Low-grade Meningiomas Research Articles

BIOM-16. A TARGETED GENE EXPRESSION BIOMARKER PREDICTS LOW GRADE MENINGIOMA RECURRENCE AND OVERALL SURVIVAL

Abstract Targeted gene expression profiling improves risk stratification for meningiomas, but the utility of this approach for low grade meningiomas is incompletely understood. To address this, 466 meningiomas that were initially used to validate a 34-gene expression biomarker were combined with 270 previously unpublished samples for an analysis of biomarker performance in newly diagnosed (n=691) or recurrent (n=45) WHO grade 1 meningiomas treated with gross total (GTR) or subtotal resection (STR), and newly diagnosed WHO grade 2 meningiomas treated with GTR. Prediction of local freedom from recurrence (LFFR) or overall survival (OS) was measured using Cox proportional hazards models and the Kaplan-Meier method. The cohort included 736 patients, 69.4% female, with a median age at diagnosis of 58 years. There were 635 WHO grade 1 meningiomas, 498 with GTR and 133 with STR, and 101 WHO grade 2 meningiomas with GTR. The median follow-up was 4.6 years, the local recurrence rate was 12.0% and the rate of death was 8.4%. The biomarker classified 51.5% of meningiomas as intermediate risk and 9.6% as high risk. Combining the biomarker with extent of resection identified 19.7% as unfavorable (intermediate molecular risk with STR or high molecular risk), including 7.4% of newly diagnosed WHO grade 1 meningiomas with GTR. The risk score was prognostic for LFFR overall (hazard ratio per 0.1 increase in risk score 1.89, 95% confidence interval 1.58-2.25) and across WHO grades, extents of resection, and newly diagnosed or recurrent settings. Gene expression risk groups were prognostic for LFFR, with improved outcomes among low molecular risk compared to intermediate molecular risk (Log-rank, p=0.0002) and high molecular risk meningiomas (Log-rank, p<0.0001). These data suggest that a targeted gene expression biomarker can identify low grade meningiomas that are more likely to recur after surgery, possibly changing management for approximately one-fifth of cases.

Study of prediction model for high-grade meningioma using fractal geometry combined with radiological features.

To establish a prediction model combining fractal geometry and radiological features, which consider the complexity of tumour morphology advancing beyond the limitations of previous models. A total of 227 patients at the First Affiliated Hospital of Harbin Medical University from July 2021 to November 2023 were included. Fractal geometry was calculated and the radiomics features were extracted from regions of interest (ROIs). Weighted Gene Co-Expression Network Analysis (WGCNA) was employed for preliminary screening to identify those that were significantly associated with high-grade meningioma. In the training cohort, the least absolute shrinkage and selection operator (LASSO) regression was employed for further screening the radiomics features. Area under curve (AUC) was to evaluate models' performance. In entire patient cohort, low-grade meningiomas had significantly lower fractal dimensions (P = 0.01), while high-grade meningiomas had higher lacunarity (P = 0.049). Fractal dimension (OR 6.8, 95% CI 1.49-36.51, P = 0.017), lacunarity (OR 3.7, 95% CI 1.36-11.75, P = 0.014), and Rscore (OR 2.8, 95% CI 1.55-5.75, P = 0.002) were independent risk factors for high-grade meningiomas. The final results demonstrated that the "fractal geometry + radiological features (semantic features + radiomics features)" model exhibited the most optimal performance in predicting high-grade meningioma, with an AUC of 0.854 in the training cohort and 0.757 in the validation cohort. Significant differences in fractal dimension and lacunarity exist between high-grade and low-grade meningiomas, which can be potential predictive factors. The developed predictive model demonstrated good performance in predicting high-grade meningiomas.

A targeted gene expression biomarker predicts clinic low-risk meningioma recurrence.

