Quantification of plasma Epstein-Barr virus DNA in patients with advanced nasopharyngeal carcinoma
Quantification of plasma Epstein-Barr virus DNA in patients with advanced nasopharyngeal carcinoma
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DOI：
10.1056/nejmoa032260
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发表时间：
2004-06-10
影响因子：
158.5
通讯作者：
Jiang, RS
中科院分区：
文献类型：
--
作者：
Lin, JC;Wang, WY;Jiang, RS
方法99例经活检证实为III期或IV期鼻咽癌且无转移迹象（M0）的患者接受10周化疗后放疗，并观察其血浆EB-巴尔病毒（EBV）DNA浓度的变化。对患者的血浆样本进行实时定量聚合酶链反应测定。对99例患者治疗前血浆和原发肿瘤配对标本的EBV基因型进行了比较，发现94例患者治疗前血浆EBV DNA阳性，而40例健康对照组和20例治愈患者治疗前血浆EBV DNA阴性。25例III期疾病患者的血浆EBV DNA中位浓度为681拷贝/毫升，74例IV期疾病患者为1703拷贝/毫升，19例远处转移的对照患者为291，940拷贝/毫升（P< 0.001）。复发患者治疗前血浆EBV DNA浓度显著高于未复发患者（中位数，3035对1202拷贝/毫升; P=0.02）。血浆和原发性肿瘤配对样本中EBV DNA的一致基因分型表明循环中的无细胞EBV DNA可能来源于原发性肿瘤。与复发患者的血浆EBV DNA浓度反弹不同，完全临床缓解患者的血浆EBV DNA浓度持续较低或检测不到。治疗前血浆EBV DNA浓度至少为1500拷贝/毫升的患者的总生存率（P< 0.001）和无复发生存率（P=0.02）显著低于浓度低于1500拷贝/毫升的患者。放疗结束后1周，血浆EBV DNA持续检测者的总生存率（P< 0.001）和无复发生存率（P< 0.001）明显低于血浆EBV DNA阴性者。
BACKGROUNDWe investigated the clinical significance of plasma concentrations of Epstein - Barr virus (EBV) DNA in patients with advanced nasopharyngeal carcinoma.METHODSNinety-nine patients with biopsy-proven stage III or IV nasopharyngeal carcinoma and no evidence of metastasis (M0) received 10 weekly chemotherapy treatments followed by radiotherapy. Plasma samples from the patients were subjected to a real-time quantitative polymerase-chain-reaction assay. EBV genotypes of paired samples from plasma and primary tumor were compared.RESULTSPlasma EBV DNA was detectable before treatment in 94 of the 99 patients, but not in 40 healthy controls or 20 cured patients. The median concentrations of plasma EBV DNA were 681 copies per milliliter among 25 patients with stage III disease, 1703 copies per milliliter among 74 patients with stage IV disease, and 291,940 copies per milliliter among 19 control patients with distant metastasis (P< 0.001). Patients with relapse had a significantly higher plasma EBV DNA concentration before treatment than those who did not have a relapse ( median, 3035 vs. 1202 copies per milliliter; P=0.02). The consistent genotyping of EBV DNA between paired samples of plasma and primary tumor suggested that the circulating cell-free EBV DNA may originate from the primary tumor. Unlike the rebound of plasma EBV DNA concentrations in the patients who had a relapse, the plasma EBV DNA concentration was persistently low or undetectable in patients with a complete clinical remission. Overall survival ( P< 0.001) and relapse-free survival ( P=0.02) were significantly lower among patients with pretreatment plasma EBV DNA concentrations of at least 1500 copies per milliliter than among those with concentrations of less than 1500 copies per milliliter. Patients with persistently detectable plasma EBV DNA had significantly worse overall survival ( P< 0.001) and relapse-free survival ( P< 0.001) than patients with undetectable EBV DNA one week after the completion of radiotherapy.CONCLUSIONSQuantification of plasma EBV DNA is useful for monitoring patients with nasopharyngeal carcinoma and predicting the outcome of treatment.