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 next-generation sequencing (NGS) performed on samples of tumor tissue and circulating cell-free tumor DNA (ctDNA) in patients with metastatic colorectal cancer showed an overall high level of concordance between these 2 types of assays. The findings from this study were reported at the European Society for Medical Oncology (ESMO) Congress 2019 in Barcelona, Spain.

Multiple biopsies are frequently needed to characterize underlying genomic alterations associated with treatment resistance in cancer. However, the invasive nature of tumor-tissue biopsies makes NGS of liquid biopsy specimens involving ctDNA an attractive alternative to multiple tumor tissue biopsies. Nevertheless, questions remain regarding the level of concordance between sequencing results obtained using tumor tissue vs ctDNA. 

Related Articles

This study involved an evaluation of NGS results performed on matched samples of tumor and ctDNA from 92 patients with metastatic colorectal cancer using commercially available sequencing assays. Separate analyses were performed depending on whether samples were collected from patients before (27 individuals) or after treatment was initiated (65 individuals). Clonal alterations (ie, alterations present in all tumor cells) were distinguished from subclonal alterations (ie, alterations present in only a fraction of tumor cells) in assays of ctDNA using a cutoff of 50% of the highest variant allele frequency reported for a particular alteration. 

A key finding of this study was that the concordance rate between the 2 types of assays with respect to clonal alterations was very high (96.3%) when samples were collected prior to treatment initiation, although it dropped to 64.6% when the samples were collected after treatment had been started (P =.001). 

Regarding the detection of subclonal alterations, similar concordance rates between the 2 types of assays were observed when biopsies were performed before (77.8%) or after (67.7%) the start of treatment (P =.452). 

Notably, the overall concordance rate with respect to detection of alterations in BRAF was 98.9%, and this result was independent of treatment or whether BRAF mutations were classified as clonal or subclonal. A similar finding was also reported for subclonal alterations in RAS, although for clonal RAS alterations, concordance rates were 96.3% and 80.0% for samples collected before and after treatment respectively (P =.058). 

Another finding of this study was a treatment-related decline in the concordance rate for gene amplifications (ie, 81.5% [before treatment]; 63.1% [after treatment]; P =.092) and with respect to the median of the highest variant allele frequency detected using a ctDNA sequencing assay (3.1% [before treatment]; 1.1% [after treatment] P =.092), although these differences were not statistically significant. 

In their concluding comments, the study authors wrote in the abstract that “liquid biopsies show a very high concordance rate in patients with metastatic colorectal cancer. It is important to take the timing of the assay into consideration alongside relevant clonal mutations while assessing the concordance of liquid biopsies, not just for metastatic colorectal cancer but for other malignancies.”

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

Reference

Kasi PM, Kamatham S, Shahjehan F, et al. Liquid biopsy concordance based on clonality and timing of testing in patients with metastatic colorectal cancer. Presented at: European Society for Medical Oncology (ESMO) Congress 2019; September 27–October 1, 2019: Barcelona, Spain. Abstract 622P.