Cancer in Context: Rise of GI Cases

[MUSIC PLAYING] Welcome, everyone. I'm Dr. John Whyte, chief medical officer at WebMD, and you're watching "Cancer in Context."

Today, I want to talk about GI cancer. Are we making any progress? What are the risk factors? What treatments are out there, and what's on the horizon? So to provide some insights, I've asked Dr. Timothy Cannon. He's a medical oncologist at the Inova Schar Cancer Institute. Dr. Cannon, thanks for joining me.

Thank you for having me, Dr. Whyte.

Let's start off with explaining to our audience, what do we consider GI, gastrointestinal malignancies, GI cancers?

Well, it encompasses all of the cancers that occur where your food goes, so from the esophagus, stomach, pancreas, liver-- of course, pancreas and liver aren't exactly where food goes, but they're part of the digestive system-- and your intestine small intestine colon, rectum.

And people are very familiar with pancreatic cancer. They've heard about it, often celebrities, colorectal cancer, but less so about stomach cancer and esophageal cancer. Where are we in terms of the incidence? The total number of GI cancers typically is less than 6%, is that right? But in terms of the rate of new cases, what progress have we made?

Well, you're right. It is not as common as colorectal cancer and pancreatic cancer, and it certainly gets a lot less attention recently, because of celebrity diagnoses of both pancreatic and colon cancer. And I feel like they've dominated the news in the last year or two.

Epigastric and esophageal cancer are also very common. They're the third most common type of GI cancer. And unlike colon cancer, the incidence of, at least, lower esophageal cancer is increasing.

As far as where we are now, gastroesophageal cancer has changed a lot in the last couple of years I think there's two really major changes. I think one of them is in localized gastroesophageal cancer cases, where probably 10 years ago, a lot of patients, or maybe most patients, were getting surgery first. And now it's mostly chemoradiation first. And even more and more, we're doing chemotherapy first, then chemoradiation and surgery. In other words, we're pushing the surgery further back in time, typically.

Let's talk about risk factors, particularly those things that one can control. And you mentioned about the GI tract, what we consume, in some ways. What is the role of diet in terms of the rate of GI cancers? Is it the issue of red meat? What do we see?

Well, there is a strong relationship between dietary factors and lifestyle factors and gastric cancer and lower esophageal cancer.

JOHN WHYTE: And colorectal cancer.

TIMOTHY CANNON: And colorectal cancer. And there have been some studies showing red meat, for instance, does increase the risk of colorectal cancer. Processed meats do as well-- the study that compared people who eat a lot of processed meats to those who don't, and that they do have a slightly higher incidence. And so we know that these are likely risk factors. It's sometimes a little hard to tell how strong, but they're certainly risk factors.

Do we see an association with pancreatic cancer? We don't hear as much about it in terms of the pancreas.

It has been a lot harder to tease out the risk factors for pancreatic cancer. Some studies have shown smoking and obesity and alcohol to be three risk factors that potentially increase your risk of pancreatic cancer, but they haven't been consistently shown in all epidemiological studies.

The other thing we've learned in recent years is the role of infection in terms of cancers. And people sometimes are surprised-- how can infection cause cancer? We see that with HPV and cervical cancer. But explain to people the role of infection in certain GI cancers.

Right. Well, there's a strong relationship between certain infections and GI cancers. One example of that is H. pylori, Helicobacter pylori infection, which is the cause of many gastric cancers and lower esophageal cancers. The bacteria causes recurrent cell turnover, which leads to cancer.

Similarly, hepatitis B and C, of course, cause liver cancer. And then you mentioned HPV, which is a cause of anal cancer. So there's a strong relationship between infectious diseases and cancers. There's also probably links between infectious disease and cancer that we don't know yet.

And that's why it's important to make sure we get adequate treatment for those conditions, as well as get vaccination, for those ones that do have the opportunity to be vaccinated.

Let's move to treatment. And you've been a big proponent of the role of pharmacogenomics in terms of guiding treatment, as really one of those major changes and advances. Help explain to our audience what pharmacogenomics is and how it works with GI cancers.

Absolutely . So for a number of cancers, we can't cure them with surgery alone, and so we rely a lot on what we call systemic therapies, which include chemotherapy, immunotherapy, or targeted therapies.

In other words, they're-- if you think about cancer like flowers and seeds, where you have this one tumor, and the tumor cells are circulating in the bloodstream and the lymphatics, and you really need a treatment that will be able to get at all of that simultaneously. Those are systemic therapies.

And so we're often giving these systemic therapies to the patients. But yet we notice that every person who receives these tolerates these treatments differently. The same type of chemotherapy, for instance, may make one person very sick, while another person may barely notice any side effects at all.

And the same is true of immunotherapy, these newer therapies that enhance your immune response to a cancer, or targeted therapies, which are basically therapies that target different protein changes in the tumor that aren't in your normal cells. So again, some people may tolerate them while other people don't. Why is that?

And pharmacogenomics is the study of, basically, genetics and DNA and how that influences our ability to metabolize different drugs or to utilize different drugs to treat a cancer. And so we're interested in finding newer and better ways to predict, hey, this person, because they have this polymorphism or this change in this gene, is going to have more trouble tolerating this drug, so we have to give a lower dose.

How are we doing? How are we doing with that?

Well, I think we have a lot of room for improvement. There have been some recent research findings that have really improved treatment in the clinic, whether it's with the UGT1A1 gene, with irinotecan or the DPD gene and with-- quite a few of these are common chemotherapy drugs that we use in GI cancers. There have been some findings that have been useful, but I think we're still a long ways away from this being something that helps every patient.

