Zheng Wei-Hong, He Xiao-Jun, Chen Fo-Ping, Lin Li, Huang Xiao-Dan, Zhou Hua-Qiang, Kou Jia, Lv Jia-Wei, Ma Jun, Zhou Guan-Qun, Sun Ying
Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
State Key Laboratory of Oncology in South China, Guangzhou 510060, China.
Ann Transl Med. 2020 Feb;8(4):83. doi: 10.21037/atm.2020.01.13.
Significance of plasma Epstein-Barr virus deoxyribonucleic acid (EBV DNA)-a proven robust indicator for nasopharyngeal carcinoma (NPC)-is not yet clarified in risk stratification of metastatic NPC (mNPC). We aim to establish effective M1 stage subdivisions in mNPC by integrating radiological features and EBV DNA at diagnosis of metastasis (mEBV DNA).
The study comprised 1,007 mNPC patients, including 817 metachronous mNPC (mmNPC) patients randomized into training (n=613) and internal validation (n=204) cohorts, and 190 synchronous mNPC (smNPC) patients defined as smNPC validation cohort. Primary clinical end-point was overall survival (OS). Covariate inclusion to recursive partitioning analysis (RPA)-generated risk stratification was qualified by a multivariable two-sided P<0.05. Performances of different models were compared using area under ROC curve (AUC), Harrell's concordance index (c-index) and Akaike information criterion (AIC).
Compared with other simply image-based models, the ultimate RPA-EBV-stage presented a best performance [c-index =0.68 (training), 0.70 (internal validation), 0.64 (smNPC validation); AUC =0.69 (training), 0.72 (internal validation), 0.70 (smNPC validation)]: M1a (low mEBV DNA + oligo lesion), M1b (low mEBV DNA + multiple lesions), M1c (high mEBV DNA + no liver involvement), and M1d (high mEBV DNA + liver involvement). Corresponding 3-year OS rates were 49.9%, 33.4%, 22.6%, and 6.7%, respectively (P<0.001). In mmNPC patients, compared with chemotherapy alone, addition of local treatment demonstrated superiority in M1a and M1b; systemic therapy combined with targeted therapy conferred benefit on patients of M1c and M1d (P<0.05).
This RPA-EBV-stage provided favorable prognostic value for survival outcomes and could assist clinical and investigative management. Low-risk patients are considered suitable candidate for curative local treatment, and high-risk patients are recommended to undergo intensive systemic treatment.
血浆爱泼斯坦-巴尔病毒脱氧核糖核酸（EBV DNA）作为鼻咽癌（NPC）一种已证实的可靠指标，在转移性鼻咽癌（mNPC）的风险分层中的意义尚未明确。我们旨在通过整合放射学特征和转移诊断时的EBV DNA（mEBV DNA）来建立有效的mNPC的M1期细分。
该研究纳入1007例mNPC患者，包括817例异时性mNPC（mmNPC）患者，随机分为训练队列（n = 613）和内部验证队列（n = 204），以及190例同步性mNPC（smNPC）患者作为smNPC验证队列。主要临床终点为总生存期（OS）。通过多变量双侧P<0.05来确定纳入递归划分分析（RPA）生成的风险分层的协变量。使用ROC曲线下面积（AUC）、Harrell一致性指数（c指数）和赤池信息准则（AIC）比较不同模型的性能。
与其他单纯基于影像的模型相比，最终的RPA-EBV分期表现最佳[c指数 = 0.68（训练队列），0.70（内部验证队列），0.64（smNPC验证队列）；AUC = 0.69（训练队列），0.72（内部验证队列），0.70（smNPC验证队列）]：M1a（低mEBV DNA + 寡发病灶），M1b（低mEBV DNA + 多发病灶），M1c（高mEBV DNA + 无肝脏受累），和M1d（高mEBV DNA + 肝脏受累）。相应的3年总生存率分别为49.9%、33.4%、22.6%和6.7%（P<0.001）。在mmNPC患者中，与单纯化疗相比，加用局部治疗在M1a和M1b患者中显示出优势；全身治疗联合靶向治疗对M1c和M1d患者有益（P<0.05）。
这种RPA-EBV分期对生存结局具有良好的预后价值，并有助于临床和研究管理。低风险患者被认为是根治性局部治疗的合适候选者，而高风险患者建议接受强化全身治疗。
