Peripheral blood circulating tumor DNA (ctDNA) and tumor tissue next-generation sequencing (NGS) is routinely performed to guide therapy in cancer patients. However, little is known about the concordance or discordance between commercially available tissue genomics testing panels and ctDNA. The aim of our study was to assess concordance between matched cancer tissue genomics and blood based ctDNA in lung and gastrointestinal (GI) cancers.
Tissue genomic analysis was performed with Paradigm® (n = 17)/Caris® (n = 11) and ctDNA was analyzed with Guardant360® (n = 28). Samples included, non-small cell lung cancer (n = 10), small cell lung cancer (n = 4), colorectal cancer (n = 5), hepatocellular carcinoma (n = 2), intrahepatic cholangiocarcinoma (n = 1), pancreatobiliary adenocarcinoma (n = 3), esophageal adenocarcinoma (n = 2) and gastric adenocarcinoma (n = 1).
We identified 6 (21%) patients with at least one gene mutation that was detected by both tissue genomic and ctDNA analysis. Total number of gene mutations identified in 28 patients were 106, but only 8 (7.5%) were detected by both tissue and ctDNA panels. When this testing was done within 90 days the concordance increased to 10.20%. Table.Table:
|Patients with at least one mutation detected by both platforms||21% (n = 6/28)|
|Mutations detectable by both platforms||7.54% (n = 8/106)|
|Mutations detectable by both platforms if interval between tissue and blood collection |
We identified significant discordance between tissue and ctDNA mutational profiles in lung and GI cancers. Therefore, the results from NGS platforms should be interpreted with extreme caution. Our analysis reveals that these platforms should not be used interchangeably. The discordance rate may be due to tissue heterogeneity and/or spatial and temporal clonal evolution. Standardization of the sequencing techniques and education of practicing oncologists about the limitations of liquid biopsies needs to be highlighted.
Clinical trial identification
Legal entity responsible for the study
Saint Luke’s Health System
J. Subramanian: Paradigm Advisory board. All other authors have declared no conflicts of interest.