Daniel C. Chung, MD1, Darrell M. Gray, MD, MPH2, Harminder Singh, MBBS, MD, MPH, FACG3, Rachel B.. Issaka, MD, MAS4, Victoria M.. Raymond, MS5, Craig Eagle, MD6, Sylvia Hu, PhD7, Darya Chudova, PhD6, AmirAli Talasaz, PhD6, Joel K. Greenson, MD8, Frank A. Sinicrope, MD9, Samir Gupta, MD10, William M.. Grady, MD11 1Massachusetts General Hospital, Boston, MA; 2Gray Area Strategies LLC, Owings Mills, MD; 3University of Manitoba, Winnipeg, MB, Canada; 4Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer Center, Seattle, WA; 5Guardant Health, San Diego, CA; 6Guardant Health, Palo Alto, CA; 7Guardant Health, Fort Lee, NJ; 8University of Michigan, Ann Arbor, MI; 9Mayo Clinic, Rochester, MN; 10UC San Diego, San Diego, CA; 11Fred Hutchinson Cancer Center, Seattle, WA
Introduction: Blood-based CRC screening tests provide a non-invasive CRC screening modality that can be completed at any healthcare encounter. Data have shown that incorporating blood-based testing as a CRC screening option improves overall screening rates. With the introduction of these new tests, it is important to understand the implications of “false positive” result and if additional follow-up, beyond colonoscopy, is necessary to evaluate for non-colorectal cancer malignancies. To address this outstanding question, we report on the one-year clinical outcomes of individuals enrolled and tested with Shield in the ECLIPSE study.
Methods: ECLIPSE is a prospective, observational, multi-center study to evaluate a cfDNA blood-based CRC screening test (Shield) in average risk individuals, age 45-84. Enrolled individuals provided a blood sample prior to colonoscopy, followed by standard of care colonoscopy. Sensitivity and specificity of the blood-based test were determined as compared to the reference colonoscopy. Individuals were followed at one- and two-years post study enrollment date to evaluate for interval malignancies, both CRC and non-CRC.
Results: ECLIPSE enrolled 22,877 average risk individuals. The final evaluable cohort was 7,861 persons. We previously reported that the study met its co-primary objectives; CRC sensitivity was 83% (95%CI 72 – 90%) and AN specificity was 90% (95%CI 89-90%). Test positivity rate was 11.4%. 698 individuals had a “false positive” cfDNA blood-based test (positive blood-based test and no colonoscopy finding of CRC or advanced precancerous lesion). 640/698 (92%) had one year of clinical follow-up and 0.8% (5/640) of them had a diagnosis of a non-colorectal cancer (95%CI 0.3 – 1.8) at one year of follow-up. In the 5,982 individuals with a “true negative” Shield result (negative cfDNA blood based test and colonoscopy that was negative for CRC or advanced precancerous lesion), 92% (5,502) had one year of clinical follow-up. 0.9% (51/5,502) had a non-colorectal cancer (95%CI 0.7-1.2) within one year of enrollment. There were no diagnoses of post-colonoscopy colorectal cancer identified during the one-year follow-up period.
Discussion: Data from ECLIPSE demonstrate that the rate of non-colorectal malignancies does not differ in those who tested positive with the cfDNA blood-based test as compared to those who tested negative. Clinical follow-up is ongoing and will continue to gather one- and two-year cancer diagnosis in enrolled individuals.
Disclosures:
Daniel Chung: Guardant Health – Advisory Committee/Board Member. Iterative Health – Grant/Research Support. Janssen – Grant/Research Support.
Darrell Gray: Guardant Health Inc. – Advisor or Review Panel Member.
Daniel C. Chung, MD1, Darrell M. Gray, MD, MPH2, Harminder Singh, MBBS, MD, MPH, FACG3, Rachel B.. Issaka, MD, MAS4, Victoria M.. Raymond, MS5, Craig Eagle, MD6, Sylvia Hu, PhD7, Darya Chudova, PhD6, AmirAli Talasaz, PhD6, Joel K. Greenson, MD8, Frank A. Sinicrope, MD9, Samir Gupta, MD10, William M.. Grady, MD11, 28, Evaluating the Risk of Non-Colorectal Cancers in Individuals With a False Positive Blood-Based Colorectal Cancer Screening Test, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.
