Analytical validation of a hybrid-approach combining tumor-informed and tumor-agnostic bespoke ctDNA panel assay for the sensitive detection of minimal residual disease

Abstract

Minimal residual disease (MRD) is a small group of cancer cells not eliminated by anti-cancer treatment. Because of its small size, conventional imaging system may not be able to detect the MRD in routine clinical practice. Although the liquid biopsy tests can detect the circulating tumor DNA (ctDNA) when the tumor is present in the body, the fraction of ctDNA is considered lower than the 0.01% which is unreachable by current state-of-the-art liquid biopsy assay relying on fixed-gene panel approach. Here, we describe the analytical validation result of our previously developed a tumor-informed MRD test, CancerDetect TM (formerly reported as AlphaLiquid ® Detect), leveraging large-scale mutation spectrum profiling strategy to enhance detection sensitivity. The CancerDetect TM is a hybrid-approach MRD test combining both personalized (bespoke) mutations and tumor-agnostic clinically actionable targets (hotspot mutations) with hybridization capture technology. The analytical validation result of CancerDetect TM showed limit of detection successfully reached down to 0.001% (10 −5 ) with 99.9% specificity.