Glioblastoma, IDH-wildtype, is the most common and aggressive primary malignant brain tumor in adults. Under WHO 2021 classification, this molecularly defined entity requires absence of IDH1/2 mutations and presence of at least one of three molecular features: TERT promoter mutation, EGFR amplification, or combined gain of chromosome 7 and loss of chromosome 10 (+7/-10). These tumors are characterized by rapid growth, extensive infiltration, florid microvascular proliferation, and necrosis. Despite multimodal therapy, prognosis remains poor with median survival of 14-16 months. Key molecular alterations include TERT promoter mutations (80%), EGFR amplification (40-50%), PTEN loss, and homozygous CDKN2A deletion.
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name: Glioblastoma, IDH-Wildtype
creation_date: '2026-01-26T02:55:13Z'
updated_date: '2026-04-22T20:13:21Z'
description: >-
Glioblastoma, IDH-wildtype, is the most common and aggressive primary malignant
brain tumor in adults. Under WHO 2021 classification, this molecularly defined
entity requires absence of IDH1/2 mutations and presence of at least one of three
molecular features: TERT promoter mutation, EGFR amplification, or combined gain
of chromosome 7 and loss of chromosome 10 (+7/-10). These tumors are characterized
by rapid growth, extensive infiltration, florid microvascular proliferation, and
necrosis. Despite multimodal therapy, prognosis remains poor with median survival
of 14-16 months. Key molecular alterations include TERT promoter mutations (80%),
EGFR amplification (40-50%), PTEN loss, and homozygous CDKN2A deletion.
categories:
- Central Nervous System Neoplasm
- Adult Brain Tumor
- Molecularly Defined Tumor
- High-Grade Glioma
parents:
- diffuse glioma
epidemiology:
- name: Most common primary malignant brain tumor
description: Glioblastoma is the most common and most malignant primary brain tumor in adults.
evidence:
- reference: PMID:41569770
reference_title: "Glioblastoma eroding through falx cerebri: a rarity or commonly seen? Illustrative case."
supports: SUPPORT
snippet: Glioblastoma, isocitrate dehydrogenase-wildtype CNS WHO grade 4 (formerly primary glioblastoma multiforme), is the most common and most malignant primary brain tumor.
explanation: This abstract explicitly identifies IDH-wildtype glioblastoma as the most common and most malignant primary brain tumor.
has_subtypes:
- name: Giant Cell Glioblastoma
description: >-
Histological variant characterized by numerous bizarre multinucleated giant cells.
May have slightly better prognosis than conventional glioblastoma. Often shows
TP53 mutations.
- name: Gliosarcoma
description: >-
Variant with biphasic pattern showing areas of glial differentiation and
malignant mesenchymal (sarcomatous) component. Similar prognosis to conventional
glioblastoma. Sarcomatous component often shows divergent molecular features.
- name: Epithelioid Glioblastoma
description: >-
Aggressive variant with epithelioid morphology, frequent BRAF V600E mutations,
and loss of INI1 expression. Often occurs in younger patients and may have
worse prognosis than conventional glioblastoma.
pathophysiology:
- name: TERT Promoter Activation
description: >-
TERT promoter mutations (C228T or C250T) occur in approximately 80% of
IDH-wildtype glioblastomas. These mutations create de novo ETS transcription
factor binding sites, leading to TERT upregulation and telomerase reactivation.
This enables unlimited replicative potential and is a defining molecular feature.
evidence:
- reference: PMID:30333046
reference_title: "TERT promoter wild-type glioblastomas show distinct clinical features and frequent PI3K pathway mutations."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "TERT promoter (TERTp) mutations are found in the majority of World Health Organization (WHO) grade IV adult IDH wild-type glioblastoma (IDH-wt GBM)."
explanation: Reports TERT promoter mutations in the majority of IDH-wildtype glioblastomas, supporting TERT promoter activation as a defining molecular feature.
cell_types:
- preferred_term: astrocyte
term:
id: CL:0000127
label: astrocyte
biological_processes:
- preferred_term: telomere maintenance via telomerase
modifier: INCREASED
term:
id: GO:0007004
label: telomere maintenance via telomerase
locations:
- preferred_term: brain
term:
id: UBERON:0000955
label: brain
downstream:
- target: Unlimited Replicative Potential
description: Telomerase reactivation enables unlimited cell division
- name: Chromosome 7 Gain and Chromosome 10 Loss
description: >-
Combined gain of chromosome 7 (+7) and loss of chromosome 10 (-10) is a
defining molecular feature of IDH-wildtype glioblastoma, present in over 90%
of cases. Chromosome 7 gain amplifies EGFR and MET. Chromosome 10 loss deletes
PTEN and other tumor suppressors.
biological_processes:
- preferred_term: chromosome organization
modifier: ABNORMAL
term:
id: GO:0051276
label: chromosome organization
downstream:
- target: EGFR/MET Pathway Activation
description: Chromosome 7 gain increases EGFR and MET copy number
- target: PTEN Tumor Suppressor Loss
description: Chromosome 10 loss eliminates PTEN
- name: EGFR/MET Pathway Activation
description: >-
EGFR is amplified in 40-50% and MET in 5% of glioblastomas. EGFR amplification
is often accompanied by EGFRvIII, a constitutively active deletion variant
lacking exons 2-7. These alterations drive proliferation through RAS/RAF/MAPK
and PI3K/AKT pathways.
biological_processes:
- preferred_term: MAPK cascade
modifier: INCREASED
term:
id: GO:0000165
label: MAPK cascade
- preferred_term: phosphatidylinositol 3-kinase signaling
modifier: INCREASED
term:
id: GO:0043491
label: phosphatidylinositol 3-kinase/protein kinase B signal transduction
downstream:
- target: Uncontrolled Cell Proliferation
description: Receptor tyrosine kinase signaling drives tumor growth
- name: PTEN Tumor Suppressor Loss
description: >-
PTEN loss through chromosome 10 deletion, mutation, or epigenetic silencing
occurs in 40-50% of glioblastomas. Loss of PTEN phosphatase activity leads to
constitutive PI3K/AKT/mTOR pathway activation, promoting survival and growth.
biological_processes:
- preferred_term: negative regulation of phosphatidylinositol 3-kinase signaling
modifier: DECREASED
term:
id: GO:0051898
label: negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
downstream:
- target: PI3K/AKT/mTOR Pathway Hyperactivation
description: Loss of PTEN removes brake on PI3K signaling
- name: PI3K/AKT/mTOR Pathway Hyperactivation
description: >-
Constitutive PI3K/AKT/mTOR activation through EGFR amplification, PIK3CA/PIK3R1 mutation,
or PTEN loss promotes cell survival, proliferation, metabolism, and angiogenesis.
PIK3CA/PIK3R1 mutations are particularly enriched in the TERT promoter-wildtype subset
of IDH-wildtype glioblastoma.
evidence:
- reference: PMID:30333046
reference_title: "TERT promoter wild-type glioblastomas show distinct clinical features and frequent PI3K pathway mutations."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "9 of 16 (56%) of TERTp-wt GBMs contained a PIK3CA or PIK3R1 mutation, while only 16/93 (17%) of TERTp-mutant GBMs harbored these alterations"
explanation: Reports PIK3CA/PIK3R1 mutations enriched in TERTp-wildtype IDH-wildtype glioblastomas (56%) compared to TERTp-mutant cases (17%), supporting recurrent PI3K pathway activation through somatic mutation in this disease.
biological_processes:
- preferred_term: cell population proliferation
modifier: INCREASED
term:
id: GO:0008283
label: cell population proliferation
- preferred_term: apoptotic process
modifier: DECREASED
term:
id: GO:0006915
label: apoptotic process
- name: Unlimited Replicative Potential
description: >-
Telomerase reactivation through TERT promoter mutations enables glioblastoma
cells to bypass replicative senescence and achieve unlimited proliferative
capacity, a hallmark of cancer.
biological_processes:
- preferred_term: cell population proliferation
modifier: INCREASED
term:
id: GO:0008283
label: cell population proliferation
- name: Uncontrolled Cell Proliferation
description: >-
Multiple converging pathways (RTK signaling, PI3K/AKT/mTOR, cell cycle
dysregulation) drive rapid proliferation characteristic of glioblastoma.
High mitotic index and proliferation markers (Ki-67 often >20%) are typical.
cell_types:
- preferred_term: astrocyte
term:
id: CL:0000127
label: astrocyte
biological_processes:
- preferred_term: cell population proliferation
modifier: INCREASED
term:
id: GO:0008283
label: cell population proliferation
histopathology:
- name: Astrocytic Glioma
finding_term:
preferred_term: Astrocytoma
term:
id: NCIT:C60781
label: Astrocytoma
frequency: VERY_FREQUENT
description: Glioblastoma is a malignant astrocytic glioma.
evidence:
- reference: PMID:17974913
reference_title: "Malignant astrocytic glioma: genetics, biology, and paths to treatment."
supports: SUPPORT
snippet: "Malignant astrocytic gliomas such as glioblastoma are the most common and lethal"
explanation: Abstract groups glioblastoma among malignant astrocytic gliomas.
phenotypes:
- category: Neurological
name: Headache
frequency: VERY_FREQUENT
description: >-
Headache from mass effect and increased intracranial pressure is common,
often progressive and worse in the morning.
phenotype_term:
preferred_term: Headache
term:
id: HP:0002315
label: Headache
- category: Neurological
name: Seizure
frequency: FREQUENT
description: >-
Seizures occur in 25-40% of patients, more commonly with cortical involvement.
