Astrocytic Tumors Research Articles

Brain Tumor Imaging in Adolescents and Young Adults: 2021 WHO Updates for Molecular-based Tumor Types.

Published in 2021, the fifth edition of the World Health Organization (WHO) classification of tumors of the central nervous system (CNS) introduced new molecular criteria for tumor types that commonly occur in either pediatric or adult age groups. Adolescents and young adults (AYAs) are at the intersection of adult and pediatric care, and both pediatric-type and adult-type CNS tumors occur at that age. Mortality rates for AYAs with CNS tumors have increased by 0.6% per year for males and 1% per year for females from 2007 to 2016. To best serve patients, it is crucial that both pediatric and adult radiologists who interpret neuroimages are familiar with the various pediatric- and adult-type brain tumors and their typical imaging morphologic characteristics. Gliomas account for approximately 80% of all malignant CNS tumors in the AYA age group, with the most common types observed being diffuse astrocytic and glioneuronal tumors. Ependymomas and medulloblastomas also occur in the AYA population but are seen less frequently. Importantly, biologic behavior and progression of distinct molecular subgroups of brain tumors differ across ages. This review discusses newly added or revised gliomas in the fifth edition of the CNS WHO classification, as well as other CNS tumor types common in the AYA population.

CDKN2A/B deletion in IDH-mutant astrocytomas: An evaluation by Fluorescence in-situ hybridization.

CDKN2A/B homozygous deletion is one of the defining features of grade 4 in IDH-mutant astrocytic tumours. To evaluate CDKN2A/B-deletion in IDH-mutant astrocytic tumours and its clinicopathological impact. CDKN2A/B-deletion was evaluated by Fluorescence in-situ hybridisation (FISH) and interpreted by two recently accepted methods. Eighty-three out of 94 cases (histologically-grade 2: 3, grade 3: 46, grade 4: 34) were interpretable on FISH. Concordant CDKN2A/B-deletion was observed in 71% (27/38) of lower-grade tumours (n = 49) and 90% (27/30) of histological grade 4 tumours (n = 34). Both the interpretation methods showed good agreement (Kappa = 0.75). CDKN2A/B-deletion showed an inverse correlation for < 10% MIB-1 labeling index (p = 0.01) while that by method-2 showed a significant correlation for grade 4 (p = 0.02). No significant correlation was observed for any other clinicopathological parameters. Twenty-four patients showed progression/recurrence (including deaths), and no significant difference in frequency of CDKN2A/B deletion was observed among cases with disease progression across different histological grades. CDKN2A/B-deletion was observed across all the histological grades of IDH-mutant astrocytic tumours, expectedly more in the higher grade. FISH, as a method, can be used for the detection of CDKN2A/B homozygous deletion, when there is concordant interpretation.

Kinin Receptors and Kinin-Related Gene Expression in Astrocytic Brain Tumors.

Kinins are a set of peptides present in tissues that are involved in the inflammatory response and cancer progression. However, studies showing the expression of kinin receptors in human glioma samples are still incomplete and contradictory. The aim of the present study was to ascertain the expression of BDKRB1 and BDKRB2 genes, as well as the level of B1R and B2R proteins in human gliomas, depending on the degree of malignancy. Additionally, representative kinin-dependent genes with altered expression were indicated. The expression profile of kinin-dependent genes was determined using oligonucleotide microarray technique. In addition, RT-qPCR was used to assess the expression level of selected differentiating genes. The location of kinin receptors in brain gliomas was assessed using immunohistochemical methods. The oligonucleotide microarray method was used to identify 12 mRNA IDs of kinin-related genes whose expression was upregulated or downregulated in gliomas of different grades. In immunohistochemically stained samples, the concentrations of BR1 and BR2 proteins, measured by optical density, were statistically significantly higher in grade G3 vs. G2 and G4 vs. G3. Increased expression of kinin receptors BDKRB1 and BDKRB2 in brain gliomas, depending on the degree of malignancy, suggests the involvement of kinins and their receptors in the disease's pathogenesis. Quantitative assessment of mRNA BDKRB1, PRKAR1A, MAP2K, and EGFR in patients with brain tumors may hold diagnostic and therapeutic significance.

Relationship of Serum Microsomal Prostaglandin E2 Levels with Residual Tumor Volume in Patients with Astrocytoma.

