Melanie Cole, MS (Host): Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole. And today, we're joined by Dr. Laura Kulik. She's a Professor of Medicine in the Departments of Gastroenterology and Hepatology, Interventional Radiology and Transplant Surgery at Northwestern Medicine. She's here today to highlight transplant oncology for us.

Dr. Kulik, thank you so much for joining us today. Tell us a little bit about this field of transplant oncology.

Dr Laura Kulik: Thank you so much for inviting me today. So, transplant oncology is really an emerging concept, and it's really based on the premise of improving the overall survival as well as the quality of life in patients who are suffering from hepatobiliary malignancies and these include hepatocellular carcinoma as well as intrahepatic cholangiocarcinoma. And it also extends to those patients who have non-metastatic non-hepatobiliary carcinoma such as colon cancer or neuroendocrine tumors. And it's really important to highlight that this concept is really built on the expertise as well as the input of several disciplines, and this includes oncology, transplant surgery, transplant medicine and interventional radiology, as well as interventional radiation oncology.

Melanie Cole, MS: Well, thank you for that. And I would like to get more into that multidisciplinary approach later in the podcast. But tell us a little bit how this field has evolved when it comes to transplant hepatocellular carcinoma. You mentioned primary and secondary metastases. Tell us a little bit about how this has evolved to become transplant options for these cancers.

Dr Laura Kulik: So traditionally, and this dates back to 1996, patients with hepatocellular carcinoma, were chosen for transplant based on having early liver cancer. And this is based on size and number. And what we realized is that we were excluding patients who were beyond early HCC, who would enjoy an improved overall survival compared to not having had a transplant. And so, this has led to the concept of downstaging to transplant. And this primarily has been done with using local regional therapy, such as chemoembolization or radioembolization. But more recently, there has been multiple drugs that are called immune checkpoint inhibitors, which really take advantage of one's own immune system to unleash the power of the immune system to attack tumors. And now, we are looking at the use of these therapies either alone or in conjunction with local regional therapy to downstage patients to transplant. Patients that we would never have thought of performing a transplant, even patients with what's called portal vein invasion, which had been for many years an absolute contraindication for transplantation.

Melanie Cole, MS: Well, it's not only hepatocellular carcinomas. There are other cancers that could be considered for transplant potentially. Tell us about those.

Dr Laura Kulik: So, the other primary liver cancer that has not been considered for transplantation for many years due to poor outcomes is intrahepatic cholangiocarcinoma. However, it's been recently found that there is a group of patients who have very early intrahepatic cholangiocarcinoma carcinoma that you can select by using a biopsy of that tumor. Unlike HCC, where a biopsy is not needed, intrahepatic cholangiocarcinoma, a biopsy is required to make that diagnosis. And if the patient does not have poorly differentiated tumor, this is a group of people that could be considered for transplantation. Additionally, there is the use of chemotherapy and showing stability over a course of time. And in those patients, even with more advanced disease, transplantation is now being explored.

Other cancers that are being looked at include metastatic disease that is to the liver only in patients with colorectal cancer, which unfortunately, this is the most common organ in that colon cancer metastasize to, is the liver as well as neuroendocrine tumors.

Melanie Cole, MS: Tell us a little bit, Dr. Kulik, how Northwestern is really uniquely positioned to see patients with some of these cancers.

Dr Laura Kulik: Liver cancer, like other facets in medicine, it's become necessary that you need multiple experts or what's called a multidisciplinary approach. And this has really been shown to improve overall survival in many disease states. And while many centers have a multidisciplinary approach and have the expertise, I would say that what is very unique to Northwestern is that we have established a group of people who have all invested their time to be all present at the same moment that the patient is being seen. So, we have the surgeons, we have hepatologists, interventional radiologists, oncology, as well as interventional radiation oncologists. And this allows the patient to be seen in one day. See all these different experts, devise a plan and initiate that plan from the moment that they're seen as opposed to having to wait to see these individuals at separate visits. So, I do think that that is very unique. The patients really do enjoy the fact that they have to drive in once and that, by the time they leave, that there is a solid plan in place.

Melanie Cole, MS: Tell us a little bit about some insights into the advancements when you're talking about transplant as this new way to deal and treat these cancers. What about organ allocation, Dr. Kulik? Because that's a problem when you think of all transplants.

