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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.
Relapse in groups 3 and 4 is almost always fatal, recurs in the same molecular group, and typically occurs in the leptomeninges rather than the tumour bed; temozolomide, irinotecan and bevacizumab, re-irradiation and high-dose chemotherapy buy time. The current trials assign therapy by methylation subgroup: SJMB12 and the SIOP PNET5 and HIT-MED studies reduce therapy for low-risk group 4 (chromosome 11 loss or whole chromosome 17 gain without metastases) and intensify it for MYC-amplified group 3. No targeted drug has worked: MYC and MYCN have no inhibitor, and immunotherapy trials to date have shown little in an immunologically cold tumour. The long-term price of craniospinal radiotherapy, in intellect, hearing, endocrine function, stroke and second tumours, is why proton therapy is the preferred modality where available and why the dose question keeps being asked.
Groups 3 and 4 together make up about 60 to 65 percent of medulloblastoma: group 4 is the commonest single group and group 3, often MYC-amplified and metastatic in young children, the most lethal.
Gliomas infiltrate along white matter and can cross the corpus callosum, medulloblastoma sits in the cerebellum, and CNS lymphoma favours deep periventricular tissue; none spread through lymph nodes.
No conventional lymphatics: gliomas spread along white matter tracts and, rarely, through cerebrospinal fluid; medulloblastoma can seed the spine.
Same organ: Lactotroph pituitary neuroendocrine tumour (prolactinoma), Somatotroph pituitary neuroendocrine tumour (acromegaly), Corticotroph pituitary neuroendocrine tumour (Cushing disease and silent corticotroph tumour), Gonadotroph pituitary neuroendocrine tumour (non-functioning adenoma), Thyrotroph pituitary neuroendocrine tumour (TSH-secreting), Pineocytoma and pineal parenchymal tumour of intermediate differentiation, Pineoblastoma, Papillary tumour of the pineal region, Choroid plexus carcinoma, Glioma & glioblastoma, Primary CNS lymphoma, Medulloblastoma, Paediatric low-grade glioma, Diffuse midline glioma, H3 K27-altered (including DIPG), Atypical teratoid/rhabdoid tumour (ATRT), Ependymoma, Craniopharyngioma, Pituitary tumours (pituitary neuroendocrine tumours) and pituitary carcinoma, Brain and spinal cord tumours (all types), Astrocytoma, IDH-mutant (grades 2 to 4), Oligodendroglioma, IDH-mutant and 1p/19q-codeleted, Paediatric high-grade glioma (excluding diffuse midline glioma), Meningioma, Brain metastases (secondary brain tumours), Vestibular schwannoma (acoustic neuroma), Central nervous system germ cell tumours (germinoma and non-germinomatous), Spinal cord tumours (intramedullary and intradural), WNT-activated medulloblastoma, SHH-activated medulloblastoma
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Also on OnCo: Symptoms and red flags · Early detection roadmap.
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.
36 Gy craniospinal radiotherapy with boost, daily carboplatin during radiotherapy for group 3 (ACNS0332), then cisplatin, vincristine and cyclophosphamide.
Intensive chemotherapy with methotrexate, then high-dose consolidation with stem cell rescue, to avoid or delay craniospinal radiotherapy.
Temozolomide with irinotecan, bevacizumab, re-irradiation or high-dose chemotherapy; almost never curative; early-phase trials.
Neurocognitive, endocrine, hearing, vascular and second-tumour follow-up for life.
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Tumour-bed boost is standard in average-risk medulloblastoma, while craniospinal dose reduction is reserved for the WNT-activated subgroup in trials.
Carboplatin radiosensitisation is used for high-risk group 3 medulloblastoma, an example of subgroup-directed therapy.
Every brain tumour page on this site uses these names and grades; a tumour called glioblastoma before 2021 may now be an IDH-mutant astrocytoma with a different outlook and treatment.
Subtype-level classification, particularly separating infant and TP53-mutant SHH tumours and MYC-amplified group 3 tumours, guides current risk stratification and trial design.
The medulloblastoma subtype pages on this site follow this scheme, which entered the WHO classification in 2016 and drives current de-escalation and intensification trials.
Query for this cancer: (TITLE:"Group 3 and group 4 medulloblastoma" OR ABSTRACT:"Group 3 and group 4 medulloblastoma" OR TITLE:"non-WNT/non-SHH" OR ABSTRACT:"non-WNT/non-SHH" OR TITLE:"Non-WNT/non-SHH medulloblastoma" OR ABSTRACT:"Non-WNT/non-SHH medulloblastoma" OR TITLE:"Group 3 medulloblastoma" OR ABSTRACT:"Group 3 medulloblastoma" OR TITLE:"Group 4 medulloblastoma" OR ABSTRACT:"Group 4 medulloblastoma" OR TITLE:"MYC-amplified medulloblastoma" OR ABSTRACT:"MYC-amplified medulloblastoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Group 3 and group 4 medulloblastoma (non-WNT/non-SHH), not a curated reading list.
The targets of this cancer's medicines and the ones linked to it directly.
Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Bleeding that does not stop by itself, bleeding from more than one site, or new bruising in several places or one large area.
Sudden severe abdominal pain, a hard or very tender abdomen, or abdominal pain with vomiting and fever. Boxed warning for gastrointestinal perforation on bevacizumab.
UGT1A1*28 homozygotes: consider a lower starting dose (neutropenia). Cholinergic syndrome: atropine.
Take on an empty stomach or at bedtime to reduce nausea; PJP prophylaxis during concurrent chemoradiation.
Fatal if given intrathecally: label all syringes.
Dose by Calvert formula using GFR (see the calculators).
See all on the product pages:BevacizumabCarboplatinCisplatinCyclophosphamideIrinotecan (and liposomal irinotecan)Lomustine (CCNU)MethotrexateTemozolomideThiotepaVincristine·Printable cards in the navigator
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