OS4.8 Improving the intra-operative diagnosis of high-grade glioma using a fluorescence biomarker - A Progress Report of The GALA-BIDD Study

Abstract

BACKGROUND: Intrinsic brain cancers (Gliomas) are classified as low and high-grade tumours. Correctly distinguishing high-grade glioma (HGG) from low-grade glioma (LGG) during surgery can influence the surgical procedure, enhancing resection and improving survival. To date there is no biomarker available to aid decision making in real time during surgery. Improving diagnostic accuracy is important because knowing that a tumour is high-grade will aid surgical decision-making. Nests of HGG can be «hidden» in some tumours that appear less aggressive. Because the nests cannot be seen under white light they may be missed at surgery. AIMS: 1. To prospectively investigate whether sampling visible tumour fluorescence improves the diagnostic accuracy during surgery. Currently the error rate for missing high-grade diagnoses for patients with visible fluorescence intra-operatively is around 10%. The proposed surgical biomarker will be acceptable in practice if the error rate is <1%. 2. To recruit 80 patients with visible fluorescence into the study. With ≥78 patients confirmed high grade, we could conclude that the diagnostic error rate is <1%, versus >10%, with a 1% significance level and 95% power. METHODS: 5-aminolevulinic acid (5-ALA) will be used to generate visible fluorescence. Samples of this fluorescent tissue will be sent for perioperative histopathological analysis to establish an intra-operative diagnosis of low-grade or high-grade cancer. These data will be compared with the final pathological diagnosis. PRIMARY OBJECTIVE: to validate the presence of visible fluorescence as a pragmatic intra-operative diagnostic surgical biomarker of high-grade disease within a tumour mass. Since January 2015 this neurosurgical study has been open to recruitment at 3 centres in the UK to patients judged by MR imaging to have an intrinsic glioma grade II (thought to be transforming to a higher grade), III or IV. A total of 39 patients have been recruited to 31 January 2016. Progress to date will be presented, including challenges that have been encountered and lessons that have been learnt from our experiences of running this study.