Next-generation sequencing (NGS) of cell-free circulating tumor DNA and tumor tissue in patients with advanced urothelial cancer: a pilot assessmen... - PubMed - NCBI
Ann Oncol. 2017 Oct 1;28(10):2458-2463. doi: 10.1093/annonc/mdx405.
Next-generation sequencing (NGS) of cell-free circulating tumor DNA and tumor tissue in patients with advanced urothelial cancer: a pilot assessment of concordance.
Barata PC1,
Koshkin VS1,
Funchain P1,
Sohal D1,
Pritchard A1,
Klek S1,
Adamowicz T2,
Gopalakrishnan D3,
Garcia J1,
Rini B1,
Grivas P1.
Abstract
BACKGROUND:
Advances in cancer genome sequencing have led to the development of various next-generation sequencing (NGS) platforms. There is paucity of data regarding concordance of different NGS tests carried out in the same patient. METHODS:
Here, we report a pilot analysis of 22 patients with metastatic urinary tract cancer and available NGS data from paired tumor tissue [FoundationOne (F1)] and cell-free circulating tumor DNA (ctDNA) [Guardant360 (G360)]. RESULTS:
The median time between the diagnosis of stage IV disease and the first genomic test was 23.5 days (0-767), after a median number of 0 (0-3) prior systemic lines of treatment of advanced disease. Most frequent genomic alterations (GA) were found in the genes TP53 (50.0%), TERT promoter (36.3%); ARID1 (29.5%); FGFR2/3 (20.5%), PIK3CA (20.5%) and ERBB2 (18.2%). While we identified GA in both tests, the overall concordance between the two platforms was only 16.4% (0%-50%), and 17.1% (0%-50%) for those patients (n = 6) with both tests conducted around the same time (median difference = 36 days). On the contrary, in the subgroup of patients (n = 5) with repeated NGS in ctDNA after a median of 1 systemic therapy between the two tests, average concordance was 55.5% (12.1%-100.0%). Tumor tissue mutational burden was significantly associated with number of GA in G360 report (P < 0.001), number of known GA (P = 0.009) and number of variants of unknown significance (VUS) in F1 report (P < 0.001), and with total number of GA (non-VUS and VUS) in F1 report (P < 0.001). CONCLUSIONS:
This study suggests a significant discordance between clinically available NGS panels in advanced urothelial cancer, even when collected around the same time. There is a need for better understanding of these two possibly complementary NGS platforms for better integration into clinical practice. KEYWORDS:
bladder cancer; cell-free circulating tumor DNA; genomic alterations; next-generation sequencing; urothelial carcinoma
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