Amit Singal MD, a Gastroenterologist and Transplant Hepatologist, Associate Professor of Medicine, David Bruton Jr Professor in Clinical Cancer Care at UT Southwestern Medical Center talks about the increase in liver cancer and how his team’s process can inform patients and potentially save lives.
Interview conducted by Ivanhoe Broadcast News in May 2018.
You came here about eight years ago and what was the basic clinic that you started here?
Dr. Singal: I completed my training at the University of Michigan in 2010 and was recruited to UT Southwestern Medical Center to start up the Liver Tumor program. Our Liver Tumor program includes a multidisciplinary clinic as well as a robust research program ranging from prevention and early detection to novel treatments for liver cancer. While our program includes almost any mass in the liver, whether benign or cancerous, we primarily focus on hepatocellular carcinoma, the most common type of primary liver cancer.
How significant is your program in the national picture?
Dr. Singal: We are one of the top-tier liver cancer programs in the country from a clinical and research standpoint. We have a multi-disciplinary clinic that includes transplant hepatologists, surgical oncologists, interventional radiologists, radiation oncologists, and medical oncologists. We care for several hundred liver cancer patients, including 200 patients with a diagnosis of liver cancer each year. We have grant funding from the National Institute of Health (NIH), Department of Defense (DOD), Agency for Health Care Research and Quality (AHRQ), and state funding such as Cancer Prevention Research Institute of Texas (CPRIT). Our research investigates several important questions including how to best prevent liver cancer, how to detect liver cancer at an early stage, and how can we better treat liver cancer to improve survival.
What are you finding?
Dr. Singal: One of the problems is that most patients with liver cancer are found at an advanced stage when we don’t have curative options available. This is a big issue because the prognosis, the average life expectancy, depends on the stage of the cancer. If a patient is found at an early stage, we can provide curative therapies, including liver transplantation, resection or ablation, and the average life expectancy is often 10 to 20 years. However, if a patient is diagnosed at more advanced stages, the life expectancy is much shorter, closer to 1-2 years. Therefore, one of the main questions that we’re tackling through our research program is how we can best find liver cancer at an early stage.
Why is it that we’re finding people at an earlier stage?
Dr. Singal: There are likely two main reasons why we find most patients at an advanced stage. First, liver cancer screening is not performed as often as it should be done in clinical practice. Second, the tools that we use for liver cancer screening aren’t perfect. Let me start with liver cancer screening being underused. While guidelines recommend people with liver disease get liver cancer screening every six month, we found that less than one in five people who are high risk for liver cancer are actually getting screening. That means four out of five high-risk persons are not getting liver cancer screening! Therefore, one of our main goals is to increase liver cancer screening rates in the United States. For the second issue, our screening tools for liver cancer screening are far from perfect. While the tests, an abdominal ultrasound and a blood test, are simple, they can miss up to one-third of cancers when they’re at an early stage. This can be quite upsetting when a patient is still diagnosed with advanced liver cancer despite getting regular screening. We are working hard to find better screening tools that can improve our ability to detect liver cancer early.
Why aren’t we doing better?
Dr. Singal: While there may be several reasons why liver cancer screening is underused, the most common reason is that doctors simply aren’t ordering it enough in high-risk patients. When we have talked to primary care doctors, we find that there are several barriers. One of the most important barriers is that doctors only get a limited amount of time with patients and liver cancer screening falls low on the list of priorities. Further, there are some doctors that aren’t educated enough about the benefits of liver cancer screening. It’s clear we have to do a better job educating doctors about the importance of liver cancer screening and its ability to improve liver cancer survival.
Let’s say someone is getting their regular physical, what could doctors be doing that they’re not doing?
Dr. Singal: Unfortunately there’s nothing on physical exam or routine blood work that would show a patient has liver cancer. The doctor would need to do dedicated liver cancer screening with an abdominal ultrasound and a blood test called alpha fetoprotein. That’s one of the things that can make it hard; it’s not something you can just squeeze in with the rest of your annual exam.
