HCC management

HCC management

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

Today INSPIRE, tomorrow immunotherapies combos

Liver cancer, of which hepatocellular carcinoma (HCC), is the most common type, is the third-leading cause of cancer death with an estimated 900,000 people worldwide diagnosed in 2020.1
Transarterial chemoembolization with Lipiodol® Ultra-Fluid (Iodinated ethyl esters of fatty acids of poppy seed oil), also called conventional TACE (cTACE), was developed in the early 1980s and is nowadays widely adopted worldwide 2 and and TACE established as the standard of care for HCC BCLC stage A and B , with preserved liver function, no cancer-related symptoms (PS 0) and no vascular invasion or extrahepatic spread. 3 4

More recently, immunotherapies have been shown to increase survival in patients with HCC and have changed the landscape for advanced disease. Trials on the role of systemic immunotherapy have not just been limited to advanced disease but are now extending towards patients with early or intermediate-stage disease who are suitable for existing treatments including TACE.5

Can we still further refine cTACE clinical outcomes?

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."  6

At the dawn of a new era in unresectable HCC

For over 20 years, TACE has been a standard of care for embolization-eligible uHCC; however, most people with uHCC treated with TACE progress within 1 year. (1)

Embolization creates a proinflammatory tumor microenvironment and increases VEGF signals; clinical studies have established the role of immune checkpoint inhibitors and VEGF inhibitors in advanced HCC (1). Most recently, EMERALD-1 Trial has shown PFS benefit with addition of durvalumab/bevacizumab to TACE in Unresectable, Embolization-Eligible HCC (2).

Watch Doctor Rimassa’s presentation of Emerald-1 trial, done during last Guerbet's Sponsored Symposium organized during ECIO 2024​, in Palma de Mallorca. Doctor Rimassa is medical doctor and associate Professor of Medical Oncology​ at Humanitas University and IRCCS Humanitas Research Hospital, Milan, Italy.

References

1Lencioni et all. EMERALD-1: A phase 3, randomized, placebo-controlled study of transarterial chemoembolization combined with durvalumab with or without bevacizumab in participants with unresectable hepatocellular carcinoma eligible for embolization. Journal of clinical oncology. January 22, 2024. 

2EMERALD-1 Trial Shows PFS Benefit With Addition of Durvalumab/Bevacizumab to TACE in Unresectable, Embolization-Eligible HCC (ascopubs.org) 

Maria

Emerald-1 trial results have been recently communicated during the ASCO-GI congress

For patients with unresectable HCC eligible for embolization, adding both durvalumab and bevacizumab to TACE is associated with a significant improvement in PFS over TACE alone, according to results of the randomized, global phase 3 EMERALD-1 trial presented at the 2024 ASCO Gastrointestinal Cancers Symposium. These results have the potential to reshape the treatment of uHCC (1).

Watch Doctor Maria Reig's presentation of “Today practices and future evolution in uHCC”​, done during last Guerbet Sponsored Symposium organized during ECIO 2024​, in Palma de Mallorca. Doctor Maria Reig is Head of Liver Oncology Unit - BCLC group​ and Consultant of Liver Unit​ in Hospital Clinic, IDIBAPs and CIBEREHD​.

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References

1 EMERALD-1 Trial Shows PFS Benefit With Addition of Durvalumab/Bevacizumab to TACE in Unresectable, Embolization-Eligible HCC (ascopubs.org)

Maxime Ronot

Watch Professor
Maxime Ronot at the
ILCA 2023 conference

In his presentation at the ILCA 2023 conference, Professor Maxime Ronot (Beaujon Hospital -Clichy, France) illustrates how to improve the definition of HCC patients eligiblity to a superselective cTACE, and to standardize the procedure, with the aim of maximizing the anti-tumoral effect while minimizing the collateral damages of the surrounding liver parenchyma.6
Prof. Ronot also shares his expectations as an interventional radiologist, regarding immunotherapies combined with TACE.

References

1 WHO. Liver Cancer Fact Sheet. Available at: https://gco.iarc.fr/today/data/factsheets/cancers/11-Liver-fact-sheet.pdf. Accessed November 2023
2 T. de Baere et all Treatment of Liver Tumors with Lipiodol TACE: Technical Recommendations from Experts Opinion. Cardiovasc Intervent Radiol (2016) 39:334–343. DOI 10.1007/s00270-015-1208-y
3 Maria Reig et all. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. Journal of Hepatology. VOLUME 76, ISSUE 3, P681-693, MARCH 2022. DOI:https://doi.org/10.1016/j.jhep.2021.11.018
4 A. Vogel et all. Hepatocellular carcinoma. ESMO Clinical Practices guidelinesfor diagnostic, treatment and follow up. © 2021 ESMO. esmo.org/Guidelines/Gastrointestinal-Cancers/Hepatocellular-Carcinoma
5 Jonathan Tibballs et all. Immunotherapy and Transarterial therapy of HCC: What the interventional radiologist needs to know about the changing landsc. J Med Imaging Radiat Oncol. 2022 Jun; 66(4): 478–482. doi: 10.1111/1754-9485.13405
6 T. de Baere et all. Initiative on Superselective Conventional Transarterial Chemoembolization Results (INSPIRE). Cardiovasc Intervent Radiol. 2022 Oct;45(10):1430-1440. doi: 10.1007/s00270-022-03233-9. Epub 2022 Aug 17

