Pediatric low-grade glioma treatment guidelines

What is A pediatric low-grade glioma?

The most common brain tumors in children are pediatric low-grade gliomas (pLGG), which grow more slowly and are less dangerous than high-grade gliomas. Despite having a high long-term survival rate, these tumours can cause serious health issues depending on where they are located in the brain.

Overview of Pediatric Low-Grade Gliomas: PGLGs are brain tumours that develop from brain support cells, specifically glial cells. Subtypes include pilocytic, diffuse, pleomorphic, and ganglioglioma.

brain tumors in children

Prevalence:

They make up 30% of CNS tumors, making them the most prevalent brain tumour in children.

Presentation and Symptoms

• Depend on tumour size and location.
• Vision difficulties (if near optic pathway)
• Common in cortical tumours: seizures
• Near the hypothalamus, endocrine malfunction
• Balance or motor difficulties (cerebellum or brainstem)
• Due to intracranial pressure, headaches, nausea, vomiting, and developmental delays may occur.

Prognosis

• Survival: 20-year survival rates reach 87%.
• Quality of life: Children may experience vision loss, epilepsy, or cognitive issues despite good survival rates.

Methods of Treatment

The video is about the Treatment for brain tumour of children

Surgery:

• Complete removal can cure malignancies in accessible regions like the cerebellum.
• In problematic places (optic pathway, brainstem), surgery may be limited.

Chemotherapy:

• Primary treatment for progressive or recurring cancers.
• Preferred for younger children to avoid radiation.

Radiotherapy:

• Used sparingly in older children or when other treatments fail.
• Modern methods like proton and conformal photon treatment limit brain tissue damage.

Targeted Therapy:

• Newer medicines block tumor-driving pathways using BRAF or MEK inhibitors.
• Clinical trials compare these to regular chemotherapy.

Considerations, Risks

• Even slow-growing tumors can cause neurological or endocrine issues.
• Genetic syndromes: Some pLGGs are connected to NF1 or tuberous sclerosis, necessitating genetic counseling and monitoring.

Pediatric Low-Grade Glioma Types

The main types of pediatric low-grade gliomas

• Subtype: WHO Grade Common Location Key Features
• Grade 1 pilocytic astrocytoma: cerebellum, optic pathway, brainstem. The most frequent type of pLGG is cystic with a mural nodule, and it has a good prognosis if it is entirely resected.
• Diffuse astrocytoma, Grade 2, cerebral hemispheres. It is infiltrative and difficult to remove, with a danger of progression to a higher grade.
• Grade 2 Pleomorphic xanthoastrocytoma (PXA) in the temporal lobe. Seizures, BRAF mutations, and variable prognosis.
• Ganglioglioma: Grade 1–2 Temporal lobe, cerebral cortex Mixed neuronal and glial tumors; seizures prevalent; surgery often cures.
• Grade 1 angiocentric glioma in the cerebral cortex is rare, closely linked to epilepsy, and slow-growing.
• Dysplastic neuroepithelial tumor, Grade 1: Temporal lobe, a benign epilepsy-associated tumour with a good surgical prognosis.

Molecular Features

• Many PLGGs are caused by MAPK pathway changes, such as BRAF mutations or fusions.
• These molecular fingerprints are increasingly relevant for diagnosis and targeted therapy.

Clinical Notes

• Pilocytic astrocytoma is the most common and usually treatable surgically.
• Because they invade brain tissue, diffuse astrocytomas are harder.
• Surgery generally cures epilepsy caused by gangliogliomas and DNETs.
• Mutation-targeted medicines like BRAF or MEK inhibitors are revolutionizing tumor treatment.

Modern molecular diagnosis for pediatric low-grade glioma

As much as histology, molecular drivers identify pediatric low-grade gliomas (pLGGs), with RAS/MAPK pathway abnormalities (particularly BRAF mutations and fusions) being practically universal. Molecular diagnostics provide tailored medicines that change results.

Also read https://link.springer.com/article/10.1007/s00381-024-06631-1.

Molecular Era in Pediatric Low-Grade Glioma

1. Switch from Histology to Molecular Profiling

• Histology usually characterizes pLGGs as pilocytic, diffuse, or gangliogliomas.
• NGS, RNA sequencing, and fusion detection are now essential for diagnosis and risk stratification.

2. Key Molecular Drivers

• RAS/MAPK pathway activation characterizes pLGGs.
• Changes often include:
• V600E BRAF mutation
• Fusion of BRAF and KIAA1549 in pilocytic astrocytomas
• Other fusions (FGFR1, NTRK, MYB)

3. Diagnostics

• RNA-NGS and bioinformatics fusion callers (Arriba, Archer, STAR-Fusion) discover rearrangements.
• Arriba (97.7%), Archer (88.6%), and STAR-Fusion (67%) detect it. Clinical diagnostics instrument selection is crucial.

