Lipiodol as an intra-procedural imaging biomarker for liver tumor response to transarterial chemoembolization: Post-hoc analysis of a prospective clinical trial.
Lipiodol as an intra-procedural imaging biomarker for liver tumor response to transarterial chemoembolization: Post-hoc analysis of a prospective clinical trial.
复制标题
DOI：
10.1016/j.clinimag.2021.05.007
复制
发表时间：
2021-10
期刊：
影响因子：
2.1
通讯作者：
Chapiro J
中科院分区：
文献类型：
--
作者：
Letzen BS;Malpani R;Miszczuk M;de Ruiter QMB;Petty CW;Rexha I;Nezami N;Laage-Gaupp F;Lin M;Schlachter TR;Chapiro J
在传统的肝动脉化疗栓塞术(CTACE)中使用乙碘化油-碘油，在为肝癌提供选择性药物靶向和动脉栓塞术的过程中，确保了显影给药的不透明性。碘油作为化疗药物的载体用于靶向治疗，作为栓塞剂，通过外流到门静脉来增强药物效应，并预测肿瘤的反应和生存。目的：前瞻性地评价cTACE术后即刻CBCT上三维定量评估肝肿瘤内碘油沉积作为预测cTACE治疗结果的生物标志物的作用。这是对IRB批准的前瞻性临床试验数据的事后分析。32例肝细胞癌或肝转移瘤患者在cTACE后即刻行CBCT增强扫描，在cTACE后24小时行多层螺旋CT平扫，术后30、90、180天进行随诊。碘油沉积在cTACE后在CBCT上被量化，并按顺序分为4个水平：≤25%，>；25-50%，>；50-75%，>；75%。通过随访的MRI评估肿瘤反应。评估影像上的碘油沉积，碘油沉积与肿瘤反应标准的相关性，以及碘油覆盖率与中位总生存期(MOS)的相关性。图像分析显示CBCT上的碘油沉积与TACE后24小时CT上的碘油沉积高度一致，Bland-Altman图像上的碘油沉积图的偏差为2.75%，95%的一致性限：−为16.6%至22.1%。在二维EASL中，有反应者和无反应者的碘油沉积之间的负相关在30天(p=0.02)和90天(p=0.05)达到统计学意义。比较实体肿瘤改良反应评估标准(MRECIST)应答者和无应答者的碘油沉积，欧洲肝脏研究协会(EASL)应答者的体积沉积显著高于欧洲肝脏研究协会(EASL)-30d、EASL-90d和定量EASL-180d。相对碘化油沉积与增强的肿瘤体积变化呈负相关(30d：P<；0.001；Rho=−0.63)。Kaplan-Meier分析显示，高与低碘脂肪沉积患者的MOS分别为46个月与33个月(p=0.05)。在接受cTACE治疗的原发性或转移性肝癌患者中，术中CBCT上碘油沉积的3D定量是一个预测预后的生物标志物。术中CBCT上碘油沉积的3D定量与CTACE后24小时的MDCT在空间和体积上是一致的。术中CBCT上的碘油沉积与cTACE后24小时的MDCT在空间和体积上的一致性可能表明，在cTACE后24小时获得MDCT是多余的。重要的是，碘化油覆盖肿瘤的水平与cTACE后肿瘤反应的程度和时间线之间的关系强调了碘化油作为肿瘤反应的术中替代物的作用，这对预测生存具有潜在的意义。
The use of the ethiodized oil- Lipiodol in conventional trans-arterial chemoembolization (cTACE) ensures radiopacity to visualize drug delivery in the process of providing selective drug targeting to hepatic cancers and arterial embolization. Lipiodol functions as a carrier of chemo drugs for targeted therapy, as an embolic agent, augmenting the drug effect by efflux into the portal veins as well as a predictor for the tumor response and survival. To prospectively evaluate the role of 3D quantitative assessment of intra-procedural Lipiodol deposition in liver tumors on CBCT immediately after cTACE as a predictive biomarker for the outcome of cTACE. This was a post-hoc analysis of data from an IRB-approved prospective clinical trial. Thirty-two patients with hepatocellular carcinoma or liver metastases underwent contrast enhanced CBCT obtained immediately after cTACE, unenhanced MDCT at 24 hours after cTACE, and follow-up imaging 30-, 90- and 180-days post-procedure. Lipiodol deposition was quantified on CBCT after cTACE and was characterized by 4 ordinal levels: ≤25%, >25–50%, >50–75%, >75%. Tumor response was assessed on follow-up MRI. Lipiodol deposition on imaging, correlation between Lipiodol deposition and tumor response criteria, and correlation between Lipiodol coverage and median overall survival (MOS) were evaluated. Image analysis demonstrated a high degree of agreement between the Lipiodol deposition on CBCT and the 24hr post-TACE CT, with a Bland-Altman plot of Lipiodol deposition on imaging demonstrated a bias of 2.75, with 95%-limits-of-agreement: −16.6 to 22.1%. An inverse relationship between Lipiodol deposition in responders versus non-responders for two-dimensional EASL reached statistical significance at 30 days (p=0.02) and 90 days (p=0.05). Comparing the Lipiodol deposition in Modified Response Evaluation Criteria in Solid Tumors (mRECIST) responders versus non-responders showed a statistically significant higher volumetric deposition in responders for European Association for the Study of the Liver (EASL)-30d, EASL-90d, and quantitative EASL-180d. The correlation between the relative Lipiodol deposition and the change in enhancing tumor volume showed a negative association post-cTACE (30-day: p<0.001; rho=−0.63). A Kaplan-Meier analysis for patients with high vs. low Lipiodol deposition showed a MOS of 46 vs. 33 months (p=0.05). 3D quantification of Lipiodol deposition on intra-procedural CBCT is a predictive biomarker of outcome in patients with primary or metastatic liver cancer undergoing cTACE. There are spatial and volumetric agreements between 3D quantification of Lipiodol deposition on intra-procedural CBCT and 24h post-cTACE MDCT. The spatial and volumetric agreement between Lipiodol deposition on intra-procedural CBCT and 24hr post-cTACE MDCT could suggest that acquiring MDCT 24 hours after cTACE is redundant. Importantly, the demonstrated relationship between levels of tumor coverage with Lipiodol and degree and timeline of tumor response after cTACE underline the role of Lipiodol as an intra-procedural surrogate for tumor response, with potential implications for the prediction of survival.
登录
查看更多内容
影响因子：
5.9
作者：
Chockalingam, Arun;Duran, Rafael;Lin, MingDe
通讯作者：
Lin, MingDe
DOI：
10.1016/j.jvir.2013.08.017
发表时间：
2013-12-01
影响因子：
2.9
作者：
Chen, Rongxin;Geschwind, Jean-Francois;Lin, MingDe
通讯作者：
Lin, MingDe
影响因子：
5.9
作者：
Savic, Lynn J.;Chapiro, Julius;Schlachter, Todd
通讯作者：
Schlachter, Todd
影响因子：
4.6
作者：
Stark S;Wang C;Savic LJ;Letzen B;Schobert I;Miszczuk M;Murali N;Oestmann P;Gebauer B;Lin M;Duncan J;Schlachter T;Chapiro J
通讯作者：
Chapiro J
影响因子：
3.3
作者：
Chapiro, Julius;Duran, Rafael;Geschwind, Jean Francois
通讯作者：
Geschwind, Jean Francois