Evaluation of a sensitive blood test for the detection of colorectal advanced adenomas in a prospective cohort using a multiomics approach

• Published in: Journal of clinical oncology Vol. 39; no. 3_suppl; p. 43
• Main Authors: Lin, Jimmy, Ariazi, Eric, Dzamba, Michael, Hsu, Teng-Kuei, Kothen-Hill, Steven, Li, Kang, Liu, Tzu-Yu, Mahajan, Shivani, Palaniappan, Krishnan K, Pasupathy, Amit, Polonskaia, Alina, St. John, John, Steiger, Dan, Ulz, Peter, Wang, Irving, Xiao, Jiajie, Yang, Rui, Putcha, Girish, Shaukat, MD, MPH, Aasma
• Format: Journal Article
• Language: English
• Published: 20.01.2021
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2021.39.3_suppl.43

Abstract only 43 Background: Blood-based screening tests for colorectal cancer (CRC) with high sensitivity and specificity are needed to improve adherence, facilitate early detection, and ultimately reduce mortality from CRC. Current stool-based tests have a sensitivity of 24-42% for colorectal advanced adenomas (AAs), while blood tests that rely on tumor-derived cell-free DNA (cfDNA) methylation signatures have shown limited sensitivity for AAs. Here we demonstrate the ability to detect AAs from blood using a multiomics test that incorporates both tumor- and immune-derived signatures, and compare it to the performance of a cfDNA methylation-only test. Methods: Participants enrolled in a prospective study (NCT03688906) were included in this analysis. The multiomics test includes signatures for cell-free nucleic acids based on next-generation sequencing, and for plasma proteins based on high-throughput multiplexed assays. Signatures are integrated computationally with a combination of convolutional neural networks and regularized logistic regression. We compared the multiomics test with one based on cfDNA methylation only. Results: This sub-study included 542 participants (AA: n = 122; colonoscopy-confirmed negative controls: n = 420). Participants with AA were 56% male with a mean age of 63 years, and colonoscopy-confirmed negative controls were 54% male with a mean age of 61 years. The multiomics test achieved a sensitivity of 41% (n = 50/122, 95% CI 34-48%) at 90% specificity (377/420). By contrast, the cfDNA methylation-only test achieved a sensitivity of 20% (24/122, 95% CI 15-25%) at 91% specificity (383/420). Performance was also analyzed by histological subtype and location, and superiority of the multiomics test to the cfDNA-methylation-only test was consistently observed. Conclusions: A novel multiomics blood test can detect colorectal AAs at a sensitivity and specificity comparable to existing stool-based tests. Combining signatures from both tumor- and immune-derived sources resulted in AA sensitivity greater than that of cfDNA-methylation alone.