P3.02-001 Clinical Significance of Plasma Epstein-Barr Virus DNA in Pulmonary Lymphoepithelioma-Like Carcinoma (LELC) Patients

Abstract

Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare subtype of non-small-cell lung cancer (NSCLC) and an Epstein-Barr virus (EBV)-associated epithelial neoplasm. We investigated the clinical significance of plasma concentrations of EBV DNA in pulmonary LELC patients. Two independent sets of plasma samples from a total of 429 patients with pulmonary LELC patients (287 initial and 142 confirmatory) were available for EBV DNA determination. Plasma samples from the patients were subjected to a real-time quantitative polymerase chain reaction (qPCR) before treatment and three months after radical resection. Cutoff points were determined for pretreatment plasma EBV DNA (low, <4000 copies/mL; high, ≥4000 copies/mL) on the basis of a measure of heterogeneity with the log-rank test statistic with respect to overall survival. Kaplan-Meier method and Cox regression were used to evaluate the relationship between plasma EBV DNA concentrations and clinical outcome. Among advanced stage pulmonary LELC patients who underwent sequential blood draws, we evaluated the relationship between change in disease status and change in EBV DNA concentrations using nonparametric tests. High EBV DNA concentration was associated with poor OS in the initial, confirmatory, and combined data sets (combined data set: hazard ratio (HR), 3.67; 95% CI, 2.72 to 4.38; P <0.001). These findings persisted after multivariable adjustment. Compared with low EBV DNA concentration, high EBV DNA concentration was associated with poor OS in patients with any stage. High EBV DNA concentration was also associated with poor disease-free survival (DFS) in patients with stage I/II disease. Patients with persistently detectable plasma EBV DNA had significantly poor OS (P <0.001) and DFS (P <0.001) than patients with undetectable EBV DNA three months after radical resection. In patients who underwent sequential evaluation of EBV DNA, an association was identified between an increase in EBV DNA concentration and a poor response to treatment and disease progression of pulmonary LELC. High baseline EBV DNA concentration is an independent poor prognostic marker in pulmonary LELC patients. These results should be confirmed in larger prospective trials.