Astrocytic Tumors Research Articles

PATH-14. UTILITY OF DNA METHYLATION ANALYSIS IN HISTOLOGICALLY-CONFIRMED PA PATIENTS WITH POOR PROGNOSIS

Abstract INTRODUCTION Pilocytic astrocytoma (PA) is a circumscribed low-grade astrocytic glioma, generally considered to be associated with a good prognosis. However, some PA patients experience unfavorable outcomes; advanced age was known as an independent poor prognostic factor. This study retrospectively reviewed PA patients and conducted molecular analyses for elderly patients. METHODS We analyzed data from 29 histologically confirmed PA patients treated at a single center from 2002 to 2021 and conducted integrated molecular analyses including DNA methylation profiling for elderly PA patients. RESULTS The median age at diagnosis was 14 years (range 3-82 years), with 4 patients (14%) being elderly (patients≥60years old). Elderly patients had significantly worse progression-free survival and overall survival. DNA methylation analysis was performed on 2 of the 4 elderly patients. Despite histological diagnoses of PA, methylation profiling classified one case as high-grade astrocytoma with piloid features (methylation class scores below 0.3 in both v11b4 and v12.5) and the other as glioblastoma, IDH-wildtype (score over 0.5 in both v11b4 and v12.5), using classifiers from the German Cancer Research Center and t-SNE analysis. CONCLUSION Elderly patients with PA morphology showed unfavorable outcomes in this cohort. In those patients, DNA methylation profiling revealed the possibility of high-grade astrocytic tumors, including newly defined entities.

SURG-40. PEDIATRIC LOWER GRADE GLIOMA SURGERY IN THE ERA OF GENOMIC MEDICINE

Abstract INTRODUCTION In the 2021 WHO Brain Tumor Classification, pediatric-type gliomas are distinctly categorized from their adult counterparts. The continual evolution of cancer genomics has significantly broadened the spectrum of available treatment options. Here we would like to consider surgery for pediatric low-grade gliomas. METHODS We retrospectively analyzed 41 cases of low-grade gliomas or glioneuronal tumors in pediatric patients who underwent surgery at our institute from 2002 to 2023. We discussed surgical strategies based on molecular classification. RESULTS Among the cases, there were 34 gliomas and 7 glioneuronal tumors. According to the new WHO classification, they corresponded to 1) Adult-type diffuse gliomas, 2) Pediatric-type diffuse low-grade gliomas, 3) Circumscribed astrocytic tumors, or 4) Glioneuronal and neuronal tumors. Cases without molecular diagnosis were also considered in light of the new WHO classification. Among molecularly diagnosed astrocytomas involving the cerebral hemisphere, brain stem, spinal cord, there were no cases of 1), and 2) 3) were the main cases. It is important in surgical selection to note that these cases generally have a more favorable prognosis compared to the adult type and have usefulness in diagnosing MAPK pathway abnormalities leading to the selection of molecularly targeted drugs. 3) includes pilocytic astrocytoma, subependymal giant cell astrocytoma, and pleomorphic xanthoastrocytoma. Among these, in the treatment of pilocytic astrocytoma of the visual tract and hypothalamus, biopsy is essential for molecular diagnosis and therapeutic agent selection. 4) is mainly an epilepsy-related tumor. While their removal contributes to genetic diagnosis and epileptic seizure control, total removal may not always be deemed necessary. CONCLUSION Based on the new WHO classification, a reevaluation of treatment strategies for pediatric brain tumors is necessary.

Use of Heber FERON as Part of the Treatment in Diffuse brain tumors: Report of Two Cases and Literature Review

Glioblastomas are the most common and malignant tumor among glial neoplasms (1). According to the Central Brain Tumor Registry of the United States (CBTRUS), the age-adjusted annual incidence rate of malignant primary brain tumors is 7.06/100,000 inhabitants and glioblastoma was 49.1% of them (2). It is characterized by being a fast-growing tumor, composed of a heterogeneous mixture of poorly differentiated astrocytic tumor cells, with pleomorphism, necrosis and vascular proliferation. According to the fifth classification of the World Health Organization, this type of tumor does not present a mutation in the IDH gene and usually presents a mutation in the EGFR gene, a mutation of the TERT promoter, trisomy of chromosome 7 and monosomy of chromosome 10 (3). It can manifest at any age, but it mainly affects adults, with a peak incidence between 45 and 70 years (3).The failure of current therapeutic approaches (focusing on surgical resection followed by radiotherapy and chemotherapy) is due to the dissemination that occurs in these tumors. Gliomas are highly infiltrating neoplasms, with solitary tumor cells or clusters of neoplastic cells that migrate extensively throughout the brain. In addition, malignant gliomas are an important stimulator of angiogenesis in a physiological manner, and angiogenesis in turn, may be a significant component in the progression of glial tumors. (5)This situation shows that the population of patients with malignant gliomas does not have therapeutic options to prolong their life, for this reason these two cases are presented to whom a therapeutic option with HeberFERON was offered to patients with diffuse brain tumors with a poor prognosis, also evaluating its antitumor effect (Imaging).

