肝癌根治性切除术后早期复发危险因素分析及预测模型构建

Risk factors of primary hepatocellular carcinoma patients early term recurrence after radical resection and prediction model establishment

目的肝癌根治性切除术是原发性肝细胞癌(hepatocellular carcinoma,HCC)最有效的治疗方式,但术后早期复发(<2年)严重影响治疗效果。本研究旨在探讨HCC患者根治性切除术后早期(<2年)复发的相关危险因素,并构建复发预测模型。方法回顾性分析四川省人民医院2005-01-01-2014-12-30行根治性切除术且经病理确诊的564例HCC患者的病历信息资料,并对患者的术后早期复发情况进行追踪随访。采用Kaplan-Meier法计算患者的术后早期复发率,绘制患者的无复发生存曲线。运用多因素Cox比例风险回归模型分析患者术后早期复发的独立危险因素,并建立复发预测模型。结果中位随访时间43个月,术后6、12、24个月累积复发率分别为27.0%(152/564)、39.7%(224/564)和45.6%(257/564)。早期复发率为70.4%(257/365),肝内复发率为56.2%(205/365)。早期复发HCC患者中肝外转移比例为50.2%(129/257),明显高于非早期复发HCC患者中肝外转移的比例28.7%(31/108),差异有统计学意义,χ~2=14.265,P<0.001。共有293例HCC患者死亡,死于肿瘤复发转移273例(93.2%)。早期复发HCC患者中肿瘤复发病死率为82.5%(212/257),明显高于非早期复发HCC患者的肿瘤复发病死率56.5%(61/108),差异有统计学意义,χ~2=27.286,P<0.001。564例HCC患者中位生存时间63个月,1、3、5年累积生存率分别为90.6%、66.5%和50.8%;中位无复发生存时间为38个月,1、3、5年累积无复发生存率分别为74.0%、53.9%和33.8%。进行多因素Cox比例风险回归模型分析显示,肿瘤最大直径>5cm、肿瘤结节数≥2个、肿瘤血管侵犯、肿瘤肝外侵犯是HCC患者术后早期复发的独立危险因素,P<0.05。HCC患者术后早期复发风险函数模型表达式为h(t)=h0exp(1.126 X1+1.473 X2+2.215 X3+2.299 X4)。结论肿瘤最大直径>5cm、肿瘤结节数≥2个、肿瘤血管侵犯和肿瘤肝外侵犯是HCC患者术后早期复发的独立危险因素。

OBJECTIVE The aim of this study is to explore risk factors of primary hepatocellular carcinoma patients early term recurrence after radical resection and to establish prediction model for recurrent primary hepatocellular carcinoma.METHODS From January 1,2005 to December 30,2014,the clinical and follow up data of 564 patients with primary hepatocellular carcinoma who underwent radical surgery at Sichuan Provincial People＇s Hospital were retrospectively analyzed.Kaplan-Meier method was used to estimate early postoperative recurrence rate and to plot relapse-free survival curves of primary hepatocellular carcinoma patients.Multivariate Cox proportional hazards model was used to analysis independent risk factors of patients＇ relapse and establish prediction model for recurrent primary hepatocellular carcinoma.RESULTS The median follow-up time was 43 months,and the cumulative recurrence rate was 27.0%（152/564）,39.7%（224/564）and 45.6%（257/564）at 6 months,12 months and 24 months after operation.Early recurrence occurred in 257 patients（70.4%,257/365）,and intrahepatic recurrence occurred in 205 cases（56.2%,205/365）.The percentage of extrahepatic metastasis in patients with early recurrence of HCC was 50.2%（129/257）,which was higher than that of non early recurrence HCC patients（28.7%）,and the difference was statistically significant（χ^2=14.265,P〈0.001）.A total of 293 patients with HCC died and 273 died（93.2%）of tumor recurrence and metastasis.In the early recurrent HCC patients,the mortality rate of tumor recurrence was 82.5%（212/257）,higher than that of non early recurrence HCC patients,and the fatality rate was 56.5%（61/108）,the difference was statistically significant（chi,χ^2=27.286,P〈0.001）.564 cases of HCC patients with a median survival time of 63 months,1,3,5 year survival rates were 90.6%,66.5%,50.8%;the median disease-free survival time was 38 months,1,3,5 year cumulative relapse free survival rates were74.0%,53.9%,33.8%.Multivariate Cox proportional hazard regression model analysis showed that the maximum diameter of the tumor5 cm and tumor nodules number less than 2,vascular invasion and tumor extrahepatic invasion are independent risk factors for early recurrence of HCC after surgery（P〈0.05）.The risk function model of early recurrence in patients with HCC was expressed as：h（t）=h0 exp（1.126 X1 ＋1.473 X2 ＋2.215 X3 ＋2.299 X4）.CONCLUSION The maximum diameter of tumor,〉5 cm tumor nodules number more than 2,vascular invasion and tumor extrahepatic invasion are independent risk factors for early recurrence of HCC after surgery.