Updated: Jan 21
Hepatocellular carcinoma (HCC) can be treated with surgical resection, liver transplantation, chemotherapy, and/or locoregional therapies. Treatment options vary based on a variety of factors including distribution/extent of malignancy (stratified via Milan criteria to assess suitability for liver transplantation), location of lesions, severity of underlying liver disease, presence/absence of extrahepatic metastases, social circumstances/support system, and severity of comorbid conditions. Transplant Surgeon Dr. Jennifer Berumen and Interventional Radiologist Dr. Isabel Newton discuss clinical work-up for HCC patients, multi-specialty collaboration, and why locoregional therapies are important for both transplant and non-transplant candidates.
We’ve provided the highlight reel below, but you can listen to the full podcast here.
The BackTable Brief
Liver transplantation, when feasible, is the preferred treatment option for HCC in the setting of hepatic cirrhosis. Although Milan criteria are the standard for establishing transplant eligibility, a multitude of additional clinical and social elements are considered in evaluating potential transplant candidates in order to optimize survival of both grafts and recipients. Examples include serum alpha-fetoprotein (AFP) levels, cardiopulmonary comorbidities, portal hypertension, and social support system. Dr. Newton notes that patients with poor social support systems are considered poor candidates for transplantation, as are those with significant portal hypertension.
Locoregional therapies are often utilized to control disease and prolong survival in patients with HCC who are not candidates for resection or transplantation. In select patients, liver directed therapy can potentially downstage disease to meet Milan criteria and facilitate transplantation. Furthermore, for established transplant candidates, locoregional treatments are often employed to bridge patients to transplant by controlling disease during the waiting period for a donor liver. A recent study published in the Annals of Surgery (https://pubmed.ncbi.nlm.nih.gov/30870180/) demonstrated lower recurrence rates and superior survival in patients who experienced complete pathologic response to locoregional therapy prior to transplantation.
Drs. Isabel Newton and Jennifer Berumen help lead a multidisciplinary liver tumor board that includes hepatology, medical oncology, radiation oncology, and hepatobiliary/transplant surgery services. This conference fosters collaborative discussion of both new and established patients with HCC in order to optimize treatment at all stages of disease.
Image Courtesy of Michael Barraza MD
Disclaimer: The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.
Patient Selection and Clinical Evaluation for HCC Treatment
Patients with hepatocellular carcinoma (HCC) are selected for either surgical resection, liver transplantation, locoregional therapy, or systemic therapy. Those deemed to be transplant candidates may undergo locoregional therapy performed by radiation oncology or interventional radiology to “bridge” them to transplantation by controlling disease during the six-month waiting period. HCC patients who aren’t transplant candidates at initial presentation can potentially be “downgraded” to meet Milan criteria via liver-directed therapy. Patients with extrahepatic metastases may require both locoregional and systemic treatments. Beyond Milan criteria, numerous additional pathologic, clinical, and social factors are considered to delineate treatment options for each HCC patient.
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?
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.
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?
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.
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?
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.
So, Isabel, over to you. Can you talk a little bit about your initial patient evaluation with this population?
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.
A Multidisciplinary and Collaborative Liver Tumor Board
Dr. Isabel Newton and Dr. Jen Berumen sit on a liver tumor board that includes hepatology, medical oncology, radiation oncology, surgery, and the transplant team. The liver tumor board is led by interventional radiology and involves discussing the treatment and management of HCC patients, whether they are new, undergoing a new therapy, or have a change in circumstances.
I work closely with the members of our liver tumor board, which is comprised of a multi-disciplinary team and includes Jen Berumen. And this is the only liver tumor board that I know of that's led by interventional radiology, so we really get a front row view of all the patients who are referred to the VA with the hepatocellular carcinoma. We discuss these with everyone who is present at the liver tumor board, which includes hepatology, medical oncology, radiation oncology, surgery and also the transplantation team. And as a result of those conversations, we make decisions about management and treatment together.
Once someone is sent over to interventional radiology, have they been vetted and discussed by the tumor board or can you see referral patterns from all over, like oncology, surgery, maybe hepatology?
In the past, before we successfully launched our liver tumor board at the VA in San Diego, we would get referrals from all over the place. It could even be from primary care. There was less of a regular referral pattern, although the more common players were the ones we'd get them, or commonly from. But now that we have the liver tumor board, we all understand that any new patient with HCC will be discussed. And any patient who is undergoing treatment and has a change in the circumstances, either their disease progresses or they have a change in their social situation, or anything else that would impact their eligibility for treatment, we bring them up and discuss them again at liver tumor board. I really appreciate the fact that we all speak about every patient, even patients that don't end up coming to interventional radiology, who I never see. Many times, we will just do consultations with these patients so they understand the breadth of the options that are out there and to introduce them to all the different players of the team that will be impacting their care.
It’s incredibly important to have good interventional radiology as well as good communication with your interventional radiologists, so that we can communicate, "How long is it going to be before this patient gets transplanted and how aggressive do we need to be with our local regional therapy?" We talk openly about the tumors the patient has and how well the treatments are going and how high risk the patient is.
Treating liver cancer is an evolving and complex endeavor that involves many different players, including the patient and educating them. If they are a borderline patient or their tumor seems to be borderline, [we can still] give them all the information that they can use to make an educated decision for themselves. We’re not here paternalistically as this liver tumor board who comes in and tells the patient, "Now you will undergo this." We make our recommendation and then we tell the patient all the information that we have gathered. We explain to them and show them, "This is the treatment that was done to you, this is how your tumor responded. You had a good response, you didn't have a good response." I have found that when we do that, patients become much more active in their own health care and can accept the reality of what's happening to them in a much more tangible way. And since [liver cancer] is constantly evolving, you really do need somebody who is a professional who can tell you, "Hey, these are the guidelines and this is why I recommended that,” or "Hey, let's not waste the patient's time because the patient would never fall into the criteria for transplant." For anyone out there who does treat interventional oncology patients, patients with HCC, and does not have a liver tumor board to discuss these patients, I would encourage you to develop one and develop a really good relationship with your surgeons.
The Importance of Locoregional Therapy
Locoregional therapies have an established role in the treatment of HCC in patients who are transplant candidates, as well as in those who aren’t. In transplant candidates treated with locoregional therapy, those with complete pathologic response have demonstrated significantly lower recurrence rates and improved survival following transplantation. Furthermore, for patients who aren’t candidates for transplantation or resection, locoregional therapy can often control disease progression and significantly prolong survival.
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?
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.
What were your big takeaways from this paper and the importance of it?
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.
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.
Dr. Jennifer Berumen is a transplant surgeon and assistant professor with the UCSD Department of Surgery in San Diego.
Dr. Isabel Newton is a practicing interventional radiologist at UC San Diego Health in San Diego, CA.
Host Dr. Christopher Beck is a practicing interventional radiologist with Regional Radiology Group in New Orleans.
Cite this podcast:
BackTable, LLC (Producer). (2020, May 21). Ep. 64 – Bridging to Transplant for HCC [Audio podcast]. Retrieved from https://www.backtable.com/podcasts
The Materials available on the BackTable Blog are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.
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