Medulloblastoma is the most common malignant childhood brain tumour and affects around 90 children a year across the UK. While 70% of children survive the disease, current treatment options are aggressive, meaning that many are left with debilitating long-term side-effects and limited chances of recovery. Research at Northumbria University is paving the way for much-needed personalised therapies, enabling clinicians to use less harmful treatments for patients with specific types – or molecular subgroups – of medulloblastoma that have more favourable outcomes.
In 2012, scientists reached the consensus that there were four molecular subgroups of medulloblastoma, each of which had distinct characteristics with varying impacts on patient outcomes. One year later, Dr Edward Schwalbe, Associate Professor in Bioinformatics and Biostatistics at Northumbria University, and colleagues, were the first to describe a means of distinguishing these subgroups using DNA methylation microarrays.
DNA methylation microarrays are widely used in research, but their high costs exclude them from routine clinical use. Dr Schwalbe and colleagues have developed a far simpler methylation classifier assay (MIMIC). Significantly, the novel MIMIC test can identify the subgroup in as little as three-to-four days, compared with three-to-four weeks for established diagnostics, making it applicable for decision making in treatment.
MIMIC is already being used in the current European PNET5 clinical trial of standard-risk medulloblastoma, with the Royal Victoria Infirmary Hospital at Newcastle coordinating samples from 11 centres in the UK. After surgical removal of the tumour, patients recover for 30 days before receiving chemo- and/or radiotherapy, and any molecular analysis needs to be completed within this time. MIMIC helps to rapidly identify patients with a WNT subgroup tumour. In the trial, patients are treated with lower-intensity therapies, aimed at minimising the side effects of treatment whilst maintaining the rate of cure. The dose of radiotherapy is reduced to 18Gy instead of the current standard dose of 23Gy.
The lessened intensity of radiotherapy means that children with WNT medulloblastoma can have better quality of life after the treatment. The ultimate aim of Northumbria researchers is to expand this novel test to include all brain tumours – in childhood and adulthood – laying vital diagnostic foundations for even more cancers.
