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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).
The reframing is from a cancer to be eradicated to a chronic condition to be controlled while the brain matures: the open questions are how long to treat, whether tumours regrow when inhibitors stop, the long-term effects of MAPK inhibition on growth and bone, and how to protect vision in optic pathway tumours. Molecular diagnosis at presentation (fusion and point-mutation testing, methylation profiling) is now the standard entry point to care.
The most common brain tumour of childhood, roughly a third of all paediatric central nervous system tumours (NCI PDQ); many children live for decades with the disease.
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.
No conventional lymphatics: gliomas spread along white matter tracts and, rarely, through cerebrospinal fluid; medulloblastoma can seed the spine.
Same organ: Lactotroph pituitary neuroendocrine tumour (prolactinoma), Somatotroph pituitary neuroendocrine tumour (acromegaly), Corticotroph pituitary neuroendocrine tumour (Cushing disease and silent corticotroph tumour), Gonadotroph pituitary neuroendocrine tumour (non-functioning adenoma), Thyrotroph pituitary neuroendocrine tumour (TSH-secreting), Pineocytoma and pineal parenchymal tumour of intermediate differentiation, Pineoblastoma, Papillary tumour of the pineal region, Choroid plexus carcinoma, Glioma & glioblastoma, Primary CNS lymphoma, Medulloblastoma, 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), Astrocytoma, IDH-mutant (grades 2 to 4), 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), WNT-activated medulloblastoma, SHH-activated medulloblastoma, Group 3 and group 4 medulloblastoma (non-WNT/non-SHH)
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Also on OnCo: Symptoms and red flags · Early detection roadmap.
Maximal safe resection; gross total resection is curative in most and no adjuvant therapy is given. Observation for stable residual disease.
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).
Tovorafenib (FIREFLY-1; FDA accelerated approval April 2024 for patients aged six months and over), or a MEK inhibitor such as selumetinib in trials.
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.
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One cancer page and one trial page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
One cancer page and one trial page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
Query for this cancer: (TITLE:"Paediatric low-grade glioma" OR ABSTRACT:"Paediatric low-grade glioma" OR TITLE:"Childhood astrocytoma" OR ABSTRACT:"Childhood astrocytoma" OR TITLE:"pLGG" OR ABSTRACT:"pLGG" OR TITLE:"Pilocytic astrocytoma" OR ABSTRACT:"Pilocytic astrocytoma" OR TITLE:"Optic pathway glioma" OR ABSTRACT:"Optic pathway glioma" OR TITLE:"Childhood glioma low grade" OR ABSTRACT:"Childhood glioma low grade") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Paediatric low-grade glioma, not a curated reading list.
Packer and colleagues show chemotherapy can defer radiotherapy in young children.
Tandem duplication at 7q34 found in most pilocytic astrocytomas (Jones and colleagues), defining pLGG as a MAPK-pathway disease.
PBTC-029 phase 2 (Fangusaro, Lancet Oncology) reports responses in BRAF-altered and NF1-associated tumours.
Higher response rate and longer progression-free survival than carboplatin-vincristine in BRAF V600E pLGG (NEJM); FDA approval in March 2023.
FIREFLY-1 (Nature Medicine 2024) shows durable responses across fusions and V600E; FDA accelerated approval April 2024.
The targets of this cancer's medicines and the ones linked to it directly.
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.
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Bleeding that does not stop by itself, bleeding from more than one site, or new bruising in several places or one large area.
Fainting, near-fainting, or an irregular or racing heartbeat; several kinase inhibitors prolong the QT interval and the labels require ECG and electrolyte monitoring.
Dabrafenib: take on an empty stomach. Trametinib: take on an empty stomach; both cause pyrexia.
Fatal if given intrathecally: label all syringes.
Dose by Calvert formula using GFR (see the calculators).
Reactions around the moment a drug is given: chills, fever or breathlessness from antibodies (infusion reactions), true allergy (hypersensitivity, rarely anaphylaxis), and leakage of a damaging drug into tissue around the vein (extravasation).
See all on the product pages:CarboplatinDabrafenib + trametinibVinblastineVincristine·Printable cards in the navigator
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