The first 60 days: Diffuse midline glioma, H3 K27-altered (including DIPG)
Diffuse midline glioma grows through the brainstem and cannot be removed surgically. A single change in a histone protein (H3 K27M) rewires how the tumour reads its DNA. Radiotherapy was long the only help; in 2025 the first drug aimed at this tumour, dordaviprone (ONC201), was approved after durable shrinkage in some patients, and GD2 CAR-T cells have produced striking early responses. Below, week by week, is what OnCo's record of Diffuse midline glioma, H3 K27-altered (including DIPG) says about the first two months: the order is typical, the timing is yours to ask about. Sections appear only where the record has something to say. Orientation, not medical advice.
What happens now
Staging tests establish exactly what and where the cancer is. Everything else follows from the answers.
Stereotactic biopsy for molecular diagnosis and trial eligibility, then focal radiotherapy (about six weeks; hypofractionated schedules are non-inferior); steroids for symptoms. Enrolment in a trial such as ACTION (dordaviprone after radiotherapy) is recommended.
Ask which of these were tested and what the results were; see the report reader for what each value means.
These specialties appear in the standard of care for this cancer. In most centres they meet weekly as a tumour board to agree each plan; you can ask when yours was discussed and what was decided.
- PathologistNamed in the standard of care for: Newly diagnosed.
- SurgeonNamed in the standard of care for: Recurrent, trial-eligible.
- Medical oncologistNamed in the standard of care for: Newly diagnosed, Progressive after radiotherapy, H3 K27M-mutant.
- Clinical oncologist (radiotherapy)Named in the standard of care for: Newly diagnosed, Progressive after radiotherapy, H3 K27M-mutant.
- Transplant and cell therapy teamNamed in the standard of care for: Recurrent, trial-eligible.
- Palliative and supportive care teamNamed in the standard of care for: All stages.
A second opinion from a centre that treats many similar cases is normal, not rude; the standard of care tells you what to compare it against.
Each row is a setting from the standard of care, in the order it usually arises. Not all will apply to you; your stage and biomarkers decide which do. The guideline grade, where recorded, says how strong the evidence is.
Dordaviprone (ONC201), FDA accelerated approval August 2025 for patients aged one year and older with progressive disease; re-irradiation is an alternative or addition.
GD2 CAR-T (phase 1, Stanford and others), convection-enhanced delivery, epigenetic and combination trials through consortium networks.
Early palliative care, steroid-sparing strategies, and support for the family; tissue donation at autopsy has been central to research progress.
Generated from this cancer's standard of care, biomarkers and open problems. Take the group that matches where you are. To tick, add your own and print, open the one-page appointment sheet.
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example H3 K27M by immunohistochemistry or sequencing, Loss of H3K27me3, TP53, ACVR1, PDGFRA, PIK3CA co-alterations, EGFR alteration, Cerebrospinal-fluid cell-free tumour DNA for H3 K27M), and what were the results?These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Recognised subtypes for this cancer include H3.3 K27M, H3.1 K27M, H3-wild-type with EZHIP overexpression.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
- For my situation (newly diagnosed), which of the standard options do you recommend and why?Guideline options include: Stereotactic biopsy for molecular diagnosis and trial eligibility, then focal radiotherapy (about six weeks; hypofractionated schedules are non-inferior); steroids for symptoms. Enrolment in a trial such as ACTION (dordaviprone after radiotherapy) is recommended.
- Am I a candidate for Dordaviprone, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of ACTION apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Progressive after radiotherapy, H3 K27M-mutant
- For my situation (progressive after radiotherapy, h3 k27m-mutant), which of the standard options do you recommend and why?Guideline options include: Dordaviprone (ONC201), FDA accelerated approval August 2025 for patients aged one year and older with progressive disease; re-irradiation is an alternative or addition.
- Am I a candidate for Dordaviprone, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Recurrent, trial-eligible
- For my situation (recurrent, trial-eligible), which of the standard options do you recommend and why?Guideline options include: GD2 CAR-T (phase 1, Stanford and others), convection-enhanced delivery, epigenetic and combination trials through consortium networks.
