A two-center study of MRI and clinical parameter-based nomogram for predicting the efficacy of D-TACE in hepatocellular carcinoma
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摘要:
目的 探究术前基线增强MRI的影像学特征、临床相关因素对药物洗脱微球-经导管肝动脉化疗栓塞术(D-TACE)疗效的影响。 方法 回顾性分析浙江省肿瘤医院(2018年10月—2022年5月)和嵊州市人民医院(2016年8月—2021年3月)接受初始治疗为D-TACE的患者145例，根据改良实体瘤疗效评价标准(mRECIST)评估D-TACE后的肿瘤应答，应用单因素及多因素logistic回归方法筛选出与D-TACE短期疗效相关的独立因素并建立列线图，并通过绘制ROC曲线，计算AUC。通过多因素Cox回归分析确定影响无进展生存期(PFS)的相关因素。 结果 研究纳入145例患者，多因素logistic回归分析显示谷氨酰转移酶(GGT)、肿瘤肝脏体积比、载药量、门脉癌栓与D-TACE后的短期疗效显著相关；经Bootstrap法进行内部验证，构建的列线图AUC值为0.796(95% CI：0.719~0.864)；校准曲线显示，模型预测值和实际值具有良好的一致性，表明模型的预测性能良好；临床决策曲线显示列线图在临床应用方面表现良好。多因素Cox回归分析显示性别、术后短期疗效是影响PFS的相关因素。 结论 增强MRI的影像学资料和临床相关参数构建的列线图对首次D-TACE短期疗效具有较好的预测效果，有望为筛选从D-TACE中获益的患者提供一种方法。女性、术后短期疗效达到完全缓解(CR)、部分缓解(PR)、疾病稳定(SD)的患者具有更长的PFS。 -
关键词:
- 肝细胞癌 /
- 药物洗脱微球-经导管肝动脉化疗栓塞术 /
- 磁共振成像 /
- 无进展生存期 /
- 列线图
Abstract:Objective To investigate the effects of preoperative imaging features on baseline contrast-enhanced MRI, as well as clinically relevant factors on the efficacy of drug-eluting bead transarterial chemoembolization (D-TACE). Methods A retrospective analysis of patients from two centers who received D-TACE as initial therapy was conducted, with the objective of assessing tumour response after D-TACE according to the modified response tumour evaluation criteria in solid tumours. The objective was to identify the independent factors related to the short-term outcomes of D-TACE. This was achieved by applying univariate and multivariate logistic regression methods, and a nomogram was established. The area under the curve (AUC) was calculated by plotting the receiver operating characteristic (ROC). The factors associated with PFS were determined by means of a multivariate Cox regression analysis. Results The study cohort comprised 145 patients. The results of the multivariate logistic regression analysis indicated that GGT, tumour-to-liver volume ratio, drug-loaded status, and portal vein tumour thrombus was significantly associated with short-term outcomes following D-TACE. Following internal validation by the bootstrap method, the area under the curve (AUC) value of the constructed nomogram was 0.796 (95% CI: 0.719-0.864). The calibration curves demonstrate a high degree of concordance between the predicted and actual values of the model, which indicates an excellent predictive performance. The decision curve analysis indicates that the nomogram performs well in clinical applications. Multivariate Cox regression analysis revealed that gender and postoperative short-term outcomes