Clinical validation of a spectroscopic liquid biopsy for earlier detection of brain cancer

Cameron, James M. and Brennan, Paul M. and Antoniou, Georgios and Butler, Holly J. and Christie, Loren and Conn, Justin J.A. and Curran, Tom and Gray, Ewan and Hegarty, Mark G. and Jenkinson, Michael D. and Orringer, Daniel and Palmer, David S. and Sala, Alexandra and Smith, Benjamin R. (2022) Clinical validation of a spectroscopic liquid biopsy for earlier detection of brain cancer. Neuro-Oncology Advances, 4 (1). vdac024. ISSN 2632-2498 (https://doi.org/10.1093/noajnl/vdac024)

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Abstract

Abstract Background Diagnostic delays impact the quality of life and survival of patients with brain tumors. Earlier and expeditious diagnoses in these patients are crucial to reduce the morbidities and mortalities associated with brain tumors. A simple, rapid blood test that can be administered easily in a primary care setting to efficiently identify symptomatic patients who are most likely to have a brain tumor would enable quicker referral to brain imaging for those who need it most. Methods Blood serum samples from 603 patients were prospectively collected and analyzed. Patients either had non-specific symptoms that could be indicative of a brain tumor on presentation to the Emergency Department, or a new brain tumor diagnosis and referral to the neurosurgical unit, NHS Lothian, Scotland. Patient blood serum samples were analyzed using the Dxcover® Brain Cancer liquid biopsy. This technology utilizes infrared spectroscopy combined with a diagnostic algorithm to predict the presence of intracranial disease. Results Our liquid biopsy approach reported an area under the receiver operating characteristic curve of 0.8. The sensitivity-tuned model achieves a 96% sensitivity with 45% specificity (NPV 99.3%) and identified 100% of glioblastoma multiforme patients. When tuned for a higher specificity, the model yields a sensitivity of 47% with 90% specificity (PPV 28.4%). Conclusions This simple, non-invasive blood test facilitates the triage and radiographic diagnosis of brain tumor patients while providing reassurance to healthy patients. Minimizing time to diagnosis would facilitate the identification of brain tumor patients at an earlier stage, enabling more effective, less morbid surgical and adjuvant care.

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