Brain Tumor In Adults Research Articles

Analysis of Gliomas DNA Methylation: Assessment of Preanalytical Variables

Precision oncology is driven by biomarkers. For glioblastoma multiforme (GBM), the most common malignant adult primary brain tumor, O6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation is an important prognostic and treatment clinical biomarker. Time-consuming preanalytical steps such as biospecimen storage, fixation, sampling, and processing are sources of data irreproducibility, and all these preanalytical variables are confounded by intratumor heterogeneity of MGMT promoter methylation. To assess the effect of preanalytical variables on GBM DNA methylation, tissue storage/sampling (CryoGrid), sample preparation multisonicator (PIXUL), and 5-methylcytosine DNA immunoprecipitation (Matrix-MeDIP-qPCR/seq) platforms were used. MGMT promoter methylation status assayed by MeDIP-qPCR was validated with methylation-specific PCR. MGMT promoter methylation levels in frozen and formalin-fixed paraffin-embedded sample pairs were not statistically different, confirming the reliability of formalin-fixed paraffin-embedded for MGMT promoter methylation analysis. Warm ex vivo ischemia (up to 4 hours at 37 °C) and 3 cycles of repeated sample thawing and freezing did not statistically impact 5-methylcytosine at MGMT promoter, exon, and enhancer regions, indicating the resistance of DNA methylation to common variations in sample processing conditions that might be encountered in research and clinical settings. Twenty-six percent to 34% of specimens exhibited intratumor heterogeneity in the MGMT DNA promoter methylation. These data demonstrate that variations in sample fixation, ischemia duration and temperature, and DNA methylation assay technique do not have a statistically significant impact on MGMT promoter methylation assessment. However, intratumor methylation heterogeneity underscores the value of multiple biopsies at different GBM geographic tumor sites in the evaluation of MGMT promoter methylation status. Matrix-MeDIP-seq analysis revealed that MGMT promoter methylation status clustered with other differentially methylated genomic loci (eg, HOXA and lncRNAs) that are resilient to variation in the above preanalytical conditions. These observations offer new opportunities to develop more granular data-based epigenetic GBM biomarkers. In this regard, the high-throughput CryoGrid-PIXUL-Matrix toolbox could be useful.

Use of a Single-Fiber Optical Probe for the Detection of Tumor Fluorescence in High-Grade Glioma.

High-grade glioma (HGG) is the most common primary brain tumor in adults. The overall median survival is between 14 and 16 months. Fluorescence-guided surgery by detection of protoporphyrin IX (PpIX) fluorescence has been shown to improve the extent of resection, translating to improved progression-free survival. Microscope-based fluorescence detection techniques are associated with several pain points, some of which may be addressed by using contact-based spectroscopy. We aimed to investigate the accuracy of an optical fiber at detecting PpIX fluorescence by performing real-time spectroscopy in patients with HGG. Adult patients undergoing fluorescence-guided surgery for suspected HGG were recruited prospectively. Intraoperatively, samples from cortex, white matter, and tumor were taken. These samples were interrogated using standard white and blue light microscope techniques and the optical fiber. These specimens were then assessed by neuropathology to determine whether the tumor tissue was present within them. We collected 89 samples from 28 patients. There was an equal ratio of men to women, with a median age of 66.5 years. The accuracy of the probe for detecting PpIX fluorescence was 75.9%, compared with 56.6% for the operating microscope, with a significant improvement in sensitivity (χ2 = 11.84, P < .001). The optical fiber probe was more accurate than the operating microscope for detecting PpIX fluorescence. This technology has potential value in improving the accuracy of fluorescence-guided surgery and has potential practical benefits relating to surgical workflow.

