Abstract LB547: Ultra-deep targeted sequencing of circulating tumor DNA with colorectal cancer patients for prediction of treatment response and post-surgical follow-up

Abstract

Abstract Purpose: Colorectal cancer (CRC) patients require effective biomarkers to evaluate treatment efficacy and monitor minimal residual disease. However, current monitoring tools such as tumor markers and imaging methods have limited prognostic performance. Circulating-tumor DNA (ctDNA) could be a useful biomarker for monitoring patients with CRC. In this study, we evaluated the targeted next-generation sequencing (NGS) panel using ctDNA in monitoring clinical decision-making in CRC. Experimental Design: We prospectively enrolled 100 CRC patients and collected 197_ plasma samples. Specimens were collected post-surgery from 74 patients, 42 of whom were also monitored during the immediate post-surgery and adjuvant therapy follow-up. Twenty-six patients’ bloods were received after adjuvant therapy without surgery. A total of patients performed ultra-deep sequencing of CRC-related 14 genes respectively and matched with tissue samples at the time of blood collection as possible. NGS results were assessed correlation with clinicopathologic characteristics and clinical outcome. Results: Levels of ctDNA measurements were correlated with tumor stage. Stage IV patients had significantly higher ctDNA concentration than Stage I patients. ctDNA testing detected 112 alterations in 14 genes were identified in 69% of the patients (n=100). The results showed that APC (29%), TP53 (25%), KRAS (19%), and EGFR (5%) were the most frequently mutated genes. RAS family gene mutations were detected in 37 patients, yielding a concordance of 89% with tissue samples. Also, ctDNA detection was found to be a greater predictive performance when compared with CEA. Dynamics of ctDNA mutation levels reflected five follow-up patients’ clonal evolution and clinical outcomes. These data showed ctDNA is a sensitive monitoring biomarker for any clinical condition of the patients. Conclusions: The present study suggests that the use of ctDNA in CRC patients can be a valuable non-invasive monitoring tool for monitoring disease states during or after treatment. Serial ctDNA testing can contribute to improving patient management through monitoring disease progression and clonal evolution. Citation Format: Hyeonah Lee, Doo A Kim, Jieun Seo, Saeam Shin, Han Sang Kim, Joong Bae Ahn, Seung-Tae Lee, Jong Rak Choi. Ultra-deep targeted sequencing of circulating tumor DNA with colorectal cancer patients for prediction of treatment response and post-surgical follow-up [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB547.