PO10AN INVESTIGATION INTO THE POTENTIAL OF THE KETOGENIC DIET IN THE CELLULAR METABOLISM OF PAEDIATRIC BRAIN TUMOURS

Abstract

INTRODUCTION: Paediatric high grade gliomas (pHGGs) are aggressive malignant tumours with very poor prognosis. Advances in treatment have been limited and so novel therapies are needed. The Ketogenic Diet (KD) is a high fat diet which forces the body to burn fat instead of carbohydrate, thus starving the glycolytic dependent tumour cells whilst providing ketone bodies as an energy source for normal neurons and glial cells. The KD has also been shown to increase sensitivity to radiotherapy and chemotherapy in HGG animal models and to have anti-angiogenic effects. We aimed to discover how many pHGG patients may benefit from this adjuvant therapy. METHOD: Expression of the ketolytic enzymes (potential markers for KD response) 3-oxoacid CoA-transferase (OXCT1) and D-beta-hydroxybutyrate dehydrogenase (BDH1) were evaluated by immunohistochemistry using formalin-fixed paraffin embedded material of 69 pHGG cases. Expression was assessed as either low (,20%) or high (.20%). RESULTS: IHC showed that 75% of samples were low expressors of OXCT1 and 77% of samples were low expressors of BDH1. Patients with low expression of the ketolytic enzymes, OXCT1 and/or BDH1 are more likely to benefit from participating in a KD trial. Whilst the patients in this cohort did not undertake the KD, the mean overall survival and event free survival was higher in those patients who had low expression of these enzymes. CONCLUSION: Our results suggest that IHC in a routine histopathology laboratory could be used to indicate those patients who may respond to the KD. In our cohort at least 75% of pHGG patients were low expressors of OXCT1 and BDH1 suggesting that the majority of pHGG patients may benefit from a KD.