Despite reassuring clinical and histological features, low grade meningiomas can recur after surgery. Targeted gene expression profiling improves risk stratification of meningiomas, but the utility of this approach for clinical low-risk meningiomas is incompletely understood. This was a multicenter retrospective cohort study of meningiomas from patients who were treated at 4 institutions from 1992 to 2023. Adult patients with newly diagnosed or recurrent World Health Organization (WHO) grade 1 meningiomas that were treated with gross total resection (GTR) or subtotal resection (STR), or newly diagnosed WHO grade 2 meningiomas that were treated with GTR, were included. A 34-gene expression biomarker and gene expression risk score (continuous from 0 to 1) was evaluated in all samples. The study cohort was comprised of 723 patients, none of which were used for discovery or training of the gene expression biomarker and 265 of which were previously unreported. There were 626 WHO grade 1 meningiomas, 490 with GTR and 126 with STR, and 97 WHO grade 2 meningiomas with GTR. Targeted gene expression profiling classified 51.3% of clinical low-risk meningiomas as molecular intermediate-risk and 9.5% as molecular high-risk. Combining the gene expression biomarker with extent of resection revealed 19.8% of clinical low-risk meningiomas had unfavorable local freedom from recurrence (LFFR) and overall survival (OS), including 7.1% of newly diagnosed WHO grade 1 meningiomas with GTR. The risk score was prognostic for LFFR (HR per 0.1 increase in risk score 1.89, 95% CI 1.58-2.25) across all WHO grades, extents of resection, and newly diagnosed or recurrent presentations. Targeted gene expression profiling can identify clinical low-risk meningiomas that are likely to recur after surgery.

Functional precision medicine assay for recurrent meningioma: a proof of principle. Illustrative case.

Meningiomas are the most prevalent primary central nervous system tumors. Although low-grade meningiomas are considered benign tumors, a subset of these can behave aggressively, showing progression and recurrence. In such cases, functional assays could influence treatment decisions and improve patient outcomes. A 78-year-old female presented with a long-standing history of a supratentorial meningioma that was initially resected and treated with Gamma Knife radiosurgery. Surveillance revealed progression. She began systemic therapy with everolimus and octreotide but was lost to follow-up and did not continue the treatment. She returned because of a rapid decline in her neurological status. Biopsy with advanced molecular characterization by next-generation sequencing revealed NF2 and CREBBP mutations, and a commercial functional assay was done. This assay successfully isolated cancer stem cells (CSCs) from biopsy cores and identified potential drugs based on cellular sensitivity profiles. This is the first reported case in which a commercial functional drug screen was used for a meningioma. In cases in which meningiomas exhibit specific genetic alterations and characteristics of aggressiveness, functional assays can be a useful tool for isolating CSCs. The authors report success in obtaining drug-screen profiling for a World Health Organization grade 1 meningioma. Multimodal approaches utilizing multi-omics analyses with functional assays can improve patient outcomes. https://thejns.org/doi/10.3171/CASE24242.

Meningioma grading via diagnostic imaging: A systematic review and meta-analysis

PurposeMeningioma is the most common intracranial tumor, graded on pathology using WHO criteria to predict tumor course and treatment. However, pathological grading via biopsy may not be possible in cases with poor surgical access due to tumor location. Therefore, our systematic review aims to evaluate whether diagnostic imaging features can differentiate high grade (HG) from low grade (LG) meningiomas as an alternative to pathological grading.MethodsThree databases were searched for primary studies that either use routine magnetic resonance imaging (MRI) or computed tomography (CT) to assess pathologically WHO-graded meningiomas. Two investigators independently screened and extracted data from included studies.Results24 studies met our inclusion criteria with 12 significant (p < 0.05) CT and MRI features identified for differentiating HG from LG meningiomas. Cystic changes in the tumor had the highest specificity (93.4%) and irregular tumor-brain interface had the highest positive predictive value (65.0%). Mass effect had the highest sensitivity (81.0%) and negative predictive value (90.7%) of all imaging features. Imaging feature with the highest accuracy for identifying HG disease was irregular tumor-brain interface (79.7%). Irregular tumor-brain interface and heterogenous tumor enhancement had the highest AUC values of 0.788 and 0.703, respectively.ConclusionOur systematic review highlight imaging features that can help differentiate HG from LG meningiomas.

