Hepatocellular Carcinoma (HCC)

Hepatocellular Carcinoma

Lipiodol® Ultra-Fluid
(Iodinated ethyl esters of fatty acids of poppy seed oil)

Lipiodol® clinical data in HCC


Selective cTACE, a standardized procedure to obtain HCC tumor control

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INSPIRE consensus paper

Super-Selective cTACE : a new gold standard in HCC management

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Thierry de Baere et al. (2022)(1)

Initiative on Superselective Conventional Transarterial Chemoembolization Results (INSPIRE)

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Goal & Methods

"Recent recommendations coming from the European Association for the Study of the Liver (EASL) and European Society of Medical Oncology (ESMO) highlighted that TACE must be used in Hepatocellular Carcinoma (HCC) ‘‘selectively targetable’’ and ‘‘accessible to supraselective catheterization". The goal of the manuscript is to better define such population and to standardize superselective cTACE (ss-cTACE) technique."
"Our goal is to help optimize procedure standardization and level out variability across centers."
"An expert panel with extensive clinical-procedural experience in TACE, have come together in a virtual meeting to generate recommendations and express their consensus."

Patient Selection

"The expert panel recommends
- That anytime cTACE is proposed, it should aim at being ss-cTACE.
- That ss-cTACE should be ideally proposed to patients with tumors smaller than 5 cm (and possibly
up to 7 cm), aiming at a complete response.
- That ss-cTACE should be recommended for patients with less than five lesions and a maximum number of two segments involved"

Treatment Delivery

"The expert panel recommends
- That the whole tumor volume should be covered during ss-cTACE to obtain the best response possible. Adding peritumoral margins is encouraged but is not considered mandatory.
- That tumor coverage should be assessed immediately after treatment with non-contrast CBCT.
- That angio-CBCT should be used to detect enhancing tumors, tumor feeders and to guide tumor targeting. The use of navigation or simulation software is encouraged.
- That 2.4 French is recognized as the upper caliber limit accepted to perform ss-cTACE, but lower microcatheter caliber, down to 1.5–2.0 F, is preferred and recommended.
- That a semi-wedge positioning of the catheter in the feeders is acceptable. The microcatheter should be slightly pulled back to a more proximal position for final additional embolization.
- That the treatment should be injected as a water-inoil emulsion of 70–100 microns droplets. To achieve this, the emulsion should be prepared with a lipiodol/drug ratio of 2 or 3 to 1, using lipiodol resistant 3- or 4-way stopcocks and syringes. The use of dedicated preparation devices is encouraged. At least 20 pumping exchanges through the stopcock should be done, and the incremental method be favored.
- That the quality of the emulsion should be assessed with the ‘drop test’.
- That the emulsion should be prepared at the time of administration and be used promptly after preparation.
- That additional feeder embolization should be systematically performed after emulsion"


"The expert panel
- Suggests that a median OS of 25–30 months is probably a valid goal to consider after ss-cTACE.
- Recommends that tumors amenable to ablation should be proposed to ss-cTACE only in the scenario of treatment stage migration or when patients are enlisted for a liver transplant.
- Stresses that superselectivity decreases the incidence of adverse effects and improves tolerance."

Post-Treatment Care and Imaging Follow-Up

"The exper panel
- Recommends the use of immediate post-treatment MDCT or CBCT to assess tumor targeting.
- Recommends the use of contrast-enhanced CT as initial imaging on first follow-up after ss-cTACE
- Recommends the use of MRI if remaining tumor viability cannot be confidently assessed on CT
- Acknowledges that if no response is obtained after two ss-cTACE sessions performed within six months, the patient must be considered TACE-refractory and proposed for alternative therapy.
- Recommends that patients should be treated with TACE until they are considered TACE unsuitable."


"The subgroup allocated to TACE is a population with well-defined nodules, preserved portal
flow, in whom selective vascular access to the tumors(s) is possible, which clearly corresponds to what we defined in this paper as the best candidates for ss-cTACE."
"These recommendations from the Expert meeting have been drafted to encourage treatment standardization in HCC patients, including patient selection and ss-cTACE delivery. They may be used as a general guide, but the interventional radiologist treating the patient is ultimately responsible for the treatment approach. Referring physicians must be aware of the treatment selected, with all possible complications, adverse effects, and post-treatment care. Finally, patients are best served by multidisciplinary decision-making, and interventional radiologists should take an active role in patient selection, treatment allocation, and post-procedural care."

