Elsevier

Seminars in Oncology

Volume 37, Issue 2, April 2010, Pages 127-138
Seminars in Oncology

Regional therapies for cancers in the liver
Locoregional Management of Hepatic Metastasis From Primary Uveal Melanoma

https://doi.org/10.1053/j.seminoncol.2010.03.014Get rights and content

Uveal melanoma is the most common primary ocular malignancy in adults and has a significant predilection for metastasis to the liver. Despite successful treatment of the primary uveal melanoma, up to 50% of patients will subsequently develop a systemic metastasis, with the liver involved in up to 90% of these individuals. Metastatic uveal melanoma has proven to be resistant to currently available systemic chemotherapies. Recognition of the poor prognosis associated with liver metastasis has led to the evaluation of various locoregional treatment modalities primarily designed to control tumor progression in the liver, including surgical resection, hepatic arterial chemotherapy, transarterial chemoembolization (TACE), immunoembolization, radiosphere, drug-eluting beads, isolated hepatic perfusion (IHP), and percutaneous hepatic perfusion. This article reviews the efficacies, and morbidities of currently available locoregional therapies.

Section snippets

Diagnostic Procedure to Detect Metastatic Uveal Melanoma

Despite the controversy over lead-time bias, it is the general consensus that early discovery of hepatic metastasis will provide benefit to patients by facilitating pursuit of various treatment options. In defining a follow-up program for uveal melanoma patients, one must define the high-risk population for systemic metastasis and the best modality to detect early hepatic metastasis. Traditionally, clinico-histopathological characteristics have been used to identify high-risk patients,

Surgical and Ablative Treatment

Since the liver is the first and in many cases the only site of metastasis in uveal melanoma patients, a local treatment aimed at controlling liver metastases holds promise in managing this otherwise highly chemo-resistant tumor. Total resection of the solitary metastasis in the liver or other sites18, 19 offers a distinct survival advantage. We reported protracted survival with surgery for visceral metastases from uveal melanoma. Among 12 patients with metastatic uveal melanoma, nine of whom

Rationale for Transarterial Treatment for Metastatic Melanoma to the Liver

From the anatomic and physiologic points of view, the liver is the organ that allows interventional transarterial treatments to achieve control of the cancer while reducing or eliminating unnecessary systemic toxicity.27, 28, 29 It is well established that both primary and secondary liver tumors derive their blood supply from the hepatic artery,30 while approximately 50% of the oxygen supply to normal liver is from the portal system.31, 32 This makes intrahepatic arterial embolization treatment

Chemoembolization

Transarterial chemoembolization (TACE) consists of hepatic artery embolization with simultaneous infusion of concentrated doses of chemotherapeutic drugs. Patients considered for TACE must have disease limited to or dominant in the liver, a patent main portal vein, and no sign of liver failure such as elevation of total bilirubin (≥2.0 mg/dL), ascites, or hepatic encephalopathy. Biliary obstruction, bile duct stent, and previous major biliary surgery except cholecystectomy are relative

Immunoembolization

Despite better disease control than can be achieved with systemic chemotherapy, the majority of uveal melanoma patients treated with TACE subsequently experience progression of systemic extrahepatic metastases after successful control of their hepatic metastases. Of 17 patients who achieved CR, PR, or SD after TACE with BCNU, 12 patients experienced progression of extrahepatic metastases as an initial sign of disease progression; eight patients had progression in extrahepatic metastases alone.37

Selective Internal Radiation Therapy

Selective internal radiation therapy (SIRT, radioactive microspheres) has been used to deliver high-dose radiation to tumor, while minimizing damage to surrounding normal tissues. The pure beta-emitting isotope 90Y has been used most commonly for treatment of hepatic tumors. The therapeutic advantage in this approach is based on the unique dual vascular supply of the liver. It is known that hepatic tumors receive 80% to 100% of afferent blood exclusively from the hepatic artery.30 Due to their

Drug-Eluting Beads

Over the last few years, efforts have been made to deliver a more accurate dose of drugs to the liver over a more prolonged period. Embolization of vessels supplying malignant hypervascular tumor(s) with drug-eluting beads delivers a local, controlled, sustained dose of chemotherapeutic medications to the tumor(s). Drug-eluting beads (DC/LC Beads, Biocompatibles, Surrey, UK) comprise a range of hydrogel microspheres that are biocompatible, hydrophilic, non-resorbable, precisely calibrated, and

Hepatic Intra-Arterial Chemotherapy

Hepatic intra-arterial chemoinfusion with an agent that has a rapid systemic clearance rate and a high hepatic extraction rate allows maximum local drug exposure. Regional chemotherapy concepts are mostly based on the use of implantable hepatic catheters in order to deliver intra-arterial chemotherapy directly to hepatic lesions. Thus, a higher concentration of chemotherapeutic agents can be locally delivered, with lower systemic toxicity. The results of intrahepatic arterial chemotherapy for

Hepatic Arterial Perfusion

The goal of isolated hepatic perfusion (IHP) is to expose the liver containing metastatic melanoma to high doses of chemotherapy to achieve maximal tumor shrinkage but not to cause fatal hepatotoxicity. Seminal work on IHP for hepatic metastases from uveal melanoma was done by Alexander's group at the National Cancer Institute.68, 69, 70, 71 They initially reported their results with IHP using melphalan with or without tumor necrosis factor (TNF) in 22 patients with uveal melanoma metastatic to

Summary and Future Prospective

Various locoregional treatments have been developed for the treatment of uveal melanoma metastatic to the liver. Since there has been no prospective randomized trial to compare the efficacy of individual treatments, current choice of treatment in uveal melanoma patients with hepatic metastasis depends on the availability of treatment modalities and the experience at individual institutions. Figure 2 shows the flowchart for the selection of treatment for individual patients at Thomas Jefferson

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