This study aimed to investigate the relationship between tumor volume and serum microsomal prostaglandin E2 (mPGE2) levels in patients with astrocytic tumors. The study included patients with astrocytic tumors who were treated at our clinic between August 2015 and December 2016. Preoperative and postoperative contrast-enhanced cranial magnetic resonance imaging (MRI) scans were performed (within the first 24 h), and preoperative and postoperative residual tumor volumes were calculated. Microsomal prostaglandin E2 (mPGE2) levels were measured and compared in the serum samples of the patients before surgery, on the first day after surgery, and at 1 week after the surgery. The study included 20 patients, 13 of whom were males and 7 were females, with a mean age of 57.20 ± 14.66 yr. The mean postoperative tumor volume was 9,180.69 mm3 (range, 0.00-41,961.60), which was significantly lower than the preoperative mean tumor volume of 37,323.84 mm3 (range, 4,457.40-108,247.20; z = -3.920, p 0.001). On the first postoperative day, the mean mPGE2 level was 1,776.50 pg/ml (range, 771-5,010), which was similar to the preoperative mean mPGE2 level of 1,769.20 pg/ml (range, 681-3,480). On the seventh postoperative day, the mean mPGE2 level was 955.50 pg/ml (range, 31-2,130), which was significantly lower than the preoperative and postoperative first-day mean mPGE2 levels (p 0.001). No correlation was found between preoperative and postoperative tumor volumes and mPGE2 levels. Compared with preoperative mPGE2 levels, mPGE2 levels decreased significantly on the seventh postoperative day. However, no correlation was observed between the tumor volume removed and decrease in mPGE2 levels.

Histopathological Spectrum of Central Nervous System Tumours in Adolescent and Young Adults: A Cross-sectional Study from Punjab, Northern India

Introduction: Central Nervous System (CNS) tumours are a common cause of cancer-related deaths in adolescents and young adults. The challenges in diagnosing and treating CNS tumours in this age group are unique and require special attention. Aim: To study the histopathological spectrum of CNS tumours in Adolescents and Young Adults (AYA). Materials and Methods: Present five-year cross-sectional study was conducted on CNS biopsies received in the Department of Pathology at Dayanand Medical College and Hospital, Ludhiana, Punjab, India, from July 1, 2016, to June 30, 2021, to analyse the histopathological spectrum of CNS tumours in the AYA group based on the site of the lesion, age, gender, and Isocitrate Dehydrogenase (IDH) status. Results: During the study period, a total of 215 cases of CNS tumours were identified, of which 52 (24.2%) belonged to the AYA group. Of these, 35 (67.3%) were males and 17 (32.7%) were females. The majority of the patients presented with complaints of headache (50/52, 96.1%), with the frontal lobe being the most common site of involvement (21/52, 40.4%). Diffuse astrocytic and oligodendroglial tumours were the most commonly observed (23/52, 44.2%). Conclusion: CNS tumours are one of the most common cancer diagnosis among the AYA group, and awareness should be enhanced among histopathologists and oncologists regarding these tumours based on the updated classification.

Treatments for Spinal Cord Malignant Astrocytic Tumors : Up to Date

Treatments for Spinal Cord Malignant Astrocytic Tumors : Up to Date

10006-PEDT-1 PEDIATRIC LOWER GRADE GLIOMA SURGERY IN THE ERA OF GENOMIC MEDICINE

Abstract INTRODUCTION In the new WHO Brain Tumor Classification of 2021, pediatric-type gliomas are classified separately from adult-type tumors. Additionally, with the advancement of cancer genomics, treatment options have expanded. Here we consider surgery for pediatric low-grade gliomas. METHODS We retrospectively analyzed 41 cases of low-grade gliomas or glioneuronal tumors in patients under 18 years of age who underwent surgery at our institute from 2002 to March 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. DISCUSSION 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 astrocytomas located in the optic pathway and hypothalamus, biopsy becomes necessary for molecular diagnosis and the selection of appropriate therapeutic agents. Conversely, for unilateral optic nerve gliomas, options other than resection may be considered. 4) is primarily associated with epilepsy-related tumors. Surgical resection holds the promise of controlling epilepsy in these cases. However, various genetic abnormalities have been identified, which could prove useful in diagnosis and treatment. CONCLUSION Based on the new WHO classification, a reevaluation of treatment strategies for pediatric brain tumors is necessary.

