Initial Approaches in Locally Advanced HCC

Transcript:Richard S. Finn, MD: This group of patients, who are probably the largest proportion that we see who are probably locally advanced, are patients that are technically Barcelona stage B. These are patients who will have multifocal tumors, and I think one of the limitations of surgery in radiofrequency ablation is that the whole liver is affected by the virus, by cirrhosis. You might burn 1 tumor or cut out 1 tumor, but then new tumors occur—sometimes over time or even all at once—by the time the cancer is found. Jordi, what is your general approach to patients who have Barcelona stage B intermediate disease with no vascular invasion? Just a big tumor burden in the liver?

Jordi Bruix, MD: For a big tumor burden, the first thing you have to consider is TACE, because this is what has been proven to improve survival. The selection has to be done according to the standard recommendations. The patients have to be compensated, with minimal symptoms and no vascular invasion. As soon as the patients have vascular invasion, the outcome is going to be worse. The results are not so good. And when they're in follow-up, even if you get a good response, the liver may deteriorate, the symptoms may appear, or the tumor may spread out or invade the vessels. Then, the patient is no longer indicated. So, the standard we do is, first, 2 sessions of chemoembolization. And if the patient has partial response—necrosis and so on—then we do TACE at intervals of 6 months.

Richard S. Finn, MD: The practice, often, has been, “Do a chemoembolization, get a scan, and if everything is okay, wait until they recur.” In your opinion, because you say to do 2 TACEs, do you do 2 TACEs right after?

Jordi Bruix, MD: We saw this at the beginning of using TACE in my place. What we learned, and did, is that when you do a first chemoembolization, you may have clotting. All of a sudden, you detect that the treatments are far better—and we are doing all sorts of imaging research. But you would have vessels that you would not find in the first angiography, and they would supply the tumor. In the second session, you detect them and then you increase the response rate. You have more patients obtaining a more significant objective response. This was the basis for these 2 sessions. At follow-up, we decided to do it at longer intervals because if you have response, you will need to decide when to screen for progression and what the magnitude of progression is, which you want to take into account to decide to do, again, a TACE. So, we decided to go for longer intervals to check for contraindications and to keep the patient out of progression. When this happens, and there is no response, then the patients are shifted to systemic therapy.

We have always followed the concept that we should do what is beneficial for the patients but not what is feasible to be done. There is lots of interest in combining things to get a better response, better necrosis, or better whatever else. But they ask, “Is this really beneficial or is it just a cosmetic improvement in the local efficacy where long-term is not improved?” This is why trials have to be in place—in the segment of patients with tumors that are 3 cm and 5 cm in size—to see the real value of the combination. But right now, we follow the recommendations. We do evaluations of new devices and new spheres, and we will continue from there.

Richard S. Finn, MD: Technology has improved outcomes in many areas of medicine. Chemoembolization has been around for decades. There’s now radioembolization. There has been interest in different beads. Dr. Marshall, can you give us an idea of where things are today?

Richard H. Marshall, MD: I’m glad we’re talking about this today. This is not something that would have received a whole lot of attention a few years ago, but we’ve seen great advances in the amount of research that’s done, especially in interventional radiology and with radioembolization. Of note is the recently revealed SARAH trial. This is the first reported randomized controlled trial that compares Y-90 in locally advanced hepatocellular carcinoma to sorafenib.

Richard S. Finn, MD: Can you give us an idea of what Y-90 is? It’s not, I don’t think, available at every center. And can you also discuss the approach?

Richard H. Marshall, MD: I’m glad you brought that up. Most people talk about embolization, and embolization is a broad stroke. When we talk about chemoembolization, it’s a totally different mechanism than radioembolization. In chemoembolization, we try to deliver chemotherapy to a tumor and we also try to induce ischemia or infarction by cutting off a blood supply.

In radioembolization, the approach is different. We deliver very small particles that are radioactive into the liver, and they follow the blood flow—which, preferentially, goes to tumors. This results in a microembolic effect, which does not cut off the blood supply to normal liver parenchyma, and then it delivers radiation. This has resulted in different complications and different symptoms after the procedures, most notably in patients treated with Y-90 radioembolization. Their symptoms tend to be much lower and their quality of life scores tend to be much better. But at the same time, this therapy might not be available everywhere. TACE may be the only option for those patients. But again, they’re 2 mechanistically, very different approaches to treating a tumor.

Transcript Edited for Clarity