诱导化疗后循环 EBV DNA 水平可预测晚期鼻咽癌的预后。
Circulating Epstein-Barr virus DNA level post induction chemotherapy contributes to prognostication in advanced-stage nasopharyngeal carcinoma.
机构信息
Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-Sen University Cancer Center, No. 651 Dongfeng Eastern Road, Guangzhou, 510060, China.
Department of Radiation Oncology, Guangzhou Concord Cancer Center, Guangzhou, 510045, Guangdong, China.
出版信息
Eur J Cancer. 2021 Jul;151:63-71. doi: 10.1016/j.ejca.2021.03.052. Epub 2021 May 5.
BACKGROUND
To investigate the value of post-induction chemotherapy (IC) cell-free Epstein-Barr virus DNA (cfEBV DNA) for prognostication in locally advanced nasopharyngeal carcinoma (LA-NPC).
METHODS
A total of 910 histologically proven LA-NPC undergoing radical IC + concurrent chemo-radiotherapy (CCRT) or targeted radiotherapy (CTRT) or both (CTCRT) were involved. The concentration of cfEBV DNA was measured by quantitative polymerase chain reaction pre-IC (cfEBV DNA) and at IC completion. CfEBV DNA was classified as undetectable (0 copy/ml) and detectable (>0 copy/ml). Recursive partitioning analysis (RPA) with respect to the overall survival (OS) was applied to construct a risk stratification system incorporating cfEBV DNA and critical risk factors.
RESULTS
We observed that 660 (72.5%) and 250 (27.5%) patients had cfEBV DNA undetectable and detectable respectively. CfEBV DNA positive was associated with a significant inferior 5-year OS (76.2% versus 85.9%), metastasis-free survival (DMFS, 71.7% versus 86.4%) and disease-free survival (DFS, 57.7% versus 80.1%) than cfEBV DNA negative (P < 0.001 for all). Additionally, cfEBV DNA was independently significant for OS (hazard ratio [HR] 1.90, 95% CI 1.40-2.59), DMFS (1.99, 1.45-2.71) and DFS (2.38, 1.86-3.06) in multivariate analyses (P < 0.001 for all). RPA modelling yielded three distinct risk groups: low-risk (N0-1 and undetectable cfEBV DNA or N2-3 and pre-treatment cfEBV DNA [cfEBV DNA] <7000), median-risk (N0-1 and detectable cfEBV DNA or N2-3 and cfEBV DNA ≥7000 with undetectable cfEBV DNA) and high-risk (N2-3 and cfEBV DNA ≥7000 with detectable cfEBV DNA), with 5-year OS of 88.1%, 79.2% and 66.9%, respectively. Our risk stratification outperformed TNM classification for predicting death (AUC, 0.631 versus 0.562; P = 0.012) and distant metastasis (0.659 versus 0.562; P = 0.004).
CONCLUSIONS
CfEBV DNA represents an effective indicator of prognostication in LA-NPC. We developed a risk classification system that provides improved OS prediction over the current staging system by combining cfEBV DNA, cfEBV DNA and N-stage classification in LA-NPC.
背景
为了探讨诱导化疗后游离 Epstein-Barr 病毒 DNA（cfEBV DNA）在局部晚期鼻咽癌（LA-NPC）预后评估中的价值。
方法
共纳入 910 例经组织学证实的行根治性诱导化疗（IC）+同期放化疗（CCRT）或靶向放疗（CTRT）或两者联合（CTCRT）的 LA-NPC 患者。在 IC 前（cfEBV DNA）和 IC 完成时，采用实时聚合酶链反应定量检测 cfEBV DNA。cfEBV DNA 分为不可检测（0 拷贝/ml）和可检测（>0 拷贝/ml）。采用总体生存（OS）的递归分区分析（RPA）构建包含 cfEBV DNA 和关键危险因素的风险分层系统。
结果
我们观察到 660（72.5%）例和 250（27.5%）例患者的 cfEBV DNA 不可检测和可检测。cfEBV DNA 阳性与显著的 5 年 OS（76.2%比 85.9%）、无转移生存（DMFS，71.7%比 86.4%）和无病生存（DFS，57.7%比 80.1%）较差相关（均 P<0.001）。此外，cfEBV DNA 在多变量分析中对 OS（危险比 [HR]1.90，95%CI1.40-2.59）、DMFS（1.99，1.45-2.71）和 DFS（2.38，1.86-3.06）具有独立的显著意义（均 P<0.001）。RPA 模型产生了三个不同的风险组：低危组（N0-1 和不可检测的 cfEBV DNA 或 N2-3 和治疗前 cfEBV DNA[cfEBV DNA] <7000）、中危组（N0-1 和可检测的 cfEBV DNA 或 N2-3 和不可检测的 cfEBV DNA 但 cfEBV DNA ≥7000）和高危组（N2-3 和 cfEBV DNA ≥7000 且 cfEBV DNA 可检测），5 年 OS 分别为 88.1%、79.2%和 66.9%。我们的风险分层系统在预测死亡（AUC，0.631 比 0.562；P=0.012）和远处转移（0.659 比 0.562；P=0.004）方面优于 TNM 分期。
结论
cfEBV DNA 是 LA-NPC 预后评估的有效指标。我们通过结合 cfEBV DNA、cfEBV DNA 和 N 分期分类，建立了一种风险分类系统，在 LA-NPC 中提供了比当前分期系统更好的 OS 预测。
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