A multi-center, clinical analysis of IDH-mutant gliomas, WHO Grade 4: implications for prognosis and clinical trial design.

Mutations in the Isocitrate Dehydrogenase (IDH) genes, IDH1 or IDH2, define a group of adult diffuse gliomas associated with a younger age at diagnosis and better prognosis than IDH wild-type glioblastoma. Within IDH mutant gliomas, a small fraction of astrocytic tumors present with grade 4 histologic features and poor prognosis. In molecular studies, homozygous deletion of CDKN2A/B is independently predictive of poor prognosis and short survival. As a consequence, 2021 WHO classification now also recognizes this molecular feature, CDKN2A/B deletion, as sufficient for classifying an astrocytoma as IDH-mutant, WHO Grade 4, regardless of histological grading. Here, we investigate outcomes of patients with WHO Grade 4 IDH-mutant astrocytoma both with and without CDKN2A/B deletion, to compare these groups and evaluate clinical and radiographic factors that contribute to survival. We retrospectively identified 79 patients with IDH-mutant astrocytoma with CDKN2A/B deletion detected at initial diagnosis across five international institutions as well as a comparison group of 51 patients with IDH-mutant, astrocytoma, histologically Grade 4 without detectable CDKN2A/B deletion. We assembled clinical and radiographic features for all patients. We find that CDKN2A/B deletion was associated with significantly worse overall survival (OS; p = 0.0004) and progression-free survival (PFS; p = 0.0026), with median OS of 5.0 years and PFS of 3.0 years, compared to 10.1 and 5.0 years for tumors with a grade 4 designation based only on histologic criteria. Multivariate analysis confirmed CDKN2A/B deletion as a strong negative prognosticator for both OS (HR = 3.51, p < 0.0001) and PFS (HR = 2.35, p = 0.00095). In addition, in tumors with CDKN2A/B deletion, preoperative contrast enhancement is a significant predictor of worse OS (HR 2.19, 95% CI 1.22-3.93, p = 0.0090) and PFS (HR = 1.74, 95% CI = 1.02-2.97, p = 0.0420). These findings underscore the severe prognostic impact of CDKN2A/B deletion in IDH-mutant astrocytomas and highlight the need for further refinement of tumor prognostic categorization. Our results provide a key benchmark of baseline patient outcomes for therapeutic trials, underscoring the importance of CDKN2A/B status assessment, in addition to histologic grading, in clinical trial design and therapeutic decision-making for IDH-mutant astrocytoma patients.

Distribution of astrocytic tumors and brain metastases by anatomical location: a study conducted on 91 patients

Distribution of astrocytic tumors and brain metastases by anatomical location: a study conducted on 91 patients

VEGFA contributes to tumor property of glioblastoma cells by promoting differentiation of myeloid-derived suppressor cells

BackgroundGlioblastoma (GBM) is a malignant astrocytic tumor and its progression involves the regulation of vascular endothelial growth factor-A (VEGFA). However, the mechanism of VEGFA in regulating GBM progression remains unclear.MethodsVEGFA mRNA expression was analyzed by quantitative real-time polymerase chain reaction. Protein expression of VEGFA, cluster of differentiation 9 (CD9), CD81, and transforming growth factor-β1 (TGF-β1) was detected by western blotting assay. Flow cytometry assay was conducted to assess cell proliferation, cell apoptosis and myeloid-derived suppressor cell (MDSC) differentiation. TUNEL cell apoptosis detection kit was utilized to analyze cell apoptosis of tumors. Angiogenic capacity was investigated by tube formation assay. Transwell assay was used to assess cell migration and invasion. The effect of VEGFA on tumor formation was determined by a xenograft mouse model assay. Immunohistochemistry assay was used to analyze positive expression rate of VEGFA in tumor tissues. TGF-β1 level was detected by enzyme-linked immunosorbent assay.ResultsVEGFA expression was upregulated in GBM tissues, GBM cells, and exosomes from GBM patients and GBM cells. VEGFA silencing led to decreased cell proliferation, tube formation, migration and invasion and increased cell apoptosis. Moreover, VEGFA knockdown also delayed tumor formation. VEGFA promoted MDSC differentiation and TGF-β1 secretion by MDSCs by being packaged into exosomes. In addition, TGF-β1 knockdown displayed similar effects with VEGFA silencing on GBM cell phenotypes, and MDSCs attenuated VEGFA knockdown-induced effects by secreting TGF-β1 in A172 and U251 cells.ConclusionVEGFA contributed to tumor property of GBM cells by promoting MDSC differentiation and TGF-β1 secretion by MDSCs, providing potential targets for GBM treatment.