Shi M. et. al. (2012)(2)

  • Multicenter, single blind, randomized, controlled clinical trial
  • 365 patients with HCC stage B/C with -good performance status & liver function
    • Arm 1 = "Triple drug - cTACE" (lobaplatin + epirubicin + mitomycin C) with sponge embolization: 122 patients
    • Arm 2 = "Triple drug - TAC" (lobaplatin + epirubicin + mitomycin C) without embolization: 121 patients
    • Arm 3 = "Triple drug - cTACE" (epirubicin) with sponge embolization: 122 patients
  • ary endpoint = overall survival


"...to compare the efficacy and safety of: 1) transarterial chemolipiodolization with gelatin sponge embolization vs  chemolipiodolization without embolization, and 2) chemolipiodolization with triple chemotherapeutic agents vs. epirubicin alone"


"Chemolipiodolization played an important role in transarterial chemoembolization, and the choice of chemotherapy regimen may largely affect survival outcomes..."


Llovet J.M. et al. (2003)(3)

  • Systematic review of RCTs (Randomized Clinical Trials)  identifying survival benefits of medical interventions (arterial embolization/chemoembolization) for unresectable HCC in comparison with conservative management or suboptimal therapies
  • Meta-analysis of 7 RCTs: 6 studies reporting 2-year death rates (503 patients) + 1 study reporting 1 year survival*(42 patients)
Lin et al.
(Gastroenterology 1998)
Particles or gelatin
Particles or gelatin + 5-FU
5-FU 63 25 (TAE)
20(TAE +5-FU)
13 (Ctrl)
Pelletier et al.*
(J. Hepatol. 1990) 
Doxorubicin + gelatin Conservative management 42 24 (TACE)
33 (Ctrl)
Group Etude & Traitement du
(Nejm 1995)
Lipiodol®+cisplatin+gelatin Conservative management 96 37 (cTACE)
26 (Ctrl)
Bruix et al.
(Hepatology 1998)
Radiological contrast medium + gelatin Conservative management 80 49 (TAE)
50 (Ctrl)
Pelletier et al. 
(J. Hepatol. 1998)
Lipiodol® + cisplatin + lecithin + gelatin + tamoxifen Tamoxifen 73 24 (cTACE)
26 (Ctrl)
Lo et. al.
(Hepatology 2002)
Lipiodol®+cisplatin+gelatin Conservative management 79 31(cTACE)
11 (Ctrl)
Llovet et. al.
(The Lancet 2002)
Conservative management 112 50 (TAE)
63 (cTACE)
27 (Ctrl)


"...Meta-analysis of RCTs comparing 2-year survival with chemoembolization/embolization versus conservative management or suboptimal therapies for unresectable HCC (core group). Random effects model (OR, 0.53;95% CI, 0.32-0.89; P = .017)..."


"...chemoembolization improves survival of patients with unresectable HCC and may become the standard treatment."

Lo C.M. et al. (2002)(4)

  • Single center, open-label, randomized, controlled clinical trial
  • 79 Asien patients with unresectable HCC (OkudaI/II stage)
    • Chemoembolization group (cTACE with Lipiodol® + cisplatin repeated every 2-3 months): 40 patients
    • Control group (symptomatic treatment): 39 patients
  • 1ary endpoint = survival



"...assessed the efficacy of transarterial Lipiodol (Lipiodol® ultrafluide, Laboratoire Guerbet, Aulnay-Sous-Bois, France) chemoembolization in patients with unresectable hepatocellular carcinoma." 



"...transarterial Lipiodol® chemoembolization (...) prolongs the survival of a selected group of Asian patients with unresectable hepatocellular carcinoma and is an effective palliative treatment option."


1. De Baere T. et al. Initiative on Superselective Conventional Transarterial Chemoembolization Results (INSPIRE) CardioVascular and Interventional Radiology volume 45, pages1430–1440 (2022)

2. Shi M. et al. High Roles Played by Chemolipiodolization and Embolization in Chemoembolization for Hepatocellular Carcinoma: Single_blind, Randomized Trial 2012; 105: 59-68

3. Llovet J.M et al.,  Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival, Hepatology. 2003 Feb;37(2):429-42

4. Lo C.M. et al. Randomized Controlled Trial of Transarterial Lipiodol Chemoembolization for Unresectable Hepatocellular Carcinoma, Hepatology 2002; 5, 1164-1171.