Glioma is the umbrella class of primary central nervous system tumors that arise from glial cells or glial/neural precursor cells — encompassing astrocytic, oligodendroglial, ependymal, and mixed neuronal-glial lineages and spanning WHO CNS grades 1-4. Under the 5th-edition WHO Classification of Tumors of the Central Nervous System (WHO CNS5, 2021), gliomas are organized primarily by molecular type rather than histology alone, using a layered "integrated diagnosis." Adult-type diffuse gliomas collapse into three molecularly defined types (astrocytoma, IDH-mutant; oligodendroglioma, IDH-mutant and 1p/19q-codeleted; and glioblastoma, IDH-wildtype), while pediatric-type diffuse gliomas, circumscribed astrocytic gliomas, and ependymal tumors form separate families. Shared molecular axes — IDH1/2 mutation, 1p/19q codeletion, TERT promoter mutation, EGFR amplification, combined chromosome 7 gain / chromosome 10 loss (+7/-10), CDKN2A/B homozygous deletion, and H3 alterations — define entities and increasingly drive grading. This root entry captures the conserved glial-tumor mechanism and cross-references the molecularly/histologically defined children curated as standalone dismech entries.
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name: Glioma
creation_date: "2026-07-08T00:00:00Z"
category: Cancer
parents:
- neuroepithelial neoplasm
disease_term:
preferred_term: glioma
term:
id: MONDO:0021042
label: glioma
description: >-
Glioma is the umbrella class of primary central nervous system tumors that
arise from glial cells or glial/neural precursor cells — encompassing
astrocytic, oligodendroglial, ependymal, and mixed neuronal-glial lineages and
spanning WHO CNS grades 1-4. Under the 5th-edition WHO Classification of Tumors
of the Central Nervous System (WHO CNS5, 2021), gliomas are organized primarily
by molecular type rather than histology alone, using a layered "integrated
diagnosis." Adult-type diffuse gliomas collapse into three molecularly defined
types (astrocytoma, IDH-mutant; oligodendroglioma, IDH-mutant and
1p/19q-codeleted; and glioblastoma, IDH-wildtype), while pediatric-type diffuse
gliomas, circumscribed astrocytic gliomas, and ependymal tumors form separate
families. Shared molecular axes — IDH1/2 mutation, 1p/19q codeletion, TERT
promoter mutation, EGFR amplification, combined chromosome 7 gain / chromosome
10 loss (+7/-10), CDKN2A/B homozygous deletion, and H3 alterations — define
entities and increasingly drive grading. This root entry captures the conserved
glial-tumor mechanism and cross-references the molecularly/histologically
defined children curated as standalone dismech entries.
has_subtypes:
- name: Glioblastoma, IDH-Wildtype
description: >-
Most aggressive adult-type diffuse glioma (WHO grade 4), IDH-wildtype,
diagnosable by classic histology or by glioblastoma-defining molecular
features (TERT promoter mutation, EGFR amplification, and/or +7/-10). Curated
as a standalone dismech entry (Glioblastoma_IDH_Wildtype; MONDO:0850335).
evidence:
- reference: PMID:35869291
reference_title: "2021 WHO classification of tumours of the central nervous system: a review for the neuroradiologist."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The principal updates in adult tumours concern the molecular definition of glioblastoma, restructuring of diffuse gliomas, and the introduction of several new tumour types."
explanation: WHO CNS5 gives glioblastoma a molecular (IDH-wildtype) definition, the basis for this subtype.
- name: IDH-Mutant Astrocytoma
description: >-
Adult-type diffuse glioma (WHO grade 2-4) defined by IDH1/2 mutation without
1p/19q codeletion, commonly with ATRX loss and TP53 mutation; prognosis is
significantly better than IDH-wildtype glioblastoma. CDKN2A/B homozygous
deletion upgrades the tumor to grade 4. Curated as a standalone dismech entry
(IDH_Mutant_Astrocytoma; MONDO:0956994).
evidence:
- reference: PMID:36717507
reference_title: "Updates on the WHO diagnosis of IDH-mutant glioma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "For the first time molecular features are not only relevant for the classification of IDH-mutant gliomas but may impact grading as well."
explanation: IDH mutation (without 1p/19q codeletion) with astrocytic-lineage markers defines IDH-mutant astrocytoma under WHO CNS5, where molecular features also drive grading.
- name: IDH-Mutant and 1p/19q-Codeleted Oligodendroglioma
description: >-
Adult-type diffuse glioma (WHO grade 2-3) defined by the combination of
IDH1/2 mutation and whole-arm 1p/19q codeletion; generally the most
favorable-prognosis adult diffuse glioma. Curated as a standalone dismech entry
(IDH_Mutant_Oligodendroglioma; MONDO:0859592).
evidence:
- reference: PMID:36717507
reference_title: "Updates on the WHO diagnosis of IDH-mutant glioma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "For the first time molecular features are not only relevant for the classification of IDH-mutant gliomas but may impact grading as well."
explanation: IDH mutation status (with 1p/19q codeletion for oligodendroglioma) defines and grades this subtype under WHO CNS5.
- name: Diffuse Midline Glioma, H3 K27-Altered
description: >-
Pediatric-type diffuse high-grade glioma (WHO grade 4) of midline structures,
defined by loss of H3 K27 trimethylation (H3 K27M mutation or EZHIP
overexpression). Curated as a standalone dismech entry
(H3_K27_Altered_Diffuse_Midline_Glioma; MONDO:1060171).
evidence:
- reference: PMID:35869291
reference_title: "2021 WHO classification of tumours of the central nervous system: a review for the neuroradiologist."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "establishing separate tumour families for paediatric-type gliomas"
explanation: WHO CNS5 established separate paediatric-type glioma families, the framework under which diffuse midline glioma, H3 K27-altered is defined.
- name: Mixed Neuronal-Glial Tumor
description: >-
Tumors with combined neuronal and glial differentiation (e.g., ganglioglioma,
dysembryoplastic neuroepithelial tumor), typically low-grade and frequently
epilepsy-associated. Curated as a standalone dismech entry
(Mixed_Neuronal-Glial_Tumor; MONDO:0016729).
evidence:
- reference: PMID:35869291
reference_title: "2021 WHO classification of tumours of the central nervous system: a review for the neuroradiologist."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "revision of diagnostic criteria for some of the existing neoplasms"
explanation: WHO CNS5 revised diagnostic criteria across CNS tumour families, including the neuronal and mixed neuronal-glial tumours grouped here.
- name: Pilocytic Astrocytoma
description: >-
Circumscribed astrocytic glioma (WHO grade 1), the most common paediatric
glioma, typically driven by KIAA1549-BRAF fusion or BRAF V600E and a distinct
WHO CNS5 family from the adult-type diffuse gliomas. Curated as a standalone
dismech entry (Pilocytic_Astrocytoma; MONDO:0016691).
evidence:
- reference: PMID:35869291
reference_title: "2021 WHO classification of tumours of the central nervous system: a review for the neuroradiologist."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "WHO CNS5 places greater emphasis on organising tumours by molecular type to reflect biology"
explanation: WHO CNS5 organises tumours by molecular type; pilocytic astrocytoma is defined by its characteristic BRAF alteration within the circumscribed astrocytic glioma family.
pathophysiology:
- name: Glial-Lineage Neoplastic Transformation
description: >-
Gliomas arise from neoplastic transformation of glial cells or glial/neural
stem and progenitor cells, producing highly infiltrative (diffuse) or
circumscribed CNS tumors. Cell-of-origin lineage (astrocytic,
oligodendroglial, ependymal, or mixed neuronal-glial) together with molecular
alterations underpins the WHO CNS5 integrated diagnosis.
cell_types:
- preferred_term: glial cell
term:
id: CL:0000125
label: glial cell
- preferred_term: neural stem cell
term:
id: CL:0000047
label: neural stem cell
biological_processes:
- preferred_term: gliogenesis
term:
id: GO:0042063
label: gliogenesis
modifier: ABNORMAL
- preferred_term: cell population proliferation
term:
id: GO:0008283
label: cell population proliferation
modifier: INCREASED
downstream:
- target: IDH-Mutation Oncometabolite Epigenetic Reprogramming
description: Transformed glial-lineage cells acquire the canonical molecular lesions that define glioma type.
- target: TERT Promoter Mutation and Telomere Maintenance Reactivation
description: Transformed cells acquire TERT promoter mutation, a glioblastoma-defining lesion enabling replicative immortality.
- target: Chromosomal Copy-Number Alteration and Genomic Instability
description: Transformed cells acquire large-scale copy-number alterations (+7/-10, 1p/19q codeletion, CDKN2A/B loss) that define glioma type and grade.
- target: EGFR Amplification and RTK-RAS-PI3K Mitogenic Signaling
description: Transformed cells acquire EGFR amplification (a glioblastoma-defining lesion) driving constitutive mitogenic signaling.
- target: Diffuse Infiltrative Growth
description: Transformed cells infiltrate brain parenchyma along white-matter tracts.
evidence:
- reference: PMID:36534419
reference_title: "Adult type diffuse gliomas in the new 2021 WHO Classification."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Adult-type diffuse gliomas represent a group of highly infiltrative central"
explanation: Adult-type diffuse gliomas are highly infiltrative CNS tumors of glial lineage.
- name: IDH-Mutation Oncometabolite Epigenetic Reprogramming
description: >-
IDH1 or IDH2 mutation is the primary biological divider of adult-type diffuse
glioma. Mutant IDH acquires neomorphic activity producing the oncometabolite
D-2-hydroxyglutarate, which competitively inhibits
alpha-ketoglutarate-dependent dioxygenases (TET DNA demethylases and histone
demethylases),
yielding a glioma CpG-island methylator phenotype and a block in glial
differentiation. IDH-mutant tumors carry a more favorable prognosis than
IDH-wildtype.
cell_types:
- preferred_term: astrocyte
term:
id: CL:0000127
label: astrocyte
biological_processes:
- preferred_term: chromatin organization
term:
id: GO:0006325
label: chromatin organization
modifier: ABNORMAL
- preferred_term: demethylation
term:
id: GO:0070988
label: demethylation
modifier: DECREASED
- preferred_term: glial cell differentiation
term:
id: GO:0010001
label: glial cell differentiation
modifier: DECREASED
evidence:
- reference: PMID:36717507
reference_title: "Updates on the WHO diagnosis of IDH-mutant glioma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "For the first time molecular features are not only relevant for the classification of IDH-mutant gliomas but may impact grading as well."
explanation: IDH mutation is the defining molecular feature separating IDH-mutant from IDH-wildtype gliomas and informs grading.
- reference: PMID:38760442
reference_title: "IDH inhibition in gliomas: from preclinical models to clinical trials."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "D-2-HG promotes DNA and histone hypermethylation."
explanation: The IDH-mutant oncometabolite D-2-hydroxyglutarate drives DNA and histone hypermethylation, the epigenetic reprogramming underlying the glioma CpG-island methylator phenotype.
- reference: PMID:36534419
reference_title: "Adult type diffuse gliomas in the new 2021 WHO Classification."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Diagnosis of adult type diffuse gliomas, IDH"
explanation: WHO CNS5 anchors adult-type diffuse glioma diagnosis on IDH mutation status.
- name: TERT Promoter Mutation and Telomere Maintenance Reactivation
conforms_to: "enabling_replicative_immortality#Telomere Maintenance Reactivation"
description: >-
TERT promoter mutation reactivates telomerase, enabling telomere maintenance
and replicative immortality. TERT promoter mutation is one of the three
glioblastoma-defining molecular markers (with EGFR amplification and +7/-10)
and also occurs frequently in oligodendroglioma.
biological_processes:
- preferred_term: telomere maintenance
term:
id: GO:0000723
label: telomere maintenance
modifier: INCREASED
- preferred_term: cell population proliferation
term:
id: GO:0008283
label: cell population proliferation
modifier: INCREASED
downstream:
- target: Diffuse Infiltrative Growth
description: Telomerase reactivation confers replicative immortality that sustains continued tumor-cell proliferation and growth.
evidence:
- reference: PMID:38760442
reference_title: "IDH inhibition in gliomas: from preclinical models to clinical trials."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "bind the mutated TERT promoter and upregulate TERT expression"
explanation: RNA polymerase II binding the mutated TERT promoter upregulates TERT expression, reactivating telomerase and enabling telomere maintenance in glioma.
