The first 60 days: Group 3 and group 4 medulloblastoma (non-WNT/non-SHH)

Below, week by week, is what OnCo's record of Group 3 and group 4 medulloblastoma (non-WNT/non-SHH) says about the first two months: the order is typical, the timing is yours to ask about. Group 3 and group 4 medulloblastoma are the two commonest forms of this cerebellar brain tumour and the ones without a druggable driver. Group 3 strikes young children, often with extra copies of MYC and spread through the spinal fluid; group 4 affects older boys. Both get surgery, craniospinal radiotherapy and chemotherapy; trials showed the radiation dose cannot be cut for young children. Sections appear only where the record has something to say. Orientation, not medical advice.

Weeks 1 to 2

What happens now

Staging tests establish exactly what and where the cancer is. Everything else follows from the answers.

Biomarkers your report may list

DNA methylation profiling (non-WNT/non-SHH subgroups I to VIII)MYC and MYCN amplification Isochromosome 17q Chromosome 11 loss and whole chromosome 17 gain (low-risk group 4)Metastatic staging by spinal MRI and CSF cytology (Chang M stage)Residual tumour on postoperative MRI Large-cell/anaplastic histology

Ask which of these were tested and what the results were; see the report reader for what each value means.

Tests and imaging linked to this cancer

DNA methylation profiling

Weeks 1 to 3

Who is on your team

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.

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.

Weeks 2 to 6

Decisions coming up

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.

1.Infants under three NCI PDQ: Childhood Medulloblastoma and Other CNS Embryonal Tumors Treatment (health professional version)
Intensive chemotherapy with methotrexate, then high-dose consolidation with stem cell rescue, to avoid or delay craniospinal radiotherapy.
Methotrexate Cyclophosphamide Vincristine Carboplatin Thiotepa Autologous stem cell transplant (high-dose therapy)
2.High risk (metastatic, residual disease or MYC amplification)NCI PDQ: Childhood Medulloblastoma and Other CNS Embryonal Tumors Treatment (health professional version)
36 Gy craniospinal radiotherapy with boost, daily carboplatin during radiotherapy for group 3 (ACNS0332), then cisplatin, vincristine and cyclophosphamide.
Carboplatin IMRT / IGRT (modern external beam)Proton therapy Cisplatin Vincristine Cyclophosphamide
3.Average risk (aged 3 or over, no metastases, residual under 1.5 square centimetres)NCI PDQ: Childhood Medulloblastoma and Other CNS Embryonal Tumors Treatment (health professional version)
Maximal safe resection, 23.4 Gy craniospinal radiotherapy with tumour-bed boost (ACNS0331 showed 18 Gy is inferior), then cisplatin, vincristine and cyclophosphamide or lomustine.
Proton therapy IMRT / IGRT (modern external beam)Cisplatin Vincristine Cyclophosphamide Lomustine (CCNU)COG ACNS0331
4.Relapsed NCI PDQ: Childhood Medulloblastoma and Other CNS Embryonal Tumors Treatment (health professional version)
Temozolomide with irinotecan, bevacizumab, re-irradiation or high-dose chemotherapy; almost never curative; early-phase trials.
Temozolomide Irinotecan (and liposomal irinotecan)Bevacizumab Autologous stem cell transplant (high-dose therapy)IMRT / IGRT (modern external beam)
5.Survivorship NCI PDQ: Childhood Medulloblastoma and Other CNS Embryonal Tumors Treatment (health professional version)
Neurocognitive, endocrine, hearing, vascular and second-tumour follow-up for life.
Late effects and survivorship toxicity Survivorship care and late-effects surveillance

Every visit

Questions to ask at each visit

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 DNA methylation profiling, MYC and MYCN amplification, Isochromosome 17q, Chromosome 11 loss and whole chromosome 17 gain, Metastatic staging by spinal MRI and CSF cytology), 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 Group 3 medulloblastoma, MYC-amplified, Group 3 medulloblastoma without MYC amplification, Group 4 medulloblastoma, low risk.
Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.

Average risk (aged 3 or over, no metastases, residual under 1.5 square centimetres)

For my situation (average risk (aged 3 or over, no metastases, residual under 1.5 square centimetres)), which of the standard options do you recommend and why?Guideline options include: Maximal safe resection, 23.4 Gy craniospinal radiotherapy with tumour-bed boost (ACNS0331 showed 18 Gy is inferior), then cisplatin, vincristine and cyclophosphamide or lomustine.
Am I a candidate for Cisplatin, Vincristine, Cyclophosphamide or related drugs, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of COG ACNS0331 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.

High risk (metastatic, residual disease or MYC amplification)

For my situation (high risk (metastatic, residual disease or myc amplification)), which of the standard options do you recommend and why?Guideline options include: 36 Gy craniospinal radiotherapy with boost, daily carboplatin during radiotherapy for group 3 (ACNS0332), then cisplatin, vincristine and cyclophosphamide.
Am I a candidate for Carboplatin, Cisplatin, Vincristine or related drugs, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.

Infants under three

For my situation (infants under three), which of the standard options do you recommend and why?Guideline options include: Intensive chemotherapy with methotrexate, then high-dose consolidation with stem cell rescue, to avoid or delay craniospinal radiotherapy.
Am I a candidate for Methotrexate, Cyclophosphamide, Vincristine or related drugs, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.

Relapsed

For my situation (relapsed), which of the standard options do you recommend and why?Guideline options include: Temozolomide with irinotecan, bevacizumab, re-irradiation or high-dose chemotherapy; almost never curative; early-phase trials.
Am I a candidate for Temozolomide, Irinotecan (and liposomal irinotecan), Bevacizumab, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.

Survivorship

For my situation (survivorship), which of the standard options do you recommend and why?Guideline options include: Neurocognitive, endocrine, hearing, vascular and second-tumour follow-up for life.

Any stage

Are there clinical trials I could join, for example of DNA methylation profiling, Proton therapy, Temozolomide, Bevacizumab?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 “MYC and MYCN have no inhibitor, and relapse is almost always fatal”. How does that affect my plan?Open problems are where trials and second opinions matter most.
I read that “Craniospinal radiotherapy dose cannot be reduced in young children without losing cures”. How does that affect my plan?Open problems are where trials and second opinions matter most.

Weeks 3 to 8

Trials to ask about

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.

SJMB12Phase 2 · active · NCT01878617Newly diagnosed medulloblastoma aged 3 to 39, stratified by molecular subgroup and clinical risk: reduced craniospinal irradiation (15 Gy) for low-risk WNT tumours, vismodegib added for skeletally mature SHH tumours, and pemetrexed and gemcitabine added for intermediate- and high-risk group 3 and 4 tumours, with exercise and cognitive remediation randomisations

From day one

Help that costs nothing

Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.

Any time

What to read next

Words this page and the cancer page use

Medulloblastoma molecular groups (WNT, SHH, group 3, group 4): Medulloblastoma is four diseases under one microscope: the WNT group is almost always cured, the SHH group depends on age and TP53, and groups 3 and 4 carry most of the deaths, so the group now steers how much radiation and chemotherapy a child receives.
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.