, biochemical, proteomic and single-cell approaches to show meningiomas are composed of three DNA methylation groups with distinct clinical outcomes, biological drivers and therapeutic vulnerabilities. Merlin-intact meningiomas (34%) have the best outcomes and are distinguished by NF2/Merlin regulation of susceptibility to cytotoxic therapy. Immune-enriched meningiomas (38%) have intermediate outcomes and are distinguished by immune infiltration, HLA expression and lymphatic vessels. Hypermitotic meningiomas (28%) have the worst outcomes and are distinguished by convergent genetic and epigenetic mechanisms driving the cell cycle and resistance to cytotoxic therapy. To translate these findings into clinical practice, we show cytostatic cell cycle inhibitors attenuate meningioma growth in cell culture, organoids, xenografts and patients.

Meningiomas are the most common primary central nervous system neoplasm. Despite promising recent progress in elucidating the genomic landscape and underlying biology of these histologically, molecularly, and clinically diverse tumors, the mainstays of meningioma treatment remain maximal safe resection and radiation therapy. The aim of this review of meningioma radiotherapy is to provide a concise summary of the history, current evidence, and future for application of radiotherapy in meningioma treatment.

BackgroundWe evaluated the potential role of birth characteristics in the etiology of early-onset meningioma.MethodsLeveraging a population-based linkage of California birth records (from 1978 to 2015) and cancer registry data (from 1988 to 2015), we identified 362 nonmalignant meningioma cases aged 0-37 years and selected 18 100 controls matched on year of birth. Cases and controls were compared with regard to birth characteristics, with adjusted odds ratios (ORs) and 95% confidence intervals (CIs) estimated from unconditional multivariable logistic regression models. We also conducted stratified analyses by race/ethnicity and age.ResultsFemale sex (compared to male: OR = 1.43, 95% CI: 1.16 to 1.79; P < .01) and Black race (compared to White: OR = 1.46, 95% CI: 1.02 to 2.07; P = .04) were associated with higher risk of meningioma. Higher birth order (OR = 0.90, 95% CI: 0.81 to 0.99 per additional birth position; P = .04) was associated with a lower risk. No significant associations were observed between birthweight, gestational age, delivery mode, maternal age, or maternal education and meningioma risk. In the non-Latino White subgroup, higher birthweight was associated with a higher risk of meningioma (OR = 1.20, 95% CI: 1.02 to 1.41 per 500 grams; P = .03), but this was not recapitulated in the Latino subgroup. In age-stratified analyses, female sex was a risk factor for those diagnosed at the age of 20-37 years but not among younger individuals.ConclusionsIn this large population-based study less prone to selection and recall bias, higher birth order was associated with a reduced risk of early-onset meningioma, while female sex and Black race were linked to an increased risk. There were also indications of differential associations by race/ethnicity and age of diagnosis.

PurposeSpheno-orbital meningiomas are rare tumors, accounting for up to 9% of all intracranial meningiomas. Patients commonly present with proptosis, and visual deficits. These slow growing tumors are hard to resect due to extension into several anatomical compartments, resulting in recurrence rates as high as 35-50%. Although open surgical approaches have been historically used for resection, a handful of endoscopic approaches have been reported in recent years. We aimed to review the literature and describe a case of spheno-orbital meningioma with severe vision loss which was resected with an endoscopic endonasal approach achieving complete resolution of visual symptoms.MethodsA systematic review of literature was conducted in accordance with the PRISMA guidelines. PubMed, Cochrane, and Web of Science databases were queried for spheno-orbital meningiomas resected via an endoscopic endonasal approach. Furthermore, the presentation, surgical management, and post-operative outcomes of a 53-year-old female with a recurrent spheno-orbital meningioma are described.ResultsThe search yielded 26 articles, of which 8 were included, yielding 19 cases. Average age at presentation was 60.5 years (range: 44-82), and 68.4% of patients were female. More than half of the cases achieved subtotal resection. Common complications associated with endoscopic endonasal surgery included CN V2 or CN V2/V3 hypoesthesia. Following surgical intervention, visual acuity and visual field remained stable or improved in the majority of the patients.ConclusionEndoscopic approaches are slowly gaining momentum for treatment of spheno-orbital meningiomas. Further studies on the clinical benefits of this approach on patient outcomes and post-operative complications is warranted.

