Frequency and clinical impact of preoperative circulating tumor cells in resectable non-metastatic lung adenocarcinomas

Lung Cancer. 2017 Nov:113:152-157. doi: 10.1016/j.lungcan.2017.10.003. Epub 2017 Oct 9.

Abstract

Objectives: Despite successful surgery, 30-50% of patients with resectable non-small cell lung cancer develop tumor recurrence within 5 years of surgery.

Materials and methods: In this prospective study, we performed CTC enumerations in 40 patients with non-metastatic lung adenocarcinoma (NMLA) using a size-based microfilter. Additionally, cfDNA isolated from plasma was analyzed in 35 out of 40 patients.

Results: CTCs were identified in 15 out of 40 patients (37.5%) with a range of 1-44 cells, whereas mutated cfDNA was only detected in 3 out of 35 patients (8.6%). Disease-free survival (DFS) was significantly associated with CTC positivity (log-rank p=0.025), grading (log-rank p=0.019), tumor stage (log-rank p=0.025) and lymph node status (log-rank p=0.029). Multivariate analysis, including tumor stage and grading, showed that CTC positivity (p=0.006), grading (0.039) and tumor stage (p=0.022) were independently associated with DFS.

Conclusion: Our study found that microfilter-based CTC enumeration in NMLA patients is an independent predictor of worse DFS. The used NGS-based cfDNA characterization had limited sensitivity to be clinically informative in our study cohort. CTC assessment before surgery can thus identify NMLA patients at high risk of disease recurrence.

Keywords: Circulating tumor cells; Lung cancer; Non-metastatic; Preoperative; Recurrence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / blood*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / genetics
  • Cell-Free Nucleic Acids / blood
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / blood*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Neoplastic Cells, Circulating / metabolism*
  • Neoplastic Cells, Circulating / pathology
  • Preoperative Period
  • Prognosis
  • Prospective Studies

Substances

  • Biomarkers, Tumor
  • Cell-Free Nucleic Acids