Abstract 6506: Early colorectal cancer detection with a spectroscopic liquid biopsy
Authors: Cameron James M. , Antoniou Georgios , Brennan Paul M. , Conn Justin J. , King Sharon , McHardy Rose G. , Moug Susan , Nobes Jennifer , Palmer David S. , Sala Alexandra , Smith Benjamin R. , Strachan Judith , Mowat Craig , Baker Matthew J. 
Published: April 2023

Abstract
Background: Early detection of cancer is vital to improve patient survival, since earlier diagnosis and treatment maximizes the opportunity to combat or control disease progression. Specifically for colorectal cancer (CRC), the average 5-survival rate after diagnosis decreases from 91% in early-stage CRC, to as low as 15% for stage IV CRC. Furthermore, the rapid detection and subsequent removal of pre-cancerous adenomas - e.g., advanced adenomas (AA) - can improve survival rates of affected patients. Current stool-based tests, such as FIT and FIT-DNA, have poor AA sensitivities of 24% and 42%, and specificities of 95% and 87%, respectively. Recent research into liquid biopsies have shown some promise, however tests based on tumor-derived biomarkers alone have limited sensitivity, especially in early-stage disease.
Methods: We initially applied the Dxcover® Cancer Liquid Biopsy for use as a multi-cancer early detection (MCED) test. The test uses Fourier transform infrared (FTIR) spectroscopy and machine learning algorithms to build a classifier of the resultant spectral profiles to detect cancer, and can be fine-tuned to maximize either sensitivity or specificity depending on the requirements of specific international healthcare systems. Additionally, we have analyzed a retrospective cohort of serum samples comprising 100 CRC, 99 advanced adenomas removed by surgical resection and 97 colonoscopy screening controls.
Results: The CRC classifier from the discovery MCED dataset reported an area under the receiver operating characteristic curve (AUROC) value of 0.91, with 74% sensitivity and 91% specificity when differentiating CRC and non-cancer, which surpasses the targets set by the Centers for Medicare & Medicaid Services (CMS) for coverage of CRC tests. When tuned for higher sensitivity, the model produced 97% sensitivity (49% specificity), and when tailored for greater specificity (97%) the sensitivity was 47%. In this study, we have progressed these findings to examine the ability of the technology to differentiate patients with CRC, AA and colonoscopy controls.
Conclusions: Cancer treatment is more effective when given earlier and this low-cost strategy can facilitate the requisite earlier diagnosis. A rapid blood test that sensitive to AA and early-stage CRC could improve patient prognosis and ultimately reduce mortality.
Citation Format: James M. Cameron, Georgios Antoniou, Paul M. Brennan, Justin J. Conn, Sharon King, Rose G. McHardy, Susan Moug, Jennifer Nobes, David S. Palmer, Alexandra Sala, Benjamin R. Smith, Judith Strachan, Craig Mowat, Matthew J. Baker. Early colorectal cancer detection with a spectroscopic liquid biopsy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6506.