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

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

Grading of skull base meningiomas by combined perfusion: arterial spin labeling and T2* dynamic susceptibility perfusion

BackgroundConventional MRI has no distinction between high- and low-grade meningiomas, which has a crucial for choice of therapeutic plan, especially skull base meningiomas which need more meticulous endoscopy-approached surgery. The aim of our study was to evaluate role of perfusion by arterial spin labeling and dynamic susceptibility perfusion in grading of skull base meningiomas.ResultsThe relative arterial spin labeling (ASL), tumor blood flow (TBF), and tumor blood volume (TBV) ratios showed significant differences between low- and high-grade meningiomas.ConclusionsMRI perfusion is a useful in differentiation between low- and high-grade meningiomas. There is significant correlation between ASL and DSC perfusion supporting possibility of using ASL in clinical practice as an alternative technique to DSC perfusion, particularly for patients with renal impairment where no contrast injection needed.

Mast cells in meningiomas.

Meningioma represents the most frequent tumor of the central nervous system (CNS). Correlations between thepresence of mast cells (MCs) and grade or other histological features of meningioma are still debated. Our study aimed to better understand the relationship between mast cells and meningiomas and to compare our resultsbased on specific histological subtypes and novel 2021 CNS WHO grading system. We observed some differences as regards the number of MCs and meningioma grade. In low-grade (grade 1) meningiomas, MCs were observed in 7/22 cases, while they were consistently present in all eight high-grade cases (grade 2 and grade 3). Among the grade 1 meningiomas, we observed two "low-positive", two "intermediate-positive", and three "high-positive" cases. Among the group of high-grade meningiomas, the six cases grade 2 were considered as"low-positive", while the two grade 3 cases showed a higher number of MCs and were included in the "intermediate-positive" group. Even though with no statistical significance, due to the low number of cases, ourresults seem to confirm a sort of relationship between meningioma grading and the number of MCs, as demonstrated by the higher percentage of high-grade meningiomas showing MCs infiltrates, compared to low-grademeningiomas.

DOTATATE PET/MR Imaging Differentiates Secondary-Progressive from de Novo World Health Organization Grade 3 Meningiomas.

WHO grade 3 meningiomas are rare and poorly understood and have a higher propensity for recurrence, metastasis, and worsened clinical outcomes compared with lower-grade meningiomas. The purpose of our study was to prospectively evaluate the molecular profile, PET characteristics, and outcomes of patients with World Health Organization grade 3 meningiomas who were imaged with gallium 68 (68Ga) DOTATATE PET/MR imaging. Patients with World Health Organization grade 3 meningiomas enrolled in our prospective observational cohort evaluating the utility of (68Ga) DOTATATE PET/MR imaging in somatostatin receptor positive brain tumors were included. We stratified patients by de novo-versus-secondary-progressive status and evaluated the differences in the PET standard uptake value, molecular profiles, and clinical outcomes. Patients met the inclusion criteria (secondary-progressive: 7/14; de novo: 7/14). The secondary-progressive cohort had a significantly higher per-patient number of surgeries (4.1 versus 1.6; P = .011) and trended toward a higher number of radiation therapy courses (2.4 versus 1.6; P = .23) and cumulative radiation therapy doses (106Gy versus 68.3Gy; P = .31). The secondary-progressive cohort had a significantly lower progression-free survival compared with the de novo cohort (4.8 versus 37.7 months; P = .004). Secondary-progressive tumors had distinct molecular pathology profiles with higher numbers of mutations (3.5 versus 1.2; P = .024). Secondary-progressive tumors demonstrated higher PET standard uptake values (17.1 versus 12.4; P = .0021). Our study confirms prior work illustrating distinct clinical outcomes in secondary-progressive and de novo World Health Organization grade 3 meningiomas. Furthermore, our findings support (68Ga) DOTATATE PET/MR imaging as a useful management strategy in World Health Organization grade 3 meningiomas and provide insight into meningioma biology, as well as clinical management implications.

