Hepatocellular Carcinoma - Episode 9
EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD
Ghassan Abou-Alfa, MD, MBA:I’m going to come back to some points with Riad. But before I go there, there’s 1 important point, and this is a teaching point. If anything, Farshid, I’m asking you simply because you were the 1 who presented the data. Remind me, with lenvatinib, when they evaluated it as part of the REFLECT study, there was some comment with regard to how much of the vascular invasion there is. Tell us about what are, say, V4, V3, V2.
Farshid Dayyani, MD:If you just look at the top line, you might think the REFLECT study excluded any patient with portal vein thrombosis. But that was not the case. It was really just major portal vein, which is a VP4, and then as you go into the liver and they branch more and more, it becomes a VP3, VP2, or VP1. And the smaller ones were all allowed in that trial. It was just major portal vein thrombosis, VP4, that was excluded in the REFLECT trial.
Ghassan Abou-Alfa, MD, MBA:Thanks for reminding us. It’s very important to remember that it’s not an absolute criterion. As exactly Farshid is mentioning, patients with a VP4 are going to sadly be sick to begin with, so they might not be eligible for therapy anyway. But with this, let’s go back to Riad. You already mentioned that’s where you would trigger the question. You mentioned trying to take care of the whole liver. What other methodology could we have used in that setting beside chemoembolization?
Riad Salem, MD:This is a prime case in which we can bring up the discussion of radioembolization as an alternative to chemoembolization. Because the reality is 1 of the advantages of radioembolization, which is methodologically very similaryou place a catheter in the artery, and you inject something, in this case you just inject these radioactive beads—is that this therapy has been shown to be much more nimble in terms of what it can do. It] not only treats the tumor but also gives you a biologic test of time and hypertrophies the contralateral side, so it brings in a narrative of possible resection to patients with whom you might not have had that discussion up front, such as early stage B patients and challenging stage A patients, for example. And so certainly 1 thing to consider in a patient like this in the future is if you have unilobar disease—and, as we know, cirrhotic patients have small left lobes in general—you want to hypertrophy them.
One of the techniques we’ve been using that has replaced portal vein embolization in our experience is radioembolization because of the advantage. There is a high response rate, you’re treating the tumor, and you’re hypertrophying the other side. Now we have a large series of patients like this where, as we mentioned before, we’re individualizing patient care. All of a sudden you think outside the box, you’ve got good tumor biology. OK, well, you’re BCLC [Barcelona Clinic Liver Cancer] stage B, but now maybe you’re even resectable. It allows you to sort of expand the armamentarium of treating these types of patients, and that’s what we’ve done with radioembolization.
Ghassan Abou-Alfa, MD, MBA:Teach us a little more about radioembolization. Because in all fairness, some of us don’t know much about it. Teach us.
Riad Salem, MD:Radioembolization is technically very similar to chemoembolization, where the catheter is placed inside the liver of the artery feeding the tumor and, because tumors are hypervascular, whatever you’re injecting accumulates inside the tumor. In this case, you are injecting micron-size radioactive particles embedded with yttrium, with a half-life of about 2½ days or so, so you have about 14 days of activity. And it functions as a low-dose rate brachytherapy-type methodology, but most importantly, Ghassan, it’s not an embolization procedure. The issue with, say, bland embolization or chemoembolization is that you block the vessel. Blocking the vessel causes pain, ischemia to the liver. That’s how you have postembolization syndrome.
With radioembolization, you’re just injecting these beads. They don’t change the blood flow, and as a result, patients go home the same day. What you’ve done now is theoretically gotten something with a high tumor response rate on an outpatient basis without the issue of occluding vessels, which can happen after multiple chemoembolizations. It really is, in my opinion, the next-generation type of embolotherapy. When done well we can get very, very good results with this technique.
Ghassan Abou-Alfa, MD, MBA:I totally agree. That’s great to hear. Amit, I will ask you as a hepatologist. This is definitely a patient who really needs your care. What do you advise our colleagues, especially in oncology, on how to manage or maximize their liver function? What does this patient need from the hepatologist’s standpoint?
Amit Singal, MD:As we’ve discussed, these patients are really best treated in a multidisciplinary setting where the hepatologist is brought in not late in the game, after a patient decompensates, but early and follows the patient through that entire course. This patient started with ascites and lower extremity edema, so he should have been on diuretics at that time and once again monitored through the therapy.
Actually, at this point, because this patient has been treated and actually had a complete response in terms of tumor but has worse liver dysfunction, he can actually be considered as downstaged and potentially listed for transplant. Once again, he’ll have to continue having a response and stay within criteria. But this is a disease within a disease, as Riad brought up before. Now that he’s had a good response to the tumor, it really is taking care of that liver dysfunction, and transplant is a cure.
Ghassan Abou-Alfa, MD, MBA:Besides the diuretics, if needed, for ascites, lower extremity edema, and sometimes even testicular scrotal edema, what else do you give?
Amit Singal, MD:If, for example, he has hepatic encephalopathy, he may need lactulose, he may need rifaximin. You’re going to have dietary recommendations in terms of maintaining a good protein diet, low-salt diet. Otherwise he’s going to need varices surveillance. The other thing these patients can have is portal hypertension. They can have large dilated veins in the esophagus that can be prone to bleeding, so he’ll need to be followed by upper endoscopies as well.
Ghassan Abou-Alfa, MD, MBA:Beta-blockers?
Amit Singal, MD:It depends on if he has the presence of these varices. If he has varices present, then you can either band those varices and treat them mechanically or you can start them on beta-blockers. But we don’t routinely start beta-blockers outside the presence of varices.
Ghassan Abou-Alfa, MD, MBA:Well, it’s interesting becauseand I don’t know if it’s correct or wrong—I do understand that some physicians, either hepatologists or oncologists, might put the patient on a prophylactic beta-blocker. What’s the value of that? What are the data?
Amit Singal, MD:Outside them having varices, starting somebody empirically on a beta-blocker doesn’t actually prevent or delay the onset of varices. All you do is you get the adverse effects from a beta-blocker: increased fatigue, etc, without any of the benefit.
Ghassan Abou-Alfa, MD, MBA:Does it help at all in regard to the ascites?
Amit Singal, MD:You’re decreasing portal hypertension. You may have some benefit in ascites, but it’s not the primary management of ascites.
Transcript edited for clarity.