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Open research questions in Glioma Diagnosis and Treatment

86 unresolved questions extracted from the limitations and future-work sections of 517 Glioma Diagnosis and Treatment papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Weller M, van den Bent M, Preusser M, Le Rhun E, Tonn JC et al (2021) EANO guidelines on the diagnosis and treatment of dif- fuse gliomas of adulthood.

    Long-term outcomes in IDH-wildtype (IDH-wt) gliomas with historical WHO grade 2 and 3 histology · 2026 · DOI

  • Due to its insidious clinical presentation and overlapping morphological characteristics, DICER1 -mutant PIS is often challenging to diagnose accurately, and no standardized therapeutic guidelines currently exist.

    Case Report: DICER1-mutant primary intracranial sarcoma with concurrent TP53, PDGFRA, and KEAP1 somatic mutations in a 5.5-year-old boy · 2026 · DOI

  • GBM tumors are heterogeneous, with four subtypes: mesenchymal-like (MES), astrocyte-like (AC), oligodendrocyte-progenitor-like (OPC), and neural-progenitor-like (NPC), but their interactions with immune cells remain unclear.

    Reprogramming of Glioblastoma-Immune Crosstalk to Overcome Immunotherapy Failure 2258791 · 2026 · DOI

  • Abstract Purpose Whether gross total resection (GTR) remains associated with survival among MGMT-methylated IDH-wildtype glioblastoma patients receiving chemoradiation remains uncertain.

    Extent of resection and survival in IDH-wildtype glioblastoma: interaction with MGMT status and chemoradiation · 2026 · DOI

  • Conclusions: These findings suggest that GRIA1–GRIA4 expression is associated with a synaptically enriched transcriptional program in LGG, although its cellular origin remains uncertain.

    AMPAR Subunit Gene Expression Marks a Synaptic Transcriptional State in Lower-Grade Glioma · 2026 · DOI

  • Our findings reveal that tiR5s are an underappreciated molecular feature of highly aggressive GBM tumors, supporting further investigation into their biological roles and prognostic utility in GBM.

    Small-RNA Profiling Links 5'-tRNA Halves to Post-therapeutic Disease Persistence and Poor Patient Survival in Glioblastoma · 2026 · DOI

  • Abstract Background: Telomerase reverse transcriptase promoter (TERTp) mutations represent one of the most common non-coding alterations across cancers, yet their functional convergence between rare brain gliomas and colorectal cancer (CRC) remains poorly defined.

    Abstract B031: Pan-cancer dissection of TERT promoter mutations in rare gliomas and colorectal cancer: shared vulnerabilities and therapeutic implications · 2026 · DOI

  • While prior studies show that H3K27M is essential for tumor initiation, its role in established tumors, tumor microenvironment (TME) regulation, and therapeutic response remain unclear.

    Oncohistone inhibition reshapes tumor-microenvironment communication in Diffuse Midline Glioma (DMG) · 2026 · DOI

  • Finally, using machine learning models applied to chronic neural recordings from tumor-bearing mice treated with or without standard-of-care chemotherapy (temozolomide for GBM), we accurately predicted tumor burden as inferred through in vivo bioluminescence imaging.

    Neural correlates of glioma progression using implanted neural interfaces · 2026 · DOI

  • Collectively, current studies demonstrate the integrating RT into organoid and feasibility of 23 bioprinted GBM models, but also reveal important limitations, including the lack of standardized irradi- ation protocols, incomplete reporting of dosimetric parameters, and the limited use of clinically rele- vant fractionation schemes.

    Modeling glioblastoma niche-by-niche: recent advancements in bioengineering of organotypic models of glioblastoma for precision medicine · 2026 · DOI

  • The molecular features of glioblastomas, particularly in relation to the ependymal and neural stem cell zone has mixed evidence with tumours contacting the SVZ show- ing worse survival.

    Glioblastoma invasion of neural stem cell regions; molecular patterns and survival rates · 2026 · DOI

  • However, an absolute EOR threshold below which resection did not improve survival could not be established, raising concerns about prior cutoff assessments.