- name: EGFR Amplification and RTK-RAS-PI3K Mitogenic Signaling
conforms_to: "sustaining_proliferative_signaling#Constitutive Mitogenic Pathway Activation"
description: >-
EGFR amplification (often with the EGFRvIII variant) and related receptor
tyrosine kinase lesions drive constitutive RAS-MAPK and PI3K-AKT-mTOR
mitogenic signaling and growth-factor-independent proliferation. EGFR
amplification is one of the three glioblastoma-defining molecular features.
biological_processes:
- preferred_term: epidermal growth factor receptor signaling pathway
term:
id: GO:0007173
label: epidermal growth factor receptor signaling pathway
modifier: INCREASED
- preferred_term: cell population proliferation
term:
id: GO:0008283
label: cell population proliferation
modifier: INCREASED
downstream:
- target: Diffuse Infiltrative Growth
description: Sustained mitogenic signaling promotes tumor cell proliferation and invasion.
evidence:
- reference: PMID:37540408
reference_title: "SEOM-GEINO clinical guidelines for high-grade gliomas of adulthood (2022)."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "EGFR amplification, and TERT promoter mutation are diagnostic"
explanation: EGFR amplification is one of the glioblastoma-defining molecular alterations under WHO CNS5 (diagnostic of grade 4 IDH-wildtype glioblastoma). The RTK-RAS-PI3K signaling mechanism this node also describes still needs a dedicated source.
- name: Chromosomal Copy-Number Alteration and Genomic Instability
conforms_to: "genome_instability_mutation#Mutator Phenotype and Chromosomal Instability"
description: >-
Glioma types are defined in part by large-scale chromosomal copy-number
alterations: combined whole chromosome 7 gain and chromosome 10 loss (+7/-10)
and CDKN2A/B homozygous deletion in IDH-wildtype glioblastoma; whole-arm
1p/19q codeletion in oligodendroglioma; and CDKN2A/B loss upgrading IDH-mutant
astrocytoma to grade 4. These reflect underlying chromosomal instability.
biological_processes:
- preferred_term: chromosome organization
term:
id: GO:0051276
label: chromosome organization
modifier: ABNORMAL
downstream:
- target: Diffuse Infiltrative Growth
description: Chromosomal instability drives clonal evolution that sustains tumor progression and infiltrative growth.
evidence:
- reference: PMID:36717507
reference_title: "Updates on the WHO diagnosis of IDH-mutant glioma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "whole-arm 1p/19q codeletion and TERT promoter"
explanation: Whole-arm 1p/19q codeletion is a defining large-scale chromosomal copy-number alteration under WHO CNS5, exemplifying the copy-number changes this node describes.
- name: Diffuse Infiltrative Growth
description: >-
Diffuse gliomas grow by single-cell infiltration of brain parenchyma along
white-matter tracts and perivascular/subpial routes, precluding complete
surgical resection and driving recurrence despite therapy.
cell_types:
- preferred_term: glial cell
term:
id: CL:0000125
label: glial cell
biological_processes:
- preferred_term: cell migration
term:
id: GO:0016477
label: cell migration
modifier: INCREASED
evidence:
- reference: PMID:36534419
reference_title: "Adult type diffuse gliomas in the new 2021 WHO Classification."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Adult-type diffuse gliomas represent a group of highly infiltrative central"
explanation: Diffuse gliomas are characterized by highly infiltrative growth in the CNS.
phenotypes:
- name: Seizure
category: Neurological
frequency: FREQUENT
phenotype_term:
preferred_term: Seizure
term:
id: HP:0001250
label: Seizure
evidence:
- reference: PMID:37540408
reference_title: "SEOM-GEINO clinical guidelines for high-grade gliomas of adulthood (2022)."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The most prevalent symptoms include seizures"
explanation: Seizures are among the most prevalent presenting symptoms of glioma.
- name: Headache
category: Neurological
phenotype_term:
preferred_term: Headache
term:
id: HP:0002315
label: Headache
evidence:
- reference: PMID:37540408
reference_title: "SEOM-GEINO clinical guidelines for high-grade gliomas of adulthood (2022)."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "dysphagia, headache, confusion"
explanation: Headache is listed among the prevalent symptoms of high-grade glioma.
- name: Cognitive Impairment
category: Neurological
phenotype_term:
preferred_term: Cognitive impairment
term:
id: HP:0100543
label: Cognitive impairment
evidence:
- reference: PMID:37540408
reference_title: "SEOM-GEINO clinical guidelines for high-grade gliomas of adulthood (2022)."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The presence of neurological deficits and seizures can significantly impact quality of life."
explanation: Cognitive/neurological deficits are frequent, quality-of-life-limiting features of glioma.
- name: Aphasia
category: Neurological
phenotype_term:
preferred_term: Aphasia
term:
id: HP:0002381
label: Aphasia
evidence:
- reference: PMID:37540408
reference_title: "SEOM-GEINO clinical guidelines for high-grade gliomas of adulthood (2022)."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "aphasia, motor deficits, fatigue"
explanation: Aphasia is listed among the prevalent symptoms of high-grade glioma.
- name: Focal Motor Deficit
category: Neurological
phenotype_term:
preferred_term: Motor deficits
term:
id: HP:0001324
label: Muscle weakness
evidence:
- reference: PMID:37540408
reference_title: "SEOM-GEINO clinical guidelines for high-grade gliomas of adulthood (2022)."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "aphasia, motor deficits, fatigue"
explanation: Focal motor deficits are listed among the prevalent symptoms of high-grade glioma.
- name: Fatigue
category: Constitutional
phenotype_term:
preferred_term: Fatigue
term:
id: HP:0012378
label: Fatigue
evidence:
- reference: PMID:37540408
reference_title: "SEOM-GEINO clinical guidelines for high-grade gliomas of adulthood (2022)."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "aphasia, motor deficits, fatigue"
explanation: Fatigue is listed among the prevalent symptoms of high-grade glioma.
- name: Dysphagia
category: Neurological
phenotype_term:
preferred_term: Dysphagia
term:
id: HP:0002015
label: Dysphagia
evidence:
- reference: PMID:37540408
reference_title: "SEOM-GEINO clinical guidelines for high-grade gliomas of adulthood (2022)."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "dysphagia, headache, confusion"
explanation: Dysphagia is listed among the prevalent symptoms of high-grade glioma.
genetic:
- name: IDH1
gene_term:
preferred_term: IDH1
term:
id: hgnc:5382
label: IDH1
association: Somatic Missense Mutation
notes: >-
IDH1 (most often R132H) mutation defines IDH-mutant astrocytoma and
oligodendroglioma and is the primary molecular divider of adult-type diffuse
glioma. IDH-mutant tumors carry a more favorable prognosis than IDH-wildtype.
evidence:
- reference: PMID:36717507
reference_title: "Updates on the WHO diagnosis of IDH-mutant glioma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "For the first time molecular features are not only relevant for the classification of IDH-mutant gliomas but may impact grading as well."
explanation: IDH mutation is the defining, grading-relevant molecular feature of IDH-mutant glioma.
- name: IDH2
gene_term:
preferred_term: IDH2
term:
id: hgnc:5383
label: IDH2
association: Somatic Missense Mutation
notes: >-
IDH2 mutation is a less common alternative to IDH1 mutation and produces the
same D-2-hydroxyglutarate oncometabolite; it likewise defines IDH-mutant
adult-type diffuse glioma.
- name: TERT
gene_term:
preferred_term: TERT
term:
id: hgnc:11730
label: TERT
association: Promoter Mutation
notes: >-
TERT promoter mutation reactivates telomerase and is one of three
glioblastoma-defining molecular markers; also frequent in oligodendroglioma.
- name: EGFR
gene_term:
preferred_term: EGFR
term:
id: hgnc:3236
label: EGFR
association: Amplification
notes: >-
EGFR amplification (frequently with EGFRvIII) is one of three
glioblastoma-defining molecular features and activates RTK-RAS-PI3K signaling.
- name: 1p/19q
association: Whole-Arm Codeletion
notes: >-
Whole-arm codeletion of chromosomes 1p and 19q, together with IDH mutation,
defines oligodendroglioma. This is a chromosomal codeletion, not a single-gene
lesion, so it carries no gene_term.
- name: CDKN2A
gene_term:
preferred_term: CDKN2A
term:
id: hgnc:1787
label: CDKN2A
association: Homozygous Deletion
notes: >-
Homozygous deletion of CDKN2A (with the adjacent CDKN2B) is a WHO CNS5 grade-4
criterion in IDH-mutant astrocytoma and is common in IDH-wildtype glioblastoma.
- name: CDKN2B
gene_term:
preferred_term: CDKN2B
term:
id: hgnc:1788
label: CDKN2B
association: Homozygous Deletion
notes: >-
CDKN2B is co-deleted with CDKN2A at 9p21; homozygous CDKN2A/B loss upgrades
IDH-mutant astrocytoma to grade 4 and is frequent in IDH-wildtype glioblastoma.
- name: Germline Cancer-Predisposition Variants
association: Germline Pathogenic Variant
notes: >-
Most gliomas are sporadic, but a clinically meaningful minority carry
pathogenic germline variants (e.g., BRCA2, MUTYH, CHEK2, NF1, mismatch-repair
genes), with implications for surveillance and cascade testing.
evidence:
- reference: PMID:37720399
reference_title: "Prevalence of pathogenic germline variants in adult-type diffuse glioma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "We identified 152 glioma patients of which 15 (9.8%) had pathogenic"
explanation: About 10% of adult-type diffuse glioma patients harbored pathogenic germline variants in a paired tumor/normal series.
treatments:
- name: Maximal Safe Surgical Resection
description: >-
Maximal safe resection of the tumor; extent of resection is prognostic, but
the infiltrative nature of diffuse glioma precludes complete removal.
treatment_term:
preferred_term: Surgical Procedure
term:
id: NCIT:C15329
label: Surgical Procedure
- name: Radiotherapy
description: >-
Fractionated external-beam radiotherapy, a component of standard of care for
newly diagnosed high-grade glioma.
treatment_term:
preferred_term: Radiation Therapy
term:
id: NCIT:C15313
label: Radiation Therapy
evidence:
- reference: PMID:37540408
reference_title: "SEOM-GEINO clinical guidelines for high-grade gliomas of adulthood (2022)."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Radiotherapy (RT) and chemotherapy (CTX) are the current standard of care for"
explanation: Radiotherapy with chemotherapy is the standard of care for newly diagnosed high-grade glioma.
- name: Temozolomide Chemotherapy (Stupp Regimen)
description: >-
Alkylating chemotherapy with temozolomide given concomitantly with and
adjuvant to radiotherapy (Stupp regimen) for newly diagnosed high-grade
glioma/glioblastoma.
treatment_term:
preferred_term: Chemotherapy
term:
id: NCIT:C15632
label: Chemotherapy
therapeutic_agent:
- preferred_term: temozolomide
term:
id: CHEBI:72564
label: temozolomide
evidence:
- reference: PMID:37540408
reference_title: "SEOM-GEINO clinical guidelines for high-grade gliomas of adulthood (2022)."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Radiotherapy (RT) and chemotherapy (CTX) are the current standard of care for"
explanation: Chemotherapy (temozolomide) with radiotherapy is standard of care for high-grade glioma.
- name: Tumor Treating Fields (TTFields)
description: >-
Device-delivered alternating electric fields added to maintenance
temozolomide after chemoradiation in newly diagnosed glioblastoma; associated
with improved overall survival in real-world meta-analysis.
therapeutic_modality: DEVICE
treatment_term:
preferred_term: Tumor Treating Fields Therapy
term:
id: NCIT:C146882
label: Tumor Treating Fields Therapy
evidence:
- reference: PMID:37493865
reference_title: "Association of Tumor Treating Fields (TTFields) therapy with survival in newly diagnosed glioblastoma: a systematic review and meta-analysis."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "a significant improvement in OS for patients receiving"
explanation: Adding TTFields to standard chemoradiotherapy significantly improved overall survival (HR 0.63).
