Search Results (113)

Gliomas are notoriously difficult to treat owing to their pronounced heterogeneity and highly variable treatment responses. This reality drives the development of precise diagnostic and prognostic methods. This review explores the modern arsenal of bioinformatic tools aimed at refining diagnosis and stratifying glioma patients by different malignancy grades and types. We perform a comparative analysis of software solutions for processing whole-exome sequencing data, analyzing DNA methylation profiles, and interpreting transcriptomic data, highlighting their key advantages and limited applicability in routine clinical practice. Special emphasis is placed on the contribution of bioinformatics to fundamental oncology, as these tools aid in the discovery of new biomarker genes and potential targets for targeted therapy. The ninth section discusses the role of computational models in predicting immunotherapy efficacy. It demonstrates how integrative data analysis—including tumor mutational burden assessment, characterization of the tumor immune microenvironment, and neoantigen identification—can help identify patients who are most likely to respond to immune checkpoint inhibitors and other immunotherapeutic approaches. The obtained data provide compelling justification for including immunotherapy in standard glioma treatment protocols, provided that candidates are accurately selected based on comprehensive bioinformatic analysis. The tools discussed pave the way for transitioning from an empirical to a personalized approach in glioma patient management. However, we also note that this field remains largely in the preclinical research stage and has not yet revolutionized clinical practice. This review is intended for biological scientists and clinicians who find traditional bioinformatic tools difficult to use. Full article

Background: IDH1-mutant oligodendroglioma and astrocytoma differ not only in growth rate but also in growth pattern. Oligodendrogliomas tend to infiltrate white matter tracts, whereas astrocytomas more often displace them. Such difference could lead to different cognitive outcomes. This study examined differences in executive functioning before and up to one year after surgery between patients with IDH1-mutant astrocytoma and oligodendroglioma. Methods: Patients with WHO grade 2–3 IDH1-mutant oligodendroglioma (1p19q-codeleted) or astrocytoma were included. Cognition was assessed preoperatively, and at 3 and 12 months postoperatively using standardized computerized and paper-and-pencil tests. Groups were compared on demographics, tumor characteristics, surgical modality, extent of resection, adjuvant treatment, and baseline cognition. Longitudinal mixed models were performed to investigate differences in performances over time for the total sample and stratified by surgical approach (awake vs. asleep). Results: 162 patients (67 oligodendroglioma, 95 astrocytoma) were included. Oligodendroglioma patients were older, with more frontal and fewer temporal tumors. Oligodendroglioma patients showed a greater impairment prevalence on a measure of inhibition before surgery. In the awake surgery group, no longitudinal differences were found between diagnoses. In the asleep surgery group, astrocytoma patients remained stable while oligodendroglioma patients declined on a measure of cognitive flexibility, with performance at 3 and 12 months significantly lower than at baseline. Conclusions: Specific aspects of executive functioning in IDH1-mutant gliomas may differ by subtype. Oligodendroglioma patients showed postoperative decline in cognitive flexibility that did not recover to baseline level, particularly in case of surgery under general anesthesia. These results highlight the potential relevance of tumor subtype and surgical approach in limiting cognitive risks after glioma surgery. Full article

