Oligodendroglioma, IDH-mutant and 1p/19q-codeleted, is a diffuse glioma defined by the combination of IDH1/IDH2 mutation and whole-arm codeletion of chromosomes 1p and 19q. This molecular signature is the result of an unbalanced translocation t(1;19) (q10;p10) and is associated with distinct biology, excellent chemosensitivity, and favorable prognosis. The 1p/19q codeletion is mutually exclusive with TP53 and ATRX mutations, serving as a key diagnostic discriminator from IDH-mutant astrocytoma. These tumors are exquisitely sensitive to alkylating chemotherapy, particularly procarbazine-CCNU-vincristine (PCV) combination, with long-term survival even for anaplastic tumors.
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name: IDH-Mutant and 1p/19q-Codeleted Oligodendroglioma
creation_date: '2026-01-26T02:55:13Z'
updated_date: '2026-04-11T21:17:25Z'
description: >-
Oligodendroglioma, IDH-mutant and 1p/19q-codeleted, is a diffuse glioma defined
by
the combination of IDH1/IDH2 mutation and whole-arm codeletion of chromosomes 1p
and
19q. This molecular signature is the result of an unbalanced translocation t(1;19)
(q10;p10) and is associated with distinct biology, excellent chemosensitivity, and
favorable prognosis. The 1p/19q codeletion is mutually exclusive with TP53 and ATRX
mutations, serving as a key diagnostic discriminator from IDH-mutant astrocytoma.
These tumors are exquisitely sensitive to alkylating chemotherapy, particularly
procarbazine-CCNU-vincristine (PCV) combination, with long-term survival even for
anaplastic tumors.
categories:
- Central Nervous System Neoplasm
- Adult Brain Tumor
- Molecularly Defined Tumor
- Chemosensitive Tumor
parents:
- diffuse glioma
has_subtypes:
- name: Oligodendroglioma Grade 2
description: >-
Low-grade oligodendroglioma with IDH mutation and 1p/19q codeletion. Characterized
by uniform round nuclei, perinuclear halos (fried egg appearance), delicate
branching capillaries (chicken-wire vasculature), and low mitotic activity.
Median survival exceeds 15 years with appropriate treatment.
- name: Oligodendroglioma Grade 3 (Anaplastic)
description: >-
Anaplastic oligodendroglioma with IDH mutation and 1p/19q codeletion. Shows
increased cellularity, mitotic activity, microvascular proliferation, and/or
necrosis. Despite high-grade features, chemosensitivity is retained and
median survival is 10-15 years with combined chemoradiation.
pathophysiology:
- name: IDH1/2 Neomorphic Mutation
description: >-
Heterozygous IDH1 R132 or IDH2 R172 mutations produce D-2-hydroxyglutarate (2-HG),
an oncometabolite causing epigenetic dysregulation through inhibition of
alpha-ketoglutarate-dependent dioxygenases. This is an early clonal event shared
with IDH-mutant astrocytomas.
evidence:
- reference: PMID:40916936
reference_title: "Isocitrate dehydrogenase mutation and microenvironment in gliomas: do immunotherapy approaches matter?"
supports: SUPPORT
snippet: "This unique immune microenvironment is shaped by 2-hydroxyglutarate (2-HG), an oncometabolite produced by mutant IDH."
explanation: This abstract explicitly links mutant IDH to 2-HG production, supporting the neomorphic IDH mechanism.
cell_types:
- preferred_term: oligodendrocyte
term:
id: CL:0000128
label: oligodendrocyte
biological_processes:
- preferred_term: tricarboxylic acid cycle
modifier: ABNORMAL
term:
id: GO:0006099
label: tricarboxylic acid cycle
locations:
- preferred_term: brain
term:
id: UBERON:0000955
label: brain
downstream:
- target: G-CIMP Hypermethylation Phenotype
description: 2-HG accumulation causes global DNA hypermethylation
- name: 1p/19q Codeletion
description: >-
The 1p/19q codeletion results from an unbalanced translocation t(1;19)(q10;p10)
occurring early in tumorigenesis. This leads to loss of tumor suppressor genes
including CIC on 19q and FUBP1 on 1p. The codeletion is associated with
oligodendroglial differentiation and exceptional chemosensitivity.
evidence:
- reference: PMID:37743332
reference_title: "[Oligodendroglioma, IDH Mutation and 1p/19q Codeletion]."
supports: SUPPORT
snippet: "Oligodendrogliomas were clearly defined as tumors with IDH mutations and 1p/19q codeletion by the World Health Organization(WHO)in 2016."
explanation: "Abstract defines oligodendrogliomas by IDH mutation and 1p/19q codeletion."
biological_processes:
- preferred_term: chromosome organization
modifier: ABNORMAL
term:
id: GO:0051276
label: chromosome organization
downstream:
- target: CIC/FUBP1 Tumor Suppressor Loss
description: Codeletion removes key tumor suppressors on 1p and 19q
- name: G-CIMP Hypermethylation Phenotype
description: >-
Glioma CpG island methylator phenotype (G-CIMP) results from 2-HG-mediated
inhibition of TET enzymes and histone demethylases. This leads to widespread
promoter hypermethylation, altered gene expression, and blocked differentiation.
