Intra-arterial iodine 131-labeled lipiodol as adjuvant therapy after curative liver resection for hepatocellular carcinoma: A phase 2 clinical study

Abstract

Hypothesis: Intra-arterial lipiodol labeled with iodine 131 (131I-lipiodol) can be safely used as adjuvant therapy following curative liver resection for hepatocellular carcinoma (HCC). Design: Phase 2 pilot study. Setting: Large teaching hospital. Patients: Twenty-eight patients (24 men and 4 women; median age, 61.5 years; range, 33-75 years) were treated from January 1991 to June 1997. The liver was cirrhotic in 7 cases and noncirrhotic in 21 cases. An equal number of 14 patients underwent a major and a minor resection, all with clear margins. Median diameter of solitary tumors or the larger tumor when multiple tumors occurred was 5.5 cm (range, 2.5-29 cm). Tumor encapsulation was present in 12 cases and absent in 16 cases. After informed consent, patients who had no evidence of residual or recurrent tumor on computed tomographic (CT) scan and no sign of liver failure 2 to 3 months after curative resection for HCC were included in the trial. Complete follow-up was obtained (median, 51 months; range, 5-93 months). Interventions: A 1110-MBq dose of 131I-lipiodol was administered into the hepatic artery using the Seldinger technique. Patients were kept in a radio-protected room for 5 days. Postinjection radioactive whole scintiscan was performed at 5 days and an abdominal CT scan at 1 month after the injection. A second injection was performed in 16 patients 2 years later using the same protocol. Main Outcome Measure: Procedure safety. Results: All patients experienced transient fever during the first 12 hours following injection. There were no noted adverse clinical effects or significant alteration in hepatic function due to the procedure or at immediate and late follow-up. The radioactive scan demonstrated an intense liver uptake, which was homogeneous in 19 cases and heterogeneous in 9. Mild detectable thyroid and lung uptake occurred in 50% of cases. No lipiodol liver fixation was observed on the 1-month CT scan. At the time of follow-up, 6 patients had died and 12 had developed recurrences, with 5 of the 6 deaths belonging to the recurrent group. Sixteen patients remained disease free. The median time to detected recurrence was 28 months (range, 12-62 months). Overall survival rates were 86% at 3 years and 65% at 5 years. Conclusions: This pilot study failed to demonstrate any clinically significant adverse effect of adjuvant therapy by intra-arterial 131I-lipiodol after curative liver resection for HCC. Long-term survival compares favorably with those undergoing only surgery and suggests a benefit in lowering tumor recurrence. A randomized, multicenter, prospective trial comparing patients treated with intra-arterial 131I-lipiodol with a nontreated control group seems appropriate.