The abstract has been submitted for presentation to the AANS 2026 meeting being held in San Antonio, TX, USA. Introduction: Oligodendrogliomas are an uncommon subset of gliomas that are molecularly defined by 1p/19q codeletion in the setting of an isocitrate dehydrogenase (IDH) 1/2 mutation. Standard-of-care management involves maximal safe resection followed by adjuvant chemoradiation with procarbazine, lomustine, and vincristine (PCV). Although PCV confers a durable survival advantage, treatment-limiting toxicity is common and often necessitates discontinuation. IDH inhibitors such as vorasidenib have demonstrated promising efficacy and more favorable tolerability profiles, but a paucity of comparative data across therapeutic classes limits optimal treatment decision-making. Methods: A systematic search was conducted through to 7 March 2025 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Eligible studies included adult patients (≥18 years) with IDH-mutant, 1p/19q-codeleted oligodendrogliomas treated with PCV chemotherapy or IDH inhibitors and with a minimum follow-up of 12 months. Outcomes of interest included overall survival (OS), progression-free survival (PFS), and grade ≥ 3 adverse events (AEs) that led to treatment discontinuation. Results: Twenty-eight studies met the inclusion criteria, with a total of 406 patients. All 406 patients carried a confirmed diagnosis of oligodendroglioma. For mixed-histology cohorts, only oligodendroglioma-specific data were extracted and analyzed. Among PCV cohorts, median PFS ranged from 24.3 months to 8.4 years and median OS was reported up to 14.7 years in long-term follow-up from RTOG 9402 and EORTC 26951. Grade ≥ 3 AEs resulted in treatment discontinuation in 65–70% of patients, primarily due to hematologic or neurologic events. In comparison, vorasidenib achieved a median PFS of 27.7 months in the phase III INDIGO trial (HR 0.39; 95% CI 0.27–0.56; p < 0.001), with median OS not yet reached at 14.2 months of follow-up. Grade ≥ 3 AEs occurred in 22.8% of patients and led to treatment discontinuation in only 1–3%, primarily due to asymptomatic transaminitis. Early real-world data from expanded-access programs similarly support these tolerability findings. Conclusions: While PCV chemotherapy remains the standard-of-care systemic therapy for oligodendroglioma supported by mature survival data, IDH inhibitors represent a mechanistically targeted alternative with encouraging early-phase outcomes and a significantly improved safety profile. Direct comparison across these regimens is constrained by differences in study design and limited long-term OS data for IDH inhibitors. Prospective head-to-head trials are essential for defining the optimal therapeutic sequence in this evolving treatment landscape. In the interim, we provide a recommend approach for current use. Full article

Background: The androgen receptor (AR) is a ligand-dependent transcription factor of the nuclear steroid receptor superfamily, implicated in the pathogenesis of various solid tumors. The AR gene, located on chromosome Xq11–12, is accompanied by several X-linked genes that modulate AR expression and function, including FLNA, UXT, and members of the melanoma antigen gene (MAGE) family (MAGEA1, MAGEA11, MAGEC1, MAGEC2). While the AR has been investigated in multiple tumor types, its role in adult-type diffuse gliomas remains largely unexplored. Here, we characterized AR protein expression and the promoter methylation status of the AR and associated regulatory genes in adult-type diffuse gliomas. Methods: A retrospective analysis was conducted on 50 patients with adult-type diffuse gliomas, including IDH-mutant gliomas (grades 2–4) and IDH-wildtype glioblastomas (GBMs), classified according to the 2021 WHO criteria. AR nuclear expression was assessed by immunohistochemistry (IHC). Methylation-specific PCR and quantitative DNA methylation analyses were employed to evaluate promoter methylation of the AR and selected co-regulatory genes. Results: AR nuclear positivity correlated significantly with male sex (p = 0.04) and higher tumor grade, with the highest expression in IDH-wildtype GBMs (p = 0.04). In IDH-mutant gliomas, AR immunoreactivity was more prevalent in astrocytomas than in 1p/19q codeleted oligodendrogliomas (p = 0.02). AR expression was associated with unmethylated MGMT promoter status (p = 0.02). DNA methylation analysis revealed AR gene hypomethylation in tumors displaying nuclear AR positivity and in IDH-wildtype GBMs (Kruskal–Wallis p < 0.05). Additionally, methylation patterns of AR co-regulators located on the X chromosome suggest epigenetic regulation of AR signaling in gliomas. Conclusions: The findings reveal distinct AR pathway activation patterns in adult-type diffuse gliomas, particularly IDH-wildtype GBMs, suggesting that further exploration of antiandrogen therapies is warranted. Full article

