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The potential impact of tumour biology on improved clinical practice for medulloblastoma: progress towards biologically driven clinical trials
British Journal of Neurosurgery, 08/05/09

Pizer BL et al. – In a study to explore a series of molecular and histopathological biomarkers that may allow a more accurate prediction of disease outcome, it appears that feasibility studies to establish these systems are underway. Their success will require a coordinated approach by the entire multidisciplinary team, including neurosurgeons, oncologists, and neuropathologists, with the common aim of facilitating targeted delivery of individualised risk-adapted therapies for children with medulloblastoma.

• A series of molecular and histopathological biomarkers have been identified that may allow a more accurate prediction of disease outcome (eg, β-catenin status as a favourable-risk marker, MYC gene amplification and large-cell histology as high-risk markers).
• Pan-European clinical trials being planned for medulloblastoma by the SIOP Brain tumour group will assess the stratification of pts using molecular and histological biomarkers, alongside clinical indices, to select favourable, standard and high-risk treatment groups.

• This selection will underpin 2 concurrent trials; PNET 5, which will test whether treatment can be reduced for a favourable-risk disease sub-group, with the aim of maintaining survival rates while reducing late-effects, and PNET 6, which will aim to improve survival rates in the standard-risk group.
• Implementation of these trials presents important new logistical challenges within routine practice, involving development of quality-controlled sample collection and handling systems across multiple treatment centres, including the mandatory ascertainment of fresh-frozen tumour material, and delivery of standardised central biomarker analysis and histopathological review, within the approximately 30-day post-surgical window, prior to the selection and commencement of adjuvant therapy.

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