Heterozygous CDKN2A Loss is Associated with Recurrence and Survival in High, But Not Low Grade Meningiomas

INTRODUCTION: Homozygous loss of CDKN2A/B is associated with more aggressive meningiomas and is now considered in the updated WHO grading criteria. The relevance of heterozygous loss (hetloss) of CDKN2A/B is less clear and the potential association of hetloss CDKN2A with aggressive meningioma phenotype remains underexplored. METHODS: Clinical and whole exome sequencing data for patients who underwent resection of sporadic meningiomas were analyzed. RESULTS: Of the 564 meningiomas included, 16 tumors harbored hetloss of CDKN2A; 7 of these were low grade (WHO grade I) and 9 high grade (grade II or III). Compared to high-grade hetloss meningiomas, low-grade ones were less likely to have an NF2 somatic driver mutation (p = 0.041) and were more common along the skull base (p = 0.005). Low-grade meningiomas with hetloss CDKN2A had more aggressive clinical characteristics compared to wild type (WT), with higher proliferative indices (p = 0.044), increased cellularity (p = 0.032) and higher copy number variations (p = 0.004) and patients were more likely to be symptomatic (p = 0.007); there was no difference in progression-free survival (PFS) (p = 0.4). High-grade hetloss CDKN2A meningiomas, however, had higher mitotic count (p = 0.014), increased chromosomal instability (p = 0.004), and higher recurrence rates (p &lt; 0.001), as well as decreased PFS (p &lt; 0.001) and overall survival (OS) (p = 0.002), compared to high-grade WT. Interestingly, these findings remained significant amongst high-grade hetloss CDKN2A meningiomas even when controlling for underlying NF2 mutation. CONCLUSIONS: Hetloss of CDKN2A is associated with more aggressive histological and genomic characteristics in both low- and high-grade meningiomas. Only high-grade meningiomas with hetloss CDKN2A, however, differ from those without the mutation in recurrence and PFS. This effect does not seem related to underlying somatic NF2 mutation. These findings may have clinical implications for high-grade meningiomas harboring heterozygous CDKN2A mutations.

The role of preoperative hematological inflammatory markers as a predictor of meningioma grade: A systematic review and meta-analysis.

Inflammatory processes play an important role in the aggressiveness of a tumor. However, the relationship between inflammatory markers in meningioma grade is not well known. Knowledge of preoperative meningioma grade plays an important role in the prognosis and treatment of this tumor. This study aims to assess preoperative hematological inflammatory markers as a predictor of the pathological grade of meningioma. To ensure comprehensive retrieval of relevant studies, we searched the following key databases, PubMed, Science Direct, and Biomed Central, with evidence related to preoperative hematological inflammatory markers among meningioma up to September 2023. The studies involved were selected based on established eligibility criteria. The analysis in this study uses Review Manager 5.4. Six studies were obtained from the search results. The total number of patients 2789 (469 high-grade meningioma and 2320 low-grade meningioma) analysis shows elevated neutrophil-to-lymphocyte ratio (NLR) (mean difference [MD]: 0.29; 95% confidence interval [CI] 0.13-0.45; P = 0.0004), monocyte-to-lymphocyte ratio (MLR) (MD: 0.02; 95% CI 0.00-0.04; P = 0.003), and low lymphocyte-to-monocyte ratio (LMR) (MD: -0.82; 95% CI -1.46--0.18; P = 0.005) significantly associated with high-grade meningioma compared to low-grade meningioma. No significant correlation between high-grade and low-grade meningioma based on platelet-lymphocyte ratio value is observed. The parameters of NLR, MLR, and LMR have been found to be cost-effective preoperative methods that demonstrate potential value in the prediction of meningioma grade. To enhance the reliability of the findings, it is imperative to do further prospective study.

