Abstract 2962: Clinical relevance of circulating cell-free DNA using amplicon-based next-generation sequencing panel in colorectal cancer patients with liver metastasis

Abstract

Abstract Background: Recent advances in the next-generation sequencing technique (NGS) for the detection of cell-free DNA (cfDNA) will be possible to provide the utility as diagnostic and prognostic biomarkers of cancer. We conducted the study of feasibility to detect plasma cfDNA from patients with metastatic colorectal cancer (mCRC) using NGS panel and investigated their relationship with clinicopathological factors. Methods: A total of 101 mCRC patients with liver metastasis, who had been treated with chemotherapy, were enrolled in this study from February to June in 2017. We investigated i) frequency of detectable mutations in plasma cfDNA, ii) concordance rate of RAS mutation between the DNA extracted from tissues and the plasma cfDNA, iii) relationship between the mutation allele frequencies (MAF) and clinicopathological factors including tumor location, metastatic site, number of metastatic organs, tumor marker (CEA and CA19-9), LDH level, D-dimer level and sum of the tumor diameter measured based on RECIST ver1.1 criteria. Sequencing of plasma cfDNA were performed using Ion Torrent™ Oncomine™ Colon cfDNA Assay. Results: Mutations in plasma cfDNA were detected in 87.1% (88/101) of patients. The frequencies of plasma cfDNA mutation at TP53, KRAS, APC, and PIK3CA were 68.3%, 38.6%, 23.7%, and 14.8%, respectively. RAS mutational concordance rate between DNA extracted from tumor and cfDNA was 76.2% (77/101). MAF were significantly associated with CEA (P<0.0001), CA19-9 (P=0.006), LDH (P<0.0001) and number of metastatic organs (P<0.0001). Patients with liver or lymph node metastasis had significantly higher MAF compared with those without metastases (Liver: P<0.0001, Lymph node: P=0.008). Positive correlations between CEA level, CA19-9 level, LDH level, tumor diameter and MAF were observed. (CEA: r=0.52, CA19-9: r=0.34, LDH: r=0.55, tumor diameter: r=0.57) Conclusions: Our results suggested that this cfDNA Assays could detect mutations at a high rate of mCRC patients undergoing chemotherapy and cfDNA analysis using NGS panel could be useful method of diagnostic biomarkers to monitor the change of RAS status and tumor burden. <!–EndFragment–> Citation Format: Hiroki Osumi, Eiji Shinozaki, Hitoshi Zembutsu, Yoshinori Takeda, Takeru Wakatsuki, Takashi Ichimura, Yumiko Ota, Izuma Nakayama, Mariko Ogura, Mitsukuni Suenaga, Daisuke Takahari, Keisho Chin, Akio Saiura, Kensei Yamaguchi. Clinical relevance of circulating cell-free DNA using amplicon-based next-generation sequencing panel in colorectal cancer patients with liver metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2962.