Chan Anthony T C, Lo Y M Dennis, Zee Benny, Chan Lisa Y S, Ma Brigette B Y, Leung Sing-Fai, Mo Frankie, Lai Maria, Ho Stephen, Huang Dolly P, Johnson Philip J
Department of Clinical Oncology, Sir Y. K. Pao Centre for Cancer, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region.
J Natl Cancer Inst. 2002 Nov 6;94(21):1614-9. doi: 10.1093/jnci/94.21.1614.
Epstein-Barr virus (EBV) DNA can be detected and quantified in the plasma of patients with EBV-related tumors, such as nasopharyngeal carcinoma (NPC). Although NPC at early stages can be cured by radical radiotherapy, there is a high recurrence rate in patients with advanced NPC. The pretreatment level of circulating EBV DNA is a prognostic factor for NPC, but the prognostic value of post-treatment EBV DNA has not been studied. We designed a prospective study in Hong Kong, China, to investigate the value of plasma EBV DNA as a prognostic factor for NPC.
One hundred seventy NPC patients, without metastatic disease at presentation, were treated with a uniform radiotherapy protocol. Circulating EBV DNA was measured by real-time quantitative polymerase chain reaction before treatment and 6-8 weeks after radiotherapy was completed. Risk ratios (RRs) were determined with a Cox regression model, and associations of various factors with progression-free and overall survival and recurrence rates were determined with a stepwise Cox proportional hazards model. All statistical tests were two-sided.
Ninety-nine percent of patients achieved complete clinical remission. Levels of post-treatment EBV DNA dominated the effect of levels of pretreatment EBV DNA for progression-free survival. The RR for NPC recurrence was 11.9 (95% confidence interval [CI] = 5.53 to 25.43) for patients with higher post-treatment EBV DNA and 2.5 (95% CI = 1.14 to 5.70) for patients with higher pretreatment EBV DNA. Higher levels of post-treatment EBV DNA were statistically significantly associated with overall survival (P<.001; RR for NPC recurrence = 8.6, 95% CI = 3.69 to 19.97). The positive and negative predictive values for NPC recurrence for a higher level of post-treatment EBV DNA were 87% (95% CI = 58% to 98%) and 83% (95% CI = 76% to 89%), respectively.
Levels of post-treatment plasma EBV DNA in patients with NPC appear to strongly predict progression-free and overall survival and to accurately reflect the post-treatment residual tumor load.
在与爱泼斯坦-巴尔病毒（EBV）相关的肿瘤患者血浆中可检测到EBV DNA并进行定量分析，如鼻咽癌（NPC）患者。虽然早期鼻咽癌可通过根治性放疗治愈，但晚期鼻咽癌患者的复发率很高。循环EBV DNA的预处理水平是鼻咽癌的一个预后因素，但治疗后EBV DNA的预后价值尚未得到研究。我们在中国香港设计了一项前瞻性研究，以探讨血浆EBV DNA作为鼻咽癌预后因素的价值。
170例初诊时无转移疾病的鼻咽癌患者接受统一的放疗方案治疗。在治疗前以及放疗结束后6 - 8周，通过实时定量聚合酶链反应检测循环EBV DNA。用Cox回归模型确定风险比（RRs），并用逐步Cox比例风险模型确定各种因素与无进展生存期、总生存期和复发率的关联。所有统计检验均为双侧检验。
99%的患者实现了临床完全缓解。治疗后EBV DNA水平对无进展生存期的影响超过了治疗前EBV DNA水平的影响。治疗后EBV DNA水平较高的患者鼻咽癌复发的RR为11.9（95%置信区间[CI]=5.53至25.43），治疗前EBV DNA水平较高的患者为2.5（95%CI = 1.14至5.70）。治疗后EBV DNA水平较高与总生存期在统计学上有显著关联（P<0.001；鼻咽癌复发的RR = 8.6，95%CI = 3.69至19.97）。治疗后EBV DNA水平较高时，鼻咽癌复发的阳性和阴性预测值分别为87%（95%CI = 58%至98%）和83%（95%CI = 76%至89%）。
鼻咽癌患者治疗后血浆EBV DNA水平似乎能强烈预测无进展生存期和总生存期，并能准确反映治疗后残留肿瘤负荷。
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