Background/Objectives: Methionine (MET) positron emission tomography (PET) and cerebral blood volume (CBV) imaging provide complementary glioma assessment. This study compared MET and CBV across glioma subtypes defined by the 2021 World Health Organization Classification. Methods: This retrospective study enrolled 106 patients (mean age 41.9 ± 12.4 years; 57 males) with MRI non-contrast-enhanced gliomas: 21 glioblastoma, isocitrate dehydrogenase (IDH)-wildtype (G); 50 astrocytoma, IDH-mutant (A); and 35 oligodendrogliomas, IDH-mutant, and 1p/19q-codeleted (O). Relative CBVs (rCBVs) were measured in VOI-T2 and VOI-MET, and the MET tumor-to-normal (T/N) ratio was calculated. Results: MET and rCBV were significantly correlated (r = 0.5, p < 0.001); rCBV was higher in MET-positive tumors and predicted MET accumulation (area under the curve [AUC] = 0.72, cutoff = 2.99). In VOI-T2, rCBV and MET T/N ratio were the highest in G and lowest in A (p < 0.001). Receiver operating characteristic analyses showed no overall significant difference between MET and rCBV for differentiating G/A/O, but rCBV trended toward higher AUC values in key distinctions, such as G (0.736 vs. 0.612) or grade 4 (0.718 vs. 0.617). The increase in rCBV within the MET-positive region (VOI-MET/VOI-T2 rCBV ratio) was significantly higher in A (119.8%, p = 0.002) than in the other groups (p = 0.01). Conclusions: rCBV differentiated glioma subtype with accuracy comparable to MET and could predict MET accumulation. However, its reliability for identifying MET-positive regions varied by subtype, being useful in A but limited in O. Recognizing these subtype-specific differences, rCBV can serve as a practical tool for evaluating non-contrast-enhanced gliomas. Full article

The search for markers applicable for efficient differential diagnosis and personalized therapy is a priority task of experimental neuro-oncology. Modern molecular methods allow us to analyze human biopsy material; however, further actions with this extracted tumor tissue are limited. Relevant and sophisticated CNS tumor models are required for precise therapy development. Although it is possible to use human biomaterial to create 2D and 3D cultures and implant them into xenograft animals, the data generated from such models is limited. Due to changes in the classification of the CNS tumors in 2021, a representative model should have not only morphological similarity to human tumors but also key genetic aberrations for studying the mechanisms of carcinogenesis and personalized therapy (such as PDGFRa, Olig1/2, Sox2, and Mki67) for different glioma models such as astrocytoma, oligodendroglioma, and glioblastoma. On the basis of a unique scientific facility “The Collection of experimental tumors of the nervous system and neural tumor cell lines” (Avtsyn Research Institute of Human Morphology of “Petrovsky National Research Center of Surgery”), there is a biobank of chemically induced transplantable tumors of laboratory animals. Their properties, mechanisms, and progression closely correlate with malignant CNS neoplasms in humans. These are potentially useful for identifying novel signaling pathways associated with oncogenesis in the nervous system and personalizing therapeutic approaches. In our work, we characterized a tissue-transplantable brain tumor strain of rat glioma101.8 using MRI, IHC, scRNA-seq, and qPCR-RT methods. According to this study, the cellular composition of the tissue-transplantable rat glioma 101.8 strain was determined, as well as the major genetic signature characteristics of each cell population of this tissue-transplantable strain and its microenvironment. Full article

Attraction of glioblastoma cells to potassium was suspected when glioblastoma cells clustered around dying cells and migrated towards serum (high [K⁺]) and increased potassium. Potassium channel proteins (KCN family, 90 members) mediating alterations in the transmembrane flux may provide K⁺ that releases H⁺ bound to inner membranes in cancer cells for cytosolic proton transfer, possibly conformational in water (Grotthuss), to extrusion sites. Cell settling and migration assay results led to collecting 70 studies, unbiased by the authors for inclusion of KCN genes, that detected KCN differentially expressed genes (DEGs). Of 53 KCN DEGs found among 29 malignancies, 62.3% encoded H⁺-sensitive proteins. KCN DEGs encoding H⁺-sensitive proteins were more prevalent in 50 studies involving one or more categories (seven oncogenes and histone/DNA modifiers) versus those with none; p = 0.0325. Pertinent genes for lactate outflow, etc., had relatively normal levels of expression. Brain tumors in REMBRANDT (database) showed altered expression of KCN genes encoding H⁺-sensitive proteins in glioblastomas versus less invasive oligodendrogliomas of patients on anti-seizure medications, with less KCNJ16/Kir5.1; p = 5.32 × 10⁻⁸ in glioblastomas. Altered H⁺-sensitive potassium flux via the KCN family, downstream of oncogenes and histone/DNA modifiers, putatively incites proton transfers for H⁺ release during pH reversal (pHi > pHe) in cancer. Full article

