多参数磁共振成像联合CT动态增强对晚期肝细胞癌免疫治疗疗效的预测价值

The predictive value of multiparametric magnetic resonance imaging combined with CT dynamic enhancement on the efficacy of immunotherapy for patients with advanced hepatocellular carcinoma

目的 探讨多参数磁共振成像(Nuclear magnetic resonance imaging, MRI)联合CT动态增强对晚期肝细胞癌(Hepatocellular carcinoma, HCC)免疫治疗疗效的预测价值。方法 选取2020年8月—2022年8月在青岛大学附属青岛市中心医院经穿刺活检组织病理学检查确诊的晚期HCC患者123例为研究对象,均于免疫治疗前接受MRI及CT动态增强检查。随机分为训练组和验证组,86例纳入训练组,37例纳入验证组。训练组免疫治疗8周后,根据改良实体瘤疗效评价标准将所有患者分为控制组(32例)和进展组(54例),比较两组MRI参数[增强率(Enhanced response, ER)、脂肪分数(Full fat, FF)、最大下降斜率(Mean squared deviation, MSD)、最大上升斜率(Modified surface index, MSI)、平均强化时间(Mean exit time, MET)、表观扩散系数(Apparent diffusion coefficient, ADC)、容积转换常数(Ktrans)、速率常数(Kep)、血管外细胞外容积分数(Ve)、血浆容积分数(Vp)]和CT动态增强扫描定量参数[灌注值、强化峰值(Potential of hydrogen, PH)、肿块与主动脉强化峰值之比(M/A)值、肿块强化达到峰值时间(Time-to-peak tension, Tp)]。采用Spearman相关系数分析MRI参数和CT动态增强扫描定量参数与晚期HCC免疫治疗疗效的相关性,绘制受试者工作特征(ROC)曲线评估MRI参数联合CT动态增强扫描定量参数对晚期HCC免疫治疗疗效的预测价值,并在验证组中加以验证。结果 控制组ER、MSI均大于进展组,ADC、Ktrans、Ve均小于进展组(P<0.05)。控制组灌注值、PH值均小于进展组,Tp大于进展组(P<0.05)。MRI参数ER、MSI与免疫治疗疗效呈正相关性(r=0.326、0.331,均P<0.05),ADC、Ktrans、Ve与免疫治疗疗效呈负相关性(r=-0.331、-0.342、-0.350,均P<0.05);CT动态增强扫描定量参数灌注值、PH与免疫治疗疗效呈负相关性(r=-0.402、-0.394,均P<0.05),Tp与免疫治疗疗效呈正相关性(r=0.387,P<0.05)。训练组MRI参数ER、MSI、ADC、Ktrans、Ve预测免疫治疗疗效的曲线下面积(AUC)分别为0.742、0.770、0.761、0.720、0.731,CT动态增强扫描定量参数灌注值、PH、Tp预测免疫治疗疗效的AUC分别为0.730、0.743、0.699,均小于MRI参数与CT动态增强扫描定量参数联合预测的AUC(0.879)(均P<0.05)。联合预测在验证组中亦具有较好的诊断效能AUC(0.868)。结论 MRI参数联合CT动态增强扫描定量参数对于晚期HCC患者免疫治疗疗效有良好预测价值。

Objective To investigate the predictive value of multiparametric magnetic resonance imaging(mpMRI)combined with CT dynamic enhancement on the efficacy of immunotherapy for patients with advanced hepatocellular carcinoma(HCC).Methods 123 patients with advanced HCC diagnosed by histopathological examination of puncture biopsy from August 2020 to August 2022 were selected for the study.All patients received MRI and CT dynamic enhancement examination before immunotherapy.They were randomly divided into a training group and a validation group,Among them,86 cases were included in the training group and 37 cases were included in the validation group.At 8 weeks after immunotherapy,all patients in the training group were further divided into a control group(32 cases)and a progressive group(54 cases)according to the modified solid tumor efficacy evaluation criteria,and the two groups were compared for MRI parameters[i.e.,enhancement rate(ER),fat fraction(FF),maximum downward slope(MSD),maximum upward slope(MSI),mean enhancement time(MET),apparent diffusion coefficient(ADC),volume conversion constant(Ktrans),rate constant(Kep),extravascular extracellular volume fraction(Ve),plasma volume fraction(Vp)]and CT dynamic Enhancement scan quantitative parameters[i.e.,perfusion value,peak enhancement(PH),ratio of mass to peak aortic enhancement(M/A)value,and time to peak mass enhancement(Tp).Spearman’s correlation coefficient was used to analyze the correlation between MRI parameters and quantitative CT dynamic enhancement scan parameters and the efficacy of immunotherapy for advanced HCC.The receiver operating characteristic(ROC)curve were plotted to assess the predictive value of MRI parameters combined with quantitative CT dynamic enhancement scan parameters on the efficacy of immunotherapy for advanced HCC,and the efficacy was validated in the validation group.Results The ER,MSI,and Ktrans in patients of the control group were greater than those in the progressive group,and the ADC and Ve were smaller than those in the progressive group,with statistically significant differences(P<0.05).The perfusion and PH value in the control group were smaller than those in the progressive group,and Tp was larger than that in the progressive group,with statistically significant difference(P<0.05).In the mpMRI parameters,ER and MSI were positively correlated with immunotherapy efficacy(r=0.326,0.331,both P<0.05),whereas ADC,Ktrans and Ve were negatively correlated with immunotherapy efficacy(r=-0.331,-0.342,-0.350,all P<0.05).In the quantitative parameters of CT dynamic enhancement scan,the perfusion value and PH were negatively correlated with immunotherapy efficacy(r=-0.402,-0.394,both P<0.05),and Tp was positively correlated with immunotherapy efficacy(r=0.387,P<0.05).The area under the curve(AUC)of ER,MSI,ADC,Ktrans,and Ve of the MRI parameters in the training group for predicting immunotherapy efficacy was 0.742,0.770,0.761,0.720,and 0.731,respectively.And the AUCs of perfusion value,PH and Tp of the CT dynamic enhancement scan quantitative parameters for predicting immunotherapy efficacy were 0.730,0.743,and 0.699,respectively,all of which were lower than that of 0.879 as predicted by the combination of mpMRI and quantitative parameters of CT dynamic enhancement scan(all P<0.05).The joint prediction also had good diagnostic efficacy with a AUC value of 0.868 in the validation group.Conclusion The mpMRI combined with quantitative CT dynamic enhancement scan parameters have good predictive value for the efficacy of immunotherapy for advanced HCC patients.