Nadia Dandachi1, Verena Tiran2, Joerg Lindenmann3, Luka Brcic4, Nicole Fink-Neuboeck3, Karl Kashofer4, Gudrun Absenger2, Angelika Bezan2, Richard J Cote5, Ram Datar5, Marija Balic6. 1. Medical University of Graz, Division of Oncology, Department of Internal Medicine, Austria; Medical University of Graz, Research Unit Epigenetic and Genetic Cancer Biomarkers, Austria. Electronic address: nadia.dandachi@medunigraz.at. 2. Medical University of Graz, Division of Oncology, Department of Internal Medicine, Austria. 3. Medical University of Graz, Division of Thoracic and Hyperbaric Surgery, Department of Surgery, Austria. 4. Medical University of Graz, Institute of Pathology, Austria. 5. University of Miami Miller School of Medicine, Department of Pathology, Miami, FL, United States. 6. Medical University of Graz, Division of Oncology, Department of Internal Medicine, Austria; Medical University of Graz, Research Unit Circulating Tumor Cells and Cancer Stem Cells, Austria.
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.
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.