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.
Eur J Cancer. 2021 Jul;151:63-71. doi: 10.1016/j.ejca.2021.03.052. Epub 2021 May 5.
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).
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.
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).
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.
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。
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。
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。
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。
