Re: Society of Interventional Radiology Position Statement on Chemoembolization of Hepatic Malignancies

Editor: We read with great interest the position statement on chemoembolization by Brown et al (1) in the February issue of JVIR. As the authors note, there has never been a prospective trial comparing chemoembolization with bland embolization (ie, without chemotherapy) that has demonstrated any difference in survival for patients with hepatocellular carcinoma. The study by Llovet et al (2) set out to compare bland embolization with gelatin sponge embolization, chemoembolization with gelatin sponge and doxorubicin, and symptomatic therapy. The trial was terminated when an interim analysis showed a significant improvement in survival for patients in the chemoembolization group versus those who received no treatment. At that time, there was no difference in survival between the two embolization treatment groups. Unfortunately, when the study was terminated, the opportunity to answer the question of bland embolization versus chemoembolization was lost. Although Brown et al (1) suggest that, with longer follow-up, a difference between these two treatment arms might have emerged, we will never know. In addition, patients in the trial of Llovet et al (2) were analyzed on an intent-to-treat basis. All 40 patients in the chemoembolization group were treated. Two of 37 patients in the bland embolization group (5%) were never treated, including one patient who died before treatment. The results of this trial do not clearly justify the addition of chemotherapy to embolization. The wide variety of treatment regimens used makes it difficult to interpret the multitude of studies of embolotherapy for hepatocellular carcinoma. Variables include the chemotherapeutic agent used, dose mixes, dose delivered, and embolic agent used. In addition, the pharmacokinetic data justifying chemoembolization with lipiodol are weak. Because it was difficult to identify which agent or agents to use, and it was less clear that they would remain in prolonged contact with the tumor at high concentrations, at our institution we use bland embolization (ie, with particles only and no chemotherapeutic agent) to treat patients with hepatocellular carcinoma, relying on terminal vessel blockade to cause ischemic cell death. To maximize the ischemic effect of embolization, we use small polyvinyl alcohol particles (50 m) or Embospheres (40–120 m) (Biosphere Medical, Rockland, MA), which results in terminal vessel blockade. The authors of the position statement apparently thought we had used chemoembolization with ablation; however, at our institution, we perform embolization with particles alone. In our study that was cited (3), we showed that, with a median follow-up time of 2 years, patients with solitary tumors as large as 7 cm treated with bland embolization plus ablation had survival similar to that of patients who underwent surgical resection. There are many theories about how to use the hepatic artery to deliver targeted treatment for hepatocellular carcinoma. It is important to have a clear concept of how each method works so the outcome is optimized. To justify the expense, added toxicity, and procedural complexity of chemoembolization, an incremental benefit compared with bland embolization (ie, with particles only) should be demonstrable. To put it simply, sometimes less is more.