G-CIMP is associated with favorable prognosis.
biological_processes:
- preferred_term: DNA methylation
modifier: INCREASED
term:
id: GO:0006304
label: DNA modification
- name: CIC/FUBP1 Tumor Suppressor Loss
description: >-
CIC (Capicua) on 19q13 is mutated in approximately 70% of oligodendrogliomas.
FUBP1 on 1p31 is mutated in approximately 30%. These mutations cooperate with
IDH mutation and 1p/19q codeletion to drive oligodendroglioma formation.
biological_processes:
- preferred_term: negative regulation of cell population proliferation
modifier: DECREASED
term:
id: GO:0008285
label: negative regulation of cell population proliferation
downstream:
- target: Oligodendroglial Tumorigenesis
description: Loss of tumor suppressors promotes oligodendroglioma formation
- name: Oligodendroglial Tumorigenesis
description: >-
The combination of IDH mutation, 1p/19q codeletion, and CIC/FUBP1 mutations
drives oligodendroglioma formation. These tumors retain oligodendroglial
differentiation markers and maintain sensitivity to DNA-damaging agents,
likely due to intact DNA damage response pathways.
cell_types:
- preferred_term: oligodendrocyte
term:
id: CL:0000128
label: oligodendrocyte
biological_processes:
- preferred_term: cell population proliferation
modifier: INCREASED
term:
id: GO:0008283
label: cell population proliferation
phenotypes:
- category: Neurological
name: Seizures
frequency: VERY_FREQUENT
description: >-
Seizures are the most common presenting symptom, occurring in 70-90% of patients.
The high seizure frequency is attributed to cortical involvement and slow growth
pattern. Seizure control often improves with tumor treatment.
phenotype_term:
preferred_term: Seizure
term:
id: HP:0001250
label: Seizure
evidence:
- reference: PMID:26478444
reference_title: "Seizures in oligodendroglial tumors."
supports: SUPPORT
snippet: "Epilepsy develops in more than 70-90% of oligodendroglial tumors and represents a favorable indicator for long-term survival if present as the first clinical sign."
explanation: Documents the high frequency (70-90%) of seizures in oligodendroglial tumors and their prognostic significance.
- category: Neurological
name: Headache
frequency: FREQUENT
description: >-
Headache from mass effect occurs less commonly than in higher-grade tumors due
to slow growth.
phenotype_term:
preferred_term: Headache
term:
id: HP:0002315
label: Headache
- category: Neurological
name: Cognitive Impairment
frequency: FREQUENT
description: >-
Cognitive dysfunction may be subtle and develop slowly. Frontal lobe tumors may
cause personality changes and executive dysfunction.
phenotype_term:
preferred_term: Cognitive impairment
term:
id: HP:0100543
label: Cognitive impairment
histopathology:
- name: Diffuse Glioma
finding_term:
preferred_term: Diffuse Glioma
term:
id: NCIT:C129325
label: Diffuse Glioma
frequency: VERY_FREQUENT
description: Diffuse gliomas include IDH-mutant astrocytoma and oligodendroglioma subtypes.
evidence:
- reference: PMID:36651583
reference_title: "IDH-mutant diffuse gliomas: tips and tricks in the era of genomic tumor classification."
supports: SUPPORT
snippet: "oligodendroglioma IDH-mutant and 1p/19q codeleted, astrocytoma IDH-mutant, and"
explanation: Abstract lists IDH-mutant oligodendroglioma and astrocytoma among diffuse gliomas.
genetic:
- name: IDH1
association: Somatic Mutation
notes: >-
IDH1 R132H is the most common mutation but IDH1 R132C and other variants occur
more frequently in oligodendrogliomas than astrocytomas.
- name: IDH2
association: Somatic Mutation
notes: >-
IDH2 R172 mutations are more common in oligodendrogliomas (up to 5%) than
astrocytomas.
- name: CIC
association: Somatic Mutation
notes: >-
CIC (Capicua transcriptional repressor) on 19q13.2 is mutated in approximately
70% of oligodendrogliomas. Functions as a transcriptional repressor downstream
of receptor tyrosine kinase signaling.
evidence:
- reference: PMID:22072542
reference_title: "Concurrent CIC mutations, IDH mutations, and 1p/19q loss distinguish oligodendrogliomas from other cancers."
supports: SUPPORT
snippet: "overall mutation rate in oligodendrogliomas in this study to 20/29 (69%)"
explanation: Documents CIC mutation frequency of 69% in 1p/19q-codeleted oligodendrogliomas through exome sequencing.
- reference: PMID:22072542
reference_title: "Concurrent CIC mutations, IDH mutations, and 1p/19q loss distinguish oligodendrogliomas from other cancers."
supports: SUPPORT
snippet: "CIC mutations were highly associated with oligodendroglioma histology, 1p/19q co-deletion, and IDH1/2 mutation (p < 0.001)"
explanation: Establishes strong association between CIC mutations and the defining features of oligodendroglioma.
