Circulating tumor DNA reflects therapy response in colorectal cancer

B40 Somatic mutations are known to drive human tumorigenesis and are suited as highly specific markers of neoplasia. Therefore, a potential approach is to measure mutant DNA fragments released by tumor cells into the circulation to determine tumor burden and to monitor therapy response. In our study the sensitive BEAMing (Beads, Emulsion, Amplification and Magnetics) assay was used to not only detect but also quantify mutant as well as wild-type DNA fragments in plasma. In a prospective study, 162 blood samples of 18 patients with primary and metastatic colorectal cancer who underwent multimodality treatment were longitudinally collected and analyzed. The number of mutant DNA fragments was compared to radiologic findings and values of carcinoembryonic antigen during therapy. We could identify circulating tumor DNA in all patients prior to treatment. Circulating tumor DNA levels dropped rapidly after surgical resection of the tumor but were still detectable in all patients who relapsed later. Furthermore, we were able to detect recurrence before any radiological or biochemical evidence of disease. We could identify circulating tumor DNA in all patients and reliably monitor tumor burden during the course of therapy. We see this approach as a powerful and promising tool for monitoring therapy response and disease progression which could be easily extended to other cancer types in the future.