May be focal or generalized.
phenotype_term:
preferred_term: Seizure
term:
id: HP:0001250
label: Seizure
- category: Neurological
name: Cognitive Impairment
frequency: FREQUENT
description: >-
Progressive cognitive decline including memory, attention, and executive
function deficits.
phenotype_term:
preferred_term: Cognitive impairment
term:
id: HP:0100543
label: Cognitive impairment
- category: Neurological
name: Focal Neurological Deficit
frequency: FREQUENT
description: >-
Motor weakness, sensory changes, aphasia, or visual field deficits depending
on tumor location. Often progresses rapidly.
phenotype_term:
preferred_term: Hemiparesis
term:
id: HP:0001269
label: Hemiparesis
- category: Neurological
name: Personality Changes
frequency: FREQUENT
description: >-
Personality and behavioral changes, particularly with frontal lobe involvement.
May include apathy, disinhibition, or emotional lability.
phenotype_term:
preferred_term: Personality changes
term:
id: HP:0000751
label: Personality changes
genetic:
- name: TERT
association: Promoter Mutation
notes: >-
TERT promoter mutations (C228T or C250T) occur in approximately 80% of
IDH-wildtype glioblastomas. Creates ETS binding sites leading to telomerase
reactivation. One of three defining molecular features for diagnosis.
evidence:
- reference: PMID:30333046
reference_title: "TERT promoter wild-type glioblastomas show distinct clinical features and frequent PI3K pathway mutations."
supports: SUPPORT
snippet: "TERT promoter (TERTp) mutations are found in the majority of World Health Organization (WHO) grade IV adult IDH wild-type glioblastoma (IDH-wt GBM)."
explanation: "Abstract reports TERT promoter mutations in the majority of IDH-wildtype glioblastomas."
- name: EGFR
association: Amplification
notes: >-
EGFR amplification occurs in 40-50% of cases. EGFRvIII variant (deletion of
exons 2-7) present in approximately 50% of EGFR-amplified tumors. EGFR
amplification is one of three defining molecular features.
- name: PTEN
association: Loss/Mutation
notes: >-
PTEN is lost or mutated in 40-50% of glioblastomas through chromosome 10 loss,
mutation, or promoter methylation. Loss activates PI3K/AKT signaling.
- name: CDKN2A/CDKN2B
association: Homozygous Deletion
notes: >-
Homozygous deletion of CDKN2A/CDKN2B at 9p21 occurs in approximately 60% of
glioblastomas. Eliminates p16INK4a and p14ARF tumor suppressors, disrupting
both RB and p53 pathways.
- name: TP53
association: Somatic Mutation
notes: >-
TP53 mutations occur in approximately 30% of IDH-wildtype glioblastomas,
less common than in IDH-mutant tumors.
- name: NF1
association: Somatic Mutation
notes: >-
NF1 mutations occur in approximately 10-15% of glioblastomas, activating
RAS/MAPK signaling. More common in mesenchymal subtype.
biochemical:
- name: MGMT Promoter Methylation
notes: >-
MGMT promoter methylation occurs in approximately 35-45% of glioblastomas and
predicts response to temozolomide. Silencing of MGMT DNA repair enzyme improves
sensitivity to alkylating chemotherapy.
treatments:
- name: Maximal Safe Resection
description: >-
Aggressive surgical resection aims to maximize extent of resection while
preserving neurological function. Greater extent of resection correlates with
improved survival. Fluorescence-guided surgery with 5-ALA improves resection.
treatment_term:
preferred_term: surgical procedure
term:
id: MAXO:0000004
label: surgical procedure
- name: Radiation Therapy
description: >-
External beam radiation therapy (60 Gy in 30 fractions) is standard adjuvant
treatment. Hypofractionated regimens may be used in elderly or poor performance
status patients.
treatment_term:
preferred_term: radiation therapy
term:
id: MAXO:0000014
label: radiation therapy
- name: Temozolomide Chemotherapy
description: >-
Concurrent and adjuvant temozolomide (Stupp protocol) is standard of care.
Temozolomide is an oral alkylating agent that crosses the blood-brain barrier.
Benefit is greatest in MGMT methylated tumors.
treatment_term:
preferred_term: chemotherapy
term:
id: MAXO:0000647
label: chemotherapy
therapeutic_agent:
- preferred_term: temozolomide
term:
id: NCIT:C1244
label: Temozolomide
- name: Tumor Treating Fields (TTFields)
description: >-
Alternating electric fields delivered via scalp arrays disrupt tumor cell
mitosis. Added to maintenance temozolomide, TTFields extend median survival
by approximately 5 months in newly diagnosed glioblastoma.
treatment_term:
preferred_term: cranial electrical stimulation
term:
id: MAXO:0000944
label: cranial electrical stimulation
- name: Bevacizumab
description: >-
Anti-VEGF monoclonal antibody used for recurrent glioblastoma. Reduces
peritumoral edema and steroid requirements but does not clearly extend
overall survival. FDA approved for recurrent disease.
treatment_term:
preferred_term: immunotherapy
term:
id: NCIT:C15262
label: Immunotherapy
therapeutic_agent:
- preferred_term: bevacizumab
term:
id: NCIT:C2039
label: Bevacizumab
disease_term:
preferred_term: IDH-wildtype glioblastoma
term:
id: MONDO:0850335
label: IDH-wildtype glioblastoma
classifications:
icdo_morphology:
classification_value: Glioma
harrisons_chapter:
- classification_value: cancer
- classification_value: solid tumor
references:
- reference: DOI:10.1007/s00401-023-02654-1
title: “De novo replication repair deficient glioblastoma, IDH-wildtype” is a distinct glioblastoma subtype in adults that may benefit from immune checkpoint blockade
found_in:
- Glioblastoma_IDH_Wildtype-deep-research-falcon.md
findings:
- statement: Glioblastoma is a clinically and molecularly heterogeneous disease, and new predictive biomarkers are needed to identify those patients most likely to respond to specific treatments.
supporting_text: Glioblastoma is a clinically and molecularly heterogeneous disease, and new predictive biomarkers are needed to identify those patients most likely to respond to specific treatments.
evidence:
- reference: DOI:10.1007/s00401-023-02654-1
reference_title: “De novo replication repair deficient glioblastoma, IDH-wildtype” is a distinct glioblastoma subtype in adults that may benefit from immune checkpoint blockade
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Glioblastoma is a clinically and molecularly heterogeneous disease, and new predictive biomarkers are needed to identify those patients most likely to respond to specific treatments.
explanation: Deep research cited this publication as relevant literature for Glioblastoma IDH Wildtype.
- reference: DOI:10.1007/s00432-025-06171-4
title: 'Limited survival benefit in patients diagnosed with glioblastoma post-2016: a SEER population based registry analysis'
found_in:
- Glioblastoma_IDH_Wildtype-deep-research-falcon.md
findings:
- statement: 'Limited survival benefit in patients diagnosed with glioblastoma post-2016: a SEER population based registry analysis'
supporting_text: 'Limited survival benefit in patients diagnosed with glioblastoma post-2016: a SEER population based registry analysis'
- reference: DOI:10.1007/s10014-022-00446-1
title: 'Update of the 2021 WHO classification of tumors of the central nervous system: adult diffuse gliomas'
found_in:
- Glioblastoma_IDH_Wildtype-deep-research-falcon.md
findings:
- statement: 'Update of the 2021 WHO classification of tumors of the central nervous system: adult diffuse gliomas'
supporting_text: 'Update of the 2021 WHO classification of tumors of the central nervous system: adult diffuse gliomas'
- reference: DOI:10.1007/s11060-024-04682-7
title: Global post‑marketing safety surveillance of Tumor Treating Fields (TTFields) therapy in over 25,000 patients with CNS malignancies treated between 2011–2022
found_in:
- Glioblastoma_IDH_Wildtype-deep-research-falcon.md
findings:
- statement: Tumor Treating Fields (TTFields) are alternating electric fields that disrupt cancer cell processes.
supporting_text: Tumor Treating Fields (TTFields) are alternating electric fields that disrupt cancer cell processes.
evidence:
- reference: DOI:10.1007/s11060-024-04682-7
reference_title: Global post‑marketing safety surveillance of Tumor Treating Fields (TTFields) therapy in over 25,000 patients with CNS malignancies treated between 2011–2022
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Tumor Treating Fields (TTFields) are alternating electric fields that disrupt cancer cell processes.
explanation: Deep research cited this publication as relevant literature for Glioblastoma IDH Wildtype.
- reference: DOI:10.1007/s11060-024-04808-x
title: 'Glioblastoma in the real-world setting: patterns of care and outcome in the Austrian population'
found_in:
- Glioblastoma_IDH_Wildtype-deep-research-falcon.md
findings:
- statement: We present results of a retrospective population-based investigation of patterns of care and outcome of glioblastoma patients in Austria.
supporting_text: We present results of a retrospective population-based investigation of patterns of care and outcome of glioblastoma patients in Austria.
evidence:
- reference: DOI:10.1007/s11060-024-04808-x
reference_title: 'Glioblastoma in the real-world setting: patterns of care and outcome in the Austrian population'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: We present results of a retrospective population-based investigation of patterns of care and outcome of glioblastoma patients in Austria.
explanation: Deep research cited this publication as relevant literature for Glioblastoma IDH Wildtype.