    Extent of resection as an independent predictor of survival for patients with glioblastoma as defined by the new WHO 2021 classification · 2026 · DOI

  • Several limitations of this subanalysis must be acknowledged. First, the small sample size (n = 31) and marked subgroup imbalance, particularly the limited representation of oligodendroglioma (n = 2), reduce statistical power and the reliability of comparisons between histological subtypes. The retrospective design and the exclusion of 143 patients due to unmet inclusion criteria introduce potential selection bias, which may limit the generalizability of the findings. This is further compounded by the variable denominators used for advanced imaging analyses (ranging from n = 30 for diffusion to n = 4 for spectroscopy), suggesting that reported percentages may not fully represent the broader cohort. The study also lacks survival endpoints, such as overall survival, limiting the ability to assess the clinical and prognostic relevance of the imaging findings. Moreover, this descriptive subanalysis relies on imaging findings of recurrence based on histological subtypes from previous surgical interventions. Finally, several uncontrolled confounding factors, including variability in extent of resection, heterogeneity in adjuvant treatment protocols, and the overrepresentation of glioblastoma among older patients, may have influenced the observed correlations and recurrence patterns, necessitating cautious interpretation of the results. CONCLUsION This subanalysis highlights the heterogeneity of recurrence patterns in diffuse gliomas, both in terms of temporal dynamics and imaging phenotype. Glioblastoma demonstrated the shortest interval to recurrence, while lower-grade gliomas showed a more indolent course, supporting the well-established biological gradient across subtypes. At recurrence, most cases exhibited contrast enhancement, frequently adjacent to the surgical cavity, although multifocal and distant patterns were also observed. Advanced MRI techniques, including diffusion and perfusion imaging, were useful in identifying active tumors, reinforcing their complementary role in routine assessment. These findings underscore the importance of a structured and standardized follow-up approach in diffuse gliomas, aligned with international frameworks such as RANO 2.0 and EANO recommendations. Integrating conventional and advanced imaging into a coherent longitudinal workflow is essential for accurately distinguishing true progression from treatment-related changes and for guiding clinical decision-making. In this context, adapting standardized criteria to local practice through clearly defined imaging protocols and multidisciplinary collaboration may further optimize patient management in neuro-oncology.

    Clinical and imaging insights into diffuse glioma recurrence: a single-center retrospective subanalysis · 2026 · DOI

  • Potential limitations of this technique include addi- tional operative time and the reduced image quality of intraoperative MRI, which may restrict the accuracy of defining surgical margins using bone wax fiducials.

    Use of Bone Wax as a Marker in Cortex Glioma Resection under Limited Surgical Resources: First Experience and A Technical Note · 2026 · DOI

  • Abstract Background Brain tumor(BT) in children and adolescent and Young adults(AYA) show age-related heterogeneity, yet data on age-stratified incidence and multidisciplinary team (MDT)–based care from LMICs remain scarce.

    ID #763 From Infancy to Adolescent and Young Adulthood(AYA): Age-Stratified Landscape of Brain Tumors in a Large LMIC Cohort Highlighting Fragmented Multidisciplinary Care and Opportunities for Improvement · 2026 · DOI

  • Included studies were assessed according to the American Association of Neurological Surgeons and the Congress of Neurological Surgeons (AANS/CNS) grading criteria for medical evidence quality and strength of clinical recommendations. Two independent reviewers (O.A., B.G.) evaluated each study, with any disagreements resolved via discussion. The class of evidence (Class I, II, III) was determined based on cohort size, outcome measures, and follow-up duration.

    Surgical strategies and long-term survival for third ventricle chordoid gliomas: a systematic review and clinical algorithm · 2026 · DOI

