Melanie Cole, MS (Host): Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole, and joining me today is Dr. Laura M. Kulik. She's a Professor of Medicine in the Division of Gastroenterology and Hepatology, Radiology, and Organ Transplantation in the Department of Surgery at Northwestern Medicine.

In today's episode, we're delving into the critical and evolving field of liver cancer. Our guest, Dr. Kulik, is an esteemed expert in this area and she'll be shedding light on the latest advancements in diagnosis, treatment, and patient care as well as the integral role of multidisciplinary teams in managing this complex disease.

Dr. Kulik, it's always a pleasure to have you join us today as we start this discussion. What are some of the most significant advancements in the diagnosis and treatment of liver cancer that you've observed in recent years?

Dr. Laura Kulik: Well, thank you for having me today. I think there are a lot of advancements, specifically in immunotherapy, which has been a blockbuster for almost all cancers, has also had a significant role in the treatment, not only in hepatocellular carcinoma, but also in cholangiocarcinoma. We are seeing patients who would have a life expectancy of typically six months and those with advanced cancer who are now enjoying a life expectancy that may go over two years and those who have a response. This is leading us to consider transplantation in some patients that we would have never considered that as a possibility.

Additionally, we have increased knowledge in radiomics where the radiologists are becoming more and more experts in terms of looking at the characteristics of a liver lesion. And when it is malignant, they're being able to decipher the aggressiveness of some of these tumors just based on the way that it appears on imaging.

Melanie Cole, MS: This is interesting. Now, I'd like to jump back for a second, Dr. Kulik, and speak about the prevalence. Tell us about how common this is nowadays. What are you seeing in the trends as far as liver cancer?

Dr. Laura Kulik: So liver cancer, when we talk about hepatocellular carcinoma, traditionally, this occurs in 80-90% of people who have underlying cirrhosis. The exception is in patients who have chronic hepatitis B, they do not have to have the prerequisite of cirrhosis, unfortunately, to develop liver cancer. And we're also seeing that in some of our patients with the new term for fatty liver, which is now called MASH, metabolic-associated steatohepatitis, that there are some patients who will develop hepatocellular carcinoma without having underlying cirrhosis. But still, the vast majority of patients have underlying cirrhosis. And for that reason, anyone with underlying cirrhosis, regardless of the etiology, should be undergoing screening for HCC, which is an ultrasound and a tumor marker called alpha fetoprotein every six months.

Now, intrahepatic cholangiocarcinoma, on the other hand, you do not have to have underlying cirrhosis, but having cirrhosis is definitely a risk factor. But we're also seeing a younger group of population, particularly in women, and it's unclear if estrogen is playing any role in this increase in this cancer. But definitely, we are seeing this cancer in younger patients.

Melanie Cole, MS: So, tell us about the collaboration between Gastroenterology, Hepatology, Radiology, Oncology, and Surgery to enhance some of the patient outcomes in this sort of treatment. How important is a multidisciplinary management? These are complex cases, generally.

Dr. Laura Kulik: Yeah, you're absolutely correct. And I would say that a multidisciplinary team is absolutely mandatory. The majority of the patients that we see do come through our GI colleagues as they are often the ones seeing them in the community and screening them. And at Northwestern, we are one of the few sites in the United States that are fortunate enough to have a multidisciplinary team that is housed in one unit.

So many places will have ongoing clinics and they're going on at the same time and patients have to go from one place to another place. But at Northwestern, we're fortunate to have where everybody is there in the same clinic at the same time. And often, we see the patients as a group depending on what the situation calls for. So, we have an interventional radiologist, Dr. Robert Lewandowski. We have many surgeons who are present, Dr. Caicedo and Dr. Borja. Dr. Borhani is our radiologist. And we also have an oncologist who is present, which is very unusual to have an oncologist at the time that the patients are being seen in these clinics with the hepatologist. And that is Dr. Aparna Kalyan. And we also have a navigator, which is very key to getting these patients put into the clinic in a timely manner. So whenever we get a referral, we let Karen Marshall, who's our navigator, know. And she will then make sure that all the information is collected, that we have everything when we see that patient. And by the time that we see that patient, we have talked about them. And when we are finally evaluating them in person, by the time they leave, they will have a comprehensive plan as to what our plan of attack is on this tumor.

Melanie Cole, MS: Dr. Kulik, you mentioned transplantation. How has that evolved as a treatment option for these patients? I'd like you to speak about patient selection and what the process looks like when a patient gets to your transplant center, what they can expect on the waitlist and how you're managing their comorbid conditions and the condition itself while they're on the wait list.

Dr. Laura Kulik: So, you pointed out an important point. We are dealing with two underlying conditions which unfortunately are working in tandem to cause the patient morbidity and mortality. And that's the underlying cirrhosis as well as the cancer itself. And I'm speaking particularly about hepatocellular carcinoma at this point. And currently, patients are allowed an exception, which gets them increased points on the waitlist for transplantation, and that's based on size and number of tumors, which is something called the Milan Criteria, which has been in place since 1996, and this is highly regulated by the department, which is called UNOS. And so, patients are allowed to have one tumor up to five centimeters or three tumors that all have to be three centimeters or under with no evidence of disease outside the liver or evidence of what we call vascular invasion.