Application of WHO CNS Fifth Edition Criteria for Glioblastoma Multiforme Diagnosis: A single center study

Abstract Introduction/Objective The fifth edition of the WHO classification of the tumors of the central nervous system (WHO CNS 5) published in 2021 introduced major changes that incorporate molecular diagnostics in CNS tumor classification along with histology and immunohistochemistry. Glioblastomas (GBM) were diagnosed based on the histologic features of diffuse and astrocytic glioma in adults, if there is microvascular proliferation and /or necrosis. Isocitrate dehydrogenase 1 (IDH) R132 H immunohistochemical stain expression and /or mutation analysis results were used to further classify GBMs as IDH mutant or IDH wild type. In WHO CNS 5 all IDH mutant diffuse astrocytic tumors are considered a single type (Astrocytoma, IDH mutant) and graded 2, 3, or 4. Glioblastoma IDH wild type is diagnosed in the setting of an IDH wild type diffuse and astrocytic glioma with microvascular proliferation or necrosis or TERT promoter mutation or EGFR gene amplification or +7/-10 chromosome copy number changes. In this study, we analyze how the change in diagnostic criterion would affect the classification of GBMs diagnosed in our institution retrospectively. Methods/Case Report The pathology database was searched for all diffuse gliomas diagnosed as GBM between 01/2019 and 12/2021. Age of the patient, gender, location of tumor, histologic features, IDH status and molecular alterations ( Onkosight Advanced solid tumor panel, 50 genes) were reviewed. Results (if a Case Study enter NA) A total of 74 adult high grade glial neoplasms were identified out of which 25 were GBMs. The age of the patients ranged from 40 to 87 years. 14 were men and 11 were females. All tumors had histologic features of GBM such as necrosis and microvascular proliferation. 24 (96%) tumors were IDH negative by immunohistochemistry and mutation analysis, and 1 (4%) was IDH strongly positive by immunohistochemistry. Molecular studies were not performed on this tumor. Conclusion 96% of GBMS diagnosed during the time period conformed to the WHO CNS 5 diagnostic criteria. The one IDH positive tumor would be reclassified as diffuse astrocytoma, IDH mutant, Grade 4. Like previous WHO classifications, WHO CNS 5 is a work in progress attempting to introduce new knowledge into the classification hoping to provide practical guidance to pathologists and neuro-oncologists and to benefit the patients with CNS tumors.

Optimizing the risk stratification of astrocytic tumors by applying the cIMPACT-NOW Update 3 signature: real-word single center experience

Our work reports implementation of a useful genetic diagnosis for the clinical managment of patients with astrocytic tumors. We investigated 313 prospectively recruited diffuse astrocytic tumours by applying the cIMPACT-NOW Update 3 signature. The cIMPACT-NOW Update 3 (cIMPACT-NOW 3) markers, i.e., alterations of TERT promoter, EGFR, and/or chromosome 7 and 10, characterized 96.4% of IDHwt cases. Interestingly, it was also found in 48,5% of IDHmut cases. According to the genomic profile, four genetic subgroups could be distinguished: (1) IDwt/cIMPACT-NOW 3 (n = 270); (2) IDHwt/cIMPACT-NOW 3 negative (= 10); (3) IDHmut/cIMPACT-NOW 3 (n = 16); and 4) IDHmut/cIMPACT-NOW 3 negative (n = 17). Multivariate analysis confirmed that IDH1/2 mutations confer a favorable prognosis (IDHwt, HR 2.91 95% CI 1.39–6.06), and validated the prognostic value of the cIMPACT-NOW 3 signature (cIMPACT-NOW 3, HR 2.15 95% CI 1.15–4.03). To accurately identify relevant prognostic categories, overcoming the limitations of histopathology and immunohistochemistry, molecular-cytogenetic analyses must be fully integrated into the diagnostic work-up of astrocytic tumors.

Clinical application of MAO-B PET using 18F-THK5351 in neurological disorders.