- reference: DOI:10.1007/s11060-025-04946-w
title: Long-term survival, patterns of progression, and patterns of use for patients with newly diagnosed glioblastoma treated with or without Tumor Treating Fields (TTFields) in a real-world setting
found_in:
- Glioblastoma_IDH_Wildtype-deep-research-falcon.md
findings:
- statement: Long-term survival, patterns of progression, and patterns of use for patients with newly diagnosed glioblastoma treated with or without Tumor Treating Fields (TTFields) in a real-world setting
supporting_text: Long-term survival, patterns of progression, and patterns of use for patients with newly diagnosed glioblastoma treated with or without Tumor Treating Fields (TTFields) in a real-world setting
- reference: DOI:10.1016/j.esmoop.2024.102943
title: 'REGOMA-OSS: a large, Italian, multicenter, prospective, observational study evaluating the efficacy and safety of regorafenib in patients with recurrent glioblastoma'
found_in:
- Glioblastoma_IDH_Wildtype-deep-research-falcon.md
findings:
- statement: 'REGOMA-OSS: a large, Italian, multicenter, prospective, observational study evaluating the efficacy and safety of regorafenib in patients with recurrent glioblastoma'
supporting_text: 'REGOMA-OSS: a large, Italian, multicenter, prospective, observational study evaluating the efficacy and safety of regorafenib in patients with recurrent glioblastoma'
- reference: DOI:10.1038/s41467-024-51315-8
title: A real-world observation of patients with glioblastoma treated with a personalized peptide vaccine
found_in:
- Glioblastoma_IDH_Wildtype-deep-research-falcon.md
findings:
- statement: A real-world observation of patients with glioblastoma treated with a personalized peptide vaccine
supporting_text: A real-world observation of patients with glioblastoma treated with a personalized peptide vaccine
- reference: DOI:10.1038/s41467-024-52167-y
title: Glioblastoma cells increase expression of notch signaling and synaptic genes within infiltrated brain tissue
found_in:
- Glioblastoma_IDH_Wildtype-deep-research-falcon.md
findings:
- statement: Glioblastoma cells increase expression of notch signaling and synaptic genes within infiltrated brain tissue
supporting_text: Glioblastoma cells increase expression of notch signaling and synaptic genes within infiltrated brain tissue
- reference: DOI:10.1038/s41591-024-02969-w
title: A prognostic neural epigenetic signature in high-grade glioma
found_in:
- Glioblastoma_IDH_Wildtype-deep-research-falcon.md
findings:
- statement: Neural–tumor interactions drive glioma growth as evidenced in preclinical models, but clinical validation is limited.
supporting_text: Neural–tumor interactions drive glioma growth as evidenced in preclinical models, but clinical validation is limited.
evidence:
- reference: DOI:10.1038/s41591-024-02969-w
reference_title: A prognostic neural epigenetic signature in high-grade glioma
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Neural–tumor interactions drive glioma growth as evidenced in preclinical models, but clinical validation is limited.
explanation: Deep research cited this publication as relevant literature for Glioblastoma IDH Wildtype.
- reference: DOI:10.1093/neuonc/noad100
title: Molecular diagnostic tools for the World Health Organization (WHO) 2021 classification of gliomas, glioneuronal and neuronal tumors; an EANO guideline
found_in:
- Glioblastoma_IDH_Wildtype-deep-research-falcon.md
findings:
- statement: In the 5th edition of the WHO CNS tumor classification (CNS5, 2021), multiple molecular characteristics became essential diagnostic criteria for many additional CNS tumor types.
supporting_text: In the 5th edition of the WHO CNS tumor classification (CNS5, 2021), multiple molecular characteristics became essential diagnostic criteria for many additional CNS tumor types.
evidence:
- reference: DOI:10.1093/neuonc/noad100
reference_title: Molecular diagnostic tools for the World Health Organization (WHO) 2021 classification of gliomas, glioneuronal and neuronal tumors; an EANO guideline
supports: SUPPORT
evidence_source: OTHER
snippet: In the 5th edition of the WHO CNS tumor classification (CNS5, 2021), multiple molecular characteristics became essential diagnostic criteria for many additional CNS tumor types.
explanation: Deep research cited this publication as relevant literature for Glioblastoma IDH Wildtype.
- reference: DOI:10.1093/neuonc/noae085
title: Immunotherapy drives mesenchymal tumor cell state shift and TME immune response in glioblastoma patients
found_in:
- Glioblastoma_IDH_Wildtype-deep-research-falcon.md
findings:
- statement: Glioblastoma is a highly aggressive type of brain tumor for which there is no curative treatment available.
supporting_text: Glioblastoma is a highly aggressive type of brain tumor for which there is no curative treatment available.
evidence:
- reference: DOI:10.1093/neuonc/noae085
reference_title: Immunotherapy drives mesenchymal tumor cell state shift and TME immune response in glioblastoma patients
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Glioblastoma is a highly aggressive type of brain tumor for which there is no curative treatment available.
explanation: Deep research cited this publication as relevant literature for Glioblastoma IDH Wildtype.
- reference: DOI:10.1093/nop/npae036
title: Do presenting symptoms predict treatment decisions and survival in glioblastoma? Real-world data from 1458 patients in the Swedish brain tumor registry
found_in:
- Glioblastoma_IDH_Wildtype-deep-research-falcon.md
findings:
- statement: Glioblastoma is the most common malignant brain tumor in adults.
supporting_text: Glioblastoma is the most common malignant brain tumor in adults.
evidence:
- reference: DOI:10.1093/nop/npae036
reference_title: Do presenting symptoms predict treatment decisions and survival in glioblastoma? Real-world data from 1458 patients in the Swedish brain tumor registry
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Glioblastoma is the most common malignant brain tumor in adults.
explanation: Deep research cited this publication as relevant literature for Glioblastoma IDH Wildtype.
- reference: DOI:10.1093/oncolo/oyae227
title: Recent advances in Tumor Treating Fields (TTFields) therapy for glioblastoma
found_in:
- Glioblastoma_IDH_Wildtype-deep-research-falcon.md
findings:
- statement: Tumor Treating Fields (TTFields) therapy is a locoregional, anticancer treatment consisting of a noninvasive, portable device that delivers alternating electric fields to tumors through arrays placed on the skin.
supporting_text: Tumor Treating Fields (TTFields) therapy is a locoregional, anticancer treatment consisting of a noninvasive, portable device that delivers alternating electric fields to tumors through arrays placed on the skin.
evidence:
- reference: DOI:10.1093/oncolo/oyae227
reference_title: Recent advances in Tumor Treating Fields (TTFields) therapy for glioblastoma
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Tumor Treating Fields (TTFields) therapy is a locoregional, anticancer treatment consisting of a noninvasive, portable device that delivers alternating electric fields to tumors through arrays placed on the skin.
explanation: Deep research cited this publication as relevant literature for Glioblastoma IDH Wildtype.
- reference: DOI:10.1101/2025.01.16.25320661
title: Whole genome sequencing-based analysis of genetic predisposition to adult glioblastoma
found_in:
- Glioblastoma_IDH_Wildtype-deep-research-falcon.md
findings:
- statement: Glioblastoma is most commonly reported in the second (pediatric form) and seventh (adult form) decade of life.
supporting_text: Glioblastoma is most commonly reported in the second (pediatric form) and seventh (adult form) decade of life.
evidence:
- reference: DOI:10.1101/2025.01.16.25320661
reference_title: Whole genome sequencing-based analysis of genetic predisposition to adult glioblastoma
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Glioblastoma is most commonly reported in the second (pediatric form) and seventh (adult form) decade of life.
explanation: Deep research cited this publication as relevant literature for Glioblastoma IDH Wildtype.
- reference: DOI:10.1126/science.abm5214
title: Distinct myeloid-derived suppressor cell populations in human glioblastoma
found_in:
- Glioblastoma_IDH_Wildtype-deep-research-falcon.md
findings:
- statement: The role of glioma-associated myeloid cells in tumor growth and immune evasion remains poorly understood.
supporting_text: The role of glioma-associated myeloid cells in tumor growth and immune evasion remains poorly understood.
evidence:
- reference: DOI:10.1126/science.abm5214
reference_title: Distinct myeloid-derived suppressor cell populations in human glioblastoma
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: The role of glioma-associated myeloid cells in tumor growth and immune evasion remains poorly understood.
explanation: Deep research cited this publication as relevant literature for Glioblastoma IDH Wildtype.