- name: FUBP1
association: Somatic Mutation
notes: >-
FUBP1 (far upstream element binding protein 1) on 1p31.1 is mutated in
approximately 30% of oligodendrogliomas. Regulates MYC expression.
- name: TERT
association: Promoter Mutation
notes: >-
TERT promoter mutations (C228T or C250T) occur in approximately 70-80% of
oligodendrogliomas. Creates ETS binding sites leading to TERT upregulation
and telomerase activation.
- name: NOTCH1
association: Somatic Mutation
notes: >-
NOTCH1 mutations occur in approximately 10-15% of oligodendrogliomas and may
be associated with worse prognosis.
biochemical:
- name: 2-Hydroxyglutarate (2-HG)
notes: >-
D-2-hydroxyglutarate accumulates due to IDH mutation. Detectable by MR
spectroscopy at 2.25 ppm and serves as a biomarker for response assessment.
treatments:
- name: Maximal Safe Resection
description: >-
Surgical resection aims to maximize extent of resection while preserving
function. Complete resection associated with improved survival and seizure
control.
treatment_term:
preferred_term: surgical procedure
term:
id: MAXO:0000004
label: surgical procedure
- name: Radiation Therapy
description: >-
External beam radiation is standard for anaplastic oligodendroglioma. For
grade 2 tumors, timing of radiation may be deferred in favorable cases.
treatment_term:
preferred_term: radiation therapy
term:
id: MAXO:0000014
label: radiation therapy
- name: PCV Chemotherapy
description: >-
Procarbazine, CCNU (lomustine), and vincristine (PCV) combination chemotherapy
shows exceptional efficacy in 1p/19q-codeleted oligodendrogliomas. RTOG 9402
and EORTC 26951 trials demonstrated major survival benefit for PCV added to
radiation in anaplastic oligodendroglioma.
treatment_term:
preferred_term: chemotherapy
term:
id: MAXO:0000647
label: chemotherapy
evidence:
- reference: PMID:23071247
reference_title: "Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402."
supports: SUPPORT
snippet: "the median survival of those with codeleted tumors treated with PCV plus RT was twice that of patients receiving RT (14.7 v 7.3 years; HR = 0.59; 95% CI, 0.37 to 0.95; P = .03)"
explanation: Landmark RTOG 9402 phase III trial demonstrating that PCV plus radiation doubles median survival compared to radiation alone in 1p/19q-codeleted anaplastic oligodendroglioma.
- reference: PMID:23071237
reference_title: "Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951."
supports: SUPPORT
snippet: "The addition of six cycles of PCV after 59.4 Gy of RT increases both OS and PFS in anaplastic oligodendroglial tumors. 1p/19q-codeleted tumors derive more benefit from adjuvant PCV compared with non-1p/19q-deleted tumors."
explanation: EORTC 26951 phase III trial confirming survival benefit of adjuvant PCV chemotherapy with preferential benefit in 1p/19q-codeleted tumors.
- name: Temozolomide Chemotherapy
description: >-
Temozolomide is an alternative to PCV with better tolerability. Often used
concurrently with radiation followed by adjuvant cycles. Efficacy appears
similar to PCV in 1p/19q-codeleted tumors.
treatment_term:
preferred_term: chemotherapy
term:
id: MAXO:0000647
label: chemotherapy
disease_term:
preferred_term: IDH-mutant and 1p/19q-codeleted oligodendroglioma
term:
id: MONDO:0859592
label: IDH-mutant and 1p/19q-codeleted oligodendroglioma
classifications:
icdo_morphology:
classification_value: Glioma
harrisons_chapter:
- classification_value: cancer
- classification_value: solid tumor
references:
- reference: DOI:10.1002/1878-0261.13598
title: '<scp>IDH</scp> mutation, glioma immunogenicity, and therapeutic challenge of primary mismatch repair deficient <scp>IDH</scp>‐mutant astrocytoma <scp>PMMRDIA</scp>: a systematic review'
found_in:
- IDH_Mutant_Oligodendroglioma-deep-research-falcon.md
findings:
- statement: In 2021, Suwala et al. described Primary Mismatch Repair Deficient IDH‐mutant Astrocytoma (PMMRDIA) as a distinct group of gliomas.
supporting_text: In 2021, Suwala et al. described Primary Mismatch Repair Deficient IDH‐mutant Astrocytoma (PMMRDIA) as a distinct group of gliomas.
evidence:
- reference: DOI:10.1002/1878-0261.13598
reference_title: '<scp>IDH</scp> mutation, glioma immunogenicity, and therapeutic challenge of primary mismatch repair deficient <scp>IDH</scp>‐mutant astrocytoma <scp>PMMRDIA</scp>: a systematic review'
supports: SUPPORT
evidence_source: OTHER
snippet: In 2021, Suwala et al. described Primary Mismatch Repair Deficient IDH‐mutant Astrocytoma (PMMRDIA) as a distinct group of gliomas.
explanation: Deep research cited this publication as relevant literature for IDH Mutant Oligodendroglioma.