  • Representing the most comprehensive analysis of chor- doid glioma to date, this systematic review synthesizes data from 198 patients across 94 studies, utilizing robust quality Page 19 of 23 456 assessment tools and Kaplan-Meier survival analysis to provide quantitative evidence. In addition to evaluating sur- gical outcomes, this study uniquely incorporates contempo- rary molecular profiling, particularly PRKCA and BRAF mutations, alongside detailed radiological characterization to inform clinical decision-making. These strengths, however, are counterbalanced by limi- tations inherent to the study of rare pathologies, including publication bias favoring positive or successful outcomes, significant heterogeneity in data reporting standards, and the absence of randomized controlled trials. Most critically, the interpretation of our findings is constrained by a pro- found, literature-wide reporting gap regarding long-term functional and QoL outcomes. Because historical literature almost exclusively highlights the extent of resection and recurrence-free survival while omitting standardized func- tional metrics (such as the SF-36 or long-term Karnofsky Performance Status), it is impossible to reliably determine whether the survival benefits of radical resection outweigh its severe functional costs. This widespread omission severely limits the ability to make definitive clinical recom- mendations regarding aggressive surgical clearance. Furthermore, while the statistical advantage of aggres- sive resection is evident in the pooled data, these findings remain highly vulnerable to selection bias, incomplete lon- gitudinal follow-up, and the scarcity of molecular details in historical case reports. The lack of individual-level patient data also precluded multivariable adjustment for confound- ers, and survival analyses based on pooled case reports and small case series cannot fully account for biological het- erogeneity or treatment variability, thereby limiting causal inference.

    Surgical strategies and long-term survival for third ventricle chordoid gliomas: a systematic review and clinical algorithm · 2026 · DOI

  • Col- lectively, these findings add to the limited literature on CT- based molecular prediction and highlight that, for selected targets, NCCT may provide diagnostically meaningful infor- mation approaching that reported for MRI, while remaining more accessible and less costly.

    CT-based deep learning radiogenomics for predicting key glioma genotypes (IDH, ATRX, EGFR, TP53) · 2026 · DOI

  • Given the lack of standardized protocols, clinical care must remain individualized and multidisciplinary, while future progress depends on multinational registries and advanced spatial molecular profiling to transition from empirical treatment toward personalized therapeutic realities.

    Concurrent de novo glioblastoma and meningiomatosis: a case report and systematic review of clinical, molecular, and topographical characteristics · 2026 · DOI

  • Although the tumor-suppressive role of miR-219 in glioma has been reported, its molecular mechanisms and therapeutic potential remain incompletely understood, especially in the context in combination with standard-of-care treatments.

    Overexpression of miR-219 as a potential therapeutic strategy of glioblastoma cells in vitro · 2026 · DOI

  • IDH-mutant gliomas stratified by glioma CpG island methylator phenotype (G-CIMP) into High (GCH) and Low (GCL) exhibit markedly divergent clinical outcomes, yet cellular and regulatory determinants of this distinction remain incompletely defined.

    Single-nucleus multiomics unveils malignant cellular states, regulatory architectures and microenvironmental reorganization across the G-CIMP epigenomic transition in IDH-mutant glioma · 2026 · DOI

  • Background: Abnormal growth patterns and impaired final height (FH) are well- recognized long-term complications of childhood medulloblastoma, however data regarding response to growth hormone treatment (GHT) and determinants of FH are scarce.

    PREDICTORS OF RESPONSE TO GROWTH HORMONE TREATMENT AND FINAL HEIGHT IN MEDULLOBLASTOMA SURVIVORS · 2026 · DOI

  • 1K27M) are observed in [~]80% of diffuse midline gliomas (DMG), which lead to aberrant gene regulation, yet the specific RNA polymerase II (Pol2) regulators that induce transcriptional dysregulation in DMG are not fully defined.

    Elongin B orchestrates chromatin and transcriptional programs in H3K27M-mutant diffuse midline glioma · 2026 · DOI

  • However, fluorescent probe performance varies across molecularly and histopathologically distinct entities, including IDH-wildtype glioblastoma, metastatic brain tumors (MBTs), and primary central nervous system lymphoma (PCNSL), and the mechanisms underlying this variability remain poorly understood.

    Comparison of Fluorescent Probes for IDH-Wildtype Glioblastoma, Metastatic Brain Tumors, and PCNSL: A Biomechanical Perspective · 2026 · DOI

  • Regnase-1, an endoribonuclease regulating the stability of inflammation- and immunity-related mRNAs, is a central modulator of immune responses; however, its role in glioma progression and immune modulation remains poorly understood.

    High Regnase-1 Expression Is Associated with an Immunosuppressive Tumor Microenvironment and Aggressive Features in Glioma Patients · 2026 · DOI

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86 open questions have been extracted from the limitations and future-work passages of 517 Glioma Diagnosis and Treatment papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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