The following article features coverage from the European Society for Medical Oncology (ESMO) 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Results of a study comparing DNA next-generation sequencing (NGS) analyses performed on matched specimens of tumor tissue and circulating cell-free tumor DNA (ctDNA) from patients with advanced solid tumors showed concordance in only approximately one-fifth of the genes that were identified. The findings from this study were presented in a poster at the European Society for Medical Oncology (ESMO) Congress 2019 in Barcelona, Spain. 

The availability of targeted ctDNA sequencing assays — as well as the obstacles frequently encountered in obtaining tissue biopsies — make it increasingly likely that less-invasive ctDNA sequencing performed on blood specimens (ie, liquid biopsies) could someday supplant DNA sequencing assays that use tumor tissue. Nevertheless, uncertainties still exist regarding the level of concordance of these 2 approaches. 

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In the retrospective analysis, matched tumor and blood specimens obtained from 64 patients with stage III/IV solid tumors were analyzed using commercially available DNA sequencing tests, including a whole-genome assay, a whole-exome assay, or a 77-gene targeted ctDNA assay. 

A key finding from the study was that concordance between the results of these 2 types of assays was observed for only 58% of patients (37 individuals). Factors correlated with increased concordance included prior chemotherapy and a high tumor mutational burden, although the latter finding was only observed in those treated with chemotherapy. Neither the duration of time between performance of the tissue and ctDNA assays (ie, fewer than 90 days, or 90 or more days) nor the site of the tumor biopsy (ie, primary or metastatic lesion) was associated with concordance level.

When the 2 types of assays were compared at the gene level, concordance was only 21%. 

While 68 actionable alterations were identified in 31 patients using tissue-based NGS, 87 such alterations were identified in 34 patients using ctDNA-based sequencing. Notably, while 48 actionable alterations were identified by both types of assays, 59 alterations were identified by only 1 of the 2 assays. 

“When performed in isolation, tissue and ctDNA NGS can each potentially miss driver and targetable alterations,” the study authors noted. They further commented that “tissue NGS and ctDNA are complementary modalities and incorporating ctDNA with tissue NGS can increase the likelihood of capturing additional targetable alterations.”

Read more of Cancer Therapy Advisor‘s coverage of the ESMO annual meeting by visiting the conference page.

Reference

Imperial R, Nazer M, Pappas SG, et al. Matched whole-genome sequencing and whole-exome sequencing with circulating tumor DNA (ctDNA) analysis are complementary modalities in clinical practice. Presented at: European Society for Medical Oncology (ESMO) 2019 Congress; September 27-October 1, 2019: Barcelona, Spain. Abstract 2028P.