Monoamine oxidase B (MAO-B) is an enzyme localized to the outer mitochondrial membrane and highly concentrated in astrocytes. Temporal changes in regional MAO-B levels can be used as an index of astrocytic proliferation, known as activated astrocytes or astrogliosis. MAO-B is a marker to evaluate the degree of astrogliosis. Therefore, MAO-B positron emission tomography (PET) is a powerful imaging technique for visualizing and quantifying ongoing astrogliosis through the estimate of regional MAO-B levels. Each neurodegenerative disorder generally has a characteristic distribution pattern of astrogliosis secondary to neuronal loss and pathological protein aggregation. Therefore, by imaging astrogliosis, MAO-B PET can be used as a neurodegeneration marker for identifying degenerative lesions. Any inflammation in the brain usually accompanies astrogliosis starting from an acute phase to a chronic phase. Therefore, by imaging astrogliosis, MAO-B PET can be used as a neuroinflammation marker for identifying inflammatory lesions. MAO-B levels are high in gliomas originating from astrocytes but low in lymphoid tumors. Therefore, MAO-B PET can be used as a brain tumor marker for identifying astrocytic gliomas by imaging MAO-B levels and distinguishing between astrocytic and lymphoid tumors. This review summarizes the clinical application of MAO-B PET using 18F-THK5351 as markers for neurodegeneration, neuroinflammation, and brain tumors in neurological disorders. Because we assume that MAO-B PET is clinically applied to an individual patient, we focus on visual inspection of MAO-B images at the individual patient level. Geriatr Gerontol Int 2024; 24: 31-43.

BIOM-57. UNRAVELING THE DYSREGULATION OF MIR-17/92 CLUSTER IN AGGRESSIVE PEDIATRIC BRAIN TUMORS: IMPLICATIONS FOR NOVEL THERAPEUTIC STRATEGIES

Abstract The miR-17/92 cluster, commonly referred to as “OncoMir-1,” is extensively studied in cancer due to its oncogenic role, but it has yet to be fully characterized in pediatric brain tumors. In this study, we conduct a comprehensive investigation involving miRNA profiling of 262 pediatric brain tumors, along with sample-matched data from the Pediatric Brain Tumor Atlas, including WGS, RNA-sequencing, proteomics, and phospho-proteomics data. Through miRNA-based unsupervised clustering, we identified four distinct miRNA signatures that transcend histological boundaries. An aggressive cluster (consisting of Medulloblastoma, ATRT, High-Grade Astrocytic Tumors, and some Ependymomas) exhibited the shortest survival and displayed an enriched network of co-expressed miR-17/92 cluster family members and paralogues, specifically miR-106b/25 and miR-106a/363 (p&amp;lt; 0.001). These tumors exhibited significant upregulation of the MIR17HG gene, which encodes the miR-17/92 cluster of miRNAs (p&amp;lt; 0.001). Further exploration of the upstream regulatory mechanisms of MIR17HG identified n-MYC and E2F1/2/3 significantly upregulated (p&amp;lt; 0.01). Additionally, utilizing sample-matched phospho-proteomics data, we found hyperphosphorylation of RB1, the upstream regulator of E2F, at three sites, providing additional evidence of RB1-E2F regulation upstream of MIR17HG. RB1 hyperphosphorylation and subsequent complete inactivation are mediated by the CDK2/Cyclin E complex, which is inhibited by the tumor suppressor p21. Interestingly, p21 (CDKN1A) gene expression was entirely depleted in the aggressive brain tumors group. In summary, our findings reveal the aberrant upregulation of the oncogenic miR-17/92 cluster in a group of aggressive brain tumors, potentially resulting from inactivating hyperphosphorylation of RB1 caused by p21 loss. This event frees E2F transcription factors and enables transcription of MIR17HG. Additionally, our study highlights E2F1/2/3 and CDK2 as potential therapeutic targets not only for aggressive brain tumors but also for other cancers overexpressing the miR-17/92 cluster. Future research will focus on molecular validation and targeting of the miR-17/92 regulatory pathway using available brain tumor cell line models.

PATH-44. INTRA-OPERATIVE ANALYSES OF GENETIC ALTERATIONS IN THE CENTRAL NERVOUS SYSTEM TUMORS USING RAPID QUANTITATIVE PCR DEVICE