Parasagittal Meningioma in a Middle-aged Female Harbouring Metastatic Ductal Carcinoma: A Rare Case of Incidentally Detected Tumour-to-tumour Metastasis

Metastasis of a tumour particularly coming from breast into an intracranial meningioma is a rare phenomenon. Several factors related to tumour microenvironment have been suggested in the pathophysiology of these lesions, particularly the rich vascular network of meningiomas, expression of common hormonal receptors like Oestrogen Receptor (ER) and Progesterone Receptor (PR), local immunosuppression, and presence of cell adhesion molecules. Here, we present a clinicoradiologically unsuspecting case of intracranial, parasagittal meningioma who was operated for relief of symptoms of mass effect and was incidentally detected with tumour metastasis within the meningioma. A 50-year-old female presented with seizures, headache and visual disturbances since last one month. Radiology revealed a parasagittal mass which was likely to be meningioma. The patient was operated. On histopathology, a low-grade meningioma was seen with areas of metastatic adenocarcinoma. The metastatic foci were surrounded by fibroblastic meningioma cells. On Immunohistochemistry (IHC), the metastatic tumour cells were strongly positive for PR and Cytokeratin 7 (CK7) and a diagnosis of fibroblastic meningioma with intratumoural metastasis of ductal carcinoma was rendered. The patient was given radiotherapy for brain tumour and also started on chemotherapy for breast carcinoma with brain metastasis. Since the entity of “Tumour-to-tumour Metastasis (TTM)” is uncommonly thought of and its detection is not easy, it is important that both clinicians and pathologists should adequately examine tissue samples of excised meningioma, as detecting the presence of any metastatic foci within the main mass will alter the prognosis and treatment plan considerably.

Regression of multiple intracranial meningiomas after cessation of long-term synthetic progesterone (megestrol) medication: case report and autopsy.

We report the history of a woman who developed four intracranial meningiomas during 11 years of therapy with the synthetic progesterone agonist megestrol. After discontinuation of the drug at age 75 years, she improved clinically and a CT scan showed near complete regression of the meningiomas by 78 years. Autopsy was performed at 83 years of age following an accidental death. At the tumor sites, we found both collagenous tissue with small islands of low grade meningioma having strong nuclear immunoreactivity for progesterone receptor and lipomatous tissue. A literature review showed similar cases of radiologic meningioma regression following discontinuance of progestins. Our case is the first one with histopathologic characterization of the end point.

Correlation between Magnetic Resonance Imaging (MRI) Grading with Histopathological Grading of Supratentorial Meningiomas

Background: Meningiomas, common intracranial tumors originating from meningeal cells, critically impact patient outcomes. Their histologic grade influences recurrence risk and treatment decisions, including radiation therapy. Identifying advanced-grade meningiomas via pre-operative MRI is vital for surgical planning, reducing complications, and guiding adjuvant therapies. Objective: To investigate the correlation between pre-operative MRI features and histopathological grade in supratentorial meningiomas. Methods: This cross-sectional study was conducted from July 2019 to December 2020 at the Department of Neurosurgery of Dhaka Medical College and Hospital. A total of 43 patients with supratentorial meningiomas underwent resection and were analyzed in terms of neuroimaging features of pre-operative MRI. The relationships between MRI features and WHO histopathological grade were analyzed and scored quantitatively. Results: The mean age of the study population was 37±11.86 (SD) years. Male female ratio was 1:2.7. Main clinical presentation was headache (90.7%). The most common location was convexity meningioma (37.2%). Out of all patients, high, grade and low-grade meningioma were diagnosed by MRI, 9 (20.93%) and 34 (79.09%), respectively; on the other hand, high, grade and low-grade meningiomas diagnosed by histopathology 7 (16.3%) and 36 (83.7%) respectively. A positive correlation was found between MRI grading and histopathological grading of supratentorial meningiomas and statistical significance (Spearman rho-0.547, p-value &lt;0.001). A significant association was also observed between MRI grading and histopathological grading of supratentorial meningiomas (p-value 0.002). Unclear tumor brain interface, capsular enhancement, and irregular tumor margin in the MRI were identified factors in predicting advanced histopathological grade of meningiomas as p-values 0.002, 0.008, and 0.001, respectively. Conclusion: This scoring approach may be useful for neurosurgeons ...

