title: 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.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Hematology & Oncology, University of Kansas Medical Center , Westwood, KS , USA ; Subspecialty Medicine, Kansas City VA Medical Center , Kansas City, MO , USA.
authors.forename: Chao H
authors.initials: CH
authors.lastname: Huang
authors.affiliation: Department of Biostatistics, University of Kansas , Kansas City, KS , USA.
authors.forename: Jo A
authors.initials: JA
authors.lastname: Wick
authors.affiliation: Therapeutics for Rare and Neglected Diseases, National Center for Advancing Translational Sciences, National Institutes of Health , Rockville, MD , USA.
authors.forename: Gurusingham Sitta
authors.initials: GS
authors.lastname: Sittampalam
authors.affiliation: Princess Margaret Cancer Center, University Health Network , Toronto, ON , Canada.
authors.forename: Victor Sanjit
authors.initials: VS
authors.lastname: Nirmalanandhan
authors.affiliation: VA Nebraska Western Iowa Health Care System, Division of Oncology-Hematology, Department of Internal Medicine, University of Nebraska Medical Center , Omaha, NE , USA.
authors.forename: Apar Kishor
authors.initials: AK
authors.lastname: Ganti
authors.affiliation: Division of Hematology & Oncology, University of Kansas Medical Center , Westwood, KS , USA.
authors.forename: Prakash C
authors.initials: PC
authors.lastname: Neupane
authors.affiliation: Division of Hematology & Oncology, University of Kansas Medical Center , Westwood, KS , USA.
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Williamson
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Kansas Medical Center , Kansas City, KS , USA.
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Godwin
authors.affiliation: Clinical Molecular Oncology Laboratory, University of Kansas Medical Center , Kansas City, KS , USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Schmitt
authors.affiliation: Division of Hematology & Oncology, University of Kansas Medical Center , Westwood, KS , USA.
authors.forename: Nora J
authors.initials: NJ
authors.lastname: Smart
authors.affiliation: Subspecialty Medicine, Kansas City VA Medical Center , Kansas City, MO , USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Spencer
authors.affiliation: Division of Hematology & Oncology, University of Kansas Medical Center , Westwood, KS , USA ; Subspecialty Medicine, Kansas City VA Medical Center , Kansas City, MO , USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Van Veldhuizen
keywords: biomarkers; circulating tumor cells; extensive stage; prognosis; small-cell lung carcinoma