- name: Vorasidenib (Mutant IDH Inhibitor)
description: >-
Oral brain-penetrant inhibitor of mutant IDH1/IDH2; in the phase 3 INDIGO
trial it improved progression-free survival in residual/recurrent grade 2
IDH-mutant glioma after surgery only.
therapeutic_modality: SMALL_MOLECULE
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: vorasidenib
term:
id: NCIT:C152914
label: Vorasidenib
evidence:
- reference: PMID:37272516
reference_title: "Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "median progression-free survival, 27.7 months"
explanation: Vorasidenib significantly prolonged progression-free survival versus placebo in grade 2 IDH-mutant glioma.
- name: Dexamethasone (Peritumoral Edema Management)
description: >-
Corticosteroid used to control peritumoral vasogenic edema and mass-effect
symptoms; supportive rather than disease-modifying.
therapeutic_modality: SMALL_MOLECULE
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: dexamethasone
term:
id: CHEBI:41879
label: dexamethasone
- name: Levetiracetam (Seizure Management)
description: >-
First-line antiepileptic monotherapy for glioma-associated seizures;
prophylactic use in seizure-naive patients is not generally recommended.
therapeutic_modality: SMALL_MOLECULE
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: levetiracetam
term:
id: CHEBI:6437
label: levetiracetam
prevalence:
- population: Belgium (adult-type diffuse glioma)
measure_type: ANNUAL_INCIDENCE
prevalence_class: BAND_1_9_PER_100000
rate_per_100000: 8.55
notes: >-
Age-standardized incidence rate of diffuse adult-type glioma in Belgium
(2017-2019), molecular era; 6.72 per 100,000 person-years for grade 4 lesions.
evidence:
- reference: PMID:37651614
reference_title: "Epidemiology and survival of adult-type diffuse glioma in Belgium during the molecular era."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The age-standardized incidence rate of diffuse adult-type glioma in Belgium was"
explanation: Population-registry age-standardized incidence for adult-type diffuse glioma.
- population: United States (all primary brain/CNS tumors)
measure_type: ANNUAL_INCIDENCE
prevalence_class: BAND_1_9_PER_100000
rate_per_100000: 6.89
notes: >-
CBTRUS (US, 2017-2021): gliomas accounted for 22.9% of all primary brain/CNS
tumors; malignant brain/CNS tumor incidence 6.89 per 100,000.
evidence:
- reference: PMID:39371035
reference_title: "CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2017-2021."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Gliomas accounted for 22.9% of all tumors."
explanation: CBTRUS population registry reports glioma share of primary CNS tumors and malignant CNS tumor incidence.
clinical_trials:
- name: NCT04164901
phase: PHASE_III
status: COMPLETED
description: >-
INDIGO: phase 3, randomized, double-blind, placebo-controlled trial of
vorasidenib in residual or recurrent grade 2 IDH1/IDH2-mutant glioma after
surgery only.
target_phenotypes:
- preferred_term: Seizure
term:
id: HP:0001250
label: Seizure
evidence:
- reference: clinicaltrials:NCT04164901
reference_title: "A Phase 3, Multicenter, Randomized, Double-blind, Placebo-Controlled Study of AG-881 in Subjects With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation"
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "comparing the efficacy of vorasidenib to placebo in participants with residual or recurrent Grade 2 glioma with an IDH1 or IDH2 mutation who have undergone surgery as their only treatment."
explanation: Registered phase 3 trial establishing vorasidenib efficacy in grade 2 IDH-mutant glioma.
datasets:
- accession: geo:GSE339484
title: RNA-seq profiling of 14 paired primary and recurrent glioma cases
description: Glioma recurrence remains a major clinical challenge and is associated with poor patient outcomes. To characterize transcriptomic alterations associated with tumor recurrence, we performed bulk RNA sequencing on paired primary and recurrent glioma tissue specimens from 14 patients. According to the 2021 World Health Organization (WHO) Classification of Central Nervous System Tumors, glioblastoma is defined as IDH-wildtype (IDH-wt), CNS WHO grade 4. Based on these criteria, 11 paired cases were classified as glioblastoma (IDH-wt, grade 4), while three paired cases with IDH-mutant, grade 3 gliomas were included as a comparison group.
organism:
preferred_term: human
term:
id: NCBITaxon:9606
label: Homo sapiens
data_type: BULK_RNA_SEQ
sample_count: 28
publication: PMID:40658067
notes: Identified by GEO DataSets index search for Glioma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
- accession: geo:GSE327029
title: KPNA3 drives temozolomide resistance in glioblastoma by upregulating MGMT and activating STAT3 to sustain glioma stem cells
description: Glioblastoma (GBM) invariably develops resistance to temozolomide (TMZ), the frontline chemotherapeutic agent, leading to treatment failure. The molecular mechanisms underlying this resistance remain incompletely understood. Here, we identify karyopherin subunit alpha 3 (KPNA3) as a novel and critical driver of TMZ resistance. Through integrated bioinformatics analysis of temozolomide-resistant glioma cells (SF126R) and patient databases, we found KPNA3 expression is elevated in TMZ-resistant contexts and correlates with poor prognosis in TMZ-treated patients.
organism:
preferred_term: human
term:
id: NCBITaxon:9606
label: Homo sapiens
data_type: BULK_RNA_SEQ
sample_count: 12
publication: PMID:42295990
notes: Identified by GEO DataSets index search for Glioma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
- accession: geo:GSE298358
title: Endothelins influences the proliferation-migration balance of IDH1-mutant glioma cells and promotes proneural to mesenchymal transition [RNAseq-Gb7-HUVEC]
description: Adult diffuse gliomas are the deadliest brain tumours including IDH-wildtype glioblastomas of worst prognosis and diffuse low grade IDH-mutant astrocytomas and oligodendrogliomas. These glial tumours display distinct tumoral cell population defeating current therapies. Our group has unveiled the role of NOTCH signalling in glioblastoma cell plasticity and in the conversion of oligodendrocytic-like to astrocytic-like tumoral cells in IDH-mutant low-grade gliomas which escalate inevitably to higher grade malignant gliomas.
organism:
preferred_term: human
term:
id: NCBITaxon:9606
label: Homo sapiens
data_type: BULK_RNA_SEQ
sample_count: 12
publication: PMID:42026941
notes: Identified by GEO DataSets index search for Glioma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
- accession: ega:EGAS00001000579
title: Mutational analysis reveals the origin and therapy-driven evolution of recurrent glioma
description: Tumor recurrence is a leading cause of cancer mortality. Therapies for recurrent disease may fail, at least in part, because the genomic alterations driving the growth of recurrences are distinct from those in the initial tumor. To explore this hypothesis, we sequenced the exomes of 23 initial low-grade gliomas and recurrent tumors resected from the same patients. In 43% of cases, at least half of the mutations in the initial tumor were undetected at recurrence, including driver mutations inTP53, ATRX, SMARCA4, and BRAF; this suggests that recurrent tumors are often seeded by cells derived from the initial tumor at a very early stage of their evolution.
organism:
preferred_term: human
term:
id: NCBITaxon:9606
label: Homo sapiens
data_type: WES
publication: PMID:24336570
notes: 'European Genome-phenome Archive study, matched because the disease is named in the study''s own title ("Glioma"); description-level mentions were not accepted. EGA study_type: Exome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.'
- accession: ega:EGAS00001001258
title: Search for new loci and low-frequency variants influencing glioma risk by exome-array analysis
description: To identify protein altering variants (PAVs) for glioma we analysed Illumina HumanExome BeadChip exome array data on 1,882 glioma cases and 8,079 controls from three independent European populations. In addition to single variant tests we incorporated information on the predicted functional consequences of PAVs and analysed sets of genes with a higher likelihood of having a role in glioma on the basis of the profile of somatic mutations documented by large-scale sequencing initiatives. Globally there was a strong relationship between effect size and SNPs predicted to be damaging (P=2.29x10-49); however, these variants which are most likely to impact on risk, are rare (MAF<5%).
organism:
preferred_term: human
term:
id: NCBITaxon:9606
label: Homo sapiens
notes: 'European Genome-phenome Archive study, matched because the disease is named in the study''s own title ("Glioma"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.'
- accession: ega:EGAS00001001437
title: Chromatin immunoprecipitation linked to next-generation whole genome sequencing (ChIP-Seq) for H3K36me3 in paediatric high grade glioma cell lines KKNS4 and SF188 with and without a G34V mutation in H3F3A
description: Glioblastomas of children and young adults have a median survival of only 12-15months and are clinically and biologically distinct from histologically similar cancers in older adults1. They are defined by highly specific mutations in the gene encoding the histone H3.3 variant H3F3A2, occurring either at or close to key residues marked by methylation for regulation of transcription – K27 and G34. We performed chromatin immunoprecipitation linked to next-generation whole genome sequencing (ChIP-Seq) for H3K36me3 in order to test the hypothesis that, rather than total H3K36me3, the G34V mutation may instead result in differential binding of the trimethyl mark throughout the genome.
organism:
preferred_term: human
term:
id: NCBITaxon:9606
label: Homo sapiens
notes: 'European Genome-phenome Archive study, matched because the disease is named in the study''s own title ("Glioma"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.'
- accession: metabolomics_workbench:ST000199
title: IDH1 and Glioma knockdown idh1 (part II)
notes: Located via OmicsDI, which aggregates across omics repositories; this record comes from metabolomics_workbench. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title ("Glioma"). Retrieved 2026-08-02.
- accession: metabolomics_workbench:ST001064
title: Nude mice orthotopically implanted with human glioma cell lines
organism:
preferred_term: mouse
term:
id: NCBITaxon:10090
label: Mus musculus
data_type: METABOLOMICS
notes: Located via OmicsDI, which aggregates across omics repositories; this record comes from metabolomics_workbench. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title ("Glioma"). Retrieved 2026-08-02.
- accession: metabolomics_workbench:ST000820
title: '2 hydroxyglutarate prodution in neurospheres from IDH1 mouse glioma model #2'
organism:
preferred_term: mouse
term:
id: NCBITaxon:10090
label: Mus musculus
data_type: METABOLOMICS
notes: Located via OmicsDI, which aggregates across omics repositories; this record comes from metabolomics_workbench. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title ("Glioma"). Retrieved 2026-08-02.
references:
- reference: PMID:35869291
title: "2021 WHO classification of tumours of the central nervous system: a review for the neuroradiologist."
findings: []
- reference: PMID:36717507
title: "Updates on the WHO diagnosis of IDH-mutant glioma."
findings: []
- reference: PMID:36534419
title: "Adult type diffuse gliomas in the new 2021 WHO Classification."
findings: []
- reference: PMID:38927556
title: "The 2021 World Health Organization Central Nervous System Tumor Classification: The Spectrum of Diffuse Gliomas."
findings: []
- reference: PMID:39371035
title: "CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2017-2021."
findings: []
- reference: PMID:38760442
title: "IDH inhibition in gliomas: from preclinical models to clinical trials."
findings: []
Question: You are an expert researcher providing comprehensive, well-cited information.
Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies
Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.
Please provide a comprehensive research report on Glioma covering all of the disease characteristics listed below. This report will be used to populate a disease knowledge base entry. Be thorough and cite primary literature (PMID preferred) for all claims.
For each section, suggested databases/resources are listed. These are the first places you should search for information on each topic.
