S130 Multimodal Circulating Tumor DNA (ctDNA) Blood-Based Colorectal Cancer (CRC) Screening Test Demonstrates Clinically Meaningful Sensitivity Across Multiple Clinical Parameters

Introduction: Blood-based CRC screening holds potential to improve screening compliance due to ease of use and high patient and provider acceptability. A blood-based screening test must detect CRC across multiple clinical parameters in order to prove clinically meaningful in a screen-relevant population. We aimed to describe the performance of a multimodal ctDNA blood-based CRC screening test in a cohort of patients (pts) with newly diagnosed CRC. Methods: A consecutive, unselected series of pts with newly diagnosed CRC were consented to a study permitting use of clinical data and biospecimens for research. Consented pts provided a blood sample (10mL collected in EDTA) prior to surgical resection. Isolated plasma (median 3mL) from a cohort of pts with Stage I – III CRC was analyzed with a 500kb next-generation sequencing based panel and bioinformatic platform incorporating cell-free DNA (cfDNA) methylation-based partitioning to identify cancer related genomic alterations and epigenomic modifications (methylation and modifications in chromatin state). The output is a “ctDNA detected” or “ctDNA not detected” result. Final results were correlated with clinical features. Results: ctDNA results were available for 699 pts; 43% female, median age 63 years (range 20 - 89), 90% of pts were age 45 - 84. Overall sensitivity was 96% (671 / 699). The assay demonstrated sensitivity in the 88 – 100% range across cancer stage and presentation, primary tumor location, histology and grade, degree of tumor invasion, and microsatellite instability status (Table). Sensitivity in 138 pts with Stage I / II well-differentiated (low grade) CRC was 93%. CRC presentation status was known in 83% of pts with Stage I / II CRC (N = 344). Sensitivity was 90% in the 44% (N = 152) of pts who were asymptomatic at presentation. Sensitivity was 96% in the 56% (N = 192) of pts with Stage I / II disease who presented symptomatically. Specificity in age-matched cancer-free controls was 94%. Conclusion: This multimodal ctDNA CRC screening test has clinically meaningful sensitivity across multiple clinical parameters, most notably in those with early-stage asymptomatic disease and early-stage low-grade tumors. The data suggest this test will have clinically meaningful performance in an average risk screening population presenting with varying cancer stages and tumor histologic features. A prospective registrational study to evaluate the test in an average risk, screen-relevant cohort is ongoing (NCT04136002).Table 1.: Sensitivity of blood-based CRC screening test.