Huang Zhang-Zan, Wen Wen, Hua Xin, Song Chen-Ge, Bi Xi-Wen, Huang Jia-Jia, Xia Wen, Yuan Zhong-Yu
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, Guangzhou, China.
Front Oncol. 2021 Jul 15;11:583283. doi: 10.3389/fonc.2021.583283. eCollection 2021.
A higher ratio of pretreatment C-reactive protein/albumin ratio (CAR) is associated with poor prognosis in nasopharyngeal carcinoma (NPC), and Epstein-Barr virus (EBV) DNA level is known to not only participate in the occurrence of nasopharyngeal carcinoma but also affect the development and prognosis of the disease. Herein, we proposed that a combination of both these markers could improve the predictive prognostic ability.
In all, 842 NPC patients who received concurrent chemoradiotherapy (CCRT) were entered in this study. We collected all patients' blood samples and EBV DNA copy numbers within one week before any treatment. Receiver operating characteristic (ROC) curve was used to determine the optimal cut-off. We employed the Kaplan-Meier method for survival analyses and the univariate and multivariate analyses (Cox proportional hazards regression model) for statistical analysis. A nomogram was constructed based on multivariate analyses results of the validation set. The model was internally validated using 1000 bootstrap samples to avoid overfitting. Another validation of 10-fold cross-validation was also applied. Calibration curves and concordance index (C-index) were calculated to determine predictive and discriminatory capacity.
In the whole cohort, we observed that higher CAR, EBV DNA level, and CAR-EBV DNA (C-E) grade were associated with shorter overall survival (OS) and distant metastasis-free survival (DMFS) (all P<0.05). In univariate and multivariate analyses, C-E grade was an independent prognostic factor (all P<0.05). In the training set, we gained the similar results with the whole set. According to multivariate analyses of the training set, we constructed a nomogram. The results of bootstrap samples and 10-fold cross-validation showed favorable predictive efficacy. And calibration curves of the model provided credibility to its predictive capability.
C-E grade was confirmed as an independent prognostic predictor in patients with NPC who received CCRT. Higher level of pretreatment C-E grade could signify a higher risk of metastasis and shorter OS. The prognostic nomogram based on C-E grade was dependable in nasopharyngeal carcinoma patients.
治疗前C反应蛋白与白蛋白比值（CAR）升高与鼻咽癌（NPC）预后不良相关，且已知 Epstein-Barr病毒（EBV）DNA水平不仅参与鼻咽癌的发生，还影响疾病的发展和预后。在此，我们提出这两种标志物的联合使用可提高预测预后的能力。
本研究共纳入842例接受同步放化疗（CCRT）的NPC患者。我们在任何治疗前一周内收集了所有患者的血液样本和EBV DNA拷贝数。采用受试者工作特征（ROC）曲线确定最佳截断值。我们采用Kaplan-Meier法进行生存分析，并采用单因素和多因素分析（Cox比例风险回归模型）进行统计分析。基于验证集的多因素分析结果构建列线图。使用1000次自抽样对模型进行内部验证以避免过度拟合。还应用了10倍交叉验证的另一种验证方法。计算校准曲线和一致性指数（C指数）以确定预测和鉴别能力。
在整个队列中，我们观察到较高的CAR、EBV DNA水平和CAR-EBV DNA（C-E）分级与较短的总生存期（OS）和无远处转移生存期（DMFS）相关（所有P<0.05）。在单因素和多因素分析中，C-E分级是一个独立的预后因素（所有P<0.05）。在训练集中，我们得到了与整个数据集相似的结果。根据训练集的多因素分析，我们构建了一个列线图。自抽样样本和10倍交叉验证的结果显示出良好的预测效果。并且该模型的校准曲线为其预测能力提供了可信度。
C-E分级被确认为接受CCRT的NPC患者的独立预后预测指标。治疗前C-E分级水平较高可能意味着转移风险较高和OS较短。基于C-E分级的预后列线图在鼻咽癌患者中是可靠的。
