There is a major problem for cancer patients to worry about when they start chemotherapy: a blood clot. They are the third most common cardiovascular illness. Some blood clots are preventable. That said, prevention includes the use of blood thinners, which can increase the chances for bleeding. Ideally, doctors would be able to tell which cancer patients are at greater risk of forming these clots, but there are not many practical options to do that.

That’s changing. Listen to an interview with Chris Holmes, MD, hematologist and oncologist at the UVM Medical Center, about a new study that may help doctors identify cancer patients at risk for blood clots.

UVM Medical Center:  New findings from a study led by UVM Cancer Center researchers may help doctors better identify these patients by analyzing the genetics of their tumors. This information can indicate risk levels allowing for individualized approaches to treatment, which in turn could prevent complications for both those who are at risk and those who may not be. In the end, it will help improve the quality of life and even save lives, and these researchers have also started a program to help reduce the occurrence of clots in the first place. We’ll be hearing about all that from Chris Holmes, a medical doctor and PhD researcher at the University of Vermont Cancer Center. She’s also an associate professor at the Larner College of Medicine, and she led the research project with Doctor Steven Ades. Thanks very much for coming.

Chris Holmes: Thank you.

UVM Medical Center: Let’s start by helping people understand what these clots are. I’m not using the fancy name for it, but you can break that down for us.

Chris Holmes: Blood clots are clots that can form in the veins. We are referring today to the clots that form in the veins, not the arteries. In general, they can form in two places. Either in the lung, and if they form in the lung or migrate to the lung, they are called a pulmonary embolism. If the blood clots form in the legs, they’re called a DVT, or deep vein thrombosis. Both of those can have huge implications for patients, because they can get swelling of the leg, pain. It can actually affect them for years later in terms of their ability to exercise and walk. If the blood clot goes to the lungs, it can actually be fatal in a small number of cases.

UVM Medical Center: Oftentimes people don’t realize this is happening, which makes it particularly difficult for physicians, right?

Chris Holmes: That’s correct. The general public knowledge with regards to blood clots, when you compare it to something like a heart attack, is very small. People don’t understand the signs and symptoms of blood clots, such as pain or swelling in just one leg, for example. Sometimes people think you have to have pain, but really, sometimes the leg can just be swollen, just very little bit, but inside, there’d be a very big clot.

UVM Medical Center: Are there risks in the general population? I think people hear sometimes about long plane rides and other times when you’re sitting for long periods of time?

Chris Holmes: Yeah. Long plane rides are the most fashionable and well-known risk factor, although that’s a minor contributor to that actual number of blood clots that occur in the United States. The majority of blood clots, about 20% of them actually happen in cancer patients. Less of the blood clots often happen in patients who have been hospitalized, for example, have been bed-bound for some reason. Also, the risk of clotting significantly increases with obesity and as you age.

UVM Medical Center: In cancer patients, how common are they?

Chris Holmes:  About 10 to 20% of all patients with cancer will develop a blood clot at some point in their cancer course.

UVM Medical Center: I understand there’s quite a range, though. It can be much higher than that?

Chris Holmes: That’s right. It’s highly variable, which makes the field very difficult for both the doctors and the patients. For example, with some types of cancer, the risk of getting a blood clot can be up to three in 10 patients, while in other types of cancer, such as an early stage breast cancer, the risk could be as low as two or 3% of the patients. That’s a huge range to try to actually make individualized recommendations about blood clot prevention.

UVM Medical Center: That’s why having a better tool than exists now is so important, so let’s move into your research. You folks looked at genetics, which as I understand it, you weren’t confident that genetics would create this link for you.

Chris Holmes: Correct. No one had really looked at the genetics of the tumor itself. There had been researchers prior to us that had looked at the genetics of the person and thought about how that might predict clot risk when you had cancer, but no one had really looked at the genetics of the tumor. With my colleagues here at the University of Vermont Medical Center, we were actually able to look at a group of patients who had metastatic colorectal cancer. We were able to go look at the genetics of their tumors, specifically a K-ras mutation status, and we were able to then show that for patients who have a K-ras mutated tumor, they are at about two or three-fold increase risk of developing a blood clot as compared to patients who don’t have that risk factor. That is really one of the largest predictors of risk that has been shown in the literature and could be a major driver of who gets blood thinners and who doesn’t as prevention of blood clots in that particular cancer type.

UVM Medical Center: So in different cancers, you might be looking for different mutations.

Chris Holmes: Exactly. That means we’re at the very beginning of that journey, because each cancer type has different mutations, and we’ll have to look at each one and ask questions about it, particularly if it has a basis in the basic research lab to think it might be important, and then ask those same kind of questions in the clinical arena.

UVM Medical Center: When folks are thinking about DNA, it’s all very complicated to them, but you are able to basically take a little biopsy, I assume, and run that through the pathology lab. What are you looking at when you’re looking for a mutation?

Chris Holmes: Well, that’s actually done by our pathology colleagues who have an entire program to look at genetics of tumors and blood samples, for example. They actually are the ones who construct the laboratory parameters that allow you to look very specifically at one little area of the DNA and ask a question about what’s different about it.