ROR1 MRNA EXPRESSION IN GLIOMA - A NOVEL PROGNOSTIC BIOMARKER

Abstract AIMS Glioblastoma is the most common and aggressive primary brain tumour in adults. Despite maximal surgical resection followed by concomitant chemo-/radiotherapy, the three-year survival remains less than 5%. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) overexpression is associated with poor prognosis in several cancers. ROR1 therapeutics are in Phase I/II clinical trials making it an exciting novel target with translational potential to explore for glioblastoma treatment. The aim of this study was to examine the association between ROR1 mRNA expression and overall survival (OS), by applying the WHO 2021 classification of transcriptomic glioma datasets. METHOD Clinical, histological, and molecular data were extracted from four independent glioma datasets (TCGA, CGGA, Rembrandt, and Gravendeel) via the GlioVis portal and analysed using the WHO 2021 classification. Only confirmed cases of astrocytoma, oligodendroglioma, or glioblastoma, and ROR1 mRNA expression data were included (2,216 cases). Kaplan-Meier survival curves were produced for OS with low/high grade glioma versus ROR1 mRNA expression. Log-rank (Mantel-Cox) multivariate regression was applied to analyse the effect of selected covariates on OS and ROR1 mRNA expression. RESULTS We observed a significant decrease in median OS in patients with high-ROR1 mRNA expression when compared to the low-ROR1 mRNA expression cohort (20 and 70 months, respectively). High-grade gliomas represented the highest ROR1 mRNA expression across the consortium, resulting in a poor median OS of 16 months. CONCLUSION This study represents the first report of an association between OS and the oncogenic role of ROR1 in glioma, a targetable cell surface marker for novel putative treatment in glioblastoma.

UNVEILING THE MECHANISTIC INSIGHTS OF ARGININE DEPRIVATION COMBINED WITH RADIOTHERAPY FOR THE TREATMENT OF GLIOBLASTOMA

Abstract AIMS Glioblastoma is a lethal form of primary brain tumour in adults. Despite surgery, radiation and chemotherapy, life expectancy is short rendering the need for novel therapeutic approaches. Metabolic therapies provide a multifaceted effect in the heterogeneous glioblastoma microenvironment as they target its reprogrammed metabolism while overcoming therapeutic obstacles such as the blood brain barrier. We have shown that arginine deprivation combined with radiation eliminates the tumours in vivo, however, the exact mechanism of action is yet unknown. Here, using spatial transcriptomics we explore the effects of arginine deprivation and radiation, alone and combined, on the glioblastoma microenvironment. METHOD Brains collected from CT2A immunocompetent mice 6 days after treatment with ADI-PEG20 (5 IU) for arginine depletion, radiation (8 Gy) or their combination were analysed by 10X Genomics Spatial Transcriptomics. Bioinformatic analysis was performed using the R package Seurat and the Ingenuity Pathway Analysis (Qiagen). RESULTS The induction of innate immune response was observed with all treatments, however, it was the prevailing element only in the combination treatment. Upregulated pathways in all treatments involved the activation of antigen presentation cells. The pro-inflammatory cascades included key molecules of an immune response such as Type I IFNs, IFN-γ, STAT1, ISG15 and IRFs. Protein translation pathways indicating resistance to treatment dominated the changes caused by the two monotherapies, while they were absent in the combination group. The upregulation of CXCL10 and CCL5 signified the transition to adaptive immune response. Cytosolic DNA sensing by the cGAS-STING was enriched in the radiation and combination groups providing a possible trigger for the innate immune response. Pyroptosis and extracellular matrix remodelling were uniquely presented in the combination group. CONCLUSION Our analysis indicates that arginine deprivation and radiation when combined enhance each other’s effect leading to a fortified immune response that is possibly initiated by cytosolic DNA sensing.

Immunotherapy for glioblastoma: current state, challenges, and future perspectives.

Glioblastoma (GBM) is an aggressive and lethal type of brain tumor in human adults. The standard of care offers minimal clinical benefit, and most GBM patients experience tumor recurrence after treatment. In recent years, significant advancements have been made in the development of novel immunotherapies or other therapeutic strategies that can overcome immunotherapy resistance in many advanced cancers. However, the benefit of immune-based treatments in GBM is limited because of the unique brain immune profiles, GBM cell heterogeneity, and immunosuppressive tumor microenvironment. In this review, we present a detailed overview of current immunotherapeutic strategies and discuss the challenges and potential molecular mechanisms underlying immunotherapy resistance in GBM. Furthermore, we provide an in-depth discussion regarding the strategies that can overcome immunotherapy resistance in GBM, which will likely require combination therapies.