Unleash the potential of Lipiodol® in HCC

For decades, you’ve trusted Guerbet for interventional oncology treatments using anticancer drug-Lipiodol® emulsion in cTACE for hepatocellular carcinoma (HCC, or liver cancer). Indeed, conventional TACE with Lipiodol® demonstrates a median Overal Survival of 25/30 months on patients suffering from HCC(1).
Treatments continue to evolve thanks to close collaboration with physicians around the world.
Two recent studies document the power of super-selective cTACE catheterization approach and procedure standardization using Lipiodol® to help treat HCC patients(1, 2).

A gold standard, super-selective cTACE consists of positioning the catheter as distal as possible and close to the tumor, delivering at a subsegmental level using a microcatheter and reaching the tumor feeders through terminal and intersegmental collaterals while sparing the surrounding healthy liver parenchyma. Procedure standardization includes proper and consistent preparation before administration using a water-in-oil emulsion with Lipiodol®/drug ratio of 2 or 3 to 1 prepared at the time of administration(1).

The combination of super-selective catheterization and standardized cTACE delivers improved results, including:

  • Patient overall survival increased from some months to more than 3 years(3) or far more in some cases, 6 years(4) or even 10 years(5)
  • More effective than selective DEB-TACE for local tumor control in HCC patients(6)
  • Most Adverse Events (Aes) observed as grade 1 or 2, mainly related to post embolization syndrome. Serious Adverse Events were reduced(7).

References

1. Ikeda M. et al., Prospective Study of Transcatheter Arterial Chemoembolization for Unresectable Hepatocellular Carcinoma: An Asian Cooperative Study between Japan and Korea J. Vasc. Interv. Radiol. 2013; 24: 490-500

2. Lo C.M. et al. Randomized Controlled Trial of Transarterial Lipiodol Chemoembolization for Unresectable Hepatocellular Carcinoma Hepatology 2002; 35: 1164-1171

3. Llovet J.M. et al. arterial embolization or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial The Lancet 2002; 359: 1734-1739

4. Llovet J.M. et al . Systematic Review of Randomized Trials for Unresectable Hepatocellular Carcinoma: Chemoembolization Improves Survival Hepathology 2003; 37: 429-442

5. EASL-EORTC Clinical Practice Guidelines for the Management of Hepatocellular Carcinoma. J. Hepatol. 2018

6. Chen M. et al., High Dose Iodized Oil Transcatheter Arterial Chemoembolization for Patients with Large Hepatocellular Carcinoma World. gastroenterol. 2002; 8: 74-78.

7. Takayasu K. et al., Comparison of CT Findings with Resected Specimens After Chemoembolization with Iodized Oil for Hepatocellular Carcinoma AJR. 2000;175:699–704.

8. De Baere t. et al., Circulatory alterations induced by intra-arterial injection of iodized oil emulsions of iodized oil and doxorubicin: experimental study, Radiology.1995; 194: 165-170.

9. Europe: EASL-EORTC / Clinical Pratice Guidelines / Journal of Hepatology 2012 vol. 56; 908–943.

10. US Guidelines: Bruix J. AASLD Practice Guidelines; American Association for Study of the Liver Diseases;Hepatology 2011; Vol. 53, No. 3.

11. Chinese guidelines 2011 edition, Chin. Clin. Oncol. 2012; 1:10.

12. Japanese Guidelines: Hepatology Research 2010; 40 (Suppl. 1): 96–112.

13. Terayama N. et al., Accumulation of Iodized Oil Within the Non-Neoplastic Liver Adjacent to Hepatocellular Carcinoma via the Drainage Routes of the Tumor After Transcatheter Arterial Embolization CVIR. 2001; 24:383-387.

14. Georgiades C. et al. Lack of response after initial chemoembolization for hepatocellular carcinoma: Does it predict of subsequent treatment, Radiology. 2012; 265(1): 115-123.

15. Kan Z. et al. Liver anatomy: microcirculation of the liver, Sem. Intervent. Radiology 2008; 25: 77-85.

16. Thierry de Baere et al., Treatment of Liver Tumors with Lipiodol TACE: Technical Recommendations from Experts Opinion. Cardiovasc Intervent Radiol,2016;39:334–343.

17. Kudo M. et al., Orantinib versus placebo combined with transcatheter arterial chemoembolisation in patients with unresectable hepatocellular carcinoma (ORIENTAL): a randomised, double-blind, placebo-controlled, multicentre, phase 3 study. Lancet gastroenterol Hepatol.2018; (3) 37-46.

18. Ikeda M. et al.,Transarterial chemoembolization with miriplatin vs. epirubicin for unresectable hepatocellular carcinoma: a phase III randomized trial. J Gastroenterol.2018; 53:281–290.