Evaluation of Single and Combined Temozolomide and Doxorubicin Treatment Responses in Low- and High-Grade Glioma In Vitro.

Astrocytoma, the most common type of glioma, can histologically be low or high grade. Treatment recommendations for astrocytic tumors are based on the histopathological and molecular phenotype. For grade 2 astrocytoma, the combination of radiotherapy and adjuvant chemotherapy with procarbazine, lomustine, and vincristine (PCV) is better than radiotherapy alone. Temozolomide (TMZ) is being increasingly recognized as a replacement for PCV in brain tumor therapy, due to the lower myelotoxicity. TMZ is currently a well-established first-line treatment for grade 3 astrocytoma, grade 4 astrocytoma, and glioblastoma and it is also sporadically used for grade 2 astrocytoma. However, TMZ faces multiple challenges such as adverse effects and drug resistance. In this study, we compared the cytotoxic effect induced by TMZ and doxorubicin (DOXO), alone and in combination, on a low-grade astrocytoma cell line (AC1B) and a high-grade glioma cell line (GB1B). We found that TMZ and DOXO, each produced a cytotoxic effect in monotherapy. GB1B cell line was more sensitive to the treatment than AC1B cells, at a 7- and 10-day exposure to the DOXO. However, when the duration of the treatment was extended to 14 days, GB1B cells became more resistant to DOXO treatment, compared to AC1B cells. Regarding the treatment with TMZ, GB1B exhibited greater resistance to TMZ compared to AC1B, across all studied intervals and the resistance to treatment of GB1B increased with longer exposure time. However, in combined therapy, the drugs did not exert a synergistic effect on any astrocytic cell line. The current data suggest that both TMZ and DOXO exhibit efficient therapeutic effects on low- and high-grade glioma cells. However, no synergistic effect was observed for combined therapy.

Glioma Type Prediction with Dynamic Contrast-Enhanced MR Imaging and Diffusion Kurtosis Imaging-A Standardized Multicenter Study.

The aim was to explore the performance of dynamic contrast-enhanced (DCE) MRI and diffusion kurtosis imaging (DKI) in differentiating the molecular subtypes of adult-type gliomas. A multicenter MRI study with standardized imaging protocols, including DCE-MRI and DKI data of 81 patients with WHO grade 2-4 gliomas, was performed at six centers. The DCE-MRI and DKI parameter values were quantitatively evaluated in ROIs in tumor tissue and contralateral normal-appearing white matter. Binary logistic regression analyses were performed to differentiate between high-grade (HGG) vs. low-grade gliomas (LGG), IDH1/2 wildtype vs. mutated gliomas, and high-grade astrocytic tumors vs. high-grade oligodendrogliomas. Receiver operating characteristic (ROC) curves were generated for each parameter and for the regression models to determine the area under the curve (AUC), sensitivity, and specificity. Significant differences between tumor groups were found in the DCE-MRI and DKI parameters. A combination of DCE-MRI and DKI parameters revealed the best prediction of HGG vs. LGG (AUC = 0.954 (0.900-1.000)), IDH1/2 wildtype vs. mutated gliomas (AUC = 0.802 (0.702-0.903)), and astrocytomas/glioblastomas vs. oligodendrogliomas (AUC = 0.806 (0.700-0.912)) with the lowest Akaike information criterion. The combination of DCE-MRI and DKI seems helpful in predicting glioma types according to the 2021 World Health Organization's (WHO) classification.

Deep Residual Learning-Based Classification with Identification of Incorrect Predictions and Quantification of Cellularity and Nuclear Morphological Features in Digital Pathological Images of Common Astrocytic Tumors.

