Multimodal adjuvant treatment and liver transplantation for advanced hepatocellular carcinoma. A pilot study

Orthotopic liver transplantation has been used in a large number of patients with primary liver cancer because it increases the possibilities of resection of large tumors. Despite isolated cases of prolonged survival, however, the results of liver transplantation for advanced tumors have been universally disappointing because of high rates of tumor recurrence. In an attempt to reduce the recurrence rate, a pilot study testing a multimodal adjuvant treatment in patients undergoing liver replacement for hepatocellular carcinoma was undertaken.

The treatment consisted of preoperative hepatic arterial chemoembolization (iodized oil, doxorubicin, and gelatin sponge) and radiotherapy (5 Gy in one fraction immediately before surgery), and postoperative systemic chemotherapy with mitoxantrone. Nine patients entered this study. The tumor was solitary in two cases (5 cm and 8 cm) and multifocal in seven cases (2-9 nodules, 3-9 cm). The postoperative TNM stages were II in one case, III in one case, and IVA in seven cases.

Chemoembolization and radiotherapy were performed in seven cases each (five patients had both treatments). All patients underwent liver transplantation with conventional immunosuppression. One patient died of heart failure 4 days after surgery. The remaining eight patients received 4 to 10 courses of chemotherapy (mean 9). The main toxicity of chemotherapy was leucopenia. Two patients died of recurrence: one at 7 months and one at 11 months. Six patients are alive, five of them without evidence of disease, with a mean follow-up of 30 months (range 16-45) after liver transplantation. The 3-year actuarial survival is 64%.

These results show that an aggressive adjuvant therapy can be used in association with liver transplantation in the treatment of advanced hepatocellular carcinoma without increased mortality and suggest that such a protocol could be effective in preventing tumor recurrence.