Detection rate and prognostic value of circulating tumor cells and circulating tumor DNA in metastatic uveal melanoma.
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.
Department of Medical Oncology, Institut Curie, Paris, France; Laboratory of Circulating Tumor Biomarkers, Institut Curie, Paris, France.
François-Clément
FC
Bidard
Jordan
J
Madic
Pascale
P
Mariani
Sophie
S
Piperno-Neumann
Aurore
A
Rampanou
Vincent
V
Servois
Nathalie
N
Cassoux
Laurence
L
Desjardins
Maud
M
Milder
Isabelle
I
Vaucher
Jean-Yves
JY
Pierga
Ronald
R
Lebofsky
Marc-Henri
MH
Stern
Olivier
O
Lantz
D000293:Adolescent; D000328:Adult; D004273:DNA, Neoplasm / Q000097:blood*; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating; D011379:Prognosis; D014604:Uveal Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D000098943:Uveal Melanoma
D004273:DNA, Neoplasm; C554062:GNA11 protein, human; C554061:GNAQ protein, human; D044385:GTP-Binding Protein alpha Subunits; D043802:GTP-Binding Protein alpha Subunits, Gq-G11
circulating tumor DNA; circulating tumor cells; metastasis; uveal melanoma