Search first: OMIM, Orphanet, ICD-10/ICD-11, MeSH, PubMed
Search first: PubMed, Cochrane Library, UpToDate, clinical guidelines, ClinVar, ClinGen, GWAS Catalog, PheGenI, CTD, CDC, WHO, epidemiological databases
Search first: PubMed, Cochrane Library, clinical trial databases, GWAS Catalog, gnomAD, WHO, CDC, nutrition databases
Search first: CTD, PubMed, PheGenI, GxE databases
Search first: HPO (Human Phenotype Ontology), OMIM, Orphanet, PubMed, clinicaltrials.gov, MedDRA, SNOMED CT, DECIPHER, LOINC
For each phenotype, provide: - Phenotype type: symptoms, clinical signs, physical manifestations, behavioral changes, or laboratory abnormalities
For symptoms/signs: HPO, OMIM, Orphanet, PubMed For behavioral changes: HPO, DSM, RDoC (Research Domain Criteria), PubMed For laboratory abnormalities: LOINC, SNOMED CT, LabTests Online, PubMed - Phenotype characteristics: Search first: OMIM, Orphanet, HPO, PubMed - Age of symptom onset (neonatal, childhood, adult-onset, late-onset) - Symptom severity (mild, moderate, severe, variable) - Symptom progression (stable, progressive, episodic, fluctuating) - Frequency among affected individuals (percentage or qualitative) - Quality of life impact: Effects on daily functioning and well-being (per-phenotype when possible) Search first: EQ-5D database, SF-36, WHO QOL databases, PubMed - Suggest HPO (Human Phenotype Ontology) terms for each phenotype
Search first: OMIM, ClinVar, HGMD, Ensembl, NCBI Gene
Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth
Search first: DECIPHER, ClinVar, ECARUCA, UCSC Genome Browser
Search first: CTD (Comparative Toxicogenomics Database), TOXNET, PubMed, EPA databases
Search first: CDC databases, WHO, PubMed, NHANES
Search first: NCBI Taxonomy, ViPR, BV-BRC, MicrobeDB, GIDEON
Search first: KEGG, Reactome, WikiPathways, PathBank, BioCyc
Search first: Gene Ontology (GO), Reactome, KEGG, PubMed
Search first: UniProt, PDB (Protein Data Bank), InterPro, Pfam, AlphaFold
Search first: KEGG, BioCyc, HMDB (Human Metabolome Database), BRENDA
Search first: ImmPort, Immunome Database, IEDB, Gene Ontology
Search first: PubMed, Gene Ontology, Reactome
Search first: BRENDA, UniProt, KEGG, OMIM, PubMed
Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth
For each mechanism, describe: - The causal chain from initial trigger to clinical manifestation - Which mechanisms are upstream vs downstream - What cell types and biological processes are involved - Suggest GO terms for biological processes and CL terms for cell types
Search first: Uberon, FMA (Foundational Model of Anatomy), OMIM, HPO, ICD-11, MeSH, SNOMED CT
Search first: Uberon, Human Protein Atlas, Cell Ontology, Human Cell Atlas, CellMarker, PanglaoDB
Search first: Gene Ontology (Cellular Component), UniProt, Human Protein Atlas
Search first: OMIM, Orphanet, HPO, PubMed
Search first: Disease registries, longitudinal cohort databases, natural history studies, PubMed, Orphanet, OMIM
Search first: Orphanet, CDC, WHO, GBD (Global Burden of Disease), national registries, SEER, disease registries
Search first: GTR (Genetic Testing Registry), GeneReviews, ClinGen
For each treatment, suggest MAXO (Medical Action Ontology) terms where applicable.
Search first: CDC vaccine schedules, WHO immunization, FDA vaccine database
Search first: CDC, WHO, behavioral intervention databases, Cochrane Library
Search first: NSGC resources, ACMG guidelines, GeneReviews
Search first: Clinical guidelines, FDA approvals, PubMed
Search first: NCBI Taxonomy
Search first: VBO (Vertebrate Breed Ontology)
Search first: NCBI Gene
Structure your response as a comprehensive narrative organized by the sections above. For each section, provide: - Factual content with specific details (numbers, percentages, gene names, variant nomenclature) - Ontology term suggestions (HPO, GO, CL, UBERON, CHEBI, MAXO, MONDO) where applicable - Evidence citations with PMIDs - Direct quotes from abstracts to support key claims - Clear indication when information is not available or not applicable for this disease
This report will be used to populate a disease knowledge base entry with: - Pathophysiology descriptions with causal chains - Gene/protein annotations (HGNC, GO terms) - Phenotype associations (HP terms) with frequencies - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Treatment annotations (MAXO terms) - Evidence items with PMIDs and exact abstract quotes - Epidemiology, prognosis, diagnostic, and prevention information - Animal model descriptions with phenotype recapitulation details
Glioma is an umbrella term for primary central nervous system (CNS) tumors with glial or glial‑precursor lineage features; modern classification is based on integrated diagnosis combining histopathology with molecular alterations rather than morphology alone. (osborn2022the2021world pages 1-3, mcnamara20222021whoclassification pages 1-6)
In WHO CNS5 (5th edition, published 2021), adult-type diffuse gliomas were simplified into three principal, molecularly defined types: (i) astrocytoma, IDH-mutant; (ii) oligodendroglioma, IDH-mutant and 1p/19q-codeleted; (iii) glioblastoma, IDH-wildtype, with grading embedded within type (“within-type grading”). (reuss2023updatesonthe pages 1-2, mcnamara20222021whoclassification pages 6-9, osborn2022the2021world pages 1-3)
WHO CNS5 also emphasizes layered reporting, where the “integrated diagnosis” is presented as the top line, followed by histologic diagnosis, WHO grade, and the key molecular information supporting the classification. (osborn2022the2021world pages 1-3)
Key terminology changes affect how older literature maps onto WHO CNS5. Notably, “glioblastoma” is reserved for IDH‑wildtype diffuse astrocytic tumors; tumors historically called “IDH‑mutant glioblastoma” are now astrocytoma, IDH‑mutant, CNS WHO grade 4. (reuss2023updatesonthe pages 1-2, mcnamara20222021whoclassification pages 6-9)
| Concept | Common synonyms / legacy terms | Key defining features (short) | Primary authoritative source (URL + year) |
|---|---|---|---|
| Glioma (broad) | Glial tumor; glial neoplasm; diffuse glioma (when infiltrative subset is intended) | Broad umbrella for primary CNS tumors arising from glial or glial-precursor lineages; current WHO CNS5 diagnosis is integrated, combining histology with molecular features rather than morphology alone (osborn2022the2021world pages 1-3, mcnamara20222021whoclassification pages 1-6) | Louis et al., The 2021 WHO Classification of Tumors of the Central Nervous System: a summary — https://doi.org/10.1093/neuonc/noab106 (2021) |
| Adult-type diffuse glioma | Adult diffuse glioma; infiltrating adult glioma; diffuse astrocytic/oligodendroglial tumor | WHO CNS5 simplifies adult diffuse gliomas into 3 molecularly defined types: astrocytoma, IDH-mutant; oligodendroglioma, IDH-mutant and 1p/19q-codeleted; glioblastoma, IDH-wildtype. Uses integrated/layered diagnosis and molecular grading (mcnamara20222021whoclassification pages 6-9, osborn2022the2021world pages 1-3) | McNamara et al., 2021 WHO classification of tumours of the central nervous system: a review for the neuroradiologist — https://doi.org/10.1007/s00234-022-03008-6 (2022) |
| Astrocytoma, IDH-mutant | Diffuse astrocytoma, IDH-mutant; anaplastic astrocytoma, IDH-mutant; legacy “IDH-mutant glioblastoma” now grade 4 astrocytoma | Defined by IDH1 or IDH2 mutation with astrocytic lineage; typically supported by ATRX loss/mutation and TP53 alteration or absence of 1p/19q codeletion; graded CNS WHO 2–4, and CDKN2A/B homozygous deletion can justify grade 4 (reuss2023updatesonthe pages 1-2, mcnamara20222021whoclassification pages 6-9, antonelli2022adulttypediffuse pages 1-2) | Reuss, Updates on the WHO diagnosis of IDH-mutant glioma — https://doi.org/10.1007/s11060-023-04250-5 (2023) |
| Oligodendroglioma, IDH-mutant and 1p/19q-codeleted | Oligodendroglioma, IDH-mutant, 1p/19q-codeleted; anaplastic oligodendroglioma (legacy grade-based term) | Diffusely infiltrating glioma defined by both IDH mutation and whole-arm 1p/19q codeletion; often associated with TERT promoter, CIC, and FUBP1 alterations; graded CNS WHO 2–3 (reuss2023updatesonthe pages 1-2, gue2024the2021world pages 19-21) | Louis et al., The 2021 WHO Classification of Tumors of the Central Nervous System: a summary — https://doi.org/10.1093/neuonc/noab106 (2021) |
| Glioblastoma, IDH-wildtype | GBM; primary glioblastoma; glioblastoma multiforme (older term) | In WHO CNS5, the term “glioblastoma” is reserved for adult diffuse astrocytic glioma that is IDH-wildtype; diagnosis may be made by classic histology or by molecular features such as TERT promoter mutation, EGFR amplification, or combined whole chromosome 7 gain / whole chromosome 10 loss (+7/−10) even without necrosis or microvascular proliferation (mcnamara20222021whoclassification pages 6-9, osborn2022the2021world pages 1-3, mcnamara20222021whoclassification pages 1-6) | Osborn et al., The 2021 World Health Organization Classification of Tumors of the Central Nervous System: What Neuroradiologists Need to Know — https://doi.org/10.3174/ajnr.45-12.s15 (2022) |
Table: This table summarizes key WHO CNS5 glioma concepts, including current terminology, common legacy names, and the molecular features that define each entity. It is useful for normalizing disease names and aligning older literature with current integrated CNS tumor classification.
This report primarily synthesizes aggregated disease-level resources (WHO CNS5, CBTRUS population registry report) and cohort/registry studies, plus selected clinical guidelines and trials. (reuss2023updatesonthe pages 1-2, price2024cbtrusstatisticalreport pages 2-3, hainfellner2024glioblastomainthe pages 1-3)
WHO CNS5 frames adult diffuse glioma causation and taxonomy around canonical molecular alterations. For example: * Astrocytoma, IDH‑mutant is defined by IDH1/IDH2 mutation and is commonly associated with TP53 and ATRX alterations (astrocytic lineage) and generally more favorable outcomes than IDH‑wildtype tumors. (reuss2023updatesonthe pages 1-2) * Oligodendroglioma, IDH‑mutant and 1p/19q-codeleted is defined by the combination of IDH mutation and whole-arm 1p/19q codeletion (often alongside TERT promoter mutation, CIC, FUBP1), and tends to be the most favorable‑prognosis adult diffuse glioma category. (reuss2023updatesonthe pages 1-2, gue2024the2021world pages 19-21) * Glioblastoma, IDH‑wildtype can be diagnosed by classic histology or by glioblastoma‑defining molecular features (e.g., TERT promoter mutation, EGFR amplification, or combined +7/−10), even when histologic hallmarks are absent. (mcnamara20222021whoclassification pages 6-9, osborn2022the2021world pages 1-3)
A 2023 single-institution paired tumor/normal sequencing series of 152 adult-type diffuse glioma patients reported pathogenic germline variants in 9.8% (15/152), with higher prevalence in glioblastoma, IDH‑wildtype (13.1%) than in IDH‑mutant astrocytoma (7.1%) or oligodendroglioma (3.8%). (mcdonald2023prevalenceofpathogenic pages 1-2, mcdonald2023prevalenceofpathogenic pages 5-7)
Most frequent germline pathogenic variants in that cohort were BRCA2, MUTYH, and CHEK2 (each 20% of pathogenic variants), with additional variants in BRCA1, ATM, NF1, MSH2, MSH3. (mcdonald2023prevalenceofpathogenic pages 1-2, mcdonald2023prevalenceofpathogenic pages 5-7)
Implementation gap: only 40% of patients with pathogenic germline variants were referred to genetics, despite potential implications for surveillance and family cascade testing. (mcdonald2023prevalenceofpathogenic pages 2-3, mcdonald2023prevalenceofpathogenic pages 5-7)
For pediatric CNS tumors (including glioma subtypes within the broader category), an AACR Cancer Predisposition Working Group update states that germline predisposition incidence “continues to grow” and that ~50% of patients may be the first in a family identified to have a predisposition; identification enables cascade testing and early tumor surveillance and can impact management. (hansford2024updateoncancer pages 1-2)
No high-quality, specific environmental or protective factors were retrieved with tool evidence in this run; therefore, none are asserted.
No evidence was retrieved in this run for protective factors in glioma risk; therefore, none are asserted.
No gene–environment interaction evidence was retrieved in this run; therefore, none are asserted.
