Abstract 5668
Background
Concordance between whole genome sequencing (WGS)/whole exome sequencing (WES) and circulating tumor DNA (ctDNA) is not known. Therefore, we studied concordance between matched WGS/WES and ctDNA in various solid tumors. In addition, we carried out an analysis of hotspot and actionable alterations in our data.
Methods
Retrospective analysis of 64 stage III/IV solid tumors (Gastrointestinal n = 20 Breast n = 12 Lung n = 19 Other n = 13) who underwent matched WGS/WES and ctDNA (77 genes) by commercially available platforms. Concordance was determined at patient and gene levels.
Results
Patient concordance between tissue and ctDNA results was 58% (n = 37). Concordance was higher when patients received systemic chemotherapy prior to tissue NGS and ctDNA compared to no chemotherapy (78% n = 21 Vs 43% n = 12, respectively p = 0.01) and positively correlated increasing tumor mutation burden. There was no significant difference in concordance when time interval between tissue NGS and ctDNA analysis was evaluated (55% n = 24 Vs 65% n = 13, <90 days Vs > =90 days respectively p = 0.20). Similarly, no statistical difference in concordance was found when tissue NGS was done on primary or metastatic sites (48% n = 12 Vs 64% n = 25, respectively p = 0.20). TMB positively correlated with the number of ctDNA mutations only in those who received chemotherapy (r(25)=0.74 p < 0.0001) but did not correlate in chemotherapy naïve (r(27)=0.11 p = 0.60). Gene level concordance between tissue and ctDNA was 21% across all tumor types. The most common concordant genes with somatic alterations across all tumors were TP53, KRAS, and PIK3CA. 121 hotspots were identified in tumor NGS and 63 were in ctDNA. Hotspot concordance was 34%. Tissue NGS identified 68 targetable alterations in 31 patients and ctDNA analysis identified 87 in 34 patients. 48 of these were concordant and 59 were discordant (tissue 20, ctDNA 39).
Conclusions
Our analysis noted significant discordance between WGS/WES and ctDNA analysis. TMB and prior chemotherapy may affect concordance between NGS and ctDNA. Tissue NGS and ctDNA are complementary modalities and incorporating ctDNA with tissue NGS can increase the likelihood of capturing additional targetable alterations.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
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