Mian Xie1, Xiaojun Wu2, Fang Wang3, Jinjun Zhang4, Xiaosong Ben5, Jiexia Zhang6, Xiaoxiang Li7. 1. State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China; Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China. Electronic address: mianxie@gird.cn. 2. Department of General Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China; Department of Corlorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Guangdong, People's Republic of China. 3. Department of General Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China. 4. Department of Thoracic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China. 5. Department of Thoracic Surgery, Guangdong General Hospital, Guangzhou, People's Republic of China. 6. Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China. 7. Department of Thoracic Surgery, Cancer Center of Guangzhou Medical University, Guangzhou, People's Republic of China.
Abstract
INTRODUCTION: Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a histologically distinctive subtype of NSCLC and an Epstein-Barr virus (EBV)-associated epithelial neoplasm. We investigated the clinical significance of plasma concentrations of EBV DNA in patients with pulmonary LELC. METHODS: Two independent sets of plasma samples from a total of 429 patients with patients with pulmonary LELC (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 before treatment and 3 months after radical resection. Cutoff points were determined for pretreatment plasma EBV DNA concentration (low <4000 copies/mL versus high ≥4000 copies/mL) on the basis of a measure of heterogeneity with the log-rank test statistic with respect to overall survival (OS). The Kaplan-Meier method and Cox regression were used to evaluate the relationship between plasma EBV DNA concentrations and clinical outcome. Among patients with advanced-stage pulmonary LELC who underwent sequential blood draws, we evaluated the relationship between change in disease status and change in EBV DNA concentrations by using nonparametric tests. RESULTS: High EBV DNA concentration was associated with shorter OS in the initial, confirmatory, and combined data sets (combined data set hazard ratio = 3.67, 95% confidence interval: 2.72-4.38, p < 0.001). These findings persisted after multivariable adjustment. Compared with low EBV DNA concentration, high EBV DNA concentration was associated with shorter OS in patients with any stage of disease. High EBV DNA concentration was also associated with shorter disease-free survival (DFS) in patients with stage I/II disease. Patients with persistently detectable plasma EBV DNA had significantly poorer OS (p < 0.001) and DFS (p < 0.001) than did patients with undetectable EBV DNA 3 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. CONCLUSION: High baseline EBV DNA concentration is an independent poor prognostic marker in patients with pulmonary LELC. These results should be confirmed in larger prospective trials.
INTRODUCTION:Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a histologically distinctive subtype of NSCLC and an Epstein-Barr virus (EBV)-associated epithelial neoplasm. We investigated the clinical significance of plasma concentrations of EBV DNA in patients with pulmonary LELC. METHODS: Two independent sets of plasma samples from a total of 429 patients with patients with pulmonary LELC (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 before treatment and 3 months after radical resection. Cutoff points were determined for pretreatment plasma EBV DNA concentration (low <4000 copies/mL versus high ≥4000 copies/mL) on the basis of a measure of heterogeneity with the log-rank test statistic with respect to overall survival (OS). The Kaplan-Meier method and Cox regression were used to evaluate the relationship between plasma EBV DNA concentrations and clinical outcome. Among patients with advanced-stage pulmonary LELC who underwent sequential blood draws, we evaluated the relationship between change in disease status and change in EBV DNA concentrations by using nonparametric tests. RESULTS: High EBV DNA concentration was associated with shorter OS in the initial, confirmatory, and combined data sets (combined data set hazard ratio = 3.67, 95% confidence interval: 2.72-4.38, p < 0.001). These findings persisted after multivariable adjustment. Compared with low EBV DNA concentration, high EBV DNA concentration was associated with shorter OS in patients with any stage of disease. High EBV DNA concentration was also associated with shorter disease-free survival (DFS) in patients with stage I/II disease. Patients with persistently detectable plasma EBV DNA had significantly poorer OS (p < 0.001) and DFS (p < 0.001) than did patients with undetectable EBV DNA 3 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. CONCLUSION: High baseline EBV DNA concentration is an independent poor prognostic marker in patients with pulmonary LELC. These results should be confirmed in larger prospective trials.