Circulating tumor DNA (ctDNA) in nonmetastatic colorectal cancer (CRC): Potential role as a screening tool.

Abstract

518 Background: CRC screening significantly reduces cancer incidence and mortality. Participation rates in screening, both stool based and endoscopic, are often low. The value and safety of endoscopic screening in older individuals is also uncertain. Preliminary data indicate ctDNA can be detected in a high proportion of patients with early stage CRC, suggesting promise as a screening test that should have broad community acceptance. Methods: Plasma samples were collected at diagnosis from 100 patients (pts) with newly diagnosed CRC. Surgical, clinicopathologic and outcome data were prospectively captured. All samples were sent to Johns Hopkins Kimmel Cancer Center, where tumors were sequenced using a panel of 15 genes frequently mutated in CRC to identify candidate mutations for ctDNA analysis. For each pt, one tumor mutation was selected to assess for ctDNA in plasma samples using the Safe-SeqS digital genomic assay. Results: Preliminary data is available on 68 pts. Median follow-up is 15.2 months. Candidate mutations for ctDNA analysis were identified in all cases, with a matching mutation detectable in the plasma cell-free DNA in 41 pts (60%). Median mutant allele fraction was 0.24% (range 0.11% - 8.39%). Tumor stage did not appear to have a major impact on the detection rate of ctDNA (Table), and ctDNA detection was independent of CEA levels. Five pts have recurred, all of whom had detectable ctDNA at diagnosis, whereas CEA was elevated in only 1 of these cases. Conclusions: Preliminary data suggests ctDNA is detectable at diagnosis in the majority of pts with non-metastatic CRC. The potential for ctDNA as a CRC screening tool, and as a prognostic marker for patients with early stage cancer, should be further explored. [Table: see text]