Loading
9 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
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.
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.
| Setting | Approach | Guideline |
|---|---|---|
| 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). | not mapped |
| Grade 2, residual or recurrent, low risk | Observation with serial MRI, or vorasidenib for grade 2 tumours not needing immediate radiotherapy or chemotherapy (INDIGO). | not mapped |
| 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. | not mapped |
| Grade 3 | Radiotherapy followed by twelve cycles of adjuvant temozolomide (CATNON); concurrent temozolomide is not needed in non-codeleted tumours. | not mapped |
| Grade 4 | Radiotherapy with concurrent and adjuvant temozolomide, extrapolated from glioblastoma; trials of IDH inhibitors preferred where available. | not mapped |
| Recurrence | Re-resection, re-irradiation, lomustine or temozolomide re-challenge, bevacizumab for oedema and symptoms; clinical trials. | not mapped |