治疗前不同血浆EB病毒DNA水平对非高发区鼻咽癌患者预后影响的研究

Prognostic value of Epstein-Barr virus DNA level in patients with nasopharyngeal carcinoma in a non-endemic area

目的探讨血浆EB病毒(Epstein-Barr virus,EB)潜伏和活化状态对非高发区鼻咽癌患者预后的影响。方法对陕西省汉中市(非鼻咽癌高发区)中心医院2014年8月1日—2017年7月31日收治的318例鼻咽癌患者于治疗前进行EB病毒DNA水平定量检测,以治疗前EB病毒DNA定量≥500拷贝/ml为界值将患者分为EB病毒DNA阳性(EB病毒活化状态)组(n=199)和阴性(EB病毒潜伏状态)组(n=119),采用倾向值匹配法获得EB病毒DNA阳性组和EB病毒DNA阴性组各项资料均衡的鼻咽癌患者228例(1∶1匹配)。采用Kaplan-Meier法计算生存率,采用Cox回归模型进行预后因素分析。主要研究终点为无进展生存率(failure-free survival,FFS),次要研究终点为总生存率(overall survival,OS)、无局部区域进展生存率(loco-regional relapse-free survival,LRFS)和无远处转移生存率(distant metastasis-free survival,DMFS)。结果318例患者中,119例(37.4%)EB病毒DNA定量阴性鼻咽癌患者预后优于EB病毒DNA定量阳性组患者(3年FFS:90.3%vs 74.8%,χ^(2)=7.193,P=0.007;OS:92.7%vs 87.8%,χ^(2)=3.187,P=0.074;LRFS:95.3%vs 86.5%,χ^(2)=4.521,P=0.033;DMFS:95.8%vs 85.7%,χ^(2)=6.033,P=0.014)。用倾向值匹配法纳入的228例患者中,EB病毒DNA阴性组对比阳性组,3年FFS、OS、LRFS和DMFS分别为:89.9%vs 67.5%,χ^(2)=4.258,P=0.039;92.3%vs 88.7%,χ^(2)=1.210,P=0.271;95.1%vs 76.4%,χ^(2)=4.598,P=0.032和95.6%vs 86.9%,χ^(2)=2.665,P=0.103;Cox回归模型显示EB病毒DNA阳性是FFS、LRFS和DMFS的不良预后因素。结论EB病毒呈潜伏状态的非高发区鼻咽癌患者预后更好。

Objective To analyze the prognostic value of Epstain-Barr virus(EBV)in nasopharyngeal carcinoma(NPC)patients in a non-endemic area.Methods Patients with NPC(n=318)in a non-endemic area for whom plasma EBV DNA load was measured before treatment.The patients were divided into positive group(199 cases with EB virus active status)and negative group(119 cases with EB virus latent status)with the threshold value≥500 copies/ml of EB virus DNA before treatment.Patients(n=228)in both EBV DNA status groups were matched using propensity score matching(PSM)method at the ratio of 1∶1.Failure-free survival(FFS),overall survival(OS),loco-regional relapse-free survival(LRFS)and distant metastasis-free survival(DMFS)were compared using Kaplan-Meier estimates,log-rank test and Cox regression analysis.Results Of the 318 patients,119(37.4%)had undetectable pre-treatment plasma EB virus DNA level.In the original cohort of 318 patients,EB virus DNA negative group were associated with significantly better survival than the EB virus DNA positive group(3-year FFS 90.3%vs 74.8%,χ^(2)=7.193,P=0.007;OS 92.7%vs87.8%,χ^(2)=3.187,P=0.074;LRFS 95.3%vs 86.5%,χ^(2)=4.521,P=0.033 and DMFS 95.8%vs85.7%,χ^(2)=6.033,P=0.014).After matching,228 patients were identified for analysis,the 3-year FFS,OS,LRFS and DMFS rates for EB virus DNA negative group vs EB virus DNA positive group were 89.9%vs67.5%,χ^(2)=4.258,P=0.039;92.3%vs 88.7%,χ^(2)=1.210,P=0.271;95.1%vs 76.4%,χ^(2)=4.598,P=0.032 and 95.6%vs 86.9%,χ^(2)=2.665,P=0.103.In multivariate analysis,EB virus status was an independent prognostic factor for FFS,LRFS and DMFS,but not OS,in NPC patients in a non-endemic area.Conclusion Patients with nasopharyngeal carcinoma in a non-endemic area with EB virus latent status have a better prognosis.