Abstract Recent comprehensive molecular analyses of central nervous system (CNS) tumors identified several diagnostic or prognostic markers. IDH mutation, TERT promoter (pTERT) mutation and CDKN2A homozygous deletion in adult-type diffuse gliomas, BRAF p.V600E mutation in circumscribed astrocytic gliomas, histone H3 gene mutations in pediatric-type diffuse high-grade gliomas or MYD88 mutation in primary CNS lymphoma (PCNSL) are quite important markers. Intra-operative identification of these molecular alterations could be effective for decision-making of tumor removal strategy. In this study, we established intra-operative gene analysis method using rapid quantitative PCR device, GeneSoC, by which we could obtain genotype of these important genes for 20 minutes in an operating room. Using GeneSoC, we could perform 50 cycles of quantitative PCR for approximately 12 minutes. We established rapid gene analyses of mutations of IDH1 p.R132H, pTERT C225T, pTERT C250T, H3 K27M, BRAF p.V600E and homozygous deletion of CDKN2A for diffuse gliomas and circumscribed astrocytic tumors and MYD88 p.L265P for PCNSL. For elution of DNA, we incubated at least 1mg of tumor tissue at 95°for 5 minutes. Combined this boiling method with GeneSoC, we could obtain those genetic alterations for 20 minutes after collection of tumor tissue. For 42 glioma cases and 10 PCNSL cases, we could obtain accurate genetic alterations (IDH1 p.R132H, pTERT C225T, pTERT C250T for gliomas or MYD88 p.L265P for PCNSL) in all cases, using this method. For detection of CDKN2A homozygous deletion, sensitivity and specificity are 100% and 83% in analyzed 50 cases, respectively. In this study, we could obtain the genotype of important molecular markers intra-operatively, not only during tumor removal but even during tumor biopsy, using GeneSoC device. This rapid genetic analysis might be effective not only for intra-operative diagnosis but also for detection of boundary between tumor and normal tissue.

PATH-15. GLIOBLASTOMA, IDH-WILDTYPE WITHOUT KEY MOLECULAR FEATURES.

Abstract Molecular alterations that predict aggressive behavior of astrocytic tumors include EGFR amplification, TERT promoter (pTERT) mutations, gain of chromosome 7 and loss of chromosome 10. During January 2020 and February 2023, we encountered 21 cases of pathologically diagnosed glioblastoma, IDH-wildtype without the above-mentioned molecular characteristics. In this study, we tried to characterize these tumors. For all cases, genomic DNA was extracted from fresh frozen tissue. Using extracted DNA, to analyze the status of IDH mutation, 1p/19q codeletion, pTERT mutation, EGFR gene amplification, combined gain of entire chromosome 7, and loss of entire chromosome 10 (+7/− 10), whole exome sequencing, Sanger sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA) was performed. In addition, gene panel testing was performed for suspected familial cases. Among 21 cases, 2 harbored histone G34 mutation and was diagnosed as diffuse hemispheric gliomas, H3 G34-mutant. Among the rest 19 patients, CDKN2A/B homozygous deletions were detected in 7. Three of the rest 12 patients were diagnosed as patients with Li Fraumeni syndrome. Glioblastoma IDH-wildtype CNS WHO grade 4 typically presents necrosis and/or microvascular proliferation. Molecular alterations including EGFR amplification, pTERT mutations, gain of chromosome 7 and loss of chromosome 10 are key features that characterize GBM IDH-wildtype. However, some of the pathologically diagnosed GBM, do not carry these gene alterations. Among those, there existed cases harboring CDKN2A/B homozygous deletions or H3 G34 mutations, and cases suffering Li Fraumeni syndrome.

Differences and similarities in biophysical and biological characteristics between U87 MG glioblastoma and astrocyte cells.

Current cancer studies focus on molecular-targeting diagnostics and interactions with surroundings; however, there are still gaps in characterization based on topological differences and elemental composition. Glioblastoma (GBM cells; GBMCs) is an astrocytic aggressive brain tumor. At the molecular level, GBMCs and astrocytes may differ, and cell elemental/topological analysis is critical for identifying potential new cancer targets. Here, we used U87 MG cells for GBMCS. U87 MG cell lines, which are frequently used in glioblastoma research, are an important tool for studying the various features and underlying mechanisms of this aggressive brain tumor. For the first time, atomic force microscopy (AFM), scanning electron microscopy (SEM) accompanied by energy-dispersive X-ray spectroscopy (EDS), and X-ray photoelectron spectroscopy (XPS) are used to report the topology and chemistry of cancer (U87 MG) and healthy (SVG p12) cells. In addition, F-actin staining and cytoskeleton-based gene expression analyses were performed. The degree of gene expression for genes related to the cytoskeleton was similar; however, the intensity of F-actin, anisotropy values, and invasion-related genes were different. Morphologically, GBMCs were longer and narrower while astrocytes were shorter and more disseminated based on AFM. Furthermore, the roughness values of these cells differed slightly between the two call types. In contrast to the rougher astrocyte surfaces in the lamellipodial area, SEM-EDS analysis showed that elongated GBMCs displayed filopodial protrusions. Our investigation provides considerable further insight into rapid cancer cell characterization in terms of a combinatorial spectroscopic and microscopic approach.

