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

Nadia Dandachi, Verena Tiran, Joerg Lindenmann, Luka Brcic, Nicole Fink-Neuboeck, Karl Kashofer, Gudrun Absenger, Angelika Bezan, Richard J Cote, Ram Datar, Marija Balic

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)152-157
Number of pages6
JournalLung Cancer
Volume113
DOIs
StatePublished - Nov 1 2017

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Circulating Neoplastic Cells
Disease-Free Survival
Neoplasm Grading
Recurrence
Adenocarcinoma of lung
Non-Small Cell Lung Carcinoma
Neoplasms
Cohort Studies
Multivariate Analysis
Lymph Nodes
Prospective Studies

Keywords

  • Circulating tumor cells
  • Lung cancer
  • Non-metastatic
  • Preoperative
  • Recurrence

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

Dandachi, N., Tiran, V., Lindenmann, J., Brcic, L., Fink-Neuboeck, N., Kashofer, K., ... Balic, M. (2017). Frequency and clinical impact of preoperative circulating tumor cells in resectable non-metastatic lung adenocarcinomas. Lung Cancer, 113, 152-157. https://doi.org/10.1016/j.lungcan.2017.10.003

Frequency and clinical impact of preoperative circulating tumor cells in resectable non-metastatic lung adenocarcinomas. / Dandachi, Nadia; Tiran, Verena; Lindenmann, Joerg; Brcic, Luka; Fink-Neuboeck, Nicole; Kashofer, Karl; Absenger, Gudrun; Bezan, Angelika; Cote, Richard J; Datar, Ram; Balic, Marija.

In: Lung Cancer, Vol. 113, 01.11.2017, p. 152-157.

Research output: Contribution to journalArticle

Dandachi, N, Tiran, V, Lindenmann, J, Brcic, L, Fink-Neuboeck, N, Kashofer, K, Absenger, G, Bezan, A, Cote, RJ, Datar, R & Balic, M 2017, 'Frequency and clinical impact of preoperative circulating tumor cells in resectable non-metastatic lung adenocarcinomas', Lung Cancer, vol. 113, pp. 152-157. https://doi.org/10.1016/j.lungcan.2017.10.003
Dandachi, Nadia ; Tiran, Verena ; Lindenmann, Joerg ; Brcic, Luka ; Fink-Neuboeck, Nicole ; Kashofer, Karl ; Absenger, Gudrun ; Bezan, Angelika ; Cote, Richard J ; Datar, Ram ; Balic, Marija. / Frequency and clinical impact of preoperative circulating tumor cells in resectable non-metastatic lung adenocarcinomas. In: Lung Cancer. 2017 ; Vol. 113. pp. 152-157.
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AU - Dandachi, Nadia

AU - Tiran, Verena

AU - Lindenmann, Joerg

AU - Brcic, Luka

AU - Fink-Neuboeck, Nicole

AU - Kashofer, Karl

AU - Absenger, Gudrun

AU - Bezan, Angelika

AU - Cote, Richard J

AU - Datar, Ram

AU - Balic, Marija

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N2 - 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.

AB - 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.

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