Astrocytoma, IDH-mutant (grades 2 to 4)
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.
Overview
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.
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.
Red cards
From the labels and guidelines behind the standard of care. Your team's thresholds win.- Emergency services nowBleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
- Emergency services nowBowel perforation
Sudden severe abdominal pain, a hard or very tender abdomen, or abdominal pain with vomiting and fever. Boxed warning for gastrointestinal perforation on bevacizumab.
- Emergency services nowDifferentiation syndrome
Fever, cough or breathlessness, rapid weight gain or swelling, bone pain, low blood pressure or reduced urine; the labels say to start steroids and monitor at the first suspicion, and the syndrome has been fatal.
- Check before combiningFood and drink: Temozolomide
Take on an empty stomach or at bedtime to reduce nausea; PJP prophylaxis during concurrent chemoradiation.
- Check before combiningFood and drink: Vincristine
Fatal if given intrathecally: label all syringes.
- Good to knowPeripheral neuropathy (chemotherapy-induced)
Nerve damage from chemotherapy that causes numbness, tingling and pain in the hands and feet, and sometimes weakness or hearing loss. It builds up with each dose, can be permanent, and is the main reason oxaliplatin, taxanes and vincristine have to be stopped or reduced.
See all on the product pages:Bevacizumab (glioblastoma use)Lomustine (CCNU)ProcarbazineTemozolomideVincristineVorasidenib·Printable cards in the navigator
Anatomy and lymph node drainage
- Frontal lobe (glioblastoma commonest)
- Temporal lobe
- Corpus callosum (butterfly glioma)
- Lower-grade IDH-mutant glioma
- Cerebellum (medulloblastoma)
- Brainstem and spinal cord (diffuse midline glioma, cord tumours)
- Ventricles and ependymal lining (ependymoma)
- Sella and pituitary (pituitary tumours, craniopharyngioma)
- Deep periventricular tissue (CNS lymphoma)
- Meninges and convexity (meningioma)
- Grey-white junction (brain metastases)
- Cerebellopontine angle and eighth nerve (vestibular schwannoma)
- Pineal and suprasellar midline (germ cell tumours)
Gliomas infiltrate along white matter and can cross the corpus callosum, medulloblastoma sits in the cerebellum, and CNS lymphoma favours deep periventricular tissue; none spread through lymph nodes.
- Frontal lobe (glioblastoma commonest)Astrocytoma, IDH-mutant, grade 4 (necrosis, microvascular proliferation or CDKN2A/B homozygous deletion)
- Temporal lobe
- Corpus callosum (butterfly glioma)
- Lower-grade IDH-mutant gliomaAstrocytoma, 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)
- Cerebellum (medulloblastoma)
- Brainstem and spinal cord (diffuse midline glioma, cord tumours)
- Ventricles and ependymal lining (ependymoma)
- Sella and pituitary (pituitary tumours, craniopharyngioma)
- Deep periventricular tissue (CNS lymphoma)
- Meninges and convexity (meningioma)
- Grey-white junction (brain metastases)
- Cerebellopontine angle and eighth nerve (vestibular schwannoma)
- Pineal and suprasellar midline (germ cell tumours)
No conventional lymphatics: gliomas spread along white matter tracts and, rarely, through cerebrospinal fluid; medulloblastoma can seed the spine.
Same organ: Glioma & glioblastoma, Primary CNS lymphoma, Medulloblastoma, Paediatric low-grade glioma, Diffuse midline glioma, H3 K27-altered (including DIPG), Atypical teratoid/rhabdoid tumour (ATRT), Ependymoma, Craniopharyngioma, Pituitary tumours (pituitary neuroendocrine tumours) and pituitary carcinoma, Brain and spinal cord tumours (all types), Oligodendroglioma, IDH-mutant and 1p/19q-codeleted, Paediatric high-grade glioma (excluding diffuse midline glioma), Meningioma, Brain metastases (secondary brain tumours), Vestibular schwannoma (acoustic neuroma), Central nervous system germ cell tumours (germinoma and non-germinomatous), Spinal cord tumours (intramedullary and intradural)
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.
- DNA methylation profilingEstablished
- MRIStandard of care
Nothing recorded yet.
Nothing recorded yet.
Also on OnCo: Symptoms and red flags · Early detection roadmap.
Cases by country
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Maximal safe resection with awake or functional mapping where needed; integrated histological and molecular diagnosis (IDH, 1p/19q, ATRX, CDKN2A/B, methylation class).
Observation with serial MRI, or vorasidenib for grade 2 tumours not needing immediate radiotherapy or chemotherapy (INDIGO).
