Intra-operative detection of 2-Hydroxyglutarate: avoiding injury to normal brain during surgery for low grade gliomas

Mr. Stephen Price

Patients often describe living with a low grade glioma as having a “time bomb” in their brain. They commonly find they have these tumours following a fit. In some patients they are found accidentally during a scan for an unrelated problem. After detection, patients have to wait, knowing at some stage these slow growing but malignant tumours of the brain will change into aggressive tumours that will ultimately lead to their death. Their slow growth behaviour and site within the brain leads to progressive damage of parts of the brain involved with thinking and memory. This is made worse by patients having frequent fits. The side effect of drugs used to treat these fits cause further problems. Although uncommon, this is a cancer that mostly affects young, economically-active adults. The burden of disease to the individual, their family and society is heavy. The lack of any new treatments makes it more important we maximise the effect of currently available treatments.

Surgery is the key treatment of these tumours. We know that safe, maximal resection improves patient survival rates, seizure control and may help patients avoid the toxic effects of chemotherapy and radiotherapy. Achieving maximal resection, however, is very difficult as healthy and tumour tissue look the same. We have no method of telling them apart. The risk of damaging normal brain stops surgeons extending surgery too far. As a result some tumour tissue may be left behind. If we could accurately identify the margins of these tumours we could remove more tumour and avoid injuring the normal brain, as well as potentially ensuring the patient avoids the toxic effects of radiotherapy and chemotherapy. It may both reduce the burden on the patient and reduce costs for the NHS.

A feature of these tumours is that they produce very high levels of a chemical 2-hydroxyglutarate (2-HG). These tumours have 100x the levels found in normal brain. We propose to develop a method that can detect 2-HG during surgery. This will allow accurate identification of tumour cells, enabling a more complete, safe, removal of the tumour.