Prospective study of Lipiodol distribution as an imaging marker for doxorubicin pharmacokinetics during conventional transarterial chemoembolization of liver malignancies
Prospective study of Lipiodol distribution as an imaging marker for doxorubicin pharmacokinetics during conventional transarterial chemoembolization of liver malignancies
复制标题
DOI：
10.1007/s00330-020-07380-w
复制
发表时间：
2020-10-15
影响因子：
5.9
通讯作者：
Schlachter, Todd
中科院分区：
文献类型：
--
作者：
Savic, Lynn J.;Chapiro, Julius;Schlachter, Todd
目的评价碘油分布对常规经动脉化疗栓塞术（cTACE）后多柔比星（DOX）和多柔比星（DOXOL）药代动力学（PK）特征的预后潜力。（：NCT 02753881）包括30名接受cTACE治疗的肝脏恶性肿瘤连续受试者（5/2016-10/2018）使用50 mg DOX/10 mg丝裂霉素C与乙碘油（碘油）以1：2乳化。在10个时间点采集外周血，进行峰浓度（C-max）和曲线下面积（AUC）的标准非房室分析，并进行剂量归一化（DN）。成像标志物包括cTACE后CT上的碘油分布，患者分层为1个节段（n = 10）、>= 2个节段（n = 10）和肺叶cTACE（n = 10），以及基线增强肿瘤体积（ETV）。在cTACE后3-4周记录不良事件（AE）和MRI上的肿瘤缓解。统计方法包括重复测量方差分析（RM-ANOVA）、Mann-Whitney、Kruskal-Wallis、Fisher精确检验和Pearson相关分析。根据碘油分布分层，DOX-C（max）从1个节段开始升高（DOX-C-max，83.94 +/- 75.09 ng/mL; DN-DOX-C-max，2.67 +/- 2.02 ng/mL/mg）至>= 2个节段（DOX-C-max，139.66 +/- 117.73 ng/mL; DN-DOX-C-max，3.68 +/- 4.20 ng/mL/mg）与肺叶分布（DOX-C-max，334.35 +/- 215.18 ng/mL; DN-DOX-C-max，7.11 +/- 4.24 ng/mL/mg;p = 0.036）。虽然DN-DOX-AUC的差异仍然不显著，但RM-ANOVA显示DOX（p = 0.023）和DOXOL（p = 0.041）的时间浓度曲线显著分离，比较1、>= 2段和肺叶cTACE。较高DN-DOX-C（max）的其他指标为高ETV（p = 0.047）和Child-Pugh B（p = 0.009）。高ETV和肿瘤碘油覆盖率也与肿瘤缓解相关。结论：本前瞻性临床试验提供了更新的PK数据，显示碘油分布是预测肝癌cTACE后DOX-C（max）和肿瘤缓解的成像标志物。
Objectives To evaluate the prognostic potential of Lipiodol distribution for the pharmacokinetic (PK) profiles of doxorubicin (DOX) and doxorubicinol (DOXOL) after conventional transarterial chemoembolization (cTACE).Methods This prospective clinical trial (: NCT02753881) included 30 consecutive participants with liver malignancies treated with cTACE (5/2016-10/2018) using 50 mg DOX/10 mg mitomycin C emulsified 1:2 with ethiodized oil (Lipiodol). Peripheral blood was sampled at 10 timepoints for standard non-compartmental analysis of peak concentrations (C-max) and area under the curve (AUC) with dose normalization (DN). Imaging markers included Lipiodol distribution on post-cTACE CT for patient stratification into 1 segment (n = 10), >= 2 segments (n = 10), and lobar cTACE (n = 10), and baseline enhancing tumor volume (ETV). Adverse events (AEs) and tumor response on MRI were recorded 3-4 weeks post-cTACE. Statistics included repeated measurement ANOVA (RM-ANOVA), Mann-Whitney, Kruskal-Wallis, Fisher's exact test, and Pearson correlation.Results Hepatocellular (n = 26), cholangiocarcinoma (n = 1), and neuroendocrine metastases (n = 3) were included. Stratified according to Lipiodol distribution, DOX-C(max)increased from 1 segment (DOX-C-max, 83.94 +/- 75.09 ng/mL; DN-DOX-C-max, 2.67 +/- 2.02 ng/mL/mg) to >= 2 segments (DOX-C-max, 139.66 +/- 117.73 ng/mL; DN-DOX-C-max, 3.68 +/- 4.20 ng/mL/mg) to lobar distribution (DOX-C-max, 334.35 +/- 215.18 ng/mL; DN-DOX-C-max, 7.11 +/- 4.24 ng/mL/mg;p = 0.036). While differences in DN-DOX-AUC remained insignificant, RM-ANOVA revealed significant separation of time concentration curves for DOX (p = 0.023) and DOXOL (p = 0.041) comparing 1, >= 2 segments, and lobar cTACE. Additional indicators of higher DN-DOX-C(max)were high ETV (p = 0.047) and Child-Pugh B (p = 0.009). High ETV and tumoral Lipiodol coverage also correlated with tumor response. AE occurred less frequently after segmental cTACE.Conclusions This prospective clinical trial provides updated PK data revealing Lipiodol distribution as an imaging marker predictive of DOX-C(max)and tumor response after cTACE in liver cancer.