肝细胞癌TACE介入治疗后原位癌复发、转移风险模型的构建与验证

Construction and validation of a risk model for recurrence and metastasis of hepatocellular carcinoma in situ after TACE interventional therapy

目的构建并验证个体化预测肝细胞癌(HCC)肝动脉栓塞化疗栓塞术(TACE)介入治疗后原位癌复发、转移风险模型。方法选择2015年1月至2018年2月于该院收治的HCC患者192例,根据患者TACE介入治疗后原位癌复发、转移情况分为预后良好组及预后不良组,比较两组年龄、性别等一般资料及肿瘤最大径、血管侵犯等肿瘤相关资料,多因素Logistic回归分析HCC进行TACE介入治疗后原位癌复发、转移的因素。结果相较于预后良好组,预后不良组患者年龄≥50岁、甲胎蛋白(AFP)≥400μg/L、磷脂酰肌醇蛋白聚糖3(GPC3)、醇脱氢酶(ADH)水平明显升高,差异具有统计学意义(P<0.05)。相较于预后良好组,预后不良组患者血管侵犯、肿瘤多发、肿瘤最大径≥5 cm、无肿瘤包膜比例明显升高,差异有统计学意义(P<0.05)。多因素Logisitic回归分析发现,年龄、AFP、GPC3、ADH、血管侵犯、肿瘤最大径为HCC进行TACE介入治疗后原位癌复发、转移的危险因素,肿瘤包膜为HCC进行TACE介入治疗后原位癌复发、转移的保护因素(P<0.05)。根据多因素Logistic回归分析绘制列线图,经Bootstrap自抽样内部验证后,一致性指数为0.752,分辨度良好;经受试者工作特征(ROC)曲线分析该模型预测术后1年无复发生存的曲线下面积(AUC)为0.851(95%CI:0.778~0.896)。随访60个月,生存率为39.06%(75/192),中位生存时间23个月,Kaplan-Meier生存曲线分析结果显示,年龄≤50岁、AFP<400μg/L、GPC3<215 ng/L、ADH<2.8μmol/(s·L)、无血管侵犯、肿瘤最大径<5 cm、有肿瘤包膜的HCC患者生存率较高。结论年龄、AFP、GPC3、ADH、血管侵犯、肿瘤数目、肿瘤最大径等与TACE介入治疗后原位癌复发、转移情况存在密切联系,以此为指标构建风险模型在预测原位癌复发、转移情况具有一定价值,可在临床中广泛应用。

Objective To construct and validate a personalized risk model for predicting recurrence and metastasis of hepatocellular carcinoma(HCC)in situ after transcatheter arterial chemoembolization(TACE).Methods A total of 192 patients with HCC admitted to Wuhan Red Cross Hospital from January 2015 to February 2018 were selected and divided into two groups according to the recurrence and metastasis of HCC in situ after TACE intervention treatment.General data such as age,gender,and tumor related data such as tumor maximum diameter and vascular invasion were compared between the two groups.Multivariate Logistic regression analysis was conducted to analyze the factors affecting recurrence and metastasis of HCC in situ after TACE intervention treatment.Results Compared with the group with good prognosis,the patients with poor prognosis were≥50 years old and alpha fetoprotein(AFP)≥400μg/L.The levels of glypican 3(GPC3),and alcohol dehydrogenase(ADH)were significantly increased,and the difference was statistically significant(P<0.05).Compared with the group with good prognosis,the proportion of patients with poor prognosis who had vascular invasion,multiple tumors,tumor maximum diameter≥5 cm,and no tumor envelope was significantly higher,and the difference was statistically significant(P<0.05).Multivariate logistic regression analysis found that age,AFP,GPC3,ADH,vascular invasion,and tumor maximum diameter were risk factors for recurrence and metastasis of HCC in situ after TACE intervention,while tumor envelope was a protective factor for recurrence and metastasis of HCC in situ after TACE intervention(P<0.05).A nomogram was drawn based on multivariate logistic regression analysis.After internal validation by Bootstrap self sampling,the consistency index was 0.752,with good resolution;After ROC curve analysis,the model predicted a recurrence free survival area under the curve(AUC)of 0.851(95%CI:0.778-0.896)at 1 year after surgery.Following up for 60 months,the survival rate was 39.06%(75/192),and the median survival time was 23 months.Kaplan Meier survival curve analysis showed that HCC patients with age≤50 years old,AFP<400μg/L,GPC3<215 ng/L,ADH<2.8μmol/(s·L).non vascular invasion,tumor maximum diameter<5 cm,and tumor capsulehad a is higher survival rate.Conclusion Age,AFP,GPC3,ADH,vascular invasion,tumor number,and tumor maximum diameter are closely related to the recurrence and metastasis of carcinoma in situ after TACE interventional therapy.Building risk models based on these indicators has certain value in predicting the recurrence and metastasis of carcinoma in situ,and can be widely used in clinical practice.