Pretherapy quantitative measurement of circulating Epstein-Barr virus DNA is predictive of posttherapy distant failure in patients with early-stage nasopharyngeal carcinoma of undifferentiated type
Pretherapy quantitative measurement of circulating Epstein-Barr virus DNA is predictive of posttherapy distant failure in patients with early-stage nasopharyngeal carcinoma of undifferentiated type
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作者：
Leung, SF;Chan, ATC;Lo, YMD
背景资料。国际抗癌联合会(UICC)I-II期鼻咽癌(NPC)患者的预后似乎相对较好，通常被排除在综合治疗试验之外。最近，血浆/血清无细胞EB病毒(EBV)DNA已被证明在大多数鼻咽癌患者确诊时可检测到，并似乎具有预后意义。然而，在I-II期疾病中，失败事件很少发生，据我们所知，治疗前EBV DNA水平对预后的影响尚未得到解决。这一问题具有管理意义，因为目前对风险高的患者和风险低的患者采用了不同的治疗策略。方法：对90名UICC I-II期NPC(世界卫生组织2/3级组织学)患者进行了治疗前血浆/血清EBV DNA水平的定量聚合酶链式反应分析，并与治疗后失败的可能性相关。除3名患者同时接受化疗外，其余患者仅接受放射治疗。Kaplan-Meier将局部失败、远处失败和肿瘤特异性生存的概率与临床分期和EBV DNA水平进行比较。结果：中位随访时间为45个月的患者中，分别有12名患者和7名患者发生了局部失败和远处失败，其中2名患者既有局部失败又有远处失败。有远处衰竭的患者治疗前EBV DNA水平显著高于无失败的患者(中位数为13,219拷贝/毫升[区间为274,635拷贝/毫升]，中位数为423拷贝/毫升[区间为2753拷贝/毫升])。高(4000拷贝/毫升血浆)与低EBVDNA水平(P=0.0001，LOG-RANK检验)和IIB期患者的远处失败概率显著高于I期和IIA期(P=0.0149，LOG-RANK检验)，但II期和I期患者之间差异无统计学意义。EBV DNA水平高和低的患者局部失败的风险没有显著差异，临床亚期之间也没有显著差异。结论：在一组UICC I-II期鼻咽癌患者中，治疗前血浆EBV DNA水平被发现为具有与晚期疾病患者相似的远距离失败概率的低风险组。这一组患者可能需要考虑目前仅适用于III-IV期疾病的管理考虑。尽管治疗前EBV DNA水平似乎是早期鼻咽癌患者更强大的预后判别器，但根据1997年UICC分期将IIB期疾病指定为预后的意义得到了证实。(C)2003年美国癌症协会。
BACKGROUND. Patients with International Union Against Cancer (UICC) Stage I-II nasopharyngeal carcinoma (NPC) appear to have a relatively favorable prognosis and generally are excluded from trials of combined modality treatment. More recently, plasma/serum cell-free Epstein-Barr virus (EBV) DNA has been shown to be measurable in the majority of NPC patients at the time of diagnosis, and appears to have prognostic significance. However, within Stage I-II disease, in which failure events are infrequent, the prognostic impact of the pretreatment EBV DNA level has not been addressed to our knowledge. This issue has management implications because different therapeutic strategies currently are employed for patients with good-risk and those with poor-risk NPC.METHODS. A cohort of 90 patients with UICC Stage I-II NPC (World Health Organization Grade 2/3 histology) had their pretherapy plasma/serum EBV DNA levels determined by a quantitative polymerase chain reaction assay and correlated with the probability of posttherapy failure. AN patients received radiation therapy only, except for three patients who also received concurrent chemotherapy. Kaplan-Meier plots of the probability of locoregional failure, distant failure, and cancer-specific survival were compared with reference to clinical stage and EBV DNA levels.RESULTS. With a median follow-up time of 45 months, 12 patients and 7 patients, respectively, had developed locoregional and distant failures, including 2 patients with both local and distant failures. Patients with distant failure had significantly higher pretherapy EBV DNA levels than those without failure (a median of 13,219 copies/mL [interquatile-range, 274,635 copies/mL] vs. a median of 423 copies/mL [interquatile-range, 2753 copies/mL]). The probability of distant failure was significantly higher in patients with high (> 4000 copies/mL plasma) compared with low EBV DNA levels (P = 0.0001, log-rank test) and for Stage IIB disease compared with Stage I and Stage IIA disease combined (P = 0.0149, log-rank test), but was not significantly different between patients with Stage II and those with Stage I disease. The risks of locoregional failure were not significantly different between patients with high and those with low EBV DNA levels, and also was not significantly different between clinical substages. Approximately 35% of patients with Stage IIB disease were in the at-risk group for distant failure, as identified by high EBV DNA levels.CONCLUSIONS. Within a group of patients with UICC Stage I-II NPC, the pretherapy plasma EBV DNA level was found to identify a poor-risk group with a probability of distant failure similar to that of patients with advanced stage disease. This group of patients may warrant management considerations currently applicable only to cases of Stage III-IV disease. The prognostic significance of designating Stage IIB disease as per the 1997 UICC staging was confirmed, although the pretherapy EBV DNA level appears to be a more powerful prognostic discriminator in patients with early-stage NPC. (C) 2003 American Cancer Society.