Prognostic value of circulating tumor cells' reduction in patients with extensive small-cell lung cancer

Nicola Normanno, Antonio Rossi, Alessandro Morabito, Simona Signoriello, Simona Bevilacqua, Massimo Di Maio, Raffaele Costanzo, Antonella De Luca, Agnese Montanino, Cesare Gridelli, Gaetano Rocco, Francesco Perrone, Ciro Gallo

Research output: Contribution to journalArticle

Abstract

Objectives: 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. Materials and 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)314-319
Number of pages6
JournalLung Cancer
Volume85
Issue number2
DOIs
Publication statusPublished - 2014

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Keywords

  • Chemotherapy
  • Circulating tumor cells
  • Extensive stage
  • Prognosis
  • Small-cell lung cancer
  • Validation

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research
  • Medicine(all)

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