A Prospective Study of Circulating Tumor DNA to Guide Matched Targeted Therapy in Lung Cancers

作者：Joshua K. Sabari, Michael David Offin, Dennis P. Stephens, Ai Ni, Adrian V. Lee, Nick Pavlakis, Stephen John Clarke, Connie Irene Diakos, Sutirtha Datta, Nidhi Tandon, Andrés Martinez, Mackenzie L. Myers, Alex Makhnin, Ysleni Leger, Helena Alexandra Yu, Paul K. Paik, Jamie E. Chaft, Mark G. Kris, Jeong O Jeon, Laetitia A Borsu, Marc Ladanyi, Maria E. Arcila, Jennifer Hernandez, Samantha Henderson, Tristan S. Shaffer, Kavita N. Garg, Dan DiPasquo, Christopher K. Raymond, Lee P. Lim, Mark Li, Matthew David Hellmann, Alexander Edward Dela Cruz Drilon, Gregory J. Riely, Valerie W. Rusch, David R. Jones, Andreas Rimner, Charles M. Rudin, James M. Isbell, Bob T. Li · 发表于：JNCI Journal of the National Cancer Institute · 年份：2018 · DOI：10.1093/jnci/djy156 · 被引用次数：126 · 研究领域：Cancer Genomics and Diagnostics、Lung Cancer Treatments and Mutations、Lung Cancer Research Studies

BACKGROUND: Liquid biopsy for plasma circulating tumor DNA (ctDNA) next-generation sequencing (NGS) is commercially available and increasingly adopted in clinical practice despite a paucity of prospective data to support its use. METHODS: Patients with advanced lung cancers who had no known oncogenic driver or developed resistance to current targeted therapy (n = 210) underwent plasma NGS, targeting 21 genes. A subset of patients had concurrent tissue NGS testing using a 468-gene panel (n = 106). Oncogenic driver detection, test turnaround time (TAT), concordance, and treatment response guided by plasma NGS were measured. All statistical tests were two-sided. RESULTS: Somatic mutations were detected in 64.3% (135/210) of patients. ctDNA detection was lower in patients who were on systemic therapy at the time of plasma collection compared with those who were not (30/70, 42.9% vs 105/140, 75.0%; OR = 0.26, 95% CI = 0.1 to 0.5, P < .001). The median TAT of plasma NGS was shorter than tissue NGS (9 vs 20 days; P < .001). Overall concordance, defined as the proportion of patients for whom at least one identical genomic alteration was identified in both tissue and plasma, was 56.6% (60/106, 95% CI = 46.6% to 66.2%). Among patients who tested plasma NGS positive, 89.6% (60/67; 95% CI = 79.7% to 95.7%) were also concordant on tissue NGS and 60.6% (60/99; 95% CI = 50.3% to 70.3%) vice versa. Patients who tested plasma NGS positive for oncogenic drivers had tissue NGS concordance of 96...