- 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:
- IDH_Mutant_Oligodendroglioma-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/s11060-023-04250-5
title: Updates on the WHO diagnosis of IDH-mutant glioma
found_in:
- IDH_Mutant_Oligodendroglioma-deep-research-falcon.md
findings:
- statement: The WHO classification of Tumors of the Central Nervous System represents the international standard classification for brain tumors.
supporting_text: The WHO classification of Tumors of the Central Nervous System represents the international standard classification for brain tumors.
evidence:
- reference: DOI:10.1007/s11060-023-04250-5
reference_title: Updates on the WHO diagnosis of IDH-mutant glioma
supports: SUPPORT
evidence_source: OTHER
snippet: The WHO classification of Tumors of the Central Nervous System represents the international standard classification for brain tumors.
explanation: Deep research cited this publication as relevant literature for IDH Mutant Oligodendroglioma.
- reference: DOI:10.1038/s41582-022-00679-w
title: Clinical implications of the 2021 edition of the WHO classification of central nervous system tumours
found_in:
- IDH_Mutant_Oligodendroglioma-deep-research-falcon.md
findings:
- statement: Clinical implications of the 2021 edition of the WHO classification of central nervous system tumours
supporting_text: Clinical implications of the 2021 edition of the WHO classification of central nervous system tumours
- reference: DOI:10.1056/nejmoa2304194
title: Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma
found_in:
- IDH_Mutant_Oligodendroglioma-deep-research-falcon.md
findings:
- statement: Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma
supporting_text: Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma
- reference: DOI:10.1093/neuonc/noaa022
title: Imaging growth as a predictor of grade of malignancy and aggressiveness of IDH-mutant and 1p/19q-codeleted oligodendrogliomas in adults
found_in:
- IDH_Mutant_Oligodendroglioma-deep-research-falcon.md
findings:
- statement: We quantified the spontaneous imaging growth rate of oligodendrogliomas.
supporting_text: We quantified the spontaneous imaging growth rate of oligodendrogliomas.
evidence:
- reference: DOI:10.1093/neuonc/noaa022
reference_title: Imaging growth as a predictor of grade of malignancy and aggressiveness of IDH-mutant and 1p/19q-codeleted oligodendrogliomas in adults
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: We quantified the spontaneous imaging growth rate of oligodendrogliomas.
explanation: Deep research cited this publication as relevant literature for IDH Mutant Oligodendroglioma.
- reference: DOI:10.1093/neuonc/noaa168
title: 'CODEL: phase III study of RT, RT + TMZ, or TMZ for newly diagnosed 1p/19q codeleted oligodendroglioma. Analysis from the initial study design'
found_in:
- IDH_Mutant_Oligodendroglioma-deep-research-falcon.md
findings:
- statement: We report the analysis involving patients treated on the initial CODEL design.
supporting_text: We report the analysis involving patients treated on the initial CODEL design.
evidence:
- reference: DOI:10.1093/neuonc/noaa168
reference_title: 'CODEL: phase III study of RT, RT + TMZ, or TMZ for newly diagnosed 1p/19q codeleted oligodendroglioma. Analysis from the initial study design'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: We report the analysis involving patients treated on the initial CODEL design.
explanation: Deep research cited this publication as relevant literature for IDH Mutant Oligodendroglioma.
- reference: DOI:10.1093/neuonc/noab106
title: 'The 2021 WHO Classification of Tumors of the Central Nervous System: a summary'
found_in:
- IDH_Mutant_Oligodendroglioma-deep-research-falcon.md
findings:
- statement: The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), published in 2021, is the sixth version of the international standard for the classification of brain and spinal cord tumors.
supporting_text: The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), published in 2021, is the sixth version of the international standard for the classification of brain and spinal cord tumors.
evidence:
- reference: DOI:10.1093/neuonc/noab106
reference_title: 'The 2021 WHO Classification of Tumors of the Central Nervous System: a summary'
supports: SUPPORT
evidence_source: OTHER
snippet: The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), published in 2021, is the sixth version of the international standard for the classification of brain and spinal cord tumors.
explanation: Deep research cited this publication as relevant literature for IDH Mutant Oligodendroglioma.
- reference: DOI:10.1093/noajnl/vdaa109
title: Frequency of false-positive FISH 1p/19q codeletion in adult diffuse astrocytic gliomas
found_in:
- IDH_Mutant_Oligodendroglioma-deep-research-falcon.md
findings:
- statement: Oligodendroglioma is genetically defined by concomitant IDH (IDH1/IDH2) mutation and whole-arm 1p/19q codeletion.
supporting_text: Oligodendroglioma is genetically defined by concomitant IDH (IDH1/IDH2) mutation and whole-arm 1p/19q codeletion.
evidence:
- reference: DOI:10.1093/noajnl/vdaa109
reference_title: Frequency of false-positive FISH 1p/19q codeletion in adult diffuse astrocytic gliomas
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Oligodendroglioma is genetically defined by concomitant IDH (IDH1/IDH2) mutation and whole-arm 1p/19q codeletion.
explanation: Deep research cited this publication as relevant literature for IDH Mutant Oligodendroglioma.