All stages
- For my situation (all stages), which of the standard options do you recommend and why?Guideline options include: Early palliative care, steroid-sparing strategies, and support for the family; tissue donation at autopsy has been central to research progress.
Any stage
- Are there clinical trials I could join, for example of Dordaviprone, ACTION, CAR-T for glioma (IL13Rα2, GD2, EGFRvIII, multi-target), Focused-ultrasound blood-brain barrier opening?Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Supportive care improves quality of life and helps patients complete treatment.
- I read that “Most tumours still progress; dordaviprone helps a minority and the phase 3 ACTION trial will show whether earlier use extends survival”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “Drug delivery across the blood-brain barrier into infiltrating tumour: convection-enhanced delivery, focused ultrasound and intraventricular cell therapy are being tested”. How does that affect my plan?Open problems are where trials and second opinions matter most.
Trials open now for this cancer in OnCo, largest phase first. Joining a trial is a decision like any other: ask what the comparison arm is, whether a placebo is used, and what happens if you leave. The cancer page searches ClinicalTrials.gov live for more.
- ACTIONPhase 3 · recruiting · NCT05580562Newly diagnosed H3 K27M-mutant diffuse glioma after completion of radiotherapy: dordaviprone (ONC201) vs placebo, two dosing schedules
- NCI-COG Pediatric MATCH (APEC1621)Phase platform · active · NCT03155620Relapsed or refractory solid tumours, non-Hodgkin lymphomas and histiocytic disorders, age 1-21: tumour sequencing then assignment to one of a dozen single-agent targeted-therapy phase 2 arms
- A Study of VRT106 in Combination With Radiotherapy in Adult Patients With Diffuse Midline Glioma / Diffuse Intrinsic Pontine GliomaPhase 2 · recruiting · NCT07589257A Single-Arm, Open-Label, Multicenter Phase II Clinical Study of VRT106 in Combination With Radiotherapy in Adult Patients With Diffuse Midline Glioma / Including Diffuse Intrinsic Pontine Glioma
- Illuminate: A Clinical Study Evaluating CAR T Immune Cell Therapy (BCB-276) for Patients With Diffuse Intrinsic Pontine Glioma (DIPG).Phase 2 · recruiting · NCT07680439A Phase 2 Pivotal Study of BCB-276, a B7-H3-Specific CAR T Cell Locoregional Immunotherapy for Diffuse Intrinsic Pontine Glioma
- Study of Olutasidenib and Temozolomide in HGGPhase 2 · recruiting · NCT06161974Phase 2 Study of Olutasidenib With Temozolomide as Maintenance Therapy in Pediatric and Young Adult Patients Newly Diagnosed With High-Grade Glioma (HGG), Including Diffuse Intrinsic Pontine Glioma (DIPG), Which Harbor IDH1 Mutations
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- Diffuse midline glioma, H3 K27-altered (including DIPG): the full pageDiffuse midline glioma grows through the brainstem and cannot be removed surgically. A single change in a histone protein (H3 K27M) rewires how the tumour reads its DNA. Radiotherapy was long the only help; in 2025 the first drug aimed at this tumour, dordaviprone (ONC201), was approved after durable shrinkage in some patients, and GD2 CAR-T cells have produced striking early responses.
- One-page appointment sheetYour questions, the words you may hear, what to bring, and space for the answers. Print it.
- Treatment sequencingWhich treatment tends to follow which, line by line.
- NavigatorStandard of care for your stage, what you have tried, and trials near you.
- H3 K27M (diffuse midline glioma): A single change in a histone protein that defines diffuse midline glioma, the childhood brain tumour with the fewest treatment options, and now the target of the first approved drug for it.
- Blood-brain barrier (BBB): The tight seal around brain blood vessels that keeps most drugs out, one of the two main reasons brain cancer is so hard to treat.
- RACE for Children Act: A US law that makes drug companies test new targeted cancer drugs in children whenever the drug's target matters in a childhood cancer, instead of letting them skip children because their cancers are rare.
- Late effects and survivorship toxicity: Health problems appearing months or decades after treatment ends: heart damage, infertility, second cancers, lymphoedema, dry mouth, memory problems, weak bones.
Every term links to the glossary.