B-240 Multi-omic blood test for early detection of cancer and pre-cancer
Authors: Baker M , Cameron J M , Brennan P , Butler H , Antoniou G , Christie L , Conn J , Connal S , McHardy R , Sala A , Smith B , Palmer D 
Published: October 2024

Abstract

Background
The earlier diagnosis of cancer is vital to improve patient survival. Many liquid biopsy technologies are focused on single tumor-derived biomarkers, which limits test sensitivity, especially for early-stage cancers that do not shed sufficient genetic material into the bloodstream. The Dxcover liquid biopsy employs Multi-Omic Spectral Analysis (MOSA) that interrogates a blood sample with Infrared (IR) radiation and produces a distinctive signature that represents the whole biomolecular profile of the sample. This multi-omic blood test analyzes the full complement of tumor and immune-derived markers present within blood derivatives and could facilitate the earlier detection of cancer. The technology can be tuned for high sensitivity (rule out) or high specificity (rule in) depending on the desired application, clinical priorities and international healthcare markets.

Methods
Three clinical studies have been completed, assessing the technology for the detection of: (1) brain cancer, (2) multiple cancers, and (3) colorectal cancer (CRC) and pre-cancerous lesions. In the first study, we recruited 988 patients prospectively with non-specific symptoms associated with a brain tumor. Secondly, we carried out a large-scale multi-cancer evaluation (n = 2092 patients), targeting eight different cancers. Moreover, the CREATE (ColoREctal cancer & Adenoma Test Evaluation) feasibility study (3) examined 100 CRC, 92 adenoma samples and 104 colonoscopy screening control patients.

Results
In study 1, the brain cancer algorithm detected 96% of the patients with brain cancer, and 100% of glioblastomas, the most aggressive primary brain tumor. In the multi-cancer study (2), area under the receiver operating characteristic curve values were calculated for the eight cancer types versus symptomatic non-cancer controls: brain (0.90), breast (0.76), colorectal (0.91), kidney (0.91), lung (0.91), ovarian (0.86), pancreatic (0.84) and prostate (0.86). We also assessed the test performance when all eight cancer types were pooled to classify ‘any cancer’ against non-cancer patients. The cancer versus asymptomatic non-cancer classification detected 64% of stage I cancers when specificity was 99% (overall sensitivity 57%). When tuned for higher sensitivity, this model identified 99% of Stage I cancers (with specificity 59%). In the CREATE study, the test reported promising results for pre-cancer detection; at 90% specificity, the test reported sensitivities of 80% for CRC and 59% for advanced adenomas.

Conclusions
A rapid liquid biopsy that is sensitive to pre-cancerous lesions and early-stage cancer could substantially improve patient outcomes. There is a low barrier to integrating this blood test into existing diagnostic pathways as the technology is rapid, simple to use, and sample preparation is minimal. In addition, the spectroscopic liquid biopsy has the potential to be combined with other orthogonal tests, such as cell-free DNA, which could provide an efficient route to diagnosis. Cancer treatment can be more effective when given earlier, and this low-cost strategy has the potential to improve patient prognosis.