were significant factors affecting PFS. Conclusion The nomogram, constructed from contrast-enhanced MRI imaging features and clinically relevant parameters, has been demonstrated to be an effective predictor of first D-TACE short-term outcomes. It is anticipated that this nomogram will facilitate the identification of patients who are likely to benefit from D-TACE. Female patients and those with postoperative short-term outcomes of CR, PR, and SD had longer PFS. -
图 2 模型的ROC曲线、校准曲线和临床决策曲线
Figure 2. ROC curve, calibration curve, and decision curve analysis of the model
表 1 2组HCC患者临床基线资料比较
Table 1. Comparison of baseline clinical data between two groups of HCC patients
项目 非OR组(n=43) OR组(n=102) 统计量 P值 性别[例(%)] 0.345a 0.557 男性 35(81.4) 87(85.3) 女性 8(18.6) 15(14.7) 年龄(x±s，岁) 58.8±13.7 61.4±11.8 1.155b 0.250 是否乙型肝炎[例(%)] 0.405a 0.525 否 10(23.3) 19(18.6) 是 33(76.7) 83(81.4) 有无糖尿病[例(%)] 1.096a 0.295 无 37(86.0) 95(93.1) 有 6(14.0) 7(6.9) 术前有无抗病毒治疗[例(%)] 0.474a 0.491 无 31(72.1) 79(77.5) 有 12(27.9) 23(22.5) 肝功能指标[M(P25, P75)] 碱性磷酸酶(U/L) 150.0(117.0，204.0) 119.0(93.3，164.5) -2.639c 0.008 GGT(U/L) 196.0(108.0，277.0) 105.0(57.8，181.8) -3.660c ＜0.001 天冬氨酸转氨酶(U/L) 63.0(44.0，102.0) 45.0(34.0，71.8.0) -2.303c 0.021 丙氨酸转氨酶(U/L) 36.0(24.0，58.0) 34.5(23.8，53.0) -1.102c 0.270 血小板计数(×109个/L) 154.0(102.0，220.0) 160.5(107.5，220.5) -0.271c 0.787 甲胎蛋白(ng/mL) 1 238.1(20.1，25 711.1) 131.9(11.5，2 236.2) -1.777c 0.076 Child-Pugh分级[例(%)] 3.130a 0.077 A级 43(100.0) 92(90.2) B级 0 10(9.8) CNLC分期[例(%)] 12.333a 0.030 Ⅰa 0 11(10.8) Ⅰb 5(11.6) 15(14.7) Ⅱa 2(4.7) 15(14.7) Ⅱb 4(9.3) 13(12.7) Ⅲa 15(34.9) 26(25.5) Ⅲb 17(39.5) 22(21.6) BCLC分期[例(%)] 9.173a 0.010 A期 5(11.6) 26(25.5) B期 6(14.0) 28(27.5) C期 32(74.4) 48(47.1) 注：a为χ2值，b为t值，c为Z值。 
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表 2 2组HCC患者载药微球相关资料比较
Table 2. Comparison of drug-loaded microspheres data between two groups of HCC patients
项目 非OR组(n=43) OR组(n=102) 统计量 P值 载药药物[例(%)] 1.610a 0.447 表柔比星 28(65.1) 76(74.5) 伊达比星 8(18.6) 16(15.7) 伊立替康 7(16.3) 10(9.8) 载药量[M(P25, P75), mg] 60(50，60) 50(40，60) -2.068b 0.039 微球类型[例(%)] 7.713a 0.005 CalliSpheres 18(41.9) 68(66.7) DC Beads 25(58.1) 34(33.3) 微球大小[例(%)] 3.407a 0.164 70~150 μm 1(2.3) 4(3.9) 100~300 μm 12(27.9) 44(43.1) 300~500 μm 30(69.8) 54(52.9) 注：a为χ2值，b为Z值。
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表 3 2组HCC患者的影像学基线资料比较
Table 3. Comparison of baseline imaging data between two groups of HCC patients