Clinical guideline evidence emphasizes that neurologic symptoms can substantially impair quality of life in high-grade glioma. A SEOM-GEINO guideline notes common symptoms including seizures, cognitive deficits, drowsiness, dysphagia, headache, confusion, aphasia, motor deficits, fatigue, and dyspnea, varying with tumor size, location, and edema. (segura2023seomgeinoclinicalguidelines pages 2-4)
Supportive care priorities include management of brain edema (e.g., dexamethasone) and seizures (levetiracetam first-line monotherapy; prophylactic antiepileptic use generally not recommended), with attention to neurocognitive impairment as a frequent disabling complication. (segura2023seomgeinoclinicalguidelines pages 7-8, segura2023seomgeinoclinicalguidelines pages 8-9)
(These HPO IDs are provided as standard ontology mappings; this run did not retrieve HPO source documents, so they are presented as ontology suggestions rather than evidence-derived claims.)
WHO CNS5/related reviews emphasize the following diagnostic anchors: * IDH1/IDH2 mutations define IDH-mutant astrocytoma and oligodendroglioma categories; TP53/ATRX alterations support astrocytic lineage, while 1p/19q codeletion supports oligodendroglial lineage. (reuss2023updatesonthe pages 1-2, mcnamara20222021whoclassification pages 6-9) * Glioblastoma, IDH-wildtype may be defined molecularly by TERT promoter mutation, EGFR amplification, +7/−10 copy-number pattern. (mcnamara20222021whoclassification pages 6-9)
DNA methylation profiling is increasingly important for CNS tumor diagnosis and subgrouping. A 2024 review characterizes methylation profiling as a key diagnostic tool, with classifier matching scores ≥0.9 in ~50–65% of samples and “diagnostic impact” in ~10–20% of cases. (bertero2024molecularneuropathologyan pages 3-4)
In pediatric low-grade glioma diagnostics, a 2023 international registry analysis (LOGGIC) reported that adding RNA-seq increased driver detection from 75% to 97% (121/125), with 27/125 (22%) having drivers detected only by RNA-seq (22 actionable), supporting routine RNA-seq integration when standard approaches are unrevealing. (hardin2023loggiccorebioclinical pages 1-2, hardin2023loggiccorebioclinical pages 3-5)
No high-confidence environmental toxin/lifestyle/infectious causal evidence was retrieved in this run for glioma; therefore, no specific environmental claims are made.
WHO CNS5 frames glioma biology around canonical molecular alterations and their downstream phenotypes. Key upstream-to-downstream relationships emphasized in the retrieved evidence include: * IDH mutation status as a primary biological divider associated with prognostic differences and correlated molecular programs (IDH-mutant generally more favorable than IDH-wildtype). (reuss2023updatesonthe pages 1-2) * Copy-number and oncogenic alterations (e.g., EGFR amplification, TERT promoter mutation, +7/−10) serving as glioblastoma-defining markers, reflecting aggressive tumor biology independent of morphology. (mcnamara20222021whoclassification pages 6-9)
(Provided as ontology suggestions; GO source documents were not retrieved in this run.)
Gliomas are CNS tumors affecting brain and spinal cord structures; adult diffuse gliomas are typically infiltrative within brain parenchyma. Adult diffuse glioma registry analyses report frequent localization in cerebral regions (“cerebrum” predominance in SEER-based analyses cited within registry context). (zhao2024emergingtrendsin pages 11-14)
Suggested UBERON terms (examples; ontology suggestions): * Brain — UBERON:0000955 * Cerebrum — UBERON:0001869
In a Belgian population registry cohort of adult-type diffuse glioma (2017–2019), median age at diagnosis was 64 years, consistent with adult-onset predominance for diffuse adult-type gliomas in population data. (pinson2024epidemiologyandsurvival pages 1-2)
Diffuse gliomas are infiltrative and often recur/progress despite therapy; WHO CNS5 emphasizes molecular classification and grading to better predict progression risk. (mcnamara20222021whoclassification pages 6-9, osborn2022the2021world pages 1-3)
The CBTRUS Statistical Report (US; diagnosed 2017–2021; published Oct 2024) reports: * Gliomas accounted for 22.9% of all primary brain/CNS tumors. * Glioblastoma accounted for 14.0% of all tumors and 51.5% of malignant tumors. * Malignant brain/CNS tumor incidence: 6.89 per 100,000 overall; 8.06 per 100,000 in males vs 5.84 per 100,000 in females. * Malignant brain/CNS tumor mortality: 4.41 per 100,000, with 87,053 deaths during 2017–2021. * 5-year relative survival for malignant brain/CNS tumors overall: 35.7%. (price2024cbtrusstatisticalreport pages 2-3)
A Belgian national cancer registry analysis of adult-type diffuse gliomas (2017–2019; published Aug 2024) estimated an age-standardized incidence rate of 8.55 per 100,000 person-years for diffuse adult-type glioma and 6.72 per 100,000 person-years for grade 4 lesions. (pinson2024epidemiologyandsurvival pages 1-2)
| Dataset / population | Location / diagnosis years | Key epidemiology statistics | Key survival statistics | Source |
|---|---|---|---|---|
| CBTRUS Statistical Report: all primary brain and other CNS tumors, with glioma-relevant subset | United States; diagnosed 2017-2021 | Gliomas accounted for 22.9% of all primary brain/CNS tumors. Glioblastoma accounted for 14.0% of all tumors and 51.5% of all malignant tumors. Overall malignant brain/CNS tumor incidence was 6.89 per 100,000; by sex, 8.06 per 100,000 in males vs 5.84 per 100,000 in females. Malignant brain/CNS tumor mortality was 4.41 per 100,000 (average annual mortality), with 87,053 deaths during 2017-2021. (price2024cbtrusstatisticalreport pages 2-3) | 5-year relative survival for malignant brain/CNS tumors: 35.7%. (price2024cbtrusstatisticalreport pages 2-3) | Price et al., Neuro-Oncology 2024, published Oct 2024. https://doi.org/10.1093/neuonc/noae145 |
| Belgian population-based adult-type diffuse glioma registry | Belgium; diagnosed 2017-2019 | 2,233 adult-type diffuse gliomas identified; 40.1% female; median age 64 years. Age-standardized incidence rate (ASR) for diffuse adult-type glioma: 8.55 per 100,000 person-years. ASR for grade 4 lesions: 6.72 per 100,000 person-years. (pinson2024epidemiologyandsurvival pages 1-2, pinson2024epidemiologyandsurvival pages 3-4) | Median OS 9.3 months for IDH-wildtype glioblastoma; 25.9 months for grade 4 IDH-mutant astrocytoma. 3-year survival: IDH-mutant astrocytoma grade 2 86.0%, grade 3 75.7%; IDH-wildtype astrocytoma grade 2 31.6%, grade 3 5.7%; oligodendroglioma grade 2 93.4%, grade 3 64.2%; grade 4 lesions overall 6.5%. (pinson2024epidemiologyandsurvival pages 1-2, pinson2024epidemiologyandsurvival pages 3-4) | Pinson et al., Neuro-Oncology 2024, published Aug 2024. https://doi.org/10.1093/neuonc/noad158 |
| Belgian registry contextual comparison with prior US glioblastoma incidence estimate | Belgium study citing US data; US comparator largely 2015-2019 | Study notes CBTRUS-reported glioblastoma ASR in the US population of 3.26 per 100,000 person-years. (pinson2024epidemiologyandsurvival pages 4-6) | Provides context that real-world glioblastoma outcomes remain poor relative to molecularly favorable diffuse glioma subtypes. (pinson2024epidemiologyandsurvival pages 4-6) | Pinson et al., Neuro-Oncology 2024. https://doi.org/10.1093/neuonc/noad158 |
Table: This table compiles recent population-level glioma epidemiology and survival figures from the 2024 CBTRUS report and a 2024 Belgian molecular-era registry. It is useful for contrasting broad U.S. CNS tumor statistics with subtype-resolved real-world outcomes for adult-type diffuse gliomas.
Most adult diffuse gliomas are sporadic, but a clinically meaningful minority show germline pathogenic variants; a 2023 cohort found ~10% with pathogenic germline variants (see Etiology). (mcdonald2023prevalenceofpathogenic pages 1-2)
WHO CNS5-era diagnostic practice is integrated and multi-assay. Molecular markers may be detected via IHC surrogate assays, FISH for copy-number changes (including 1p/19q codeletion), and DNA/RNA next-generation sequencing; methylome profiling can classify tumors and infer copy-number alterations. (osborn2022the2021world pages 1-3)
Methylation profiling and NGS are described as core parts of the evolving molecular neuropathology toolbox, with methylation profiling “critical” for complex cases and for subgrouping heterogeneous entities; targeted sequencing is practical for routine diagnostics and may reveal targets for emerging therapies. (bertero2024molecularneuropathologyan pages 1-3, bertero2024molecularneuropathologyan pages 3-4)
Liquid biopsy remains investigational. A 2024 GBM liquid biopsy review notes analytes such as ctDNA, miRNA, CTCs, EVs/exosomes, proteins, but emphasizes major challenges including blood–brain barrier limitations, variable detection rates (ctDNA ~10–55%), small cohorts, and lack of standardized pre-analytical/analytical methods; no circulating biomarker is clinically validated for routine GBM management. (seyhan2024circulatingliquidbiopsy pages 48-49, seyhan2024circulatingliquidbiopsy pages 1-2)
For CSF cfDNA in glioma, a 2024 review reports NGS detection of tumor-specific mutations in 70% of glioma cases, 82.5% in brainstem glioma with targeted panels, and 97.3% concordance when primary tumor alterations were present—highlighting potential as an adjunct in hard-to-biopsy contexts. (otsuji2024liquidbiopsyfor pages 12-14)
| Modality | What it detects | Typical use case | Key limitations | Recent evidence/examples with year + URL |
|---|---|---|---|---|
| MRI (standard structural MRI; advanced MRI adjuncts) | Tumor location, size, contrast enhancement, edema, mass effect; supports response/progression assessment | First-line detection, surgical planning, longitudinal monitoring, distinguishing enhancing vs non-enhancing disease | Limited specificity for molecular subtype; may not reliably distinguish progression from treatment effect/pseudoprogression | Standard imaging remains central in WHO-era glioma workup; radiologists integrate imaging with molecular classification (2022, https://doi.org/10.3174/ajnr.45-12.s15) (osborn2022the2021world pages 1-3) |
| Histopathology + immunohistochemistry (IHC) | Morphology plus surrogate protein markers such as IDH1 R132H, ATRX loss, p53 overexpression, H3K27M, BRAF V600E | Core tissue diagnosis after biopsy/resection; rapid subtype orientation and grading support | Sampling bias, interobserver variability, limited sensitivity for non-canonical mutations/fusions; cannot alone resolve all integrated diagnoses | WHO CNS5 layered diagnosis still relies on histology/IHC alongside molecular data (2022, https://doi.org/10.3174/ajnr.45-12.s15) (osborn2022the2021world pages 1-3) |
| FISH | 1p/19q codeletion, EGFR amplification, CDKN2A/B deletion and other copy-number events | Confirm oligodendroglioma-defining 1p/19q status; support glioblastoma-defining alterations when needed | Target-limited assay; may miss genome-wide context or complex chromosomal architecture | FISH remains part of the molecular toolbox for diffuse glioma classification in WHO CNS5 practice (2022, https://doi.org/10.3174/ajnr.45-12.s15) (osborn2022the2021world pages 1-3) |
| DNA NGS panels | SNVs/indels in genes such as IDH1/2, TP53, ATRX, TERT promoter, H3 genes; some copy-number calls depending on panel | Practical routine molecular workup for adult and pediatric gliomas; diagnosis, prognostication, and actionable target finding | Panel content constrains discovery; may miss fusions/structural events; lower utility for epigenetic subgrouping | Targeted DNA sequencing is described as the most practical routine approach and can detect diagnostically relevant alterations in >50% of CNS tumors (2024, https://doi.org/10.1007/s00428-023-03632-4) (bertero2024molecularneuropathologyan pages 3-4, bertero2024molecularneuropathologyan pages 1-3) |
| RNA-seq | Gene fusions, splice variants, expressed rearrangements; can reveal hidden drivers such as FGFR1 ITD and rare kinase fusions | Especially valuable in pediatric low-grade glioma and fusion-driven tumors when panel/IHC are unrevealing | Requires high-quality nucleic acid/bioinformatics; less commonly informative in adult diffuse glioma; tissue handling constraints | In LOGGIC pLGG, adding RNA-seq raised driver detection from 75% to 97%; 27/125 cases had drivers found only by RNA-seq and 22 were actionable (2023, https://doi.org/10.1093/neuonc/noad078) (hardin2023loggiccorebioclinical pages 3-5, hardin2023loggiccorebioclinical pages 1-2) |
| DNA methylation profiling (classifier) | Tumor-class methylome signature plus genome-wide copy-number profile; can refine subtype, resolve ambiguous cases, and support grading/class assignment | Difficult/ambiguous cases, novel entities, subclassification, integrated diagnosis under WHO CNS5 | Not all samples achieve high-confidence match; specialized platforms/classifiers required; interpretation expertise needed | Described as a critical/most impactful diagnostic tool; match scores ≥0.9 in ~50-65% of samples with diagnostic impact in ~10-20% of cases (2024, https://doi.org/10.1007/s00428-023-03632-4); DKFZ classifier v12.5 added >10 novel methylation classes (2023, https://doi.org/10.1007/s10014-022-00446-1) (bertero2024molecularneuropathologyan pages 3-4, bertero2024molecularneuropathologyan pages 1-3, komori2023updateofthe pages 1-2) |
| CSF ctDNA liquid biopsy | Tumor-derived mutations/copy-number alterations in CSF cfDNA; can reflect IDH1, TERT, TP53, PTEN and other glioma alterations | Adjunct when biopsy is risky, deep/brainstem lesions, postoperative monitoring, molecular follow-up | Blood-brain barrier limits blood sensitivity; CSF acquisition is invasive; no standardization; not a replacement for tissue diagnosis | Reviews emphasize ctDNA/CTCs/miRNA/EVs as promising but limited by BBB and lack of standardized workflows (2024, https://doi.org/10.3390/ijms25147974; 2024, https://doi.org/10.3390/cancers16051009). Reported CSF cfDNA mutation detection includes 70% in gliomas, 82.5% in brainstem glioma, and 97.3% concordance when tumor alterations are present (2024, https://doi.org/10.3390/cancers16051009) (seyhan2024circulatingliquidbiopsy pages 48-49, seyhan2024circulatingliquidbiopsy pages 49-51, seyhan2024circulatingliquidbiopsy pages 1-2, otsuji2024liquidbiopsyfor pages 12-14) |
Table: This table summarizes the main current diagnostic modalities used in glioma care, what each modality detects, where it is most useful, and key limitations. It emphasizes the shift toward integrated molecular diagnosis in WHO CNS5, including methylation profiling, RNA-seq, and CSF liquid biopsy.
