Lipiodol-TACE With Idarubicin Based On a Specific Emulsion Ratio for Hepatocellular Carcinoma

Study Overview
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Brief Summary
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The purpose of this observational study is to evaluate properties of lipiodol-idarubicin emulsion mixed with the best regimen obtained in vitro study, including stability, viscosity，visibility under X-ray and deposition, in order to maximize the efficacy of idarubicin-cTACE for HCC.

Detailed Description
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Idarubicin is a DNA topoisomerase II inhibitor that promotes DNA strand breakage, trapping cells in the G2 phase of the cell cycle and inducing DNA cleavage and cell apoptosis. Preclinical studies have shown that idarubicin has higher antitumor activity than epirubicin, especially against SUN-449 human hepatoma cells. In recent years, foreign scholars have conducted a series of explorations in the treatment of hepatocellular carcinoma with lipiodol-idarubicin emulsion, and have obtained positive results. However, in China, idarbicin has just been applied to TACE.Many interventional physicians are accustomed to directly use contrast agents to dissolve anthracyclines in order to improve tracer performance of chemotherapeutic agent-lipiodol emulsion under X-ray and reduce intraoperative reflux and misembolization. Meanwhile, due to the high density of the nonionic contrast media, the lipiodol emulsion can be deposited in the lesion for a long time. The Clinical Practice Guidelines for transcatheter arterial chemoembolization (TACE) Treatment of hepatocellular carcinoma in China (2021 edition) also recommended to prepare the chemotherapeutic drug-lipiodol emulsion according to the standard of  dissolving drug in nonionic contrast agent then mixed with lipiodol to make an emulsion with a ratio of 1:2. At present, there is a lack of detailed objective data on the complete physical properties of the lipiodol-idarubicin emulsion, and some physicians and centers even make the emulsion based only on their habits and preferences.These all may affect the physical properties of the lipiodol emulsion, including intraoperative stability and viscosity of the emulsion, then eventually affect the operation of surgeon and the release behavior of chemotherapeutic drugs, and ultimately influence the efficacy of TACE.Therefore, the purpose of this prospective, observational study is to evaluate properties of lipiodol-idarubicin emulsion mixed with the best regimen obtained in vitro study, including stability, viscosity，visibility under X-ray and deposition, in order to maximize the efficacy of idarubicin-cTACE for HCC.

Official Title
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Transarterial Chemoembolization With Lipiodol-Idarubicin Emulsion Based On a Specific Ratio for Hepatocellular Carcinoma:a Prospective, Observational Study

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Procedure: cTACE(conventional transarterial chemoembolization)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of HCC according to histopathology or CNLC guidelines (2022 Edition); One of the following cases: 1）CNLC stage IIb-IIIa, part of stage IIIb, and CNLC stage Ib and IIa patient who is unable or unwilling to receive surgical treatment due to other reasons (such as advanced age, severe liver cirrhosis, etc.); 2).Child-Pugh class A or B; 3).ECOG PS of 0 - 2; 4)The main portal vein has not been completely obstructed, with abundant collateral vessels, or restore the blood flow by portal vein stent placement 3.At least one measurable lesion (enable to assess lipiodol deposition); 4.Be willing to participate in this study. Exclusion Criteria: Non-HCC patients treated with TACE Incomplete clinical and imaging data Poor image quality or other difficulties in assessing intratumoral lipiodol deposition, including: 1) A large amount of lipiodol was deposited around the lesion 2) Diffuse tumor distribution 3) Intratumoral lipiodol deposition from previous TACE 4) Metal artifacts from previous operations

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Water for Injection -Idarubicin -Lipiodol<br>Idarubicin is first dissolved in water for injection to make a solvent of 1mg/ml, which is then mixed with lipiodol to make an emulsion with a ratio of 1:2. Lipiodol-idarubicin emulsion is slowly injected, followed by embolization with embolic agents. | Procedure: cTACE(conventional transarterial chemoembolization)<br>* transarterial chemoembolization with lipiodol-idarubicin emulsion<br>|
| Nonionic Contrast Agent -Idarubicin -Lipiodol<br>Idarubicin is first dissolved in nonionic contrast agent to make a solvent of 1mg/ml, which is then mixed with lipiodol to make an emulsion with a ratio of 1:2. Lipiodol-idarubicin emulsion is slowly injected, followed by embolization with embolic agents. | Procedure: cTACE(conventional transarterial chemoembolization)<br>* transarterial chemoembolization with lipiodol-idarubicin emulsion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Deposition of of lipiodol-idarubicin emulsion | 1. Assessed by two or more senior radiologists as described in previous works: Excellent：>90%；Good：50%-90%；Poor：<50% 2.3D quantitative assessments of intratumoral lipiodol-emusion using the software 3d-slicer： V1=Volume of tumor (cm3) V2=volume of lipiodol deposition (cm3) Degree of iodized oil uptake:Intratumoral lipiodol retention(%)=V1/V2 | intraoperative and up to 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stability of lipiodol-idarubicin emulsion | Observe and assess the separation of emulsion（when it occures, record the percentage of aqueous phase, the persisting emulsion and the oily phase） | intraoperative | 
| Viscosity of lipiodol-idarubicin emulsion | Observe the tube-adhesion of emulsion.The subjective perception of injection is evaluated by questionnaire. | intraoperative | 
| Visibility of lipiodol-idarubicin emulsion under X-ray: image quality | Assessed by two or more senior radiologists according to Subjective Relative Evaluation of Images. | intraoperative and up to 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatocellular Carcinoma, Transarterial chemoembolization, Idarubicin, Lipiodol emulsion, prospective study