Transcript:Ghassan K. Abou-Alfa, MD: We’ll move on to the second layer in regard to the management of HCC, which is really when we come to the locoregional treatments. And maybe we’ll start with Riad. You guys like acronyms like TACE, TAE, DEB-TACE, Y-90 (yttrium-90). Can you please go over the lexicon?

Riad Salem, MD: There’s no doubt that what you’re referring to here is the transarterial embolotherapies, and they start from the simple and elegant techniques of bland embolization that involve injection of particles to complete stasis to cause tumor necrosis. The gold standard by most guidelines is conventional Lipiodol chemoembolization with doxorubicin or, in some cases, triple-drug. That evolved into drug-eluting bead chemoembolization, the idea that you can better concentrate a drug within the tumor and minimize systemic toxicities. And then there’s the radioactive particles called “radioembolization,” which is technically the same thing, but in that case, we’re just injecting a radioactive particle. So, we really have a pretty big menu of types of treatment options. I think it’s clear from where these treatments are practiced that, certainly, there’s a center individualization, a patient individualization. But all of these are clearly applied, depending on the center that you’re in.

Ghassan K. Abou-Alfa, MD: Absolutely. Laura, in regard to those local therapies, we hear about the concerns about what can happen liver toxicity-wise. So, can you guide us through that, first in regard to TACE and TAE and then talk about yttrium-90 in that regard?

Laura M. Kulik, MD: The key difference between those 2 intra-arterial therapies is that the TACE and TAE are embolic therapy with the goal of inducing ischemia to lead to tumor necrosis. Whereas, radioembolization, you actually need oxygen for the radiation to be most beneficial. And it is microembolic. You maintain the patency of the hepatic artery, which allows you to treat patients as an outpatient, whereas patients who are receiving chemoembolization still traditionally are hospitalized to manage symptoms for a short period of time, such as abdominal pain, nausea, fever, etc. Both of those treatments, though, you are trying to kill a tumor that is living, usually 90% of the time, in a diseased liver. So, there is always concern that you will actually cause necrosis of the uninvolved tumor tissue, potentially leading to further decomposition, jaundice, and encephalopathy. With recurrent treatments, you can start to see increased portal pressures, variceal bleeding, etc.

Ghassan K. Abou-Alfa, MD: Can you tell us a bit more about the long-term effects, in other words, that can happen after several months with regard to yttrium-90?

Laura M. Kulik, MD: So, there can be long-term effects. In my experience, I’ve seen this more long term in patients who have metastases as opposed to liver-directed therapy used for HCC. And there is a difference in the anatomy and the arterial blood flow. When patients have underlying cirrhosis, they start to rely more on the hepatic artery because of the portal hypertension, whereas in patients who do not have underlying liver disease, they’re maintaining most of their blood flow from the hepatic artery. So, I’ve actually seem more long-term issues in people who have metastatic disease, where they develop significant fibrosis, and that may be that you’re treating the entire liver, it may be because of differences in the blood flow, it may be that they actually potentially live longer or don’t get transplanted as opposed to patients with underlying HCC.

Ghassan K. Abou-Alfa, MD: Richard, as a medical oncologist, of course, we are comfortable within the zone of systemic therapy. We just heard it’s very important. What can we tell our colleagues in regard to yttrium-90 as an advent therapy that is currently being practiced—and I think we’ll ask Riad in a second about his experience because he has probably one of the most important experiences with the therapy worldwide. What’s our obligation as medical oncologists to make sure that we introduce those therapies to our patients as well and assure them that they are definitely appropriate and safe?

Richard S. Finn, MD: Well, there’s no doubt that locoregional therapies play a role in the management of HCC. If we look at patient stage by the Barcelona criteria, this would be the Barcelona B group or the intermediate group. These patients typically have multi-nodular disease, Child Pugh A/B, and are well compensated and have a good performance status. I think, going to that concept of the multimodality management, it’s important to recognize the limits of locoregional therapy and to stay engaged in the management of our patients because we’re seeing now that we have effective systemic treatment. And in order to get a patient on to systemic treatment, we need to capture them before they become too ill. That involves interacting with the interventional radiologist and the hepatologists to recognize when a patient is no longer an appropriate candidate for locoregional therapy, whether it be Y-90 or conventional TACE, and being able to triage those patients to an appropriate systemic treatment now in frontline and expanding that repertoire to agents effective in second-line as well.

Transcript Edited for Clarity