Circulating tumor cells and detection of EGFR mutation in cell-free tumor DNA in blood plasma in metastatic non-small cell lung cancer with EGFR mutation.

Abstract

7595 Background: The purpose of this study was to assess the correlation between the numbers of circulating tumor cells (CTCs), prognosis and the positivity of blood plasma EGFR mutation in cell-free tumor DNA in metastatic non-small cell lung cancer with positive epidermal growth factor receptor (EGFR) gene mutation in the primary site. Methods: Of the 20 patients with primary lung cancer who showed EGFR mutaion in the primary site, CTCs were counted using CellSearch system (Veridex) after the appearance of EGFR TKI resistance. Furthermore, cell-free tumor DNA was extracted from blood plasma samples of the 20 patients by QIAamp Circulating Nucleic Acid Kit (Qiagen), and was analyzed for EGFR mutation using cycleave real-time PCR assay. Results: Patient characteristics included 5 males and 15 females with a mean age of 64.1 yrs (43 to 82), performance status of 0 in 5, 1 in 11, and 2 in 4, respectively. Pathological classification of lung cancer were adenocarcinoma in 19, squamous cell carcinoma in 1, clinical stage were stage IV in 15 and recurrence after surgical resection in 5 with distant metastases, respectively. The localization of EGFR mutation in the primary site were exon 18 G719C in 1, exon 18 G725A + exon 19 deletion in 2, exon 19 deletion in 7, exon21 L858R in 9, exon 18 G791S + exon 21 L858R in 1→ exon 18 G719S + exon 21 L858R in 1, respectively. CTCs were detected in 7 out of 20 cases (35%). Numbers of CTCs ( per 7.5 ml) were 1 in 3 cases, 3 in 1 case, 8 in 1 case, 14 in 1 case, and 24 in 1 case, respectively. Negative CTCs group showed a significant longer survival than that of positive CTCs group (³a1 / 7.5 ml) from the times of detecting CTCs (MST: not reached vs. 3.8 months, p < 0.05). EGFR mutation in tumor cell-free DNA in blood plasma were detected in 6 out of 20 cases (30%). The lacalization of detected EGFR mutation were same as their primary site, without any new resistance mutation. Positive detective rates of EGFR mutation in blood plasma were 71.1% (5 out of 7 cases) in positive CTCs group and 7.7% (1 out of 13 cases) in negative CTCs group (p < 0.05). Conclusions: The numbers of CTCs were correlated not only prognosis but also the positivity of EGFR mutation in cell-free tumor DNA in blood plasma.