肝癌射频消融术后复发危险因素分析及术前预测评分

Risk factors on liver cancer recurrence after radiofrequency ablation and establishment of a preoperative prediction score

目的探讨肝细胞癌(HCC)患者射频消融术(RFA)术后复发的独立危险因素并建立术前预测评分。方法回顾性分析2016年6月至2019年9月中山大学附属中山医院收治的RFA治疗的168例HCC患者资料,应用X-tile软件确定术前循环肿瘤细胞(CTC)最佳的截断值并进行分组,分析术前不同CTC值与各临床因素之间的关系。采用Cox回归模型分析RFA术后复发的独立危险因素,按每项独立危险因素赋值为1分组成预测评分,分为低危组(0~2分)、中危组(3分)及高危组(4~5分),并运用Kaplan-Meier法绘制累积复发曲线,统计各组累积复发率。结果168例患者中男性151例,女性17例,年龄(58.33±9.53)岁。在CTC的检测中,131例肝癌患者CTC≥1个/3.2 ml(77.98%),范围为0~20个/3.2ml。X-tile软件确定HCC患者术前CTC临界值为2个/3.2ml,故CTC≤2个/3.2ml为阴性组(93例),CTC>2个/3.2ml为阳性组(75例)。分析术前CTC与各术前临床参数的关系,发现CTC与肿瘤结节数目、肿瘤最大径及甲胎蛋白(AFP)相关(P<0.05)。多因素分析显示,CTC阳性[HR(95%CI):1.990(1.332~2.974)]、AFP>20 ng/ml[HR(95%CI):1.659(1.111~2.477)]、异常凝血酶原(PIVKA-II)>40 mAU/ml[HR(95%CI):1.580(1.022~2.443)]、肿瘤结节数目≥2个[HR(95%CI):1.568(1.057~2.326)]、肿瘤最大径>30 mm[HR(95%CI):1.544(1.007~2.369)]均是HCC患者RFA术后复发的独立危险因素(P<0.05);三组患者6个月、12个月、18个月的累积复发率低危组为14.9%、35.6%、56.4%,中危组为38.9%、70.5%、85.0%,高危组为64.5%、84.5%、100%,三者患者累积复发曲线对比,差异有统计学意义(P<0.05)。结论术前CTC阳性、AFP>20 ng/ml、PIVKA-II>40 mAU/ml、肿瘤结节数目≥2个、肿瘤最大径>30 mm是HCC患者RFA术后复发的独立危险因素,基于此构建的术前预测评分,对指导临床实践治疗策略具有重要意义。

Objective To study the independent risk factors of tumor recurrence after radiofrequency ablation(RFA)in patients with hepatocellular carcinoma(HCC),and to establish a preoperative prediction score.Methods A retrospective study was conducted on 168 HCC patients treated with RFA at Zhongshan Hospital affiliated to Sun Yat-sen University from June 2016 to September 2019.The X-tile software was used to determine the optimal cut-off value of preoperative circulating tumor cells(CTC)which was then used to analyze the relationship between different CTCs values with various clinical factors.The Cox regression model was used to analyze independent risk factors of recurrence after RFA,and each independent risk factor was assigned a score of 1 to compose the prediction score.The patients were divided into the low-risk group(0-2 scores),intermediate-risk group(3 scores)and high-risk group(4-5 scores).The Kaplan-Meier method was used to draw cumulative recurrence curves in calculating the cumulative recurrence rates of the 3 different groups.Results Of 168 patients,there were 151 males and 17 females.Their age(Mean±SD)was 58.33±9.53 years.CTC≥1/3.2 ml was detected in 131 patients(77.98%)(range 0-20/3.2 ml).The X-tile software determined the preoperative CTC cut-off value of HCC patients to be 2/3.2ml which separated a CTC-negative group with 93 patients,and a positive group of 75 patients.On analyses,the relationship between preoperative CTC and various preoperative clinical parameters were related to number of tumor nodules,tumor maximum diameter and alpha-fetoprotein(AFP)levels(P<0.05).Multivariate analysis showed that CTC positivity[HR(95%CI):1.990(1.332-2.974)],AFP>20 ng/ml[HR(95%CI):1.659(1.111-2.477)],PIVKA-II>40 mAU/ml[HR(95%CI):1.580(1.022-2.443)],number of tumor nodules≥2[HR(95%CI):1.568(1.057-2.326)],and tumor diameter>30 mm[HR(95%CI):1.544(1.007-2.369)]were independent risk factors of recurrence(P<0.05)after RFA in HCC patients.The cumulative recurrence rates of patients at 6 months,12 months,and 18 months were 14.9%,35.6%,and 56.4%in the low-risk group,38.9%,70.5%,and 85.0%in the intermediate-risk group,and 64.5%,84.5%and 100%in the high-risk group.The differences were significant(P<0.05).Conclusion Preoperative CTC positivity,AFP>20 ng/ml,PIVKA-II>40 mAU/ml,tumor nodules≥2,and tumor diameter>30 mm were independent risk factors of recurrence after RFA in HCC patients.This preoperative predictive score could be used to guide clinical treatment strategies.