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Liver-Directed Therapy for Hepatic Malignancies

Murthy R. Chamarthy, MD; Sanjeeva P. Kalva, MD
Published: Monday, Feb 08, 2016

Murthy R. Chamarthy, MD

Murthy R. Chamarthy, MD


Locoregional therapies are well established in the treatment of primary and secondary hepatic malignancies and are aimed at a cure, bridging for definitive therapy or palliation. Such therapies include ablation (thermal, chemical, electroporation), hepatic artery–directed therapies (microsphere embolization, chemoembolization, selective internal radiation therapy with yttrium-90 particles), and radiation/proton therapy. This short review focuses on ablation and hepatic artery– directed therapies, and aims to provide a brief overview, indications for therapy, and outcomes from selected trials.


Liver-directed therapies for hepatic malignancies are used either in isolation [usually for hepatocellular carcinoma (HCC)] or in combination with systemic chemotherapy and/or surgery (for metastases or cholangiocarcinoma). Their role in the management of hepatic malignancies has progressed from being palliative in nature (hepatic artery–directed therapies) to curative with the introduction of ablative therapies and combination therapies (ablation plus hepatic artery–directed therapies). Additionally, these therapies form an integral part of hepatic transplantation for HCC by downsizing or controlling the tumor growth while patients await hepatic transplantation. In case of metastatic tumors, ablative therapy is often used as an adjunct to surgical resection, either to limit the extent of surgery or to treat bilobar disease. Despite the varied nature of these therapies, they all aim at providing minimally invasive therapy (as compared with surgery), minimizing the systemic effects of oncological therapy (as opposed to systemic chemotherapy), and minimizing the harmful effects on normal liver tissue while providing adequate tumor control. In addition, some of these therapies (eg, yttrium-90 [Y-90] radioembolization) appear to have a synergistic effect with systemic chemotherapy in achieving tumor control. We will discuss these therapeutic options in the management of HCC and hepatic metastases.

Hepatocellular Carcinoma

The detection and subsequent outcomes of HCC in an at-risk population are highly dependent on the surveillance programs. Small and unifocal tumors benefit from curative therapies, whereas larger and multifocal tumors typically are managed by palliative therapies. In addition, unlike other malignancies, therapy for HCC is highly dependent on the stage of underlying chronic liver disease.1 Barcelona Clinic Liver Classification (BCLC) stratifies the HCC population into very early, early, intermediate, advanced, and terminal groups, with management recommendations based on the size and number of lesions, presence of venous invasion or extrahepatic metastases, Child-Pugh status, and Eastern Cooperative Oncology Group (ECOG) functional status.2

Curative therapies include hepatic transplantation, surgical resection, and ablation. Hepatic transplantation provides the best outcomes because it replaces the tumor and the cirrhotic liver that predisposes to subsequent tumors. Given the small number of available donor livers, defined criteria (eg, Milan, University of California, San Francisco) are used to select patients for optimal outcomes following hepatic transplantation.3,4 Surgical resection is reserved for the minority of patients presenting with early disease (3 nodules <3 cm each or 1 lesion <5 cm), no vascular invasion or extrahepatic spread, absence of portal hypertension, and good liver function (Child Pugh A status) and performance status (PS; ECOG PS 0). Ablation is considered a curative therapy for very early (single lesions <2 cm, Child-Pugh A status, and ECOG PS 0) and early-stage HCC, and is practiced in patients who are not eligible for surgical resection. Multifocal and bilobar tumors in asymptomatic patients with Child Pugh A/B status and good PS are managed with transarterial therapies. Advanced disease in patients presenting with symptoms, portal or hepatic venous invasion, and extrahepatic spread are triaged to either systemic therapy with sorafenib (Child Pugh A/B status and ECOG PS 1-2) or symptomatic therapy (Child Pugh C status and ECOG PS 3-4). However, a select group of such patients may potentially benefit from transarterial therapies, especially those with limited venous invasion and relatively preserved liver function and PS.2,5

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