Patient Selection and Treatment of Hepatocellular Carcinoma

[Chris Beck]
So today, our topic is going to be about hepatocellular carcinoma and within HCC, specifically, bridging the transplant. Isabel, can you talk a little bit about your practice and your HCC population in bridging the transplant and how that fills in to your clinical practice?

[Isabel Newton]
I concentrate in the treatment of hepatocellular carcinoma at the VA and our patient population is largely an older one, mostly male, and many have had a past of hepatitis-C or poly substance abuse or fatty liver disease.

[Chris Beck]
Jen, can you tell us a little bit about your clinical practice and how it relates to HCC and specifically, that subcategory of patients who are bridging to transplant?

[Jennifer Berumen]
In our clinical practice, we do surgical resections for HCC in patients who are candidates. And patients who are not candidates for surgical resection, we'll refer them for transplant, which is also us. For those patients, we assess their tumor, we assess them for potential metastatic disease, looking at their Alpha-fetoprotein levels. We also do a chest CT and a bone scan to make sure there's no evidence of metastatic disease with HCC. Patients who are good candidates for transplant, socially and from other standpoints, some we'll refer them for transplant. Because there is a six-month waiting period [once you get on the transplant list], we'll refer those patients [who are waiting] for locoregional therapy, and that's where we'll send them to interventional radiology or radiation oncology to get treatment for their tumors in the meantime. And that's in patients who are not candidates for surgical resection.

[Chris Beck]
How many patients, roughly, end up in the bridge to transplant category, those who aren't viable candidates for surgical resection or candidates for transplant itself?

[Jennifer Berumen]
For patients that we get with tumor who aren't surgical resection candidates, those patients are pretty much all going to get referred to radiology at some point. If they have metastatic disease and there's no point in treating just their liver disease, then they're not getting referred, but pretty much every patient that we have with a tumor is presented at a tumor board and gets the interventional radiology for locoregional type of therapy. What they get depends on the tumor size and the tumor location, and that's a lot of which we discuss with interventional radiology at the time. In order to be a candidate for transplant, those patients have to meet what we call the Milan criteria with their tumor, meaning they have one tumor that's less than five centimeters or three tumors that are each less than three centimeters. Patients who are beyond those criteria, we do not refer to transplant unless they can be viewed as what is called downstage, which means that the treatment would reduce the size of the tumor… The patients who only have liver disease with tumors in the liver that are not candidates for transplant, those patients are going to go IR for treatments. And Isabel treats a lot of those patients with recurrent TACE or other procedures that will keep those tumors at bay while they're trying to get treatment.

[Chris Beck]
So, Isabel, over to you. Can you talk a little bit about your initial patient evaluation with this population?

[Isabel Newton]
Our patient evaluation process is multi-factorial. Obviously, we consider what the tumor burden is on imaging, and we typically prefer MR for our imaging. We look to see if the patient is within Milan criteria, as Jen expressed. We also look at the lab values. Not all tumors express AFP. But if they do, it allows us to have another marker that we will assess. Because if they have a high AFP, and after locoregional therapy, the Alpha-fetoprotein decreases substantially, that's a very good prognostic factor. We look also at their social situation because the different treatment options very much depend on how stable their social situation is. Other factors are location and the number of the tumors to see the feasibility of treating with ablative treatments, which are, of course, the best kind if we're doing IR type treatments because they are the only ones with curative intent. And that is, of course, if the patient isn't a resection candidate, because that still remains a gold standard versus ablation. [We look at] comorbidities such as cardiac or pulmonary or other diseases that might make it difficult for them to undergo surgery. And then a big one for us is whether they have portal hypertension or signs of varices on imaging. If there's any question, we will actually check portal pressures because this could potentially disqualify them for surgical resection if they have portal hypertension. This is how we view our patients en masse with all these different factors.

[Chris Beck]
Our discussion is partly connected to a paper that came out this year in April out of the Annals of Surgery. The name of the paper is, Pathologic Response to Pre-transplant locoregional Therapy as Predictive of Patient Outcome after Liver Transplantation for Hepatocellular Carcinoma: Analysis from the US Multi-center HCC Transplant Consortium. If you're talking about bridge to transplant, not necessarily downstaging, why does it matter whether or not they have a good pathologic response following locoregional therapy? Can you explain to the audience why this is important?

[Jennifer Berumen]
So there are a bunch of different reasons. So what complete pathological response means is that the locoregional therapy we did killed all those tumor cells. And we always say that there's no cure for hepatocellular carcinoma except for transplant, because once patients develop tumor, they're going to develop it again once they have cirrhosis. The locoregional therapy is meant to really kill those tumor cells. The reason it's really important is that one, it tells us, did they respond? Were we able to kill their tumor? And did they have tumor after the treatment at the time of liver transplant? Because their rates of recurrence of the liver cancer are going to go up. So patients with complete pathological response have less recurrence of hepatocellular carcinoma after liver transplant, which is really important for their long-term survival. locoregional therapy to treat patients with tumors that are not candidates for transplant also gives us an idea of whose responding to what and what long-term outcomes we can have treating patients who are not candidates for transplant. Isabel does a lot of that therapy where she's treating patients with tumors over and over again, who are not going to end up being able to be candidates for transplant. It really can give them an increased lifespan.

[Chris Beck]
What were your big takeaways from this paper and the importance of it?

[Jennifer Berumen]
So I think it's actually really interesting the way that they looked at everything and split it up into groups. And so they teased out who was going to be low risk for recurrence, medium risk and high risk, based on the tumor characteristics, or based on the characteristics of the patients as well. And so I think it will allow you to give a better discussion to patients who are going in for transplant to say, "You have these factors. We know that you might be okay, but we can't really say that you're not going to be. You're at higher risk for recurrence. We can't say that you're not going to have a recurrence after transplant." And the patients can potentially be involved in the discussion, decide whether or not they want to go through transplant.

[Isabel Newton]
There are so many different ways of approaching liver cancer patients and different religions surrounding them. I say religion because no one paper has defined the perfect way to do something. But since we know that it is so important to address or to unveil the response of a patient's tumors to local regional therapy, the way that we do the local regional therapy is very, very important. So some places will say, we're going to treat three times, and then assess response after that. Others will treat one time, assess response and then treat again, and assess response. What’s important though is that when we do these treatments, we are very careful to address all. If you're doing a catheter-directed therapy, address all potential feeding vessels to try to contain as much disease as possible to prevent the rebound of disease. Give the patient the best opportunity to respond by doing the most complete treatment that you can, and this can involve assessing any parasitized vessels that are extra hepatic or looking at vessels that may be unusual, like perhaps cystic artery. I tend to be in the camp of treating then assessing response and treating again. I don't have a magic number of chemoembolizations that I'll do and say this person is or is not a responder. Some people show themselves very early on to be a non-responder, like the ones where you will do a very complete chemoembolization and they come back with disease everywhere and there's extra hepatic spread. There are some you treat with chemoembolization and then it’s fine. They give very, very good response. Others you have to chip away at the disease. I tend to not apply hard rules. I can't stress enough the importance of treating each patient as an individual, and each treatment as an individual treatment session in which you do your absolute best to get as much tumor under control as you can.