- reference: DOI:10.11588/heidok.00035474
title: Tumor Pseudolineages from a Healthy Lineage Template Reveal Organizational Principles and Cell-Fate Modulators in Glioblastoma
found_in:
- Glioblastoma_IDH_Wildtype-deep-research-falcon.md
findings:
- statement: Tumor Pseudolineages from a Healthy Lineage Template Reveal Organizational Principles and Cell-Fate Modulators in Glioblastoma
supporting_text: Tumor Pseudolineages from a Healthy Lineage Template Reveal Organizational Principles and Cell-Fate Modulators in Glioblastoma
- reference: DOI:10.1186/s40478-024-01762-7
title: 'Pediatric-type high-grade gliomas with PDGFRA amplification in adult patients with Li-Fraumeni syndrome: clinical and molecular characterization of three cases'
found_in:
- Glioblastoma_IDH_Wildtype-deep-research-falcon.md
findings:
- statement: Li-Fraumeni syndrome (LFS) is an autosomal dominant tumor predisposition syndrome caused by heterozygous germline mutations or deletions in the TP53 tumor suppressor gene.
supporting_text: Li-Fraumeni syndrome (LFS) is an autosomal dominant tumor predisposition syndrome caused by heterozygous germline mutations or deletions in the TP53 tumor suppressor gene.
evidence:
- reference: DOI:10.1186/s40478-024-01762-7
reference_title: 'Pediatric-type high-grade gliomas with PDGFRA amplification in adult patients with Li-Fraumeni syndrome: clinical and molecular characterization of three cases'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Li-Fraumeni syndrome (LFS) is an autosomal dominant tumor predisposition syndrome caused by heterozygous germline mutations or deletions in the TP53 tumor suppressor gene.
explanation: Deep research cited this publication as relevant literature for Glioblastoma IDH Wildtype.
- reference: DOI:10.17879/freeneuropathology-2024-5892
title: Adult glioblastoma with Lynch syndrome-associated mismatch repair deficiency forms a distinct high-risk molecular subgroup
found_in:
- Glioblastoma_IDH_Wildtype-deep-research-falcon.md
findings:
- statement: Glioblastoma is the most frequent and malignant primary brain tumor.
supporting_text: Glioblastoma is the most frequent and malignant primary brain tumor.
evidence:
- reference: DOI:10.17879/freeneuropathology-2024-5892
reference_title: Adult glioblastoma with Lynch syndrome-associated mismatch repair deficiency forms a distinct high-risk molecular subgroup
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Glioblastoma is the most frequent and malignant primary brain tumor.
explanation: Deep research cited this publication as relevant literature for Glioblastoma IDH Wildtype.
- reference: DOI:10.32074/1591-951x-823
title: Adult type diffuse gliomas in the new 2021 WHO Classification
found_in:
- Glioblastoma_IDH_Wildtype-deep-research-falcon.md
findings:
- statement: Adult type diffuse gliomas in the new 2021 WHO Classification
supporting_text: Adult type diffuse gliomas in the new 2021 WHO Classification
- reference: DOI:10.3389/fonc.2023.1200815
title: 'Histological and molecular glioblastoma, IDH-wildtype: a real-world landscape using the 2021 WHO classification of central nervous system tumors'
found_in:
- Glioblastoma_IDH_Wildtype-deep-research-falcon.md
findings:
- statement: 'Glioblastoma (GBM), the most lethal primary brain malignancy, is divided into histological (hist-GBM) and molecular (mol-GBM) subtypes according to the 2021 World Health Organization classification of central nervous system tumors.'
supporting_text: Glioblastoma (GBM), the most lethal primary brain malignancy, is divided into histological (hist-GBM) and molecular (mol-GBM) subtypes according to the 2021 World Health Organization classification of central nervous system tumors.
evidence:
- reference: DOI:10.3389/fonc.2023.1200815
reference_title: 'Histological and molecular glioblastoma, IDH-wildtype: a real-world landscape using the 2021 WHO classification of central nervous system tumors'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Glioblastoma (GBM), the most lethal primary brain malignancy, is divided into histological (hist-GBM) and molecular (mol-GBM) subtypes according to the 2021 World Health Organization classification of central nervous system tumors.
explanation: Deep research cited this publication as relevant literature for Glioblastoma IDH Wildtype.
- reference: DOI:10.3390/biomedicines12061349
title: 'The 2021 World Health Organization Central Nervous System Tumor Classification: The Spectrum of Diffuse Gliomas'
found_in:
- Glioblastoma_IDH_Wildtype-deep-research-falcon.md
findings:
- statement: The 2021 edition of the World Health Organization (WHO) classification of central nervous system tumors introduces significant revisions across various tumor types.
supporting_text: The 2021 edition of the World Health Organization (WHO) classification of central nervous system tumors introduces significant revisions across various tumor types.
evidence:
- reference: DOI:10.3390/biomedicines12061349
reference_title: 'The 2021 World Health Organization Central Nervous System Tumor Classification: The Spectrum of Diffuse Gliomas'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: The 2021 edition of the World Health Organization (WHO) classification of central nervous system tumors introduces significant revisions across various tumor types.
explanation: Deep research cited this publication as relevant literature for Glioblastoma IDH Wildtype.
- reference: DOI:10.3390/cancers17010046
title: 'Regorafenib Treatment for Recurrent Glioblastoma Beyond Bevacizumab-Based Therapy: A Large, Multicenter, Real-Life Study'
found_in:
- Glioblastoma_IDH_Wildtype-deep-research-falcon.md
findings:
- statement: In the REGOMA trial, regorafenib demonstrated an overall survival advantage over lomustine, and it has become a recommended treatment for recurrent glioblastoma in guidelines.
supporting_text: In the REGOMA trial, regorafenib demonstrated an overall survival advantage over lomustine, and it has become a recommended treatment for recurrent glioblastoma in guidelines.
evidence:
- reference: DOI:10.3390/cancers17010046
reference_title: 'Regorafenib Treatment for Recurrent Glioblastoma Beyond Bevacizumab-Based Therapy: A Large, Multicenter, Real-Life Study'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: In the REGOMA trial, regorafenib demonstrated an overall survival advantage over lomustine, and it has become a recommended treatment for recurrent glioblastoma in guidelines.
explanation: Deep research cited this publication as relevant literature for Glioblastoma IDH Wildtype.
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 Glioblastoma, IDH-Wildtype 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
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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
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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
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Search first: Clinical guidelines, FDA approvals, PubMed
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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
Glioblastoma, IDH‑wildtype (GBM-IDHwt) is the most common adult grade 4 diffuse astrocytic tumor and is defined in WHO CNS5 (2021) by IDH-wildtype status plus either classic grade-4 histology (necrosis and/or microvascular proliferation) or one of three molecular “grade-4” signatures (TERT promoter mutation, EGFR amplification, combined whole-chromosome +7/−10) even when histology appears lower grade. (guo2023histologicalandmolecular pages 1-2, antonelli2022adulttypediffuse pages 10-11, antonelli2022adulttypediffuse media 491d0085)
In recent, large real-world cohorts explicitly restricted to pathologically verified IDH‑wildtype GBM, median survival is ~11–12 months with ~21–26% 2-year survival. (bruhn2024dopresentingsymptoms pages 1-2, hainfellner2024glioblastomainthe pages 1-3, dhingra2025limitedsurvivalbenefit pages 1-2)
Glioblastoma, IDH‑wildtype is an infiltrative diffuse astrocytic glioma lacking IDH mutation (and typically lacking histone H3 alterations) with WHO grade 4 biology. It is diagnosed either by grade-4 histology (necrosis and/or microvascular proliferation) or by specific molecular features that are sufficient to assign grade 4 in IDH‑wildtype diffuse astrocytic tumors. (antonelli2022adulttypediffuse pages 10-11, antonelli2022adulttypediffuse media 491d0085)
Direct abstract-level quote supporting definition: In a real-world WHO CNS5 reclassification study, “IDH-wildtype diffuse astrocytic tumors without the histological features of GBM… are considered as molecular GBM (mol-GBM, WHO grade 4) if they harbor any of the following molecular abnormalities: TERT promoter mutation, EGFR amplification, or chromosomal + 7/−10 copy changes.” (guo2023histologicalandmolecular pages 1-2)
This report primarily uses aggregated disease-level resources: WHO CNS5-oriented reviews and guidelines, plus population/registry real‑world cohorts (e.g., Swedish Brain Tumor Registry; Austrian national registry; SEER) and selected clinical trial/observational studies. (bruhn2024dopresentingsymptoms pages 1-2, hainfellner2024glioblastomainthe pages 1-3, dhingra2025limitedsurvivalbenefit pages 1-2)
GBM-IDHwt is driven by recurrent alterations in signaling and cell-cycle networks (RTK/RAS/PI3K; TP53; RB pathways), and is defined diagnostically by a subset of molecular hallmarks (TERT promoter mutation, EGFR amplification, and/or +7/−10). (antonelli2022adulttypediffuse pages 10-11, guo2023histologicalandmolecular pages 1-2)
Recent data highlight a rare but clinically important subset of adult IDH‑wildtype glioblastomas with mismatch-repair deficiency and hypermutation: - In a prospective genomic profiling series of 459 primary treatment-naïve adult IDH‑wildtype GBMs, a distinct “de novo replication repair deficient” subgroup comprised 2% (9/459), defined by somatic hypermutation and biallelic inactivation of a canonical MMR gene; deleterious MMR variants were often present in the germline (heterozygous) with somatic second hit, consistent with underlying Lynch syndrome. This subgroup had universal giant cell histology and lacked canonical EGFR amplification and +7/−10; median OS was 36.8 vs 15.5 months for other GBMs (p<0.001), and 4/5 patients treated with immune checkpoint blockade survived >3 years. (hadad2024“denovoreplication pages 1-2) - A separate study (n=218) described a rare germline MMR/Lynch subgroup (G3/MMR) with very poor median survival (3.25 months post-surgery) in five germline MMR-variant carriers (MLH1, PMS2, MSH2, MSH6). (georgescu2024adultglioblastomawith pages 1-2)
These studies collectively support a clinically actionable concept: a minority of GBM-IDHwt arises in the context of hereditary (or constitutional) MMR deficiency, often with hypermutation, and may have differential prognosis and potential sensitivity to checkpoint blockade. (hadad2024“denovoreplication pages 1-2, georgescu2024adultglioblastomawith pages 1-2)
A WGS-based germline analysis in an unselected cohort of 98 adult WHO grade 4 glioma patients (93.9% IDH‑wildtype) reported: - Pathogenic/likely pathogenic germline variants relevant to glioblastoma in ~11% of patients. (opijnen2025wholegenomesequencingbased pages 1-6) - Enrichment for MMR genes (e.g., MSH6, PMS2, MSH2) and other predisposition genes including TP53 (Li‑Fraumeni), NF1, BRCA1, SUFU. (opijnen2025wholegenomesequencingbased pages 1-6) - MMR deficiency as a major mechanism: 7.1% carried an MMR-gene PGV with multiple MSI cases. (opijnen2025wholegenomesequencingbased pages 15-18)
In three adult Li‑Fraumeni syndrome patients with high-grade gliomas, tumors were IDH1/2-wildtype but lacked typical GBM-IDHwt hallmarks (TERT promoter mutation, EGFR amplification, +7/−10). Instead, they showed PDGFRA amplification and methylation profiles aligning with pediatric-type high-grade glioma RTK1, suggesting that adult predisposition syndromes can yield tumors that mimic glioblastoma histologically but are molecularly distinct. (kibe2024pediatrictypehighgradegliomas pages 1-2)
Within the ingested evidence for this run, environmental/occupational risk factors were not supported by extractable primary text. The report therefore does not assert specific environmental risk magnitudes.
