Paediatric high-grade glioma: the decisions you may face
5 treatment settings, 4 with more than one named option. Each section lays out the options the standard of care names, what each is for, the trials behind them with their recorded results, the side effects and cautions on record, and questions to ask. Built from the cancer page's standard-of-care rows; nothing here is advice for your case.
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.
IMRT and IGRT shape the radiation beam to the tumour's outline from multiple angles and check the patient's position with a scan before every session, so surrounding organs receive less dose. Fewer, larger doses are now standard in breast and prostate cancer, but a low-dose bath still spreads across normal tissue.
- Conformal dose, fewer side effects
- Hypofractionation saves visits
Radiation using protons, which stop inside the tumour instead of passing through, so tissue behind it gets no dose.
- No exit dose; lower integral dose
- Reduced second cancers in children
The only chemotherapy proven to extend life in glioblastoma, given during and after radiation. It works best when the tumour has switched off a repair gene called MGMT.
Reading chemical tags on DNA that reveal a cell's identity, used to classify brain tumours and to detect cancer in blood.
- Cell-of-origin memory
- Stable analyte in blood
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
- Low-dose bath to normal tissue
- Motion management
- Cost
- Range uncertainty
- Limited randomised evidence in adults
- Take on an empty stomach or at bedtime to reduce nausea; PJP prophylaxis during concurrent chemoradiation.
- Reference cohort dependence
- Between IMRT / IGRT (modern external beam), Proton therapy, Temozolomide and the other options, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCI PDQ: childhood astrocytomas, other gliomas and glioneuronal tumours), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (newly diagnosed, child over about three years), which of the standard options do you recommend and why?Why: Guideline options include: Maximal safe resection, focal radiotherapy and temozolomide during and after radiotherapy by extrapolation from adult practice; molecular profiling of every tumour.
- Am I a candidate for Temozolomide, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Add these to your appointment list, or take the full question set for this cancer.
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.
The first drug approved for a gene fusion regardless of where the cancer started; it works in about 75% of NTRK-fusion cancers, from infant fibrosarcoma to salivary and thyroid cancers.
Entrectinib (Rozlytrek) is a pill for NTRK-fusion cancers and ROS1 lung cancer that reaches brain metastases.
Alectinib is a well-tolerated ALK pill, standard first line for years and, since 2024, the first targeted therapy given after surgery for ALK-positive lung cancer.
An ALK inhibitor with the longest disease control ever recorded for a targeted lung cancer pill: 60% progression-free at five years.
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
- Avoid grapefruit.
- Known QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.
- Take with food; exposure roughly triples with a high-fat meal, and the trials dosed with food.
- Start at 450 mg twice daily in severe impairment (Child-Pugh C).
- Between Larotrectinib, Entrectinib, Alectinib and the other options, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCI PDQ: childhood astrocytomas, other gliomas and glioneuronal tumours), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (infant-type hemispheric glioma with a fusion), which of the standard options do you recommend and why?Why: Guideline options include: Surgery and fusion-directed therapy: larotrectinib or entrectinib for NTRK fusions, alectinib or lorlatinib for ALK or ROS1 fusions; chemotherapy to defer radiotherapy.
- Am I a candidate for Larotrectinib, Entrectinib, Alectinib or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Add these to your appointment list, or take the full question set for this cancer.
BRAF V600E-mutant
Dabrafenib plus trametinib (paediatric high-grade glioma cohort 2023; tumour-agnostic approval for BRAF V600E solid tumours from age six).
Dabrafenib plus trametinib is the BRAF-plus-MEK pill combination, approved for BRAF V600E lung cancer and, since 2022, for any solid tumour with that mutation.
Dabrafenib (Tafinlar) is a capsule that switches off the faulty BRAF protein driving some melanomas, lung, thyroid and other cancers. It is almost always paired with trametinib.
Trametinib (Mekinist) blocks MEK, the protein one step below BRAF in the growth-signal chain. Paired with dabrafenib it treats BRAF-mutant melanoma, lung, thyroid and other cancers, including brain tumours in children.
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
- Dabrafenib: take on an empty stomach. Trametinib: take on an empty stomach; both cause pyrexia.
- Between Dabrafenib + trametinib, Dabrafenib and Trametinib, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (FDA label 2022 to 2023; NCI PDQ), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (braf v600e-mutant), which of the standard options do you recommend and why?Why: Guideline options include: Dabrafenib plus trametinib (paediatric high-grade glioma cohort 2023; tumour-agnostic approval for BRAF V600E solid tumours from age six).
- Am I a candidate for Dabrafenib + trametinib, Dabrafenib, Trametinib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Add these to your appointment list, or take the full question set for this cancer.
Constitutional mismatch repair deficiency
PD-1 blockade (nivolumab or pembrolizumab) for hypermutant tumours; germline counselling for the family.
Nivolumab was the second PD-1 blocker and is often combined with ipilimumab. Long-term data show about half of advanced melanoma patients alive at 10 years on the combination.
Pembrolizumab is a PD-1 blocking antibody approved in more than 40 settings, from melanoma and lung cancer to the first tumour-agnostic approval for mismatch-repair-deficient tumours in 2017, and before and after surgery in triple-negative breast cancer. A subcutaneous form arrived in 2025, and it is the backbone partner for ADCs and personalised neoantigen vaccines.
A test of the DNA you were born with, to find inherited risk genes such as BRCA or Lynch syndrome.
- Actionable for patient and relatives
- Cheap
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Colitis with ipilimumab (1+3 mg/kg) · Monotherapy pooled unless stated | 25% | 14.4% |
| Hepatitis with ipilimumab · Monotherapy pooled unless stated | 15% | 13.4% |
| Colitis · Monotherapy pooled unless stated | 2.9% | 1.7% |
| Hepatitis · Monotherapy pooled unless stated | 1.8% | 1.5% |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Hypothyroidism (immune-mediated) · Pooled monotherapy data, >2,800 patients | 8% | - |
| Pneumonitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 3.4% | - |
| Colitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 1.7% | - |
| Hepatitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 0.7% | - |
- No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
- VUS burden
- Uptake and counselling capacity
- Between Nivolumab, Pembrolizumab and Germline (hereditary) testing, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- Which side effects of Nivolumab or Pembrolizumab are most likely for me, which are reversible, and which would make us stop?Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- For my situation (constitutional mismatch repair deficiency), which of the standard options do you recommend and why?Why: Guideline options include: PD-1 blockade (nivolumab or pembrolizumab) for hypermutant tumours; germline counselling for the family.
- Am I a candidate for Nivolumab, Pembrolizumab, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Add these to your appointment list, or take the full question set for this cancer.
Recurrence
No standard; re-resection, re-irradiation, clinical trials including CAR-T and oncolytic virus studies.
Engineered immune cells delivered directly into the brain or spinal fluid. Some children with diffuse midline glioma, a brainstem tumour with no curative treatment, have had striking, if temporary, responses.
- Bypasses BBB via direct CNS delivery
- Proof of activity in DIPG and recurrent GBM
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
- Transient responses, antigen escape
- Tumour inflammation-associated neurotoxicity (TIAN)
- Manufacturing and repeat dosing logistics
- Is CAR-T for glioma (IL13Rα2, GD2, EGFRvIII, multi-target) the only reasonable path for me, or is there a trial, a different sequence or a wait-and-see option?Why: A single standard does not mean a single choice; timing and trials are decisions too.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- For my situation (recurrence), which of the standard options do you recommend and why?Why: Guideline options include: No standard; re-resection, re-irradiation, clinical trials including CAR-T and oncolytic virus studies.
Add these to your appointment list, or take the full question set for this cancer.