RGS5 augments astrocyte activation and facilitates neuroinflammation via TNF signaling

Astrocytes contribute to chronic neuroinflammation in a variety of neurodegenerative diseases, including Parkinson's disease (PD), the most common movement disorder. However, the precise role of astrocytes in neuroinflammation remains incompletely understood. Herein, we show that regulator of G-protein signaling 5 (RGS5) promotes neurodegenerative process through augmenting astrocytic tumor necrosis factor receptor (TNFR) signaling. We found that selective ablation of Rgs5 in astrocytes caused an inhibition in the production of cytokines resulting in mitigated neuroinflammatory response and neuronal survival in animal models of PD, whereas overexpression of Rgs5 had the opposite effects. Mechanistically, RGS5 switched astrocytes from neuroprotective to pro-inflammatory property via binding to the receptor TNFR2. RGS5 also augmented TNFR signaling-mediated pro-inflammatory response by interacting with the receptor TNFR1. Moreover, interrupting RGS5/TNFR interaction by either RGS5 aa 1–108 or small molecular compounds feshurin and butein, suppressed astrocytic cytokine production. We showed that the transcription of astrocytic RGS5 was controlled by transcription factor early B cell factor 1 whose expression was reciprocally influenced by RGS5-modulated TNF signaling. Thus, our study indicates that beyond its traditional role in G-protein coupled receptor signaling, astrocytic RGS5 is a key modulator of TNF signaling circuit with resultant activation of astrocytes thereby contributing to chronic neuroinflammation. Blockade of the astrocytic RGS5/TNFR interaction is a potential therapeutic strategy for neuroinflammation-associated neurodegenerative diseases.

Hemorrhagic complications during stereotactic biopsy of brain tumors

Relevance. Stereotactic biopsy (STB) is one of the main methods for diagnosing deep brain lesions. STB has several advantages over conventional intraoperative biopsy, as it is less traumatic and safer, especially for patients in critical condition. However, the most common complications of STB are hemorrhages, with a risk ranging from 0.9 % to 59.8 % depending on various studies. Intracranial hemorrhages are serious complications of surgical treatment of brain tumors, especially during biopsy using stereotactic techniques.Objective. To assess the risk of intracranial hemorrhages during STB of brain tumors and investigate possible factors influencing this risk, such as involvement of different brain regions in the neoplastic process, patient’s gender and age, degree of malignancy of the tumor, and use of different stereotactic devices.Materials and Methods. A retrospective study of data from 20 patients who underwent STB of brain tumors was conducted. Clinical data, examination results including coagulogram and aggregatogram, as well as data on involvement of different anatomical brain regions in the neoplastic process, degree of malignancy of the tumor, and use of a specific stereotactic device were analyzed.Results. Analysis of the frequency and structure of hemorrhagic complications of STB was performed, prognostic factors for high risk were identified, and preventive measures were proposed to reduce the number of hemorrhages.Conclusions. The introduction of the modern CRW Radionics stereotactic device into practice has reduced the frequency and severity of hemorrhagic complications after STB by two times. Lymphoproliferative processes and glioblastomas have a higher frequency of hemorrhages, but in most cases, they are clinically insignificant. There is a correlation between the degree of anaplasia of astrocytic tumors and the severity of hemorrhages. Ways to reduce the risks of intracranial hemorrhages during STB of brain tumors may include: careful preoperative planning of the biopsy trajectory; use of informative neurovisualization methods in planning the needle insertion trajectory; use of modern stereotactic systems by neurosurgeons who have undergone additional specialization and training on the specific device; use of modern biopsy needles. In addition, it is advisable to consider preoperative preventive hemostatic therapy in patients suspected of having a high degree of tumor anaplasia.

Central Nervous System tumor at “Prof. Dr. I.G.N.G. Ngoerah” General Hospital, Denpasar: An epidemiological study between 2020-2022

