P05.27.A INTRODUCTION OF WHOLE GENOME SEQUENCING AS NHS STANDARD OF CARE FOR GLIOMA PATIENTS IN TWO NEUROSURGICAL CENTRES: WEST MIDLANDS

Abstract BACKGROUND In 2019 the NHS Genomics Medicine Service was launched with the aspiration that the NHS will be the first health care system globally to offer Whole Genome Sequencing (WGS) as part of routine care. Since then, NHS England has commissioned WGS for all brain tumours patients. Identification of potentially ‘actionable’ variants may provide opportunities for novel treatments through clinical trials and compassionate use, and act as prognostic and predictive biomarkers. The NHS pathway for WGS is complex, requiring co-ordination of paired fresh frozen tumour, blood samples and associated forms, DNA extraction at the regional Genomics Laboratory Hub (GLH), WGS analysis at Illumina (Cambridge), WGS analysis by Genomics England (GE), return of data to be analysed/interpreted at the GLH, discussion in the Genomics Tumour Advisory Board (GTAB) before returning to the treating oncologist. Here we report our two-year experience in establishing this pathway in two Neurosurgical Centres in the West Midlands. MATERIAL AND METHODS All patients undergoing neurosurgery for radiologically presumed glioma and sampling for WGS at the Queen Elizabeth Hospital Birmingham and University Hospitals of North Midlands NHS Trust were identified retrospectively from WGS reports between 01/01/2022-30/12/2023. Data including demographics, integrated diagnosis, WGS variants reported were captured from the electronic health records. Time taken to pass through critical steps along the NHS pathway were recorded in quarterly (Q) time blocks commencing in January 2022. RESULTS 146 samples with confirmed integrated molecular diagnosis of glioma (64.8% glioblastoma) were analysed. Median age at time of surgery was 52.9 years (interquartile range IQR +/- 14.9), 65.1% of patients were male. 91% of patients underwent craniotomy with 1 cm3 sent for WGS. 10% of these were redo surgery for glioma recurrence. Median tumour content (MTC) in the WGS sample was 69%. The remainder had a stereotactic needle biopsy with one core sent for WGS with MTC of 73% Median time from neurosurgical tissue sampling to completion of WGS report from Q1 2022 (the first patients to trial this pathway) was 255 days (IQR +/- 107.5) versus Q4 2023 (following various refinements of the infrastructure) was 137 days (IQR +/- 60.5; p<0.001). 26 patients had molecular variants leading to trial recommendation and 1 GBM with high Tumour Mutational Burden (TMB) commenced anti-PD1 immunotherapy. 8 GBM patients had a RB1 variant associated with improved progression free survival. CONCLUSION WGS for brain tumour is feasible for both biopsy and craniotomy patients, however funding for infrastructural support with a WGS co-ordinator is essential to ensure it is sustainable. Time for WGS analysis on NHS has improved since commencing the pathway. Further improvement is needed, so that WGS results can catalyse the delivery of precision medicine.