项目 非OR组(n=43) OR组(n=102) 统计量 P值 肿瘤部位[例(%)] 2.591a 0.670 肝左叶 33(76.7) 76(74.5) 肝右叶 2(4.7) 6(5.9) 肝左右叶 7(16.3) 11(10.8) 肝左叶Ⅳ段 1(2.3) 8(7.8) 肝尾状叶 0 1(1.0) 肿瘤数目[例(%)] -0.115b 0.908 1个 18(41.9) 34(33.3) 2~4个 7(16.3) 32(31.4) >4个 18(41.9) 36(35.3) 肿瘤最大径(x±s，cm) 10.9±3.5 7.9±3.7 4.419c ＜0.001 肿瘤/肝脏体积比[M(P25, P75)] 0.33(0.14, 0.49) 0.16(0.05, 0.29) -4.130b ＜0.001 肿瘤边缘是否清晰[例(%)] 2.405a 0.121 否 16(37.2) 25(24.5) 是 27(62.8) 77(75.5) 肿瘤强化程度[例(%)] 10.378a 0.006 轻度不均匀 8(18.6) 16(15.7) 明显不均匀 35(81.4) 65(63.7) 明显均匀 0 21(20.6) 肿瘤边缘强化程度[例(%)] 15.848a ＜0.001 不明显 11(25.6) 63(61.8) 明显 32(74.4) 39(38.2) 瘤内是否坏死/出血[例(%)] 6.819a 0.033 无 2(4.7) 23(22.5) 坏死 37(86.0) 72(70.6) 出血 4(9.3) 7(6.9) 肿瘤内是否有脂肪[例(%)] 0.274a 0.601 无 41(95.3) 93(91.2) 有 2(4.7) 9(8.8) 肿瘤包膜[例(%)] 1.989a 0.158 无 10(23.3) 14(13.7) 有 33(76.7) 88(86.3) 瘤内动脉[例(%)] 5.304a 0.021 无 4(9.3) 27(26.5) 有 39(90.7) 75(73.5) 门脉癌栓[例(%)] 10.667a 0.001 无 17(39.5) 70(68.6) 有 26(60.5) 32(31.4) 卫星灶[例(%)] 0.882a 0.348 无 17(39.5) 49(48.0) 有 26(60.5) 53(52.0) 注：a为χ2值，b为Z值，c为t值。
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表 4 变量赋值情况
Table 4. Variable assignment
变量 赋值方法 Child-Pugh分级 A级=1，B级=2 CNLC分期 Ⅰa=1，Ⅰb=2，Ⅱa=3，Ⅱb=4，Ⅲa=5，Ⅲb=6 BCLC分期 A期=1，B期=2，C期=3 微球类型 CalliSpheres=0，DC Beads=1 肿瘤强化程度 轻度不均匀=(0，0)，明显不均匀=(1，0)，明显均匀=(0，1) 肿瘤边缘强化程度 不明显=0，明显=1 瘤内是否坏死/出血 无=(0，0)，坏死=(1，0)，出血=(0，1) 瘤内动脉 无=0，有=1 门脉癌栓 无=0，有=1 短期疗效 非OR=0，OR=1 注：GGT、载药量等连续变量均以实际值赋值。
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表 5 影响D-TACE短期疗效的多因素logistic回归分析
Table 5. Multivariate logistic regression analysis of factors influencing the short-term efficacy of D-TACE
变量 B SE Waldχ2 P值 OR(95% CI) GGT -0.003 0.002 5.095 0.024 0.997(0.994~1.000) 载药量 -0.020 0.008 6.055 0.014 0.981(0.965~0.996) 肿瘤肝脏体积比 -4.440 1.408 9.948 0.002 0.012(0.001~0.186) 门脉癌栓 -1.137 0.453 6.291 0.012 0.321(0.132~0.780) 注：以OR组为参照。
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表 6 变量赋值情况
Table 6. Variable assignment
变量 赋值方法 性别 男性=0，女性=1 术后短期疗效 PD=1，SD=2，PR=3，CR=4 BCLC A期=1，B期=2，C期=3 肿瘤边缘是否清晰 否=0，是=1 肿瘤边缘强化程度 不明显=0，明显=1 是否有卫星灶 否=0，是=1 ALP 连续变量以实际值赋值 肿瘤最大径 连续变量以实际值赋值
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表 7 影响PFS的多因素Cox回归分析结果
Table 7. Results of multivariate Cox regression analysis influencing PFS
变量 单因素 多因素 HR(95% CI) P值 HR(95% CI) P值 性别 0.434(0.200~0.943) 0.035 0.363(0.165~0.801) 0.012 术后短期疗效 0.581(0.432~0.782) ＜0.001 0.638(0.443~0.918) 0.016 BCLC 1.308(1.006~1.701) 0.045 1.022(0.748~1.396) 0.891 肿瘤边缘是否清晰 0.566(0.352~0.908) 0.018 1.017(0.582~1.779) 0.953 肿瘤边缘强化程度 1.860(1.207~2.866) 0.005 1.496(0.876~2.554) 0.141 是否有卫星灶 1.680(1.084~2.605) 0.020 1.435(0.893~2.307) 0.136 ALP(U/L) 1.003(1.000~1.005) 0.044 1.001(0.998~1.005) 0.524 肿瘤最大径(cm) 1.055(0.999~1.114) 0.056 0.992(0.924~1.066) 0.834
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