The first 60 days: SHH-activated medulloblastoma
SHH-activated medulloblastoma is driven by the sonic hedgehog growth pathway, the signal that normally tells the developing cerebellum to grow. In infants it is often cured with chemotherapy alone and no radiotherapy; in adults it responds for a time to hedgehog-blocking pills such as vismodegib; and when it carries a TP53 mutation in an older child, often inherited, it resists everything. Below, week by week, is what OnCo's record of SHH-activated medulloblastoma 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.
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: TP53-mutant.
- SurgeonNamed in the standard of care for: Children over three and adults, TP53-wildtype.
- Medical oncologistNamed in the standard of care for: Infants under three, TP53-wildtype, Children over three and adults, TP53-wildtype, TP53-mutant, Relapsed, skeletally mature, upstream PTCH1 or SMO lesion and 1 more.
- Clinical oncologist (radiotherapy)Named in the standard of care for: Infants under three, TP53-wildtype, Children over three and adults, TP53-wildtype, TP53-mutant, Relapsed, skeletally mature, upstream PTCH1 or SMO lesion and 1 more.
- Transplant and cell therapy teamNamed in the standard of care for: Infants under three, TP53-wildtype, Children over three and adults, TP53-wildtype, TP53-mutant.
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.
- 1.Infants under three, TP53-wildtypeNCI PDQ: Childhood Medulloblastoma and Other CNS Embryonal Tumors Treatment (health professional version)
HIT-SKK-type chemotherapy with intraventricular methotrexate and no radiotherapy; high-dose chemotherapy with stem cell rescue for poorer methylation subtypes.
- 2.Children over three and adults, TP53-wildtypeNCI PDQ: Childhood Medulloblastoma and Other CNS Embryonal Tumors Treatment (health professional version)
Maximal safe resection, craniospinal radiotherapy (23.4 Gy average risk, 36 Gy high risk) with boost, then cisplatin, vincristine and cyclophosphamide or lomustine.
- 3.TP53-mutantNCI PDQ: Childhood Medulloblastoma and Other CNS Embryonal Tumors Treatment (health professional version)
High-risk therapy with germline testing of the child and family; trials of novel agents; radiotherapy weighed against second-tumour risk in Li-Fraumeni syndrome.
- 4.Relapsed, skeletally mature, upstream PTCH1 or SMO lesionNCI PDQ: Childhood Medulloblastoma and Other CNS Embryonal Tumors Treatment (health professional version)
Vismodegib or sonidegib for temporary control; other relapses receive temozolomide-based chemotherapy or re-irradiation.
- 5.SurvivorshipNCI PDQ: Childhood Medulloblastoma and Other CNS Embryonal Tumors Treatment (health professional version)
Neurocognitive, endocrine and hearing follow-up; skin surveillance for basal cell carcinoma in Gorlin syndrome after radiotherapy.
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 GAB1, YAP1 and filamin A immunohistochemistry for SHH, PTCH1, SUFU and SMO mutations, TP53 mutation, somatic and germline, GLI2 and MYCN amplification, DNA methylation subtype), 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 SHH-activated medulloblastoma, TP53-wildtype, in infants, SHH-activated medulloblastoma, TP53-wildtype, in children and adults, SHH-activated medulloblastoma, TP53-mutant.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
Infants under three, TP53-wildtype
- For my situation (infants under three, tp53-wildtype), which of the standard options do you recommend and why?Guideline options include: HIT-SKK-type chemotherapy with intraventricular methotrexate and no radiotherapy; high-dose chemotherapy with stem cell rescue for poorer methylation subtypes.
- Am I a candidate for Cyclophosphamide, Vincristine, Methotrexate or related drugs, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Children over three and adults, TP53-wildtype
- For my situation (children over three and adults, tp53-wildtype), which of the standard options do you recommend and why?Guideline options include: Maximal safe resection, craniospinal radiotherapy (23.4 Gy average risk, 36 Gy high risk) with boost, 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.
TP53-mutant
- For my situation (tp53-mutant), which of the standard options do you recommend and why?Guideline options include: High-risk therapy with germline testing of the child and family; trials of novel agents; radiotherapy weighed against second-tumour risk in Li-Fraumeni syndrome.
- 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.
Relapsed, skeletally mature, upstream PTCH1 or SMO lesion
- For my situation (relapsed, skeletally mature, upstream ptch1 or smo lesion), which of the standard options do you recommend and why?Guideline options include: Vismodegib or sonidegib for temporary control; other relapses receive temozolomide-based chemotherapy or re-irradiation.
- Am I a candidate for Vismodegib, Sonidegib, Temozolomide, 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 and hearing follow-up; skin surveillance for basal cell carcinoma in Gorlin syndrome after radiotherapy.
Any stage
- Are there clinical trials I could join, for example of Vismodegib, Sonidegib, DNA methylation profiling, Proton therapy?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 “No therapy improves TP53-mutant SHH medulloblastoma”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “Smoothened inhibitors fuse growth plates and fail against downstream activation”. How does that affect my plan?Open problems are where trials and second opinions matter most.
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- SHH-activated medulloblastoma: the full pageSHH-activated medulloblastoma is driven by the sonic hedgehog growth pathway, the signal that normally tells the developing cerebellum to grow. In infants it is often cured with chemotherapy alone and no radiotherapy; in adults it responds for a time to hedgehog-blocking pills such as vismodegib; and when it carries a TP53 mutation in an older child, often inherited, it resists everything.
- 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.
- Secondary malignancy (therapy-related cancer): A new, different cancer caused by the treatment of the first one: leukaemia after alkylating chemotherapy or PARP inhibitors, solid tumours in irradiated tissue decades later, and rarely T-cell lymphoma after CAR-T.
- 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.
- Li-Fraumeni syndrome (germline TP53): Li-Fraumeni syndrome is an inherited fault in the TP53 gene giving a lifetime cancer risk near 100% in women and ~75% in men, with sarcomas, breast cancer, brain tumours, adrenal cancer and leukaemias often in childhood.
- 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.