EPCO-47. HETEROZYGOUS CDKN2A LOSS IS ASSOCIATED WITH HIGHER RECURRENCE AND LOWER SURVIVAL IN HIGH-, BUT NOT LOW-GRADE MENINGIOMAS

Abstract INTRODUCTION Homozygous loss of CDKN2A/B is known to be associated with more aggressive meningiomas and is now considered in the updated criteria for WHO grading. The relevance of heterozygous loss (hetloss) of CDKN2A/B is less clear and the potential association of hetloss CDKN2A with aggressive meningioma phenotype remains underexplored. OBJECTIVE We sought to understand the clinical associations of hetloss CDKN2A meningiomas. METHODS Clinical and whole exome sequencing (WES) data for patients who underwent resection of sporadic meningiomas were reviewed and analyzed. RESULTS Of the 564 meningiomas included, 16 tumors harbored a heterozygous mutation of CDKN2A; 6 of these were low-grade (WHO grade I) and 10 were high-grade (grade II or III). CDKN2A hetloss meningiomas were more likely to be high-grade (p=0.03) and to be diagnosed at older ages (p=0.04) than wild type (WT). Compared to high-grade hetloss meningiomas, low-grade ones were more likely to have elevated proliferative index (p=0.04) and were more common along the skull base (p=0.04). Low-grade meningiomas with hetloss CDKN2A compared to WT ones were more likely to be symptomatic (p=0.023); there was no difference in the tumor make-up or progression free survival (PFS) (p=0.4). High-grade hetloss CDKN2A meningiomas, however, had higher mitotic count (p=0.014), increased chromosomal instability (p=0.004), and higher recurrence rates (p&amp;lt; 0.001), as well as shorter PFS (p&amp;lt; 0.001) and decreased overall survival (OS) (p=0.002), compared to high-grade WT meningiomas. These findings remained significant amongst high-grade hetloss CDKN2A meningiomas even when controlling for underlying NF2 mutation. CONCLUSION Heterozygous loss of CDKN2A is associated with more aggressive histological and genomic characteristics in high-grade meningiomas. Additionally, high-grade meningiomas with hetloss CDKN2A differ from those without the mutation with higher recurrence rates and shorter PFS and lower OS, irrespective of underlying somatic NF2 mutation. These findings may have clinical implications for management.

DISP-11. PROMINENT FRONTAL BOSSING AND BLINDNESS FOLLOWING SUBTOTAL RESECTION OF LOW-GRADE MENINGIOMA: HIGHLIGHTING HEALTH DISPARITIES

Abstract Low-grade meningiomas with subtotal resection carry significantly shorter recurrence-free survival rates than those with gross total resection. We report the natural history of a case of low-grade meningioma after subtotal resection and review the literature. We aim to highlight known global health disparities in oncology treatment by describing a case of meningioma progression following subtotal resection. A 40-year-old Kenyan woman presented locally with headache, nausea, and vision loss over approximately a six month time period. A 5 cm olfactory groove meningioma was discovered, and she subsequently underwent subtotal resection that was likely limited due to hemorrhagic complications. Over the following two years, she developed progressive dizziness, nausea, gait instability, difficulty performing tasks, and visual loss prompting medical evaluation at our institution. Physical examination demonstrated blindness, bilateral proptosis with severe vertical gaze palsy, and prominent frontal bossing. MRI Brain revealed a 9 cm enhancing mass arising from the cribriform plate with elevation of an ununited overlying frontal craniotomy flap and apparent meningoceles extending through the presumed osteotomy bilaterally. She underwent successful resection with pathology demonstrating CNS WHO Grade 1 meningioma. Her postoperative neurologic exam showed subtle improvement, specifically in regards to orientation questions. In this patient, bone flap displacement from prior craniotomy allowed significant interval tumor growth while minimizing mass effect on brain parenchyma. This case highlights global health disparities in low-grade meningioma management related to appropriate healthcare access in underserved patients.