Background/Objectives: Gliomas are complex and heterogeneous brain tumors characterized by an unfavorable clinical course and a fatal prognosis, which can be improved by an early determination of tumor kind. Here, we developed explainable machine learning (ML) models for classifying three major glioma subtypes (astrocytoma, oligodendroglioma, and glioblastoma) and predicting survival rates based on RNA-seq data. Methods: We analyzed publicly available datasets and applied feature selection techniques to identify key biomarkers. Using various ML models, we performed classification and survival analysis to develop robust predictive models. The best-performing models were then interpreted using Shapley additive explanations (SHAP). Results: Thirteen key genes (TERT, NOX4, MMP9, TRIM67, ZDHHC18, HDAC1, TUBB6, ADM, NOG, CHEK2, KCNJ11, KCNIP2, and VEGFA) proved to be closely associated with glioma subtypes as well as survival. Support Vector Machine (SVM) turned out to be the optimal classification model with the balanced accuracy of 0.816 and the area under the receiver operating characteristic curve (AUC) of 0.896 for the test datasets. The Case-Control Cox regression model (CoxCC) proved best for predicting survival with the Harrell’s C-index of 0.809 and 0.8 for the test datasets. Using SHAP we revealed the gene expression influence on the outputs of both models, thus enhancing the transparency of the prediction generation process. Conclusions: The results indicated that the developed models could serve as a valuable practical tool for clinicians, assisting them in diagnosing and determining optimal treatment strategies for patients with glioma. Full article

Background: Sex differences play a significant role in the epidemiology, biology, and outcomes of many cancers, including glioblastoma (GB), the most common and aggressive primary brain tumor. GB is more frequent in males, while females tend to have longer survival, though the underlying reasons for these differences remain poorly understood. Potential contributors include hormonal influences, sex-specific risk factors, and treatment disparities. Understanding these differences is critical for optimizing personalized treatment strategies. Methods: We conducted a retrospective analysis of patients with gliomas from a neuro-oncological database, with a primary focus on GB cases. Variables collected included sex, age, tumor type, molecular biomarker, and treatment modalities. The primary objective was to assess sex-based differences in tumor characteristics and outcomes, while the secondary objective was to identify predictors of time to progression and mortality. Results: The cohort comprised 125 GB, 48 astrocytomas, and 16 oligodendrogliomas, with no significant sex-based differences in age or tumor type distribution. Among GB patients, multifocality was more prevalent in females (14% vs. 8%; p = 0.01); also, EGFR amplification was more frequent in females (25.5% vs. 52.5%; p = 0.007). Males received chemotherapy (80% vs. 63%; p = 0.04) and radiotherapy (84% vs. 67%; p = 0.03) more frequently than females. Survival was positively associated with MGMT methylation (p = 0.002) and negatively associated with TERT mutation (p = 0.01). Multivariable analysis identified TERT mutation as a predictor of increased mortality (HR = 4.1; 95% CI: 1.2–14; p = 0.025), while multifocality predicted both mortality (HR = 2.3; 95% CI: 1.3–3.9; p = 0.003) and reduced time to progression (HR = 3.3; 95% CI: 1.02–10.6; p = 0.04). Conclusions: This study underscores the importance of sex and molecular profiling in GB management, revealing distinct patterns in tumor characteristics and treatment administration between males and females. Our findings advocate for the integration of sex-specific considerations and molecular profiling into clinical decision-making to improve outcomes for GB patients. Full article

