Evaluation of circulating cell-free DNA as a molecular monitoring tool in patients with metastatic cancer

Oncol Lett. 2020 Feb;19(2):1551-1558. doi: 10.3892/ol.2019.11192. Epub 2019 Dec 9.


The clinical decisions made when treating patients with metastatic cancer require knowledge of the current tumor extent and response to therapy. For the majority of solid tumors, a response assessment, which is based on imaging, is used to guide these decisions. However, measuring serum protein biomarkers (i.e. tumor markers) may be of additional use. Furthermore, tumor markers exhibit variable specificity and sensitivity and cannot therefore be solely relied upon when making decisions regarding cancer treatment. Therefore, there is a clinical requirement for the identification of specific, sensitive and quantitative biomarkers. In recent years, circulating cell-free DNA (cfDNA) and mutation-specific circulating cell-free tumor DNA (cftDNA) have been identified as novel potential biomarkers. In the current study, cfDNA and cftDNA were compared using imaging-based staging and current tumor markers in 15 patients with metastatic colorectal, pancreatic or breast cancer. These patients were treated at the Third Medical Department of Paracelsus Medical University Salzburg (Austria). The results of the current study demonstrated a statistically significant correlation between the concentration changes of cfDNA and cftDNA and response to treatment, which was assessed by imaging. A correlation was not indicated with current clinically used tumor markers, including carcinoembryonic antigen, carcinoma antigen 15-3 and carcinoma antigen 19-9. The present study also indicated a correlation between cfDNA and cftDNA and the tumor volume of metastatic lesions, which was not observed with the current clinically used tumor markers. In conclusion, cfDNA and cftDNA exhibit the potential to become novel biomarkers for the response assessment following cancer treatment, and may serve as a tool for the estimation of tumor volume. The current study further supports the increasingly important role of cfDNA and cftDNA as new monitoring tools for use during cancer therapy.

Keywords: circulating cell-free DNA; circulating cell-free tumor DNA; liquid biopsy; serum tumor markers; tumor burden; tumor-volumetry.