Multi-parametric MRI-based machine learning model for prediction of WHO grading in patients with meningiomas

ObjectiveThe purpose of this study was to develop and validate a nomogram combined multiparametric MRI and clinical indicators for identifying the WHO grade of meningioma.Materials and methodsFive hundred and sixty-eight patients were included in this study, who were diagnosed pathologically as having meningiomas. Firstly, radiomics features were extracted from CE-T1, T2, and 1-cm-thick tumor-to-brain interface (BTI) images. Then, difference analysis and the least absolute shrinkage and selection operator were orderly used to select the most representative features. Next, the support vector machine algorithm was conducted to predict the WHO grade of meningioma. Furthermore, a nomogram incorporated radiomics features and valuable clinical indicators was constructed by logistic regression. The performance of the nomogram was assessed by calibration and clinical effectiveness, as well as internal validation.ResultsPeritumoral edema volume and gender are independent risk factors for predicting meningioma grade. The multiparametric MRI features incorporating CE-T1, T2, and BTI features showed the higher performance for prediction of meningioma grade with a pooled AUC = 0.885 (95% CI, 0.821–0.946) and 0.860 (95% CI, 0.788–0.923) in the training and test groups, respectively. Then, a nomogram with a pooled AUC = 0.912 (95% CI, 0.876–0.961), combined radiomics score, peritumoral edema volume, and gender improved diagnostic performance compared to radiomics model or clinical model and showed good calibration as the true results. Moreover, decision curve analysis demonstrated satisfactory clinical effectiveness of the proposed nomogram.ConclusionsA novel nomogram is simple yet effective in differentiating WHO grades of meningioma and thus can be used in patients with meningiomas.Clinical relevance statementWe proposed a nomogram that included clinical indicators and multi-parameter radiomics features, which can accurately, objectively, and non-invasively differentiate WHO grading of meningioma and thus can be used in clinical work.Key Points• The study combined radiomics features and clinical indicators for objectively predicting the meningioma grade.• The model with CE-T1 + T2 + brain-to-tumor interface features demonstrated the best predictive performance by investigating seven different radiomics models.• The nomogram potentially has clinical applications in distinguishing high-grade and low-grade meningiomas.

A large-scale targeted proteomics of serum and tissue shows the utility of classifying high grade and low grade meningioma tumors

BackgroundMeningiomas are the most prevalent primary brain tumors. Due to their increasing burden on healthcare, meningiomas have become a pivot of translational research globally. Despite many studies in the field of discovery proteomics, the identification of grade-specific markers for meningioma is still a paradox and requires thorough investigation. The potential of the reported markers in different studies needs further verification in large and independent sample cohorts to identify the best set of markers with a better clinical perspective.MethodsA total of 53 fresh frozen tumor tissue and 51 serum samples were acquired from meningioma patients respectively along with healthy controls, to validate the prospect of reported differentially expressed proteins and claimed markers of Meningioma mined from numerous manuscripts and knowledgebases. A small subset of Glioma/Glioblastoma samples were also included to investigate inter-tumor segregation. Furthermore, a simple Machine Learning (ML) based analysis was performed to evaluate the classification accuracy of the list of proteins.ResultsA list of 15 proteins from tissue and 12 proteins from serum were found to be the best segregator using a feature selection-based machine learning strategy with an accuracy of around 80% in predicting low grade (WHO grade I) and high grade (WHO grade II and WHO grade III) meningiomas. In addition, the discriminant analysis could also unveil the complexity of meningioma grading from a segregation pattern, which leads to the understanding of transition phases between the grades.ConclusionsThe identified list of validated markers could play an instrumental role in the classification of meningioma as well as provide novel clinical perspectives in regard to prognosis and therapeutic targets.

