Abstract

Abstract The development of a robust multi-cancer early detection (MCED) test would be transformational within the cancer diagnostics field, as earlier detection is vital to inhibit disease progression, improve patient prognosis and reduce mortality rates. In this large-scale spectroscopic study, we present the Dxcover® Cancer Liquid Biopsy, the world’s first infrared spectroscopy-based blood test for the early detection of multiple cancers. The full cohort (n=2094) was comprised of patients with a confirmed cancer diagnosis (n=1543), symptomatic non-cancer patients (n=460) and healthy volunteers (n=91). For the cancer versus non-cancer classification, receiver operating characteristic analysis produced a mean curve with an area under the curve (AUC) value of 0.86. When adjusted for greater sensitivity, our model achieved 90% sensitivity with 61% specificity, and yielded a sensitivity of 56% with 91% specificity when tailored for higher specificity. We also tuned for maximized sensitivity or specificity, whilst the other parameter was fixed above a minimum value of 45% for the cross-validation result, based upon performance levels of currently available clinically benchmarked tests. This resulted in a 94% sensitivity where specificity was 47%, and a 94% specificity with 48% sensitivity. The overall detection rates were 93% for stage I, 84% for stage II, 92% for stage III and 95% for stage IV for the sensitivity-tuned model. The specificity-tuned model detected 90% of non-cancer patients accurately, resulting in few false negatives (54/551). For the binary classifiers of individual cancer types against symptomatic control patients, promising AUC values were reported for all cancers: brain (0.90), breast (0.74), colorectal (0.91), kidney (0.91), lung (0.90), ovarian (0.85), pancreatic (0.81) and prostate (0.85). Importantly, the detection rates did not vary significantly according to cancer stage, suggesting the technology is very effective at detecting early-stage tumors, which is a necessity for MCED tests. Citation Format: James M. Cameron, Alexandra Sala, Georgios Antoniou, Paul M. Brennan, Justin J. A. Conn, Siobhan Connal, David S. Palmer, Benjamin R. Smith, Matthew J. Baker. Multi-cancer early detection with a spectroscopic liquid biopsy platform [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5920.

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