VALIDATION OF 2HG-TARGETTED MR SPECTROSCOPY FOR IDENTIFYING IDH-MUTANT GLIOMAS

Abstract AIMS Diffuse gliomas, the most common adult primary brain tumour, are classified by their histological and molecular characteristics and genetic profile. Isocitrate dehydrogenase (IDH) mutant gliomas correlate with longer mean survival and progression-free survival time. In tumour cells, IDH mutations lead to metabolic changes and the production of oncometabolite 2-hydroxyglutarate (2HG). MR spectroscopy (MRS) can assess metabolic changes in disease states in-vivo and non-invasively. In this study, we demonstrate a validation pathway for two advanced MRS methods to be used as IDH-mutation biomarkers in clinic. METHOD Simulated, phantom, and healthy volunteer experiments were performed to optimise and validate three MRS sequences tuned for measuring 2HG. A PRESS sequence was used with TR/TE of 2500/97 ms aiming at the 2HG peaks around 2.25 ppm. An edited PRESS sequence, named MEGA-PRESS, tailored to 2HG 4.02 ppm peak was used with TR/TE of 3000/68 ms, 128 averages, and with editing pulses at 1.9 and 7.5 ppm. A long TE semi-LASER MRS sequence, with improved voxel localisation, was also used (TR/TE: 2500/110 ms). RESULTS Simulations were performed to find optimised sequence parameters and to develop basis sets for analysing the phantom and healthy volunteer acquisitions. Tumour-mimicking phantoms with variable concentrations of 2HG and cystathionine were created and validated with 800 MHz NMR spectroscopy. Phantoms were then used to assess the sensitivity and specificity of the MRS for 2HG and cystathionine. MEGA-PRESS proved Synthetic in-vivo 2HG spectra, combined from healthy volunteers and simulated or phantom-2HG spectra, were used to assess the spectral quality needed to reliably measure 2HG. CONCLUSION MEGA-PRESS proved to be the most robust MRS method and demonstrated accurate and precise measurement of phantom and synthetic 2HG with acceptable SNR. Clinical validation of the technique will need to be performed on LGG patient population, and the overall accuracy will be compared with patient IDH mutation status.

The peritumoral brain zone in glioblastoma: a review of the pretreatment approach.

Glioblastomas are the most common and aggressive form of malignant primary brain tumors in adults. The standard treatment is surgical resection followed by radiotherapy and chemotherapy. Despite optimal treatment methods, the prognosis for patients remains poor. Preoperative determination of glioblastoma margins remains beneficial for the complete removal of the tumor mass. Radiotherapy is essential for post-surgery treatment, but radioresistance is a significant challenge contributing to high mortality rates. Advanced imaging technologies are used to analyze the changes in the peritumoral brain zone (PTZ). Consequently, they may lead to the development of novel therapeutic options, especially targeting the marginal parts of a tumor, which could improve the prognosis of glioblastoma patients. The clinical presentation of glioblastoma is heterogeneous and mostly depends on the location and size of a tumor. Glioblastomas are characterized by both intratumoral cellular heterogeneity and an extensive, diffuse infiltration into the normal tissue bordering a tumor called the PTZ. Neuroimaging techniques, such as diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI), perfusion-weighted imaging (PWI), proton magnetic resonance spectroscopy (1H MRS), and chemical exchange saturation transfer (CEST) are useful methods in the evaluation of the tumor infiltration and thus the resection margin.

Updated EANO guideline on rational molecular testing of gliomas, glioneuronal, and neuronal tumors in adults for targeted therapy selection - Update 1.

