Liver Cancer
Treatment of Hepatocellular Carcinoma – Integrating Loco-regional and Molecular-targeted Therapies
Riccardo Lencioni
Associate Professor of Radiology, and Head, Division of Diagnostic Imaging and Intervention, Department of Liver Transplantation, Hepatology and Infectious Diseases, University of Pisa School of Medicine
Abstract
The treatment of hepatocellular carcinoma (HCC) is rapidly evolving as loco-regional and systemic therapies continue to improve. Image-guided radiofrequency (RF) ablation is established as the treatment of choice for patients with early-stage HCC when transplantation or resection are precluded. Recent refinements to technique have substantially increased the ability of RF ablation to achieve sustained complete response of target tumours in properly selected patients, and new alternate thermal and non-thermal methods for local tumour treatment are currently under investigation. Transarterial chemo-embolisation (TACE) is the standard of care for patients with multinodular disease at the intermediate stage. The introduction of drug-eluting beads, which enhance drug delivery to the tumour and reduce systemic exposure, appears to improve anticancer activity and the safety profile of TACE compared with conventional regimens. Despite these advances, the long-term outcomes of patients treated with loco-regional therapies remain unsatisfactory because of the high rate of tumour recurrence. The introduction of molecular-targeted therapies that inhibit tumour proliferation and angiogenesis has opened new prospects in this regard. Clinical trials focused on combining interventional treatment with systemically active drugs are ongoing. The outcomes of such studies are eagerly awaited, as they have the potential to revolutionise the treatment of HCC.
Keywords
Hepatocellular carcinoma, image-guided ablation, transarterial chemo-embolisation, molecular-targeted therapies
Disclosure: The author has no conflicts of interest to declare. Received: 9 October 2009 Accepted: 11 March 2010 Citation: European Oncology, 2010;6(1):65–8 Correspondence: Riccardo Lencioni, Director, Division of Diagnostic Imaging and Intervention, Department of Liver Transplantation, Hepatology and Infectious Diseases, University of Pisa School of Medicine, Cisanello Hospital, Building 30C, Suite 197, IT-56124 Pisa, Italy. E:
lencioni@med.unipi.it
Hepatocellular carcinoma (HCC) is the sixth most common cause of cancer, and its incidence is increasing worldwide because of the dissemination of hepatitis B and C viral infections.1
In most solid
malignancies, tumour stage at presentation determines prognosis and treatment management. However, most patients with HCC have two diseases – liver cirrhosis and HCC – and complex interactions between the two have major implications for prognosis and treatment choice. Patients with Child-Pugh A or B cirrhosis, an Eastern Cooperative Oncology Group (ECOG) performance status of zero and a solitary tumour or up to three nodules smaller than three centimetres in size are classified as early-stage by the Barcelona Clinic Liver Cancer (BCLC) staging system.2
Those with an asymptomatic multinodular
tumour showing neither vascular invasion nor extra-hepatic spread comprise the intermediate stage. Patients who present with cancer- related symptoms and/or with vascular invasion or extra-hepatic spread are classified as advanced-stage. The terminal stage includes patients who have severe hepatic decompensation (Child-Pugh C) or ECOG performance status greater than two.
Loco-regional therapies play a major role in the current therapeutic management of HCC. Image-guided percutaneous ablation is established as the best therapeutic choice for patients with early-stage HCC when surgical resection or liver transplantation are precluded.3,4 Transarterial chemo-embolisation (TACE) is the standard of care for patients at the intermediate stage.4,5
Despite the advances in
© T O UCH BRIEFINGS 2010
interventional treatments, long-term outcomes of patients treated with loco-regional therapies remain unsatisfactory because of the high rate of tumour recurrence. The recent addition of molecular-targeted drugs that inhibit tumour proliferation and angiogenesi, to the therapeutic armamentarium has opened new prospects in the treatment of HCC and warrants a sharpened multidisciplinary approach to patient management to optimise treatment options across all stages of the disease. In this article, current and new loco-regional treatments for HCC are reviewed, and potential synergies between interventional approaches and molecular-targeted therapies are discussed.
Image-guided Ablation
Image-guided percutaneous ablation is currently accepted as the best therapeutic choice for non-surgical patients with early-stage HCC.3,4 Over the past two decades, several methods for chemical ablation or thermal tumour destruction through localised heating or freezing have been developed and clinically tested.6,7
Ethanol Injection
The seminal technique used for local ablation of HCC is percutaneous ethanol injection (PEI). Ethanol induces coagulation necrosis of the lesion as a result of cellular dehydration, protein denaturation and chemical occlusion of small tumour vessels. PEI is a well-established technique for the treatment of nodular-type HCC. HCC nodules have a soft consistency and are surrounded by a firm cirrhotic liver.
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