Transcription:
Updates in Hepatocellular Carcinoma

Melanie Cole (Host): Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole. And today, we're offering updates in hepatocellular carcinoma.

Joining me is Dr. Laura Kulik. She's a Professor of Medicine in the Department of Gastroenterology, Hepatology, Radiology, and Surgery at Northwestern Medicine. Dr. Kulik, it's a pleasure to have you join us today. Can you tell us a little bit as we begin this podcast about the current state of hepatocellular carcinoma, the prevalence, anything you'd like to tell us about what we know about this that we didn't know maybe 10 or 20 years ago?

Dr Laura Kulik: Well, thank you so much for having me today. So the landscape in terms of the prevalence of HCC, unfortunately, this is one of the cancers that is increasing in prevalence compared to other cancers. And this is probably several fold. This is related to increase in cirrhosis, which had been in the last 30 years due to hepatitis C. Fortunately with the new agents that we have for hepatitis C, we are able to cure hepatitis C about 97% of the time. And in doing so, we're decreasing the number of people who are developing cirrhosis. And cirrhosis is the main factor for someone being at risk for HCC. So now, we're seeing more HCC related to increased risk of cirrhosis due to alcohol, fatty liver disease also called NASH. And those are the trends that we're seeing, a decrease in hepatitis C and increases due to non-viral etiologies.

Melanie Cole (Host): Thank you for that. So, tell us a little bit about screening. Has that changed at all? And how have advances in radiologic imaging significantly augmented your therapeutic and diagnostic capabilities?

Dr Laura Kulik: So, the screening for HCC has remained the same. And, according to the United States or the AASLD guidelines, and that is an ultrasound plus the use of alpha-fetoprotein, which is a tumor marker in the blood, every six months in any patient who has underlying cirrhosis. So there is other guidelines where they are not using AFP as much. We, in the American guidelines, feel that AFP is important in screening for patients. So it's ultrasound plus AFP, never the use of AFP alone.

Some of the exciting things that may be coming up are the use of abbreviated MRIs. MRIs are very costly. They take a long time. And they may be able to do these MRIs just specifically looking at the liver and the phases that we need to screen for HCC. And this is not primetime yet, but the hope is that this will become available and will increase the detection of HCC at a very early or early stage, which is where we hope to be able to cure people. The issue with ultrasound is that there are people who will not screen well, particularly those who have a very cirrhotic liver, which tends to be patients who have decompensated liver disease, so our Child-Pugh B's and C's, patients who have underlying fatty liver and patients who have obesity, which we are seeing a rise in.

Melanie Cole (Host): So then what had been the standard treatment and how has that evolved over the years? How's the management of liver cancer in general changed in the last few years?

Dr Laura Kulik: So I would say that the largest thing that has happened is the number of increases in systemic therapy that are currently available. So for about 10 years, we had only one agent, a systemic agent, which is an oral agent known as sorafenib. And then the last two to three years, there has been an explosion in the number of agents that have been approved by the FDA for the use of patients with advanced liver cancer.

The current standard of care is a systemic therapy known as atezolizumab plus bevacizumab, which is an immune therapy plus the bevacizumab which helps decrease the rate of people developing resistance to the immunotherapy. And with that, we have now seen a median overall survival of 19.2 months in patients, which is a huge increase from what we used to quote, which was approximately six months. So there are several other agents that are available. So we now have not only first-line therapies, but second line and even third line therapies, and we are expecting the addition of more combination therapies to come to market in the near future.

I would say the other thing that is new is that radioembolization or Y90 has now been approved by the FDA as of March of 2021. Prior to that, it had been on a compassionate use basis. At Northwestern, we are very fortunate to have our skilled interventional radiologists, who have really set the groundwork for the use of radioembolization, not only in early cancer, but we are also using it in advanced cancer.

Melanie Cole (Host): Dr. Kulik, in my research, it seems there are many staging systems out there right now. And as you were just talking about all the available therapies, how are you utilizing these to provide the rationale for your clinical decision-making? What are some of the non-surgical therapies that are really exciting for primary or local regional or even systemic? Is there anything out there on the horizon that you'd like to mention?

Dr Laura Kulik: Well, the staging system that most are using is the BCLC staging system, which comes from Barcelona. And the real strength of that is it takes into account the tumor size and number as well as how well the person is doing their performance status, as well as the underlying Childs-Pugh classification, which looks at how well the liver is actually doing. And it pairs that with therapies that have been looked at. Hopefully, the goal is that across the staging system, this will all be randomized controlled trials, which is the benchmark in medicine. And this is also paired with an expected life expectancy in patients, which is patients are always asking, how long will I be expected to live with this type of cancer and how advanced my cancer is?

I think the biggest advancements is, as I said, we have the systemic therapies and local regional therapy with radioembolization, really being used across the staging system, is looking at patients who have intermediate and/or advanced cancer and the use of combining radioembolization with the systemic therapies and the hope of down staging or getting these patients to a potential curative therapy, which would include resection or potential for liver transplantation.

Melanie Cole (Host): It's a fascinating topic we're discussing today. Do you have any updates on surgical treatments to share? And have the criteria for transplant for HCC changed at all?