Not established in the retrieved evidence set.
Swedish Brain Tumor Registry (SBTR), IDH-wildtype only (n=1,458; 2018–2021): presenting symptom categories included focal neurological deficits, cognitive dysfunction, headache, epilepsy (seizures), signs of raised intracranial pressure, and cranial nerve symptoms. Median survival was 345 days (~11.5 months) and 2-year survival 21.5%. (bruhn2024dopresentingsymptoms pages 1-2)
Austrian population registry (n=1,420; 2014–2018; IDH-wildtype known in 78.5%): symptom frequencies at presentation were focal neurological deficits 42.2%, headache 17.3%, epilepsy 15.6%, personality changes 10.9%. (hainfellner2024glioblastomainthe pages 3-4)
In SBTR, initial cognitive dysfunction was associated with substantially shorter survival (median 265 vs 409 days, P<.001) and remained independently adverse after multivariable adjustment; patients with cognitive deficits were less likely to undergo radical surgery and intensive oncologic therapy. (bruhn2024dopresentingsymptoms pages 1-2)
From registry symptom categories and standard neuro-oncology presentation: - Seizures: HP:0001250 - Headache: HP:0002315 - Cognitive impairment: HP:0100543 - Focal neurological deficit / hemiparesis: HP:0001263 (or HP:0001276 for weakness; mapping may be refined by chart abstraction) - Signs of increased intracranial pressure (e.g., nausea/vomiting, papilledema): HP:0002516, HP:0002013
(These HPO mappings are ontology suggestions; the evidence sources provide symptom categories but not term IDs.) (bruhn2024dopresentingsymptoms pages 1-2, hainfellner2024glioblastomainthe pages 3-4)
WHO CNS5 defines glioblastoma, IDH‑wildtype as an IDH-wildtype diffuse astrocytic tumor with either (i) necrosis and/or microvascular proliferation, or (ii) one or more of: TERT promoter mutation, EGFR amplification, and/or +7/−10. (antonelli2022adulttypediffuse pages 10-11, antonelli2022adulttypediffuse media 491d0085)
A visual summary of this WHO diagnostic algorithm is available in Figure 2 from Antonelli & Poliani (2022). (antonelli2022adulttypediffuse media 491d0085)
Across real-world WHO CNS5 reclassification cohorts, recurrent alterations include: - EGFR, TERT, CDKN2A/B, PTEN, and copy-number changes across chromosomes including 7 and 10. (guo2023histologicalandmolecular pages 1-2)
Quote (abstract) for a cohort-level molecular summary: “Common molecular features included copy-number changes in chromosomes 1, 7, 9, 10, and 19, as well as alterations in EGFR, TERT, CDKN2A/B, and PTEN…” (guo2023histologicalandmolecular pages 1-2)
MGMT promoter methylation is a key predictive biomarker for temozolomide benefit and is incorporated into molecular-testing guidance for WHO CNS5 gliomas. (sahm2023moleculardiagnostictools pages 14-14, sahm2023moleculardiagnostictools pages 2-3) - Austrian registry: MGMT promoter methylation present in 34.3% of patients (unknown 30.2%). (hainfellner2024glioblastomainthe pages 3-4) - WHO2021 real-world reclassification cohort: MGMT promoter methylation predicted improved survival. (guo2023histologicalandmolecular pages 1-2)
Open Targets lists multiple associated targets for “glioblastoma multiforme” including EGFR, TP53, IDH1, PTEN, ATRX, RB1, NF1, TERT, among others (mapping evidence includes literature PMIDs). (antonelli2022adulttypediffuse media 491d0085)
Spatial transcriptomics in patient samples indicates that transcriptional subtype distinctions (classical/proneural/mesenchymal) are strongest in tumor cores but attenuate in infiltrated brain tissue, consistent with state convergence during invasion. (harwood2024glioblastomacellsincrease pages 1-2)
A key mechanistic theme is cell-state plasticity (e.g., transitions toward a mesenchymal program) and coupling to microenvironmental niches. (hendriksen2024immunotherapydrivesmesenchymal pages 1-3, forster2024tumorpseudolineagesfrom pages 27-30)
GBM cells disperse into adjacent parenchyma, often tracking vasculature and white matter, enabling escape from resection; recurrence is frequent and often local. A spatial-transcriptomics study notes recurrence “within resection margins in ~90% of patients within one year.” (harwood2024glioblastomacellsincrease pages 1-2)
A 2024 Nature Medicine study defined a prognostic “neural epigenetic signature” across n=1,058 glioblastoma samples; high-neural tumors showed synaptic-gene upregulation and worse outcomes (median OS 14.2 vs 21.2 months, median PFS 6.2 vs 10.0 months). (drexler2024aprognosticneural pages 1-2)
A 2025 Science study used single-cell RNA-seq (33 gliomas) and identified distinct MDSC populations in IDH-wildtype glioblastoma, including early progenitor MDSCs (E‑MDSCs) and monocytic MDSCs (M‑MDSCs). Spatial transcriptomics localized E‑MDSCs with metabolic stem-like tumor cells in pseudopalisading regions and suggested reciprocal tumor–myeloid cross-talk (tumor chemokines recruit E‑MDSCs; E‑MDSCs provide tumor-supportive growth factors). (jackson2025distinctmyeloidderivedsuppressor pages 1-3)
GO biological processes (examples): - cell proliferation; cell migration; angiogenesis; hypoxia response; antigen processing and presentation; immune suppression (conceptual mapping based on described programs). (harwood2024glioblastomacellsincrease pages 1-2, jackson2025distinctmyeloidderivedsuppressor pages 1-3)
Cell Ontology (CL) terms (examples): - tumor-associated macrophage / microglia (as described); myeloid-derived suppressor cell (E‑MDSC / M‑MDSC populations) (jackson2025distinctmyeloidderivedsuppressor pages 1-3)
WHO CNS5 requires integrated histology plus molecular assessment for many CNS tumors. For adult diffuse gliomas, when an IDH‑wildtype diffuse glioma lacks necrosis/microvascular proliferation, it should be tested for EGFR amplification, TERT promoter mutation, and +7/−10 to establish a WHO grade-4 diagnosis. (antonelli2022adulttypediffuse pages 10-11)
The EANO guideline on molecular diagnostic tools emphasizes that WHO CNS5 requires an integrated “histomolecular” diagnosis, and explicitly includes MGMT promoter methylation because of its predictive role in IDH‑wildtype GBM. (sahm2023moleculardiagnostictools pages 2-3)
For MGMT promoter methylation testing, EANO recommends reporting assay details (including CpGs interrogated), the numerical test value, and explicit cutoffs/gray zones; it discourages MGMT immunohistochemistry as the basis for clinical decision-making. (sahm2023moleculardiagnostictools pages 14-14)
Methylation-array platforms can output MGMT promoter information, but the guideline notes that “optimal methods and respective cut-offs… are debated” and that CNV-based inferences should be confirmed by orthogonal methods. (sahm2023moleculardiagnostictools pages 11-12)
The treatment backbone remains maximal safe resection followed by radiotherapy with concurrent and adjuvant temozolomide (“Stupp regimen”). (antonelli2022adulttypediffuse pages 10-11, latzer2024arealworldobservation pages 1-2)
Predictive stratifier: temozolomide benefit is greater in MGMT promoter–methylated tumors, and likely marginal in MGMT-unmethylated tumors. (antonelli2022adulttypediffuse pages 10-11, sahm2023moleculardiagnostictools pages 14-14)
Suggested MAXO terms (examples): - Maximal surgical resection: MAXO:0001175 (neurosurgical tumor resection; placeholder mapping) - Radiotherapy: MAXO:0000058 - Alkylating chemotherapy (temozolomide): MAXO:0000647 (chemotherapy; placeholder mapping)
Safety (post-marketing; 2011–2022): in a global PMS dataset of 25,898 TTFields-treated CNS tumor patients (68% newly diagnosed GBM), TTFields-related AEs occurred in 56%; the most frequent were beneath-array skin reactions (43%), electric sensation/tingling (14%), and warmth (12%). No TTFields-related systemic adverse events were reported. (mrugala2024globalpost‑marketingsafety pages 1-2)
Real-world effectiveness: a single-institution cohort (2015–2023; follow-up through 2024) of 208 newly diagnosed GBM patients showed longer survival with TTFields: median OS 21.7 vs 17.7 months (p=0.029) and PFS 12.4 vs 9.6 months (p=0.047) for TTFields vs no TTFields. (riegel2025longtermsurvivalpatterns pages 1-2)
Suggested MAXO term: TTFields (device-based electrical field therapy): MAXO:0001017 (device therapy; placeholder mapping).
