The effect of genetic alterations detected by the circulating tumor DNA-based next-generation sequencing technique on prognosis and survival in metastatic colorectal cancer

Abstract

Purpose: Studies conducted to date showed that circulating tumor DNA (ctDNA)-based next generation sequencing (NGS) panels are beneficial in the treatment strategies of patients with metastatic colorectal cancer (mCRC). In this study; we planned to determine the frequencies of various genetic alterations in patients with mCRC by ctDNA-based NGS analyses, evaluate the concordance rates by comparing these results with the results in standard polymerase chain reaction (PCR) analyses, and investigate the effect of the detected alterations on overall survival and progression-free survival. Materials and methods: The study was conducted by retrospective screening and analysis of the data on 48 patients, who were followed up with a diagnosis of mCRC and who received chemotherapy and/or biological agents. The data were analyzed using SPSS 25.0 [IBM SPSS Statistics 25 software (Armonk, NY: IBM Corp.)] package program. Results: In this study, ctDNA-based NGS analyses, compared to the quantitative PCR-based gold standard method, were found to have a sensitivity rate of 64.7%, specificity rate of 55.6% and concordance rate of 59.1% for KRAS mutation; a sensitivity rate of 100%, specificity rate of 86.7% and concordance rate of 87.1% for NRAS mutation; a sensitivity rate of 50%, specificity rate of 96.4% and concordance rate of 90.6% for BRAF mutation. In addition, concordance rates were evaluated based on to the time elapsed between the time of taking the liquid biopsy and tissue biopsy samples. As a result, concordance rates for KRAS, NRAS, and BRAF mutations were found to be 60.9%, 100%, and 100% respectively, in cases where this elapsed time was less than 6 months; and were found to be 57.1%, 78.9%, and 85% respectively, in cases where this elapsed time was more than 6 months. Furthermore, the comprehensive analyzes revealed that the frequency of many molecular changes in mCRC as well as the relationship of these changes with clinicopathological features and survival times. Conclusion: Our study demonstrates the clinical benefit of ctDNA-based NGS analyzes in patients with mCRC.