Surgeon explains influences of hepatitis C, obesity, immunotherapy

[00:00:00] Host Amber Smith: Upstate Medical University in Syracuse, New York invites you to be "The Informed Patient" with the podcast that features experts from Central New York's only academic medical center. I'm your host, Amber Smith. Many more people are surviving cancers of all types today than 20 or even 10 years ago, thanks in part to better detection and diagnosis and improved treatment strategies. Now we're going to take a look at a cancer that seems to be on the rise and another that has been difficult to catch early with Dr. Thomas VanderMeer. He's the interim director of the Upstate Cancer Center and chief of surgical oncology with a practice specializing in cancers of the liver and pancreas. Welcome back to "The Informed Patient," Dr. VanderMeer.

[00:00:43] Thomas VanderMeer, MD: Thank you, Amber. Thanks for having me.

[00:00:46] Host Amber Smith: You specialize in the liver and the pancreas, so I'd like to talk about what is happening with cancers in each of those organs. Let's start with the liver. Liver cancer incidence has tripled since 1980. Do we know why?

[00:01:01] Thomas VanderMeer, MD: We think that the rise in the incidence of liver cancer is primarily related to the high rate of infection from hepatitis C virus in baby boomers, and also the rise in obesity. These are both risk factors for the development of cirrhosis, which leads to liver cancer. There's a lot of different liver diseases that lead to cirrhosis -- but that damage and scarring and repair leads to an inflammation that we think leads to liver cancer. And the hepatitis C virus, the infection in and of itself, causes changes that lead to liver cancer.

[00:01:46] Host Amber Smith: Does liver cancer show up in a medical image, or a blood test? How do you detect it?

[00:01:53] Thomas VanderMeer, MD: It does show up on a number of different imaging studies. When people have hepatitis B or hepatitis C infections, they are screened for the development of liver cancer, and that screening is done usually with ultrasound. And so ultrasound is simple and a pretty reliable way of detecting liver cancers, but it's also seen on CT scans, and MRI is particularly sensitive for picking up liver cancers. There are blood tests that we use if somebody has an established diagnosis of liver cancer, to follow the response of the tumor to the treatment.

[00:02:42] Host Amber Smith: Well, once liver cancer is diagnosed, is surgery usually the first treatment?

[00:02:47] Thomas VanderMeer, MD: Surgery is the best treatment for liver cancer. Now, there are two types of liver cancers that are the most common. One is generally related to viral hepatitis and cirrhosis. And then there's another type that's derived from the bile ducts within the liver. So they have a slightly different treatment options and different things that we can do.

But by and large, yes, we try to do surgery whenever it's possible. There are limitations on when we can do surgery to remove the tumor. For example, some people have cirrhosis that is so severe that we can't remove part of the liver safely. Removing part of the liver in some cirrhotics, especially with advanced cirrhosis, will lead to liver failure. And so we have to be very careful about looking at the liver function, how much viable liver needs to be removed to remove that tumor. That's for resection.

Liver transplantation is also an option. It's been well shown that for patients with up to three relatively small liver tumors, the liver transplantation can be very effective. And that's especially attractive in people with advanced cirrhosis who wouldn't be able to tolerate a liver resection.

For the other type of liver cancer that arises in the bile ducts, there are centers that are investigating the utility of liver transplantation for those tumors as well.

[00:04:33] Host Amber Smith: So, for the cancers that you would not be looking at a transplant for, when you go into operate, are you removing just the tumor itself? Or do you remove part of the liver with it?

[00:04:46] Thomas VanderMeer, MD: We always try to remove a rim of normal liver around the tumor because the tumor can infiltrate, so we want to make sure that there's not even microscopic tumor left behind on the edges of what we remove.

Depending on the location of the tumor, sometimes we have to remove larger parts. For example, if the tumor is sitting right on one of the major areas of blood supply to a larger portion of the liver, then in order to remove that tumor, we have to remove that blood vessel as well. And so the consequences of that are that we have to remove the portion of the liver that is supplied by that blood vessel. So, sometimes we do have to remove a fair amount of additional liver, depending on the location.

