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Medulloblastoma drug effect only seen with molecular profiling

Modern molecular profiling of medulloblastomas recently highlighted a previously unrecognised treatment benefit in a major international clinical trial.

Clinical trials can run for many years. From start to finish, they can sometimes take a decade or longer. But science doesn’t stop during that time and new knowledge can change the context of a long-running clinical trial.

This is the case with a Children’s Oncology Group (COG) study in to treatments for children with high-risk medulloblastoma – the most common high grade childhood brain tumour.

The study, which started in 2007, added the chemotherapy drug carboplatin to the standard treatment given at that time. Almost 300 children were included in the trial and to date it’s the largest international trial involving children with high-risk medulloblastoma ever conducted. The results have been analysed and were published recently in the Journal of the American Medical Society (JAMA).

When all of the patients were evaluated as a single group, the clinical trial showed a slight trend toward higher survival, but the change wasn’t big enough to be significant. However, medulloblastoma is now acknowledged to be a broad term for the tumour type, genetically, medulloblastoma is considered to be four distinct subtypes based on molecular similarities. The subtypes are called WNT, SHH, Group 3 and Group 4.

Thanks to funding from The Brain Tumour Charity, researchers assigned tumour samples from the original trial one of the four subtypes. They then analysed the effects of carboplatin for each group separately. The interpretation of the results changed dramatically.

The new analysis showed that the number of children with a Group 3 medulloblastoma surviving beyond five years increased by 19% if they had carboplatin during radiotherapy.

How they did it

Dr Paul Northcott, from St. Jude Children’s Research Hospital, in Memphis USA, assessed the tumour samples that had been stored during the trial. His team used cutting edge methods to assign the tumours into the four molecular groups that are now part of today’s routine diagnoses.

If all the patients were lumped together, there was only a slight trend toward higher survival, but when you look specifically at Group 3, there is a 19% jump in survival. That is a dramatic improvement for such a high-risk group.

said Dr Paul Northcott from St Jude Children’s Research Hospital

No new treatments for high-risk medulloblastoma in the last decade have raised survival rates as much as this COG study suggests carboplatin may for Group 3 patients. Carboplatin is a readily accessible drug used to treat many types of cancer.

Excitingly, these findings validate the use of carboplatin in children, and provide added evidence for more recent trials that are already underway across the UK, Europe and further afield, including for children with grade 3 medulloblastoma.

“Genetic analysis is essential,” Dr James Olson, from Seattle Children’s Hospital, said. “It not only helps us decide the right treatment, but it helps us make the right diagnosis from the beginning. It helps us decide the right treatment to give to the patients who will benefit the most and avoid toxic treatment to those who won’t benefit at all. Tumors may look the same under a microscope, but if they are genetically different, they will respond differently to various types of treatment approaches.”

To read about the research grant that funded the molecular diagnosis used in this publication take a look here.