NEIM-11 DEUTERIUM METABOLIC IMAGING (DMI) DETECTS A LARGER WARBURG EFFECT IN HIGH-GRADE BRAIN TUMORS AND IN IDH WILD TYPE GLIOMAS

Abstract BACKGROUND The Warburg Effect (WE) is a metabolic change in which tumors favor glycolysis over oxidative phosphorylation and has been linked to cancer aggressiveness. Mutations in the isocitrate dehydrogenase (IDH) genes in gliomas are associated with improved outcomes. We deployed a magnetic resonance (MR) spectroscopic imaging technique coined Deuterium Metabolic Imaging (DMI) to measure the WE in multiple brain tumor types. METHODS Twenty-one patients underwent DMI, acquired on a Bruker 4T MR scanner after oral administration of 0.75g/kg of deuterated glucose. The WE was defined as the ratio of deuterated lactate, representing glycolysis, over deuterated glutamate and glutamine, representing oxidative phosphorylation. We devised an interval scale from 0 to 2 for the WE RESULTS The Wilcoxon rank sum test was performed to detect differences between groups. RESULTS The WE measurements for the largest groups, by diagnosis, showed: glioblastoma (n=9, mean=1.67); astrocytoma, IDH-mutant, WHO grade 3 (n=2, mean=0.25); oligodendroglioma, WHO grade 3 (n=3, mean=0.5); low grade glioma, IDH-mutant (n=2, mean=0); and meningioma, WHO grade 2 (n=2, mean=0). The WE for high-grade tumors (n=15, mean=1.27) was significantly different from the WE for low-grade tumors (n=5, mean=0), with a p=0.010. The WE for IDH wild type gliomas (n=9, mean=1.67) was significantly different from the WE for IDH-mutant gliomas (n=9, mean=0.44), with a p=0.007. Analysis is ongoing. CONCLUSIONS DMI successfully and non-invasively detects the WE in many types of brain tumors. The WE was larger in high-grade tumors as compared to low-grade tumors, and the WE was larger in IDH wild type gliomas as compared to IDH-mutant gliomas. If validated with future studies, our results suggest that DMI is a useful tool to measure differences in the metabolism of brain tumors with different clinical behaviors.

Clinical Factors Related to Histopathologic Grade in Meningioma

&lt;p&gt;&lt;strong&gt;Background:&lt;/strong&gt; Meningiomas are the most common intracranial tumor of central nervous system tumors. Although the prevalence is lower, the WHO grade II and III meningiomas are more aggressive, with higher mitosis rates, are more likely to recur after surgery, and have lower survival rates. The ability to differentiate between WHO I and WHO II/ III meningiomas before surgery can contribute to a significant clinical benefit in helping the neurosurgeon doing the best management planning.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods:&lt;/strong&gt; This is a retrospective cross-sectional study of meningioma patients in Siloam Hospital Lippo Village between 2014 – 2018. The sample will be recruited using consecutive sampling. The relationship between analyzed variables and meningioma grades will be investigated using a chi-square test if the data was eligible; otherwise, the Fisher-exact test will be performed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Result:&lt;/strong&gt; Ninety eight (69%) patients diagnosed as low grade meningioma, and 44 (31%) as high grade meningioma. Tumor location, size, edema, necrosis, age, and gender had significant results with p £0.05. Multivariate results also show that all six variables have a significant relationship with each other.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Tumor location, size, edema, necrosis, age, and gender have a significant relationship to histopathological meningioma grade in patients at Siloam Hospital Lippo Village in 2014-2018.&lt;/p&gt;