Supplementary Figure from A Large-Scale Prospective Concordance Study of Plasma- and Tissue-Based Next-Generation Targeted Sequencing for Advanced Non–Small Cell Lung Cancer (LC-SCRUM-Liquid)

Sugimoto, Akira; Matsumoto, Shingo; Udagawa, Hibiki; Itotani, Ryo; Usui, Yuko; Umemura, Shigeki; Nishino, Kazumi; Nakachi, Ichiro; Kuyama, Shoichi; Daga, Haruko; Hara, Satoshi; Miyamoto, Shingo; Kato, Terufumi; Sakakibara-Konishi, Jun; Tabata, Eriko; Nakagawa, Taku; Kawaguchi, Tomoya; Sakai, Tetsuya; Shibata, Yuji; Izumi, Hiroki; Nosaki, Kaname; Zenke, Yoshitaka; Yoh, Kiyotaka; Goto, Koichi

doi:10.1158/1078-0432.22488480.v1

Supplementary Figure from A Large-Scale Prospective Concordance Study of Plasma- and Tissue-Based Next-Generation Targeted Sequencing for Advanced Non–Small Cell Lung Cancer (LC-SCRUM-Liquid)

journal contribution

posted on 2023-04-01, 00:01 authored by Akira Sugimoto, Shingo Matsumoto, Hibiki Udagawa, Ryo Itotani, Yuko Usui, Shigeki Umemura, Kazumi Nishino, Ichiro Nakachi, Shoichi Kuyama, Haruko Daga, Satoshi Hara, Shingo Miyamoto, Terufumi Kato, Jun Sakakibara-Konishi, Eriko Tabata, Taku Nakagawa, Tomoya Kawaguchi, Tetsuya Sakai, Yuji Shibata, Hiroki Izumi, Kaname Nosaki, Yoshitaka Zenke, Kiyotaka Yoh, Koichi Goto

Supplementary Figure from A Large-Scale Prospective Concordance Study of Plasma- and Tissue-Based Next-Generation Targeted Sequencing for Advanced Non–Small Cell Lung Cancer (LC-SCRUM-Liquid)

History

ARTICLE ABSTRACT

We evaluated plasma cell-free DNA (cfDNA) and tissue-based sequencing concordance for comprehensive oncogenic driver detection in non–small cell lung cancer (NSCLC) using a large-scale prospective screening cohort (LC-SCRUM-Liquid). Blood samples were prospectively collected within 4 weeks of corresponding tumor tissue sampling from patients with advanced NSCLC to investigate plasma cfDNA sequencing concordance for alterations in 8 oncogenes (EGFR, KRAS, BRAF, HER2, MET, ALK, RET, and ROS1) compared with tissue-based next-generation targeted sequencing. Paired blood and tissue samples were obtained in 1,062/1,112 enrolled patients with NSCLC. Oncogenic alteration was detected by plasma cfDNA sequencing and tissue assay in 455 (42.8%) and 537 (50.5%) patients, respectively. The positive percent agreement of plasma cfDNA sequencing compared with tissue DNA and RNA assays were 77% (EGFR, 78%; KRAS, 75%; BRAF, 85%; HER2, 72%) and 47% (ALK, 46%; RET, 57%; ROS1, 18%; MET, 66%), respectively. Oncogenic drivers were positive for plasma cfDNA and negative for tissue due to unsuccessful genomic analysis from poor-quality tissue samples (70%), and were negative for plasma cfDNA and positive for tissue due to low sensitivity of cfDNA analysis (61%). In patients with positive oncogenic drivers by plasma cfDNA sequencing but negative by tissue assay, the response rate of genotype-matched therapy was 85% and median progression-free survival was 12.7 months. Plasma cfDNA sequencing in patients with advanced NSCLC showed relatively high sensitivity for detecting gene mutations but low sensitivity for gene fusions and MET exon 14 skipping. This may be an alternative only when tissue assay is unavailable due to insufficient DNA and RNA.