High-dose proton beam radiotherapy of hepatocellular carcinoma: preliminary results of a phase II trial.

This phase II trial was undertaken to determine the efficacy and toxicity of proton beam radiotherapy for patients with locally unresectable hepatocellular carcinoma. Cirrhotic patients were eligible if they had a Child-Pugh score of 10 or less. Eligible patients included those with T 1 -T 3 hepatocellular carcinoma; selected T 4 patients also were eligible. Patients with lymph node or distant metastases were ineligible. Daily proton beam radiotherapy was directed to the liver tumor with an additional 1-2 cm margin. The total dose was 63 cobalt Gray equivalents, administered in 15 divided fractions over 3 weeks. Thirty-four patients have completed treatment and have been followed up for a minimum of 6 months, with a median follow-up period of 20 months. The mean age was 65 years, and average tumor size was 5.7 cm. Posttreatment toxicity included a small but significant decline in albumin levels and increased total bilirubin; 3 experienced duodenal or colonic bleeding when bowel was immediately adjacent to the treated tumor. Two-year actuarial data showed a 75% local tumor control rate and an overall survival rate of 55%. Of patients with an elevated pretreatment alpha-fetoprotein, 85% were found to have declining alpha-fetoprotein levels from a pretreatment mean of 1405 to 35 at 6 months after treatment. Six patients underwent liver transplantation between 6 and 16 months after completion of radiotherapy with 2 showing no evidence of residual carcinoma within the explanted liver. Overall the majority of patients responded to treatment, and the therapy was well tolerated.