The standard of care for adult patients with gliomas, glioneuronal and neuronal tumors consists of combinations of surgery, radiotherapy, and chemotherapy. For many systemic cancers, targeted treatments are a major part of the standard treatment, however, the predictive significance of most of the targets for treatment in systemic cancer are less well established in central nervous system (CNS) tumors . In 2023 the EANO Guideline Committee presented evidence based recommendations for rational testing of molecular targets for targeted treatments. From all targets reviewed, only testing for BRAF V600E mutations was of proven clinical benefit; despite regulatory approvals for tumor agnostic treatment of NTRK gene fusions and high Tumor Mutational Burden (TMB) for patients with adult brain tumors, the evidence of clinical benefit for patients was still limited . This guideline has a modular structure, allowing regular updating of individual sections and adding new ones. The present version (Update 1) presents a review of the rationale of testing for PTEN, H3F3A, MTAP, RET and IDH, and presents an update of the text on TMB high and mismatch repair deficiency. It also presents an overview of therapeutic yield of routine next generation sequencing for mutations and fusion detection. The supplement accompanying this version contains the in depth review of all targets, whereas in the main manuscript the final recommendations of the revised and new targets are presented. Updates will be made on a regular basis.

Challenges and advances in glioblastoma targeted therapy: the promise of drug repurposing and biomarker exploration.

Glioblastoma remains the most prevalent and aggressive primary malignant brain tumor in adults, characterized by limited treatment options and a poor prognosis. Previous drug repurposing efforts have yielded only marginal survival benefits, particularly those involving inhibitors targeting receptor tyrosine kinase and cyclin-dependent kinase-retinoblastoma pathways. This limited efficacy is likely due to several critical challenges, including the tumor's molecular heterogeneity, the dynamic evolution of its genetic profile, and the restrictive nature of the blood-brain barrier that impedes effective drug delivery. Emerging diagnostic tools, such as circulating tumor DNA and extracellular vesicles, offer promising non-invasive methods for real-time tumor monitoring, potentially enabling the application of targeted therapies to more selected patient populations. Moreover, innovative drug delivery strategies, including focused ultrasound, implantable drug-delivery systems, and engineered nanoparticles, hold potential for enhancing the bioavailability and therapeutic efficacy of treatments.

Tackling Anticancer Drug Resistance and Endosomal Escape in Aggressive Brain Tumors Using Bioelectronics.

Resistance mechanisms in brain tumors, such as medulloblastoma and glioblastoma, frequently involve the entrapment of chemotherapeutic agents within endosomes and the extracellular expulsion of drugs. These barriers to effective treatment are exacerbated in nanotechnology-based drug delivery systems, where therapeutic nanoparticles often remain confined within endosomes, thus diminishing their therapeutic efficacy. Addressing this challenge necessitates the development of novel strategies to enhance the efficiency of cancer therapies. This study tests the hypothesis that external electrical stimuli can modulate intracellular trafficking of chemotherapeutic drugs in common malignant brain tumors in children (medulloblastoma) and adults (glioblastoma) by using gold nanoparticles (GNPs). In our experiments, alternating current (AC) stimulation ranging from 1 kHz to 5 MHz and at a strength of 1 V/cm significantly reduced cell viability in drug-resistant medulloblastoma and enhanced delivery of GNPs in glioblastoma. Low-frequency AC resulted in a 50% increase in apoptosis compared to controls and an 8-fold increase in cell death in cisplatin-resistant medulloblastoma cells, accompanied by a substantial reduction in EC50 from 2.5 to 0.3 μM. Similarly, vincristine-resistant cells demonstrated a 4-fold enhancement in drug sensitivity. Furthermore, high-frequency AC facilitated a significant increase from 20 to 75% in the endosomal escape of GNPs in glioblastoma cells. These findings underscore the potential of AC to selectively disrupt cancer cell resistance mechanisms and bolster the efficacy of nanoparticle-based therapies. The results indicate the effectiveness of AC stimulation in circumventing the limitations inherent in current nanotechnology-based drug delivery systems but also illustrates its transformative potential for treating aggressive, drug-resistant brain tumors.

