Circulating tumor cells in small-cell lung cancer: a predictive and prognostic factor.

BACKGROUND Initial response of small-cell lung cancer (SCLC) to chemotherapy is high, and recurrences occur frequently, leading to early death. This study investigated the prognostic value of circulating tumor cells (CTCs) in patients with SCLC and whether changes in CTCs can predict response to chemotherapy. Patients and methods In this multicenter prospective study, blood samples for CTC analysis were obtained from 59 patients with SCLC before, after one cycle, and at the end of chemotherapy. CTCs were measured using CellSearch systems. RESULTS At baseline, lower numbers of CTCs were observed for 21 patients with limited SCLC (median = 6, range 0-220) compared with 38 patients with extensive stage (median = 63, range 0-14,040). Lack of measurable CTCs (27% of patients) was associated with prolonged survival (HR 3.4; P ≤ 0.001). CTCs decreased after one cycle of chemotherapy; this decrease was not associated with tumor response after four cycles of chemotherapy. CTC count after the first cycle of chemotherapy was the strongest predictor for overall survival (HR 5.7; 95% CI 1.7-18.9; P = 0.004). CONCLUSION Absolute CTCs after one cycle of chemotherapy in patients with SCLC is the strongest predictor for response on chemotherapy and survival. Patients with low initial CTC numbers lived longer than those with higher CTCs.

[1]  Max S Wicha,et al.  Circulating tumor cells: not all detected cells are bad and not all bad cells are detected. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  J M Bland,et al.  Statistical methods for assessing agreement between two methods of clinical measurement , 1986 .

[3]  Yukiko Nakamura,et al.  Prognostic Impact of Circulating Tumor Cells in Patients with Small Cell Lung Cancer , 2012, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[4]  Cai-cun Zhou,et al.  The International Association for the Study of Lung Cancer Staging Project: Proposals Regarding the Clinical Staging of Small Cell Lung Cancer in the Forthcoming (Seventh) Edition of the Tumor,Node,Metastasis Classification for Lung Cancer , 2008 .

[5]  K. Pienta,et al.  Circulating Tumor Cells Predict Survival Benefit from Treatment in Metastatic Castration-Resistant Prostate Cancer , 2008, Clinical Cancer Research.

[6]  A. Beckett,et al.  AKUFO AND IBARAPA. , 1965, Lancet.

[7]  E. Felip,et al.  clinical practice guidelines Small-cell lung cancer : ESMO Clinical Practice Guidelines for diagnosis , treatment and follow-up , 2010 .

[8]  B. Trump,et al.  Pulmonary smell cell carcinoma showing tripartite differentiation in individual cells. , 1981, Human pathology.

[9]  G. Hortobagyi,et al.  Circulating tumor cells and bone metastases as detected by FDG-PET/CT in patients with metastatic breast cancer. , 2010, Annals of oncology : official journal of the European Society for Medical Oncology.

[10]  K. Chìn,et al.  Circulating tumor cells as a surrogate marker for determining response to chemotherapy in patients with advanced gastric cancer , 2010, Cancer science.

[11]  H. Groen,et al.  Prognostic classification with laboratory parameters or imaging techniques in small-cell lung cancer. , 2007, Clinical lung cancer.

[12]  D. Sargent,et al.  Assessing the measure of a new drug: is survival the only thing that matters? , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[13]  G. Botti,et al.  A "live" biopsy in a small-cell lung cancer patient by detection of circulating tumor cells. , 2009, Lung cancer.

[14]  Michael Morse,et al.  Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  M. Okada,et al.  [New response evaluation criteria in solid tumours-revised RECIST guideline (version 1.1)]. , 2009, Gan to kagaku ryoho. Cancer & chemotherapy.

[16]  Caroline Dive,et al.  Evaluation and prognostic significance of circulating tumor cells in patients with non-small-cell lung cancer. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  T. Brezicka Expression of epithelial-cell adhesion molecule (Ep-CAM) in small cell lung cancer as defined by monoclonal antibodies 17-1A and BerEP4 , 2005, Acta oncologica.

[18]  Jonathan W. Uhr,et al.  Tumor Cells Circulate in the Peripheral Blood of All Major Carcinomas but not in Healthy Subjects or Patients With Nonmalignant Diseases , 2004, Clinical Cancer Research.

[19]  B. Johnson,et al.  Management of small-cell lung cancer. , 2002, Clinics in chest medicine.

[20]  Leon W.M.M. Terstappen,et al.  Circulating Tumor Cells versus Imaging—Predicting Overall Survival in Metastatic Breast Cancer , 2006, Clinical Cancer Research.

[21]  Li Zhang,et al.  Preliminary Investigation of the Clinical Significance of Detecting Circulating Tumor Cells Enriched from Lung Cancer Patients , 2009, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[22]  Kari Chansky,et al.  The IASLC Lung Cancer Staging Project: Proposals Regarding the Relevance of TNM in the Pathologic Staging of Small Cell Lung Cancer in the Forthcoming (Seventh) Edition of the TNM Classification for Lung Cancer , 2009, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[23]  S. Chinn Statistics in respiratory medicine. 2. Repeatability and method comparison. , 1991, Thorax.

[24]  Caroline Dive,et al.  Tumorigenesis and Neoplastic Progression Evaluation of Circulating Tumor Cells and Serological Cell Death Biomarkers in Small Cell Lung Cancer Patients Undergoing Chemotherapy , 2010 .

[25]  E. Brambilla,et al.  Cytotoxic chemotherapy induces cell differentiation in small-cell lung carcinoma. , 1991, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[26]  Edward L Spitznagel,et al.  Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[27]  E. Felip,et al.  Small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. , 2010, Annals of oncology : official journal of the European Society for Medical Oncology.

[28]  N. Saijo,et al.  Phase III study of intensive weekly chemotherapy with recombinant human granulocyte colony-stimulating factor versus standard chemotherapy in extensive-disease small-cell lung cancer. The Japan Clinical Oncology Group. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[29]  Alison Stopeck,et al.  Circulating tumor cells, disease progression, and survival in metastatic breast cancer. , 2004, The New England journal of medicine.