Open research questions in Glioma Diagnosis and Treatment
1,365 gap statements mined from Glioma Diagnosis and Treatment papers in our 7.9M-paper local library, which holds 5,122 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.
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What the literature leaves open
The need to improve survival outcomes for pediatric patients with brain tumors while minimizing treatment-associated toxicity and preserving long-term quality of life. The limited efficacy of immune checkpoint inhibitors in most pediatric CNS tumors due to low tumor mutational burden and an immunosuppressive tumor microenvironment.
The limited use of intraoperative MRI in pediatric populations. The need to evaluate the benefits and limitations of its routine implementation in pediatric brain tumor surgery. The lack of understanding of intraoperative MRI's impact on the extent of resection in pediatric brain tumor surgery.
Intraoperative MRI in pediatric brain tumor surgery: Optimizing surgical decision-making and extent of resection · 2026 · DOIThe study only investigated the efficacy of inavolisib and ipatasertib in a limited number of cell lines and xenograft models. The study did not investigate the long-term effects of inavolisib and ipatasertib treatment. The study did not compare the efficacy of inavolisib and ipatasertib to other treatments.
CNS distribution and preclinical activity of the PI3K/AKT inhibitors inavolisib and ipatasertib in pediatric-type diffuse high-grade gliomas · 2026 · DOIThe lack of effective treatments for pediatric-type diffuse high-grade gliomas. The need for alternative molecular vulnerabilities to target in these tumors. The limited understanding of the PI3K/AKT signaling axis in these tumors.
CNS distribution and preclinical activity of the PI3K/AKT inhibitors inavolisib and ipatasertib in pediatric-type diffuse high-grade gliomas · 2026 · DOIThe complexity of glioma biology and the need for subtype-specific treatments. The challenge of translating preclinical findings to clinical practice. The need for further study to determine the tumor-selective mechanism of levetiracetam action.
The lack of understanding of the subtype-specific effects of levetiracetam on glioma proliferation and tumor burden. The inconsistent results of prior retrospective analyses regarding the effects of antiseizure medications on glioma patient survival. The need for further study on the therapeutic potential of levetiracetam in targeting GABAergic synapses in diffuse midline glioma.
There is a need to analyze a series of cases treated at the institution, focusing on pathological types and neurological function outcomes. The study provides valuable references for clinical management.
Pediatric intramedullary spinal tumors: Pathological and clinical outcomes in a 96-case single-institution cohort study · 2026 · DOIThe limited sample size, which may lead to Type II error. The need to integrate clinically relevant imaging biomarkers with standard prognostic factors to improve risk stratification.
MRI-based clinical radiomics nomogram for the prognostic prediction of adult diffuse low-grade gliomas · 2026 · DOIThe review highlights the need for further research to overcome these challenges and to develop effective strategies to overcome resistance to temozolomide in glioblastoma treatment.
Pharmacological targeting of xCT/system Xc− to modulate temozolomide sensitivity in glioma and glioblastoma preclinical models: a focused systematic review · 2026 · DOIThere is a need for noninvasive methods for preoperative determination of both the malignancy grade and the histomolecular profile of the tumor. The current methods for glioma grading have limitations. There is a lack of studies evaluating the diagnostic value of 3D pCASL perfusion in glioma grading according to the WHO 2021 classification.
Diagnostic value of 3D pCASL perfusion in glioma grading according to the WHO 2021 classification: a retrospective study of 530 cases · 2026 · DOILimited understanding of the relationship between intratumoral microbiota and clinical outcome. Difficulty in interpreting the apparent clustering of microbial profiles due to unequal dispersion between groups. Complexity of integrating grade-associated microbial features into prognostic models.
Intratumoral microbiota stratifies glioma malignancy and patient survival through metabolic associations · 2026 · DOIThe study notes that biopsy is commonly unfeasible in brainstem cases. The study notes that complete surgical resection is rarely feasible due to the critical anatomical location and infiltrative growth pattern. The study notes that the routine use of biopsy in children remains controversial.
Prevalence and Clinicoradiopathological Characterization of H3 K27-Altered Diffuse Midline Gliomas in Adults—A Retrospective Observational Study · 2026 · DOIResection of pediatric intramedullary spinal cord tumors remains surgically challenging. Many patients face risks of transient or permanent postoperative neurological impairment. The study notes that local recurrence after gross total resection remains rare in most patients with hemangioblastomas.
Pediatric intramedullary spinal tumors: Pathological and clinical outcomes in a 96-case single-institution cohort study · 2026 · DOILimited therapeutic options for diffuse gliomas. Poor characterization of amyloid-related pathways in gliomas. Complexity of analyzing transcriptomic data from large cohorts of patients.
Testing whether immunovascular and stromal states can stratify response to vascular-immune combination strategies. Spatial validation and functional perturbation in clinically annotated GBM samples.
