Abstract
We used computed tomography (CT) to explore the prognostic value of cell-free (cf) DNA quantification and its predictive efficacy over time after chemotherapy in non-small-cell lung cancer (NSCLC) patients. In total, 177 NSCLC patients were enrolled in a prospective biomarker trial. Consecutive paired blood collection was performed to determine cfDNA concentrations at baseline CT and throughout serial follow-ups. The best cfDNA cut-off value to predict progression-free and overall survival was determined using X-tile analysis. Among 112 chemo-naive patients with stage IV adenocarcinoma, 43 were available for follow-up analysis. Cox regression multivariate analysis indicated that a high cfDNA concentration was an independent negative prognostic factor for progression-free survival (hazard ratio: 2.60; 95% confidence interval: 1.65-4.10; p = 0.008) and overall survival (hazard ratio: 2.63; 95% confidence interval: 1.66-4.17; p < 0.001). However, cfDNA concentration changes during treatment did not correlate with radiological CT responses at first follow-up or best response. No pattern was noted in the percent change in the cfDNA concentration from baseline or subsequently measured level to progression. The serum cfDNA concentration is thus associated with NSCLC patient prognosis, but does not appear to be a clinically valid marker for tumor responses.
Highlights
Traditional biopsy from the primary tumor site has limitations due to its invasive nature [1]
Cox regression multivariate analysis indicated that a high cell-free deoxyribonucleic acid (cfDNA) concentration was an independent negative prognostic factor for progression-free survival and overall survival
The results indicated that an area under the curve (AUC) of 0.658 (p < 0.002; 95% confidence interval [Confidence interval (CI)]: 0.568-0.748) had 62.0% sensitivity and 67.5% specificity to discriminate stage IV patients (Supplementary Figure 1)
Summary
Traditional biopsy from the primary tumor site has limitations due to its invasive nature [1]. There is a renewed interest in liquid biopsy using circulating cell-free deoxyribonucleic acid (cfDNA) because of its potential to screen for tumors and disease progression in lung cancer [6]. Previous clinical trials have demonstrated that the amount of cfDNA is higher in patients with lung cancer than in healthy individuals [11, 12]. High baseline cfDNA concentrations have been found to worsen the survival outcomes of patients with lung cancer [13, 14]. Relatively few studies have investigated changes in cfDNA levels at specific periods during treatment [1521]. To date, detailed analyses of dynamic changes in the cfDNA concentration to predict the radiological tumor response have not been performed. Despite the growing interest in cfDNA as a potential biomarker for lung cancer, the clinical validity of cfDNA quantification remains inconclusive
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