国际肿瘤学杂志

国际肿瘤学杂志 ›› 2020, Vol. 47 ›› Issue (5): 278-283.doi: 10.3760/cma.j.cn371439-20190930-00018

• 论著 • 上一篇    下一篇

纳入术前肿瘤体积的列线图预测胸段食管鳞状细胞癌患者预后的价值

郭信伟1, 冀胜军2, 姬磊3, 张晗4, 周绍兵1(), 刘阳晨1   

  1. 1 扬州大学附属泰兴人民医院肿瘤放疗科,泰兴 225400
    2 南京医科大学附属苏州医院肿瘤放疗科,苏州 215002
    3 苏州大学附属第一医院肿瘤放疗科 215006
    4 南京师范大学泰州学院数学系,泰州 225300
  • 收稿日期:2019-09-30 修回日期:2020-01-20 出版日期:2020-05-08 发布日期:2020-07-02
  • 通讯作者: 周绍兵 E-mail:zsb633@163.com
  • 基金资助:
    苏州市肿瘤临床医学中心项目(Szzx201506)

Value of nomogram incorporated preoperative tumor volume on predicting the prognosis of thoracic esophageal squamous cell carcinoma patients

Guo Xinwei1, Ji Shengjun2, Ji Lei3, Zhang Han4, Zhou Shaobing1(), Liu Yangchen1   

  1. 1 Department of Radiation Oncology, Affiliated Taixing People's Hospital of Yangzhou University, Taixing 225400, China
    2 Department of Radiation Oncology, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215002, China
    3 Department of Radiation Oncology, First Affiliated Hospital of Soochow University, Suzhou 215006, China
    4 School of Mathematics, Nanjing Normal University Taizhou College, Taizhou 225300, China
  • Received:2019-09-30 Revised:2020-01-20 Online:2020-05-08 Published:2020-07-02
  • Contact: Zhou Shaobing E-mail:zsb633@163.com
  • Supported by:
    Project of Suzhou Cancer Clinical Medical Center(Szzx201506)

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摘要：

目的 探索除TNM分期外的临床病理因素,包括术前肿瘤体积、长度及最大直径对胸段食管鳞状细胞癌预后的影响,并以列线图(nomogram)的方式评价有统计学意义的临床病理变量预测总生存率的情况。方法 回顾性分析2011—2014年在扬州大学附属泰兴人民医院胸外科接受食管癌根治术的296例患者,根据术前肿瘤体积、长度及最大直径的最佳临界值进行分组,采用Kaplan-Meier法计算生存率并行log-rank检验,应用Cox模型单因素及多因素分析临床变量与生存预后的关系,最终纳入有统计学意义的临床病理参数建立列线图模型,并通过校准曲线图、一致性指数(C-index)和决策曲线图进一步验证该模型的预测价值。结果 经X-tile分析确定术前肿瘤体积的最佳临界值为32 cm 3和72 cm 3,肿瘤体积<32 cm 3(n=94)、32~72 cm 3(n=118)和>72 cm 3(n=84)的3组患者1、3、5年生存率分别为100%、84.0%、68.1%,98.3%、42.4%、24.6%和94.1%、25.0%、7.1%(χ 2=86.639,P<0.001);肿瘤长度的最佳临界值为3.0 cm和5.0 cm,肿瘤长度<3.0 cm(n=62)、3.0~5.0 cm(n=146)和>5.0 cm(n=88)的3组患者1、3、5年生存率分别为99.5%、87.1%、69.4%,98.6%、47.9%、30.1%和94.3%、29.6%、13.6%(χ 2=53.607,P<0.001);肿瘤最大直径的最佳临界值为2.5 cm和3.5 cm,肿瘤最大直径<2.5 cm(n=51)、2.5~3.5 cm(n=121)和>3.5 cm(n=124)的3组患者1、3、5年生存率分别为99.5%、84.3%、74.5%,98.3%、57.0%、36.4%和96.0%、29.0%、13.7%(χ 2=62.109,P<0.001)。单因素分析结果显示,肿瘤位置、分化程度、T分期、N分期、TNM分期、辅助治疗、术前肿瘤体积、长度及最大直径均与胸段食管鳞状细胞癌患者的总生存期(OS)密切相关(均P<0.05)。Cox多因素分析结果显示,分化程度(HR=0.514,95%CI为0.366~0.723,P=0.019)、TNM分期(HR=1.757,95%CI为1.267~2.612,P=0.015)、辅助治疗(HR=0.669,95%CI为0.503~0.889,P=0.006)和术前肿瘤体积(将<32 cm 3设为哑变量,32~72 cm 3:HR=3.689,95%CI为2.415~5.637,P<0.001;>72 cm 3:HR=5.720,95%CI为3.606~9.075,P<0.001)是影响OS的独立危险因素。根据多变量分析有统计学意义的临床病理参数而构建的列线图模型预测胸段食管鳞状细胞癌术后OS的C-index为0.722(95%CI为0.687~0.757),明显高于第7版AJCC TNM分期的C-index(0.633,95%CI为0.595~0.671)。另外,校准曲线图表明列线图模型预测5年OS率和实际观察值之间存在高度一致性,决策曲线分析也表明,列线图模型预测胸段食管鳞状细胞癌术后的生存预后比TNM分期模型具有更高的临床应用潜能。结论 纳入术前肿瘤体积的列线图在预测胸段食管鳞状细胞癌患者生存预后方面具有重要价值。