And you're chair of a steering committee of a study called TAPUR.

Right.

Tell us about that and why it's important.

TAPUR is an amazing study, both in its design and its scientific utility. So TAPUR is a study that incorporates many different drugs-- in fact, 23, I think, is the number right now. And if you enroll in TAPUR as a patient with an advanced cancer, what happens is that you've had a genetic test where they look at your tumor and see what genes may be making the cancer go. What genetic mutations are driving the cancer?

And then you're matched into a group where you may get a pill or an IV infusion that specifically targets that cancer. And we call this a basket trial. In other words, you may have breast cancer, but rather than just getting one treatment for breast cancer, you could get any one of 23, based on your genetics. And we place you in this basket, and you're assigned to that treatment based on the genetic change.

This is a little different than how trials were done traditionally, where if you had breast cancer, you got this treatment, or stomach cancer, you got this treatment. With TAPUR, we're more concerned with the genetics of the tumor, rather than where the tumor started, if that makes sense.

Now, you've been quoted as saying, you think cancer therapy is going to be completely different in 10 years. Do we have to wait 10 years, though, Dr. Cannon? What do you expect to see? Tell me what you expect to see in five years.

Well, in five years? Well, I do think things are changing rapidly.

Yes! That's why I bring that up, in terms of new molecular entities, in terms of even how we do trials, as you talked about, the use of AI. 10 years? 10 years, really?

Well, looking back to where we were five years ago, 2016 to now, I probably would have-- there has been a lot of change. But I hope there's more change by the year 2026, in this next five-year interval. I think AI will be a big factor here. A lot of data scientists will take over some aspects of research.

Why do you say AI? It seems that AI has been most successful in imaging-- is that right-- and less successful in predicting what treatments one should receive. Is that an accurate description in the current state?

Yeah, I think that's true today. I do think, though, that AI holds the promise of being able to generate a picture out of great deals-- out of a huge amount of data, and that can drive us understanding how treatments are tied to outcomes, or how genetics are tied to outcomes.

And it presents a different way of doing research. Rather than having to wait to enroll 1,000 people in a double-blind trial, maybe we can use data and AI sort through hundreds of thousands of patient data, experience data, to get a signal or understand better how well a treatment works in a certain subset of the population. So it's a different way of coming, going-- doing research that may be more efficient in some ways.

What about advances in screening? So we have good screening tools, many different tests for colorectal cancer. But the other cancers we deal with, we don't. We don't have a good one for pancreatic cancer. We're talking about tests that-- we could do blood tests, where we could look for cells, but most of those tests are done after the fact, that we already know someone has cancer, rather than predictors. Do you see advancements in screening for GI cancers other than colorectal?

Yes. Now, of course every time somebody gets diagnosed with an advanced pancreatic cancer, they say, well, why hasn't their screening progressed? And of course, that's a health, economics, and public health issue, but I think there are--

Why don't we?

Well, I think cost effectiveness and relatively low rates in the population of pancreatic cancer would hinder us there.

And the right test. And they should prepare the right test as well.

That's right, the test. I think there's a lot of interesting efforts for people who are already known to be at high risk of pancreatic cancer based on genetics and family history.

I agree.

TIMOTHY CANNON: --this consortium and my partner, Dr. Will Wadlow is leading this effort to screen everybody with a family history or has two family members or have a genetic mutation that predisposes them to pancreatic cancer. So I think that's one way we're going to get a go at it, is honing in better on the patients who need more intensive screening.

But I think the other major advance that I do expect to come in the next five to 10 years, or maybe even sooner, are blood tests that are all cancer screening-type tests, that look for genetic markers or protein markers that are characteristic of a certain cancer in the body, and being able to find this in the plasma with a simple blood test. I do think that that--

All cancers, or a specific type, meaning they could find any cancer, as opposed to, say, looking for that genetic signature on cells? And that could be more complicated, because we know that cancer isn't one disease.

Absolutely.

JOHN WHYTE: --some other conditions. There's many different types of diseases of cancer. Can we really use one blood test? Is that what you think will be on the horizon?

So in the year 2021, screening assays I'm familiar with-- they're certainly better at detecting some cancers than others, in other words, the kind that have access to the bloodstreams or have a specific genetic signature.

But I don't think it's unrealistic to think that someday, there will be this broad screening panel that will capture almost anything. I mean, nothing will be infallible or perfect, but I think the tests will get better and better. And I can imagine a day where you'll be able to pick up 75% of cancers in a blood test, yes.

Is that in 10 years?

[LAUGHS] I'd put the over-under at about 10 years.

[LAUGHTER] We're going to hold you to it. I mean, clearly we need more research into this, and these aren't for general screening yet. But it is something that we can be hopeful for.

And that's what I wanted to end with and ask you. For many people, GI malignancies, in their mind, is often a death sentence. To your point, we've made tremendous progress, but given its incidence people don't always know someone who has had it. So what do you say to those listeners that may know someone with a GI malignancy and may have been diagnosed with a GI malignancy? What do they need to hear?

The one thing that I would probably want everyone to know is that for the really advanced cancers, it is probably in your benefit to seek a clinical trial.

Some people don't want to be a guinea pig, but the truth is that it takes a long time for cancer medications to get approved, and most of the best treatments are currently in clinical trials. And statistics show that people who enroll in a clinical trial have better outcomes on average. And so I think it is really important to be open to the idea of a clinical trial for people with advanced GI cancers.

Dr. Cannon, I want to thank you for providing your insights today, for helping us understand, what are the current guidelines in terms of treatment, as well as what might be on the horizon.

Well, thank you so much for having me.

And thank you for watching "Cancer in Context."

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