Concordance of mutations identified using circulating tumor DNA (ctDNA) compared to tissue based next generation sequencing (NGS) in gastrointestinal malignancies: A single institution experience.

Abstract

e23023 Background: The role of the ctDNA in the management of solid organ malignancies is an area of active research. A potential application of this technology is for monitoring disease progression in patients who had sequencing of their tumor tissue at time of diagnosis. This approach relies on concordance between tumor tissue NGS and the ctDNA, which can vary due to biology and technology. Biologic variability can be due to tumor heterogeneity, ctDNA concentration fluctuations and genomic alterations in clonal non-malignant hematopoietic cells. Methods: We retrospectively evaluated 41 patients who had NGS with Foundation Medicine’s FM1 panel performed on tumor tissue from diagnosis and follow up ctDNA NGS using the Guardant 360 panel(G360). Only genes shared by both panels with the same level of gene coverage were evaluated. This eliminated several genes and alterations, particularly amplifications and splice site alterations. Results: Patient demographics are in Table 1. 148 alterations were identified by G360, of which 42 (28%) alterations were also seen on FM1 testing. When these alterations were restricted to KRAS, APC and TP53, the most common genes altered in GI cancers, 53 alterations were identified and 32 (60%) were also identified by FM1 testing. These results demonstrate that concordance between ctDNA and tissue NGS can be improved if restricted to driver mutations. This restriction eliminates potential passenger mutations acquired by subclones of the original tumor and controls for clonal hematopoiesis. Conclusions: It is difficult to base treatment decisions on the overall concordance seen here between ctDNA and tissue NGS. However, quantification of driver mutations using ctDNA may offer another monitoring tool for disease progression beyond tumor markers, which sometimes can be non-specific or absent.