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9 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
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.
Groups 3 and 4 arise from the upper rhombic lip and unipolar brush cell lineages and share enough that WHO 2021 groups them as non-WNT/non-SHH medulloblastoma with eight methylation subgroups. Group 3 (about a quarter of medulloblastoma) occurs in infants and young children, often with large-cell/anaplastic histology, MYC amplification in about 17 percent, GFI1 enhancer hijacking, and metastases in 40 to 45 percent at diagnosis. Group 4 (about 35 to 40 percent) affects older children and adolescents, three boys to one girl, with isochromosome 17q in most, KDM6A and PRDM6 alterations and MYCN amplification in some, and metastases in about a third. Metastatic stage, MYC amplification and residual tumour define high risk in both.
The trials that set standard therapy predate the groups. SIOP PNET3 showed pre-radiotherapy chemotherapy improved event-free survival; COG A9961 in 2006 established the average-risk regimen of 23.4 Gy craniospinal radiotherapy with a boost followed by cisplatin, vincristine and cyclophosphamide or lomustine, with five-year event-free survival of 81 percent; HIT-SIOP PNET4 found hyperfractionated radiotherapy no better than standard. ACNS0331, reported in 2021, tried to lower the craniospinal dose to 18 Gy in children aged three to seven with average-risk disease and found it inferior, five-year event-free survival 71.4 percent against 82.9 percent, while confirming that boosting the tumour bed rather than the whole posterior fossa is safe. ACNS0332, for high-risk disease, showed that carboplatin given daily during craniospinal radiotherapy improved five-year event-free survival in group 3 from 53.7 to 73.2 percent with no benefit in group 4, and that isotretinoin maintenance added nothing. Infants with group 3 disease receive intensive chemotherapy with high-dose consolidation and stem cell rescue to avoid or delay radiotherapy.
| Setting | Approach | Guideline |
|---|---|---|
| Average risk (aged 3 or over, no metastases, residual under 1.5 square centimetres) | 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. | not mapped |
| High risk (metastatic, residual disease or MYC amplification) | 36 Gy craniospinal radiotherapy with boost, daily carboplatin during radiotherapy for group 3 (ACNS0332), then cisplatin, vincristine and cyclophosphamide. | not mapped |
| Infants under three | Intensive chemotherapy with methotrexate, then high-dose consolidation with stem cell rescue, to avoid or delay craniospinal radiotherapy. | not mapped |
| Relapsed | Temozolomide with irinotecan, bevacizumab, re-irradiation or high-dose chemotherapy; almost never curative; early-phase trials. | not mapped |
| Survivorship | Neurocognitive, endocrine, hearing, vascular and second-tumour follow-up for life. | not mapped |