Clinical Significance of Plasma Epstein-Barr Virus DNA in Pulmonary Lymphoepithelioma-like Carcinoma (LELC) Patients
Clinical Significance of Plasma Epstein-Barr Virus DNA in Pulmonary Lymphoepithelioma-like Carcinoma (LELC) Patients
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肺淋巴上皮瘤样癌 (LELC) 患者血浆 Epstein-Barr 病毒 DNA 的临床意义
DOI：
10.1016/j.jtho.2017.10.031
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发表时间：
2018-02-01
影响因子：
20.4
通讯作者：
Li, Xiaoxiang
中科院分区：
文献类型：
--
作者：
Xie, Mian;Wu, Xiaojun;Li, Xiaoxiang
简介：原发性肺淋巴上皮瘤样癌（LELC）是一种组织学上独特的NSCLC亚型，是EB病毒（EBV）相关的上皮性肿瘤。我们探讨了肺LELC.Methods患者的EBV DNA的血浆浓度的临床意义：两个独立的血浆样本，共429例肺LELC患者（287初始和142确认）可用于EBV DNA测定。在治疗前和根治性切除术后3个月，对患者的血浆样本进行实时定量聚合酶链反应。根据总生存期（OS）的对数秩检验统计量的异质性测量，确定治疗前血浆EBV DNA浓度（低= 4000拷贝/mL）的临界点。采用Kaplan-Meier法和考克斯回归分析血浆EBV DNA浓度与临床预后的关系。在接受连续抽血的晚期肺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。结果：在初始、确证和合并数据集中，高EBV DNA浓度与较短OS相关（组合数据集风险比= 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EBV DNA浓度低相比，EBV DNA浓度高与任何疾病阶段患者的OS较短相关。在I/II期疾病患者中，高EBV DNA浓度也与较短的无病生存期（DFS）相关。根治性切除术后3个月，血浆EBV DNA持续可检测的患者的OS（p <0.001）和DFS（p <0.001）显著低于EBV DNA不可检测的患者。在接受序贯评价EBV DNA的患者中，EBV DNA浓度的增加与肺LELC.Conclusion治疗反应不良和疾病进展之间存在关联：高基线EBV DNA浓度是肺LELC患者预后不良的独立标志。这些结果应该在更大的前瞻性试验中得到证实。(C)2017年国际肺癌研究协会。爱思唯尔公司出版All rights reserved.
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) 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 states and change in EBV DNA concentrations by using nonparametric tests.Results: High EBV DNA concentration was associated pith 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. (C) 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.