Interobserver variations in the pathology of common astrocytic tumors impact diagnosis and subsequent treatment decisions. This study leveraged a residual neural network-50 (ResNet-50) in digital pathological images of diffuse astrocytoma, anaplastic astrocytoma, and glioblastoma to recognize characteristic pathological features and perform classification at the patch and case levels with identification of incorrect predictions. In addition, cellularity and nuclear morphological features, including axis ratio, circularity, entropy, area, irregularity, and perimeter, were quantified via a hybrid task cascade (HTC) framework and compared between different characteristic pathological features with importance weighting. A total of 95 cases, including 15 cases of diffuse astrocytoma, 11 cases of anaplastic astrocytoma, and 69 cases of glioblastoma, were collected in Taiwan Hualien Tzu Chi Hospital from January 2000 to December 2021. The results revealed that an optimized ResNet-50 model could recognize characteristic pathological features at the patch level and assist in diagnosis at the case level with accuracies of 0.916 and 0.846, respectively. Incorrect predictions were mainly due to indistinguishable morphologic overlap between anaplastic astrocytoma and glioblastoma tumor cell area, zones of scant vascular lumen with compact endothelial cells in the glioblastoma microvascular proliferation area mimicking the glioblastoma tumor cell area, and certain regions in diffuse astrocytoma with too low cellularity being misrecognized as the glioblastoma necrosis area. Significant differences were observed in cellularity and each nuclear morphological feature among different characteristic pathological features. Furthermore, using the extreme gradient boosting (XGBoost) algorithm, we found that entropy was the most important feature for classification, followed by cellularity, area, circularity, axis ratio, perimeter, and irregularity. Identifying incorrect predictions provided valuable feedback to machine learning design to further enhance accuracy and reduce errors in classification. Moreover, quantifying cellularity and nuclear morphological features with importance weighting provided the basis for developing an innovative scoring system to achieve objective classification and precision diagnosis among common astrocytic tumors.

Variances in the Expression Profile of Circadian Clock-Related Genes in Astrocytic Brain Tumors.

This study explores the role of circadian clock genes in the progression of astrocytic tumors, a prevalent type of brain tumor. The aim was to assess the expression patterns of these genes in relation to the tumor grade. Using microarray analysis, qRT-PCR, and methylation-specific PCR, we examined gene expression, DNA methylation patterns, and microRNA interactions in tumor samples from 60 patients. Our results indicate that the expression of key circadian clock genes, such as clock circadian regulator (CLOCK), protein kinase AMP-activated catalytic subunit alpha 1 (PRKAA1), protein kinase AMP-activated catalytic subunit alpha 2 (PRKAA2), protein kinase AMP-activated non-catalytic subunit beta 1 (PRKAB1), protein kinase AMP-activated non-catalytic subunit beta 2 (PRKAB2), period circadian regulator 1 (PER1), period circadian regulator 2 (PER2) and period circadian regulator 3 (PER3), varies significantly with the tumor grade. Notably, increased CLOCK gene expression and protein levels were observed in higher-grade tumors. DNA methylation analysis revealed that the promoter regions of PER1-3 genes were consistently methylated, suggesting a mechanism for their reduced expression. Our findings also underscore the complex regulatory mechanisms involving miRNAs, such as hsa-miR-106-5p, hsa-miR-20b-5p, and hsa-miR-30d-3p, which impact the expression of circadian clock-related genes. This underscores the importance of circadian clock genes in astrocytic tumor progression and highlights their potential as biomarkers and therapeutic targets. Further research is needed to validate these results and explore their clinical implications.

BIOM-13. THE MIR-17/92 CO-EXPRESSED NETWORK IS ENRICHED IN AGGRESSIVE PEDIATRIC BRAIN TUMORS

Abstract BACKGROUND Over the past two decades, the understanding of miRNA biology has drastically increased as miRNAs have been found to pervade most aspects of molecular biology–from cellular growth to apoptosis. Nevertheless, there has been little understanding of the role of miRNAs in pediatric brain tumors. In this study, we sought to correlate miRNA expression with pediatric brain tumor histologies. METHODS Weighted gene co-expression network analysis (WGCNA) was performed to determine co-expressed miRNA networks that correlated with distinct brain tumor histologies. Our study cohort consisted of miRNA-sequencing of 262 pediatric brain tumor histologies consisting of Atypical Teratoid/Rhabdoid tumors, Craniopharyngioma, Ependymomas, Ganglioglioma, Low-grade astrocytic tumors, High-grade astrocytic tumors, and Medulloblastoma. We utilized associated multi-omics data from the Open Pediatric Brain Tumor Atlas to validate the results. RESULTS WGCNA analysis revealed a distinct miRNA network consisting of 32 miRNAs with miR-17-5p as the hub miRNA that was markedly upregulated in the aggressive brain tumor group (p&amp;lt;0.001). Interestingly, the majority of the miRNA network consisted of the miR-17/92 family of miRNAs, which are known for their oncogenic role in various cancers. To determine the transcriptional regulatory mechanism of miR-17/92 miRNAs, we first looked at sample-matched RNA-sequencing data. The gene encoding for the miR-17/92 miRNAs, MIR17HG, was significantly overexpressed (p&amp;lt;0.001). Further upstream, we observed that E2F1/2/3, known transcriptional regulators of MIR17HG, gene and protein expressions were significantly overexpressed (p&amp;lt;0.01). Sample-matched phospho-proteomics data indicated the E2F regulator, RB1, being hyperphosphorylated–additionally supporting the E2F activity in these samples. CONCLUSION These findings reveal a network of oncogenic miRNAs consisting of the miR-17/92 family that are distinctly overexpressed in aggressive pediatric brain tumors. Moreover, we suggest that the E2F-RB1 axis is the upstream regulator of the miR-17/92 family of miRNAs.