- reference: DOI:10.1186/s13073-023-01175-6
title: Stalled oligodendrocyte differentiation in IDH-mutant gliomas
found_in:
- IDH_Mutant_Oligodendroglioma-deep-research-falcon.md
findings:
- statement: Roughly 50% of adult gliomas harborisocitrate dehydrogenase(IDH) mutations.
supporting_text: Roughly 50% of adult gliomas harborisocitrate dehydrogenase(IDH) mutations.
evidence:
- reference: DOI:10.1186/s13073-023-01175-6
reference_title: Stalled oligodendrocyte differentiation in IDH-mutant gliomas
supports: SUPPORT
evidence_source: OTHER
snippet: Roughly 50% of adult gliomas harborisocitrate dehydrogenase(IDH) mutations.
explanation: Deep research cited this publication as relevant literature for IDH Mutant Oligodendroglioma.
- reference: DOI:10.1200/jco.21.02543
title: 'Joint Final Report of EORTC 26951 and RTOG 9402: Phase III Trials With Procarbazine, Lomustine, and Vincristine Chemotherapy for Anaplastic Oligodendroglial Tumors'
found_in:
- IDH_Mutant_Oligodendroglioma-deep-research-falcon.md
findings:
- statement: Clinical trials frequently include multiple end points that mature at different times.
supporting_text: Clinical trials frequently include multiple end points that mature at different times.
evidence:
- reference: DOI:10.1200/jco.21.02543
reference_title: 'Joint Final Report of EORTC 26951 and RTOG 9402: Phase III Trials With Procarbazine, Lomustine, and Vincristine Chemotherapy for Anaplastic Oligodendroglial Tumors'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Clinical trials frequently include multiple end points that mature at different times.
explanation: Deep research cited this publication as relevant literature for IDH Mutant Oligodendroglioma.
- reference: DOI:10.32074/1591-951x-823
title: Adult type diffuse gliomas in the new 2021 WHO Classification
found_in:
- IDH_Mutant_Oligodendroglioma-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:10.3390/biomedicines12061349
title: 'The 2021 World Health Organization Central Nervous System Tumor Classification: The Spectrum of Diffuse Gliomas'
found_in:
- IDH_Mutant_Oligodendroglioma-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 IDH Mutant Oligodendroglioma.
- reference: DOI:10.3390/brainsci13050817
title: 'From Theory to Practice: Implementing the WHO 2021 Classification of Adult Diffuse Gliomas in Neuropathology Diagnosis'
found_in:
- IDH_Mutant_Oligodendroglioma-deep-research-falcon.md
findings:
- statement: Diffuse gliomas are the most common type of primary central nervous system (CNS) neoplasm to affect the adult population.
supporting_text: Diffuse gliomas are the most common type of primary central nervous system (CNS) neoplasm to affect the adult population.
evidence:
- reference: DOI:10.3390/brainsci13050817
reference_title: 'From Theory to Practice: Implementing the WHO 2021 Classification of Adult Diffuse Gliomas in Neuropathology Diagnosis'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Diffuse gliomas are the most common type of primary central nervous system (CNS) neoplasm to affect the adult population.
explanation: Deep research cited this publication as relevant literature for IDH Mutant Oligodendroglioma.
- reference: DOI:10.3390/cancers16152752
title: 'Targeting Isocitrate Dehydrogenase (IDH) in Solid Tumors: Current Evidence and Future Perspectives'
found_in:
- IDH_Mutant_Oligodendroglioma-deep-research-falcon.md
findings:
- statement: The isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) enzymes are involved in key metabolic processes in human cells, regulating differentiation, proliferation, and oxidative damage response.
supporting_text: The isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) enzymes are involved in key metabolic processes in human cells, regulating differentiation, proliferation, and oxidative damage response.
evidence:
- reference: DOI:10.3390/cancers16152752
reference_title: 'Targeting Isocitrate Dehydrogenase (IDH) in Solid Tumors: Current Evidence and Future Perspectives'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: The isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) enzymes are involved in key metabolic processes in human cells, regulating differentiation, proliferation, and oxidative damage response.
explanation: Deep research cited this publication as relevant literature for IDH Mutant Oligodendroglioma.
In the 2021 WHO Classification of Tumours of the Central Nervous System (WHO CNS5), oligodendroglioma is defined as an adult-type diffuse glioma that is molecularly defined by an IDH1/IDH2 mutation together with whole-arm 1p/19q codeletion, and is graded as CNS WHO grade 2 or grade 3 within the tumor type (louis2021the2021who pages 8-9, louis2021the2021who pages 6-8, komori2023updateofthe pages 1-2).
The classification statements summarized here are aggregated, disease-level resources (WHO CNS5 summaries and implementation reviews), supplemented by clinical trials and cohort studies (horbinski2022clinicalimplicationsof pages 1-2, louis2021the2021who pages 8-9).
No high-quality, disease-specific protective factors or gene–environment interaction evidence was retrieved in the assembled corpus for this run.