CuO nanoparticles for glioma treatment in vitro and in vivo.

Glioma is the most prevalent malignant brain tumor in adults. The development of engineered nanomaterials (ENMs) has led to the emergence of innovative therapeutic strategies for gliomas. Therefore, our aim is to investigate the therapeutic effect of CuO nanoparticles (NPs) on glioma and provide data support for future research. The therapeutic effect of CuO NPs on glioma rats was explored through the detection of inflammatory factors, oxidase, pathological sections, immunofluorescence, neurotransmitter, glioma biomarker proteins and genes, and rat behavioral tests. Additionally, the application prospect of CuO NPs was evaluated by treating U87MG human glioma cell line. In this study, it was found that CuO NPs can alleviate the inflammatory reaction in the hippocampus tissue of glioma rats, promote the production of ·OH and lead to the up-regulation of catalase (CAT) and superoxide dismutase (SOD) enzyme activities. Treatment with CuO NPs also inhibited the expression of matrix metalloproteinase-9 (MMP-9) biomarkers in model rats and glioma cells. Moreover, it enhanced the release of neurotransmitters, which subsequently improved spatial recognition and memory ability of glioma rats. In conclusion, CuO NPs is a potential glioma treatment for ENMs, but still needs modification and modification strategies to improve its biocompatibility and targeted delivery.

HGGL-01 GLIOBLASTOMA MULTIFORM INVOLVING MULTIPLE BRAIN REGIONS ASSOCIATED WITH MUTATIONS IN EXON 4 OF ISOCITRATE DEHYDROGENASE 1 COMPLICATED BY ACUTE KIDNEY FAILURE: A CASE REPORT

Abstract Glioblastoma multiform (GBM), WHO grade 4, is the most aggressive primary brain tumor in adults associated with poor prognosis. We present a case of a 43-year-old female, Muyira, diagnosed with GBM involving multiple brain regions and harboring mutations in exon 4 of isocitrate dehydrogenase 1, who subsequently developed acute kidney failure. The patient initially presented with progressive neurological symptoms, including headache and cognitive decline. Multiplanar multiecho MRI of the brain was performed with IV contrast in orthogonal plane and revealed a moderate sized multilobulated heterogeneously and predominantly peripherally enhancing mass lesion with irregular margins and central non enhancing areas of necrosis arising from the right corona radiata, insular cortex, external capsule, lentiform nucleus, temporal, and frontal white matter with blood products. Perilesional edema was seen. Effacement of sulcal spaces. Right sylvian fissure, compression over right ventricle and midline shift of 8mm toward left side. There was dilatation of the left lateral ventricle with periventricular cerebrospinal fluid ooze. Uncal herniation was right side. On MR spectroscopy large choline, creatinine levels were seen in the lesion with reduced N-acetyl aspartate levels as compared to the normal parenchyma. Findings were suggestive of neoplastic lesion mostly high-grade glioma. Polymerase chain reaction sequencing confirmed the presence of missense mutation R132H in exon 4 of isocitrate dehydrogenase 1 gene. Despite maximal safe surgical resection, the patient developed acute kidney failure secondary to the nephrotoxic effects of gadolinium. Management of both the primary brain tumor and renal complication necessitated a multidisciplinary approach involving neurosurgery, oncology, nephrology, and supportive care. Despite aggressive interventions, the patient’s condition deteriorated, highlighting the challenges in managing concurrent life-threatening conditions in patients with advanced GBM.

Review of Novel Surgical, Radiation, and Systemic Therapies and Clinical Trials in Glioblastoma.

Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Despite an established standard of care including surgical resection, radiation therapy, and chemotherapy, GBM unfortunately is associated with a dismal prognosis. Therefore, researchers are extensively evaluating avenues to expand GBM therapy and improve outcomes in patients with GBM. In this review, we provide a broad overview of novel GBM therapies that have recently completed or are actively undergoing study in clinical trials. These therapies expand across medical, surgical, and radiation clinical trials. We additionally review methods for improving clinical trial design in GBM.

