Adjuvant Iodine-125 Brachytherapy for Hepatocellular Carcinoma after Complete Hepatectomy: A Randomized Controlled Trial

BACKGROUND: Tumor recurrence is a major problem after curative resection of hepatocellular carcinoma (HCC). The current study evaluated the effects of adjuvant iodine-125 ((125)I) brachytherapy on postoperative recurrence of HCC. METHODOLOGY/PRINCIPAL FINDINGS: From July 2000 to June 2004, 68 HCC patients undergoing curative hepatectomy were randomly assigned into a (125)I adjuvant brachytherapy group (n = 34) and a group of best care (n = 34). Patients in the (125)I adjuvant brachytherapy group received (125)I seed implantation on the raw surface of resection. Patients in the best care control group received identical treatments except for the (125)I seed implantation. Time to recurrence (TTR) and 1-, 3- and 5-year overall survival (OS) were compared between the two groups. The follow-up ended in January 2010, and lasted for 7.7–106.4 months with a median of 47.6 months. TTR was significantly longer in the (125)I group (mean of 60.0 months vs. 36.7 months in the control). The 1-, 3- and 5-year recurrence-free rates of the (125)I group were 94.12%, 76.42%, and 73.65% vs. 88.24%, 50.00%, and 29.41% compared with the control group, respectively. The 1-, 3- and 5-year OS rates of the (125)I group were 94.12%, 73.53%, and 55.88% vs. 88.24%, 52.94%, and 29.41% compared with the control group, respectively. The (125)I brachytherapy decreased the risk of recurrence (HR = 0.310) and the risk of death (HR = 0.364). Most frequent adverse events in the (125)I group included nausea, vomiting, arrhythmia, decreased white blood cell and/or platelet counts, and were generally mild and manageable. CONCLUSIONS/SIGNIFICANCE: Adjuvant (125)I brachytherapy significantly prolonged TTR and increased the OS rate after curative resection of HCC. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12610000081011.