Clinical presentation is often insidious and related to lesion location and intracranial pressure (antonelli2022adulttypediffuse pages 4-6). Across neuroradiology-focused WHO CNS5 reviews: - Seizures are frequently the initial symptom, plausibly due to cortical involvement (gue2024the2021world pages 7-9). - Other common symptoms include headache and cognitive/personality changes (notably with frontal lobe involvement) (gue2024the2021world pages 7-9).
High-quality, phenotype-specific QoL effect size estimates for this exact entity were not retrieved in this run. However, the long expected survival in many patients makes late treatment toxicity and “quality of survival” a major concern in treatment strategy discussions (carosi2024targetingisocitratedehydrogenase pages 4-6).
WHO CNS5 defines oligodendroglioma as requiring: - IDH1 or IDH2 mutation, and - Whole-arm 1p/19q codeletion (martin2023fromtheoryto pages 2-4, louis2021the2021who pages 6-8).
WHO-aligned molecular summaries list recurrent alterations in oligodendroglioma including TERT promoter, CIC, FUBP1, and NOTCH1 (martin2023fromtheoryto pages 4-6, louis2021the2021who pages 6-8).
No robust disease-specific environmental, lifestyle, or infectious causal factors were retrieved in the evidence assembled for this run.
A 2023 Genome Medicine multi-omic analysis concludes that IDH-mutant gliomas resemble early oligodendrocyte lineage states and show a blocked myelination program, supported by DNA methylation and chromatin accessibility patterns (wei2023stalledoligodendrocytedifferentiation pages 1-2).
Often insidious presentation in adults (gue2024the2021world pages 7-9).
This tumor entity is primarily considered sporadic in routine clinical neuro-oncology practice; heritable Mendelian patterns were not supported by retrieved evidence in this run.
A WHO CNS5 implementation review reports: - Incidence: approximately 0.48 per 100,000. - Age: peak in fourth–fifth decades. - Median overall survival: approximately 10–17 years (reflecting grade and treatment heterogeneity) (martin2023fromtheoryto pages 4-6).
A practical diagnostic workflow for adult diffuse gliomas is: 1. Test for IDH1/2 (IHC for IDH1 R132H and/or sequencing). 2. In IDH-mutant tumors, assess ATRX: loss supports astrocytoma; retained ATRX prompts 1p/19q testing. 3. If whole-arm 1p/19q codeletion is present, diagnose oligodendroglioma, IDH-mutant and 1p/19q-codeleted (martin2023fromtheoryto pages 2-4).
Because FISH is locus-based, it may not distinguish partial from whole-arm losses, producing “false-positive” 1p/19q results when partial losses mimic codeletion (ball2020frequencyoffalsepositive pages 1-2). In an adult diffuse astrocytic glioma series, the estimated false-positive FISH rate was 3.6% (8/223), with similar rates in IDH-mutant vs IDH-wildtype tumors (ball2020frequencyoffalsepositive pages 2-2). The authors recommend selective testing and/or confirmation with whole-arm–resolving platforms such as CMA when morphology/molecular context is discordant (ball2020frequencyoffalsepositive pages 2-2, ball2020frequencyoffalsepositive pages 13-14).
Common imaging features reported across WHO-2021 radiology reviews include: - Location: frontal lobe predilection; cortical/subcortical involvement (gue2024the2021world pages 7-9, antonelli2022adulttypediffuse pages 4-6). - CT: hypodense/isodense lesion; calcifications are common (reported ~90% in one review) (martin2023fromtheoryto pages 4-6). - MRI: typically T1 hypointense, T2 hyperintense, often heterogeneous with indistinct margins (gue2024the2021world pages 9-12). - Contrast enhancement: variable; one review reports enhancement in <20% of grade 2 but >70% of grade 3 oligodendrogliomas (gue2024the2021world pages 9-12). - Perfusion: may show elevated rCBV reflecting vascularity (antonelli2022adulttypediffuse pages 4-6).
Long-term randomized trial evidence (RTOG 9402 and EORTC 26951) demonstrates substantial benefit from adding PCV chemotherapy to radiotherapy in 1p/19q-codeleted anaplastic oligodendroglial tumors, with median OS on the order of a decade or longer and durable long-term survivors.
Key statistics include: - RTOG 9402 (JCO 2013): in codeleted tumors, median OS 14.7 years with PCV+RT vs 7.3 years with RT alone (HR 0.59; P=0.03) (cairncross2013phaseiiitrial pages 1-2). - Joint final report (JCO 2022): in the codeleted subgroup, probable 20-year OS ~37% with PCV+RT versus ~15% without PCV in RTOG 9402; and ~37% with PCV versus ~14% without PCV in EORTC 26951 (lassman2022jointfinalreport pages 1-2). The Kaplan–Meier curves and numbers-at-risk are shown in Figure 2 (lassman2022jointfinalreport media 697c589d).
The initial CODEL trial design analysis showed inferior PFS with temozolomide alone compared with RT-containing regimens in newly diagnosed 1p/19q-codeleted grade 3 oligodendroglioma (jaeckle2021codelphaseiii pages 1-2). This led to redesign of CODEL to compare RT+PCV vs RT+TMZ rather than including a TMZ-only arm (jaeckle2021codelphaseiii pages 1-2, jaeckle2021codelphaseiii pages 9-10).
