Global validation of a brain cancer liquid biopsy.

2052 Background: Delayed diagnosis of brain cancer leads to approximately two-thirds of patients being identified only after presentation to the emergency department with advanced symptoms or established neurological deficits. Implementation of a simple liquid biopsy test as a rule-out test prior to confirmatory imaging, could facilitate earlier and more efficient triage of patients presenting with non-specific symptoms suggestive of brain cancer, enabling prioritization for those most at-risk and accelerate diagnostic pathways. Methods: Presented here is the clinical validation of the Dxcover Brain Cancer Liquid Biopsy Platform obtained to support regulatory approvals. The multi-centre and observational ‘Early and tiMely detection of BRAin CancEr’ (‘EMBRACE’) study was conducted with prospective patient recruitment across seven sites in Europe. The target population consisted of patients with symptoms indicative of brain cancer. Test performance was assessed by comparison of the liquid biopsy result to diagnostic imaging. Furthermore, the liquid biopsy test was then independently tested on an additional clinical dataset obtained from a US patient population (n=234) as part of a CLIA laboratory validation study. Results: In the EMBRACE performance evaluation, 2554 patients were enrolled across the seven collection sites; 2324 were deemed eligible and taken forward for test assessment. There were 697 brain tumours in total, of which 395 were malignant, and 1627 non-tumour diagnoses. In the intended use population, the reported diagnostic performance was 86% sensitivity for brain cancer detection with 44% specificity, and a 99% negative predictive value (NPV). Notably, for the most prevalent and most aggressive brain cancer, glioblastoma, 86% of cases were successfully identified. Additionally, 94% of patients with central nervous system lymphoma, and 90% of brain metastases were predicted correctly as having tumours. The test has gained regulatory approval for use in the UK and in Europe, gaining UKCA and CE – IVDR certification respectively. The CLIA validation has provided additional confirmation of the clinical utility of the liquid biopsy test in the US population. Conclusions: Existing symptom-based referral pathways are ineffective for the detection of brain cancer, and there is an urgent need for new tests to help with clinical decision making. With a NPV of 99%, the Dxcover Liquid Biopsy test could aid with the efficient stratification of patients toward diagnostic imaging.