100 Introduction of Whole Genome Sequencing for brain metastases in West Midlands

Abstract Introduction Whole genome sequencing (WGS) for brain tumours was introduced in the NHS test directory in 2018 to identify clinically actionable mutations for precision oncology therapies. Since 2019, the West Midlands has delivered WGS alongside standard of care (SoC) testing for brain tumour patients. We evaluated our regional experience of WGS in patients with brain metastases. Methods Between January 2022 and March 2025, 110 patients underwent WGS at Queen Elizabeth Hospital Birmingham and Royal University Hospital Stoke. Data was collected for baseline, time to achieve SoC diagnosis, time for WGS pathway, and clinical actions taken based on WGS results. Results Most common tumours were lung (34.5%), breast (21.8%) and melanoma (18.2%). Median time from surgery to SoC diagnosis was 12.50(9.25,27.75) days and to WGS report 141.50(114,172.75). This took a median 14(8.25,28) days from surgery to sample receipt, further 80(57,116.75) days for plating and sequencing, and further 31(22.25,44) days from results ratification at the Genomic Tumour Advisory Board (GTAB) to WGS report receipt. 66%(73/110) of patients have actionable somatic variants, whilst 8.2%(9/110) were not actionable. 75%(55/73) had an identified immunotherapy and/or trial, whereas 30.9%(17/55) were already on immunotherapy based on SoC diagnosis and 38.2%(21/55) were ineligible for further treatment (ongoing chemoradiotherapy, progression or surveillance). No patient was started on immunotherapy and/or recruited on a trial based on WGS results. Overall, 35%(39/110) died before the results be acted upon. 6.4%(7/110) patients were identified to have a germline mutation; one was known from SoC diagnosis, and all were investigated by clinical genetics. Conclusion The long WGS testing pathway is a challenge to clinically act upon actionable results. Optimising testing pathway, technologies, timings and patient selection could improve WGS’s role in this patient population.