Dr Laura Kulik: So starting with surgical criteria, you know, as the surgeons have become more advanced in their ability to perform these surgeries in a minimally invasive manner, this has decreased blood loss, which is important for a liver that is generally sick with underlying cirrhosis. The less blood loss there is the less chance for decompensation. We are still using similar criteria that patients have to have good liver function, so they have to be a Child-Pugh A and there has to be lack of what we call clinically significant portal hypertension. The best way to determine that is by doing a transjugular approach, where we measure the pressures in the liver to get an estimate, and this should be less than 10. Surrogates for this can be the presence of varices, a spleen larger than 12 centimeters, platelets less than 100,000 and the presence of ascites. In those patients, we know that they are likely to have a pressure gradient that is above 10.

I would say that we are being a little bit more aggressive if the amount of liver that you have to remove is small in doing these surgeries. The other thing is now that we have so many people who have been cured from their hepatitis C, the pressures in the liver may decrease. So patients that we weren't able to do a resection in the past, we may now be able to do because the cause of their underlying liver disease has been abated and, therefore, the pressures in the liver have decreased.

In terms of transplant, the Milan criteria, which come from Professor Mazzaferro since 1996 have remained the same. This is a one lesion up to five centimeters or up to three lesions with all being less than or equal to three centimeters with no evidence of vascular invasion or disease outside the liver. But we are being more aggressive and downstaging patients. So what that means is if you have someone who, for example, has a 7.5 centimeter lesion that's solitary by using local regional therapy, if you decrease that lesion to 5 centimeters or less, you can now say that they're in the Milan criteria and ask for what we call an upgrade to allow them extra priority for transplant in the hope of getting them to transplantation.

So that is something that as we've had new tools in our toolbox, that we are being more aggressive in using these tools to try to get these patients to less of a tumor burden that may qualify them for transplantation.

Melanie Cole (Host): And speak a little bit about the approach that you take for patients at Northwestern Medicine. And given the complexity and with increasingly complex treatment algorithms that are adding these new options to your armamentarium of available therapies, tell us a little bit about a multidisciplinary approach and management for these patients and the approach that you're taking at Northwestern Medicine.

Dr Laura Kulik: Yes, that is a very important question. So I am fortunate enough work with an amazing team that is very dedicated to the care of these patients. We have Dr. Lewandowski who leads our oncology, interventional radiology; Dr. Aparna Kalyan, who is the main oncologist that I've been working with as well as additional oncologists. Karen Grace is one of our nurses who is phenomenal in guiding these patients through this very intense and emotionally challenging journey that these patients take. And then several of our transplant surgeons, including Dr. Daniel Borja and Dr. Juan Carlos Caiced and this whole group meets several times a week. We have a clinic, where these patients will see all of the people that I have mentioned, as well as a review that occurs several days after that clinic, where we kind of get together and powwow and decide what the best course of treatment will be for these patients. And our primary question is can we get these patients to a potential curative option. The other issue is do they fit into criteria for one of the several trials that may be going on at Northwestern, which mainly will include the use of local regional therapy and/or the use of systemic therapies that are currently being looked at under investigation.

So I think the real strength is that we have a very dedicated team and that these patients will be able to get to treatment in a very quick fashion after they are seen in this multidisciplinary clinic, which meets once a week. So patients, when we get contacted, we can get them in usually in less than a week. And then within a week or so, they are slated for a treatment plan that would be starting.

Melanie Cole (Host): Such an interesting topic we're discussing here today. As we get ready to wrap up, does there still remain a compelling need for novel biomarkers and therapies for treating HCC? I'd like you to mention any of those clinical trials or research you would like other providers to know about and also when you feel it's important that they refer to the clinic at Northwestern Medicine.

Dr Laura Kulik: There are several different clinical trials. Some are going on in interventional radiology. One particularly that Dr. Lewandowski has in our ___ is when we have patients that we can do a resection because they don't have clinically significant portal hypertension and they're a Child-Pugh A, but the problem is, is they may not have enough remaining liver, which is called a future liver remnant. And one of the things that we are doing is using radioembolization to treat the cancer, for example, on the right side of the liver. And we've found that this radiation with time will force the left side of the liver to grow and that increases the future liver remnant to the point that some of these patients will now be able to undergo a resection, which they would have not been able to had they not received this therapy. So there is a specific trial looking at this. There are also trials being run through oncology, looking at various different combinations of immunotherapies combined with other immunotherapies and/or what's called tyrosine kinase inhibitors. So a lot of different exciting areas that are going on in this specific cancer.

So I think thing that's most important is referral. When patients have this type of cancer, there are many different treatments that may be available and they may not stay within the particular stage that they are at a diagnosis. And a patient should be given the opportunity at an experienced academic center to say, "Is this person a resection candidate? Can we get them to transplant? Are there clinical trials that may benefit this patient?" So I would encourage people to refer patients if there is something that is just the standard of care in terms that they will receive, those patients would be referred back to those physicians as it is much more convenient to receive their standard of care closer to home. But there are patients that we will be able to offer them therapy such as resection or transplantation that may not have been considered or thought possible.

Melanie Cole (Host): Thank you so much, Dr. Kulik. What an interesting podcast and so informative. Thank you again for joining us. And to refer your patient or for more information, please visit our website at breakthroughsforphysicians.nm.org/gastro to get connected with one of our providers. That concludes this episode of Better Edge, a Northwestern Medicine podcast for physicians.

For more updates on the latest medical advancements and breakthroughs, please follow us on your social channels. I'm Melanie Cole.