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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.
The SHH group arises from cerebellar granule neuron precursors and is defined by activation of the sonic hedgehog pathway: loss of PTCH1 or SUFU, activating SMO mutations, or amplification of GLI2 or MYCN downstream. Age fixes the biology. Infants have PTCH1 or SUFU alterations (germline in a fifth, including Gorlin syndrome), desmoplastic/nodular or extensive-nodularity histology and a good prognosis; adults have PTCH1 and SMO mutations and an intermediate outcome; children aged around eight to seventeen carry TP53 mutations, half of them germline (Li-Fraumeni syndrome), with GLI2 and MYCN amplification and chromothripsis, and do very badly. WHO 2021 therefore splits SHH-activated tumours into TP53-wildtype and TP53-mutant.
The German HIT-SKK'92 trial, reported in the New England Journal of Medicine in 2005, treated infants with cyclophosphamide, vincristine, methotrexate, carboplatin, etoposide and intraventricular methotrexate without radiotherapy and found that desmoplastic histology, which is nearly all SHH, predicted a high cure rate, so radiotherapy-sparing chemotherapy became the infant standard; ACNS1221, which tried to reproduce this without the intraventricular methotrexate, closed early for excess relapses, showing the intraventricular drug matters. For children over three, SHH tumours receive the same craniospinal radiotherapy and chemotherapy as other groups, and TP53-mutant SHH disease relapses despite it: a 2013 pooled analysis found five-year overall survival of 41 percent with a TP53 mutation against 81 percent without in the SHH group. Smoothened inhibitors developed for basal cell carcinoma were tested by the Pediatric Brain Tumor Consortium: vismodegib produced responses only in SHH tumours with upstream PTCH1 or SMO lesions, mostly in adults, that lasted months, and it fuses growth plates in growing children, so it is limited to skeletally mature patients.
Nothing yet helps TP53-mutant SHH disease, which resists radiotherapy and chemotherapy and cannot use SMO inhibitors because its pathway activation is downstream; CDK4/6 inhibitors, bromodomain inhibitors aimed at GLI and MYCN, and immunotherapy are in early trials, and germline TP53 testing at diagnosis matters for the family and for avoiding radiotherapy-induced second tumours. For infants the question is which SHH tumours can be cured with less: SJYC07 and the current SIOP and COG trials stratify by methylation subtype, with high-dose chemotherapy and stem cell rescue kept for the poorer subgroups. Adult SHH medulloblastoma is treated with craniospinal radiotherapy and, increasingly, chemotherapy, with SMO inhibitors reserved for relapse in patients whose tumours carry an upstream mutation.
Averages across everyone diagnosed, often years ago. A median is the middle of a group: half the people counted lived longer than the figure shown, and some lived far longer. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
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, Group 3 and group 4 medulloblastoma (non-WNT/non-SHH)
Nothing recorded yet.
Nothing recorded yet.
Also on OnCo: Symptoms and red flags · Early detection roadmap.
HIT-SKK-type chemotherapy with intraventricular methotrexate and no radiotherapy; high-dose chemotherapy with stem cell rescue for poorer methylation subtypes.
Maximal safe resection, craniospinal radiotherapy (23.4 Gy average risk, 36 Gy high risk) with boost, then cisplatin, vincristine and cyclophosphamide or lomustine.
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.
Vismodegib or sonidegib for temporary control; other relapses receive temozolomide-based chemotherapy or re-irradiation.
Neurocognitive, endocrine and hearing follow-up; skin surveillance for basal cell carcinoma in Gorlin syndrome after radiotherapy.
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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.
Vismodegib or sonidegib is reserved for skeletally mature patients with relapsed SHH medulloblastoma and upstream pathway mutations, a niche defined by this trial.
SHH-activated, TP53-mutant medulloblastoma is a separate WHO entity treated as very high risk, and its diagnosis prompts germline testing of the child and family.
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:"SHH-activated medulloblastoma" OR ABSTRACT:"SHH-activated medulloblastoma" OR TITLE:"SHH medulloblastoma" OR ABSTRACT:"SHH medulloblastoma" OR TITLE:"Sonic hedgehog medulloblastoma" OR ABSTRACT:"Sonic hedgehog medulloblastoma" OR TITLE:"Desmoplastic/nodular medulloblastoma" OR ABSTRACT:"Desmoplastic/nodular medulloblastoma" OR TITLE:"SHH-activated TP53-mutant medulloblastoma" OR ABSTRACT:"SHH-activated TP53-mutant medulloblastoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about SHH-activated medulloblastoma, not a curated reading list.
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Bleeding that does not stop by itself, bleeding from more than one site, or new bruising in several places or one large area.
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).
Dose reduce or avoid for CrCl below 60 (carboplatin is the alternative).
Reduce to 75% for CrCl 15-50.
See all on the product pages:CarboplatinCisplatinCyclophosphamideEtoposideLomustine (CCNU)MethotrexateTemozolomideThiotepaVincristine·Printable cards in the navigator
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