​ Real-World Insights into the Accuracy and Precision of the Decentralized MSK-ACCESS powered with SOPHiA DDM Solution

Presented by Florian Klemm, MD, PhD 
Technical Product Management Expert, Genomic Research, SOPHiA GENETICS​

Liquid biopsy (LBx) is a powerful, non-invasive approach to identify treatment selection or resistance markers, assess treatment efficacy, monitor disease, and predict relapse. To facilitate genomic profiling of cell-free DNA (cfDNA) in cancer SOPHiA GENETICS has developed a decentralized version of MSK-ACCESS (Memorial Sloan Kettering Cancer Center – Analysis of Circulating cfDNA to Evaluate Somatic Status). The MSK-ACCESS powered with SOPHiA DDM solution interrogates 146 cancer-associated genes for somatic variants and exhibits a high concordance to the original single-site test. It incorporates white blood cell (WBC) sequencing to reduce the risk of including germline and clonal hematopoiesis (CH) alterations in the tumor variant set. To evaluate the real-world performance of MSK-ACCESS powered with SOPHiA DDM an observational, multi-center study was initiated to evaluate accuracy (concordance to orthogonal tests and tumor tissue analyses) and precision (repeatability & reproducibility).

 Interim real-world results of the MSK-ACCESS powered with SOPHiA DDM solution illustrate its accuracy in clinical samples. By distinguishing cfDNA from CH/germline origin variants, potential biological false positives were removed. Further analyses of patient-matched tissue will be used to establish concordance between cfDNA and tumor tissue genomic profiles and investigate causes of discordance, including biological, technical and protocol factors. The assay’s observed precision demonstrates that site-to-site discordance, a major barrier to the adoption of LBx testing, has been addressed by this solution.