A 2023 high-grade glioma guideline states glioblastoma has a grim prognosis with median overall survival ~15 months and 5-year survival 5–10%. (segura2023seomgeinoclinicalguidelines pages 1-2)
In real-world Austrian population data (2014–2018; published Aug 2024), median OS for 1,420 glioblastoma patients was 11.6 months overall and 16.1 months among patients ≤65 years receiving postoperative standard-of-care therapy; ≥5-year survival occurred in 4.9% of those with ≥5-year follow-up. (hainfellner2024glioblastomainthe pages 1-3)
A Belgian registry study (2017–2019) showed marked survival differences by molecular subtype: median OS 9.3 months for IDH‑wildtype glioblastoma vs 25.9 months for grade 4 IDH‑mutant astrocytoma; 3‑year survival for IDH‑mutant astrocytoma was 86.0% (grade 2) and 75.7% (grade 3). (pinson2024epidemiologyandsurvival pages 1-2)
Guidelines emphasize multimodal treatment with maximal safe resection, radiotherapy, and temozolomide-based chemotherapy (Stupp regimen). (segura2023seomgeinoclinicalguidelines pages 4-5, segura2023seomgeinoclinicalguidelines pages 2-4)
A 2023 systematic review/meta-analysis of real-world TTFields studies found improved OS when TTFields was added to standard chemoradiotherapy (pooled HR 0.63, 95% CI 0.53–0.75), with pooled median OS 22.6 months (TTFields) vs 17.4 months (no TTFields). (ballo2023associationoftumor pages 1-2)
A 2024 global post-marketing safety surveillance analysis (>25,000 treated CNS malignancy patients) reported most common TTFields-related adverse events were localized scalp reactions: beneath-array skin reaction 43%, tingling 14%, warmth 12%, with no TTFields-related systemic adverse events reported. (mrugala2024globalpost‑marketingsafety pages 1-2)
The phase 3 INDIGO trial (NEJM, Aug 2023; DOI: https://doi.org/10.1056/NEJMoa2304194) enrolled 331 patients with residual/recurrent grade 2 IDH1/2-mutant glioma after surgery only. Vorasidenib significantly improved median imaging-based PFS (27.7 vs 11.1 months, HR 0.39) and delayed time to next intervention (HR 0.26). (mellinghoff2023vorasidenibinidh1 pages 1-3)
Safety: grade ≥3 alanine aminotransferase elevation occurred in ~9.6–10% of vorasidenib patients vs 0% placebo in trial reporting. (mellinghoff2023vorasidenibinidh1 pages 1-3, ruda2024idhinhibitionin pages 6-7)
ClinicalTrials.gov identifier: NCT04164901. (mellinghoff2023vorasidenibinidh1 pages 1-3)
Guidelines highlight dexamethasone for edema (preferred dose range 4–16 mg/day) and seizure management with levetiracetam as first-line monotherapy for patients with seizures. (segura2023seomgeinoclinicalguidelines pages 7-8)
| Intervention | Indication/subtype | Evidence type | Key efficacy outcomes | Key safety/QoL points | Source with URL and year | MAXO term suggestion |
|---|---|---|---|---|---|---|
| Stupp regimen (maximal safe resection + radiotherapy + concomitant/adjuvant temozolomide) | Newly diagnosed glioblastoma / adult high-grade glioma | Guideline + real-world registry | Standard of care; guideline cites median OS ~15 months and 5-year survival 5-10% for GBM; in Austrian real-world cohort, median OS 11.6 months overall, 16.1 months in patients ≤65 years receiving postoperative standard-of-care therapy (segura2023seomgeinoclinicalguidelines pages 1-2, segura2023seomgeinoclinicalguidelines pages 4-5, hainfellner2024glioblastomainthe pages 1-3) | Extent of resection is prognostic; symptoms affecting QoL include seizures, cognitive deficits, headache, aphasia, motor deficits, fatigue; postoperative therapy started at median 31 days in Austrian practice (segura2023seomgeinoclinicalguidelines pages 2-4, hainfellner2024glioblastomainthe pages 1-3) | SEOM-GEINO guideline 2023: https://doi.org/10.1007/s12094-023-03245-y; Austrian registry 2024: https://doi.org/10.1007/s11060-024-04808-x (segura2023seomgeinoclinicalguidelines pages 2-4, hainfellner2024glioblastomainthe pages 1-3, segura2023seomgeinoclinicalguidelines pages 4-5) | MAXO: surgical resection; radiotherapy; temozolomide treatment; combined chemoradiotherapy |
| Tumor Treating Fields (TTFields) + standard of care / maintenance temozolomide | Newly diagnosed glioblastoma after chemoradiation; considered when available | Systematic review/meta-analysis + post-marketing surveillance + post-approval real-world study | Meta-analysis: OS HR 0.63 (95% CI 0.53-0.75) vs SOC alone; pooled median OS 22.6 vs 17.4 months; 2-year OS 46.8% vs 32.3%; higher adherence (≥75%) associated with longer survival (ballo2023associationoftumor pages 1-2, ballo2023associationoftumor pages 5-6) | Most common treatment-related AEs: beneath-array skin reactions 43%, tingling 14%, warmth 12%; no TTFields-related systemic AEs in >25,000-patient surveillance; Japanese post-approval study found local skin reactions in 60%, mostly mild-moderate (mrugala2024globalpost‑marketingsafety pages 1-2, nishikawa2023safetyandefficacy pages 1-2) | Meta-analysis 2023: https://doi.org/10.1007/s11060-023-04348-w; global surveillance 2024: https://doi.org/10.1007/s11060-024-04682-7; Japanese post-approval 2023: https://doi.org/10.1093/jjco/hyad001 (mrugala2024globalpost‑marketingsafety pages 1-2, ballo2023associationoftumor pages 1-2, nishikawa2023safetyandefficacy pages 1-2, ballo2023associationoftumor pages 5-6) | MAXO: tumor treating fields therapy; adjuvant device-based therapy |
| Vorasidenib | Residual or recurrent grade 2 IDH1/2-mutant astrocytoma or oligodendroglioma after surgery only | Phase 3 randomized trial (INDIGO) + approval summary | INDIGO: median imaging-based PFS 27.7 vs 11.1 months; HR for progression/death 0.39; time to next intervention HR 0.26; 18-month freedom from next intervention 85.6% vs 47.4% (mellinghoff2023vorasidenibinidh1 pages 1-3, lamb2024vorasidenibfirstapproval pages 4-5) | Grade ≥3 AEs more frequent with vorasidenib; grade ≥3 ALT elevation 9.6-10%; common AEs include elevated liver enzymes, fatigue, headache, diarrhea, nausea, dizziness; HRQoL reportedly maintained over ~13 months (mellinghoff2023vorasidenibinidh1 pages 1-3, lamb2024vorasidenibfirstapproval pages 4-5, ruda2024idhinhibitionin pages 6-7) | NEJM 2023: https://doi.org/10.1056/NEJMoa2304194; approval review 2024: https://doi.org/10.1007/s40265-024-02097-2 (mellinghoff2023vorasidenibinidh1 pages 1-3, lamb2024vorasidenibfirstapproval pages 4-5, ruda2024idhinhibitionin pages 6-7) | MAXO: IDH inhibitor therapy; targeted small-molecule therapy |
| Supportive care: dexamethasone | Symptomatic brain edema/increased intracranial pressure in high-grade glioma | Guideline/expert consensus | Improves mass-effect/edema-related symptoms; integral adjunct to oncologic therapy rather than disease-modifying treatment (segura2023seomgeinoclinicalguidelines pages 7-8) | Preferred dose range 4-16 mg/day; used to relieve edema-related neurologic symptoms and maintain function/QoL (segura2023seomgeinoclinicalguidelines pages 7-8) | SEOM-GEINO guideline 2023: https://doi.org/10.1007/s12094-023-03245-y (segura2023seomgeinoclinicalguidelines pages 7-8) | MAXO: corticosteroid therapy; cerebral edema management |
| Supportive care: levetiracetam | Seizure management in glioma/high-grade glioma | Guideline/expert consensus | Recommended as first-line antiepileptic monotherapy for patients with seizures; prophylactic AED use is not generally recommended (segura2023seomgeinoclinicalguidelines pages 7-8) | Supports seizure control and QoL; neurocognitive impairment is common and AED-related cognitive effects may require dose adjustment or agent substitution (segura2023seomgeinoclinicalguidelines pages 7-8, segura2023seomgeinoclinicalguidelines pages 8-9) | SEOM-GEINO guideline 2023: https://doi.org/10.1007/s12094-023-03245-y (segura2023seomgeinoclinicalguidelines pages 7-8, segura2023seomgeinoclinicalguidelines pages 8-9) | MAXO: anticonvulsant treatment; seizure management |
Table: This table summarizes current glioma treatments and real-world implementation evidence, including standard chemoradiotherapy, TTFields, vorasidenib, and supportive care. It highlights efficacy, safety, and ontology-ready MAXO action terms for knowledge base use.
No population screening or primary prevention strategies were retrieved with tool evidence in this run. Prevention is therefore largely limited to: * Tertiary prevention/supportive care to reduce complications (edema, seizures, thrombosis, neurocognitive decline) in diagnosed patients. (segura2023seomgeinoclinicalguidelines pages 7-8) * Genetic counseling/surveillance for individuals with cancer predisposition syndromes, with pediatric surveillance guidance emphasizing early tumor surveillance and cascade testing. (hansford2024updateoncancer pages 1-2)
Naturally occurring canine gliomas are used in comparative oncology. An in vitro comparative study tested human and canine glioma cell lines and noted similarities supporting canine glioma as a surrogate model; cannabidiol showed cytotoxicity in the ~4.9–8.2 μg/ml range, with mitochondrial dysfunction (reduced oxygen consumption, swollen mitochondria) contributing to apoptosis. (gross2021cannabidiolinducesapoptosis pages 1-2)
This run retrieved limited explicit model-organism methodology evidence beyond the comparative canine in vitro model above; thus, additional statements about specific GEMMs/PDX/organoid resources are not asserted.
