Chemoembolization for Hepatocellular Carcinoma

Clinical Relevance

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, ranking fifth for men and seventh for women as a source of primary malignancy. Cirrhosis secondary to chronic infection with hepatitis B and/or hepatitis C is the main risk factor for developing HCC. Nonalcoholic fatty liver disease–related cirrhosis is a rising risk factor in developed countries. Increasing incidence rates of HCC, in conjunction with poor overall survival rates, have made HCC the fastest rising cause of cancer-related death in the United States. Application of generalizable treatment strategies in HCC is complicated by wide variations in prognostic features present at diagnosis, severity of underlying liver disease, and access to medical services around the world.

For early-stage HCC, potentially curative treatment options include liver resection, transplantation, and image-guided ablation, with reported 5-year survival rates of 60%–80%. In patients with more advanced stages of HCC and preserved liver function, transarterial chemoembolization (TACE) is the treatment of choice because it has been shown to be an effective treatment that prolongs patient survival. In the latest guidelines of the American Association for the Study of Liver Diseases for the treatment of HCC, there is a strong recommendation for locoregional treatments over no treatment in patients with cirrhosis and HCC (T2 or T3, without vascular involvement) who are not candidates for resection of transplantation, with a “moderate” quality of available evidence for TACE.

TACE combines the effects of targeted ischemia with high local chemotherapeutic drug concentration and prolonged drug dwell time in the tumor. In contrast to normal hepatic parenchyma, HCC receives blood primarily from hepatic arterial branches, which is the basis of targeted tumor treatment via the hepatic artery. TACE is performed either with a lipiodol/chemotherapeutic drug emulsion followed by particle embolization, often referred to as conventional TACE (cTACE) or with embolic drug-eluting microspheres (“beads,” DEB-TACE).

Lipiodol, a contrast agent of iodized esters of poppy seed oil, is predominantly retained within hypervascularized tumors and serves as the delivery vehicle of the chemotherapeutic agents in cTACE. The opacity of Lipiodol allows for real-time monitoring of therapy during embolization. Moreover, the uptake and retention of lipiodol is an imaging biomarker of tumor response and patient survival. Particle embolization after infusion of the chemotherapy emulsion increases the dwell time of the cytotoxic agents by slowing the rate of their efflux from the hepatic circulation, and is associated with improved survival.

In DEB-TACE, polyvinyl alcohol embolic microspheres are used, which are modified with sulphonate groups for controlled loading, delivery, and elution of chemotherapeutic drugs. These microspheres combine a local ischemic and cytotoxic effect, with a low systemic toxicity profile.

An alternative to TACE is radioembolization with yttrium-90 microspheres, discussed in a separate chapter. There are no large prospective comparative studies of radioembolization and TACE; however, retrospective analyses have not demonstrated an overall survival benefit of one treatment over another.

Indications

TACE is the most widely used primary treatment for unresectable HCC, with best outcomes in patients with reasonably preserved liver function (Child-Pugh class A–B [ Table 34.1 ]), Eastern Cooperative Oncology Group (ECOG) performance status of 0–1 ( Table 34.2 ), and without macrovascular invasion or extrahepatic spread. In addition, TACE is used as a “bridge” therapy in patients awaiting liver transplantation, decreasing the risk of tumor progression outside acceptable transplant criteria.

Contraindications

The only absolute contraindication to TACE is decompensated baseline liver function. Patients at high risk of acute liver failure include those with the constellation of greater than 50% replacement of liver by tumor, lactate dehydrogenase level above 425 IU/L, aspartate aminotransferase level above 100 IU/L, and total bilirubin level above 2 mg/dL.

Relative contraindications include those unlikely to benefit from therapy due to poor prognosis, such as wide metastatic disease, Child-Pugh class C liver disease, or decompensated performance status (ECOG 3–4). Patients at risk for liver failure include those with markedly elevated bilirubin, hepatic encephalopathy, transjugular intrahepatic portosystemic shunt, main portal vein occlusion, or hepatofugal portal blood flow. In these settings, segmental or subsegmental TACE may be performed. TACE in the setting of biliary stenting, sphincterotomy, or bilioenteric anastomosis increases the risk of abscess formation. Portal vein thrombosis can be managed by adjustment of the embolization protocol to limit the degree of embolization and distribution of chemotherapeutic agent or by documenting that sufficient hepatic collateral flow is present to compensate for lack of portal flow.

Contraindications to the angiographic procedure include anaphylactoid contrast media allergy, renal insufficiency, uncorrectable coagulopathy, and peripheral vascular disease preventing establishment of arterial access.

Equipment

• Fluoroscopic unit capable of digital subtraction angiography, preferably equipped with cone-beam computed tomography (CT) capability

• Visceral catheters/wires

  • A 4F hydrophilic Cobra catheter and hydrophilic guidewire suffice for about one-third of procedures

  • Standard reverse curve visceral catheters (Simmons, SOS, Rosch)

  • Microcatheters 105–130 cm in length with 0.025–0.027-inch inner lumen are specifically designed for TACE

  • 0.014–0.018-inch guidewires for use with microcatheters

• For cTACE

  • Contrast agent and oil suspension: Lipiodol

  • Chemotherapy agents (e.g., doxorubicin, epirubicin, cisplatin, mitomycin C)

  • Embolization agents: 100–300-μm spherical embolic particles

• For DEB-TACE

  • Drug-eluting beads: DC/LC Bead (BTG International, Conshohocken, PA), Hepasphere/QuadraSphere (Merit Medical, South Jordan, UT), Tandem/Embozene (Boston Scientific, Natick, MA), LifePearl (Terumo Medical, Somerset, NJ); usually 100–300 μm

  • Chemotherapy agents: typically doxorubicin 75–150 mg

  • Nonionic contrast medium (5–10 mL per liter of microspheres)