Clinical Impact of Molecular Diagnostics

Risk Classification:

Clinical factors (location, resectability) and molecular markers predict progression and personalize treatment.

Therapeutic Targets:

• Dabrafenib and vemurafenib for BRAF V600E mutations.
• Activating MAPK pathways with selumetinib trametinib is a key therapeutic strategyinib.
• These drugs show promise in clinical trials, often with fewer long-term negative effects than chemotherapy or radiotherapy.

Reduced Radiation Use:

Molecularly guided therapies reduce neurocognitive and endocrine problems in children by avoiding or delaying radiation.

Histology vs. Molecular Era

Aspect: 

• Era of Molecular Era Classification Type of tumor by microscope Genetic driver + tumor type
• Location and resection determine prognosis. Molecular risk + clinical features
• Treatment options include surgery, chemo, radiation, and targeted therapy (BRAF/MEK inhibitors).
• Morbidity but favourable survival. Higher survival + lower morbidity

Challenges and Future Plans

• Not all pLGGs behave the same; incomplete resections proceed.
• Test Access: Resource-constrained environments may hinder advanced molecular diagnosis.
• Long-term Data: Targeted medicines are promising, but kid safety is unknown.

Pediatric low-grade glioma—rare?

Thirty to forty percent of CNS cancers are pediatric low-grade gliomas (pLGG), the most common brain tumour in children. Though “rare” in cancer terms, it is the most common diagnosis in childhood brain tumours.

How Common Is Pediatric Low-Grade Glioma?

• Incidence: pLGGs account for 35–40% of juvenile CNS tumours, the largest category.
• Age group: Most instances are diagnosed in children and adolescents between 5 and 15.
• Survival is good, with many children living into adulthood, although tumour location and treatment side effects might impact quality of life

Why do some call them “rare”

• Compared to adult cancers, juvenile brain tumours are rare.
• Since pLGGs impact a small population compared to adult malignancies, advocacy groups and regulatory bodies like the FDA designate them as “rare diseases” for therapeutic development.

A common kind of childhood brain tumour.

Childhood brain tumours are rarer than adult malignancies; pLGGs are still rare in the general population.

Clinical significance: Though "low-grade," they can induce visual loss, seizures, and endocrine disruption depending on location.

How are low-grade gliomas diagnosed?

Low-grade gliomas are diagnosed by clinical examination, imaging (particularly MRI), and tissue sample with molecular testing. Imaging can indicate gliomas, but a sample is needed to confirm the diagnosis and verify the tumor's grade and genetic profile.

How to Diagnose Low-Grade Glioma

1. Clinical Assessment

• Vision, hearing, balance, reflexes, strength, and coordination are all assessed during the neurologic exam.
• Headaches, seizures, vision problems, weakness, or cognitive issues warrant investigation.

Imaging Studies

MRI: Magnetic resonance imaging

• Glioma detection gold standard.
• T1 hypointense and T2/FLAIR hyperintense lesions characterize low-grade gliomas.
• Their contrast enhancement is usually less than that of high-grade gliomas.
• CT scans: Less sensitive than MRI but sometimes utilized.
• Advanced imaging: MR, diffusion, and PET scans reveal tumor metabolism and aggressiveness.

3. Histopathology/biopsy

• Tissue samples come from a stereotactic needle biopsy or surgery.
• Pathologists study cells under a microscope to determine tumor type and grade.
• Histology is no longer enough—molecular testing is routine.

4. Molecular Diagnostics

• Testing tumor tissue for genetic alterations.
• Common low-grade glioma markers:
• Adult diffuse astrocytomas and oligodendrogliomas carry IDH mutations.
• Oligodendrogliomas occur with 1p/19q co-deletion.
• BRAF mutations/fusions (common in pediatric gliomas).
• These markers improve diagnosis, therapy, and prognosis.

Important Considerations

• A biopsy is needed to confirm the grade after imaging.
• Classification and treatment planning now require molecular profiling.
• Biopsy presents a small risk of bleeding, infection, or neurological damage but provides essential diagnostic information.

Conclusion

Pediatric low-grade gliomas (pLGGs), the most frequent childhood brain tumors, are slow-growing and have favorable long-term survival. They can cause major neurological and developmental issues depending on their location.

Modern molecular diagnosis and treatment focus on RAS/MAPK pathway changes, specifically BRAF mutations and fusions, rather than histology classification. This has enabled tailored medicines like BRAF and MEK inhibitors to reduce radiation use and improve children's quality of life.

Molecular diagnoses and targeted treatments are improving results for juvenile low-grade gliomas, changing the focus from survival to function and quality of life.