[00:05:43] Host Amber Smith: Are there other therapies that are used in coordination with surgery?

[00:05:48] Thomas VanderMeer, MD: There are alternatives to surgery for people that they can't have surgery for whatever reason. By and large, surgery -- resection of the tumor -- is the best treatment. And additional treatments beyond that have not been shown to be effective. So when we're talking about all the other different things that can be done, there are alternatives. And which alternative we use depends on how localized the tumor is.

So, if a tumor is localized and small, but the condition of the liver, the location of it, makes it not amenable to removal, there are devices we have where we can use microwaves to destroy the tumor. Increasingly, we're looking at high dose radiation to the tumor, and that can be very effective as well.

We can also access the arteries that take blood to the tumor and inject things like radioactive microspheres that implant in the tumor and give a local dose of radiation internally to the tumor. We can also target the blood supply to it. We can clot that off and so kill the tumor in that way.

And then for more widespread liver tumors, then we're looking more at the tumors that are spread widely through the liver and potentially through the body. So, in those cases, we're talking about what we call systemic drugs that get through the body, so, immunotherapy, medications and other things that are given intravenously.

[00:07:36] Host Amber Smith: What do you see on the horizon for liver cancer?

[00:07:40] Thomas VanderMeer, MD: So, like with most cancers, there's really exciting work being done around the harnessing the body's own immune system to attack the tumor and kill it. And so there's a lot of different ways to do that. We're also understanding the different genetic profiles of these tumors so that we can have much more targeted therapies just like with a lot of other tumors.

Liver cancers have been kind of lagging behind the advances made in some other tumors like lung cancer, where there's lots and lots of different immunotherapy options. What we've recently found is that drugs that prevent the tumor from creating blood vessels to supply itself with nutrients, we can interrupt that process with some medications. That's been shown to be effective.

And other things like viral therapy are being investigated actively, as are more direct radiation techniques. And then just from a population health standpoint, getting more people screened who are at risk for developing liver cancer, that I can make a huge difference in terms of early detection.

[00:09:11] Host Amber Smith: This is Upstate's "The Informed Patient" podcast. I'm your host, Amber Smith. I'm talking with Dr. Thomas VanderMeer. He's a surgeon and the interim director of the Upstate Cancer Center.

Pancreatic cancer is 3% of all cancers, but 7% of cancer deaths. Is the relative death rate high because it's particularly hard to detect this cancer early?

[00:09:34] Thomas VanderMeer, MD: Yeah, that's part of it. But also it's a difficult cancer to treat. So it will present often late in its course, because there aren't symptoms early on in a lot of cases. And so the tumor is often metastasized, or disseminated through the body without anybody really having any symptoms to notice it.

And then we have relatively limited treatment options for it, although there are some emerging technologies and techniques and medications that are looking very promising.

[00:10:09] Host Amber Smith: What causes pancreatic cancer?

[00:10:12] Thomas VanderMeer, MD: Like most cancers, the cause is related to mutations in the genes. And what I mean by that is that our bodies are made up of cells. And the cells will normally divide, to refresh our body and keep it functional. And then the original cell will die off.

But mutations can cause dysregulation of the growth of cells. And so in pancreatic cancer, there's four specific genes that trigger these changes in growth of the cells. But the other thing that these cancer cells do is that they put the brakes on our own immune system so that they can escape the normal process that our bodies use to rid itself of things that are not good for us, like viruses and abnormal cells. So once a cancer gets started, it does things to our immune system that kind of put the brakes on it.

[00:11:16] Host Amber Smith: But, like you said, we might not have symptoms of this or know that this is happening. How does pancreatic cancer usually get discovered, then?