Shouldn’t they add the blood test from one of the lab tests that they do?
Dr. Singal: Liver cancer primarily develops in people with advanced liver disease, which is also called cirrhosis. In fact, over ninety percent of liver cancers in the United States happen in the setting of cirrhosis. So it’s not like you order liver cancer screening on everyone; it is really only for those people who are high risk. This can also make it more difficult because doctors have to first determine if a patient has underlying liver disease, are they at high-risk for liver cancer, and should I do liver cancer screening. If they are able to do that, they can then add the screening blood test to the patient’s other routine labs. However, it’s not just the blood test; they would still need to do the abdominal ultrasound, which also isn’t a routine test we do in all patients.
Would the blood test be an indicator of a need to do the ultrasound?
Dr. Singal: The blood test can identify people who have liver cancer, independent of the ultrasound; however, by itself, it only finds about one third of people with liver cancer at an early age. So it’s really not accurate enough to use alone. It’s something that we use in combination with ultrasound. If either of the tests are positive, then we need to do further evaluation such as a CT or MRI scan.
Tell me the numbers again about the number of people that ought to be getting this test and the number of people that are actually getting this test?
Dr. Singal: We don’t have great numbers to accurately know how many people have cirrhosis, as this can often be asymptomatic in its early stages. However, it’s clear the number of people with cirrhosis is increasing. In the past, the most common cause for cirrhosis was hepatitis C. Hepatitis C is very common, particularly in people born between 1945 and 1965, given risk factors when those persons were growing up. However, in parallel with the obesity and diabetes epidemics in the United States, we are seeing an increasing number of people with non-alcoholic fatty liver disease which also can cause cirrhosis. This is now the most common form of liver disease and the most common reason to need a liver transplant in the United States. Overall, we believe the number of people with cirrhosis is going to continue increasing over the next one to two decades.
Not because of alcohol?
Dr. Singal: Not because of alcohol. The number of patients with alcohol-related cirrhosis is fairly steady over time. The future of cirrhosis is primarily going to be driven by this condition called non-alcohol fatty liver disease, which is related to obesity and diabetes.
Another problem with gaining weight.
Dr. Singal: Exactly, yet another problem due to a high fat diet and sedentary lifestyles where we can’t find time for exercise.
What did we do as baby boomers that put us in this higher level of Hep C and what’s the cause. Many of us are under the impression that Cirrhosis is a disease based on drinking too much alcohol. Would you kind of put that all in perspective for us?
Dr. Singal: Hepatitis C is an infection that is spread through blood. It is common among baby boomers, that is persons born between 1945 and 1965, because of a clustering of risk factors in those people. Baby boomers lived through the 1970s and the early 1980s when IV drug and cocaine use was more common, and those behaviors, particularly sharing needles, placed people at risk for contracting hepatitis C. Unfortunately, we didn’t know about hepatitis C then so even the simple act of receiving a blood transfusion or tattoo could have exposed individuals to hepatitis C. And so even baby boomers who don’t have obvious risk factors could still have Hepatitis C. It’s an issue because hepatitis C doesn’t often cause symptoms until it’s at an advanced stage so can go unrecognized for decades. This is part of the reason why the CDC and US Preventive Services Task Force both recommended all people born between 1945 to 1965 undergo hepatitis C screening at least once in their lifetime.
And Hepatitis C is a precursor to liver cancer?
Dr. Singal: This is correct. Hepatitis C increases your risk of developing cirrhosis, which then places you at high risk for developing liver cancer. Once somebody develops cirrhosis, they have a 2-3% risk of developing liver cancer every year. So the risk of developing liver cancer continues to go up the longer you have cirrhosis.
I read in one of your releases that’s associated with your work that basically liver cancer is on the increase.