Prospective observational (REGOMA-OSS; 30 Italian centers; n=190; 92.4% IDH-wildtype): median OS 7.9 months, median PFS 2.6 months; grade 3–4 drug-related AEs 22.6%; dose reductions 36%; no treatment-related deaths. (caccese2024regomaossalarge pages 1-2)
Third-line after bevacizumab (Turkey; n=65; IDH-wildtype): median PFS 2.5 months, median OS 4.1 months; no drug-related deaths reported. (tunbekici2024regorafenibtreatmentfor pages 1-2)
Platform trial update (GBM AGILE; NCT03970447): a reported analysis indicated regorafenib accrual was stopped for futility with mean hazard ratios >1 and low Bayesian probability of benefit across signatures, highlighting uncertainty/heterogeneity in benefit and the need for biomarker-driven selection. (khagi2025recentadvancesin pages 7-8)
Suggested MAXO term: multi-kinase inhibitor therapy: MAXO:0000647 (chemotherapy/targeted therapy; placeholder mapping).
DCVax-L (autologous tumor lysate-loaded dendritic cell vaccine; NCT00045968): in an externally controlled phase 3 study, median OS for newly diagnosed GBM was 19.3 months vs 16.5 months in controls (HR 0.80; P=.002), with 60-month survival 13.0% vs 5.7%; in recurrent GBM, median OS was 13.2 vs 7.8 months (HR 0.58; P<.001). (liau2023…cellvaccination pages 1-2)
Personalized neoantigen peptide vaccine (real-world “individual healing attempt”; n=173; 2015–2023): median OS from first diagnosis 31.9 months (95% CI 25.0–36.5); immune response detected in 90% (87/97) monitored patients; multiple vaccine-induced T-cell responses associated with longer survival (53 vs 27 months, P=0.03). (latzer2024arealworldobservation pages 1-2)
Expert analysis note: Recent literature highlights that glioblastoma immunotherapy outcomes must be interpreted cautiously due to heterogeneous trial designs and immunosuppressive microenvironments, and may require combination strategies targeting myeloid suppression and/or mesenchymal programs. (hendriksen2024immunotherapydrivesmesenchymal pages 1-3, jackson2025distinctmyeloidderivedsuppressor pages 1-3)
Not addressed in the retrieved evidence set for this run.
Not comprehensively retrieved in this run. However, mechanistic studies cited here relied on spatial transcriptomics in patients (harwood2024glioblastomacellsincrease pages 1-2), scRNA-seq/spatial in human tumors (jackson2025distinctmyeloidderivedsuppressor pages 1-3), and xenograft modeling noted in neural-signature work (drexler2024aprognosticneural pages 1-2).
Figure 2 in Antonelli & Poliani (2022) provides a WHO CNS5 diagnostic algorithm showing that GBM-IDHwt can be diagnosed by histologic grade-4 features or by molecular criteria (TERT promoter mutation, EGFR amplification, and/or +7/−10). (antonelli2022adulttypediffuse media 491d0085)
| Category | Marker / criterion | What it means in glioblastoma, IDH-wildtype | Representative frequency / note from provided sources |
|---|---|---|---|
| WHO CNS5 histologic criterion | Necrosis and/or microvascular proliferation in an IDH-wildtype diffuse astrocytic glioma | Sufficient for diagnosis of glioblastoma, IDH-wildtype, CNS WHO grade 4 when integrated with molecular exclusion of IDH/H3-altered entities (antonelli2022adulttypediffuse pages 10-11, gue2024the2021world pages 9-12, antonelli2022adulttypediffuse media 491d0085) | WHO CNS5 defines GBM as IDH-wildtype with either these histologic features or specified molecular features (gue2024the2021world pages 9-12, antonelli2022adulttypediffuse pages 10-11, antonelli2022adulttypediffuse media 491d0085) |
| WHO CNS5 molecular criterion | TERT promoter mutation | Can upgrade an otherwise lower-grade appearing IDH-wildtype diffuse astrocytic glioma to molecular glioblastoma; less specific than EGFR amplification or +7/−10 when present alone (guo2023histologicalandmolecular pages 1-2, antonelli2022adulttypediffuse pages 10-11) | 66.3% in one WHO2021-classified GBM cohort; editorial cites ~64–82% in molecular subclasses (guo2023histologicalandmolecular pages 1-2, komori2023updateofthe pages 1-2) |
| WHO CNS5 molecular criterion | EGFR amplification | Diagnostic molecular feature for GBM, IDH-wildtype; also associated with poorer OS in IDH-wildtype diffuse gliomas/GBM (antonelli2022adulttypediffuse pages 10-11, guo2023histologicalandmolecular pages 1-2) | 85.5% in GBM in one real-world study; ~50% cited in review literature; 58.7% in a modern RT/TMZ cohort using FISH/NGS/IHC (antonelli2022adulttypediffuse pages 8-10, hainfellner2024glioblastomainthe pages 1-3) |
| WHO CNS5 molecular criterion | Combined whole chromosome 7 gain / chromosome 10 loss (+7/−10) | Diagnostic molecular signature for GBM, IDH-wildtype; often used to identify molecular GBM when histology is lower grade (gue2024the2021world pages 9-12, guo2023histologicalandmolecular pages 1-2, antonelli2022adulttypediffuse pages 10-11) | Common hallmark of conventional IDH-wildtype GBM; noted as absent in a rare de novo replication-repair-deficient GBM subtype (guo2023histologicalandmolecular pages 1-2, antonelli2022adulttypediffuse pages 8-10) |
| Core genomic alteration | PTEN loss / deletion / mutation | Common tumor-suppressor alteration in PI3K-AKT signaling; generally adverse biology/prognosis, not itself diagnostic under WHO CNS5 (antonelli2022adulttypediffuse pages 10-11) | 60% PTEN alterations in one high-grade glioma sequencing cohort; poor-prognosis association reported in IDH-wildtype GBM (hainfellner2024glioblastomainthe pages 1-3, komori2023updateofthe pages 1-2) |
| Core genomic alteration | CDKN2A/B deletion / homozygous deletion | Frequent cell-cycle alteration in GBM; adverse prognostic factor in GBM though not a WHO CNS5 stand-alone diagnostic criterion for IDH-wildtype GBM (guo2023histologicalandmolecular pages 1-2, antonelli2022adulttypediffuse pages 10-11) | Common alteration in GBM cohorts; in one prognostic study, CDKN2A/B homozygous deletion was statistically significant for worse outcome in GBM (guo2023histologicalandmolecular pages 1-2, komori2023updateofthe pages 1-2) |
| Predictive biomarker | MGMT promoter methylation | Predicts better benefit from temozolomide and is associated with improved survival; important for treatment planning, not diagnostic (antonelli2022adulttypediffuse pages 10-11, sahm2023moleculardiagnostictools pages 2-3) | 34.3% methylated in Austrian registry; 49.1% methylated in one IDH-wildtype GBM RT/TMZ cohort; associated with better survival in real-world WHO2021 GBM cohort (hainfellner2024glioblastomainthe pages 3-4, hainfellner2024glioblastomainthe pages 1-3, guo2023histologicalandmolecular pages 1-2) |
| Diagnostic workflow note | IDH / H3 exclusion before calling GBM, IDH-wildtype | Reviews and algorithms stress confirming IDH-wildtype status and considering H3-altered pediatric-type gliomas, especially in younger patients, before applying molecular GBM criteria (antonelli2022adulttypediffuse pages 10-11, antonelli2022adulttypediffuse media 491d0085) | Practical algorithm: if no necrosis/vascular proliferation, test EGFR amplification, TERT promoter mutation, and +7/−10; also evaluate H3 alterations in relevant clinical settings (antonelli2022adulttypediffuse pages 10-11) |
| Representative clinical-genomic profile | Conventional IDH-wildtype GBM landscape | Recurrent alterations cluster in RTK/RAS/PI3K, TP53, and RB pathways; EGFR, TERT, PTEN, CDKN2A/B are repeatedly reported as common (antonelli2022adulttypediffuse pages 10-11, guo2023histologicalandmolecular pages 1-2) | In WHO2021-classified GBM series: common changes involved chromosomes 1, 7, 9, 10, 19 and EGFR, TERT, CDKN2A/B, PTEN (guo2023histologicalandmolecular pages 1-2) |
| Important caveat | Isolated TERT promoter mutation | Supports WHO CNS5 molecular GBM classification, but multiple sources caution that isolated TERTp mutation in a low-grade-appearing diffuse glioma should be interpreted carefully because of limited specificity (antonelli2022adulttypediffuse pages 10-11) | Review explicitly states TERT promoter mutation is the least specific of the three WHO molecular criteria (antonelli2022adulttypediffuse pages 10-11) |
Table: This table summarizes WHO CNS5 diagnostic rules and major biomarkers for glioblastoma, IDH-wildtype, including their diagnostic, prognostic, or predictive roles. It also gives representative frequencies and practical notes from the cited real-world and review sources.
