磁共振成像定量在儿童及青少年侵袭性成熟B细胞非霍奇金淋巴瘤嵌合抗原受体T细胞治疗疗效预测中的价值

The value of ouantitative parameters of magnetic resonance imaging in predicting the efficacy of chimeric antigen receptor T-cell therapy for children and adolescents with mature aggressive B-cell non-Hodgkin lymphoma

目的:探讨磁共振成像(MRI)定量参数在儿童及青少年侵袭性成熟B细胞非霍奇金淋巴瘤(NHL)嵌合抗原受体T细胞(CAR-T)治疗中的预测价值。方法:本研究为多中心回顾性研究,收集2016年1月至2023年1月在河南省肿瘤医院、北京高博博仁医院、新乡医学院第一附属医院确诊为儿童及青少年侵袭性成熟B细胞NHL的44例患儿资料。依据国际儿童NHL评价标准评估患者疗效,分为完全缓解(CR)组及非CR组;基于CAR-T输注前及输注后2周内MRI测定T2信号强度、最小表观扩散系数(ADC)值(ADCmin)、最大ADC值(ADCmax)、ADC值的平均值(ADCmean)等定量值,探究其与患者疗效是否达到CR的关系。采用组内相关系数(ICC)评估观察者一致性。采用独立样本t检验比较组间差异,通过二元逻辑回归分析探讨影响患者治疗效果达到CR的因素并建立预测模型,采用受试者工作特征曲线(ROC)评估其效能。结果:CR组与非CR组输注前T2信号强度比较差异有统计学意义(267±152比364±160,P=0.048),输注后2周内MRI测定ADCmin(0.94±0.38比0.53±0.28,P<0.05)、ADCmax(1.73±0.69比0.84±0.43,P<0.05)、ADCmean(1.28±0.48比0.67±0.33,P<0.05)及T2信号强度(198±139比345±168,P=0.004)比较差异均有统计学意义。基于以上定量参数建立单因素预测模型中,输注前T2信号强度预测完全缓解的曲线下面积(AUC)为0.800,特异度、敏感度和准确度分别为84.0%、57.9%和72.7%;输注后ADCmax的AUC为0.958,特异度、敏感度和准确度分别为88.0%、78.9%和84.1%;输注后T2信号强度的AUC为0.869,特异度、敏感度和准确度分别为84.0%、68.4%和77.3%。结论:MRI定量参数ADC及T2信号强度对早期预测儿童及青少年侵袭性成熟B细胞NHL CAR-T疗效具有重要临床意义,其中ADCmax具有较好的预测效能,可以作为预测CAR-T治疗能否达到CR的最佳指标。

ObjectiveTo investigate the value of quantitative parameters of magnetic resonance imaging(MRI)in predicting the efficacy of chimeric antigen receptor T-cell(CAR-T)therapy for children and adolescents with mature aggressive B-cell non-Hodgkin lymphoma(NHL).MethodsIt was a retrospective multicenter study.Clinical data of 44 children and adolescents diagnosed with mature aggressive B-cell NHL between January 2016 and January 2023 in Henan Cancer Hospital,Beijing Gaobo Boren Hospital,and the First Affiliated Hospital of Xinxiang Medical University were retrospectively analyzed.Patients were divided into complete response(CR)group and non-CR group based on the international criteria for the diagnosis of pediatric NHL.Quantitative parameters of MRI,including T2 signal intensity,the minimal apparent diffusion coefficient(ADCmin),maximal ADC(ADCmax),and the mean ADC(ADCmean)were measured before and within 2 weeks after CAR-T infusion.The correlation between the above parameters and the achievement of CR was analyzed.The intraclass correlation coefficient(ICC)was used to assess the inter-observer agreement among observers in measuring quantitative parameters of MRI.Differences between groups were analyzed using the independent samplet-test.Factors influencing CR were identified through the binary Logistic regression analysis,and a prediction model was established.Model performance was evaluated by plotting receiver operating characteristic(ROC)curves.ResultsSignificant differences were observed between the CR group and non-CR group in T2 signal intensity before CAR-T infusion(267±152 vs.364±160,P=0.048),and ADCmin(0.94±0.38 vs.0.53±0.28,P<0.05),ADCmax(1.73±0.69vs.0.84±0.43,P<0.05),ADCmean(1.28±0.48vs.0.67±0.33,P<0.05),and T2 signal intensity within 2 weeks after CAR-T infusion(198±139vs.345±168,P=0.004).A univariate prediction model was created by introducing the above quantitative parameters.The area under the curve(AUC),specificity,sensitivity,and accuracy of T2 signal intensity before CAR-T infusion in predicting the efficacy on children and adolescents with mature aggressive B-cell NHL were 0.800,84.0%,57.9%,and 72.7%,respectively.The AUC,specificity,sensitivity,and accuracy of ADCmax within 2 weeks of CAR-T infusion were 0.958,88.0%,78.9%,and 84.1%,respectively.The AUC,specificity,sensitivity,and accuracy of T2 signal intensity within 2 weeks of CAR-T infusion were 0.869,84.0%,68.4%,and 77.3%,respectively.ConclusionsQuantitative parameters of MRI,including ADC values and T2 signal intensity,are of great significance in the early prediction of CAR-T therapy efficacy on children and adolescents with mature aggressive B-cell NHL.Among these parameters,ADCmax presents the strongest predictive performance and serves as a valuable indicator for predicting a complete response with CAR-T treatment.