Dr. Singal: Yes, that is unfortunately true. When you look at the last ten year period that has been evaluated by cancer registries in the United States, the number of new cases for most common cancers has decreased. So the number of new cases and mortality for colon cancer, breast cancer, and lung cancer are all decreasing. However, one of the cancers that’s really causing a problem today is liver cancer. Over the last ten year period with available date, liver cancer had the highest increase in new cases as well as deaths.
Do you consider this to be an alarming trend?
Dr. Singal: Yes, its’ clear we need to do something now. If we want to fix this and reverse these trends, we need to be actively engaged in interventions to reduce the number of new cases and to reduce liver cancer mortality. Like we discussed before, one of the key things that we can do is increase liver cancer screening to find cases at an early stage. Another thing we can do is treat people with hepatitis C infection, which can reduce the risk of liver cancer. This is important because we have very effective treatments for Hepatitis C. Patients can undergo hepatitis C therapy for 2-3 months with essentially side effect free medication and be cured from hepatitis C lifelong. Curing hepatitis C can reduce the chance of developing liver cancer by nearly seventy five percent.
How many people that experience the Hep C and the complications, how many of them end up with liver transplants?
Dr. Singal: There are about 7000-8000 liver transplants that occur every year, with many of them having hepatitis C infection; however, there are many more people who have hepatitis C and could benefit from liver transplant but can’t get it done. Unfortunately, the number of available organs falls far short of what we really need. Similar to what we discussed about liver cancer being more related to nonalcoholic fatty liver disease now, we’re seeing a similar shift in liver transplantation. Non-alcoholic fatty liver disease is now the most common reason for needing a liver transplant in the United States.
Which increases the need for transplants which means more donors are needed and everything else.
Dr. Singal: Exactly. As the number of people with liver disease and the need for transplant increases, it will create more and more demand for donors. However, we haven’t really seen a dramatic increase in the number of donors, and it’s unclear if this will change in the near future.
What’s your message to the greater medical community as well as the general population based on your research? What should we do?
Dr. Singal: From a liver cancer standpoint, two of the most easy and most effective things that we can do right now are 1) increasing hepatitis C treatment and 2) increasing liver cancer screening. Doctors should be very active in screening people at risk for hepatitis C, and referring them for treatment. Doctors also need to be aware of liver cancer screening for those patients with underlying cirrhosis. If we do both of these things, we can really make a big dent in liver cancer death in the United States.
You said this screening needs to be done every six months; that’s very frequent.
Dr. Singal: You’re right, every 6 months can seem very frequent, making it more difficult. Silver lining is that the tests are simple and non-invasive. It’s an abdominal ultrasound, just like we use for pregnant women, and a simple blood test.
Why do these screenings need to be so frequent?
Dr. Singal: Patients with cirrhosis are at continual risk for forming new cancers. The six month interval is largely based on the frequency at which people develop new cancers and the rate at which liver cancers grows. Studies have shown 12 months is too long and 3 months is too short. It like Goldilocks and the three bears… 6 months is just right!
It sounds like they can grow pretty quickly.
Dr. Singal: Unfortunately, it can be a fairly aggressive cancer so we need to be equally aggressive in terms of screening.
And you were doing that with the certain population that you’re working with.
Dr. Singal: As we discussed, liver cancer screening is unfortunately underused in clinical practice. In fact, only one in five at-risk patients get liver cancer screening Even though it seems like a pretty simple thing, there’s several small steps that go in to this. A patient has to go in andsee their doctor, their doctor has to recognize them as being high-risk, the doctor has to think about ordering liver cancer screening, and the patient has to actually complete the test. Each of these small steps is prone to potential failure. One of the things that we’ve started doing is using the electronic medical record to identify high-risk people and sending them a letter. The letter reminds the patient they are at increased risk for developing liver cancer because of their liver disease and it’s important for them to complete liver cancer screening. We call them a few days letter to discuss it further. Assuming the patient is willing to get the screening done, we place the orders and the patient can get their ultrasound and blood test done without having to see their provider in clinic. We’ve shown that this simple intervention can significantly increase liver cancer screening rates. In a study of nearly two thousand people, we tripled liver cancer screening rates using this simple intervention compared to usual care.