DSC-PWI presurgical differentiation of grade 4 astrocytoma and glioblastoma in young adults: rCBV percentile analysis across enhancing and non-enhancing regions

PurposeThe presurgical discrimination of IDH-mutant astrocytoma grade 4 from IDH-wildtype glioblastoma is crucial for patient management, especially in younger adults, aiding in prognostic assessment, guiding molecular diagnostics and surgical planning, and identifying candidates for IDH-targeted trials. Despite its potential, the full capabilities of DSC-PWI remain underexplored. This research evaluates the differentiation ability of relative-cerebral-blood-volume (rCBV) percentile values for the enhancing and non-enhancing tumor regions compared to the more commonly used mean or maximum preselected rCBV values.MethodsThis retrospective study, spanning 2016–2023, included patients under 55 years (age threshold based on World Health Organization recommendations) with grade 4 astrocytic tumors and known IDH status, who underwent presurgical MR with DSC-PWI. Enhancing and non-enhancing regions were 3D-segmented to calculate voxel-level rCBV, deriving mean, maximum, and percentile values. Statistical analyses were conducted using the Mann-Whitney U test and AUC-ROC.ResultsThe cohort consisted of 59 patients (mean age 46; 34 male): 11 astrocytoma-4 and 48 glioblastoma. While glioblastoma showed higher rCBV in enhancing regions, the differences were not significant. However, non-enhancing astrocytoma-4 regions displayed notably higher rCBV, particularly in lower percentiles. The 30th rCBV percentile for non-enhancing regions was 0.705 in astrocytoma-4, compared to 0.458 in glioblastoma (p = 0.001, AUC-ROC = 0.811), outperforming standard mean and maximum values.ConclusionEmploying an automated percentile-based approach for rCBV selection enhances differentiation capabilities, with non-enhancing regions providing more insightful data. Elevated rCBV in lower percentiles of non-enhancing astrocytoma-4 is the most distinguishable characteristic and may indicate lowly vascularized infiltrated edema, contrasting with glioblastoma’s pure edema.

Prognostic Impact of TERT Promoter Mutations in Adult-Type Diffuse Gliomas Based on WHO2021 Criteria.

Mutation in the telomerase reverse transcriptase promoter (TERTp )is commonly observed in various malignancies, such as central nervous system (CNS) tumors, malignant melanoma, bladder cancer, and thyroid carcinoma. These mutations are recognized as significant poor prognostic factors for these tumors. In this investigation, a total of 528 cases of adult-type diffuse gliomas diagnosed at a single institution were reclassified according to the 2021 WHO classifications of CNS tumors, 5th edition (WHO2021). The study analyzed clinicopathological and genetic features, including TERTp mutations in each tumor. The impact of known prognostic factors on patient outcomes was analyzed through Kaplan-Meier survival and Cox regression analysis. TERTp mutations were predominantly identified in 94.1% of oligodendrogliomas (ODG), followed by 66.3% in glioblastoma, IDH-wildtype (GBM-IDHwt), and 9.2% of astrocytomas, IDH-mutant (A-IDHm). When considering A-IDHm and GBM as astrocytic tumors (Group 1) and ODGs (Group 2), TERTp mutations emerged as a significant adverse prognostic factor (p = 0.013) in Group 1. However, within each GBM-IDHwt and A-IDHm, the presence of TERTp mutations did not significantly impact patient prognosis (p = 0.215 and 0.268, respectively). Due to the high frequency of TERTp mutations in Group 2 (ODG) and their consistent prolonged survival, a statistical analysis to evaluate their impact on overall survival was deemed impractical. When considering MGMTp status, the combined TERTp-mutated and MGMTp-unmethylated group exhibited the worst prognosis in OS (p = 0.018) and PFS (p = 0.034) of GBM. This study confirmed that the classification of tumors according to the WHO2021 criteria effectively reflected prognosis. Both uni- and multivariate analyses in GBM, age, MGMTp methylation, and CDKN2A/B homozygous deletion were statistically significant prognostic factors while in univariate analysis in A-IDHm, grade 4, the Ki-67 index and MYCN amplifications were statistically significant prognostic factors. This study suggests that it is important to classify and manage tumors based on their genetic characteristics in adult-type diffuse gliomas.

