# Astrocytoma, IDH-mutant (grades 2 to 4)

Source: https://onco.cc/cancers/idh-mutant-astrocytoma/  
OnCo record `idh-mutant-astrocytoma` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

IDH-mutant astrocytoma is the slow-growing form of adult glioma, defined by a mutation in the IDH1 or IDH2 gene that makes the tumour produce a chemical which rewires its own cells. Surgery first, and then either watchful waiting, the new pill vorasidenib, or radiotherapy with chemotherapy, depending on grade and how much tumour is left.

## Summary

Astrocytoma, IDH-mutant is a single WHO 2021 tumour type graded 2, 3 or 4, defined by an IDH1 or IDH2 mutation without 1p/19q codeletion and usually with ATRX loss and TP53 mutation. Grade 4 is assigned on necrosis, microvascular proliferation or homozygous CDKN2A/B deletion, and the old term glioblastoma is no longer used for IDH-mutant tumours. The mutant enzyme produces 2-hydroxyglutarate, which blocks demethylases and gives the tumour its hypermethylated (G-CIMP) phenotype; that dependence is the target of vorasidenib.

Maximal safe resection comes first, with awake mapping where language or motor cortex is close. For grade 2 disease with residual or recurrent tumour and no urgent need for radiotherapy, INDIGO (NEJM 2023) showed vorasidenib prolonged progression-free survival to a median of 27.7 months against 11.1 months on placebo and delayed the next intervention; the FDA approved it in August 2024 for grade 2 astrocytoma and oligodendroglioma from the age of 12. For higher-risk grade 2 disease (age 40 or over, or subtotal resection) RTOG 9802 showed radiotherapy followed by PCV chemotherapy lengthened median survival from 7.8 to 13.3 years compared with radiotherapy alone; EORTC 22033-26033 found temozolomide alone was not superior to radiotherapy alone. For grade 3 (1p/19q non-codeleted) tumours CATNON established radiotherapy followed by twelve cycles of adjuvant temozolomide; concurrent temozolomide added nothing overall. Grade 4 IDH-mutant tumours are treated with radiotherapy and temozolomide by extrapolation from glioblastoma.

At recurrence the options are re-resection, re-irradiation, lomustine or temozolomide re-challenge and bevacizumab for symptom control. Hypermutation after temozolomide, CDKN2A/B loss and methylation class shape prognosis. Open questions are whether vorasidenib should replace or merely defer radiotherapy, how to treat grade 3 and 4 IDH-mutant tumours with IDH inhibitors (safusidenib, olutasidenib and others are in trials), and how to weigh the cognitive cost of radiotherapy in people who will live with the disease for decades.

## Fields

- Kind: Cancer
- Last checked: 2026-09-17
- Also known as: IDH-mutant astrocytoma; Diffuse astrocytoma, IDH-mutant; Anaplastic astrocytoma, IDH-mutant; Lower-grade glioma; Low-grade glioma (adult)
- Tags: subtype-page; cns
- Group: central nervous system
- Burden: A minority of adult diffuse gliomas, presenting mostly in people in their twenties to forties, often with a seizure; it grows slowly for years and then transforms, so patients live with it for a long time and treatment is timed as much as chosen.
- Subtypes: Astrocytoma, IDH-mutant, grade 2 (diffuse, slow growing); Astrocytoma, IDH-mutant, grade 3 (anaplastic features); Astrocytoma, IDH-mutant, grade 4 (necrosis, microvascular proliferation or CDKN2A/B homozygous deletion); Gemistocytic astrocytoma (IDH-mutant morphological variant)
- Biomarkers: IDH1 R132H immunohistochemistry, with sequencing of IDH1 and IDH2 for non-canonical mutations; 1p/19q status (intact; codeletion defines oligodendroglioma); ATRX loss and TP53 mutation; CDKN2A/B homozygous deletion (assigns grade 4); DNA methylation class and G-CIMP status; MGMT promoter methylation (less informative than in glioblastoma); Extent of resection on post-operative MRI