An oncolytic HSV-1 vector induces a therapeutic adaptive immune response against glioblastoma

BackgroundGlioblastoma (GBM) is the most frequent and aggressive brain tumor in adults with the lowest survival rates five years post-diagnosis. Oncolytic viruses (OVs) selectively target and damage cancer cells, and for this reason they are being investigated as new therapeutic tools also against GBM.MethodsAn oncolytic herpes simplex virus type 1 (oHSV-1) with deletions in the γ34.5 neurovirulence gene and the US12 gene, expressing enhanced green fluorescent protein (EGFP-oHSV-1) as reporter gene was generated and tested for its capacity to infect and kill the murine GL261 glioblastoma (GBM) cell line. Syngeneic mice were orthotopically injected with GL261cells. Seven days post-implantation, EGFP-oHSV-1 was administered intratumorally. Twenty-one days after parental tumor challenge in the opposite brain hemisphere, mice were sacrified and their brains were analysed by immunohistochemistry to assess tumor presence and cell infiltrate.ResultsoHSV-1 replicates and induces cell death of GL261 cells in vitro. A single intracranial injection of EGFP-oHSV-1 in established GL261 tumors significantly prolongs survival in all treated mice compared to placebo treatment. Notably, 45% of treated mice became long-term survivors, and rejected GL261 cells upon rechallenge in the contralateral brain hemisphere, indicating an anamnestic antitumoral immune response. Post-mortem analysis revealed a profound modification of the tumor microenvironment with increased infiltration of CD4 + and CD8 + T lymphocytes, intertumoral vascular collapse and activation and redistribution of macrophage, microglia, and astroglia in the tumor area, with the formation of intense fibrotic tissue suggestive of complete rejection in long-term survivor mice.ConclusionsEGFP-oHSV1 demonstrates potent antitumoral activity in an immunocompetent GBM model as a monotherapy, resulting from direct cell killing combined with the stimulation of a protective adaptive immune response. These results open the way to possible application of our strategy in clinical setting.

THOC1 complexes with SIN3A to regulate R-loops and promote glioblastoma progression.

Glioblastoma (GBM), the most common and aggressive malignant brain tumor in adults, has a median survival of 21 months. To identify drivers of GBM proliferation, we conducted a CRISPR-knockout screen, which revealed THO Complex 1 (THOC1) as a key driver. Knocking down THOC1 significantly reduced GBM cell viability across patient-derived xenograft (PDX) lines, enhancing survival (p<0.01) in primary PDX models. Conversely, overexpressing THOC1 in non-cancerous cells bolstered viability, decreasing survival and causing tumor engraftment in vivo (p<0.01). Further investigation revealed THOC1's robust interaction with SIN3A, a histone deacetylase complex. Histone deacetylation has been previously shown to prevent the buildup of R-loops, structures that form normally during transcription but can be lethal in excess. We found that THOC1-knockdown leads to elevated R-loop levels and reduced histone deacetylation levels. Next, to understand the networks specifically regulated by THOC1-mediated R-loop prevention, we conducted unbiased RNA-sequencing on control and THOC1-knockdown GBM cells. We found that THOC1's role in R-loop prevention primarily affects telomeres, critical regions for cell replication. We further show that THOC1-knockdown results in significantly increased telomeric R-loop levels and shortened telomeres. Ultimately, this study suggests that targeting THOC1 shows promise as a therapeutic strategy to disrupt the delicate R-loop landscape and undermine GBM's replicative potential.

CASCADES, a novel SOX2 super-enhancer-associated long noncoding RNA, regulates cancer stem cell specification and differentiation in glioblastoma.