关键词: 食管肿瘤, 列线图, 预后, 肿瘤体积

Abstract:

Objective To explore the influence of clinicopathological factors besides TNM stage, including preoperative tumor volume, length and maximum diameter, on survival prognosis of patients with thoracic esophageal squamous cell carcinoma (ESCC), and to evaluate the predictive survival rate of clinicopathological variables with statistical significance by nomogram. Methods A total of 296 patients with ESCC treated by radical resection at the Department of Thoracic Surgery of Affiliated Taixing People's Hospital of Yangzhou University from 2011 to 2014 were retrospectively analyzed. These patients were grouped for further analysis according to the optimal threshold of preoperative tumor volume, length and maximum diameter. Kaplan-Meier method was used to calculate survival rate and survival comparison was performed by log-rank test. The univariate and multivariate Cox models were used to analyze the relationships between clinical variables and survival prognosis. Finally, nomogram model was established by integrating statistically significant clinicopathological parameters, and the predictive value of this model was further verified by calibration curve, concordance index (C-index) and decision curve. Results The optimal thresholds of preoperative tumor volume were 32 cm 3 and 72 cm 3 by X-tile analysis, and among the patients whose tumor volume was <32 cm 3 (n=94), the 1-, 3- and 5-year survival rates were 100%, 84.0% and 68.1%; in the 32-72 cm 3 group (n=118), the 1-, 3- and 5-year survival rates were 98.3%, 42.4% and 24.6%; in the >72 cm 3 group (n=84), the 1-, 3- and 5-year survival rates were 94.1%, 25.0 and 7.1% (χ 2=86.639, P<0.001). The optimal cutoff values of tumor length were 3.0 cm and 5.0 cm, and among the patients with tumor length <3.0 cm (n=62), the 1-, 3-, and 5-year survival rates were 99.5%, 87.1% and 69.4%; in the 3.0-5.0 cm group (n=146), the 1-, 3-, and 5-year survival rates were 98.6%, 47.9% and 30.1%; in the >5.0 cm group (n=88), the 1-, 3-, and 5-year survival rates were 94.3%, 29.6%, 13.6%, respectively (χ 2=53.607, P<0.001). The thresholds of tumor maximum diameter were 2.5 cm and 3.5 cm, and among these, the 1-, 3- and 5-year survival rates were 99.5%, 84.3% and 74.5% in the maximum diameter <2.5 cm group (n=51); 98.3%, 57.0% and 36.4% in the 2.5-3.5 cm group (n=121); and 96.0%, 29.0% and 13.7% in the maximum diameter >3.5 cm group (n=124, χ 2=62.109, P<0.001). In univariate analysis, the following factors were significantly associated with overall survival (OS): tumor location, differentiation grade, T stage, N stage, TNM stage, adjuvant therapy, preoperative tumor volume, length and maximum diameter (all P<0.05). Furthermore, multivariate Cox regression analysis showed that differentiation grade (HR=0.514, 95%CI: 0.366-0.723, P=0.019), TNM stage (HR=1.757, 95%CI: 1.267-2.612, P=0.015), adjuvant therapy (HR=0.669, 95%CI: 0.503-0.889, P=0.006), preoperative tumor volume (set <32 cm 3 as the dummy variable, 32-72 cm 3: HR=3.689, 95%CI: 2.415-5.637, P<0.001; >72 cm 3: HR=5.720, 95%CI: 3.606-9.075, P<0.001) were independent risk factors for OS. Finally, the C-index of OS by nomogram incorporated the statistically significant clinicopathological parameters was predicted to be 0.722 (95%CI: 0.687-0.757), which was significantly higher than the 7th AJCC TNM stage, the C-index 0.633 (95%CI: 0.595-0.671). In addition, the calibration curve of nomogram model was highly consistent with actual observation for the five-year OS rate, and the decision curve analysis also showed that nomogram model had higher clinical application potentials than TNM staging model in predicting survival prognosis of thoracic ESCC after surgery. Conclusion The nomogram incorporated preoperative tumor volume is of great value in predicting survival prognosis of patients with thoracic ESCC.

Key words: Esophageal neoplasms, Nomograms, Prognosis, Tumor volume