# Paediatric low-grade glioma

Source: https://onco.cc/cancers/paediatric-low-grade-glioma/  
OnCo record `paediatric-low-grade-glioma` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-10
- Also known as: Childhood astrocytoma; pLGG; Pilocytic astrocytoma; Optic pathway glioma; Childhood glioma (low grade)
- Tags: nci-coverage; paediatric; cns
- Group: paediatric
- Burden: 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.
- Subtypes: Pilocytic astrocytoma (KIAA1549-BRAF fusion in most); Ganglioglioma and pleomorphic xanthoastrocytoma (often BRAF V600E); NF1-associated optic pathway glioma; Diffuse astrocytoma, MYB or MYBL1-altered; FGFR1-altered glioma (dysembryoplastic neuroepithelial tumour, rosette-forming glioneuronal tumour); Subependymal giant cell astrocytoma (tuberous sclerosis; mTOR inhibitors)
- Biomarkers: KIAA1549-BRAF fusion; BRAF V600E (worse response to chemotherapy, target of BRAF/MEK inhibitors); NF1 germline status; FGFR1 mutation or fusion; CDKN2A deletion (with V600E, marks higher risk); Methylation-based classification; Visual acuity and visual fields in optic pathway glioma

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/paediatric-low-grade-glioma/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/paediatric-low-grade-glioma/#overview [1 subtype, 4 state-of-the-art points]
- What it is (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/paediatric-low-grade-glioma/#what-it-is [7 subtypes]
- Finding it (on the hub): How it shows itself, how it is confirmed, what screening exists, and the biomarkers clinicians test for. https://onco.cc/cancers/paediatric-low-grade-glioma/#finding-it [7 biomarkers]
- Treating it (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/paediatric-low-grade-glioma/#treating-it [4 settings, 1 decision with options]
- Evidence (on the hub): Trials recruiting now, the landmark trials, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/paediatric-low-grade-glioma/#evidence [4 trials, 2 key papers, 5 milestones]
- The science (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/paediatric-low-grade-glioma/#science [11 targets, 2 pathways]
- Where you are (own page): Cases by country, the UK and NHS pathway and other country lenses, and the expert centres with trials on record. https://onco.cc/cancers/paediatric-low-grade-glioma/where-you-are/ [2 centres]
- Living with it (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/paediatric-low-grade-glioma/#living-with-it [18 questions, 6 red cards]
- What is coming (own page): Everything in development, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/paediatric-low-grade-glioma/coming/ [7 medicines, 3 trials, 4 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/paediatric-low-grade-glioma/data/ [58 connected records]

## Standard of care

- Resectable tumour: Maximal safe resection; gross total resection is curative in most and no adjuvant therapy is given. Observation for stable residual disease. ([MRI](https://onco.cc/technologies/mri/))
- 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). ([Dabrafenib + trametinib](https://onco.cc/drugs/dabrafenib-trametinib/), [TADPOLE (CDRB436G2201)](https://onco.cc/trials/tadpole/))
- 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. ([Tovorafenib](https://onco.cc/drugs/tovorafenib/), [FIREFLY-1](https://onco.cc/trials/firefly-1/))
- 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. ([Carboplatin](https://onco.cc/drugs/carboplatin/), [Vincristine](https://onco.cc/drugs/vincristine/), [Vinblastine](https://onco.cc/drugs/vinblastine/), [Proton therapy](https://onco.cc/technologies/proton-therapy/))

## State of the art

- pLGG is a single-pathway (RAS-MAPK) disease in almost every case; molecular testing at diagnosis now decides therapy.
- Targeted therapy has displaced chemotherapy for BRAF V600E tumours (dabrafenib plus trametinib) and gives a second option for fusion-driven tumours (tovorafenib); FIREFLY-2/LOGGIC tests tovorafenib first line.
- Radiotherapy is deferred or avoided in young children because of its cost to cognition, vision and endocrine function; proton therapy is used when radiation cannot be avoided.
- The disease is increasingly managed as a chronic condition: the aim is to preserve vision, hormones and learning through childhood, not only to shrink the tumour.

## Open problems

- How long to continue MAPK inhibitors and whether tumours regrow on stopping; intermittent dosing and stop rules are being studied in FIREFLY-2 and the COG selumetinib trials.
- Long-term effects of RAF and MEK inhibition on growth plates, skin and heart in children who may take them for years; registries and trial follow-up are collecting these data.
- Preserving vision in optic pathway glioma, where imaging response and visual outcome do not always agree; visual endpoints are now built into trials.
- Access to molecular testing and to the new drugs outside high-income countries.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Pilocytic_astrocytoma
- NCI PDQ: childhood astrocytomas, other gliomas and glioneuronal tumours: https://www.cancer.gov/types/brain/hp/child-astrocytoma-treament-pdq
- TADPOLE: dabrafenib plus trametinib in BRAF V600E pLGG (NEJM 2023): https://doi.org/10.1056/NEJMoa2303815
- FIREFLY-1: tovorafenib in relapsed BRAF-altered pLGG (Nature Medicine 2024): https://doi.org/10.1038/s41591-023-02668-y

