Prognostic value of circulating tumour cells in limited-stage small-cell lung cancer: analysis of the concurrent once-daily versus twice-daily radiotherapy (CONVERT) randomised controlled trial

Ann Oncol. 2019 Jul 1;30(7):1114-1120. doi: 10.1093/annonc/mdz122.

Abstract

Background: The clinical significance of circulating tumour cells (CTCs) in limited-stage small-cell lung cancer (LS-SCLC) is not well defined. We report a planned exploratory analysis of the prevalence and prognostic value of CTCs in LS-SCLC patients enrolled within the phase III randomised CONVERT (concurrent once-daily versus twice-daily chemoradiotherapy) trial.

Patients and methods: Baseline blood samples were enumerated for CTCs using CellSearch in 75 patients with LS-SCLC who were enrolled in the CONVERT trial and randomised between twice- and once-daily concurrent chemoradiation. Standard statistical methods were used for correlations of CTCs with clinical factors. Log-rank test and Cox regression analyses were applied to establish the associations of 2, 15 and 50 CTC thresholds with progression-free survival (PFS) and overall survival (OS). An optimal CTC count threshold for LS-SCLC was established.

Results: CTCs were detected in 60% (45/75) of patients (range 0-3750). CTC count thresholds of 2, 15 and 50 CTCs all significantly correlate with PFS and OS. An optimal CTC count threshold in LS-SCLC was established at 15 CTCs, defining 'favourable' and 'unfavourable' prognostic risk groups. The median OS in <15 versus ≥15 CTCs was 26.7 versus 5.9 m (P = 0.001). The presence of ≥15 CTCs at baseline independently predicted ≤1 year survival in 70% and ≤2 years survival in 100% of patients.

Conclusion: We report the prognostic value of baseline CTC count in an exclusive LS-SCLC population at thresholds of 2, 15 and 50 CTCs. Specific to LS-SCLC, ≥15 CTCs was associated with worse PFS and OS independent of all other factors and predicted ≤2 years survival. These results may improve disease stratification in future clinical trial designs and aid clinical decision making.

Trial registration: ClinicalTrials.gov identifier: NCT00433563.

Keywords: chemoradiotherapy; circulating tumour cells; limited disease; limited stage; prognosis; small-cell lung cancer.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chemoradiotherapy
  • Disease Progression
  • Dose Fractionation, Radiation
  • Female
  • Follow-Up Studies
  • Humans
  • Lung Neoplasms / blood*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neoplastic Cells, Circulating / drug effects
  • Neoplastic Cells, Circulating / pathology*
  • Neoplastic Cells, Circulating / radiation effects
  • Small Cell Lung Carcinoma / blood*
  • Small Cell Lung Carcinoma / pathology
  • Small Cell Lung Carcinoma / therapy*
  • Survival Rate

Associated data

  • ClinicalTrials.gov/NCT00433563