Hepatic metastases to the liver are significantly more common than primary liver malignancy and comprise approximately 90% of hepatic malignancies. Each year, approximately 140,000 new cases of colorectal cancer (CRC) are diagnosed in the United States, with hepatic metastases complicating 10% to 25% of cases.1,2 Two-thirds of these patients die from their disease as a result of liver involvement.2 In addition, numerous other malignancies metastasize to the liver. For instance, approximately 50% of patients with uveal melanoma develop liver metastases within 2 to 5 years after initial diagnosis, and 90% of metastatic uveal melanoma patients die with disease burden in the liver due to inefficacious systemic chemotherapy.3 Neuroendocrine tumors (NETs) also have propensity to metastasize to the liver as well as breast cancer, esophageal cancer, gastric cancer, gastrointestinal stromal tumors (GISTs), sarcoma, gynecologic and urologic malignancies, and melanoma.4 Therefore, because of the significant number of patients impacted by either primary or secondary liver malignancy, there is an increasing need for effective locoregional therapy. Surgical resection as a part of multimodal therapy is generally considered the gold standard.5-8 However, resection is often not a reasonable option secondary to disease burden, tumor location, insufficient estimated future liver remnant, extrahepatic disease, and medical comorbidities. In fact, surgical resection for metastatic disease to the liver is only feasible in approximately 20% of patients.9 Therefore, alternative options are necessary in the 60% to 80% of patients with metastatic disease to the liver in whom surgery is not possible.9 These nonresective techniques are the focus of this chapter.
Malignant tumors confined to the liver that cannot be addressed with curative intent are best treated with locoregional therapy. Primary liver lesions such as hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcionma as well as metastatic liver lesions such as colorectal, neuroendocrine, breast, melanoma, and renal can be palliated or down-staged with arterial-directed therapy. Transarterial directed therapy includes bland embolization, chemoembolization, drug-eluting beads (DEBs), and radioembolization. Bland embolization induces tumor ischemia by arterial disruption but does not use chemotherapeutic agents; therefore, tumor necrosis is simply accomplished by restricted blood supply. Chemoembolization, DEB, and radioembolization deliver toxic agents via the arterial system which preferentially supplies the tumor, in contrast to normal hepatocytes which derive much of their blood supply from the portal venous system.10 The latter three techniques are the focus of the arterial-directed therapy section.
Transcatheter Arterial Chemoembolization
Transcatheter arterial chemoembolization also known as transarterial chemoembolization (TACE) was first introduced in 1980 for treatment of unresectable liver tumors, and since that time has expanded to include treatment of numerous malignant processes (HCC, neuroendocrine metastases, cholangiocarcinoma, melanoma, colorectal metastases).11 Conceptually, liver tumors preferentially utilize hepatic arterial supply, and therefore chemotherapeutic agents with subsequent embolization can selectively target malignant cells while preserving surrounding liver parenchyma. Specific delivery of chemotherapeutic agents reduces systemic ...