Meningiomas are the most common primary intracranial neoplasm. While traditionally viewed as benign, meningiomas are associated with significant patient morbidity, and certain meningioma subgroups display more aggressive and malignant behavior with higher rates of recurrence. Historically, the risk stratification of meningioma recurrence has been primarily associated with the World Health Organization histopathological grade and surgical extent of resection. However, a growing body of literature has highlighted the value of utilizing molecular characteristics to assess meningioma aggressiveness and recurrence risk. In this review, we discuss preclinical and clinical evidence surrounding the use of molecular classification schemes for meningioma prognostication. We also highlight how molecular data may inform meningioma treatment strategies and future directions.

The Grade of meningioma has significant implications for selecting treatment regimens ranging from observation to surgical resection with adjuvant radiation. For most patients, meningiomas are diagnosed radiologically, and Grade is not determined unless a surgical procedure is performed. The goal of this study is to train a novel auto-classification network to determine Grade I and II meningiomas using T1-contrast enhancing (T1-CE) and T2-Fluid attenuated inversion recovery (FLAIR) magnetic resonance (MR) images. Ninety-six consecutive treatment naïve patients with pre-operative T1-CE and T2-FLAIR MR images and subsequent pathologically diagnosed intracranial meningiomas were evaluated. Delineation of meningiomas was completed on both MR images. A novel asymmetric 3D convolutional neural network (CNN) architecture was constructed with two encoding paths based on T1-CE and T2-FLAIR. Each path used the same 3 × 3 × 3 kernel with different filters to weigh the spatial features of each sequence separately. Final model performance was assessed by tenfold cross-validation. Of the 96 patients, 55 (57%) were pathologically classified as Grade I and 41 (43%) as Grade II meningiomas. Optimization of our model led to a filter weighting of 18:2 between the T1-CE and T2-FLAIR MR image paths. 86 (90%) patients were classified correctly, and 10 (10%) were misclassified based on their pre-operative MRs with a model sensitivity of 0.85 and specificity of 0.93. Among the misclassified, 4 were Grade I, and 6 were Grade II. The model is robust to tumor locations and sizes. A novel asymmetric CNN with two differently weighted encoding paths was developed for successful automated meningioma grade classification. Our model outperforms CNN using a single path for single or multimodal MR-based classification.

Progression-free survival (PFS) and overall survival (OS) for WHO grade 2 and 3 intracranial meningiomas are poorly described, and long-term results and data evaluating the routine use of supplementary fractionated radiotherapy (RT) or stereotactic radiosurgery (SRS) has been inconclusive. The aim of this study was to determine the long-term PFS and OS at a center that does not employ routine adjuvant RT. For this purpose, a retrospective population-based cohort study was conducted of all WHO grade 2 and 3 meningiomas surgically treated between 2005 and 2013. The cohort was uniformly defined according to the WHO 2007 criteria to allow comparisons to previously published reports. Patient records were reviewed, and patients were then prospectively contacted for structured quality-of-life assessments. In total, 51 consecutive patients were included, of whom 43 were WHO grade 2 and 8 were grade 3. A Simpson grade 1–2 resection was achieved in 62%. The median PFS was 31 months for grade 2 tumors, and 3.4 months for grade 3. The median OS was 13 years for grade 2, and 1.4 years for grade 3. The MIB-1-index was significantly associated with an increased risk for recurrence (p = 0.018, OR 1.12). The median PFS was significantly shorter for high-risk tumors compared to the low-risk group (10 vs. 46 months; p = 0.018). The surviving meningioma patients showed HRQoL measures comparable to that of the general population, with the exception of significantly more anxiety and depression. All patients who worked before surgery returned to work after their treatment. In conclusion, we confirm dismal prognoses in patients with grade 2 and 3 meningiomas, with tumor-related deaths resulting in severely reduced OS. However, the cohort was heterogenous, and a large subgroup of both grade 2 and 3 meningiomas was alive at 10 years follow-up, suggesting that a cure is possible. In addition, fractionated radiotherapy and chemotherapy had little benefit when introduced for recurrent and pr

Purpose: To investigate the association between fertility drugs and tumors of the central nervous system (CNS). Methods: This cohort study was based on The Danish Infertility Cohort and included 148,016 infertile women living in Denmark (1995–2017). The study cohort was linked to national registers to obtain information on use of specific fertility drugs, cancer diagnoses, covariates, emigration, and vital status. Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for all CNS tumors and separately for gliomas, meningiomas and diverse benign tumors of the brain and other parts of the CNS. Results: During a median 11.3 years of follow-up, 328 women were diagnosed with CNS tumors. No marked associations were observed between use of the fertility drugs clomiphene citrate, gonadotropins, gonadotropin-releasing hormone receptor modulators and progesterone and CNS tumors. However, use of human chorionic gonadotropin was associated with a decreased rate of meningiomas (HR 0.49 95% CI 0.28–0.87). No clear associations with CNS tumors were observed according to time since first use or cumulative dose for any of the fertility drugs. Conclusion: No associations between use of most types of fertility drugs and CNS tumors were observed. However, our findings only apply to premenopausal women and additional studies with longer follow-up time are necessary.