Unusual location of pleomorphic xanthoastrocytoma: a case report

BackgroundPleomorphic xanthoastrocytoma is a rare astrocytic tumor often diagnosed at a young age. Typically, they appear as supratentorial cortical tumors, frequently involving the temporal lobe with few reported rare locations. The prognosis is favorable following surgical excision; however, recurrence, dissemination, and anaplastic transformation occurred in some cases.Case presentationA 50-year-old female presented with convulsions and an altered consciousness. Imaging showed a periventricular mixed solid and cystic lesion. Histopathological examination revealed features of pleomorphic xanthoastrocytoma WHO grade 2 without necrosis or mitotic activity.ConclusionsThis report highlights the classic imaging findings of pleomorphic xanthoastrocytoma but in an atypical periventricular location. Although rare, pleomorphic xanthoastrocytoma should be considered in the differential diagnosis of mixed solid and cystic periventricular lesions.

Predicting Isocitrate Dehydrogenase Status in Non-Contrast-Enhanced Adult-Type Astrocytic Tumors Using Diffusion Tensor Imaging and 11C-Methionine, 11C-Choline, and 18F-Fluorodeoxyglucose PET.

We aimed to differentiate the isocitrate dehydrogenase (IDH) status among non-enhanced astrocytic tumors using preoperative MRI and PET. We analyzed 82 patients with non-contrast-enhanced, diffuse, supratentorial astrocytic tumors (IDH mutant [IDH-mut], 55 patients; IDH-wildtype [IDH-wt], 27 patients) who underwent MRI and PET between May 2012 and December 2022. We calculated the fractional anisotropy (FA) and mean diffusivity (MD) values using diffusion tensor imaging. We evaluated the tumor/normal brain uptake (T/N) ratios using 11C-methionine, 11C-choline, and 18F-fluorodeoxyglucose PET; extracted the parameters with significant differences in distinguishing the IDH status; and verified their diagnostic accuracy. Patients with astrocytomas were significantly younger than those with glioblastomas. The following MRI findings were significant predictors of IDH-wt instead of IDH-mut: thalamus invasion, contralateral cerebral hemisphere invasion, location adjacent to the ventricular walls, higher FA value, and lower MD value. The T/N ratio for all tracers was significantly higher for IDH-wt than for IDH-mut. In a composite diagnosis based on nine parameters, including age, 84.4% of cases with 0-4 points were of IDH-mut; conversely, 100% of cases with 6-9 points were of IDH-wt. Composite diagnosis using all parameters, including MRI and PET findings with significant differences, may help guide treatment decisions for early-stage gliomas.

Can the metabolic characteristics of diffuse glioma on &lt;sup&gt;11&lt;/sup&gt;C-methionine PET/CT serve as a marker of its IDH status? Cross sectional study

