Prognostic role of circulating tumor cells in patients with EGFR-mutated or ALK-rearranged non-small cell lung cancer

Thorac Cancer. 2018 May;9(5):640-645. doi: 10.1111/1759-7714.12631. Epub 2018 Mar 27.

Abstract

Background: Circulating tumor cell (CTC) counts at baseline and follow-up are an independent prognostic factor in patients receiving standard chemotherapy for non-small cell lung cancer (NSCLC). This study further explored the role of CTCs in EGFR-mutated and ALK-rearranged NSCLC patients administered targeted therapies as first-line treatment.

Methods: CTCs were enumerated with a novel high-efficiency detection method from the blood of 43 patients with EGFR-mutated or ALK-rearranged NSCLC at baseline and at disease-progression. Patients were stratified into favorable and unfavorable groups with baseline CTC counts of < 8 or ≥ 8 CTCs/3.2 mL, respectively.

Results: A total of 76.7% of the patients were positive for ≥ 2 CTCs /3.2 ml blood at baseline. The median progression-free survival (PFS) and overall survival (OS) rates of the favorable compared to the unfavorable group were longer (11.6 vs. 8.5 months, P = 0.004 for PFS; 21.00 vs. 17.7 months, P = 0.013 for OS). Multivariate analysis demonstrated that baseline CTC count was a strong predictor of PFS (hazard ratio 2.835; 95% confidence interval 1.240-6.483; P = 0.014) and OS (hazard ratio 3.317; 95% confidence interval 1.360-8.092; P = 0.008).

Conclusion: Baseline CTC count could be a predictive biomarker for EGFR-mutated and ALK-rearranged NSCLCs, which allows for better guidance and monitoring of patients over the course of molecular targeted therapies.

Keywords: ALK; EGFR; circulating tumor cells; molecular targeted therapy; non-small cell lung cancer.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anaplastic Lymphoma Kinase / genetics*
  • Biomarkers, Tumor / genetics
  • Carcinoma, Non-Small-Cell Lung / blood
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Count
  • Crizotinib / administration & dosage
  • Crown Ethers / administration & dosage
  • Disease-Free Survival
  • ErbB Receptors / genetics
  • Female
  • Gefitinib / administration & dosage
  • Gene Rearrangement
  • Humans
  • Male
  • Middle Aged
  • Molecular Targeted Therapy
  • Neoplastic Cells, Circulating / metabolism
  • Neoplastic Cells, Circulating / pathology
  • Prognosis
  • Quinazolines / administration & dosage

Substances

  • Biomarkers, Tumor
  • Crown Ethers
  • Quinazolines
  • Crizotinib
  • icotinib
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • EGFR protein, human
  • ErbB Receptors
  • Gefitinib