Immunohistochemical quantification of H3K27me3 was reported to distinguish meningioma patients with an unfavorable prognosis but is not yet established as a prognostic biomarker within WHO grade 3 meningiomas. We studied H3K27me3 loss in a series of biopsies from primary and secondary malignant meningioma to validate its prognostic performance and describe if loss of H3K27me3 occurs during malignant transformation. Two observers quantified H3K27me3 status as “complete loss”, < 50% and > 50% stained cells in 110 tumor samples from a population-based consecutive cohort of 40 WHO grade 3 meningioma patients. We found no difference in overall survival (OS) in patients with > 50% H3K27me3 retention compared to < 50% in the cohort of patients with WHO grade 3 meningioma (Wald test p = 0.5). H3K27me3 staining showed heterogeneity in full section tumor slides while staining of the Barr body and peri-necrotic cells complicated quantification further. H3K27me3 expression differed without a discernible pattern between biopsies from repeated surgeries of meningioma recurrences. In conclusion, our results were not compatible with a systematic pattern of immunohistochemical H3K27me3 loss being associated with OS or malignant transformation of meningiomas and did not support H3K27me3 loss as a useful immunohistochemical biomarker within grade 3 meningiomas due to staining-specific challenges in quantification.

Background Fatigue is prevalent in patients with a brain tumor and high levels of fatigue persist after neurosurgical tumor resection. The underlying mechanisms are insufficiently understood and this study examines the role of autonomic nervous system dysregulation and objective sleep characteristics in fatigue among post-surgical patients. MethodsPatients undergoing craniotomy (N = 52; age 52.1 +/- 15.0 years; 44% women) were evaluated at 3 months after surgery (median = 86 days). Fatigue was measured using the Multidimensional Fatigue Inventory. Autonomic nervous system indices were based on 24-h heart rate variability (HRV) analysis. Sleep parameters were measured using actigraphy: total sleep duration, efficiency, onset latency and wake after sleep onset (WASO). Data analyses of this cross-sectional study included correlation and multiple regression analysis. Results Fatigue scores were significantly elevated in tumor resection patients compared to healthy reference norms (p's < 0.05) with no differences between patients with glioma (N = 32) versus meningioma (N = 20). Associations between HRV indices and fatigue were non-significant (r values 0.25). Sleep duration was associated with physical fatigue (r = 0.35, p = 0.02), whereas WASO was associated with mental fatigue levels (r = 0.40, p = 0.006). Disturbed sleep measures were associated with HRV indices of reduced parasympathetic nervous system activity in glioma patients but not in meningioma patients. Conclusions Multiple nocturnal awakenings may result in mental fatigue and longer sleep time was associated with physical fatigue, which may reflect compensatory sleep patterns. Future intervention studies addressing sleep quality may be beneficial in treating fatigue in patients following neurosurgery for tumor resection.

BACKGROUND: Meningioma is the most common primary CNS tumour. Most meningiomas are benign, and most patients are 65 years or older. Surgery is usually the primary treatment option. Most prior studies on early surgical outcomes in older patients with meningioma are small, and there is a lack of larger population-based studies to guide clinical decision-making. We aimed to explore the risks for perioperative mortality and morbidity in older patients with meningioma and to investigate changes in surgical incidence over time. METHODS: In this retrospective population-based study on patients in Sweden, 65 years or older with surgery 1999-2017 for meningioma, we used data from the Swedish Brain Tumour Registry. We analysed factors contributing to perioperative mortality and morbidity and used official demographic data to calculate yearly incidence of surgical procedures for meningioma. RESULTS: The final study cohort included 1676 patients with a 3.1% perioperative mortality and a 37.6% perioperative morbidity. In multivariate analysis, higher age showed a statistically significant association with higher perioperative mortality, whereas larger tumour size and having preoperative symptoms were associated with higher perioperative morbidity. A numerical increased rate of surgical interventions after 2012 was observed, without evidence of worsening short-term surgical outcomes. CONCLUSIONS: Higher mortality with increased age and higher morbidity risk in larger and/or symptomatic tumours imply a possible benefit from considering surgery in selected older patients with a growing meningioma before the development of tumour-related symptoms. This study further underlines the need for a standardized method of reporting and classifying complications from neurosurgery.