Published in:
01-07-2017 | Original Article
Prognostic value of chemotherapy-resistant CK19mRNA-positive circulating tumor cells in patients with advanced/metastatic non-small cell lung cancer
Authors:
G. Milaki, I. Messaritakis, F. Koinis, A. Kotsakis, S. Apostolaki, E. K. Dermitzaki, M. Perraki, D. Hatzidaki, V. Georgoulias
Published in:
Cancer Chemotherapy and Pharmacology
|
Issue 1/2017
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Abstract
Background
The detection of circulating tumor cells (CTCs) is of prognostic significance in several tumor types. The present study evaluated the detection and the clinical relevance of CK19mRNA(+) CTCs in patients with advanced/metastatic non-small cell lung cancer before and after front-line chemotherapy.
Patients and methods
Peripheral blood was obtained from 642 patients with treatment-naïve unresectable stage IIIB and IV non-small cell lung cancer and from 455 patients after the completion of 1st line chemotherapy. RNA was extracted from peripheral blood mononuclear cells and the detection of CK19mRNA-positive cells was performed using a quantitative PCR assay.
Results
Based on the detection limit of the assay, 167 (26.0%) patients had detectable CK19mRNA(+) CTCs at baseline. The detection of CK19mRNA(+) CTCs before treatment was not associated with the clinical outcome, but their detection at the end of chemotherapy was associated with significantly decreased PFS and OS [PFS: 2.6 vs 3.8 months (p = 0.008); OS: 5.7 vs 10.0 months (p = 0.006) for CK19mRNA(+) vs CK19mRNA(−) patients, respectively]. Multivariate analysis revealed that the detection of CK19mRNA(+) CTCs both before and after chemotherapy emerged as an independent factor associated with reduced PFS (HR: 1.778; p < 0.001) and OS (HR: 1.608; p = 0.001).
Conclusion
The detection of peripheral blood CK19mRNA(+) CTCs before and after the completion of front-line chemotherapy is an adverse prognostic factor associated with poor clinical outcome in patients with stage IIIB/IV non-small cell lung cancer.