Kinetics of plasma cell-free DNA as a prospective biomarker to predict the prognosis and radiotherapy effect of esophageal cancer

Purpose. - The lack of reliable biomarkers for the prognosis and radiotherapy efficacy in esophageal cancer (EC) necessitates further research. The aim of our study was to investigate the predictive utility of plasma cell-free DNA (cfDNA) kinetics in patients with EC. Materials and methods. - We retrospectively analyzed the clinical data and cfDNA levels (pre-radiotherapy [pre-RT] and post-radiotherapy [post-RT]) and the cfDNA kinetics (cfDNA ratio: post-RT cfDNA/pre-RT cfDNA) of 88 patients. We employed Kaplan-Meier curves to examine the relationship between cfDNA and overall survival (OS) as well as progression-free survival (PFS). Univariate and multivariate Cox regression analyses were executed to ascertain the independent risk factors in EC. Results. - The pre-RT cfDNA levels were positively correlated with clinical stage (P = 0.001). The pre-RT cfDNA levels (cutoff value = 16.915 ng/mL), but not the post-RT cfDNA levels, were linked to a diminished OS (P < 0.001) and PFS (P = 0.0137). CfDNA kinetics (cutoff value = 0.883) were positively associated with OS (P = 0.0326) and PFS (P = 0.0020). Notably, we identified independent risk factors for OS in EC treated with RT, including cfDNA ratio (high/low) (HR = 0.447 [0.221-0.914] P = 0.025), ECOG (0/1/2) (HR = 0.501 [0.285-0.880] p = 0.016), and histological type (esophagal squamous cell carcinoma [ESCC]/non-ESCC) (HR = 3.973 [1.074-14.692] P = 0.039). Conclusion. - Plasma cfDNA kinetics is associated with prognosis and radiotherapy effect in EC undergoing RT, suggesting potential clinical application of a cheap and simple blood-based test.