## Connected records

- cancers: [Astrocytoma, IDH-mutant (grades 2 to 4)](https://onco.cc/cancers/idh-mutant-astrocytoma/), [Brain and spinal cord tumours (all types)](https://onco.cc/cancers/brain-tumours/), [Childhood cancers (all types)](https://onco.cc/cancers/childhood-cancers/), [Craniopharyngioma](https://onco.cc/cancers/craniopharyngioma/), [Diffuse midline glioma, H3 K27-altered (including DIPG)](https://onco.cc/cancers/dipg-dmg/), [Ependymoma](https://onco.cc/cancers/ependymoma/), [Glioma & glioblastoma](https://onco.cc/cancers/glioblastoma/), [Oligodendroglioma, IDH-mutant and 1p/19q-codeleted](https://onco.cc/cancers/oligodendroglioma/), [Optic pathway glioma](https://onco.cc/cancers/optic-pathway-glioma/), [Paediatric high-grade glioma (excluding diffuse midline glioma)](https://onco.cc/cancers/paediatric-high-grade-glioma/)
- terms: [CDKN2A/B homozygous deletion](https://onco.cc/terms/cdkn2a-homozygous-deletion/), [Late effects and survivorship toxicity](https://onco.cc/terms/late-effects/), [RACE for Children Act](https://onco.cc/terms/race-for-children-act/)
- technologies: [DNA methylation profiling](https://onco.cc/technologies/methylation-profiling/), [Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/), [Intraoperative MRI and CT](https://onco.cc/technologies/intraoperative-mri-ct/), [Laser interstitial thermal therapy systems (NeuroBlate, Visualase)](https://onco.cc/technologies/litt-systems/), [MRI](https://onco.cc/technologies/mri/), [Proton therapy](https://onco.cc/technologies/proton-therapy/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/), [Survivorship care and late-effects surveillance](https://onco.cc/technologies/survivorship-care-plan/), [Transcranial focused ultrasound systems (Exablate Neuro, SonoCloud)](https://onco.cc/technologies/transcranial-focused-ultrasound-systems/)
- targets: [BRAF](https://onco.cc/targets/braf/), [FAM174B](https://onco.cc/targets/fam174b/), [KDM3B](https://onco.cc/targets/kdm3b/), [LATS2](https://onco.cc/targets/lats2/), [LDB1](https://onco.cc/targets/ldb1/), [MYB](https://onco.cc/targets/myb/), [PPM1D](https://onco.cc/targets/ppm1d/), [PRKAR1A](https://onco.cc/targets/prkar1a/), [SUFU](https://onco.cc/targets/sufu/), [TCF4](https://onco.cc/targets/tcf4/)
- drugs: [Carboplatin](https://onco.cc/drugs/carboplatin/), [Dabrafenib](https://onco.cc/drugs/dabrafenib/), [Dabrafenib + trametinib](https://onco.cc/drugs/dabrafenib-trametinib/), [Tovorafenib](https://onco.cc/drugs/tovorafenib/), [Trametinib](https://onco.cc/drugs/trametinib/), [Vinblastine](https://onco.cc/drugs/vinblastine/), [Vincristine](https://onco.cc/drugs/vincristine/)
- companies: [Children's Cancer and Leukaemia Group](https://onco.cc/companies/cclg/), [Children's Oncology Group (COG)](https://onco.cc/companies/childrens-oncology-group/), [Day One Biopharmaceuticals](https://onco.cc/companies/day-one-biopharmaceuticals/), [Innovative Therapies for Children with Cancer (ITCC)](https://onco.cc/companies/itcc/), [Novartis](https://onco.cc/companies/novartis/)
- institutions: [ACCELERATE](https://onco.cc/institutions/accelerate-platform/), [SIOP Europe (European Society for Paediatric Oncology)](https://onco.cc/institutions/siop-europe/)
- pathways: [Glioma (KEGG map)](https://onco.cc/pathways/glioma-signalling/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/)
- trials: [DAY101 vs. Standard of Care Chemotherapy in Pediatric Participants With Low-Grade Glioma Requiring First-Line Systemic Therapy (LOGGIC/FIREFLY-2)](https://onco.cc/trials/nct05566795/), [FIREFLY-1](https://onco.cc/trials/firefly-1/), [NCI-COG Pediatric MATCH (APEC1621)](https://onco.cc/trials/pediatric-match/), [TADPOLE (CDRB436G2201)](https://onco.cc/trials/tadpole/)
- bottlenecks: [Rare and paediatric cancers without markets](https://onco.cc/bottlenecks/b-rare-cancers/), [Survivorship and late effects are neglected](https://onco.cc/bottlenecks/b-survivorship/)
- key papers: [Dabrafenib plus Trametinib in Pediatric Glioma with BRAF V600 Mutations](https://onco.cc/key-papers/paper-bouffet-n-engl-j-med/), [The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial](https://onco.cc/key-papers/paper-kilburn-nat-med/)
- biomarkers: [BRAF fusion or rearrangement](https://onco.cc/biomarkers/braf-fusion/), [BRAF V600E (and V600K)](https://onco.cc/biomarkers/braf-v600e/)
- roadmaps: [Paediatric oncology roadmap: cooperative-group cures → engineered immunity → drugs developed for children first](https://onco.cc/roadmaps/paediatric-oncology-roadmap/)
- journals: [Brain tumor pathology](https://onco.cc/journals/brain-tumor-pathology/), [CNS oncology](https://onco.cc/journals/cns-oncology/), [Journal of neuro-oncology](https://onco.cc/journals/journal-of-neuro-oncology/)

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