Scott Webb (Host): The liver is a large organ that does a lot of multitasking in our bodies, and today we're going to discuss the essential functions of the liver, cancer of the liver, and the various treatment options that include a new therapy called Y-90. And I'm joined today by Dr. Carl Valentin. He's a Board Certified Radiologist and Independent Physician who chooses to practice at Franciscan Health.

This is the Franciscan Health Doc Pod. I'm Scott Webb.

Doctor, it's, nice to have you here today. I must confess, I know we're going to talk about the liver and new therapies for liver cancer and Y-90 and a whole bunch of good stuff, but just foundationally, like at a basic level, I hate to admit this, but I'm not 100 percent on what the liver does exactly. And so I'm really glad to have you and your expertise here.

So before we get too far along here for me and everybody else, what does the liver do?

Carl Valentin, MD: It's an interesting question. The liver is a really dynamic organ. It's an actor in many of the sort of processes of the body and whereas you can look at the heart and brain and sort of say, well, you know, they seem very important. They do that one important thing. But the liver does several really important things. It's involved in clearing the bloodstream of toxins. And this goes way back to evolutionary time when we're living in the wild and you would, you know, eat things in the woods that are poisonous. And so the liver developed to be a very robust organ for taking in toxins, neutralizing them and excreting them.

So that's, that's one of its most important roles. And that's kind of the most well known. It's also very important in digestion. It creates bilirubin out of the waste products of old red blood cells. And bilirubin is held as bile in your gallbladder. And when you eat something fatty, It excretes it into the digestive tract to help you digest fats.

And so it's very important in fat metabolism and the clearance of bilirubin from the body. It also has this whole other aspect where it makes proteins and these proteins are necessary to keep fluid in your bloodstream as opposed to having it leaking out into the other parts of your body. So when you get swelling in your legs or arms or something, that can be a sign that the liver is not making enough of this protein known as albumin to hold the fluid where it's supposed to be.

And then the last very important thing that's very critical is it regulates blood clotting. So it creates many of the proteins and enzymes that allow your body to clot when it needs to, but not overly clot blood when it doesn't need to. And so it's very central in metabolizing your ability to stop bleeding, but also not clot off areas where you need blood flow.

And that's, a cursory look at the functions of the liver.

Host: Right. Yeah, I was good. I was with you like through the toxins part. Like if someone had ever asked me, if a child had asked me, Hey dad, what does the liver do? I'd be saying toxins, you know, but all that other stuff. So I knew that I would benefit and the listeners would benefit from your expertise. So let's get into liver cancer. How does one get, if you will, liver cancer? And do you know if you have cancer of the liver?

Carl Valentin, MD: So I think the first thing to address there is when we talk about cancer, we typically name a cancer for the organ it came from. So if you have, say, colon cancer or breast cancer or pancreatic cancer, all of those are called by their organ of origin. But many of these cancers do spread to the liver.

Unfortunately, the liver is a large organ. It has a lot of blood flow, and so when tumors metastasize, they often end up in the liver. So when we talk about liver cancer, we're kind of talking about two broad categories. One is cancers that originate in the liver, and those are what's properly known as liver cancer.

 But we're also, to some extent, referring to the many cancers that can just end up there. And in treating these other cancers that end up in the liver, often the liver becomes the most important organ for treatment. Because it may be the one that's life limiting, that your, life expectancy is based on how well liver disease can be controlled within the liver. Now in terms of I think the question, the root question which we'll get to is how do you get liver cancer? So one is you get another form of cancer that spreads to the liver. However, the way you get a primary liver cancer has to do with other health conditions. So the most common liver cancer that originates in the liver, is hepatocellular carcinoma, or HCC. And that has a strong correlation with a history of hepatitis, so inflammation of the liver either due to prior infection. Worldwide, the most common infection is hepatitis C, which is the main risk factor for developing a primary liver cancer. However, chronic alcoholism is also a common cause, especially in the United States.

Where HCC is not as common as it is in other countries and continents. So, primary liver cancer, the main risk factor is chronic inflammation of the liver. There's also another slightly more unusual liver cancer, which develops in the bile ducts, which are part of the liver, but not the main liver cell. This is known as cholangiocarcinoma. That is somewhat random, however, there are risk factors associated with chronic bile duct disease.

