Department of Radiology and Biomedical Imaging, Yale University School of Medicine, 330 Cedar Street, New Haven, CT 06520, USA.
Department of Radiology and Biomedical Imaging, Yale University School of Medicine, 330 Cedar Street, New Haven, CT 06520, USA; Department of Radiology, Charité University School of Medicine, Charitépl. 1, 10117 Berlin, Germany.
Clin Imaging. 2021 Oct;78:194-200. doi: 10.1016/j.clinimag.2021.05.007. Epub 2021 May 18.
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.
MATERIALS & METHODS: 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 h 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 24 h 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 24 h post-cTACE MDCT. The spatial and volumetric agreement between Lipiodol deposition on intra-procedural CBCT and 24 h post-cTACE MDCT could suggest that acquiring MDCT 24 h 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.
在传统经动脉化疗栓塞术（cTACE）中使用碘化油-利福霉素可确保放射不透性，以便在为肝癌和动脉栓塞提供选择性药物靶向的过程中可视化药物输送。利福霉素作为靶向治疗的化疗药物载体，作为栓塞剂，通过流出门静脉增强药物效果，以及预测肿瘤反应和存活的指标。
前瞻性评估 cTACE 后即刻 CBCT 上肝肿瘤内利福霉素沉积的 3D 定量评估作为 cTACE 结果的预测生物标志物的作用。
这是一项经机构审查委员会批准的前瞻性临床试验数据的事后分析。32 名肝细胞癌或肝转移患者在 cTACE 后立即接受对比增强 CBCT、cTACE 后 24 小时的非增强 MDCT 以及 30、90 和 180 天的随访成像。在 cTACE 后对 CBCT 上的利福霉素沉积进行定量，并通过 4 个有序水平进行特征描述：≤25%、>25-50%、>50-75%、>75%。在随访 MRI 上评估肿瘤反应。评估成像上的利福霉素沉积、利福霉素沉积与肿瘤反应标准之间的相关性以及利福霉素覆盖范围与中位总生存期（MOS）之间的相关性。
图像分析显示 CBCT 上的利福霉素沉积与 24 小时后 CT 上的利福霉素沉积之间具有高度一致性，Bland-Altman 图显示成像上的利福霉素沉积存在 2.75 的偏差，95%-一致性界限：-16.6 至 22.1%。在 30 天（p=0.02）和 90 天（p=0.05）时，应答者与非应答者的二维 EASL 利福霉素沉积之间的反向关系达到统计学意义。在改良实体瘤反应评估标准（mRECIST）应答者与非应答者之间，EASL-30d、EASL-90d 和定量 EASL-180d 的应答者的体积沉积量更高，具有统计学意义。cTACE 后，相对利福霉素沉积与增强肿瘤体积变化之间的相关性呈负相关（30 天：p<0.001；rho=-0.63）。高 vs. 低利福霉素沉积患者的 Kaplan-Meier 分析显示 MOS 为 46 与 33 个月（p=0.05）。
在原发性或转移性肝癌患者中，cTACE 过程中 CBCT 上利福霉素沉积的 3D 定量是预测结局的生物标志物。在 cTACE 过程中 CBCT 上的利福霉素沉积的 3D 定量与 24 小时后 cTACE MDCT 之间存在空间和体积一致性。cTACE 过程中 CBCT 上利福霉素沉积与 24 小时后 cTACE MDCT 之间的空间和体积一致性可能表明在 cTACE 后获得 MDCT 是多余的。重要的是，肿瘤覆盖程度与利福霉素之间的关系以及 cTACE 后肿瘤反应的程度和时间线的证明强调了利福霉素作为肿瘤反应的术中替代物的作用，这可能对预测生存有影响。
