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. 2014 Mar 1;134(5):1207-13.
doi: 10.1002/ijc.28436. Epub 2013 Sep 3.

Detection rate and prognostic value of circulating tumor cells and circulating tumor DNA in metastatic uveal melanoma

François-Clément Bidard  1 , Jordan Madic, Pascale Mariani, Sophie Piperno-Neumann, Aurore Rampanou, Vincent Servois, Nathalie Cassoux, Laurence Desjardins, Maud Milder, Isabelle Vaucher, Jean-Yves Pierga, Ronald Lebofsky, Marc-Henri Stern, Olivier Lantz
Affiliations

Detection rate and prognostic value of circulating tumor cells and circulating tumor DNA in metastatic uveal melanoma

François-Clément Bidard et al. Int J Cancer. .

Abstract

Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) have been recently investigated in several cancer types, but their respective clinical significance remains to be determined. In our prospective study, we compared the detection rate and the prognostic value of these two circulating biomarkers in patients with metastatic uveal melanoma. GNAQ/GNA11 mutations were characterized in archived tumor tissue. Using a highly sensitive and mutation-specific bidirectional pyrophosphorolysis-activated polymerization (bi-PAP) technique, GNAQ c.626A>T, GNAQ c.626A>C and GNA11 c.626A>T copy numbers were quantified in plasma from 12 mL of blood. CTCs were detected at the same time in 7.5 mL of blood by the CellSearch technique. Patient characteristics and outcome were prospectively collected. CTCs (≥1) were detected in 12 of the 40 included patients (30%, range 1-20). Among the 26 patients with known detectable mutations, ctDNA was detected and quantified in 22 (84%, range 4-11,421 copies/mL). CTC count and ctDNA levels were associated with the presence of miliary hepatic metastasis (p = 0.004 and 0.03, respectively), with metastasis volume (p = 0.005 and 0.004) and with each other (p < 0.0001). CTC count and ctDNA levels were both strongly associated with progression-free survival (p = 0.003 and 0.001) and overall survival (p = 0.0009 and <0.0001). In multivariate analyses, ctDNA appeared to be a better prognostic marker than CTC. In conclusion, ctDNA and CTC are correlated and both have poor prognostic significance. CTC detection can be performed in every patient but, in patients with detectable mutations, ctDNA was more frequently detected than CTC and has possibly more prognostic value.

Keywords: circulating tumor DNA; circulating tumor cells; metastasis; uveal melanoma.

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