The effect of primary tumor volume on the prognosis of nasopharyngeal carcinoma in era of volumetric modulated arc therapy: a propensity score matched cohort study

Abstract Objective The role of Primary Tumor Volume (PTV) in Nasopharyngeal Carcinoma (NPC) treated with Volumetric Modulated Arc Therapy (VMAT) is still unclear. The aim of this study was to access the effect of PTV in prognosis prediction of nasopharyngeal carcinoma in era of VMAT. Methods Between January 20 and November 2011, 498 consecutive NPC patients with stage I-IVA disease who received VMAT at a single center were retrospectively analyzed. Receiver Operating Characteristic (ROC) was performed to access the cut-off point of PTV. Univariate Kaplan-Meier and multivariate Cox regression analyses were used to evaluate prognostic value for PTV. The Propensity Score Matching (PSM) was used to adjust baseline potential confounders. Results The 5-year Locol-Regional Failure-Free (L-FFR), Distant Failure-Free Survival (D-FFR), Disease-Free Survival (DFS) and Overall Survival (OS) were 90.6%, 83.7%, 71.5% and 79.3%, respectively. Before PSM, the 5-year L-FFR, D-FFR, DFS, OS rates for NPC patients with PTV ≤ 38 mL vs. PTV > 38 mL were 94.1% vs. 90.4% (p= 0.063), 87.9% vs. 76.3% (p< 0.001), 78.5% vs. 58.5% (p< 0.001) and 86.3% vs. 66.7% (p< 0.001) respectively. Multivariate analysis showed PTV was an independent prognostic factor for D-FFS (p= 0.034), DFS (p= 0.002) and OS (p= 0.001). PTV classified was still an independent prognostic factor for OS after PSM (HR = 2.034, p= 0.025. Conclusions PTV had a substantial impact on the prognosis of NPC patients treated with VMAT before and after PSM simultaneously. PTV > 38 mL may be considered as an indicator of the clinical stage of nasopharyngeal carcinoma. Level of evidence III.

摘要 研究目的：容积旋转调强放射治疗（Volumetric Modulated Arc Therapy，VMAT）时代下，原发肿瘤体积（Primary Tumor Volume，PTV）在鼻咽癌（Nasopharyngeal Carcinoma，NPC）治疗中的作用仍不明确。本研究旨在探讨接受VMAT治疗的NPC患者中，PTV对预后预测的影响。

研究方法：回顾性分析2011年1月至2011年11月期间，单中心接受VMAT治疗的498例连续纳入的I~IVA期NPC患者。采用受试者工作特征（Receiver Operating Characteristic，ROC）曲线确定PTV的最佳截断值；通过单因素卡普兰-迈耶（Kaplan-Meier）分析及多因素Cox回归分析评估PTV的预后价值；采用倾向得分匹配（Propensity Score Matching，PSM）校正基线潜在混杂因素。

研究结果：患者的5年局部区域无失败生存率（Locoregional Failure-Free，L-FFR）、远处无失败生存率（Distant Failure-Free Survival，D-FFR）、无病生存率（Disease-Free Survival，DFS）及总生存率（Overall Survival，OS）分别为90.6%、83.7%、71.5%及79.3%。倾向得分匹配前，PTV≤38 mL组与PTV>38 mL组鼻咽癌患者的5年L-FFR分别为94.1%与90.4%（p=0.063），D-FFR分别为87.9%与76.3%（p<0.001），DFS分别为78.5%与58.5%（p<0.001），OS分别为86.3%与66.7%（p<0.001）。多因素分析显示，PTV是D-FFR（原文笔误为D-FFS）、DFS及OS的独立预后因素（p分别为0.034、0.002及0.001）。倾向得分匹配后，PTV分层仍为OS的独立预后因素（风险比=2.034，p=0.025）。

研究结论：无论倾向得分匹配前后，PTV均对接受VMAT治疗的鼻咽癌患者预后具有显著影响。PTV>38 mL可作为鼻咽癌临床分期的参考指标。本研究证据等级为III级。