Comprehensive Genomic Analysis of Patients With Non-Small-Cell Lung Cancer Using Blood-Based Circulating Tumor DNA Assay: Findings From the BFAST Database of a Single Center in Taiwan.

Abstract

The Blood First Assay Screening Trial (BFAST) is a prospective study using next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) in treatment-naïve advanced/metastatic non-small-cell lung cancer (NSCLC). We compared liquid biopsy to tissue testing and analyzed genomic alterations in Taiwanese patients with NSCLC using the BFAST database. A total of 269 patients underwent FoundationOne Liquid Companion Diagnostic (F1LCDx) assay at the National Taiwan University Hospital, of whom 264 underwent tissue-based genetic testing also. We analyzed the actionable mutations and the concordance between tissue-based genetic testing, which was limited to <i>EGFR</i>, <i>ALK</i>, <i>ROS1</i>, and <i>BRAF</i>, in a real-life clinical setting and blood-based NGS in the clinical trial. Additionally, we analyzed the co-occurring genomic alterations from the blood-based ctDNA assay. A total of 76.2% patients showed actionable mutations. Standard tissue testing did not detect known driver alterations in about 22.7% of the patients (sensitivity, 70.24%). Liquid NGS detected additional mutations (<i>RET</i>, <i>KRAS</i>, <i>MET</i>, and <i>ErbB2</i>) in 14% of the patients, which went undetected by the standard-of-care testing. The complementary use of ctDNA NGS increased the detection rate by 42%. The F1LCDx assay had a sensitivity of 83.41%. Lower tumor and metastasis stages predicted nondetected blood-based NGS ctDNA results. Common co-occurring mutations in the blood-based NGS ctDNA assay were <i>TP53</i>, <i>DNMT3A</i>, <i>TET2</i>, <i>PIK3CA</i>, <i>CTNNB1</i>, and <i>RB1</i>. Among the patients with EGFR-mutated NSCLC, <i>TET2</i> co-occurring alterations correlated with shorter progression-free survival of EGFR tyrosine kinase inhibitor treatment. NGS ctDNA analysis in comprehensive genetic testing improves actionable mutation identification, vital for treating Asian NSCLC cases with high actionable mutation rates. Lower stages correlated with undetected blood-based NGS ctDNA assay results.