SHH-activated medulloblastoma: 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.
Infants under three, TP53-wildtype
HIT-SKK-type chemotherapy with intraventricular methotrexate and no radiotherapy; high-dose chemotherapy with stem cell rescue for poorer methylation subtypes.
Cyclophosphamide is an alkylating chemotherapy that damages DNA in dividing cells. It is part of CHOP for lymphoma, AC for breast cancer and VAC for childhood sarcomas, clears lymphocytes before CAR-T and prevents graft-versus-host disease after transplant; bladder bleeding, infertility and secondary leukaemia are its harms.
A plant-derived chemotherapy from the Madagascar periwinkle that has been in almost every childhood leukaemia and lymphoma regimen since the 1960s.
The 1948 antifolate that produced the first chemotherapy remissions in childhood leukaemia and the first cure of a solid tumour; still essential in ALL, lymphoma, osteosarcoma and CNS lymphoma.
Carboplatin is a platinum chemotherapy that crosslinks DNA; it is part of the standard pre-surgery regimen for triple-negative breast cancer.
Etoposide is a chemotherapy from the mayapple plant, essential to curing testicular cancer (BEP), treating small-cell lung cancer, lymphomas, childhood sarcomas and leukaemias, and used in transplant conditioning.
Thiotepa is an old chemotherapy with a modern job: at high doses it prepares patients for stem cell transplants, and it is still instilled into the bladder or body cavities for superficial bladder cancer and malignant effusions.
Autologous stem cell transplant collects the patient's own blood-forming stem cells, gives melphalan or another chemotherapy at a dose that would otherwise destroy the marrow, then returns the cells to rebuild it. It is standard consolidation in myeloma and for relapsed lymphoma, though CAR-T has displaced it in early-relapsing large B-cell lymphoma.
- Permits dose intensity impossible otherwise
- Decades of outcome data
- Widely available
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
- Fatal if given intrathecally: label all syringes.
- High-dose methotrexate requires normal renal function, hydration, urine alkalinisation and leucovorin rescue with level monitoring.
- Dose by Calvert formula using GFR (see the calculators).
- Reduce to 75% for CrCl 15-50.
- Treatment-related mortality ~1-2% (myeloma) to higher in children
- Infertility, second malignancies, prolonged cytopenias
- Being challenged by CAR-T and MRD-guided deferral
- Between Cyclophosphamide, Vincristine, Methotrexate 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 Medulloblastoma and Other CNS Embryonal Tumors Treatment (health professional version)), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (infants under three, tp53-wildtype), which of the standard options do you recommend and why?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?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.
Children over three and adults, TP53-wildtype
Maximal safe resection, craniospinal radiotherapy (23.4 Gy average risk, 36 Gy high risk) with boost, then cisplatin, vincristine and cyclophosphamide or lomustine.
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
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
Cisplatin is the original platinum chemotherapy, discovered by accident in 1965; it cures testicular cancer and makes radiation work better in cervical and head and neck cancer.
A plant-derived chemotherapy from the Madagascar periwinkle that has been in almost every childhood leukaemia and lymphoma regimen since the 1960s.
Cyclophosphamide is an alkylating chemotherapy that damages DNA in dividing cells. It is part of CHOP for lymphoma, AC for breast cancer and VAC for childhood sarcomas, clears lymphocytes before CAR-T and prevents graft-versus-host disease after transplant; bladder bleeding, infertility and secondary leukaemia are its harms.
An old chemotherapy pill used when glioblastoma comes back, and the control arm most new glioblastoma drugs must beat.
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
- Cost
- Range uncertainty
- Limited randomised evidence in adults
- Low-dose bath to normal tissue
- Motion management
- Dose reduce or avoid for CrCl below 60 (carboplatin is the alternative).
- Fatal if given intrathecally: label all syringes.
- Between Proton therapy, IMRT / IGRT (modern external beam), Cisplatin 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 Medulloblastoma and Other CNS Embryonal Tumors Treatment (health professional version)), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (children over three and adults, tp53-wildtype), which of the standard options do you recommend and why?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?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.
TP53-mutant
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.
Carboplatin is a platinum chemotherapy that crosslinks DNA; it is part of the standard pre-surgery regimen for triple-negative breast cancer.
Cisplatin is the original platinum chemotherapy, discovered by accident in 1965; it cures testicular cancer and makes radiation work better in cervical and head and neck cancer.
A plant-derived chemotherapy from the Madagascar periwinkle that has been in almost every childhood leukaemia and lymphoma regimen since the 1960s.
Cyclophosphamide is an alkylating chemotherapy that damages DNA in dividing cells. It is part of CHOP for lymphoma, AC for breast cancer and VAC for childhood sarcomas, clears lymphocytes before CAR-T and prevents graft-versus-host disease after transplant; bladder bleeding, infertility and secondary leukaemia are its harms.
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.
- Dose by Calvert formula using GFR (see the calculators).
- Dose reduce or avoid for CrCl below 60 (carboplatin is the alternative).
- Fatal if given intrathecally: label all syringes.
- VUS burden
- Uptake and counselling capacity
- Between Carboplatin, Cisplatin, Vincristine 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 Medulloblastoma and Other CNS Embryonal Tumors Treatment (health professional version)), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (tp53-mutant), which of the standard options do you recommend and why?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?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.
Relapsed, skeletally mature, upstream PTCH1 or SMO lesion
Vismodegib or sonidegib for temporary control; other relapses receive temozolomide-based chemotherapy or re-irradiation.
Vismodegib was the first hedgehog-pathway drug, for basal cell carcinomas too advanced for surgery; it shrinks most tumours but muscle cramps, taste loss and hair loss make long-term use hard.
Sonidegib (Odomzo) is the second hedgehog inhibitor for locally advanced basal cell carcinoma, similar in effect and side effects to vismodegib.
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.
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
- Take on an empty stomach or at bedtime to reduce nausea; PJP prophylaxis during concurrent chemoradiation.
- Between Vismodegib, Sonidegib and Temozolomide, 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 Medulloblastoma and Other CNS Embryonal Tumors Treatment (health professional version)), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (relapsed, skeletally mature, upstream ptch1 or smo lesion), which of the standard options do you recommend and why?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?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.
Survivorship
Neurocognitive, endocrine and hearing follow-up; skin surveillance for basal cell carcinoma in Gorlin syndrome after radiotherapy.
This setting names no product or technology record yet; the approach above is the standard as written. Ask your team which specific treatments they mean.
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
No side-effect rates or interaction flags are recorded for these options yet. The side-effect lookup and interaction checker cover the products that have them.
- Which specific treatments are you proposing for this setting, and what are the alternatives?Why: The standard of care here is described in words rather than named products; ask for the names.
- 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 Medulloblastoma and Other CNS Embryonal Tumors Treatment (health professional version)), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (survivorship), which of the standard options do you recommend and why?Why: Guideline options include: Neurocognitive, endocrine and hearing follow-up; skin surveillance for basal cell carcinoma in Gorlin syndrome after radiotherapy.
Add these to your appointment list, or take the full question set for this cancer.