Attempts were made to retrieve a WHO CNS5 classification figure/table and a CBTRUS survival table using the image retrieval tool, but the tool failed to fetch images from available text chunks in this run; therefore, no figure/table image citations are provided.
References
(osborn2022the2021world pages 1-3): A.G. Osborn, D.N. Louis, T.Y. Poussaint, L.L. Linscott, and K.L. Salzman. The 2021 world health organization classification of tumors of the central nervous system: what neuroradiologists need to know. American Journal of Neuroradiology, 45:S15-S24, Jun 2022. URL: https://doi.org/10.3174/ajnr.45-12.s15, doi:10.3174/ajnr.45-12.s15. This article has 265 citations and is from a peer-reviewed journal.
(mcnamara20222021whoclassification pages 1-6): Cillian McNamara, Kshitij Mankad, Stefanie Thust, Luke Dixon, Clara Limback-Stanic, Felice D’Arco, Thomas S. Jacques, and Ulrike Löbel. 2021 who classification of tumours of the central nervous system: a review for the neuroradiologist. Neuroradiology, 64:1919-1950, Jul 2022. URL: https://doi.org/10.1007/s00234-022-03008-6, doi:10.1007/s00234-022-03008-6. This article has 123 citations and is from a peer-reviewed journal.
(reuss2023updatesonthe pages 1-2): David.E. Reuss. Updates on the who diagnosis of idh-mutant glioma. Journal of Neuro-Oncology, 162:461-469, Jan 2023. URL: https://doi.org/10.1007/s11060-023-04250-5, doi:10.1007/s11060-023-04250-5. This article has 80 citations and is from a peer-reviewed journal.
(mcnamara20222021whoclassification pages 6-9): Cillian McNamara, Kshitij Mankad, Stefanie Thust, Luke Dixon, Clara Limback-Stanic, Felice D’Arco, Thomas S. Jacques, and Ulrike Löbel. 2021 who classification of tumours of the central nervous system: a review for the neuroradiologist. Neuroradiology, 64:1919-1950, Jul 2022. URL: https://doi.org/10.1007/s00234-022-03008-6, doi:10.1007/s00234-022-03008-6. This article has 123 citations and is from a peer-reviewed journal.
(antonelli2022adulttypediffuse pages 1-2): Manila Antonelli and Pietro Luigi Poliani. Adult type diffuse gliomas in the new 2021 who classification. Pathologica, 114:397-409, Dec 2022. URL: https://doi.org/10.32074/1591-951x-823, doi:10.32074/1591-951x-823. This article has 80 citations.
(gue2024the2021world pages 19-21): Racine Gue and Dhairya A. Lakhani. The 2021 world health organization central nervous system tumor classification: the spectrum of diffuse gliomas. Biomedicines, 12:1349, Jun 2024. URL: https://doi.org/10.3390/biomedicines12061349, doi:10.3390/biomedicines12061349. This article has 21 citations.
(price2024cbtrusstatisticalreport pages 2-3): Mackenzie Price, Christine Ballard, Julia Benedetti, Corey Neff, Gino Cioffi, Kristin A Waite, Carol Kruchko, Jill S Barnholtz-Sloan, and Quinn T Ostrom. Cbtrus statistical report: primary brain and other central nervous system tumors diagnosed in the united states in 2017-2021. Neuro-oncology, 26 Supplement_6:vi1-vi85, Oct 2024. URL: https://doi.org/10.1093/neuonc/noae145, doi:10.1093/neuonc/noae145. This article has 587 citations and is from a domain leading peer-reviewed journal.
(hainfellner2024glioblastomainthe pages 1-3): Andreas Hainfellner, Martin Borkovec, Lukas Seebrecht, Magdalena Neuhauser, Thomas Roetzer-Pejrimovsky, Lisa Greutter, Birgit Surböck, Andrea Hager-Seifert, Doris Gorka-vom Hof, Tadeja Urbanic-Purkart, Martin Stultschnig, Clemens Cijan, Franz Würtz, Bernadette Calabek-Wohinz, Josef Pichler, Isolde Höllmüller, Annette Leibetseder, Serge Weis, Waltraud Kleindienst, Michael Seiberl, Lara Bieler, Constantin Hecker, Christoph Schwartz, Sarah Iglseder, Johanna Heugenhauser, Martha Nowosielski, Claudius Thomé, Patrizia Moser, Markus Hoffermann, Karin Loibnegger, Karin Dieckmann, Matthias Tomschik, Georg Widhalm, Karl Rössler, Christine Marosi, Adelheid Wöhrer, Johannes A. Hainfellner, and Stefan Oberndorfer. Glioblastoma in the real-world setting: patterns of care and outcome in the austrian population. Journal of Neuro-Oncology, 170:407-418, Aug 2024. URL: https://doi.org/10.1007/s11060-024-04808-x, doi:10.1007/s11060-024-04808-x. This article has 7 citations and is from a peer-reviewed journal.
(mcdonald2023prevalenceofpathogenic pages 1-2): Malcolm F McDonald, Lyndsey L Prather, Cassandra R Helfer, Ethan B Ludmir, Alfredo E Echeverria, Shlomit Yust-Katz, Akash J Patel, Benjamin Deneen, Ganesh Rao, Ali Jalali, Shweta U Dhar, Chris I Amos, and Jacob J Mandel. Prevalence of pathogenic germline variants in adult-type diffuse glioma. Neuro-oncology practice, 10 5:482-490, Jun 2023. URL: https://doi.org/10.1093/nop/npad033, doi:10.1093/nop/npad033. This article has 9 citations and is from a peer-reviewed journal.
(mcdonald2023prevalenceofpathogenic pages 5-7): Malcolm F McDonald, Lyndsey L Prather, Cassandra R Helfer, Ethan B Ludmir, Alfredo E Echeverria, Shlomit Yust-Katz, Akash J Patel, Benjamin Deneen, Ganesh Rao, Ali Jalali, Shweta U Dhar, Chris I Amos, and Jacob J Mandel. Prevalence of pathogenic germline variants in adult-type diffuse glioma. Neuro-oncology practice, 10 5:482-490, Jun 2023. URL: https://doi.org/10.1093/nop/npad033, doi:10.1093/nop/npad033. This article has 9 citations and is from a peer-reviewed journal.
(mcdonald2023prevalenceofpathogenic pages 2-3): Malcolm F McDonald, Lyndsey L Prather, Cassandra R Helfer, Ethan B Ludmir, Alfredo E Echeverria, Shlomit Yust-Katz, Akash J Patel, Benjamin Deneen, Ganesh Rao, Ali Jalali, Shweta U Dhar, Chris I Amos, and Jacob J Mandel. Prevalence of pathogenic germline variants in adult-type diffuse glioma. Neuro-oncology practice, 10 5:482-490, Jun 2023. URL: https://doi.org/10.1093/nop/npad033, doi:10.1093/nop/npad033. This article has 9 citations and is from a peer-reviewed journal.
(hansford2024updateoncancer pages 1-2): Jordan R. Hansford, Anirban Das, Rose B. McGee, Yoshiko Nakano, Jack Brzezinski, Sarah R. Scollon, Surya P. Rednam, Jaclyn Schienda, Orli Michaeli, Sun Young Kim, Mary-Louise C. Greer, Rosanna Weksberg, Douglas R. Stewart, William D. Foulkes, Uri Tabori, Kristian W. Pajtler, Stefan M. Pfister, Garrett M. Brodeur, and Junne Kamihara. Update on cancer predisposition syndromes and surveillance guidelines for childhood brain tumors. Clinical cancer research : an official journal of the American Association for Cancer Research, 30:2342-2350, Apr 2024. URL: https://doi.org/10.1158/1078-0432.ccr-23-4033, doi:10.1158/1078-0432.ccr-23-4033. This article has 62 citations.
(segura2023seomgeinoclinicalguidelines pages 2-4): Pedro Pérez Segura, Noelia Vilariño Quintela, María Martínez García, Sonia del Barco Berrón, Regina Gironés Sarrió, Jesús García Gómez, Almudena García Castaño, Luis Miguel Navarro Martín, Oscar Gallego Rubio, and Estela Pineda Losada. Seom-geino clinical guidelines for high-grade gliomas of adulthood (2022). Clinical & Translational Oncology, 25:2634-2646, Aug 2023. URL: https://doi.org/10.1007/s12094-023-03245-y, doi:10.1007/s12094-023-03245-y. This article has 46 citations and is from a peer-reviewed journal.
(segura2023seomgeinoclinicalguidelines pages 7-8): Pedro Pérez Segura, Noelia Vilariño Quintela, María Martínez García, Sonia del Barco Berrón, Regina Gironés Sarrió, Jesús García Gómez, Almudena García Castaño, Luis Miguel Navarro Martín, Oscar Gallego Rubio, and Estela Pineda Losada. Seom-geino clinical guidelines for high-grade gliomas of adulthood (2022). Clinical & Translational Oncology, 25:2634-2646, Aug 2023. URL: https://doi.org/10.1007/s12094-023-03245-y, doi:10.1007/s12094-023-03245-y. This article has 46 citations and is from a peer-reviewed journal.
(segura2023seomgeinoclinicalguidelines pages 8-9): Pedro Pérez Segura, Noelia Vilariño Quintela, María Martínez García, Sonia del Barco Berrón, Regina Gironés Sarrió, Jesús García Gómez, Almudena García Castaño, Luis Miguel Navarro Martín, Oscar Gallego Rubio, and Estela Pineda Losada. Seom-geino clinical guidelines for high-grade gliomas of adulthood (2022). Clinical & Translational Oncology, 25:2634-2646, Aug 2023. URL: https://doi.org/10.1007/s12094-023-03245-y, doi:10.1007/s12094-023-03245-y. This article has 46 citations and is from a peer-reviewed journal.
(bertero2024molecularneuropathologyan pages 3-4): Luca Bertero, Luca Mangherini, Alessia Andrea Ricci, Paola Cassoni, and Felix Sahm. Molecular neuropathology: an essential and evolving toolbox for the diagnosis and clinical management of central nervous system tumors. Virchows Archiv, 484:181-194, Sep 2024. URL: https://doi.org/10.1007/s00428-023-03632-4, doi:10.1007/s00428-023-03632-4. This article has 25 citations and is from a peer-reviewed journal.
(hardin2023loggiccorebioclinical pages 1-2): Emily C Hardin, Simone Schmid, Alexander Sommerkamp, Carina Bodden, Anna-Elisa Heipertz, Philipp Sievers, Andrea Wittmann, Till Milde, Stefan M Pfister, Andreas von Deimling, Svea Horn, Nina A Herz, Michèle Simon, Ashwyn A Perera, Amedeo Azizi, Ofelia Cruz, Sarah Curry, An Van Damme, Miklos Garami, Darren Hargrave, Antonis Kattamis, Barbara Faganel Kotnik, Päivi Lähteenmäki, Katrin Scheinemann, Antoinette Y N Schouten-van Meeteren, Astrid Sehested, Elisabetta Viscardi, Ole Mikal Wormdal, Michal Zapotocky, David S Ziegler, Arend Koch, Pablo Hernáiz Driever, Olaf Witt, David Capper, Felix Sahm, David T W Jones, and Cornelis M van Tilburg. Loggic core bioclinical data bank: added clinical value of rna-seq in an international molecular diagnostic registry for pediatric low-grade glioma patients. Neuro-oncology, 25:2087-2097, Apr 2023. URL: https://doi.org/10.1093/neuonc/noad078, doi:10.1093/neuonc/noad078. This article has 33 citations and is from a domain leading peer-reviewed journal.
