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10 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.
High-grade gliomas in children look like adult glioblastoma under the microscope but are driven by different genes, so they are now classified separately. Surgery and radiotherapy remain the mainstay and chemotherapy adds little; the real gains are in small subsets with a targetable gene change, such as BRAF V600E tumours and the fusion-driven tumours of infants.
WHO 2021 separates paediatric-type diffuse high-grade gliomas from adult glioblastoma into four types: diffuse midline glioma, H3 K27-altered (covered on its own page); diffuse hemispheric glioma, H3 G34-mutant, of adolescents and young adults with TP53 and ATRX mutations; diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, with PDGFRA amplification, MYCN amplification or EGFR alteration defining methylation subgroups; and infant-type hemispheric glioma, defined by NTRK, ALK, ROS1 or MET fusions in children under about three. Hypermutant tumours arising in constitutional mismatch repair deficiency and radiation-induced gliomas after treatment of another childhood cancer are distinct further groups. Methylation profiling is essential because morphology cannot separate these entities and some low-grade-appearing tumours prove high grade molecularly.
Treatment is maximal safe resection followed by focal radiotherapy, with temozolomide during and after radiotherapy adopted from adult practice although the ACNS0126 study did not show it clearly improved on historical outcomes; the HERBY trial (2018) showed adding bevacizumab did not help. Radiotherapy is deferred or avoided in infants, whose tumours are chemosensitive and in whom fusion-directed drugs work: larotrectinib and entrectinib for NTRK fusions, alectinib or lorlatinib for ALK and ROS1 fusions, with responses that can allow less surgery. In BRAF V600E-mutant high-grade glioma dabrafenib plus trametinib produced durable responses in the paediatric cohort reported in 2023, and the combination has a tumour-agnostic approval for BRAF V600E solid tumours from the age of six. Constitutional mismatch repair deficiency tumours respond to PD-1 blockade.
| Setting | Approach | Guideline |
|---|---|---|
| Newly diagnosed, child over about three years | Maximal safe resection, focal radiotherapy and temozolomide during and after radiotherapy by extrapolation from adult practice; molecular profiling of every tumour. | not mapped |
| Infant-type hemispheric glioma with a fusion | Surgery and fusion-directed therapy: larotrectinib or entrectinib for NTRK fusions, alectinib or lorlatinib for ALK or ROS1 fusions; chemotherapy to defer radiotherapy. | not mapped |
| BRAF V600E-mutant | Dabrafenib plus trametinib (paediatric high-grade glioma cohort 2023; tumour-agnostic approval for BRAF V600E solid tumours from age six). | not mapped |
| Constitutional mismatch repair deficiency | PD-1 blockade (nivolumab or pembrolizumab) for hypermutant tumours; germline counselling for the family. | not mapped |
| Recurrence | No standard; re-resection, re-irradiation, clinical trials including CAR-T and oncolytic virus studies. | not mapped |