The study PNET 5 MB has been designed for children with medulloblastoma of standard risk (according to the risk-group definitions which have been used so far; e.g. in PNET 4). With the advent of biological parameters for stratification into clinical medulloblastoma trials, the ß-catenin status will be the only criterion according to which study patients will be assigned to either treatment arm PNET 5 MB - LR or to PNET 5 MB - SR, respectively. The initial diagnostic assessments (imaging, staging, histology, and tumor biology) required for study entry are the same for both treatment arms. With the amendment for version 12 of the protocol, patients who have a WNT-activated medulloblastoma with clinically high-risk features can be included in the PNET 5 MB WNT-HR study, and patients with a high-risk SHH medulloblastoma with TP53 mutation (both somatic or germline including mosaicism) can be included in the PNET5 MB SHH-TP53 study.
Data on patients with pathogenic germline alteration or cancer predisposition syndrome, who cannot be included in any prospective trial due to unavailability or due to physician or family decision, can be documented within the observational PNET 5 MB registry.
Who can participate
Age range3 Years – 21 Years
SexALL
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Inclusion criteria
✓. Age at diagnosis, at least 3 - 5 years (depending on the country) and less than 22 years (LR-arm: less than 16 years). The date of diagnosis is the date on which surgery is undertaken.
✓. Histologically proven medulloblastoma, including the following subtypes, as defined in the WHO classification (2007): classic medulloblastoma, desmoplastic/nodular medulloblastoma. Pre-treatment central pathology review is considered mandatory.
✓. Standard-risk medulloblastoma, defined as;
✓. Submission of high quality biological material including fresh frozen tumor samples for the molecular assessment of biological markers (such as the assessment of myelocytomatosis oncogene (MYC) copy number status) in national biological reference centers. Submission of blood is mandatory for all patients, who agree on germline DNA studies. Submission of CSF is recommended.
✓. No amplification of MYC or MYCN (determined by FISH).
✓. For LR-arm: Low-risk biological profile, defined as WNT subgroup positivity. The WNT subgroup is defined by the presence of (i) ß-catenin mutation (mandatory testing), or (ii) ß-catenin nuclear immuno-positivity by IHC (mandatory testing) and ß-catenin mutation, or (iii) ß-catenin nuclear immuno-positivity by IHC and monosomy 6 (optional testing).
✓. No prior therapy for medulloblastoma other than surgery.
What they're measuring
1
3-year Event-Free Survival (EFS)
Timeframe: LR-arm after 9 years, SR-arm after 105 events (approx. 10 years)
✓. Radiotherapy aiming to start no more than 28 days after surgery. Foreseeable inability to start radiotherapy within 40 days after surgery renders patients ineligible for the study.
Exclusion criteria
✕. One of the inclusion criteria is lacking.
✕. Brainstem or supratentorial primitive neuro-ectodermal tumour.
✕. Atypical teratoid rhabdoid tumour.
✕. Medulloepithelioma; Ependymoblastoma
✕. Large-cell medulloblastoma, anaplastic medulloblastoma, or medulloblastoma with extensive nodularity (MBEN), centrally confirmed.
✕. Unfavourable or undeterminable biological profile, defined as amplification of MYC or MYCN, or MYC or MYCN or WNT subgroup status not determinable.
✕. Metastatic medulloblastoma (on CNS MRI and/or positive cytospin of postoperative lumbar CSF).
✕. Patient previously treated for a brain tumour or any type of malignant disease.