References
(antonelli2022adulttypediffuse media 491d0085): 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 67 citations.
(gue2024the2021world pages 9-12): 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 13 citations.
(antonelli2022adulttypediffuse pages 10-11): 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 67 citations.
(guo2023histologicalandmolecular pages 1-2): Xiaopeng Guo, Lingui Gu, Yilin Li, Zhiyao Zheng, Wenlin Chen, Yaning Wang, Yuekun Wang, Hao Xing, Yixin Shi, Delin Liu, Tianrui Yang, Yu Xia, Junlin Li, Jiaming Wu, Kun Zhang, Tingyu Liang, Hai Wang, Qianshu Liu, Shanmu Jin, Tian Qu, Siying Guo, Huanzhang Li, Yu Wang, and Wenbin Ma. Histological and molecular glioblastoma, idh-wildtype: a real-world landscape using the 2021 who classification of central nervous system tumors. Frontiers in Oncology, Jul 2023. URL: https://doi.org/10.3389/fonc.2023.1200815, doi:10.3389/fonc.2023.1200815. This article has 98 citations.
(bruhn2024dopresentingsymptoms pages 1-2): Helena Bruhn, Björn Tavelin, Lena Rosenlund, and Roger Henriksson. Do presenting symptoms predict treatment decisions and survival in glioblastoma? real-world data from 1458 patients in the swedish brain tumor registry. Neuro-Oncology Practice, 11:652-659, Apr 2024. URL: https://doi.org/10.1093/nop/npae036, doi:10.1093/nop/npae036. This article has 9 citations and is from a 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 6 citations and is from a peer-reviewed journal.
(dhingra2025limitedsurvivalbenefit pages 1-2): Shaurya Dhingra, Matthew Koshy, and Mark Korpics. Limited survival benefit in patients diagnosed with glioblastoma post-2016: a seer population based registry analysis. Journal of Cancer Research and Clinical Oncology, Jun 2025. URL: https://doi.org/10.1007/s00432-025-06171-4, doi:10.1007/s00432-025-06171-4. This article has 7 citations and is from a peer-reviewed journal.
(hadad2024“denovoreplication pages 1-2): Sara Hadad, Rohit Gupta, Nancy Ann Oberheim Bush, Jennie W. Taylor, Javier E. Villanueva-Meyer, Jacob S. Young, Jasper Wu, Ajay Ravindranathan, Yalan Zhang, Gayathri Warrier, Lucie McCoy, Anny Shai, Melike Pekmezci, Arie Perry, Andrew W. Bollen, Joanna J. Phillips, Steve E. Braunstein, David R. Raleigh, Philip Theodosopoulos, Manish K. Aghi, Edward F. Chang, Shawn L. Hervey-Jumper, Joseph F. Costello, John de Groot, Nicholas A. Butowski, Jennifer L. Clarke, Susan M. Chang, Mitchel S. Berger, Annette M. Molinaro, and David A. Solomon. “de novo replication repair deficient glioblastoma, idh-wildtype” is a distinct glioblastoma subtype in adults that may benefit from immune checkpoint blockade. Acta Neuropathologica, Dec 2024. URL: https://doi.org/10.1007/s00401-023-02654-1, doi:10.1007/s00401-023-02654-1. This article has 38 citations and is from a highest quality peer-reviewed journal.
(georgescu2024adultglioblastomawith pages 1-2): Maria-Magdalena Georgescu. Adult glioblastoma with lynch syndrome-associated mismatch repair deficiency forms a distinct high-risk molecular subgroup. Free Neuropathology, Dec 2024. URL: https://doi.org/10.17879/freeneuropathology-2024-5892, doi:10.17879/freeneuropathology-2024-5892. This article has 5 citations and is from a peer-reviewed journal.
(opijnen2025wholegenomesequencingbased pages 1-6): Mark P. van Opijnen, Devin R. van Valkengoed, Joep de Ligt, Filip Y.F. de Vos, Marike L.D. Broekman, Edwin Cuppen, and Roelof Koster. Whole genome sequencing-based analysis of genetic predisposition to adult glioblastoma. MedRxiv, Jan 2025. URL: https://doi.org/10.1101/2025.01.16.25320661, doi:10.1101/2025.01.16.25320661. This article has 1 citations.
(opijnen2025wholegenomesequencingbased pages 15-18): Mark P. van Opijnen, Devin R. van Valkengoed, Joep de Ligt, Filip Y.F. de Vos, Marike L.D. Broekman, Edwin Cuppen, and Roelof Koster. Whole genome sequencing-based analysis of genetic predisposition to adult glioblastoma. MedRxiv, Jan 2025. URL: https://doi.org/10.1101/2025.01.16.25320661, doi:10.1101/2025.01.16.25320661. This article has 1 citations.
(kibe2024pediatrictypehighgradegliomas pages 1-2): Yuji Kibe, Fumiharu Ohka, Kosuke Aoki, Junya Yamaguchi, Kazuya Motomura, Eiji Ito, Kazuhito Takeuchi, Yuichi Nagata, Satoshi Ito, Nobuhiko Mizutani, Yoshiki Shiba, Sachi Maeda, Tomohide Nishikawa, Hiroki Shimizu, and Ryuta Saito. Pediatric-type high-grade gliomas with pdgfra amplification in adult patients with li-fraumeni syndrome: clinical and molecular characterization of three cases. Acta Neuropathologica Communications, Apr 2024. URL: https://doi.org/10.1186/s40478-024-01762-7, doi:10.1186/s40478-024-01762-7. This article has 9 citations and is from a peer-reviewed journal.
(hainfellner2024glioblastomainthe pages 3-4): 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 6 citations and is from a peer-reviewed journal.
(harwood2024glioblastomacellsincrease pages 1-2): D. Harwood, V. Pedersen, N. Bager, A. Schmidt, T. Stannius, A. Areškevičiūtė, Knud Josefsen, D. Nørøxe, David Scheie, Hannah Rostalski, M. Lü, A. Locallo, U. Lassen, F. Bagger, J. Weischenfeldt, D. Heiland, Kristoffer Vitting-Seerup, S. Michaelsen, and BW Kristensen. Glioblastoma cells increase expression of notch signaling and synaptic genes within infiltrated brain tissue. Nature communications, 15 1:7857, Sep 2024. URL: https://doi.org/10.1038/s41467-024-52167-y, doi:10.1038/s41467-024-52167-y. This article has 47 citations and is from a highest quality peer-reviewed journal.
(sahm2023moleculardiagnostictools pages 14-14): Felix Sahm, Sebastian Brandner, Luca Bertero, David Capper, Pim J French, Dominique Figarella-Branger, Felice Giangaspero, Christine Haberler, Monika E Hegi, Bjarne W Kristensen, Kathreena M Kurian, Matthias Preusser, Bastiaan B J Tops, Martin van den Bent, Wolfgang Wick, Guido Reifenberger, and Pieter Wesseling. Molecular diagnostic tools for the world health organization (who) 2021 classification of gliomas, glioneuronal and neuronal tumors; an eano guideline. Neuro-Oncology, 25:1731-1749, Jun 2023. URL: https://doi.org/10.1093/neuonc/noad100, doi:10.1093/neuonc/noad100. This article has 110 citations and is from a domain leading peer-reviewed journal.
(sahm2023moleculardiagnostictools pages 2-3): Felix Sahm, Sebastian Brandner, Luca Bertero, David Capper, Pim J French, Dominique Figarella-Branger, Felice Giangaspero, Christine Haberler, Monika E Hegi, Bjarne W Kristensen, Kathreena M Kurian, Matthias Preusser, Bastiaan B J Tops, Martin van den Bent, Wolfgang Wick, Guido Reifenberger, and Pieter Wesseling. Molecular diagnostic tools for the world health organization (who) 2021 classification of gliomas, glioneuronal and neuronal tumors; an eano guideline. Neuro-Oncology, 25:1731-1749, Jun 2023. URL: https://doi.org/10.1093/neuonc/noad100, doi:10.1093/neuonc/noad100. This article has 110 citations and is from a domain leading peer-reviewed journal.
