The diagnostic and prognostic values of plasma Epstein-Barr virus DNA for residual cervical lymphadenopathy in nasopharyngeal carcinoma patients:a retrospective study

Background:Currently,the diagnosis and treatment of nasopharyngeal carcinoma(NPC)patients with residual cervical lymphadenopathy following radical radiotherapy with or without chemotherapy are challenging.We investigated the prognosis of NPC patients with residual cervical lymphadenopathy and assessed the diagnostic and prognostic values of Epstein-Barr virus(EBV)DNA in these patients.Methods:This study included 82 NPC patients who were diagnosed with suspected residual cervical lymphadenopathy following completion of antitumor therapy.Their plasma EBV DNA levels were measured using quantitative polymerase chain reaction(qPCR)before the initiation of treatment and before neck dissection.Fine needle aspiration cytology(FNAC)was performed in 21 patients.All patients had undergone neck dissection and postoperative pathological examination to identify the nature of residual cervical lymphadenopathy.The overall survival(OS),progression-free survival(PFS),distant metastasis-free survival(DMFS),and locoregional relapse-free survival(LRRFS)were calculated using the Kaplan-Meier method and compared using the log-rank test.The Cox proportional hazards model was used to calculate hazard ratios(HRs)with 95%confidence intervals(CIs).Multivariable analysis was used to estimate the effect of potential prognostic factors on survival.Results:Following a median follow-up of 52.6 months,compared with patients with negative postoperative pathological findings for residual cervical lymphadenopathy,the patients with positive findings had a significantly lower 3-year PFS rate(49.9%vs.83.3%,P=0.008).Among NPC patients with residual cervical lymphadenopathy,the patients with preoperative plasma EBV DNA>0 copy/mL had a lower 3-year PFS rate than did those with no detectable EBV DNA(43.7%vs.61.1%,P=0.031).In addition,combining FNAC with preoperative EBV DNA detection improved the diagnostic sensitivity.Multivariable analysis demonstrated that residual cervical lymphadenopathy with positive postoperative pathological result was an independent prognostic factor for PFS and that detectable preoperative plasma EBV DNA was an independent prognostic factor for OS.Conclusions: Using FNAC combined with preoperative EBV DNA detection improves the sensitivity in diagnosing NPC with residual cervical lymphadenopathy. Compared with patients with undetectable EBV DNA, patients with detectable preoperative plasma EBV DNA have worse prognosis and may require a more aggressive treatment strategy.

淋巴结EBV-DNA检测在鼻咽癌颈淋巴结转移中的诊断价值

目的 探讨淋巴结细针抽吸活检（FNA）洗脱液EB病毒（EBV）-DNA浓度测定对鼻咽癌颈部淋巴结转移的诊断价值。方法 选取2016年8月至12月在中山大学肿瘤防治中心病理确诊为鼻咽癌的患者36例及非EBV相关的其他肿瘤患者9例，所有患者行头颈部MRI、血清和颈部淋巴结FNA洗脱液EBVDNA检测。结果 淋巴结EBVDNA检测中位浓度（1.39×105 copies/ml）高于血清EBVDNV检测中位浓度（2.00×103 copies/ml），差异有统计学意义（χ2=16.723，P=0.004）。淋巴结FNA洗脱液EBVDNA检测的敏感性86.2%（25/29）、特异性71.4%（10/14）、准确率81.4%（35/43），优于MRI的敏感性72.4%（21/29）、特异性50.0%（7/14）、准确率65.1%（28/43）与血清EBVDNA检测的敏感性55.2%（16/29）、特异性71.4%（10/14）、准确率60.5%（26/43）。对颈Ⅰb区淋巴结的诊断计算曲线下面积（AUC），FNA洗脱液EBVDNA检测的AUC（0.688）大于MRI（0.583），差异有统计学意义（Z=2.476，P=0.008）。非EBV相关性的其他肿瘤患者淋巴结FNA洗脱液中EBVDNA拷贝数为0 copy/ml。结论 FNA洗脱液EBVDNA检测可提高鼻咽癌颈部淋巴结转移诊断的敏感性，对Ⅰb区淋巴结靶区勾画具有指导意义。