Clinical studies in hepatocellular carcinoma.

Abstract

According to clinicaltrials.gov (a clinical trials registration site), there are currently 31 trials that are evaluating selective internal radiation therapy (SIRT) in hepatocellular carcinoma (HCC; consisting of nine completed studies, 20 ongoing studies and two studies of unknown status). These studies reflect the considerable interest in the potential application of this procedure in not only advanced HCC, but also in intermediate HCC (with studies evaluating SIRT vs transarterial chemoembolization [TACE]), early HCC as a bridge to transplantation (based on retrospective studies and a new trial from a French institution that will evaluate SIRT vs TACE) and in the neoadjuvant treatment setting (presurgery). To date, the best published evidence for SIRT comes from retrospective and prospective cohort studies and case–control studies in advanced HCC [1–4]. One of the largest retrospective clinical case series evaluated 325 patients (from 2003 to 2009) with multinodular disease (75.9%) who had been treated with SIRT at eight European centers. The median duration of survival was 12.8 months (95% CI: 10.9–15.7) with elevated bilirubin reported as the main grade 3 adverse event in 5.8% of patients [2]. As discussed by Sangro in this supplement, SIRT (using either resin or glass microspheres) is effective across the spectrum of patients with earlyto advanced-stage HCC [3,5,6], including patients with main and branch portal vein thrombosis (PVT), who generally have a poor prognosis (Figure 1) [2,7]. As a consequence, a number of prospective Phase III studies are evaluating SIRT in advanced HCC (stratifying patients with or without PVT). Some of these studies are combining SIRT plus sorafenib, while others are comparing SIRT versus sorafenib (Table 1).