诱导化疗±同期放化疗对血浆EBV—DNA〉4000copies／ml的N2—3M0期鼻咽癌的临床研究

A clinical study of induction chemotherapy _＋ concurrent chemoradiotherapy for stage N2-3M0 nasopharyngeal carcinoma with plasma Epstein-Barr virus DNA〉4000 copies/ml

目的探讨诱导化疗在血浆EBV—DNA〉4000copies／ml的N2-3M0期鼻咽癌治疗中的价值。方法回顾分析2009--2013年间收治的210例血浆EBV—DNA〉4000copies／ml的N2-3M0期鼻咽癌患者的临床资料，101例行诱导化疗＋同期放化疗（NCRT），109例行同期放化疗（CCRT）。Kaplan—Meier法计算生存率并Logrank检验和单因素分析诱导化疗后血浆EBV—DNA水平变化对预后的影响。结果3年样本数为154例。NCRT组和CCRT组3年OS、DFS、DMFS分别为88．0％和80．4％（P=0．210）、80．1％和70．6％（P=0．029）、87．1％和76．0％（P=0．036）。N2期NCRT组3年DFS、DMFS高于CCRT组（P=0．031、0．014），N3期NCRT组3年OS、DFS、DMFS高于CCRT组（P=0．029、0．012、0．019）。全组诱导化疗2、3、4个周期的3年OS、DMFS依次提高（P=0．020、0．021）。NCRT组放疗前诱导化疗2、3、4个周期后血浆EBV—DNA转阴率分别为51．85％、76．92％、88．57％（P=0．004），将上述血浆EBV-DNA水平降为0作为预测进展指标的敏感性分别为62．50％、66．67％、75．00％（P=0．910），特异性分别为57．89％、90．00％、96．77％（P=0．000）。结论诱导化疗提高EBV—DNA〉4000copies／ml的N2-3M0期鼻咽癌患者的DFS、DMFS和N3期OS，不提高RFS。诱导化疗疗程与预后呈正比。随着诱导化疗周期增加血浆EBV—DNA转阴率逐渐增加，4个周期化疗后血浆EBV—DNA降0作为预测进展指标的敏感性和特异性均优于其他两组。

Objective To investigate the value of induction chemotherapy in the treatment of stage N2-3M0 nasopharyngeal carcinoma with plasma Epstein-Burr virus （EBV） DNA〉4000 copies/mh Methods A retrospective study was performed on clinical data from 210 patients with stage N2-3M0 nasopharyngeal carcinoma and plasma EBV DNA〉4000 copies/ml who were admitted to our hospital from 2009 to 2013. In the 210 patients, 101 received induction chemotherapy plus concurrent chemoradiotherapy （NCRT） and 109 concurrent chemoradiotherapy alone （CCRT）. The survival rates were calculated by the Kaplan-Meier method. The log-rank test was used for the analysis of survival rates and univariate analysis of the impacts of the changes in the plasma EBV DNA level after induction chemotherapy on the prognosis. Results The 3- year sample size was 154.The NCRT group had significantly higher 3-year disease-free survival （DFS） and distant metastasis-free survival （DMFS） rates than the CCRT group （80. 1% vs. 70. 6%, P= 0. 029;87. 1% vs. 76.0%, P= 0. 036）, while there was no significant difference in 3-year overall survival （OS） rate between the two groups （88.0% vs. 80. 4%, P= 0. 210）. Patients with stage N2 disease in the NCRT group had significantly higher 3-year DFS and DMFS rates than those in the CCRT group （P= 0. 031,0. 014）. Patients with stage N3 disease in the NCRT group had significantly higher 3-year OS, DFS, and DMFS rates than those in the CCRT group （P= 0. 029,0. 012,0. 019）. In all the patients, the 3-year OS and DMFS rates were improved with the increase in the cycle number of induction chemotherapy （P= 0. 020,0. 021 ）. In the NCRT group, patients treated with 2, 3, and 4 cycles of induction chemotherapy before radiotherapy had plasma EBV-DNA clearance rates of 51.85%, 76. 92%, and 88.57%, respectively （P=0. 004）. Using the complete clearance of plasma EBV-DNA as a predictor of progression, the sensitivity for the above three groups was 62. 50%, 66. 67% and 75.00 （P= 0. 910）, respectively, and the specificity was 57.89%, 90. 00% and 96.77% （ P= 0. 000 ） , respectively. Conclusions In the treatment of nasopharyngeal carcinoma with plasma EBV DNA 〉 4 000 copies/M, induction chemotherapy improves DFS and DMFS in patients with stage N2-3M0 disease and OS in patients with stage N3 disease;induction chemotherapy dose not improve recurrence-free survival rate. The prognosis and plasma EBV DNA clearance rate are improved with the increase in the cycle nmnber of induction chemotherapy. Using the complete clearance of plasma EBV DNA as a predictor of progression, the sensitivity and specificity in patients treated with 4 cycles of chemotherapy are superior over those in patients treated with 2 or 3 cycles of chemotherapy.