And there has been a lot of research that has looked into this and why we've had good outcomes using these stringent criteria. Many believe that is, in fact, too stringent and that we should be expanding this criteria. And it's very timely because we now have better local regional therapies, particularly radioembolization and the systemic therapies that I had briefly mentioned earlier. And we are seeing patients that have larger tumors, even patients who have vascular invasion, although those are the minority of people who make it to transplant, but we are considering transplanting patients that we would have never considered in the past. So, I would say what's changing is that we are becoming more aggressive with selecting patients with more advanced tumor than what we had in the past as the field has advanced.

Melanie Cole, MS: What do you see as the greatest single challenge facing patients on that waitlist today, the constraints to meeting that annual demand for liver transplantation, whether we're talking about living donor or deceased? What do you see happening in the future, Dr. Kulik, and what do you see as some of the bigger challenges?

Dr. Laura Kulik: Well, whenever someone is on a wait list for a transplant, it's a very dangerous place to be because you've deemed them sick enough that they need a transplant. And in this case, we're talking about cancer, which can continue to progress and make them no longer a transplant candidate.

And so, as they're waiting, there is risk of what we refer to as dropout. And those patients either become too sick or their cancer progresses or they die while they're waiting. So, I think the biggest thing for these patients is that anxiety of knowing that they're waiting for an organ to become available and hoping that their cirrhosis will not progress or that their tumor will make them no longer a candidate. And we're doing different things to try to optimize that. We're pushing living donors. We have a very robust living donor program that is led by Dr. Andreas Duarte as well as Dr. Justin Boike. And we also are fortunate at Northwestern to have two separate machines and possibly a third in the future that they're looking at that are called perfusion machines. And these are helping us take livers that we may not have used in the past, because of the fact that these livers, once they're outside of a beating human heart, they then have to go into what we call the buckets as they're waiting to get put into the recipient. And now, these machines are being used to preserve these livers so that these livers can withstand being outside of another person until they're placed into the recipient. And this has really allowed a greater access for organs, and we're fortunate that we have this capability at Northwestern. We have seen that this has increased our ability to transplant patients in a more timely fashion.

Melanie Cole, MS: What strategies would you like to recommend as the expert that you are to other providers for managing the patients who are not candidates for surgery or transplantation? As we discussed a little bit, the comorbid conditions of cirrhosis plus their liver cancer are to be managed. So, what do you recommend for whom those aren't options?

Dr. Laura Kulik: We have these newer therapies. And unfortunately, with the systemic therapies, there's no prediction model to say who will and who will not have a robust response. It's approximately, with the current medications, about 30%. There are newer ones that we're anticipating will be coming to approval through the FDA and that number will hopefully increase. But of those patients who do have a response, these responses tend to be very sustained and prolonged. So, I think it's important to let patients know, that this isn't necessarily an immediate death sentence, but it's also very important to let them know that this treatment is palliative, that we don't think that this will lead to an absolute cure.

Now, there are some where we're definitely shocked and there are patients who have been cured despite having advanced HCC with some of these medicines. And I do think it's very important that these patients be introduced to palliative care to help them deal with not only their anxiety, but some of their other symptoms to improve their quality of life.

And as far as treating their underlying cirrhosis, we make sure that patients undergo endoscopies as these patients are at higher risk of having varices, which when they bleed, they're at higher risk of mortality. Making sure that if they're candidates for a medicine called carvedilol or Coreg, to decrease the risk of bleeding. Managing their ascites by making sure they're educated, they've seen a dietician, they're on the appropriate diuretics, if they need to be on medication such as an antibiotic to prevent an infection in that fluid called SBP. And then, also managing their encephalopathy, trying to keep them robust in terms of their strength, particularly muscle mass. These are all things that can improve their quality of life and decrease their chances of further complications related to their cirrhosis.

Melanie Cole, MS: Are there any emergent therapies or clinical trials in hepatocellular carcinoma that you find particularly promising?

Dr. Laura Kulik: I do. There's one here at Northwestern that we're doing that's called Emerald-Y90. And we have used radioembolization at Northwestern for the last 20 plus years. And systemic therapy as I opened this podcast with has really been a breakthrough in not only HCC, but many other cancers. There's currently no data in terms of robust trials at looking at the combination of radioembolization plus systemic therapy. There has been some data looking at another type of local regional therapy called chemoembolization. And we really do believe that giving something like radioembolization before starting the systemic therapy may improve the robustness of the response of the immune system to increase the chances of having a response and, therefore, translating into an improvement in control of the tumor and in overall survival. And there is currently a trial that is specifically looking at that named Emerald-Y90. There are other ongoing trials that are going on at other institutions. And I think this combination approach of using local regional therapy plus systemic therapy to get patients either to resection or transplant, both of those consider potential curative options is going to be the way that the field is going to move towards.

Melanie Cole, MS: What an exciting time in your field, Dr. Kulik. As we wrap up, any final thoughts, key takeaways that you'd like to leave other providers with about hepatocellular carcinoma and the work that you're doing at Northwestern Medicine?

Dr. Laura Kulik: I think it's just important that providers know that we do have a team that is very dedicated to these patients. We see these patients on a weekly basis and then we also meet on a weekly basis to go over those results and their scans and, again, formulate their plan and know that there are people who are interested and dedicated and have the expertise to take care of these very complicated patients.

Melanie Cole, MS: Thank you so much, as always, Dr. Kulik, for joining us today and sharing your incredible expertise. And to refer your patients or for more information, please visit our website at breakthroughsforphysicians.nm.org/gastroenterology to get connected with one of our providers. That concludes this episode of Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole. Thanks so much for joining us today.