ERCC1 expression in circulating tumor cells (CTCs) using a novel detection platform correlates with progression-free survival (PFS) in patients with metastatic non-small-cell lung cancer (NSCLC) receiving platinum chemotherapy

Lung Cancer. 2012 Aug;77(2):421-6. doi: 10.1016/j.lungcan.2012.04.005. Epub 2012 May 1.

Abstract

Purpose: To utilize a novel circulating tumor cell (CTC) technology to quantify ERCC1 expression on CTCs and determine whether ERCC1 expression levels predict efficacy of platinum-based chemotherapy in patients with metastatic non-small-cell lung cancer (NSCLC).

Experimental design: ERCC1 expression was measured in 17 metastatic NSCLC patients who received platinum-based therapy and had ≥2 intact CTCs with acceptable ERCC1 expression assay results. ERCC1 levels were determined from average expression on individual CTCs in each sample. Progression-free survival (PFS) was calculated from the date of therapy initiation.

Results: PFS decreased with increasing ERCC1 expression (p<0.04, F-test, linear regression). Lack of ERCC1 expression was associated with longer PFS (266 days versus 172 days, log-rank, p<0.02) in a Kaplan-Meier analysis using ERCC expression level of 1 as a cutoff (range 0-30). The difference in survival was statistically significant with a hazard ratio of 4.20 (95% CI 1.25-14.1, p<0.02, log-rank). PFS was also observed to decrease with increased cytokeratin (CK) expression (p<0.01 long-rank (Cox regression) and F-test (linear regression)). The hazard ratio is 4.38 (95% CI 1.76-10.9) for each log-change in CK value until progression was noted on imaging.

Conclusion: Low expression of ERCC1 on CTCs correlates with PFS in patients with metastatic NSCLC receiving platinum-based therapy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Endonucleases / genetics
  • Endonucleases / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality*
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplastic Cells, Circulating / metabolism*
  • Platinum / therapeutic use

Substances

  • Antineoplastic Agents
  • DNA-Binding Proteins
  • Platinum
  • ERCC1 protein, human
  • Endonucleases