[00:11:27] Thomas VanderMeer, MD: Depending on what part of the pancreas the tumor is located in, the tumor may block the bile duct. And that's a fortunate thing because people then get jaundiced. And so those tumors tend to get detected pretty early.

If it's in another part of the pancreas, then it can grow to be pretty big before it infiltrates nerves and causes pain or causes pancreatitis. Or sometimes it's already advanced so far that people are already starting to lose weight, and so they just go to the doctor because they're not feeling well. And usually it's a CAT scan that is the 1st test to detect this.

[00:12:14] Host Amber Smith: Is surgery part of the treatment for pancreatic cancer?

[00:12:18] Thomas VanderMeer, MD: Surgery is the most effective treatment that we currently have for pancreatic cancer. There's generally just two operations that are done, depending on the location of the tumor. And increasingly we're using minimally invasive surgical techniques so that we can avoid a big incision and really improve the recovery.

It is very important to get chemotherapy around the time of surgery, either before and after, or after. So it's important that the recovery from the surgery be relatively straightforward and quick and uncomplicated so that patients can get on to their next phase of treatment, which is chemotherapy.

[00:13:09] Host Amber Smith: Have immunotherapies been helpful?

[00:13:11] Thomas VanderMeer, MD: Not significantly. There are a small percentage of pancreatic cancers that are amenable to immunotherapy and responsive to immunotherapy that we currently have. But there's been some novel techniques that have been tried that have shown some very early promise.

[00:13:34] Host Amber Smith: What can you tell us about an experimental mRNA vaccine that's being tested against pancreatic cancer?

[00:13:41] Thomas VanderMeer, MD: So that was one of the new techniques that I was kind of referring to. There was a pretty exciting study -- it was only about 20 patients, I think -- but what those investigators did was they actually partnered with the same vaccine company that created one of the COVID vaccines, to use mRNA technology to train the cells so the immune cells would be able to attack that particular cancer. So what they did was they removed the tumor. Then they processed the tumor, and they found out what the proteins were on the surface of that particular cancer. And they're different depending on the person. And then they generated a vaccine against those exact proteins that were on the surface of that cancer. And then they injected the mRNA vaccine, and about half the people had a really good response.

And in terms of response, what they looked at was whether or not the immune cells in that patient were able to specifically attack those proteins that they intended to have them attack. And only about half of them were successful and in generating those T cells. But of those people, at I think 1-year follow up or so, very few of those patients had any recurrence; where the patients who didn't have such a good response, most of them had their cancer recur within a year. So not only did they show that they could engineer these immune cells to attack that particular cancer, but they also were starting to show that there was a difference in survival and prolonging tumor recurrence. So, a pretty exciting study.

I think the next thing for them to work on is to see how they can get more of the patient's immune cells to adopt these receptors.

[00:15:53] Host Amber Smith: So it sounds like this new approach holds some promise.

[00:15:57] Thomas VanderMeer, MD: Very much so. Yeah. And there's been other investigators that -- I think it was pretty big in the news a few months ago -- it was only one patient, but the patient had pretty widespread metastatic pancreas cancer, and, again, they programmed her immune cells to attack that particular cancer. And I think it was like a 72% response, but the response generated over a long period of time, and they showed that these immune cells had been replicating in the patient's body. And so we are still waiting to hear, but the hope was that once those cells were there, they'll continue to fight the cancer over a long period of time.

[00:16:44] Host Amber Smith: Well, Dr. VanderMeer, thank you so much for making time for this interview.

[00:16:49] Thomas VanderMeer, MD: Well, thank you for having me, Amber.

[00:16:51] Host Amber Smith: My guest has been Dr. Thomas VanderMeer. He specializes in hepatobiliary and pancreatic surgery, and he serves as the interim director of the Upstate Cancer Center. "The Informed Patient" is a podcast covering health, science and medicine, brought to you by Upstate Medical University in Syracuse, New York, and produced by Jim Howe. Find our archive of previous episodes at upstate.edu/informed. This is your host, Amber Smith, thanking you for listening.