Use of Liquid Biopsy in Monitoring Colorectal Cancer Progression Shows Strong Clinical Correlation.

BACKGROUND: Patients with colorectal cancer (CRC) who are sensitive to epidermal growth factor antibodies inevitably acquire drug resistance. This study aimed to determine the usefulness of liquid biopsies for prognosis and clinical correlation.

MATERIALS AND METHODS: For liquid biopsy tests, we extracted blood from 140 CRC patients with matched tumor samples. Circulating tumor cells (CTCs) and tumor DNA (ctDNA) were extracted before surgery and treatment. Samples were quantified and tested for mutations in KRAS, NRAS and BRAF. Kaplan-Meier analyses were performed for different groups of patients for association to overall survival.

RESULTS: Among the 140 CRC cases, we observed good agreement collectively in the molecular signatures of CTCs and ctDNA with matched tumor specimens (97% concordance). Patients who were subsequently refractory to either cetuximab or panitumumab showed changes in the molecular profiles and were positive for KRAS, NRAS or BRAF. Interestingly, we observed that most of these changes were detected in CTCs analyses first. Stratified analyses conducted by the change in molecular profiles showed this group of patients to have worse survival outcome compared with the wild type group.

CONCLUSIONS: Monitoring CRC patients' molecular changes in response to treatment via CTCs and ctDNA can provide real-time information to disease changes. The study demonstrated that the emergence of secondary mutations were strongly associated to poorer survival after treatment.