Host: Gotcha. So there is, you know, liver cancer proper, if you will, cancers that originate in the liver. And then there's the spread of other cancers to the liver. And I've heard that, that sort of life expectancy can often be based on how the liver responds to the treatment of the other cancer. And a lot to think about here, doctor, as I'm sure there is for you on a daily basis. So let's talk about the treatment options for liver cancer.

Carl Valentin, MD: And again, it depends on what primary cancer we're referring to. For metastatic disease, by definition, any cancer you have that's also in the liver, that comes from somewhere else, is stage 4 disease. And the primary treatment for most stage 4 disease is chemotherapy. The treatments for some cancers that arise in the liver include potentially curable disease because it's not metastatic and it may be definitively cured.

Metastatic disease can occasionally be cured from other sources, but the success rate of Stage 4 disease is much lower than a contained stage 1 or stage 2 cancer. So setting aside metastatic disease to the liver; for hepatocellular carcinoma, if it's isolated to a certain area of the liver and it's smaller than a certain size, surgery to remove that portion of the liver can be curative. It cures the cancer because you no longer have it. It hasn't spread and it's been removed by surgery. The other cures, potentially for liver cancer are transplants. So if the disease status meets certain criteria, it hasn't spread beyond the liver and it's small enough, you can undergo a liver transplant. If you're on the liver transplant list and you, you know, your name comes up. That can also be curative of hepatocellular carcinoma. Interestingly, the treatment that we're going to discuss today in more detail is Y-90 or Yttrium-90, which is a therapy. We'll get into the details of which shortly, but the caveat with regard to the potential to have a surgical cure, sometimes patients present with a tumor that's too large to undergo surgical removal or transplant. And they don't meet that criteria.

Y90, can be a treatment that shrinks the tumor size such that the patient isn't cured by that, but they then become a candidate for other therapies such as surgery and transplant, which may be curative. So it has a role, in multiple stages of the disease process depending on the clinical presentation.

Host: Yeah, it's interesting. Nice preview there. Let's talk about it. Let's roll up our sleeves a little bit and talk more about TheraSphere Y-90. As you said, the Y has a longer word attached. Well, let's talk about Y-90, how it works, and it sounds like it's a relatively new therapy.

Carl Valentin, MD: Yes. It's something old and something new. It's an evolution of techniques that have been developing for 30 or 40 years, since we developed the ability to get a small catheter into a small blood vessel and target what we put into that blood vessel. So in the case of liver cancer or cancer that is spread to the liver, maybe 30 to 40 years ago, doctors started experimenting with ways to get a small angiographic catheter from the aorta, which is the main blood vessel in your body, usually accessed through a vessel in the leg or the arm, much the way an angiogram would be performed. And that small catheter is sort of directed through the arteries that branch from the aorta into the hepatic arteries, the arteries that supply blood to the liver.

And then various different products over the years have been injected to modify the disease course in the liver. The first agents which were injected were just embolics, which means that they blocked blood flow, and when directed to the tumor, that meant that the tumor got less blood flow, and the tumor would shrink or die.

That first round of therapy, was somewhat effective, but shortly thereafter, they developed another strategy, which was to inject chemotherapy, or even more specifically, small particles that are infused with chemotherapy. into the liver so that chemotherapy agents could be introduced in a higher concentration directly to the tumor than you could otherwise systemically give in your bloodstream because the toxicity levels would be lower to the body, but higher to the liver tumor.

So that was the next step in the process; the chemoembolization, so called, of liver tumors. And then Yttrium-90 is just one step beyond that in terms of technology and efficacy, where instead of particles with no activity, subsequently particles with chemotherapy, we now have particles that are radioactive.

And so the radioactivity is a type that travels very small distances within the body, usually only a millimeter or two. But when directly injected into tumors in the liver, that very small distance multiplied by, you know, hundreds of thousands of particles, emits enough radiation to kill the liver tumors.

The radiation, however, to the rest of your body is very minimal or almost nothing. Because the radioactive particles can only emit for a very short distance. And so that's basically what Yttrium is. It's a radioactive therapy, but it's one that instead of being targeted from outside of the body, it's targeted from inside the tumor through direct catheterization of the arteries we discussed.

