Improving the intra-operative diagnosis of high-grade glioma using a fluorescence biomarker – result of the UK NCRI GALA-BIDD study


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Colin Watts1,Keyoumars Ashkan2,Michael Jenkinson3,Kathreena Kurian4,Wendi Qian5,Stephen Price5,Tomasz Matys6,Gail Doughton5,Andrea Machin5,Josephine Jung2,Ibrahim Jalloh3,Chloe Harman5,Katrina Gatley5,Gemma Young5,Richard Hardy5,Alimu Dayimu7

1University of Birmingham,2Kings College Hospital,3University of Liverpool,4Southmead Hospital,5Cambridge University Hospitals NHS Foundation Trust,6University of Cambridge,7Shandong University

Abstract

Background

Correctly distinguishing gliomas as low or high grade (LGG or HGG) during surgery can influence the surgical procedure, enhancing resection and improving survival. The GALA-BIDD study was designed to prospectively investigate whether the presence of visible fluorescence is a pragmatic intra-operative diagnostic surgical biomarker of high grade disease within a tumour mass in real time during surgery.

Method

Patients with suspected intrinsic glioma discussed at neuro-oncology Multidisciplinary Team meetings and suitable for fluorescence guided cytoreductive surgery were eligible. 5-aminolevulinic acid (5-ALA) was used to generate visible fluorescence. Tissue samples were sent for peri-operative histopathological analysis to establish an intra-operative diagnosis of LGG or HGG. Presence of visible fluorescence was collected. These data were compared with the final central pathological diagnosis.

Results

From Feb 2015 to March 2017 in the UK, 106 patients were recruited: median age 59 (range 23-77); 59% male; 25% WHO radiological grade II transforming to a higher grade and 55% grade IV. 5-ALA were given for 103 patients with a median dose of 1500mg (range 960-2200mg). 67% of patients classified as HGG at local per-operative diagnosis were confirmed by the central review (weighted Kappa 0.37 (95%CI=0.21-0.54)). 88 patients were evaluable for the primary endpoint: 81 had visible fluorescence of the tumour with central histopathology diagnosis as 1 LGG, 78 HGG (a 99% concordance in HGG classification with the 99%CI=91%-99.9%) and 2 not assessed; 7 patients had no visible fluorescence and were diagnosed as 6 LGG and 1 HGG.

Conclusion

There is an urgent need to improve the local peri-operative diagnosis. The presence of visible fluorescence can be used as an additional pragmatic intra-operative diagnostic surgical biomarker of high-grade disease within a tumour mass. Use for assessment of low-grade disease needs further investigation.