Predictive and prognostic value of folate receptor-positive circulating tumor cells in small cell lung cancer patients treated with first-line chemotherapy

Oncotarget. 2017 Jul 25;8(30):49044-49052. doi: 10.18632/oncotarget.17039.

Abstract

To assess the predictive and prognostic significance of folate receptor (FR)-positive circulating tumor cells (CTCs) in patients with small cell lung cancer (SCLC) received first-line chemotherapy. Eligible patients with chemotherapy-naïve, unresectable SCLC were enrolled and blood samples were collected. CTCs were enumerated using ligand-targeted polymerase chain reaction (LT-PCR) at baseline, after two cycles of chemotherapy regimen and on disease progression. In total, 80 patients were enrolled and 67 (83.8%) had positive CTC count at baseline (CTCs ≥ 8.7 FU/3mL). The baseline CTC counts in patients with partial response (PR) were significantly higher than those with progression disease (PD) (P = 0.0365). An obvious reduction of CTC enumeration after two cycles of chemotherapy was significantly correlated with PR (P = 0.0380), instead of SD (P = 0.4934). Among positive CTC count group, patients with relative low CTC level had significantly longer progression-free survival (PFS) and overall survival (OS) than those with high CTC level (PFS: 9.1 vs 6.9 months, P = 0.0458; OS: 11.1 vs 8.6 months, P = 0.056). In multivariate analysis, distant metastases (HR = 1.466, P = 0.021) and relative low CTC level (HR = 0.656, P = 0.049) were the independent predictive factors for patients with SCLC received first-line chemotherapy. The present results demonstrated that baseline CTC counts could be the valuable predictive and prognostic biomarker for patients with SCLC received first-line chemotherapy. The reduction of CTC enumeration after two cycles of chemotherapy was a potential predictor of chemotherapeutic response in SCLC.

Keywords: circulating tumor cell; count; small cell lung cancer.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor
  • Cell Count
  • Disease Progression
  • Female
  • Folate Receptors, GPI-Anchored / metabolism*
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neoplastic Cells, Circulating / metabolism*
  • Neoplastic Cells, Circulating / pathology
  • Prognosis
  • Small Cell Lung Carcinoma / drug therapy
  • Small Cell Lung Carcinoma / metabolism*
  • Small Cell Lung Carcinoma / mortality*
  • Small Cell Lung Carcinoma / pathology
  • Survival Analysis
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Folate Receptors, GPI-Anchored