A shared vascular-hypoxic transcriptional program is associated with immune organization in glioblastoma · 2026 · DOIClinical studies are needed to confirm whether maintenance chemotherapy produces survival benefits for patients with WHO grade 1 gliomas - Further research is needed to understand the role of chemotherapy in tumor control - More aggressive treatment for brainstem LGG should be pursued due to its generally favorable…
Delayed Imaging Response After Chemoradiotherapy in a Patient with Unresectable Brainstem Pilocytic Astrocytoma · 2026 · DOIThe sample size, though sufficient for initial model development, remains modest (N = 72) - Variable selection for the multivariable Cox proportional hazards model was not based solely on statistical significance to avoid Type II…
MRI-based clinical radiomics nomogram for the prognostic prediction of adult diffuse low-grade gliomas · 2026 · DOIInvestigate the relationship between imaging features and outcome in a larger cohort, - Examine the impact of gross-total resection on overall survival, - Explore the role of Ki-67 in predicting…
Outcomes after surgical resection of spinal ependymomas: extent of resection, imaging phenotype, and survival · 2026 · DOILimited characterization of historical cases, - Lack of specific laboratory or CSF data from outside centers, - Small sample size, - Limited understanding of the prognostic impact of a strictly cervical primary Non-WNT, Non-SHH…
Primary cervical multifocal medulloblastoma: a unique case report and review of the literature · 2026 · DOIInvestigation of the prognostic impact of a strictly cervical primary Non-WNT, Non-SHH medulloblastoma, - Study of the molecular mechanisms underlying the development of ectopic medulloblastomas, - Research on the optimal treatment approaches for medulloblastomas with aggressive biological…
Primary cervical multifocal medulloblastoma: a unique case report and review of the literature · 2026 · DOIFurther studies are needed to confirm the findings and to explore the potential of xCT/system Xc--relevant inhibitors in glioma/glioblastoma treatment, - Investigation of the effects of different xCT/system Xc--relevant inhibitors on TMZ sensitivity, - Elucidation of the underlying mechanisms of xCT/system Xc--relevant inhibition and ferroptosis…
Pharmacological targeting of xCT/system Xc− to modulate temozolomide sensitivity in glioma and glioblastoma preclinical models: a focused systematic review · 2026 · DOIThe study had a retrospective design, - The diagnosis was retained as NOS in cases where the available data were insufficient for a definitive integrated diagnosis, - The study included a limited number of patients with certain types…
Diagnostic value of 3D pCASL perfusion in glioma grading according to the WHO 2021 classification: a retrospective study of 530 cases · 2026 · DOIThe contralateral ROI was not standardized due to the limited scan volume, - The volume of contrast agent used for the preload was determined empirically, - The scan level was manually selected by an experienced…
CT Perfusion in the differential diagnosis of glioblastomas and primary central nervous system lymphomas · 2026 · DOIFurther studies are needed to evaluate the performance of CT perfusion in the differential diagnosis of glioblastomas and PCNSL, - The potential benefit of surgery in carefully selected patients with solitary and superficial lesions and more favorable clinical condition should be…
CT Perfusion in the differential diagnosis of glioblastomas and primary central nervous system lymphomas · 2026 · DOIRetrospective study, - Limited sample size, - Restricted to IDH wildtype cases, - No significant between-group differences in the frequency of involvement across different CNS…
Prevalence and Clinicoradiopathological Characterization of H3 K27-Altered Diffuse Midline Gliomas in Adults—A Retrospective Observational Study · 2026 · DOI
Most-cited papers in Glioma Diagnosis and Treatment
- Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma · New England Journal of Medicine · 2005 · 18,935 citations
- The 2021 WHO Classification of Tumors of the Central Nervous System: a summary · Neuro-Oncology · 2021 · 11,494 citations
- Comprehensive genomic characterization defines human glioblastoma genes and core pathways · Nature · 2008 · 6,755 citations
- MGMT Gene Silencing and Benefit from Temozolomide in Glioblastoma · New England Journal of Medicine · 2005 · 6,358 citations
- Identification of human brain tumour initiating cells · Nature · 2004 · 6,188 citations
- IDH1andIDH2Mutations in Gliomas · New England Journal of Medicine · 2009 · 5,154 citations
- An Integrated Genomic Analysis of Human Glioblastoma Multiforme · Science · 2008 · 4,987 citations
- Malignant Gliomas in Adults · New England Journal of Medicine · 2008 · 3,415 citations
- Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas · New England Journal of Medicine · 2015 · 2,809 citations
- A Randomized Trial of Bevacizumab for Newly Diagnosed Glioblastoma · New England Journal of Medicine · 2014 · 2,489 citations
Most recent work
- A human tumor-immune organoid model of glioblastoma · Cell Reports · 2026
- Immunosuppressive mechanisms and therapeutic interventions shaping glioblastoma immunity · Nature Cancer · 2026
- Cancer neuroscience: The past, the present, and the road ahead · Cell · 2026
- cIMPACT-NOW Update 12: Refining pathology-based risk stratification and grading for IDH-mutant gliomas · Neuro-Oncology · 2026
- M-PACT leverages cell-free DNA methylomes to achieve robust classification of pediatric brain tumors · Nature Cancer · 2026
- IDH-mutant gliomas arise from glial progenitor cells harboring the initial driver mutation · Science · 2026
- Microglia-glioblastoma crosstalk mediates glioblastoma invasion at the far infiltration zone · Immunity · 2026
- Reactive oligodendrocytes promote glioblastoma progression through CCL5/CCR5-mediated glioma stem cell maintenance · Neuron · 2026
- Meningeal blood vessel blockage enhances anti-glioblastoma immunity · Cell · 2026
- Targeting immunosuppressive network in glioblastoma: Emerging strategies to overcome immunodeficiency and enhance therapeutic efficacy · Acta Pharmaceutica Sinica B · 2026
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