Central nervous system (CNS) tumor with BCL6 corepressor gene BCOR/BCORL1 fusion is an extremely rare tumor entity, with fewer than 40 cases reported. These tumors are distinct from the WHO 2021-defined CNS tumor with BCOR internal tandem duplication. Even rarer are CNS tumors that match to the methylation class of CNS tumors with BCOR/BCORL1 fusion, but lack fusions and instead harbor truncating small nucleotide variants in BCOR. To our knowledge, only two other cases of this scenario have been previously reported. Due to their scarcity and morphological features that mimic oligodendrogliomas and ependymomas, the diagnosis of CNS tumor with BCOR/BCORL1 fusion can be challenging, and misdiagnoses are not uncommon. Histologic findings of Olig2 positivity with focal to absent GFAP warrant further evaluation for this tumor entity. Moreover, no standard of care therapy exists for these tumors, making treatment selection difficult. We present a case of a 37-year-old woman with a midline CNS tumor with BCOR/BCORL1 fusion, harboring a pathogenic BCOR c.626del (p.S209Cfs*7) (Exon 4) variant, who was successfully treated with definitive radiation therapy and adjuvant temozolomide. Notably, EMA showed focal strong dot-like perinuclear immunoreactivity, which has not been previously reported in these tumors. This case adds to the limited but growing body of evidence supporting the use of radiation and temozolomide in treating tumors matching the methylation class of CNS tumors with BCOR/BCORL1 fusion without a detectable fusion. Full article

Gliomas are incurable, heterogeneous brain tumors, with rare forms often constituting diagnostic and treatment challenges. Molecular diagnostics, mainly implemented through the World Health Organization (WHO) 2021 guidelines, have refined the classification, but highlight difficulties in diagnosing rare gliomas remain. This case series analyzes four patients with rare gliomas treated at the University Hospital, Ulm, between 2002 and 2024. Patients were selected based on unique histopathological features and long-term clinical follow-up. Clinical records, imaging, and histological data were reviewed. Molecular diagnostics followed WHO 2021 guidelines. Quality of life was assessed using standardized tools including the EQ-5D-5L, EQ VAS, the Distress Thermometer, and the Montreal Cognitive Assessment (MoCA). In the first case, a 51-year-old male’s diagnosis evolved from pleomorphic xanthoastrocytoma to a high-grade glioma with pleomorphic and pseudopapillary features, later identified as a neuroepithelial tumor with a PATZ1 fusion over 12 years. Despite multiple recurrences, extensive surgical interventions led to excellent outcomes. The second case involved a young female with long-term survival of astroblastoma, demonstrating significant improvements in both longevity and quality of life through personalized care. The third case involved a patient with oligodendroglioma, later transforming into glioblastoma, emphasizing the importance of continuous diagnostic reevaluation and adaptive treatment strategies, contributing to prolonged survival and quality of life improvements. Remarkably, the patient has achieved over 20 years of survival, including 10 years of being both therapy- and progression-free. The fourth case presents a young woman with neurofibromatosis type 1, initially misdiagnosed with glioblastoma based on histopathological findings. Subsequent molecular diagnostics revealed a subependymal giant cell astrocytoma-like astrocytoma, highlighting the critical role of early advanced diagnostic techniques. These cases underscore the importance of precise molecular diagnostics, individualized treatments, and ongoing diagnostic reevaluation to optimize outcomes. They also address the psychological impact of evolving diagnoses, stressing the need for comprehensive patient support. Even in complex cases, extensive surgical interventions can yield favorable results, reinforcing the value of adaptive, multidisciplinary strategies based on evolving tumor characteristics. Full article

Background/Objectives: This study evaluates intratumoral susceptibility signals (ITSS) as imaging markers for glioma grade prediction and their association with molecular and histopathologic features, in the context of the fifth edition of the World Health Organization Classification of Tumors of the Central Nervous System (WHO CNS5). Methods: We retrospectively analyzed patients with adult diffuse gliomas who underwent pretreatment magnetic resonance imaging. ITSS were semiquantitatively graded by two radiologists: grade 0 (no signal), grade 1 (1–5), grade 2 (6–10), and grade 3 (≥11). Relative cerebral blood volume (rCBV) and tumor volume were also obtained. Histopathologic features included tumor grade, Ki-67, mitotic count, necrosis, microvascular proliferation, and molecular alterations (isocitrate dehydrogenase [IDH], 1p/19q, cyclin-dependent kinase inhibitors 2A and 2B [CDKN2A/B], and p53). Regression models predicted tumor grade (low: 1–2, high: 3–4) using ITSS, tumor volume, and rCBV. ROC curves and diagnostic performance metrics were analyzed. Results: 99 patients were included. ITSS grading correlated with rCBV, tumor volume, mitotic count, Ki-67, and tumor grade (p < 0.001). ITSS grades 0–1 were associated with oligodendrogliomas and astrocytomas (p < 0.001), IDH mutations (p < 0.001), and 1p/19q co-deletions (p = 0.01). ITSS grades 2–3 were linked to glioblastomas (p < 0.001), necrosis (p < 0.001), microvascular proliferation (p < 0.001), and CDKN2A/B homozygous deletions (p = 0.02). Models combining ITSS with rCBV and volume showed AUC of 0.94 and 0.96 (p < 0.001), outperforming univariate models. Conclusions: Semiquantitative ITSS grading correlates with key histopathologic and molecular glioma features. Combined with perfusion and volumetric parameters, ITSS enhance non-invasive glioma grading, in alignment with WHO CNS5. Full article

