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.

Chao H Huang,Nora J Smart,Jo A Wick,Gurusingham Sitta Sittampalam,Sarah Schmitt,Andrew K Godwin,Peter J Van Veldhuizen,Prakash C Neupane,Victor Sanjit Nirmalanandhan,Apar Kishor Ganti,Sarah Spencer,Stephen K Williamson

doi:10.3389/fonc.2014.00271

Abstract

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.

Highlights

Lung cancer is the leading cause of cancer death among men and women in the United States [1]
We enrolled 26 patients with EX-Small-cell lung cancer (SCLC), 1 was excluded due to ineligibility, all were treated with platinum and etoposide
If validated in other prospective studies, circulating tumor cells (CTCs) could be a useful biomarker in the management of EX-SCLC by predicting patients’ clinical responses to therapy

Summary

Introduction

Lung cancer is the leading cause of cancer death among men and women in the United States [1]. Small-cell lung cancer (SCLC) is a variant of lung cancer marked by early metastases, and it accounts for 13% of all lung cancers diagnosed in the United States. While we continue to pursue novel therapies for this disease, it is imperative that we concurrently pursue other strategies such as biomarker development to accurately monitor therapeutic responses, detect early progression, and predict clinical outcomes. 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

Results

Discussion

Conclusion