title: Prognostic value of circulating tumor cells' reduction in patients with extensive small-cell lung cancer.
abstract: OBJECTIVE
  Circulating tumor cells (CTCs) have been hypothesized to be a prognostic factor in small-cell lung cancer (SCLC), and different cutoffs have been proposed to identify patients at high risk. We assessed the prognostic value of CTCs in patients with extensive SCLC.
  
  
  METHODS
  CTCs were assessed with the CellSearch system in 60 extensive SCLC patients. CTC count at baseline or after one cycle of chemotherapy (cycle-1) or as change after chemotherapy were analyzed separately. Primary outcome was overall survival. The accuracy of prognostic role was assessed by Harrell's c-index. "Optimal" cutoffs were derived by bootstrap resampling to reduce the overfitting bias; accuracy improvement was estimated by calculating the difference of c-indexes of models including clinical variables with or without CTCs.
  
  
  RESULTS
  CTCs were identified in 90% (54/60) of patients at baseline, in which CTC count ranged from 0 to 24,281. CTC count was strongly associated with the number of organs involved. The prognostic accuracy was only marginally increased by the addition to clinical information of "optimal" CTC cutoffs at baseline and after cycle-1. Conversely, a reduction of CTC count higher than 89% following chemotherapy significantly improved prognostic accuracy (bootstrap p-value=0.009) and was associated with a lower risk of death (HR 0.24, 95% CI 0.09-0.61). When previously proposed cutoffs were applied to our cohort, they showed only marginal improvement of the prognostic accuracy.
  
  
  CONCLUSIONS
  CTCs have useful prognostic role in extensive SCLC, but only the change of CTC count after the first cycle of chemotherapy provides clinically relevant information. Previously reported CTC cutoffs were not prognostic in our cohort of patients.
authors.affiliation: Cell Biology and Biotherapy Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - IRCCS, Napoli, Italy. Electronic address: nicnorm@yahoo.com.
authors.forename: Nicola
authors.initials: N
authors.lastname: Normanno
authors.affiliation: Division of Medical Oncology, S.G. Moscati Hospital, Avellino, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rossi
authors.affiliation: Medical Oncology Unit, Department of Thoracic Surgical and Medical Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - IRCCS, Napoli, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Morabito
authors.affiliation: Medical Statistics, Second University, Napoli, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Signoriello
authors.affiliation: Cell Biology and Biotherapy Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - IRCCS, Napoli, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Bevilacqua
authors.affiliation: Clinical Trials Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - IRCCS, Napoli, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Maio
authors.affiliation: Medical Oncology Unit, Department of Thoracic Surgical and Medical Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - IRCCS, Napoli, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Costanzo
authors.affiliation: Cell Biology and Biotherapy Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - IRCCS, Napoli, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: De Luca
authors.affiliation: Medical Oncology Unit, Department of Thoracic Surgical and Medical Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - IRCCS, Napoli, Italy.
authors.forename: Agnese
authors.initials: A
authors.lastname: Montanino
authors.affiliation: Division of Medical Oncology, S.G. Moscati Hospital, Avellino, Italy.
authors.forename: Cesare
authors.initials: C
authors.lastname: Gridelli
authors.affiliation: Division of Thoracic Surgery, Department of Thoracic Surgical and Medical Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - IRCCS, Napoli, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Rocco
authors.affiliation: Clinical Trials Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - IRCCS, Napoli, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Perrone
authors.affiliation: Medical Statistics, Second University, Napoli, Italy.
authors.forename: Ciro
authors.initials: C
authors.lastname: Gallo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002452:Cell Count; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011379:Prognosis; D015203:Reproducibility of Results; D055752:Small Cell Lung Carcinoma / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology*
keywords: Chemotherapy; Circulating tumor cells; Extensive stage; Prognosis; Small-cell lung cancer; Validation