A major recent advance is the phase 3 INDIGO trial of vorasidenib in post-surgical residual/recurrent grade 2 IDH-mutant glioma (including oligodendroglioma and astrocytoma, stratified by 1p/19q status) (mellinghoff2023vorasidenibinidh1 pages 3-5).
Direct abstract quote supporting the key efficacy claim: - “Progression-free survival was significantly improved in the vorasidenib group as compared with the placebo group (median progression-free survival, 27.7 months vs. 11.1 months; hazard ratio … 0.39 …; P<0.001).” (mellinghoff2023vorasidenibinidh1 pages 1-3)
Safety signal of note: - Grade ≥3 ALT elevation occurred in 9.6% on vorasidenib vs 0% on placebo (mellinghoff2023vorasidenibinidh1 pages 16-18).
Primary prevention and population-level screening strategies are not established for sporadic adult diffuse gliomas in the retrieved evidence. Secondary prevention largely consists of surveillance imaging in diagnosed patients following surgery and/or adjuvant therapy (carosi2024targetingisocitratedehydrogenase pages 4-6).
No naturally occurring non-human disease analogs were retrieved in this run.
No specific oligodendroglioma model-organism systems were retrieved in the assembled evidence for this run; however, mechanistic multi-omics studies in human tumor samples (bulk and single-cell transcriptome, methylation, scATAC-seq) provide strong in situ evidence for differentiation blockade and epigenetic mechanisms (wei2023stalledoligodendrocytedifferentiation pages 1-2).
| Trial | Population | Interventions | Key efficacy outcomes | Publication | PMID | URL |
|---|---|---|---|---|---|---|
| Joint Final Report: EORTC 26951 + RTOG 9402 | Newly diagnosed anaplastic oligodendroglial tumors; key molecular subgroup: 1p/19q-codeleted tumors | RT alone vs RT + PCV | EORTC 26951, codeleted subgroup (n=80): median OS 9.3 y without PCV vs 14.2 y with PCV; HR 0.60 (95% CI 0.35-1.03), P=.063; 14-y OS 26.2% vs 51.0%; probable 20-y OS 13.6% vs 37.1%. RTOG 9402, codeleted subgroup (n=125): median OS 7.3 y without PCV vs 13.2 y with PCV; HR 0.61 (95% CI 0.40-0.94), P=.02; 14-y OS 25.0% vs 46.1%; probable 20-y OS 14.9% vs 37.0%. Median follow-up 18-19 y. (lassman2022jointfinalreport pages 1-2, lassman2022jointfinalreport pages 2-3) | Journal of Clinical Oncology (2022) | Not available in retrieved context | https://doi.org/10.1200/JCO.21.02543 |
| RTOG 9402 long-term results | 291 eligible patients with anaplastic oligodendroglioma/oligoastrocytoma; 1p/19q-codeleted subgroup analyzed | Intensive PCV then RT vs RT alone | Overall cohort: median OS 4.6 y vs 4.7 y; HR 0.79 (95% CI 0.60-1.04), P=.1. Codeleted tumors: median OS 14.7 y with PCV+RT vs 7.3 y with RT alone; HR 0.59 (95% CI 0.37-0.95), P=.03. Non-codeleted: no benefit (2.6 y vs 2.7 y; HR 0.85, P=.39). (cairncross2013phaseiiitrial pages 1-2) | Journal of Clinical Oncology (2013) | Not available in retrieved context | https://doi.org/10.1200/JCO.2012.43.2674 |
| EORTC 26951 long-term follow-up | 368 patients with newly diagnosed anaplastic oligodendroglioma; molecular data available for 316; key subgroup: 1p/19q-codeleted tumors | RT alone vs RT followed by adjuvant PCV | Overall cohort: median OS 30.6 mo with RT vs 42.3 mo with RT/PCV; HR 0.75 (95% CI 0.60-0.95). Median PFS 13.2 mo vs 24.3 mo; HR 0.66 (95% CI 0.52-0.83). Codeleted tumors: median PFS 76 mo vs 11 mo for non-codeleted; HR 0.39 (95% CI 0.28-0.53); median OS 123 mo vs 23 mo for non-codeleted; HR 0.36 (95% CI 0.27-0.49). In the codeleted treatment comparison, OS was not reached with RT/PCV vs 112 mo with RT; HR 0.56 (95% CI 0.31-1.03). (bent2013adjuvantprocarbazinelomustine pages 2-3, bent2013adjuvantprocarbazinelomustine pages 1-2) | Journal of Clinical Oncology (2013) | Not available in retrieved context | https://doi.org/10.1200/JCO.2012.43.2229 |
| CODEL initial design analysis | Newly diagnosed 1p/19q-codeleted WHO grade 3 oligodendroglioma; 36 randomized patients | RT alone vs RT + concomitant/adjuvant TMZ vs TMZ alone; key comparison pooled RT-containing arms vs TMZ alone | With median follow-up 7.5 y: progression in 83.3% (10/12) on TMZ alone vs 37.5% (9/24) on RT-containing arms. PFS significantly shorter with TMZ alone: HR 3.12 (95% CI 1.26-7.69), P=0.014; adjusted HR 3.33 (95% CI 1.31-8.45), P=0.011. Median PFS 2.9 y with TMZ alone vs not reached with RT-containing arms; 3-y/5-y PFS 50%/33% vs 83%/56%. OS comparison underpowered and not significant. (jaeckle2021codelphaseiii pages 5-7, jaeckle2021codelphaseiii pages 1-2, jaeckle2021codelphaseiii pages 9-10) | Neuro-Oncology (2021) | Not available in retrieved context | https://doi.org/10.1093/neuonc/noaa168 |
