Abstract

Circulating Tumor DNA in Advanced-Stage Cancer Patients – Somatic Genomic Landscape and its Clinical Utility

AmirAli Talasaz, Co-Founder, President & COO, Guardant Health

Next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) enables non-invasive profiling of solid tumor cancers. Liquid biopsy studies to date have been limited to modest-size cohorts and case studies. Somatic genomic profiles of over 15,000 patients with advanced-stage clinical cancer were determined by a highly accurate, deep-coverage ctDNA NGS test targeting 70 genes (Guardant360). Frequencies of somatic ctDNA alterations per gene were compared to those previously described in tissue sequencing projects (e.g., TCGA). Accuracy of ctDNA sequencing (PPV) was assessed by comparing with matched tissue tests. Different classes of clinical outcome benefits have been observed by liquid biopsy by detecting actionable mutations in cases with tissue QNS or actionable mutations emerging at time of progression or under-genotyped tumors.