(hardin2023loggiccorebioclinical pages 3-5): Emily C Hardin, Simone Schmid, Alexander Sommerkamp, Carina Bodden, Anna-Elisa Heipertz, Philipp Sievers, Andrea Wittmann, Till Milde, Stefan M Pfister, Andreas von Deimling, Svea Horn, Nina A Herz, Michèle Simon, Ashwyn A Perera, Amedeo Azizi, Ofelia Cruz, Sarah Curry, An Van Damme, Miklos Garami, Darren Hargrave, Antonis Kattamis, Barbara Faganel Kotnik, Päivi Lähteenmäki, Katrin Scheinemann, Antoinette Y N Schouten-van Meeteren, Astrid Sehested, Elisabetta Viscardi, Ole Mikal Wormdal, Michal Zapotocky, David S Ziegler, Arend Koch, Pablo Hernáiz Driever, Olaf Witt, David Capper, Felix Sahm, David T W Jones, and Cornelis M van Tilburg. Loggic core bioclinical data bank: added clinical value of rna-seq in an international molecular diagnostic registry for pediatric low-grade glioma patients. Neuro-oncology, 25:2087-2097, Apr 2023. URL: https://doi.org/10.1093/neuonc/noad078, doi:10.1093/neuonc/noad078. This article has 33 citations and is from a domain leading peer-reviewed journal.
(zhao2024emergingtrendsin pages 11-14): Yuxin Zhao, Zihan Xu, Yong Zhang, Ying Liu, Ming Ye, Rui Chen, Zhongyu Cao, Hong Zhou, and Yang Zhou. Emerging trends in glioma incidence and prognostic factors: a comprehensive analysis of the united states (2000-2018). Unknown journal, Feb 2024. URL: https://doi.org/10.21203/rs.3.rs-3913327/v1, doi:10.21203/rs.3.rs-3913327/v1.
(pinson2024epidemiologyandsurvival pages 1-2): Harry Pinson, Geert Silversmit, Dimitri Vanhauwaert, Katrijn Vanschoenbeek, Jean-Pierre Kalala Okito, Steven De Vleeschouwer, Tom Boterberg, and Cindy De Gendt. Epidemiology and survival of adult-type diffuse glioma in belgium during the molecular era. Neuro-oncology, 26:191-202, Aug 2024. URL: https://doi.org/10.1093/neuonc/noad158, doi:10.1093/neuonc/noad158. This article has 28 citations and is from a domain leading peer-reviewed journal.
(pinson2024epidemiologyandsurvival pages 3-4): Harry Pinson, Geert Silversmit, Dimitri Vanhauwaert, Katrijn Vanschoenbeek, Jean-Pierre Kalala Okito, Steven De Vleeschouwer, Tom Boterberg, and Cindy De Gendt. Epidemiology and survival of adult-type diffuse glioma in belgium during the molecular era. Neuro-oncology, 26:191-202, Aug 2024. URL: https://doi.org/10.1093/neuonc/noad158, doi:10.1093/neuonc/noad158. This article has 28 citations and is from a domain leading peer-reviewed journal.
(pinson2024epidemiologyandsurvival pages 4-6): Harry Pinson, Geert Silversmit, Dimitri Vanhauwaert, Katrijn Vanschoenbeek, Jean-Pierre Kalala Okito, Steven De Vleeschouwer, Tom Boterberg, and Cindy De Gendt. Epidemiology and survival of adult-type diffuse glioma in belgium during the molecular era. Neuro-oncology, 26:191-202, Aug 2024. URL: https://doi.org/10.1093/neuonc/noad158, doi:10.1093/neuonc/noad158. This article has 28 citations and is from a domain leading peer-reviewed journal.
(bertero2024molecularneuropathologyan pages 1-3): Luca Bertero, Luca Mangherini, Alessia Andrea Ricci, Paola Cassoni, and Felix Sahm. Molecular neuropathology: an essential and evolving toolbox for the diagnosis and clinical management of central nervous system tumors. Virchows Archiv, 484:181-194, Sep 2024. URL: https://doi.org/10.1007/s00428-023-03632-4, doi:10.1007/s00428-023-03632-4. This article has 25 citations and is from a peer-reviewed journal.
(seyhan2024circulatingliquidbiopsy pages 48-49): Attila A. Seyhan. Circulating liquid biopsy biomarkers in glioblastoma: advances and challenges. International Journal of Molecular Sciences, 25:7974, Jul 2024. URL: https://doi.org/10.3390/ijms25147974, doi:10.3390/ijms25147974. This article has 76 citations.
(seyhan2024circulatingliquidbiopsy pages 1-2): Attila A. Seyhan. Circulating liquid biopsy biomarkers in glioblastoma: advances and challenges. International Journal of Molecular Sciences, 25:7974, Jul 2024. URL: https://doi.org/10.3390/ijms25147974, doi:10.3390/ijms25147974. This article has 76 citations.
(otsuji2024liquidbiopsyfor pages 12-14): Ryosuke Otsuji, Yutaka Fujioka, Nobuhiro Hata, Daisuke Kuga, Ryusuke Hatae, Yuhei Sangatsuda, Akira Nakamizo, Masahiro Mizoguchi, and Koji Yoshimoto. Liquid biopsy for glioma using cell-free dna in cerebrospinal fluid. Cancers, 16:1009, Feb 2024. URL: https://doi.org/10.3390/cancers16051009, doi:10.3390/cancers16051009. This article has 36 citations.
(komori2023updateofthe pages 1-2): Takashi Komori. Update of the 2021 who classification of tumors of the central nervous system: adult diffuse gliomas. Brain Tumor Pathology, 40:1-3, Dec 2023. URL: https://doi.org/10.1007/s10014-022-00446-1, doi:10.1007/s10014-022-00446-1. This article has 13 citations and is from a peer-reviewed journal.
(seyhan2024circulatingliquidbiopsy pages 49-51): Attila A. Seyhan. Circulating liquid biopsy biomarkers in glioblastoma: advances and challenges. International Journal of Molecular Sciences, 25:7974, Jul 2024. URL: https://doi.org/10.3390/ijms25147974, doi:10.3390/ijms25147974. This article has 76 citations.
(segura2023seomgeinoclinicalguidelines pages 1-2): Pedro Pérez Segura, Noelia Vilariño Quintela, María Martínez García, Sonia del Barco Berrón, Regina Gironés Sarrió, Jesús García Gómez, Almudena García Castaño, Luis Miguel Navarro Martín, Oscar Gallego Rubio, and Estela Pineda Losada. Seom-geino clinical guidelines for high-grade gliomas of adulthood (2022). Clinical & Translational Oncology, 25:2634-2646, Aug 2023. URL: https://doi.org/10.1007/s12094-023-03245-y, doi:10.1007/s12094-023-03245-y. This article has 46 citations and is from a peer-reviewed journal.
(segura2023seomgeinoclinicalguidelines pages 4-5): Pedro Pérez Segura, Noelia Vilariño Quintela, María Martínez García, Sonia del Barco Berrón, Regina Gironés Sarrió, Jesús García Gómez, Almudena García Castaño, Luis Miguel Navarro Martín, Oscar Gallego Rubio, and Estela Pineda Losada. Seom-geino clinical guidelines for high-grade gliomas of adulthood (2022). Clinical & Translational Oncology, 25:2634-2646, Aug 2023. URL: https://doi.org/10.1007/s12094-023-03245-y, doi:10.1007/s12094-023-03245-y. This article has 46 citations and is from a peer-reviewed journal.
(ballo2023associationoftumor pages 1-2): Matthew T. Ballo, Patrick Conlon, Gitit Lavy-Shahaf, Adrian Kinzel, Josef Vymazal, and Aaron M. Rulseh. Association of tumor treating fields (ttfields) therapy with survival in newly diagnosed glioblastoma: a systematic review and meta-analysis. Journal of Neuro-Oncology, 164:1-9, Jul 2023. URL: https://doi.org/10.1007/s11060-023-04348-w, doi:10.1007/s11060-023-04348-w. This article has 94 citations and is from a peer-reviewed journal.
(mrugala2024globalpost‑marketingsafety pages 1-2): Maciej M. Mrugala, Wenyin Shi, Fabio Iwomoto, Rimas V. Lukas, Joshua D. Palmer, John H. Suh, and Martin Glas. Global post‑marketing safety surveillance of tumor treating fields (ttfields) therapy in over 25,000 patients with cns malignancies treated between 2011–2022. Journal of Neuro-Oncology, 169:25-38, Jun 2024. URL: https://doi.org/10.1007/s11060-024-04682-7, doi:10.1007/s11060-024-04682-7. This article has 25 citations and is from a peer-reviewed journal.
(mellinghoff2023vorasidenibinidh1 pages 1-3): Ingo K. Mellinghoff, Martin J. van den Bent, Deborah T. Blumenthal, Mehdi Touat, Katherine B. Peters, Jennifer Clarke, Joe Mendez, Shlomit Yust-Katz, Liam Welsh, Warren P. Mason, François Ducray, Yoshie Umemura, Burt Nabors, Matthias Holdhoff, Andreas F. Hottinger, Yoshiki Arakawa, Juan M. Sepulveda, Wolfgang Wick, Riccardo Soffietti, James R. Perry, Pierre Giglio, Macarena de la Fuente, Elizabeth A. Maher, Steven Schoenfeld, Dan Zhao, Shuchi S. Pandya, Lori Steelman, Islam Hassan, Patrick Y. Wen, and Timothy F. Cloughesy. Vorasidenib in idh1- or idh2-mutant low-grade glioma. Aug 2023. URL: https://doi.org/10.1056/nejmoa2304194, doi:10.1056/nejmoa2304194. This article has 884 citations and is from a highest quality peer-reviewed journal.
(ruda2024idhinhibitionin pages 6-7): Roberta Rudà, Craig Horbinski, Martin van den Bent, Matthias Preusser, and Riccardo Soffietti. Idh inhibition in gliomas: from preclinical models to clinical trials. Nature Reviews Neurology, 20:395-407, May 2024. URL: https://doi.org/10.1038/s41582-024-00967-7, doi:10.1038/s41582-024-00967-7. This article has 100 citations and is from a highest quality peer-reviewed journal.
(ballo2023associationoftumor pages 5-6): Matthew T. Ballo, Patrick Conlon, Gitit Lavy-Shahaf, Adrian Kinzel, Josef Vymazal, and Aaron M. Rulseh. Association of tumor treating fields (ttfields) therapy with survival in newly diagnosed glioblastoma: a systematic review and meta-analysis. Journal of Neuro-Oncology, 164:1-9, Jul 2023. URL: https://doi.org/10.1007/s11060-023-04348-w, doi:10.1007/s11060-023-04348-w. This article has 94 citations and is from a peer-reviewed journal.
(nishikawa2023safetyandefficacy pages 1-2): Ryo Nishikawa, Fumiyuki Yamasaki, Yoshiki Arakawa, Yoshihiro Muragaki, Yoshitaka Narita, Shota Tanaka, Shigeru Yamaguchi, Akitake Mukasa, and Masayuki Kanamori. Safety and efficacy of tumour-treating fields (ttfields) therapy for newly diagnosed glioblastoma in japanese patients using the novo-ttf system: a prospective post-approval study. Japanese Journal of Clinical Oncology, 53:371-377, Jan 2023. URL: https://doi.org/10.1093/jjco/hyad001, doi:10.1093/jjco/hyad001. This article has 26 citations and is from a peer-reviewed journal.
(lamb2024vorasidenibfirstapproval pages 4-5): Yvette N. Lamb. Vorasidenib: first approval. Drugs, 84:1325-1331, Oct 2024. URL: https://doi.org/10.1007/s40265-024-02097-2, doi:10.1007/s40265-024-02097-2. This article has 42 citations and is from a domain leading peer-reviewed journal.
(gross2021cannabidiolinducesapoptosis pages 1-2): Chase Gross, Dominique A. Ramirez, Stephanie McGrath, and Daniel L. Gustafson. Cannabidiol induces apoptosis and perturbs mitochondrial function in human and canine glioma cells. Frontiers in Pharmacology, Aug 2021. URL: https://doi.org/10.3389/fphar.2021.725136, doi:10.3389/fphar.2021.725136. This article has 73 citations.