Circulating tumor cells as a prognostic factor in patients with small cell lung cancer

Abstract

The detection of circulating tumor cells (CTCs) in peripheral blood is currently an important field of study. Detection of CTCs by the OBP-401 assay (TelomeScan^®) has previously been reported to be useful in the diagnosis, prognosis and evaluation of therapeutic efficacy in breast and gastric cancer. The aim of the present study was to evaluate the OBP-401 assay as a novel method of detecting CTCs of small cell lung cancer (SCLC) patients and to evaluate whether CTC count is associated with prognosis. Prospectively, 30 consecutively diagnosed SCLC patients who had commenced chemotherapy or chemoradiotherapy were enrolled as subjects of the current study. Peripheral blood specimens were collected from the SCLC patients prior to and following the initiation of treatment and the viable CTCs were detected in the specimens following incubation with a telomerase-specific, replication-selective, oncolytic adenoviral agent, which was carrying the green fluorescent protein gene. CTCs were detected in 29 patients (96%). The group of 21 patients with a CTC count of <2 cells/7.5 ml prior to treatment (baseline) had a significantly longer median survival time than the group of eight patients with a CTC count of ≥2 cells/7.5 ml prior to treatment (14.8 and 3.9 months, respectively; P=0.007). The results of a multivariate analysis showed that the baseline CTC count was an independent prognostic factor for survival time (hazard ratio, 3.91; P=0.026). Among the patients that achieved a partial response to treatment, patients who had a CTC count of <2 cells/7.5 ml following two cycles of chemotherapy tended to have a longer median progression-free survival compared with patients who had a CTC count of ≥2 cell/7.5 ml (8.3 and 3.8 months, respectively; P=0.07). Therefore, CTCs may be detected via OBP-401 assay in SCLC patients and the CTC count prior to treatment appears to be a strong prognostic factor.

Keywords: OBP-401 assay; circulating tumor cells; prognostic factor; small cell lung cancer.

Figure 1

Immunocytochemical analysis of a GFP-positive cell from a small cell lung cancer patient. The glass slides of circulating tumor cells were processed by immuocytochemical analysis. Cytokeratin was detected with anti-pan cytokeratin antibody (magnification, ×20). GFP, green fluorescent protein.

Figure 2

Overall survival of patients according to the CTC count at baseline. CTC, circulating tumor cell; CI, confidence interval.

Figure 3

Progression-free survival according to the CTC count of patients with a partial response following two cycles of chemotherapy. CTC, circulating tumor cell; CI, confidence interval.