Glioblastoma is the most common primary malignant brain tumor in adults, with a median survival of just over 1 year. The failure of available treatments to achieve remission in patients with glioblastoma (GBM) has been attributed to the presence of cancer stem cells (CSCs), which are thought to play a central role in tumor development and progression and serve as a treatment-resistant cell repository capable of driving tumor recurrence. In fact, the property of "stemness" itself may be responsible for treatment resistance. In this study, we identify a novel long noncoding RNA (lncRNA), cancer stem cell-associated distal enhancer of SOX2 (CASCADES), that functions as an epigenetic regulator in glioma CSCs (GSCs). CASCADES is expressed in isocitrate dehydrogenase (IDH)-wild-type GBM and is significantly enriched in GSCs. Knockdown of CASCADES in GSCs results in differentiation towards a neuronal lineage in a cell- and cancer-specific manner. Bioinformatics analysis reveals that CASCADES functions as a super-enhancer-associated lncRNA epigenetic regulator of SOX2. Our findings identify CASCADES as a critical regulator of stemness in GSCs that represents a novel epigenetic and therapeutic target for disrupting the CSC compartment in glioblastoma.

Vorasidenib- A Paradigm Shift in IDH1- or IDH2-Mutant Low-Grade Glioma Treatment.

Low-grade gliomas (LGGs) pose significant challenges in cancer research and treatment due to their infiltrative nature and tendency for recurrence, making them the most common brain tumour in adults. Most of the LGGs have the propensity to cause notable alterations in the microenvironment of the tumour thus making them difficult to treat. These alterations can be attributed to the prevalent mutations in the genes that produce isocitrate dehydrogenase (IDH) enzymes, especially in grade 2 diffuse gliomas. [1] Despite its inability to provide a complete cure, chemoradiation has been adopted as the standard therapy in grade 3 gliomas since it can lead to long-lasting remission. Chemoradiotherapy, when administered promptly, can help prevent tumour progression, and recurrence after surgery and improve long-term outcomes. Nevertheless, immediate adjuvant chemoradiotherapy is not administered in patients afflicted with tumours containing IDH mutant grade 2 gliomas. This decision is often made to circumvent potential harm such as radiation-induced cognitive problems, chemotherapy-related DNA mutations, and other negative effects on their health. [2] Due to the intricacies associated with the treatment decisions and the inclination to delay aggressive therapies to avoid adverse events, creates a necessity for a novel therapeutic strategy that is both effective and well tolerated. Vorasidenib, an oral medication specifically designed to deal with IDH mutations has displayed promise despite existing challenges. By aiming to specifically target aberrant metabolic pathways triggered by mutant IDH enzymes, Vorasidenib offers a potential treatment capable of interrupting tumour growth and could subsequently result in better patient outcomes. Among the many reasons that make Vorasadenib an appealing option are its capability to penetrate the blood-brain barrier and its promising safety profile, resulting in effective treatment while alleviating potential side effects. [3] Vorasidenib’s efficacy is derived from its ability to halt the metabolic cascades driven by mutant IDH enzymes thus leading to decreased progression of the gliomas. Clinical studies elicit the substantial value Vorasadenib has to offer by enhancing progression-free survival and postponing the advancement of the illness in patients with grade 2 IDH-mutant gliomas. This offers an optimistic prospect for delaying the need for more aggressive treatments in these patients. [2,4] Hence, to conclude Vorasadenib can transform treatment norms and enhance outcomes for those suffering from IDH-mutant LGG. Furthermore, it is crucial to investigate different treatment combinations, finding markers that would help assess clinical response to treatment, which in turn would be an important milestone in the treatment journey.

Reporting standards in randomized controlled trials involving neuro-oncology caregivers: A systematic review report from the RANO-Cares working group