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/idh-mutant-astrocytoma/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/idh-mutant-astrocytoma/#overview [3 state-of-the-art points]
- Types and stages (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/idh-mutant-astrocytoma/#what-it-is [4 subtypes]
- Symptoms and diagnosis (on the hub): How this cancer shows itself, how the diagnosis is confirmed, and the biomarkers clinicians test for. https://onco.cc/cancers/idh-mutant-astrocytoma/#finding-it [7 biomarkers]
- Treatment (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/idh-mutant-astrocytoma/#treating-it [6 settings, 6 decisions with options]
- Trials and papers (on the hub): Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/idh-mutant-astrocytoma/#evidence [9 trials, 4 key papers, 8 milestones]
- Biology and targets (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/idh-mutant-astrocytoma/#science [3 targets, 1 pathway]
- Countries and centres (own page): Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes. https://onco.cc/cancers/idh-mutant-astrocytoma/where-you-are/
- Decisions and support (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/idh-mutant-astrocytoma/#living-with-it [24 questions, 6 red cards]
- Pipeline and open problems (own page): Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/idh-mutant-astrocytoma/coming/ [8 medicines, 8 trials, 4 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/idh-mutant-astrocytoma/data/ [53 connected records]

## Standard of care

- Newly diagnosed, all grades: Maximal safe resection with awake or functional mapping where needed; integrated histological and molecular diagnosis (IDH, 1p/19q, ATRX, CDKN2A/B, methylation class). ([Extent of resection (RANO resect classes)](https://onco.cc/terms/extent-of-resection/), [DNA methylation profiling](https://onco.cc/technologies/methylation-profiling/), [MRI](https://onco.cc/technologies/mri/))
- Grade 2, residual or recurrent, low risk: Observation with serial MRI, or vorasidenib for grade 2 tumours not needing immediate radiotherapy or chemotherapy (INDIGO). ([Vorasidenib](https://onco.cc/drugs/vorasidenib/), [INDIGO](https://onco.cc/trials/indigo/), [Active surveillance](https://onco.cc/technologies/active-surveillance/))
- Grade 2, high risk (age 40 or over, subtotal resection): Radiotherapy followed by PCV (procarbazine, lomustine, vincristine) as in RTOG 9802, or radiotherapy with temozolomide; temozolomide alone was not better than radiotherapy alone in EORTC 22033. ([IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Procarbazine](https://onco.cc/drugs/procarbazine/), [Lomustine (CCNU)](https://onco.cc/drugs/lomustine/), [Vincristine](https://onco.cc/drugs/vincristine/), [Temozolomide](https://onco.cc/drugs/temozolomide/), [EORTC 22033-26033](https://onco.cc/trials/eortc-22033/))
- Grade 3: Radiotherapy followed by twelve cycles of adjuvant temozolomide (CATNON); concurrent temozolomide is not needed in non-codeleted tumours. ([IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Temozolomide](https://onco.cc/drugs/temozolomide/), [CATNON (EORTC 26053-22054)](https://onco.cc/trials/catnon/))
- Grade 4: Radiotherapy with concurrent and adjuvant temozolomide, extrapolated from glioblastoma; trials of IDH inhibitors preferred where available. ([IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Temozolomide](https://onco.cc/drugs/temozolomide/), [EORTC 26981 / NCIC CE.3 (Stupp trial)](https://onco.cc/trials/eortc-26981/))
- Recurrence: Re-resection, re-irradiation, lomustine or temozolomide re-challenge, bevacizumab for oedema and symptoms; clinical trials. ([Lomustine (CCNU)](https://onco.cc/drugs/lomustine/), [Temozolomide](https://onco.cc/drugs/temozolomide/), [Bevacizumab (glioblastoma use)](https://onco.cc/drugs/bevacizumab-glioma/), [Re-irradiation](https://onco.cc/terms/re-irradiation/))

## State of the art

- Vorasidenib is the first drug to act on the defining mutation of a diffuse glioma and the first new systemic therapy for low-grade glioma in decades.
- Grading now integrates CDKN2A/B deletion, so a tumour that looks grade 2 under the microscope can be treated as grade 4.
- Radiotherapy plus PCV or temozolomide remains the backbone for higher-risk and higher-grade disease, and the trials that set it took a decade or more to read out.

## Open problems

- Whether vorasidenib should replace radiotherapy and chemotherapy or only defer them, and what to do at progression on it.
- No IDH inhibitor has yet shown benefit in grade 3 or 4 IDH-mutant astrocytoma.
- Cognitive decline after radiotherapy in people who live decades with the disease.
- Temozolomide-induced hypermutation at recurrence has no specific treatment.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Astrocytoma
- Wikipedia: https://en.wikipedia.org/wiki/Astrocytoma
- INDIGO: vorasidenib in IDH-mutant grade 2 glioma (NEJM 2023): https://doi.org/10.1056/NEJMoa2304194
- RTOG 9802: radiation plus PCV in low-grade glioma (NEJM 2016): https://doi.org/10.1056/NEJMoa1500925