 And that brings about a whole different set of sort of characteristics, how it kills tumor, how it's less toxic, how safe it is to use. And, you know, those are more complex details that anyone could address with their physician if they were having a, you know, the next level discussion.

Host: Yeah. Yeah, it definitely should, right? Best addressed to experts. I want to find out, Doctor, who's a good candidate, if you will, or who's qualified to try this therapy?

Carl Valentin, MD: A lot of these decisions happen after a patient's already seen their oncologist or their hepatologist. And so there's a few different algorithms. One is the early cancer, that can be definitely cured. It's primary in the liver or not say definitely, but potentially cured, it's primary in the liver. And those candidates will usually see a hepatologist first. And if they have a tumor size and what we call tumor burden, meaning if you have several tumors, how much space the total amount of tumor takes up. If they're candidates, they can, undergo a Y-90 therapy fairly early in the disease process.

Now there's another group of patients, and we're referring to metastatic disease, where say there is pancreatic cancer, and you've been on chemotherapy for a while, and you're doing well. Most of the disease is controlled, you may have a small lung nodule, you may have a small lymph node somewhere, but these aren't going to be that dangerous to your life expectancy.

And then, in the course of your process, the process of your, you know, treatment, you have liver metastases that seem to be growing faster than the other lesions. And the liver then can become the life limiting or life expectancy limiting organ. In those patients, they can become a candidate for Y-90 therapy.

They would take a break from their normal chemotherapy, undergo a liver directed therapy to just knock down the disease in the liver. And then they resume their other chemotherapy regimen as they normally would. And this type of candidate, although it's not considered curative, life expectancy can be increased from months to upward of a year in correctly selected patients.

Host: Yeah. So let's talk about the duration or, you know, how long does Y-90 take or how long is, does someone go through Y-90 therapy?

Carl Valentin, MD: There's two aspects of that. One is the actual therapy is about a two hour procedure. You come into the hospital as an outpatient. You undergo an arterial catheterization or an angiogram in which the particles are injected. And then you typically go home the same day. So that's a relatively quick procedure. The recovery period is relatively short. Because of the arterial access in your leg. You have to lie flat for a couple hours. And you may feel a little bit ill for a couple of weeks as the efficacy of the tumor death and the tumor in the liver takes place, but generally it's a well tolerated procedure.

There's however a workup, and that consists of first coming to clinic to meet with one of the physicians to discuss everything in detail. The second step is a special type of CT exam that looks at the anatomy of the liver, the arteries and the tumors. The next step is you come in for an actual angiogram, so it's an IR procedure, interventional radiology procedure, in which we put catheters in the same places which we ultimately will for the therapy, but we do this just to map out the vessels and know where everything is. Then you come back for the final procedure, which is the Y-90 administration, usually about a week after the mapping is done. So the whole process can take a few weeks, but as I said, the actual Y-90 administration is a one day therapy.

Now, there's a caveat there, and that is that it's usually broken into a couple stages of therapy. We don't want to hit the whole liver at once with the radioactive particles because there is potential for toxicity. So typically, the liver will be divided in roughly two. We'll treat half of the liver, make sure the patient recovers from that, and about a month to six or eight weeks later, come back and do the procedure again on the other half of the liver.

It seems somewhat complicated in terms of how many steps are required, but the good news is that the actual treatment days are short and well tolerated and typically people go home the same day.

Host: As you say, a couple of weeks before, a couple of weeks after, may not feel well, but generally speaking, the actual therapy session or sessions, if you will, is relatively short. Let's talk about the risks and the side effects.

Carl Valentin, MD: You know, all therapies have risks, and they have some side effects. The goal, of course, is to assess and address each patient's individual needs and see what their risks and benefits are, potentially of undergoing this therapy or any therapy. The actual procedural risks are relatively small, approximately 1 percent risk of complications related to the angiogram, and recovery and sedation and anesthesia if anesthesia is needed.

 Just worth noting, many of these procedures are done under what's called moderate sedation, so you're in a twilight state, such as you would be for colonoscopy. Some patients with more complex medical problems; will have general anesthesia to ensure the medical stability during the procedure.

