Transcript:Ghassan K. Abou-Alfa, MD: Well, let’s shift to therapy. I expect that there will be a little bit of further debate over here, because nothing is clear. If anything, let’s talk about Barcelona Clinic Liver Cancer (BCLC), which is more of a roadmap, because BCLC not only classifies patients in different categories in regard to the performance of their liver and the extent of the cancer of their liver, but it might also recommend some therapy. It’s rather a little bit boxed where, in other words, a small-disease good liver might go into surgery, a small-disease bad liver might go into transplant, a little bit more advanced disease in the liver might go into some form of local therapy, and probably some further advanced disease or metastatic disease might go into sorafenib or a clinical trial. But, obviously, there’s a lot of gray zone, as you could imagine, like in any other road mapping that we can do for any disease. So, let’s start dissecting a little bit on the surgery front and discuss some of those aspects. I would say a patient that you might see, Amit, in the clinic, maybe he’s followed or being seen for a hepatitis screen, and ends up with some lesion in the liver, 1 cm. Transplant or surgery?
Amit G. Singal, MD: So, this is actually a common debate that people have. I think if you ask 10 people, you’re going to get different answers from most of them.
Ghassan K. Abou-Alfa, MD: Maybe 20 answers.
Amit G. Singal, MD: Yes, exactly. So, I think it’s the type of thing where, in my mind, it’s a clear distinction. I think it really comes down to the degree of liver dysfunction. For patients who are either non-cirrhotic—which is a minority of patients in the United States—surgical resection should be your primary treatment, unless it’s not possible for other reasons. If you have a patient with well-compensated liver disease—so no ascites, no encephalopathy, and no portal hypertension—and with a unifocal lesion (almost independent of the size, it’s more so about good liver function), and if you have enough of a liver remnant, surgical resection should be your primary therapy. Only patients who are not surgical candidates for either degree of liver dysfunction or multifocality should be considered for liver transplant if they’re within the criteria. I think the branch point for me is the degree of liver dysfunction.
Ghassan K. Abou-Alfa, MD: Fair enough. I can understand. Can you please tell us, what are the criteria? Maybe we’ll start with the Milan just because it’s probably the most acknowledged one.
Amit G. Singal, MD: Yes. With the Milan criteria, you need either a unifocal HCC less than 5 cm, or two to three lesions—with the largest being 3 cm—in the absence of vascular invasion or distant metastases.
Ghassan K. Abou-Alfa, MD: Fair enough, and that’s very important because the criteria were actually built based on a trial by Mazzaferro and colleagues from Milan—and that’s why it’s called the Milan criteria, which has been reported in the New England Journal of Medicine. It really kind of shaped the world or the field of transplant where pretty much we are transplanting based on the liver disease—as we just heard from the expert, from Dr. Singal—and not based on the extent of the cancer. And, as such, the best outcome where you have survival that reaches up to 5 years is really dependent on having limited disease rather than way too much disease. If you happen to be in New York, and sometimes there is a transplant meeting, you’re going to hear about something called the MetroCard, where pretty much here in New York if you ride on the subway, you pay the same price wherever you go in the five boroughs. But, if you are in Europe, the further you are away from the center of town, the further you’re going to pay for your Metro ticket. Is that right in Italy?
Riccardo Lencioni, MD: Yes. You pay for what you get.
Ghassan K. Abou-Alfa, MD: Fair enough. Exactly. You pay for what you get. And, as such, if there is further extent of the disease, the chance of recurrence is much higher. This is the price of the ticket, and, as such, there should be some kind of assessment and a very frank discussion in regard to whether this is really the appropriate choice of therapy or not. Now, let’s switch to the other perspective. Remember, livers are not necessarily always in abundance. And this is the reality of transplant. So, we depend on the Model for End-Stage Liver Disease (MELD) score. Can you tell us a little bit more?
Amit G. Singal, MD: Yes. So, the MELD score is an objective score based on three lab values: the bilirubin, the INR, and the creatinine. Based on these three lab values, you get a score called the MELD score. And the MELD score is really the priority score for liver transplantation. So, the higher your MELD score, the higher you are on the transplant list. Now, traditionally, what used to happen with HCC is you would get an exception score. You would jump up to a score of 22 and then continue to accrue extra points every 3 months. This scoring system was just changed in the last year where now patients are listed with their natural MELD—once again, based on these three lab values. They are on the list for 6 months, and then they jump up to a score of 28. Now, depending on which region of the country you are in, a score of 28 or around 30 will get you transplanted. So, in Dallas, we’re transplanting around a score of around 30. I believe in LA you’re transplanting at much higher MELD scores?
Richard Finn, MD: For sure, for sure. And now with the new MELD system, the liver cancer patient is going to max out at a score of 34, which is the true impact of that in the future.
Amit G. Singal, MD: Yes. I think in certain areas, such as parts of California and likely even in New York, you’re going to see HCC patients that actually can’t receive transplants because the average MELD score that people are getting transplanted at exceeds that 34 and is closer to 37, 38.
Ghassan K. Abou-Alfa, MD: So, what does that mean to oncologists? That’s a very critical component, because if anything here, we’re talking about the rationing of a limited resource, which is the explants or the transplanted liver that we can put in patients that are in need. And, as such, if you happen to have a patient that has limited disease, it’s very critical and imperative that this patient be referred to a transplant service where they can be evaluated and put on a transplant list as soon as possible. Because, as we just heard, this is a matter of localization of the resource and, at the same time, building the scores as we go. And that’s why it’s very critical to move in that direction. I know he did not necessarily bring it up from that perspective. But if I may correct you Riccardo, however, you said that for Child-Pugh C patients, not much therapy. I know you put it from the perspective of local therapy, but that’s fascinating. This is a patient that probably should go to transplant before anybody else if they have limited disease, because this is their only chance of a cure or potential survival from that illness.
Transcript Edited for Clarity