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Treatment of Nonresectable Hepatocellular Carcinoma with Intrahepatic ⁹⁰Y-Microspheres

Departments of Radiology, Medicine, and Medical Imaging, The Toronto General Hospital and Princess Margaret Hospital, University of Toronto, Toronto, Ontario; Center for Addiction and Mental Health, Toronto, Ontario, Canada; and DataMedix Corporation, Media, Pennsylvania

Treatment for nonresectable hepatocellular carcinoma (HCC) is palliative. The relatively greater arteriolar density of hepatic tumors compared with normal liver suggests that intrahepatic arterial administration of ⁹⁰Y-microspheres can be selectively deposited in tumor nodules and results in significantly greater radiation exposure to the tumor than external irradiation. The purpose of this study was to determine the proportion (frequency) and duration of response, survival, and toxicity after intrahepatic arterial injection of ⁹⁰Y-microspheres in patients with HCC. Methods: Patients with documented HCC, Eastern Cooperative Oncology Group performance status 0–3, adequate bone marrow, and hepatic and pulmonary function were eligible for study. Patients who had significant shunting of blood to the lungs or gastrointestinal (GI) tract or who could not undergo cannulation of the hepatic artery were excluded. Patients received a planned dose of 100 Gy through a catheter placed into the hepatic artery. Results: Twenty-two patients were treated with ⁹⁰Y-microspheres; 20 of the treated patients (median age, 62.5 y) were evaluated for treatment efficacy. Nine patients were Okuda stage I, and 11 were Okuda stage II. The median dose delivered was 104 Gy (range, 46–145 Gy). All 22 treated patients experienced at least 1 adverse event. Of the 31 (15%) serious adverse events, the most common were elevations in liver enzymes and bilirubin and upper GI ulceration. The response rate was 20%. The median duration of response was 127 wk; the median survival was 54 wk. Multivariable analysis suggested that a dose >104 Gy (P = 0.06), tumor-to-liver activity uptake ratio >2 (P = 0.06), and Okuda stage I (P = 0.07) were associated with longer survival. Conclusion: Significantly higher doses of radiation can be delivered to a HCC tumor by intrahepatic arterial administration of ⁹⁰Y-microspheres than by external beam radiation. This treatment appears to be beneficial in nonresectable HCC with acceptable toxicity.

Key Words: hepatocellular carcinoma • ⁹⁰Y • intrahepatic arterial therapy

Received Sep. 17, 1999; revision accepted Mar. 2, 2000.

For correspondence or reprints contact: Janet E. Dancey, MD, Investigational Drug Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, 6130 Executive Blvd., EPN 715, Rockville, MD 20852-7426.

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