Background. Central Nervous System (CNS) tumor is neoplasm that located in central nervous system, which include brain and medulla spinalis. Despite its significant raise of incidence and morbidities, limited epidemiological data was available. Therefore, this study aimed to describe the epidemiological characteristic of CNS tumor over a 3-year period in a single tertiary hospital in Bali, Indonesia. Methods. This study was a descriptive study with cross sectional design. This study included all patients aged 18 year or over who were histopathologically diagnosed with central nervous tumor at “Prof. Dr. I.G.N.G. Ngoerah General Hospital”, Denpasar, between January 2020 and December 2022. Data about age, gender, tumor location, histopathological type, tumor grading, and source of metastases in secondary CNS tumor were obtained from medical record. Result. A total of 221 cases were recorded during this study period. The prevalence of primary CNS tumor was 81.9% while secondary CNS tumor was 18.1%. The majority of case, both in primary and secondary CNS tumor were female in age group of 50-59. Supratentorial constituted the most common lesion site in primary and secondary CNS tumor. The most frequent histopathological type of primary CNS tumor was meningioma, making up 48.1% of cases, followed by diffuse astrocytic and oligodendroglial tumors (26.5%), and tumor of the cranial and paraspinal nerve (9.9%). Carcinoma is the most common histological type in secondary CNS tumor with lung and breast tumor being the majority source of secondary CNS tumor, found in 40% and 27.5%, respectively. Conclusion. Adult female with age of 50-59 is the most affected group in CNS tumor. Primary CNS tumor were commonly found in supratentorial with meningioma and WHO grade I being the most frequent histopathological type and grade. Secondary CNS tumor were mostly found in supratentorial and originated from primary lung tumor.

Impact of Frontline Ivosidenib on Volumetric Growth Patterns in Isocitrate Dehydrogenase-mutant Astrocytic and Oligodendroglial Tumors.

Isocitrate dehydrogenase (IDH)-mutant gliomas are usually treated with radiotherapy and chemotherapy, which increases the risk for neurocognitive sequelae during patients' most productive years. We report our experience using off-label first-in-class mutant IDH1 inhibitor ivosidenib and its impact on tumor volume in IDH-mutant gliomas. We retrospectively analyzed patients ages ≥18 years with radiation/chemotherapy-naïve, mutant IDH1, nonenhancing, radiographically active, grade 2/3 gliomas, and ≥2 pretreatment and ≥2 on-treatment ivosidenib MRIs. T2/FLAIR-based tumor volumes, growth rates, and progression-free survival (PFS) were analyzed. log-linear mixed-effect modeling of growth curves adjusted for grade, histology, and age was performed. We analyzed 116 MRIs of 12 patients [10 males, median age 46 years (range: 26-60)]: 8 astrocytomas (50% grade 3) and 4 grade 2 oligodendrogliomas. Median on-drug follow-up was 13.2 months [interquartile range (IQR): 9.7-22.2]. Tolerability was 100%. A total of 50% of patients experienced ≥20% tumor volume reduction on-treatment and absolute growth rate was lower during treatment (-1.2 ± 10.6 cc/year) than before treatment (8.0 ± 7.7 cc/year; P ≤ 0.05). log-linear models in the Stable group (n = 9) showed significant growth before treatment (53%/year; P = 0.013), and volume reduction (-34%/year; P = 0.037) after 5 months on treatment. After treatment, volume curves were significantly lower than before treatment (after/before treatment ratio 0.5; P < 0.01). Median time-to-best response was 11.2 (IQR: 1.7-33.4) months, and 16.8 (IQR: 2.6-33.5) months in patients on drug for ≥1 year. PFS at 9 months was 75%. Ivosidenib was well tolerated and induced a high volumetric response rate. Responders had significant reduction in tumor growth rates and volume reductions observed after a 5-month delay. Thus, ivosidenib appears useful to control tumor growth and delay more toxic therapies in IDH-mutant nonenhancing indolently growing gliomas. See related commentary by Lukas and Horbinski, p. 4709.

“A tumour registry initiative”

BackgroundPublished literature on epidemiological profile of paediatric brain tumours in India is limited. Aim: To present a retrospective analysis of the histological spectrum of 158 paediatric age group central nervous system tumours operated in a single tertiary care hospital in Coastal South India between January 2015 and December 2021. Material and methodsRetrospective analysis of the data regarding frequencies of various primary brain tumours among 158 paediatric patients (<18 years of age). The tumours were categorised according to the revised 4th edition of World Health Organization (WHO) classification of tumours of the Central Nervous system. ResultsPaediatric CNS constituted 8.5% of total intracranial tumours (158/1860) operated in the study period. The mean age of the patients was 10.2 years and a definite male predominance was noted (1.54:1) Astrocytomas, glioneuronal tumours, and neuronal tumours constituted the majority (72/158; 45.6%) followed by embryonal tumours (31/158; 19.6%) and craniopharyngiomas(24/158; 15.4%).Of the glial neoplasms majority were pilocytic and other astrocytic tumours(41.6%), followed by mixed neuroglial tumours (19.4%), diffuse high grade astrocytomas (Grade III/IV) (11.1%), diffuse low -grade astrocytomas (Grade II) (9.7%) and ependymomas (13.8%). Our series also included six meningiomas (3.8%), five germ cell tumours (3.16%), four nerve sheath tumours (2.53%), two choroid plexus tumours (1.26%), two pineal parenchymal tumours (1.26%) and one metastasis from a soft tissue sarcoma from the thigh. Supratentorial tumours (58.2%) were more common than posterior fossa (34.6%) and spinal tumours (7.6%) and visual pathway gliomas accounted for 5.6% of all our tumours. ConclusionsPaediatric central nervous system tumours are more common in boys and in the second decade of life. Astrocytomas are the most common paediatric brain tumours followed by medulloblastomas and craniopharyngiomas. Pediatric tumours affect the supratentorial compartment more often than the infratentorial compartment. The profile of paediatric brain tumours in our series is similar to that reported from other Indian centres as well as most western literature.