INTRODUCTION: Since 2016, molecular markers, in particular, mutations in isocitrate dehydrogenase (IDH) 1 and 2, have been introduced as a classifying feature of cerebral gliomas that provided superior prognostication. The search for non-invasive biomarkers of the molecular profile of gliomas is necessary to improve the quality of preoperative diagnostics, identify patients with good and poor prognosis and determine treatment tactics.OBJECTIVE: Was to study the relationship between the IDH genotype of diffuse cerebral gliomas and metabolic biomarkers according to the results of PET/CT with [11C]methionine.MATERIALS AND METHOD: The results of PET/CT with 11C-methionine were identified to a retrospective analysis of 260 patients aged 18 to 75 years (median 40 years) with untreated cerebral glioma. Based on histological and molecular genetic studies of the surgical material including the determination of a mutation in the isocitrate dehydrogenase 1 (IDH1132H) gene, diffuse gliomas were classified according to the 2016 WHO classification of CNS tumors. Metabolic biomarkers included the calculation of tumor-to-brain ratio of 11С-methionine (TBRmax, TBRpeak and TBRmean) as well as the metabolic tumor volume (MTV). Statistics. Non-parametric tests were performed to compare the differences among patient groups. ROC curve analysis was performed to screen the optimal parameter and its best cutoff value for the discrimination of glioma genotype. All data analyses were performed using “Statistica 10,0” and “MedCalc” ststistical software. p-values less than 0.05 were considered statistically significant.RESULTS: According to the 2016 WHO classification astrocytic and oligodendroglial tumors of the adult type were divided into three groups: astrocytic gliomas with a mutation in the IDH1 gene (IDH1 mut) (n=95), astrocytic gliomas without a mutation in the IDH1 gene (IDH1 wild type — IDH1 wt) (n=103), and IDH1-mutant oligodendrogliomas (n=62). Significant differences in all ratios between the three molecular groups of gliomas were established. TBRmax cutoff of 2.27 differentiated between IDH1 wt and IDH1 mut gliomas with a sensitivity of 61% and a specificity of 77% (area under curve — AUC 0.752). When considering subgroups of gliomas that are homogeneous in terms of the IDH1 status or Grade, the dependence of TBR on the glioma histotype and grading was additionally established. In IDH1 mut oligodendrogliomas, TBR was significantly higher than in mutant astrocytomas, and in IDH1 wt astrocytomas, significant differences in TBR were established between Grade 2 and Grade 3–4. TBRmax was not a predictor of glioma type according to the WHO 2016 classification due to significant overlap of individual of TBR values. But TBRmax allowed diagnosing a cluster of malignant gliomas, including glioblastoma and astrocytoma Grade 3 IDH wt, as well as oligodendroglioma Grade 3 IDH1 mut, with a sensitivity of 65% and a specificity of 89% (AUC 0.848) at a cutoff of TBR=2.7. A strong correlation between the three tumor-to-brain ratios allows any ratio to be used in diagnostics. There were no significant differences in MTV between molecular types of gliomas.DISCUSSION: Distinguishing glioma types based on the 2016 WHO classification of the CNS tumors on the basis of 11Cmethionine uptake seems to be not reliable due to many factors that affect its uptake. In astrocytomas high TBR is associated with malignant grade and wild type IDH1 gene. However, the lack of differences in TBR between these astrocytomas and Grade 3 IDH1-mutant oligodendrogliomas does not allow one to predict the IDH1 status of the tumor in the absence of other radiological signs of the glioma histotype. The absence of differences in TBR between Grade 2 and Grade 3 astrocytomas IDH1 mut supports the view that they are considered as a single subgroup of lower grade gliomas. CONCLUSION: PET/CT with 11C-methionine has limited potential to assess the IDH status of diffuse gliomas. High TBR is associated with malignant glioma with wild-type IDH1 gene or oligodendroglial structure.

The Spectrum of Central Nervous System Tumors at a Tertiary Care Center Primarily Serving a Rural Population.

Background Central nervous system (CNS) tumors cause significant mortality and morbidity in all age groups. There was no data about the histological spectrum of all CNS tumors in the tertiary care center serving primarily the rural population of Uttar Pradesh. Aims and objectives The present study aimed to describe the histopathological spectrum of all CNS tumors reported in a rural tertiary care center at Saifai, Uttar Pradesh. It also aimed to provide an overview of the descriptive epidemiology of CNS tumors. Material and methods This was a retrospective, cross-sectional study. The study duration was three years. A total of 115 cases of CNS tumors were studied during that period. Cases were classified according to their histological types, and results were analyzed. Results The most common histological group was neuroepithelial tumors, with 53 cases (46.08%). This group had 36 cases of astrocytic tumors (31.3%), three cases of oligodendroglial tumors (2.6%), five cases of oligoastrocytic tumors (4.34%), five cases of ependymal tumors (4.34%), and four cases of embryonal tumors (3.47%). The second most common tumor wasmeningeal tumors, with 32 cases (27.82%). The male/female ratio (M/F) ratio was 0.7. Females were found to be more affected by almost all histologic categories. Most meningiomas (89.6%) were of World Health Organization (WHO) grade I (26 cases out of 29). Astrocytic tumors showed WHO grade I, II, III, and IV tumors in two cases (5.5%), twelve cases (33.3%), four cases (11.1%), and eighteen cases (50%), respectively. In the younger age group (0-20 years), ependymoma and medulloblastoma were most common, followed by pilocytic astrocytoma and schwannoma. Conclusion In this region, neuroepithelial tumors were seen more commonly than meningioma. Females were found to be more affected by CNS tumors. This study has provided relevant data, which can be used for research and better patient management. Further studies with the incorporation of advanced radiological investigation and immunohistochemistry have been recommended.

