REVIEW OF THE INTRODUCTION OF WHOLE GENOME SEQUENCING AS NHS STANDARD OF CARE FOR BRAIN TUMOUR PATIENTS AT QUEEN ELIZABETH HOSPITAL BIRMINGHAM, UK

Abstract

Abstract AIMS Describe delays in the NHS pathway from initial consent for whole genome sequencing (WGS) to delivery of the final WGS report (WGS-R) to the treating oncologist. Review number of patients with mutations that inform, diagnosis, prognosis or treatment. METHOD Prospective audit of time to key stages along WGS pathway and review of final WGS-R. RESULTS WGS pathway and process: Data snapshot at 24/02/2023 showed 96 patients consented for WGS: 12/96 awaiting surgery; 41/96 awaiting GTAB discussion; 1/96 WGS sample used for histopathological diagnosis, 1/96 ineligible. 41/96 WGS results discussed at a GTAB meeting; 39/44 with complete WGS-R sent to the treating oncologist, including discussion at the local neuro-oncology multi-disciplinary team meeting. Median time from consent to final WGS-R was 225 days (range 145-567). WGS results: 4 patients with glioblastoma (GBM) have RB1 variant, associated with improved progression-free and overall survival (Dono et al 2021). 10 patients had clinically actionable mutations with recommended trials or compassionate-use drugs. 1/10 patient with GBM and High Tumour Mutational Burden who completed standard of care (SOC) treatment has commenced anti-PD1 immunotherapy (Nivolumab; Goodman et al 2017). 5/10 patients are currently on SOC treatment, 3/10 had deteriorated and 1/10 were deceased at time of WGS-R. Excellent concordance of WGS data with SOC genetic/immunohistochemistry testing. No germline mutations identified. CONCLUSIONS Nearly a third of patients had genetic variants that may have the potential to inform future clinical management. Further investment in the WGS pathway is required to deliver timely results to allow application of precision medicine for brain cancer patients.