A multicenter pilot study examining the role of circulating tumor cells as a blood-based tumor marker in patients with extensive small-cell lung cancer

Background: Small-cell lung cancer (SCLC), a variant of lung cancer marked by early metastases, accounts for 13% of all lung cancers diagnosed in US. Despite high response rates to treatment, it is an aggressive disease with a median survival of 9-11 months for patients with extensive stage (EX-SCLC). Detection of circulating tumor cells (CTCs) is a novel laboratory technique currently in use to determine response to therapy and to predict prognosis in breast, colorectal, and prostate cancer. We initiated a pilot study to analyze the role of CTCs as a biomarker of response and relapse in patients with EX-SCLC. Methods: We collected blood samples from chemotherapy naïve patients with EX-SCLC prior to initiation of therapy, after completion of systemic therapy, and follow-up every 6-8 weeks and at relapse. The number of CTCs was determined using the cell search system in a central laboratory. The study was conducted in four different sites, and it was reviewed and approved by respective research review committees and IRBs. Results: We enrolled 26 patients with EX-SCLC, 1 was excluded due to ineligibility, all were treated with platinum and etoposide. We observed partial response in 16 patients, stable disease in 3 patients, 1 patient with disease progression, and 6 patients were not assessed (5 deceased, 1 not available). The overall median number of CTCs in 24 patients measured at baseline and post-tx was 75 (range 0-3430) and 2 (range 0-526), respectively. A significant reduction in CTCs from baseline to post-treatment was identified for 15 subjects; the median reduction was 97.4% (range -100 to +100%, p < 0.001). Higher baseline CTCs and percentage change in post-treatment CTCs were associated with decreased survival. Conclusion: We demonstrated that it is feasible to detect CTCs in EX-SCLC. If validated in other prospective studies, CTCs could be a useful biomarker in the management of EX-SCLC by predicting patients' clinical responses to therapy.