肝细胞癌射频消融后早期复发的影响因素分析及列线图预测模型构建

Analysis of risk factors and construction of predictive nomogram for early recurrence after radiofrequency ablation of hepatocellular carcinoma

目的探讨肝细胞癌(HCC)射频消融后早期复发和晚期复发的最佳分界时间,构建预测早期复发的列线图模型。方法选取2012年1月至2017年12月在中国医学科学院肿瘤医院行射频消融治疗后复发的HCC患者119例,根据患者的复发后生存期(PRS),采用最小P值法确定早期和晚期复发的最佳界值。采用单因素和多因素Logistic回归分析确定早期复发的临床及影像影响因素,构建列线图预测模型并进行内部验证。结果HCC射频消融后早期复发和晚期复发的最佳界值是射频消融后12个月(P=0.005)。据此将患者分为早期复发组(47例)和晚期复发组(72例)。早期复发组患者的下四分位PRS(Q1-PRS)和下四分位总生存期(Q1-OS)分别为11.1和19.1个月,均短于晚期复发组(分别为31.6和81.0个月,P值分别为0.005和<0.001)。多因素Logistic回归分析显示,患者的甲胎蛋白(OR=8.459,95%CI为2.231~32.073)、白蛋白(OR=0.251,95%CI为0.047~1.339)、病灶数量(OR=3.842,95%CI为1.424~10.365)和瘤周强化(OR=8.05,95%CI为1.23~52.80)是早期复发的独立影响因素,将这些因素纳入构建HCC射频消融后早期复发的列线图预测模型。内部验证结果显示,其受试者工作特性曲线的曲线下面积为0.839,灵敏度为68.1%,特异度为93.1%。校准曲线显示,列线图模型的预测曲线接近理想曲线。Hosmer-Lemeshow检验显示,列线图模型的预测结果与实际发生情况差异无统计学意义(P=0.424)。结论射频消融后12个月是HCC早期复发和晚期复发的最佳分界时间。结合临床和影像学特征的列线图预测模型可用于预测HCC射频消融后的早期复发,并可为患者的个体化治疗或随访策略提供指导。

Objective To assess the optimal cut-off value between early recurrence and late recurrence of patients with hepatocellular carcinoma(HCC)after radiofrequency ablation(RFA),and to construct a nomogram to predict early recurrence.Methods A total of 119 patients with HCC who recurred after RFA in Cancer Hospital,Chinese Academy of Medical Sciences from January 2012 to December 2017 were identified.The optimal cut-off value to distinguish early and late recurrence was determined based on differences in post recurrence survival(PRS)by minimum P-value approach.The clinical and radiographic risk factors for early recurrence were identified by univariate and multivariate Logistic regression analysis.The predictive nomogram was constructed by these factors and internally validated.Results The optimal cut-off value to distinguish early recurrence and late recurrence was 12 months after RFA(P=0.005).The patients were divided into early recurrence group(47 cases)and late recurrence group(72 cases).The lower quartile PRS(Q1-PRS)and lower quartile overall survival(Q1-OS)were 11.1 and 19.1 months in the early recurrence group,which were shorter than 31.6 and 81.0 months in the late recurrence group(P=0.005 and P<0.001,respectively).The independent risk factors of early recurrence were alpha fetoprotein(AFP)(OR=8.459,95%CI:2.231-32.073),albumin(ALB)(OR=0.251,95%CI:0.047-1.339),number of lesions(OR=3.842,95%CI:1.424-10.365)and peritumoral enhancement(OR=8.05,95%CI:1.23-52.80),which were further incorporated into constructing the predictive nomogram of early recurrence of HCC after RFA.Internal validation results showed the area under the curve,sensitivity,specificity of the receiver operating characteristic(ROC)curve were 0.839,68.1%and 93.1%,respectively.The calibration curve showed the predicted curve of nomogram was close to the ideal curve.Hosmer-Lemeshow test showed there was no significant difference between the predicted results of nomogram and the actual results(P=0.424).Conclusions An interval of 12 months after RFA is the optimal cut-off value for defining early recurrence and late recurrence.The nomogram is integrated by clinical and radiographic features,which can potentially predict early recurrence of HCC after RFA and may offer useful guidance for individual treatment or follow up.