摘要
目的 探讨系统免疫炎症指数(SII)联合肿瘤负荷评分(TBS)(以下简称STS)对于肝内胆管癌(ICC)患者根治性切除术后的预后预测价值,并构建列线图模型.方法 回顾性分析2016年1月1日至2020年1月31日在郑州大学人民医院(170例,训练集)和郑州大学肿瘤医院(88例,验证集)就诊并接受根治性切除术的258例ICC患者的临床资料(包括肿瘤分化程度、脉管癌栓、淋巴结转移等),并进行SII、TBS和STS分级.应用多因素Cox回归分析ICC患者预后的独立影响因素,绘制Kaplan-Meier生存曲线和受试者操作特征曲线(ROC)评估SII、TBS和STS对ICC患者根治性切除术后总生存期的预测效能,构建列线图预测模型并采用一致性指数(C-index)和校准曲线评估列线图效能.结果 训练集170例ICC患者中,SII 1级106例,2级64例;TBS 1级137例,2级33例;STS分级1级98例,2级47例,3级25例.验证集88例患者中,SII 1级33例,2级55例;TBS 1级66例,2级22例;STS 1级30例,2级39例,3级19例.多因素Cox回归分析结果显示,肿瘤分化程度[高分化对比中分化HR=0.157,95％置信区间(95％CI)0.045～0.546;高分化对比低分化 HR=0.452,95％CI 0.273～0.750]、STS(3 级对比 2 级HR=1.966,95％CI 1.148～3.469;3 级对比 1 级HR=1.405,95％CI 0.890～2.216)、脉管癌栓(HR=2.006,95％CI 1.313～3.066)、神经侵犯(HR=1.865,95％CI 1.221～2.850)、淋巴结转移(HR=1.802,95％CI 1.121～2.896)是 ICC患者根治性切除术后总生存期的独立影响因素(均P＜0.05).Kaplan-Meier生存曲线分析显示,SII、TBS和STS均是ICC患者根治性切除术后总生存期的独立影响因素(均P＜0.05).ROC分析显示,SII、TBS和STS预测ICC患者根治性切除术后总生存期的曲线下面积分别为 0.566(95％CI 0.479～0.652)、0.585(95％CI 0.499～0.672)、0.657(95％CI 0.522～0.692).纳入肿瘤分化程度、脉管癌栓、神经侵犯、淋巴结转移、STS构建列线图模型,训练集和验证集基于列线图模型的 C-index 分别为 0.792(95％CI0.699～0.825)和0.776(95％CI 0.716～0.833).训练集和验证集的生存率校准曲线均与参考线贴近,列线图模型在训练集和验证集中预测能力均较佳.结论 术前进行STS分级是预测ICC患者根治性切除术后总生存期有效且实用的方法,相较于单独的SII和TBS对ICC患者预后具有更好的预测价值.
Abstract
Objective To explore the prognostic value of systemic immune-inflammatory index(SII)combined with tumor burden score(TBS)(hereinafter referred to as STS)in patients with intrahepatic cholangiocarcinoma(ICC)after radical resection,and to construct a nomogram model.Methods The clinical data(including the degree of tumor differentiation,vascular cancer thrombus,and lymph node metastasis,etc.)of 258 ICC patients who received radical resection at People's Hospital of Zhengzhou University(170 cases,training set)and Cancer Hospital of Zhengzhou University(88 cases,validation set)from January 1,2016 to January 31,2020 were retrospectively analyzed and graded by SII,TBS and STS.Multivariate Cox regression analysis were used to identify independent factors affecting the prognosis of patients with ICC.Kaplan-Meier survival curve and receiver operating characteristic curve(ROC)were drawn to evaluate the predictive efficiency of SII,TBS and STS in the overall survival of patients with ICC after radical resection.The nomogram prediction model was constructed and evaluate the performance of nomogram model using consistency index(C-index)and calibration curve.Results Among 170 ICC patients in the training set,there were 106 cases of SII grade 1 and 64 cases of SII grade 2;137 cases of TBS grade 1 and 33 cases of TBS grade 2;and 98 cases of STS grade 1,47 cases of STS grade 2,and 25 cases of STS grade 3.Among 88 ICC patients in the validation set,there were 33 cases of SII grade 1 and 55 cases of SII grade 2;66 cases of TBS grade 1 and 22 cases of TBS grade 2;and 30 case of STS grade 1,39 cases of TBS grade 2,and 19 cases of TBS grade 3.The multivariate Cox regression analysis showed that tumor differentiation degree(highly differentiated vs.moderately differentiated HR=0.157,95％confidence interval(95％CI)0.045 to 0.546,highly differentiated vs.poorly differentiated HR=0.452,95％CI0.273 to 0.750),STS(grade 3 vs.grade 2 HR=1.966,95％CI 1.148 to 3.469;grade 3 vs.grade 1 HR=1.405,95％CI 0.890 to 2.216),vascular cancer thrombus(HR=2.006,95％CI 1.313 to 3.066),nerve invasion(HR=1.865,95％CI 1.221 to 2.850),and lymph node metastasis(HR=1.802,95％CI 1.121 to 2.896)were independent influencing factors of overall survival in ICC patients after radical resection(all P＜0.05).The Kaplan-Meier survival curve showed that SII,TBS,and STS were independent influencing factors of overall survival in ICC patients(all P＜0.05).The results of ROC analysis showed that the areas under the curve of SII,TBS and STS in predicting overall survival of ICC patients after radical resection were 0.566(95％CI 0.479 to 0.652),0.585(95％CI0.499 to 0.672),and 0.657(95％CI 0.522 to 0.692),respectively.Tumor differentiation,vascular tumor thrombus,nerve invassion,lymph node metastasis,and STS were included to constract the nomogram model.The C-indexes of the training set and validation set based on the nomogram model were 0.792(95％CI 0.699 to 0.825)and 0.776(95％CI0.716 to 0.833),respectively.The calibration curves of the survival rate of the training set and the validation set were close to the reference lines,and the nomogram model had better predictive ability in both the training set and the validation set.Conclusions Preoperative STS grading is an effective and practical predictor of overall survival in ICC patients after radical section.Compared with SII and TBS alone,it has better predictive value for the prognosis of patients with ICC.
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