Yttrium-90 microspheres for the treatment of hepatocellular carcinoma

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Unresectable hepatocellular carcinoma is extremely difficult to treat. TheraSphere consists of yttrium-90 (a pure beta emitter) microspheres, which are injected into the hepatic arteries. This article reviews the safety and survival of patients with hepatocellular carcinoma who were treated with yttrium-90 microspheres. Eighty patients were selected from a database of 108 yttrium-90 microsphere-treated patients and were staged by using Child-Pugh, Okuda, and Cancer of the Liver Italian Program scoring systems. Patients were treated with local, regional, and whole-liver approaches. Survival from first treatment was analyzed with Kaplan-Meier and Cox regression methods. Adverse events and complications of treatment were coded by using the Southwest Oncology Group toxicity scoring system. Patients received liver doses ranging from 47 to 270 Gy. Thirty-two patients (40%) received more than 1 treatment. Survival correlated with pretreatment Cancer of the Liver Italian Program scores (P = .002), as well as with the individual Cancer of the Liver Italian Program components, Child-Pugh class, alpha-fetoprotein levels, and percentage of tumor replacement. Patients classified as Okuda stage I (n = 54) and II (n = 26) had median survival durations and 1-year survival rates of 628 days and 63%, and 384 days and 51%, respectively (P = .02). One patient died of liver failure judged as possibly related to treatment. Thus, in selected patients with hepatocellular carcinoma, yttrium-90 microsphere treatment is safe and well tolerated. On the basis of these results, a randomized controlled trial is warranted comparing yttrium-90 microsphere treatment with transarterial chemoembolization by using the Cancer of the Liver Italian Program system for prospective stratified randomization.

Section snippets

Patients selected

Data from 80 patients were included in the analysis. The centers providing data were The Toronto General Hospital (n = 17), the University of Pittsburgh Medical Center Starzl Transplant Institute (n = 51), the Hospital of the University of Pennsylvania (n = 7), and Johns Hopkins University Hospital (n = 5). Patients were treated under 2 fixed-dose protocols. The Toronto Protocol, using a nominal fixed dose of 100 Gy, began enrolling patients in March 1992 and ended enrollment in March 1996.18

Study population

The study population is characterized in Table 1, Table 2, Table 3, Table 4. The population was predominantly older, white, and male, and 35 patients (44%) had bilobar disease. Fifty-six (70%) patients had documented cirrhosis, 10 (13%) had ascites, and 13 (16%) had >50% of their liver replaced by tumor. The serum bilirubin level was increased in 13 (16%) patients, and 72 (90%) were characterized as having Child-Pugh class A liver disease. HCC staging resulted in 54 (68%) patients being

Discussion

Most patients diagnosed with unresectable HCC succumb to liver failure as a result of advancing cirrhosis or tumor progression.29 Because tumor burden in the liver is a major threat to patient survival and well-being and because systemic chemotherapy is ineffective, local liver-directed therapies have been developed to reduce tumor burden, providing palliation and the potential for increased survival. Decreasing tumor burden unintentionally results in compromised liver function through

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    Supported in part by MDS Nordion, Ottawa, Ontario, Canada.

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