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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.
Paediatric low-grade gliomas are slow-growing brain tumours driven almost always by a single overactive signal, the MAPK pathway, most often through a BRAF gene change. Because the switch is known, pills that block it (dabrafenib with trametinib, and tovorafenib) now shrink tumours far more often than chemotherapy, and children are increasingly spared radiation to the developing brain.
Paediatric low-grade glioma (pLGG) is a family of WHO grade 1 and 2 tumours (pilocytic astrocytoma, ganglioglioma, diffuse astrocytoma, pleomorphic xanthoastrocytoma and others) that is biologically distinct from adult glioma: it is a single-pathway disease. The KIAA1549-BRAF fusion is the most common driver, BRAF V600E the second, with NF1 loss, FGFR1 alterations and other RAS-MAPK lesions accounting for most of the rest. Tumours rarely transform, but they sit in places (optic pathway, hypothalamus, brainstem, thalamus) where surgery cannot remove them and where growth costs vision, hormones and cognition. Children with neurofibromatosis type 1 make up a large minority of optic pathway gliomas.
Complete resection is curative where it is possible. For unresectable or progressive disease the historical standard was carboplatin and vincristine (or vinblastine monotherapy), chosen so that radiotherapy could be deferred or avoided in young children. The field has now moved to pathway inhibition. In the phase 2 TADPOLE trial (NEJM 2023) dabrafenib plus trametinib produced far more responses and longer progression-free survival than carboplatin-vincristine in BRAF V600E tumours, leading to the first FDA approval of a targeted first-line therapy for a childhood glioma in March 2023. The type II RAF inhibitor tovorafenib, which works on BRAF fusions as well as V600E, produced durable responses in relapsed disease in FIREFLY-1 (Nature Medicine 2024) and received FDA accelerated approval in April 2024; FIREFLY-2/LOGGIC is testing it first line against chemotherapy. The MEK inhibitor selumetinib showed activity in the PBTC-029 studies and is being compared with carboplatin-vincristine in the COG trials ACNS1831 (NF1) and ACNS1833 (non-NF1).
| Setting | Approach | Guideline |
|---|---|---|
| Resectable tumour | Maximal safe resection; gross total resection is curative in most and no adjuvant therapy is given. Observation for stable residual disease. | not mapped |
| Unresectable or progressive, BRAF V600E | Dabrafenib plus trametinib first line (TADPOLE: higher response rate and longer progression-free survival than carboplatin-vincristine; FDA approval March 2023 for patients aged one year and over). | not mapped |
| Relapsed or refractory, BRAF fusion or V600E | Tovorafenib (FIREFLY-1; FDA accelerated approval April 2024 for patients aged six months and over), or a MEK inhibitor such as selumetinib in trials. | not mapped |
| Unresectable, no targetable alteration or targeted drug unavailable | Carboplatin and vincristine, or weekly vinblastine, to defer radiotherapy; focal conformal or proton radiotherapy is reserved for older children and for progression after systemic options. | not mapped |