(hendriksen2024immunotherapydrivesmesenchymal pages 1-3): Josephine D Hendriksen, Alessio Locallo, Simone Maarup, Olivia Debnath, Naveed Ishaque, Benedikte Hasselbach, Jane Skjøth-Rasmussen, Christina Westmose Yde, Hans S Poulsen, Ulrik Lassen, and Joachim Weischenfeldt. Immunotherapy drives mesenchymal tumour cell state shift and tme immune response in glioblastoma patients. Neuro-oncology, 26:1453-1466, May 2024. URL: https://doi.org/10.1093/neuonc/noae085, doi:10.1093/neuonc/noae085. This article has 17 citations and is from a domain leading peer-reviewed journal.
(forster2024tumorpseudolineagesfrom pages 27-30): Leo Carl Förster. Tumor pseudolineages from a healthy lineage template reveal organizational principles and cell-fate modulators in glioblastoma. Text, Jan 2024. URL: https://doi.org/10.11588/heidok.00035474, doi:10.11588/heidok.00035474. This article has 0 citations and is from a peer-reviewed journal.
(drexler2024aprognosticneural pages 1-2): Richard Drexler, Robin Khatri, Thomas Sauvigny, Malte Mohme, Cecile L. Maire, Alice Ryba, Yahya Zghaibeh, Lasse Dührsen, Amanda Salviano-Silva, Katrin Lamszus, Manfred Westphal, Jens Gempt, Annika K. Wefers, Julia E. Neumann, Helena Bode, Fabian Hausmann, Tobias B. Huber, Stefan Bonn, Kerstin Jütten, Daniel Delev, Katharina J. Weber, Patrick N. Harter, Julia Onken, Peter Vajkoczy, David Capper, Benedikt Wiestler, Michael Weller, Berend Snijder, Alicia Buck, Tobias Weiss, Pauline C. Göller, Felix Sahm, Joelle Aline Menstel, David Niklas Zimmer, Michael B. Keough, Lijun Ni, Michelle Monje, Dana Silverbush, Volker Hovestadt, Mario L. Suvà, Saritha Krishna, Shawn L. Hervey-Jumper, Ulrich Schüller, Dieter H. Heiland, Sonja Hänzelmann, and Franz L. Ricklefs. A prognostic neural epigenetic signature in high-grade glioma. Nature Medicine, 30:1622-1635, May 2024. URL: https://doi.org/10.1038/s41591-024-02969-w, doi:10.1038/s41591-024-02969-w. This article has 110 citations and is from a highest quality peer-reviewed journal.
(jackson2025distinctmyeloidderivedsuppressor pages 1-3): Christina Jackson, Christopher Cherry, Sadhana Bom, Arbor G. Dykema, Rulin Wang, Elizabeth Thompson, Ming Zhang, Runzhe Li, Zhicheng Ji, Wenpin Hou, Wentao Zhan, Hao Zhang, John Choi, Ajay Vaghasia, Landon Hansen, William Wang, Brandon Bergsneider, Kate M. Jones, Fausto Rodriguez, Jon Weingart, Calixto-Hope Lucas, Jonathan Powell, Jennifer Elisseeff, Srinivasan Yegnasubramanian, Michael Lim, Chetan Bettegowda, Hongkai Ji, and Drew Pardoll. Distinct myeloid-derived suppressor cell populations in human glioblastoma. Science, 387 6731:eabm5214, Jan 2025. URL: https://doi.org/10.1126/science.abm5214, doi:10.1126/science.abm5214. This article has 78 citations and is from a highest quality peer-reviewed journal.
(sahm2023moleculardiagnostictools pages 11-12): Felix Sahm, Sebastian Brandner, Luca Bertero, David Capper, Pim J French, Dominique Figarella-Branger, Felice Giangaspero, Christine Haberler, Monika E Hegi, Bjarne W Kristensen, Kathreena M Kurian, Matthias Preusser, Bastiaan B J Tops, Martin van den Bent, Wolfgang Wick, Guido Reifenberger, and Pieter Wesseling. Molecular diagnostic tools for the world health organization (who) 2021 classification of gliomas, glioneuronal and neuronal tumors; an eano guideline. Neuro-Oncology, 25:1731-1749, Jun 2023. URL: https://doi.org/10.1093/neuonc/noad100, doi:10.1093/neuonc/noad100. This article has 110 citations and is from a domain leading peer-reviewed journal.
(latzer2024arealworldobservation pages 1-2): Pauline Latzer, Henning Zelba, Florian Battke, Annekathrin Reinhardt, Borong Shao, Oliver Bartsch, Armin Rabsteyn, Johannes Harter, Martin Schulze, Thomas Okech, Alexander Golf, Christina Kyzirakos-Feger, Simone Kayser, Natalia Pieper, Magdalena Feldhahn, Julian Wünsche, Christian Seitz, Dirk Hadaschik, Claus Garbe, Till-Karsten Hauser, Christian la Fougère, Dirk Biskup, Dawn Brooke, David Parker, Uwe M. Martens, Gerald Illerhaus, Deborah T. Blumenthal, Ryan Merrell, Luisa Sánchez Lorenzo, Máté Hidvégi, Paula de Robles, Sied Kebir, William W. Li, Vincent W. Li, Matthew Williams, Alexandra M. Miller, Santosh Kesari, Michael Castro, Annick Desjardins, David M. Ashley, Henry S. Friedman, Patrick Y. Wen, Elisabeth C. Neil, Fabio M. Iwamoto, Bence Sipos, Karsten Geletneky, Lars Zender, Martin Glas, David A. Reardon, and Saskia Biskup. A real-world observation of patients with glioblastoma treated with a personalized peptide vaccine. Nature Communications, Aug 2024. URL: https://doi.org/10.1038/s41467-024-51315-8, doi:10.1038/s41467-024-51315-8. This article has 52 citations and is from a highest quality 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 19 citations and is from a peer-reviewed journal.
(riegel2025longtermsurvivalpatterns pages 1-2): Devon C. Riegel, Britta L. Bureau, Patrick Conlon, Gordon Chavez, and Jennifer M. Connelly. Long-term survival, patterns of progression, and patterns of use for patients with newly diagnosed glioblastoma treated with or without tumor treating fields (ttfields) in a real-world setting. Journal of Neuro-Oncology, 173:49-57, Mar 2025. URL: https://doi.org/10.1007/s11060-025-04946-w, doi:10.1007/s11060-025-04946-w. This article has 11 citations and is from a peer-reviewed journal.
(caccese2024regomaossalarge pages 1-2): M. Caccese, I. Desideri, V. Villani, M. Simonelli, M. Buglione, S. Chiesa, E. Franceschi, P. Gaviani, I. Stasi, C. Caserta, S. Brugnara, I. Lolli, E. Bennicelli, P. Bini, A.S. Cuccu, S. Scoccianti, M. Padovan, S. Gori, A. Bonetti, P. Giordano, A. Pellerino, F. Gregucci, N. Riva, S. Cinieri, V. Internò, M. Santoni, G. Pernice, C. Dealis, L. Stievano, F. Paiar, G. Magni, G.L. De Salvo, V. Zagonel, and G. Lombardi. Regoma-oss: a large, italian, multicenter, prospective, observational study evaluating the efficacy and safety of regorafenib in patients with recurrent glioblastoma. ESMO Open, 9:102943, Apr 2024. URL: https://doi.org/10.1016/j.esmoop.2024.102943, doi:10.1016/j.esmoop.2024.102943. This article has 16 citations and is from a domain leading peer-reviewed journal.
(tunbekici2024regorafenibtreatmentfor pages 1-2): Salih Tünbekici, Haydar cagatay Yuksel, Caner Acar, Gökhan Sahin, Seval Orman, Nargiz Majidova, Alper Coskun, Mustafa Seyyar, Mehmet sıddık Dilek, Mahmut Kara, Ahmet Kursat Dıslı, Teyfik Demir, Nagihan Kolkıran, Mustafa Sahbazlar, Erkut Demırcıler, Fatih Kuş, Ali Aytac, Serkan Menekse, Hakan Yucel, Sedat Biter, Tolga Koseci, Ahmet Unsal, Ahmet Ozveren, Alper Sevınc, Erdem Goker, and Pınar Gürsoy. Regorafenib treatment for recurrent glioblastoma beyond bevacizumab-based therapy: a large, multicenter, real-life study. Cancers, 17:46, Dec 2024. URL: https://doi.org/10.3390/cancers17010046, doi:10.3390/cancers17010046. This article has 2 citations.
(khagi2025recentadvancesin pages 7-8): Simon Khagi, Rupesh Kotecha, Na Tosha N Gatson, Suriya Jeyapalan, Huda Ismail Abdullah, Nicholas G Avgeropoulos, Eleni T Batzianouli, Moshe Giladi, Leonardo Lustgarten, and Samuel A Goldlust. Recent advances in tumor treating fields (ttfields) therapy for glioblastoma. The Oncologist, Oct 2025. URL: https://doi.org/10.1093/oncolo/oyae227, doi:10.1093/oncolo/oyae227. This article has 43 citations.
(liau2023…cellvaccination pages 1-2): LM Liau, K Ashkan, S Brem, and JL Campian. … cell vaccination with extension of survival among patients with newly diagnosed and recurrent glioblastoma: a phase 3 prospective externally controlled cohort trial. Unknown journal, 2023.
(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 12 citations and is from a peer-reviewed journal.
(antonelli2022adulttypediffuse pages 8-10): 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 67 citations.