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.
Radiotherapy followed by twelve cycles of adjuvant temozolomide (CATNON); concurrent temozolomide is not needed in non-codeleted tumours.
Radiotherapy with concurrent and adjuvant temozolomide, extrapolated from glioblastoma; trials of IDH inhibitors preferred where available.
Re-resection, re-irradiation, lomustine or temozolomide re-challenge, bevacizumab for oedema and symptoms; clinical trials.
Subtypes & biomarkers
top- 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)
- 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
How often this target appears
- 2008IDH1 mutations found in glioma
Parsons and colleagues sequence glioblastoma exomes (Science) and find IDH1 mutations concentrated in younger patients and secondary tumours.
- 2009IDH1 and IDH2 mutations define a glioma lineage
Yan and colleagues (NEJM) show IDH mutations in most grade 2 and 3 gliomas and their better prognosis.
- 2016RTOG 9802: radiotherapy plus PCV doubles survival in high-risk low-grade glioma
Buckner and colleagues (NEJM) report median overall survival of 13.3 years against 7.8 years with radiotherapy alone.
- 2016WHO 2016 classification makes IDH status part of the diagnosis
- 2017CATNON: adjuvant temozolomide after radiotherapy for grade 3 non-codeleted glioma
- 2021WHO 2021 renames the type astrocytoma, IDH-mutant, grades 2 to 4, with CDKN2A/B deletion as a grade 4 criterion
- 2023INDIGO: vorasidenib delays progression in grade 2 IDH-mutant glioma
Mellinghoff and colleagues (NEJM): median progression-free survival 27.7 versus 11.1 months.
- 2024FDA approves vorasidenib for grade 2 IDH-mutant astrocytoma and oligodendroglioma
Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 15 changes by month →- 2026-09-17This recordAstrocytoma, IDH-mutant (grades 2 to 4)Facts on this page last checked
When this page itself was last checked or edited.
- 2024-08-06RegulatoryVorasidenibVorasidenib: approval (US)
Grade 2 IDH-mutant astrocytoma or oligodendroglioma after surgery, age ≥12 (INDIGO): first targeted therapy for low-grade glioma
- 2024ApprovalVorasidenibVorasidenib approved in US
Grade 2 IDH-mutant astrocytoma or oligodendroglioma after surgery, age ≥12
- 2024MilestoneVorasidenibFDA approves vorasidenib for grade 2 IDH-mutant astrocytoma and oligodendroglioma
A milestone in how this cancer is treated.
- 2023Trial resultINDIGOINDIGO reported
PFS 27.
- 2023MilestoneVorasidenibINDIGO: vorasidenib delays progression in grade 2 IDH-mutant glioma
Mellinghoff and colleagues (NEJM): median progression-free survival 27.7 versus 11.1 months.
What is in development for Astrocytoma, IDH-mutant (grades 2 to 4), drawn from the whole corpus: 4 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.
Drugs in phase 3 · 1
Trials reported · 3
- CATNON (EORTC 26053-22054) · phase 3 · 2017 · positive
- EORTC 22033-26033 · phase 3 · 2016 · negative
- INDIGO · phase 3 · 2023 · positive
Open problems and what is being done
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.
and how the field plans to fix it →What is being done about thisRecurrence and residual diseaseAvailable now- OlutasidenibApproved
In trialsNothing recorded yet.
Ideas and roadmapsNothing recorded yet.
Also on OnCo: Treatment journeys · Survivorship planner.
Trials
topTrials recruiting now
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Landmark trials
Expert centres
topExpert centres
Heidelberg · cancer center | Germany | none recorded | 0 | 3,456 | 45,745 | #18 | |
Brussels · consortium | Belgium | none recorded | 2 | not matched | - | none recorded | - |
Heidelberg · research institute | Germany | none recorded | 0 | 2,202 | 32,575 | - | |
Utrecht · cancer center | Netherlands | none recorded | 0 | 1,422 | 20,323 | - | |
Tianjin · cancer center | China | none recorded | 0 | 1,219 | 11,455 | - | |
Hangzhou · cancer center | China | none recorded | 0 | 1,219 | 17,635 | - | |
Rozzano (Milan) · hospital | Italy | none recorded | 0 | 1,031 | 10,720 | - | |
Changsha · cancer center | China | none recorded | 0 | 930 | 14,477 | - | |
Jinan · cancer center | China | none recorded | 0 | 920 | 7,804 | - | |
Dresden · cancer center | Germany | none recorded | 0 | 728 | 7,984 | - | |
| United Kingdom | none recorded | 0 | 693 | 7,168 | - | ||
Aarhus · hospital | Denmark | none recorded | 0 | 624 | 4,497 | - | |
Freiburg im Breisgau · cancer center | Germany | none recorded | 0 | 549 | 5,261 | - | |
Singapore · cancer center | Singapore | none recorded | 0 | 493 | 5,212 | - | |
Geneva · hospital | Switzerland | none recorded | 0 | 441 | 6,485 | - |
These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with Astrocytoma, IDH-mutant but is thinly recorded here will look small.
Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.
Questions to ask
topQuestions to ask your oncologist about Astrocytoma, IDH-mutant
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example IDH1 R132H immunohistochemistry, with sequencing of IDH1 and IDH2 for non-canonical mutations, 1p/19q status, ATRX loss and TP53 mutation, CDKN2A/B homozygous deletion, DNA methylation class and G-CIMP status), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include Astrocytoma, IDH-mutant, grade 2, Astrocytoma, IDH-mutant, grade 3, Astrocytoma, IDH-mutant, grade 4.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Newly diagnosed, all grades
- For my situation (newly diagnosed, all grades), which of the standard options do you recommend and why?Why: Guideline options include: Maximal safe resection with awake or functional mapping where needed; integrated histological and molecular diagnosis (IDH, 1p/19q, ATRX, CDKN2A/B, methylation class).
Grade 2, residual or recurrent, low risk
- For my situation (grade 2, residual or recurrent, low risk), which of the standard options do you recommend and why?Why: Guideline options include: Observation with serial MRI, or vorasidenib for grade 2 tumours not needing immediate radiotherapy or chemotherapy (INDIGO).
- Am I a candidate for Vorasidenib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of INDIGO apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Grade 2, high risk (age 40 or over, subtotal resection)
- For my situation (grade 2, high risk (age 40 or over, subtotal resection)), which of the standard options do you recommend and why?Why: Guideline options include: 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.
- Am I a candidate for Procarbazine, Lomustine (CCNU), Vincristine or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of EORTC 22033-26033 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Grade 3
- For my situation (grade 3), which of the standard options do you recommend and why?Why: Guideline options include: Radiotherapy followed by twelve cycles of adjuvant temozolomide (CATNON); concurrent temozolomide is not needed in non-codeleted tumours.
- Am I a candidate for Temozolomide, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of CATNON (EORTC 26053-22054) apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Grade 4
- For my situation (grade 4), which of the standard options do you recommend and why?Why: Guideline options include: Radiotherapy with concurrent and adjuvant temozolomide, extrapolated from glioblastoma; trials of IDH inhibitors preferred where available.
- Am I a candidate for Temozolomide, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of EORTC 26981 / NCIC CE.3 (Stupp trial) apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Recurrence
- For my situation (recurrence), which of the standard options do you recommend and why?Why: Guideline options include: Re-resection, re-irradiation, lomustine or temozolomide re-challenge, bevacizumab for oedema and symptoms; clinical trials.
- Am I a candidate for Lomustine (CCNU), Temozolomide, Bevacizumab (glioblastoma use), and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Are there clinical trials I could join, for example of Vorasidenib, Safusidenib, Olutasidenib, DNA methylation profiling?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “Whether vorasidenib should replace radiotherapy and chemotherapy or only defer them, and what to do at progression on it”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “No IDH inhibitor has yet shown benefit in grade 3 or 4 IDH-mutant astrocytoma”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
Newly diagnosed? Read the first 60 days with Astrocytoma, IDH-mutant, then print the one-page appointment sheet with room for the answers.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
9targets
3drugs
8companies
5pathways
1terms
4trials
5Latest papers
topQuery for this cancer: (TITLE:"Astrocytoma, IDH-mutant" OR ABSTRACT:"Astrocytoma, IDH-mutant" OR TITLE:"grades 2 to 4" OR ABSTRACT:"grades 2 to 4" OR TITLE:"IDH-mutant astrocytoma" OR ABSTRACT:"IDH-mutant astrocytoma" OR TITLE:"Diffuse astrocytoma, IDH-mutant" OR ABSTRACT:"Diffuse astrocytoma, IDH-mutant" OR TITLE:"Anaplastic astrocytoma, IDH-mutant" OR ABSTRACT:"Anaplastic astrocytoma, IDH-mutant" OR TITLE:"Lower-grade glioma" OR ABSTRACT:"Lower-grade glioma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Astrocytoma, IDH-mutant (grades 2 to 4), not a curated reading list.
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