Dr Laura Kulik: Sure. And that's an excellent point. So, you have to operate under the rules of the governing bodies that organize transplant. And not everybody with these types of cancers will be granted what's called a MELD exception, meaning that they're given extra points or a priority that allows them access to get a deceased donor. Now, if someone has a living donor, that is under the actual organization of the institution to make the decision if they feel that this will be a successful transplant and lead to an improved overall survival, opposed to not doing a transplant.

The biggest, I would say, things that we have seen that have really catapulted the field forward has been these new systemic options known as immune checkpoint inhibitors, as well as the ability to detect tumors where we can do liquid biopsies. And as opposed to just looking at the response in the imaging, they are now using circulating free DNA to tell if the tumor present. And we are using this with all the cancers that we are transplanting, primarily colon cancer as well as HCC when it's in a more advanced state.

Melanie Cole, MS: You mentioned earlier about the neoadjuvant or adjuvant therapies that have evolved in the context of liver transplantation for HCC. Dr. Kulik, speak a little bit more about those and some of the outcomes that you've seen as these are combined therapies.

Dr Laura Kulik: So, I would say each institution has a different approach. And at Northwestern, we really enveloped and welcomed the ability to do radioembolization, which has been something that we have been using since 2003, particularly in patients with vascular invasion. And for many years now, we have been marrying this concept with systemic therapy. So, our patients will get radioembolization. And then within two to four weeks, we will initiate systemic therapy with the thought process being that we really want to give patients the absolute benefit of every opportunity to see an improvement in their tumor so that we could potentially get them to the road of transplantation.

Melanie Cole, MS: And now, I'd like you to expand on that continuing collaboration between the relevant subspecialties because there are a lot of them. Your transplant colleagues and hepatologists, gastroenterologists, I mean there's so many of these. Speak about that multidisciplinary approach and collaboration as essential in the management of HCC patients who are candidates for liver transplantation.

Dr Laura Kulik: Yes. As you said, it's very critical. And this has been shown in several different studies to lead to improvement and outcomes. And I think the majority of that improvement is that you are looking at patients from different angles based on what your expertise is. So, unfortunately, we cannot offer life-saving therapy to every single person, because we know that there's going to be high chance of tumor recurrence. So by bringing in all these different experts, it helps us determine what patients we think are going to have the best benefit from transplantation.

And this is not just in the clinic. There's constant communication between the groups, as well as, you know, patients end up at other hospitals during this course. So, being able to communicate with the outside physicians as well, knowing when it's time to get a patient over to Northwestern, and I would say that that communication is key to the patient's success and satisfaction.

Melanie Cole, MS: Well, certainly patient selection is critical to your outcomes. As we get ready to wrap up, and this is so interesting, Dr. Kulik, what recommendations do you have for other healthcare providers and researchers that are interested in keeping up-to-date with the latest developments in transplant oncology?

Dr Laura Kulik: So, there are many different areas that people could improve their knowledge and education on this. There are several different forums. There is the ILCA Conference, which is going to be happening in Amsterdam starting tomorrow. There's HCC Live, which is another multidisciplinary, specific conference for hepatobiliary malignancies. That will be in February. Certainly at the SSLD as well as EASL. These concepts are always talked about. And then, there are consensus statements for these various different tumors as well as foundations that you could also get information.

But I would say that the quickest and easiest way is reaching out to your local experts in that field to get the patient in to be seen. I would say that, you know, you may see a patient and it may look like transplant is far from being possible, and that may be true. But the one thing that we can't predict is how patients will respond. So, having those patients see a group such as a multidisciplinary team once after therapy to just say that you agree that, yes, transplantation is not in this person's future or, yes, we do think we can get this person to transplant and we need to start talking about things such as living donation, which Northwestern has been a leader in for many years.

Melanie Cole, MS: Thank you so much, Dr. Kulik, for joining us today. To refer your patient or for more information, please visit our website at breakthroughsforphysicians.nm.org to get connected with one of our providers. That concludes this episode of Better Edge, a Northwestern Medicine podcast for physicians. Please always remember to subscribe, rate and review this podcast and all the other Northwestern Medicine podcasts. I'm Melanie Cole.