The new morphologic classification of the hand motor cortex with magnetic resonance imaging in glioma patients

PurposeThe hand motor cortex (HMC) is a reliable anatomical landmark for identifying the precentral gyrus. The current study aimed to investigate the morphology of HMC on axial MRI of glioma patients, propose a new morphological classification of HMC and analyze the effect of tumors on the morphology of HMC. MethodsA retrospective study of 276 adult right-handed glioma patients was conducted. The morphology of HMC was assessed using T2 axial images. Subsequently, the distribution of morphological subtypes was compared between the bilateral hemispheres and the tumor-affected and healthy hemispheres. Finally, the influence of tumor pathology on the morphology of HMC was investigated. ResultsA new morphological classification of HMC with four subtypes (Ω, ε, Ω-ε and ε-Ω) was proposed. No significant difference was identified in the distribution of morphological subtypes between the bilateral hemispheres (p = 0.0901, Chi-square test), or between the tumor-affected and healthy hemispheres (p = 0.3507, Chi-square test), and the morphology of HMC between the bilateral hemispheres were consistent (p < 0.0001, Kappa test). In addition, a significant difference was identified in the distribution of morphological subtypes between astrocytic and oligodendroglial tumors (p = 0.0135, Chi-square test). ConclusionIn the current study, we proposed a new morphological classification of HMC, and found that tumor could affect the morphology of HMC in glioma patients. The results can help our clinical practice, enabling us to further understand the spatial structure of the cerebral hemispheres.

Retrospective study of CNS tumors in a tertiary care centre in Western Odisha - A 4 year study

Central nervous system (CNS) tumors comprise nearly 3% of all malignancies world-wide whereas in India it accounts for about 2%. In recent years there has been an increase in CNS tumors with new potential risk factors being observed. The aim of the present study is to highlight the histopathological spectrum of brain tumors in a single tertiary care centre in Western Odisha.This retrospective histopathological analysis of CNS tumors was conducted in the Department of Pathology, VIMSAR, Burla, Odisha, India from October 2016 to September 2020. In the span of 4 years, a total of 94 neurosurgical biopsies were studied. Histopathological examination of routinely processed tissue and hematoxylin and eosin (H&amp;E) stained sections of corresponding cases were thoroughly examined. Immunohistochemistry (IHC) was done whenever required. Thereafter an approach was made to diagnose the cases, based on WHO classification system of 2016.A wide range of histopathological spectrum of CNS tumors was observed and was classified according to the WHO classification system of 2016. The primary CNS tumors were graded from Grade I to Grade IV. The most common CNS tumor in our study we found to be Astrocytic tumors (21 cases, 22.34%) followed by Schwannoma (19 cases, 20.21%) and meningiomas (18 cases, 19.14%). The incidence was more among males (59.51%) as compared to females (40.4%). This study provides an information regarding the prevalence of disease in Western Odisha. Use of modern imaging technique helps to a major extent in making a provisional.

Primary central nervous system tumors survival in children in ten Colombian cities: a VIGICANCER report.

Primary central nervous system (CNS) tumors are the second most common cancer in children and adolescents, leading to premature death and disability. Population-based survival estimates aid decision-making in cancer control, however data on survival for primary CNS tumors in Latin America is lacking. We describe survival rates for children with primary CNS tumors treated in ten Colombian cities. We analyzed data from children and adolescents newly diagnosed with cancer between 2012 and 2021, participating in the Childhood Cancer Clinical Outcomes Surveillance System (VIGICANCER) in ten cities in Colombia. VIGICANCER collects information on clinical outcomes from twenty-seven pediatric oncology units and conducts active follow-up every three months. VIGICANCER does not register craniopharyngiomas; we excluded intracranial germ cell tumors for this report. We used the Kaplan-Meier method to estimate the overall survival probability, stratified by sociodemographic variables, topography, WHO grading, receipt of radiation therapy, and type of surgical resection. We analyzed the prognostic capacity of variables using multivariate proportional Cox's regression, stratified by city and year of diagnosis. During the study period, VIGICANCER included 989 primary CNS tumors in 879 children and 110 adolescents. The cohort median age was 9 years; 53% of patients were males, and 8% were Afro-descendants. Most common tumors were supratentorial astrocytomas (47%), astrocytic tumors (35%), medulloblastomas (20%), ependymomas (11%), and mixed and unspecified gliomas (10%). Five-year overall survival of the entire cohort was 54% (95% CI, 51-58); for supratentorial gliomas, WHO grade I was 77%, II was 62%, III-IV was 27%, respectively, and for medulloblastoma was 61%. The adjusted hazard rate ratio for patients with WHO grade III and IV, for those with subtotal resection, for brainstem location, and for those not receiving radiation therapy was 7.4 (95% CI, 4.7-11.8), 6.4 (95% CI, 4.2-9.8), 2.8 (95% 2.1-3.8), 2.0 (95% CI, 1.3-2.8) and 2.3 (95% CI, 1.7-3.0), respectively. We found that half of Colombia's children and adolescents with primary CNS tumors survive five years, compared to 70% to 80% in high-income countries. In addition to tumor biology and location, gross total resection was crucial for improved survival in this cohort. Systematic monitoring of survival and its determinants provides empirical data for guiding cancer control policies.