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.
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.
J Thorac Oncol. 2018 Feb;13(2):218-227. doi: 10.1016/j.jtho.2017.10.031. Epub 2017 Nov 27.
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.
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.
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.
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.
原发性肺淋巴上皮瘤样癌（LELC）是一种具有独特组织学特征的非小细胞肺癌（NSCLC）亚型，是一种与 EBV 相关的上皮性肿瘤。我们研究了肺 LELC 患者血浆 EBV DNA 浓度的临床意义。
共有 429 例肺 LELC 患者（287 例初始和 142 例证实）的两组独立血浆样本可用于 EBV DNA 测定。在根治性切除术前和 3 个月后，对患者的血浆样本进行实时定量聚合酶链反应。基于对数秩检验统计量对总生存（OS）的异质性，确定治疗前血浆 EBV DNA 浓度的截断值（低 <4000 拷贝/ml 与高 ≥4000 拷贝/ml）。Kaplan-Meier 法和 Cox 回归用于评估血浆 EBV DNA 浓度与临床结局的关系。在接受序贯采血的晚期肺 LELC 患者中，我们使用非参数检验评估疾病状态变化与 EBV DNA 浓度变化之间的关系。
高 EBV DNA 浓度与初始、确认和综合数据集的 OS 较短相关（综合数据集危险比=3.67，95%置信区间：2.72-4.38，p<0.001）。这些发现在多变量调整后仍然存在。与低 EBV DNA 浓度相比，高 EBV DNA 浓度与任何疾病阶段的患者 OS 较短相关。高 EBV DNA 浓度也与 I/II 期疾病患者的无病生存（DFS）较短相关。持续检测到血浆 EBV DNA 的患者的 OS（p<0.001）和 DFS（p<0.001）明显差于根治性切除术后 3 个月时 EBV DNA 不可检测的患者。在对 EBV DNA 进行序贯评估的患者中，发现 EBV DNA 浓度的增加与肺 LELC 治疗反应不良和疾病进展有关。
高基线 EBV DNA 浓度是肺 LELC 患者的独立不良预后标志物。这些结果应在更大的前瞻性试验中得到证实。
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