Sabari JK, et al. - Researchers investigated whether circulating tumor DNA (ctDNA) next-generation sequencing (NGS) was clinically significant in guiding the treatment course in patients with advanced lung cancers with no known oncogenic driver or who had developed resistance to current targeted therapy (n=210). They determined whether it should be used in clinical practice. Participants had plasma NGS, targeting 21 genes. They succeeded at identifying a variety of oncogenic drivers with a shorter test turnaround time (TAT) by means of plasma ctDNA NGS vs tissue NGS and matched patients to targeted therapy with clinical response. A high concordance was observed between positive findings on plasma NGS and those on tissue NGS. Positive findings on plasma NGS could guide immediate therapy; however, a negative finding in plasma requires further testing. The potential incorporation of plasma NGS into practice guidelines was supported.