| INDIGO (vorasidenib) | Residual or recurrent grade 2 IDH1/2-mutant glioma after surgery only; included oligodendroglioma and astrocytoma; no prior RT/chemotherapy | Vorasidenib 40 mg daily vs placebo | 331 randomized. Median PFS 27.7 mo vs 11.1 mo; HR 0.39 (95% CI 0.27-0.56), P<0.001. Time to next intervention HR 0.26 (95% CI 0.15-0.43); median time to next intervention not reached vs 17.8 mo. Grade >=3 adverse events 16.2%-22.8% with vorasidenib vs 5.5%-13.5% with placebo across excerpts; grade >=3 ALT increase 9.6% vs 0%. About half of enrolled tumors had 1p/19q codeletion. (mellinghoff2023vorasidenibinidh1 pages 1-3, mellinghoff2023vorasidenibinidh1 pages 6-8, mellinghoff2023vorasidenibinidh1 pages 3-5, mellinghoff2023vorasidenibinidh1 pages 16-18) | New England Journal of Medicine (2023) | Not available in retrieved context | https://doi.org/10.1056/NEJMoa2304194 |
Table: This table summarizes pivotal clinical trials and long-term outcome statistics relevant to IDH-mutant, 1p/19q-codeleted oligodendroglioma and related anaplastic oligodendroglial tumor populations. It is useful for comparing historical RT/PCV evidence, temozolomide-era trial data, and recent IDH-targeted therapy results.
Kaplan–Meier overall survival and progression-free survival curves for 1p/19q-codeleted subgroups comparing RT vs RT+PCV across EORTC 26951 and RTOG 9402 are shown in the joint final report figure (lassman2022jointfinalreport media 697c589d).
Several template fields (ICD codes, MeSH/Orphanet/OMIM, population-level prevalence estimates, detailed environmental risk factors, structured HPO frequency estimates, and curated animal model resources) were not retrievable from the evidence assembled in this tool run and therefore are not asserted here.
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(mellinghoff2023vorasidenibinidh1 pages 16-18): 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. New England Journal of Medicine, 389:589-601, Aug 2023. URL: https://doi.org/10.1056/nejmoa2304194, doi:10.1056/nejmoa2304194. This article has 772 citations and is from a highest quality peer-reviewed journal.
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(bent2013adjuvantprocarbazinelomustine pages 1-2): Martin J. van den Bent, Alba A. Brandes, Martin J.B. Taphoorn, Johan M. Kros, Mathilde C.M. Kouwenhoven, Jean-Yves Delattre, Hans J.J.A. Bernsen, Marc Frenay, Cees C. Tijssen, Wolfgang Grisold, László Sipos, Roelien H. Enting, Pim J. French, Winand N.M. Dinjens, Charles J. Vecht, Anouk Allgeier, Denis Lacombe, Thierry Gorlia, and Khê Hoang-Xuan. Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of eortc brain tumor group study 26951. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 31 3:344-50, Jan 2013. URL: https://doi.org/10.1200/jco.2012.43.2229, doi:10.1200/jco.2012.43.2229. This article has 1457 citations.
(jaeckle2021codelphaseiii pages 5-7): Kurt A Jaeckle, Karla V Ballman, Martin van den Bent, Caterina Giannini, Evanthia Galanis, Paul D Brown, Robert B Jenkins, J Gregory Cairncross, Wolfgang Wick, Michael Weller, Kenneth D Aldape, Jesse G Dixon, S Keith Anderson, Jane H Cerhan, Jeffrey S Wefel, Martin Klein, Stuart A Grossman, David Schiff, Jeffrey J Raizer, Frederick Dhermain, Donald G Nordstrom, Patrick J Flynn, and Michael A Vogelbaum. Codel: phase iii study of rt, rt + tmz, or tmz for newly diagnosed 1p/19q codeleted oligodendroglioma. analysis from the initial study design. Neuro-Oncology, 23:457-467, Jul 2021. URL: https://doi.org/10.1093/neuonc/noaa168, doi:10.1093/neuonc/noaa168. This article has 122 citations and is from a domain leading peer-reviewed journal.
(mellinghoff2023vorasidenibinidh1 pages 6-8): 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. New England Journal of Medicine, 389:589-601, Aug 2023. URL: https://doi.org/10.1056/nejmoa2304194, doi:10.1056/nejmoa2304194. This article has 772 citations and is from a highest quality peer-reviewed journal.