The T2FLAIR mismatch novel radiogenomic marker in the newly suspected low-grade gliomas

Background. The T2-FLAIR (fluid-attenuated inversion recovery) mismatch sign has been defined over the last few years as an important novel radiogenomic marker highly suggestive of isocitrate dehydrogenase mutated (IDH-mut) 1p19q non-codeleted gliomas (astrocytomas). Existing studies have demonstrated that this has good specificity but limited sensitivity for IDH-mut astrocytomas. Thenew 2021 WHO Classification of Tumors of the Central Nervous System (WHO CNS5) has introduced a layered grading system in which all IDH mutant diffuse astrocytic tumours are considered a single type (Astrocytoma, IDH-mutant) and are graded as CNS WHO grade 2, 3, or 4. Because of the growing importance of molecular information in CNS tumour classification, diagnoses and diagnostic reports need to combine different data types into a single diagnosis. Whether the T2FLAIR mismatch sign is of clinical relevance for the management of low-grade gliomas still needs to be further determined.Methods. We included histologically verified supratentorial low-grade gliomas (LGG) WHO grade 2-3 retrospectively during the period 2013–2018 (n=18). For the period 2019–2023 (n=27), patients with a radiological presumptive diagnosis of low-grade glioma were prospectively included, and we took into consideration the fact that in this group we could encounter other diagnoses than glioma.Clinical, radiological and histology data were collected. We aimed to examine the association of the T2-FLAIR mismatch sign (where identified) with clinical factors and outcomes. We evaluated the diagnostic reliability of the mismatch sign and its relation to the definitive histological diagnosis, the co-existence of an MR spectroscopy signature; we have also tried to determine whether the identification of the radiogenomic marker had any impact on the clinical outcome through the decision-making in neurosurgical management.Results. Out of 45 patients with radiological suspected glioma, 30 had a definitive diagnosis of diffuse astrocytoma grade 2 and 3 (Astrocytoma, IDH-mutant according to WHOCNS5). 6 patients had a diagnosis of glioblastoma (Glioblastoma, IDH-wildtype according to WHOCNS5). 8 patients have been diagnosed with oligodendroglioma (Oligodendroglioma, IDH-mutant, and 1p/19q-codeleted according to WHOCNS5) and 1 case had a definitive histology of cerebral abscess. Out of the 30 patients with IDH-mut astrocytoma, 6 (20.0%) showed a mismatch sign. The sensitivity and specificity of the mismatch sign for IDH-mut astrocytoma detection were 20% and98.6%, respectively. There were no differences between patients with an IDH-mut astrocytoma with or without T2FLAIR mismatch sign when grouped according to this with related to baseline characteristics, clinical outcome and presenting symptoms. MR spectroscopy sequences were analyzed where available for the retrospective and prospective cohort. There were 7 cases where MR spectroscopy was performed and, for the IDH-mut astrocytoma cases (n=4) it showed a persistent high Cho/NAA ratio without any difference between the patients with or without the T2FLAIR mismatch sign.Conclusion. In our relatively small retrospective and prospective cohorts, the T2-FLAIR mismatch sign, where identified, was not correlated with clinical features at presentation, prognosis or outcome. Until recently, the grading of CNS tumours has been focusing mainly on histology characteristics, but specific molecular markers can now be used for valuable prognostic information. For this reason, molecular-specific information has been added as an essential feature in grading and it is considered very useful for further estimation of prognosis within variable tumor types. We could not determine if the IDH-mut astrocytomas with mismatch sign represent a specific subgroup. Our study has confirmed that the T2-FLAIR mismatch sign is a reliable and specific marker of IDH-mut astrocytomas.