Abstract 3990: Circulating tumor DNA assessed through amplicon-based next-generation sequencing and its clinical application

Abstract

Abstract Circulating tumor DNA (ctDNA) studies focusing on only one or a few genes to monitor the disease progress or treatment response are unlikely to find its clinical significance. Hence, the development of cell-free DNA (cfDNA) panel covering hundreds of mutation hotspots is important for the establishment of clinically practical ctDNA detection system. We enrolled 101 patients with metastatic colorectal cancer (mCRC) who received chemotherapy. Amplicon-based genomic profiling of 14 genes, which are commonly mutated in CRC, in plasma by next-generation sequencing (NGS) was performed to evaluate the feasibility of this assay, and was compared with their clinical parameters and RAS status in matched tissue samples. Somatic mutations of the 14 genes in plasma cfDNA were detected in 88 patients (87.1%) with mCRC. Mutations in TP53, KRAS and APC genes were detected in 70 (69.3%), 39 (38.6%) and 24 (23.7%) patients, respectively. Mutant allele frequencies in cfDNA were significantly associated with metastasis (liver, P=0.00004, lymph node, P=0.008, number of metastatic organs, P=0.0006), tumor markers (CEA, P=0.000007, CA19-9, P=0.006, LDH, P=0.00001), and tumor diameter (maximum, P=0.00002, sum of diameter, P=0.00009). The overall concordance rate of RAS status between ctDNA and matched tissue was 77.2% (78/101). Furthermore, we enrolled 76 patients with stage lV pancreatic cancer, and their genomic profiling of 14 genes in plasma were performed to evaluate the feasibility of the cfDNA panel. We observed that patients with lower ctDNA level showed significantly longer overall survival (P=0.00000026). Our data confirmed that mutant allele in cfDNA can be sensitively detected by amplicon-based NGS system. These results suggest that ctDNA could be a novel diagnostic biomarker to monitor changes in mutational status and tumor burden in patients with mCRC, and a predictive marker for survival in patients with advanced pancreatic cancer. Citation Format: Hitoshi Zembutsu, Hiroki Osumi, Eiji Shinozaki, Kensei Yamaguchi, Masato Ozaka, Takashi Sasaki, Marie Muramatsu, Naoki Sasahira. Circulating tumor DNA assessed through amplicon-based next-generation sequencing and its clinical application [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3990.