Clinical importance of circulating tumor cells in lung cancer patients.

Abstract

e22109 Background: Assessment of the circulating tumor cells (CTCs) in lung cancer patients could prevent burdensome surgery in understaged cases. Therefore we have tested the hypothesis that the presence of CTCs is a negative prognostic factor in these patients and correlates with poor survival. Methods: This was a prospective study to test the presence of CTCs in peripheral blood, pulmonary blood and bone marrow in 108 lung cancer patients (75 males, 33 females; mean age 66.2 years, ranging from 29 to 82 years) at the time of surgery using real-time RT-PCR for carcinoembryonic antigen (CEA), epidermal growth factor receptor (EGFR), lung-specific X protein (LUNX) and hepatocyte growth factor receptor (c-met). Results: We found a statistically significant association between c-met expression level in the pulmonary blood and clinical stage (p<0.044) and lymph node involvement (p<0.0023). C-met marker also showed significantly higher positivity ratio in the peripheral (p<0.034) and pulmonary (p<0.04) blood in patients with histologically proven lymphatic metastases than in patients with negative lymph nodes. The positivity of CTCs in peripheral blood or bone marrow using c-met was independent of clinical stage, age, sex and grading using Cox regression analysis (p=0.006, resp. 0.001). 82 patients followed up for more than 1 year were involved into the overall survival (OS) analysis. 27 of them (32.9 %) died, the OS median was 19.8 months. The patients with the presence of CTCs in the peripheral blood or the bone marrow using c-met had significantly shorter OS and higher hazard ratio (p<0.024; HR=4.39 [95% CI: 1.58-12.22], resp. p<0.008; HR=5.08 [95% CI: 1.79-14.43]). In addition, patients with the presence of CTCs detected in bone marrow using CEA and/or c-met had significantly shorter OS (p<0.025; HR=3.08 [95% CI: 1.26-7.5]). Conclusions: Our study demonstrates that the presence of CTCs is independent negative prognostic factor in lung cancer patients. The analysis of CTCs is clinically feasible, reproducible and further studies focused on early clinical stages should demonstrate its applicability in individualization of adjuvant therapy in lung cancer patients and identification of individuals who would not benefit from extensive lung surgery.