Abstract BACKGROUND Family caregivers in neuro-oncology (e.g., spouse, family member, friend to a patient) have high unmet support needs, yet intervention trials and effective support options are scarce. The Response Assessment in Neuro-Oncology (RANO-) Cares working group investigated the methodological quality of neuro-oncology caregiver outcomes reporting in randomized controlled trials (RCTs). METHODS A systematic review was performed to evaluate to what extent RCTs assessing outcomes of caregivers of adult primary brain tumor patients adhere to minimum reporting standards. A 33-item checklist (23 applicable to secondary analysis reports) based on the International Society for Quality of Life Research (ISOQOL) criteria for patient-reported outcome (PRO) reporting was used. Risk of bias was assessed per RCT. RESULTS Fifteen publications from 11 unique RCTs included 676 neuro-oncology caregivers, with low overall risk of bias. Ten publications (66%) reported on caregiver outcomes as a primary aim, of which eight (80%) satisfied ≥2/3 of the key methodological criteria. Of the five secondary analysis reports (33%) two (40%) met ≥2/3 of applicable key criteria. Criteria often not reported adequately included sample size calculations (reported adequately in n=8, 53%), participant flow (n=9, 60%) window for data collection (n=1, 6%), and extent of (n=10, 66%), reasons for (n=9, 60%), and statistical approaches in dealing with (n=4, 26%) missing data. CONCLUSION Whilst there are opportunities to enhance reporting standards, RCTs that include neuro-oncology caregiver outcomes generally adhere to high quality reporting standards, and have low risk of bias, indicating good potential to impact clinical practice.

Contribution of [18F]FET PET in the Management of Gliomas, from Diagnosis to Follow-Up: A Review.

Gliomas, the most common type of primary malignant brain tumors in adults, pose significant challenges in diagnosis and management due to their heterogeneity and potential aggressiveness. This review evaluates the utility of O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET) positron emission tomography (PET), a promising imaging modality, to enhance the clinical management of gliomas. We reviewed 82 studies involving 4657 patients, focusing on the application of [18F]FET in several key areas: diagnosis, grading, identification of IDH status and presence of oligodendroglial component, guided resection or biopsy, detection of residual tumor, guided radiotherapy, detection of malignant transformation in low-grade glioma, differentiation of recurrence versus treatment-related changes and prognostic factors, and treatment response evaluation. Our findings confirm that [18F]FET helps delineate tumor tissue, improves diagnostic accuracy, and aids in therapeutic decision-making by providing crucial insights into tumor metabolism. This review underscores the need for standardized parameters and further multicentric studies to solidify the role of [18F]FET PET in routine clinical practice. By offering a comprehensive overview of current research and practical implications, this paper highlights the added value of [18F]FET PET in improving management of glioma patients from diagnosis to follow-up.

Metastatic brainstem medulloblastoma: a clinical case report

Medulloblastoma (MB) is one of the most common tumors of the central nervous system (CNS) of embryonic origin. MB is a malignancy that is quite common in pediatric patients; it represents a small proportion of brain tumors in young people, with an incidence of 0.6 per million per year. The peak age of diagnosis among the pediatric population is 3-6 years, while patients between 15 and 44 years old account for only 25%. The purpose of the study: to demonstrate a clinical case of surgical treatment of a patient with CNS metastasis of brainstem medulloblastoma. Methods. The article presents our clinical case of surgical treatment of a patient with medulloblastoma metastasis to the right temporal lobe. Results. Medulloblastoma is a heterogeneous brain tumor that is very rare in adults, especially those over 40 years of age, and accounts for less than 1% of all primary brain tumors in adults. Medulloblastoma metastases are most often found in the spinal cord and its membranes, less often in the cerebral hemispheres and ventricular system, which is associated with cerebrospinal fluid pathways. In foreign and Russian literature, there are relatively few publications on studies of metastatic lesions of medulloblastoma in adults; these studies are either considered as separate clinical observations or in conjunction with the development of medulloblastoma metastases in children. Non-specific neurological symptoms of medulloblastoma in adults can lead to later instrumental studies and specific therapy, and can also act as an unfavorable prognostic factor for the disease. Conclusion. Early detection and neurosurgical intervention are the key to preventing mortality and improving patient outcomes. Currently, only a few cases of medulloblastoma in adults are known; to prevent patient mortality, more detailed genetic and molecular studies of MB, including cerebrospinal fluid, risk stratification, description of oncological treatment, and monitoring of results to analyze MB sensitivity to chemotherapy and EBRT, as well as maintaining a registry of patients over 18 years old with brain medulloblastoma and dynamic observation of their family members in connection with oncological vigilance are needed.