Having said that, the side effects and risks for the procedure itself, I mentioned were about 1%. There are also risks related to the radiation therapy, within the liver. A small percentage of patients will develop a sort of a chronic inflammation of the liver. And in those patients, they may not be a candidate to treat the second side of the liver, but as the liver is a relatively large organ and we're careful to treat a portion at a time, although it may limit the subsequent ability to undergo a Y-90 treatment in the other lobe of the liver; the true complication of that consequence is minimized by the fact that we treat half the liver at a time.

 The side effects, as I previously mentioned, there's just a slight sense of illness like you would have during a bad cold or a flu when you just don't feel well. And that's actually due to something called tumor necrosis factor. And as the tumor cells die, the tumor cells release chemicals into the bloodstream that create that sense of illness.

It's, in a sense, not a true illness because it's a consequence of the tumor cells dying, not due to your actual illness. But nonetheless you do feel ill for a couple of weeks afterwards. It should be relatively mild and self limiting. And after a couple of weeks, most patients return to their baseline overall sense of wellness.

Host: Yeah. And sort of just thinking this through, like, you know, if you don't feel well for a week or two, well, then you know that probably the therapy was effective, right?

Carl Valentin, MD: Indeed. Yeah. And we keep a lookout for potential other causes but that's the primary, primary reason.

Host: Right. The frustrating thing about the human body, Doctor is it could be something else as well. Right. It just, you just never know. That's why we have doctors and nurses and hospitals and all that. So let's talk about the efficacy or the effectiveness of the treatment. You said it might be, you know, you might go from life expectancy of months to maybe a year or more. Take us through that.

Carl Valentin, MD: Indeed. And as I mentioned it, it's used in different clinical scenarios. The first scenario can be curative. If there's a localized liver tumor, the patient may not be a candidate for surgery or transplant. It's possible to have complete tumor death in that area without recurrence. So that's one of the great scenarios.

 The second setting in efficacy is that you can bridge them to other therapies. They may not be a candidate for transplant or surgery, but by shrinking the tumor, they then become a candidate, and then they can go on to a curative surgery. The next category of patients are people with advanced metastatic disease; in which cure is not typically the goal. The goal is to manage the chronic disease, keep it at bay as long as possible and maintain as healthy a life and satisfaction with your abilities in life as long as possible. So in those patients, it can vary greatly depending on patient selection and the disease process.

But, the overall efficacy in prolonging length of life in patients with metastatic disease can be months to over a year on average.

Host: Well, it's all really amazing, and I really appreciate this. A lot of things in my head, a lot of things to sort through, but you've done a great job getting a lot of information out in a short period of time. Really appreciate your expertise. Just want to finish up, Doctor, if someone's heard this and listened to this podcast, and hopefully they have, and unfortunately has liver cancer. As you say, there's different types of quote unquote liver cancer, but you know, we'll just speak sort of broadly here. If they want to explore Y-90 as a part of their treatment plan or a treatment option, how best to do that?

Carl Valentin, MD: So there are a couple of broad categories. There's one patient that's out there and they may have concerns about their health and they don't have any diagnosis. They don't know that anything's wrong. They'll want to look out for the symptoms that can be associated with a problem in the liver.

Jaundice or yellowing of the eyes, or yellowing of the skin. Also pain in the right upper abdomen. And those patients will usually present to their primary care physician for a workup. Setting that group aside, we're talking about patients that already have a cancer diagnosis. If they have a primary liver cancer, they're probably seen by a hepatologist.

And so they'll ask their hepatologist, about their treatment options. And there's a very specific algorithm for what is done and why and when in those patients. The other group of patients are people that already have a diagnosis of a metastatic cancer, and they'll be seeing their oncologist routinely. And they can ask their oncologist if they're a candidate for liver directed therapy if they have metastatic liver disease.

Host: Well, Doctor, you are a wealth of information. A lot to think about, a lot of great options, therapy options, but especially this Y-90 that we've spoken about today. Really appreciate your time, your expertise, your compassion. Thank you so much.

Carl Valentin, MD: Certainly. Thank you, Scott.

Host: And please visit franciscanhealth.org/cancercare to learn more about cancer treatments available near you. And if you found this podcast helpful, please share it on your social channels and be sure to check out the full podcast library for additional topics of interest. This is the Franciscan Health Doc Pod. I'm Scott Webb. Stay well, and we'll talk again next time.