UVM Medical Center: Yeah, which is amazing, and they’re able to use that same technique to tailor treatments because people have a particular kind of cancer that might respond to this type of chemotherapy and not the other kind of chemotherapy.

Chris Holmes:  Correct. Absolutely.

UVM Medical Center: This is part of what people, I think, are starting to hear about, personalized or precision medicine. Do you see more of this coming in your field?

Chris Holmes: Personalized medicine is the future. We know that not all cancer is the same, and we know that not all cancer behaves the same in a particular individual. The future will be in individualized, personalized medicine, and that even within the field of thrombosis is something that we’ve been working on to actually personalize the approach to preventing blood clots in an individual cancer patient by assessing both their risk of clotting and their risk of bleeding along with their other risk factors.

UVM Medical Center: This is pretty amazing. A big development, I think you would say, in your field?

Chris Holmes: Absolutely. A very game-changing development over time, so that patients will be able to get treatment that is tailored specifically for them or their tumor.

UVM Medical Center: The other thing we mentioned at the beginning is a separate project that’s helping patients reduce the occurrence of blood clots in the first place. Tell me about that.

Chris Holmes: That’s a very novel program that we’ve developed here in conjunction with the Jeffords Institute for Quality. They have set up with our research group, and our research group is huge, because it really includes everyone who takes care of cancer patients at the UVM Medical Center. We’ve set up a program where our goal is to reduce the number of blood clots that form in patients who start chemotherapy without increasing the risk of having them bleed.

UVM Medical Center: How do you go about that?

Chris Holmes: Well, what we’ve done is really combine the forces of the thrombosis expertise at our institution with the oncology expertise, integrate our nursing colleagues and our pharmacy colleagues, in a program that every single patient who starts chemotherapy at the University of Vermont Cancer Center is screened for the risk of both clotting and bleeding. Also, thanks to our nursing colleagues largely, every single patient receives education with regards to what to look for in terms of signs and symptoms of a blood clot. If they were to develop one, we could treat it early before it became life threatening.

When we screen patients, for patients who are screened at what we would call high risk for having a blood clot, those patients are then offered a referral to the thrombosis and hemostasis program. There, they’ll meet with a thrombosis expert, an expert in bleeding as well. They’ll look at their individualized care plan, for example. We also have a pharmacy colleague involved who looks at all the patient’s medications, thinks about the chemotherapy they’re going to get. Thinks about their risk of developing, for example, kidney issues. Puts all that together, and then we sit down with the patient and talk about what would be the risk of not going on blood thinners. What are the benefits of going on blood thinners. Together we work with the patient to make an individualized plan.

UVM Medical Center: Yeah. I think from the patient perspective, when they’re in the doctor’s office, they’re talking to a doctor, maybe a resident or a fellow, but are not aware of this entire team behind the physician that’s giving them the information they need to speak to the patient about particular things.

Chris Holmes: That’s somewhat of our goal. We want this to happen without a lot of effort from the patient, because this is a difficult time for patients when they’ve just been diagnosed with cancer. The team is called VTE PACS, so Venus Thromboembolism Prevention in the Ambulatory Cancer Clinic. That team now has been in place for over almost three years, working in the first two years to make this program seamless, as you said, and behind the scenes, but actually benefiting patients. Now we’re in the process of actually assessing our program to understand whether or not this very unique program, that really exists nowhere else in the country, actually reduces blood clot risk.

UVM Medical Center: As we wrap up here, I was actually wondering, what are you looking forward to the next four or five years?

Chris Holmes:  Sure. Well again, in combination with the Jeffords Institute for Quality, our first goal is really to document our success. The preliminary data does look like we’ve dropped our blood clot rate from about 12% of patients starting chemotherapy down to about 4%. As I said, we want zero. We will be able to assess our program, look for the patients who are outliers who, via the mechanisms that we are using, are not currently capturing. Modify our risk assessment. The goal being no patients developing blood clots as they start their cancer therapy. I think that’s really important because patients who actually develop blood clots during their chemotherapy or at any time in their cancer course have an increased risk of death. We need to prevent those blood clots to reduce that death risk.

UVM Medical Center: Yeah, and take that risk off the table.

Chris Holmes: Exactly. For as much as possible, we want to take that risk off the table. Then, once we do that and show that this program works … By the way, I’ll just say that we’re very unique here at the University of Vermont Cancer Center and Medical Center because we are one of the few programs in the country that have this tightly integrated oncology and hematology division so that we can actually do this work. One of the obvious next steps is once we show that this works, is to actually begin to implement it first in our network, for example, and understand how that will work, and how we can actually get those resources to bear at all of our other network sites. Then also, how do you roll that out to the northeast or to the country? We know there’s not enough thrombosis experts to go around, and we need them, but we’re looking at innovative ways to actually have this combined program available for all patients. Our goal would be to take this nationwide.

UVM Medical Center: Well, that’s exciting, to be able to build on what already is really impressive work. I’m afraid we’re going to have to leave it there, but I want to thank my guest today, Chris Holmes, a medical doctor and PhD researcher at the University of Vermont Cancer Center and an associate professor at the Larner College of Medicine. Thanks very much for being here.

Chris Holmes: Thank you.


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