## Connected records

- cancers: [Brain and spinal cord tumours (all types)](https://onco.cc/cancers/brain-tumours/), [Diffuse midline glioma, H3 K27-altered (including DIPG)](https://onco.cc/cancers/dipg-dmg/), [Glioma & glioblastoma](https://onco.cc/cancers/glioblastoma/), [Oligodendroglioma, IDH-mutant and 1p/19q-codeleted](https://onco.cc/cancers/oligodendroglioma/), [Paediatric high-grade glioma (excluding diffuse midline glioma)](https://onco.cc/cancers/paediatric-high-grade-glioma/), [Paediatric low-grade glioma](https://onco.cc/cancers/paediatric-low-grade-glioma/)
- technologies: [Active surveillance](https://onco.cc/technologies/active-surveillance/), [DNA methylation profiling](https://onco.cc/technologies/methylation-profiling/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [MRI](https://onco.cc/technologies/mri/)
- terms: [1p/19q codeletion](https://onco.cc/terms/1p19q-codeletion/), [Blood-brain barrier (BBB)](https://onco.cc/terms/blood-brain-barrier/), [CDKN2A/B homozygous deletion](https://onco.cc/terms/cdkn2a-homozygous-deletion/), [Extent of resection (RANO resect classes)](https://onco.cc/terms/extent-of-resection/), [MGMT promoter methylation](https://onco.cc/terms/mgmt/), [Re-irradiation](https://onco.cc/terms/re-irradiation/)
- targets: [IDH1 / IDH2](https://onco.cc/targets/idh/), [TP53](https://onco.cc/targets/tp53/)
- drugs: [Bevacizumab (glioblastoma use)](https://onco.cc/drugs/bevacizumab-glioma/), [Lomustine (CCNU)](https://onco.cc/drugs/lomustine/), [Olutasidenib](https://onco.cc/drugs/olutasidenib/), [Procarbazine](https://onco.cc/drugs/procarbazine/), [Safusidenib](https://onco.cc/drugs/safusidenib/), [Temozolomide](https://onco.cc/drugs/temozolomide/), [Vincristine](https://onco.cc/drugs/vincristine/), [Vorasidenib](https://onco.cc/drugs/vorasidenib/)
- companies: [Servier](https://onco.cc/companies/servier/)
- pathways: [Glioma (KEGG map)](https://onco.cc/pathways/glioma-signalling/)
- trials: [A Study of DS-1001b in Patients With Chemotherapy- and Radiotherapy-Naive IDH1 Mutated WHO Grade II Glioma](https://onco.cc/trials/nct04458272/), [A Study of PLB1001 Enteric Capsules in the Treatment of sGBM/IDH Mutant Glioblastoma Patients With the ZM Fusion Gene (FUGEN).](https://onco.cc/trials/nct06105619/), [CATNON (EORTC 26053-22054)](https://onco.cc/trials/catnon/), [EORTC 22033-26033](https://onco.cc/trials/eortc-22033/), [EORTC 26981 / NCIC CE.3 (Stupp trial)](https://onco.cc/trials/eortc-26981/), [INDIGO](https://onco.cc/trials/indigo/), [NOA-08](https://onco.cc/trials/noa-08/), [Safety and Efficacy Study in Recurrent or Progressive Grade III or IV IDH1 Mutated Glioma](https://onco.cc/trials/nct02704858/), [SIGMA (Safusidenib in IDH1 Mutant Glioma Maintenance)](https://onco.cc/trials/nct05303519/)
- key papers: [CATNON: concurrent and adjuvant temozolomide in anaplastic glioma without 1p/19q codeletion](https://onco.cc/key-papers/paper-catnon-lancet-2017/), [INDIGO: vorasidenib, the first targeted drug for IDH-mutant low-grade glioma](https://onco.cc/key-papers/paper-indigo-nejm-2023/), [RTOG 9802: radiation plus procarbazine, lomustine and vincristine in high-risk low-grade glioma](https://onco.cc/key-papers/paper-rtog-9802-buckner-nejm-2016/), [The 2021 WHO classification of tumours of the central nervous system: a summary](https://onco.cc/key-papers/paper-who-2021-cns-louis-neuro-oncology-2021/)
- people: [Jan C. Buckner](https://onco.cc/people/jan-buckner/)
- biomarkers: [1p/19q codeletion](https://onco.cc/biomarkers/1p19q-codeletion-readout/), [IDH1 R132 mutation](https://onco.cc/biomarkers/idh1-r132/), [IDH2 mutation (R140 and R172)](https://onco.cc/biomarkers/idh2-mutation/), [MGMT promoter methylation](https://onco.cc/biomarkers/mgmt-promoter-methylation/)

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JSON: https://onco.cc/api/v1/entities/idh-mutant-astrocytoma.json