In this review, we discuss how mutations in glioma are associated with prognosis and treatment efficacy. A fascinating characteristic of glioma and all cancers is that while common growth and developmental pathways are altered, the characteristic mutations are distinct depending on the specific type of tumor with concomitant prognoses. Next-generation sequencing, precision medicine, and artificial intelligence are boosting the employment of molecular biomarkers in cancer diagnosis and treatment. Understanding the biological underpinnings of distinct mutations on critical signaling pathways is crucial for developing novel therapies for glioma. Full article

Oligodendroglioma is a central nervous system tumor defined by IDH1/2 mutations and 1p/19q co-deletion. Current management involves maximal resection followed by radiotherapy/chemotherapy, yielding a 20-year survival rate of 37% for grade 3 tumors according to the WHO 2021 classification. As these tumors primarily affect young to middle-aged patients, novel therapies are urgently needed to improve outcomes. Immunotherapy has revolutionized tumor treatment by modulating immune responses. However, its application in oligodendrogliomas faces two major hurdles, including the immunosuppressive tumor microenvironment (TME) and the blood–brain barrier’s restrictive properties. This review first examines oligodendroglioma’s molecular alterations to refine diagnosis and guide targeted therapies. Next, we focus on the oligodendroglioma TME to evaluate emerging immunotherapies, including oncolytic viruses, immune checkpoint blockade, chimeric antigen receptor (CAR) T-cell therapy, and cancer vaccines. Finally, we discuss current challenges and future directions to overcome therapeutic limitations and advance treatment strategies. Full article

Aim: The management of low-grade gliomas (LGGs) is evolving with new insights into disease biology. Furthermore, recently, the phase III INDIGO¹ study highlighted the benefits of an IDH inhibitor, vorasidenib, in treating residual or recurrent grade 2 IDH-mutant gliomas following surgery alone. We aimed to characterise the current patterns of care for patients with LGGs in Australia and New Zealand, including the role of vorasidenib. Methods: An online survey examining respondents’ practice setting, caseload, and preferred treatment approach to three clinical scenarios was distributed through the Cooperative Trials Group for Neuro-Oncology, New Zealand Aotearoa Neuro-Oncology Society, and the Australian and New Zealand Society for Neuropathology in December 2023 with three reminders in April, June, and September of 2024. Results: The survey response rate was 19.6% (57/291), 87.7% from Australia, and 12.3% from New Zealand, spanning medical oncology (45.7%), pathology (22.8%), radiation oncology (17.5%), and neurosurgery (14.0%). Case 1 examined an IDH-mutant grade 2 astrocytoma following gross total resection. Observation alone was recommended by 93%. Case 2 examined an incompletely resected IDH-mutant grade 2 astrocytoma. If feasible, 38% recommended further surgery and 83% adjuvant chemotherapy and radiotherapy. After 12 months of disease stability, 53% of the respondents preferred vorasidenib over the existing therapies. Case 3 examined an incompletely resected IDH-mutant grade 3 oligodendroglioma. No respondents recommended observation alone, with 26% recommending salvage surgery and 97% recommending further chemotherapy and radiotherapy. Conclusions: This study describes current management practices for LGGs in Australia and New Zealand, showing ongoing variation and a cautious approach to integrating IDH inhibitors. This highlights the critical role of multidisciplinary team-based decision-making in increasingly complex clinical situations. Full article