AbstractPurpose:. Liquid biopsy (LBx) for tumor profiling is increasingly used, but concerns remain regarding negative results. A lack of results may truly reflect tumor genomics, or it may be a false negative that would be clarified by tissue testing. A method of distinguishing between these scenarios could help clarify when follow-on tissue testing is valuable.Experimental Design:. Here we evaluate circulating tumor DNA (ctDNA) tumor fraction (TF), a quantification of ctDNA in LBx samples, for utility in identifying true negative results. We assessed concordance between LBx and tissue-based results, stratified by ctDNA TF, in a real-world genomic dataset of paired samples across multiple disease types. We also evaluated the frequency of tissue results identifying driver alterations in patients with lung cancer after negative LBx in a real-world clinicogenomic database.Results:. The positive percent agreement and negative predictive value between liquid and tissue samples for driver a

AbstractPurpose:. Liquid biopsy (LBx) for tumor profiling is increasingly used, but concerns remain regarding negative results. A lack of results may truly reflect tumor genomics, or it may be a false negative that would be clarified by tissue testing. A method of distinguishing between these scenarios could help clarify when follow-on tissue testing is valuable.Experimental Design:. Here we evaluate circulating tumor DNA (ctDNA) tumor fraction (TF), a quantification of ctDNA in LBx samples, for utility in identifying true negative results. We assessed concordance between LBx and tissue-based results, stratified by ctDNA TF, in a real-world genomic dataset of paired samples across multiple disease types. We also evaluated the frequency of tissue results identifying driver alterations in patients with lung cancer after negative LBx in a real-world clinicogenomic database.Results:. The positive percent agreement and negative predictive value between liquid and tissue samples for driver a