A simple intervention but if you’re the recipient of that letter it would kind of scare the hell out of you.
Dr. Singal: It’s important to remember the people who receive the letter all have known chronic liver disease. So they already had seen a provider in the past and been told they have chronic liver disease. This would not be the way that you would want to inform a patient that they have liver disease for the first time. And so we were very careful in terms of selecting our patients who would undergo this intervention.
Okay that makes sense, that’s like a Dear John letter.
Dr. Singal: Haha, agree. Definitely not the way that you want to be told for the first time that you have cirrhosis and are at risk for liver cancer.
Someone has already told you?
Dr. Singal: Yes. So, all patients included in our study had already been seen by a provider and previously informed that they had liver disease. We are just helping their providers do the follow-up testing for patients with cirrhosis, as recommended by guidelines.
And you get access to these electronic medical records from what data? How do you get access to these records?
Dr. Singal: The electronic medical records we use are all housed by the health system. We were able to do this intervention because we are employed by the health system. We obviously work very closely with the health system to access those medical records in a HIPAA compliant manner. So patient privacy was maintained while also advancing high-quality patient care at the same time.
So this is a good example of how electronic medical records can be extremely useful.
Dr. Singal: Yes, electronic medical records, if leveraged the right way, can be useful. We hear about big data and electronic medical records making health care better but we’re at the very beginning stages. So far, electronic medical records have simply housed a lot of data. Very few people are using these data in an effective manner to do population health interventions where big data and electronic medical records are leveraged to make patient outcomes better.
So science and technology come together to make for better outcomes right?
Dr. Singal: I think that is the future, science and technology coming together to really improve outcomes. But once again we’re just at the beginning stages.
We’re going to interview a patient of yours in a few minutes so he’s part of your clinical study?
Dr. Singal: Yeah, I’ve been seeing him for several years now.
I was curious to know how Mr. Strassman’s case is exemplary of what we’re talking about.
Dr. Singal: I think his case demonstrates how liver cancer screening can benefit somebody. Mr. Strassman was under the care of our liver group here at UT Southwestern and was undergoing liver cancer screening every 6 months. When he developed liver cancer, we found it at an early stage. Therefore, he was able to undergo transplant, offering a curative approach for his liver cancer. This really highlights that patients under good clinical care can help lead to good clinical outcomes. Unfortunately Mr. Strassman isn’t the rule, he’s the exception. Most patients with liver cancer weren’t in a liver cancer screening program and aren’t found at early stage, so don’t have curative treatments as an option.
Do you recall how many years ago it was he had the liver transplant?
Dr. Singal: He underwent liver transplantation in 2012 and has done well since that time.
That sounds like a better outcome than the typical numbers would show, especially if he didn’t have a transplant right?
Dr. Singal: Yes, he’s definitely done better than most people with liver cancer. Patients found at an advanced stage have an average survival of 1-2 years. So if Mr. Strassman was found at a more advanced cancer stage, he wouldn’t be with us today. It really highlights the importance of screening; it can literally save lives. You can see that by Mr. Strassman being here to conduct the interview today.
So you must feel good about the work you’re doing, you chose this specialty and you developed it and you must get a certain amount of job satisfaction and personal satisfaction out of your work.
Dr. Singal: I love my job, and I’m really proud about the work we’ve done. I think that we’ve done some good work that can truly help people – not theoretically down the road someday in the future but help people today. While I feel good about that, we still have a lot more to do. We’re just getting started!
You’ve got to get the word out and that’s why even stories like this are useful because it’s helping spread the word of something that you and a lot of smart people have identified and we could save lives.
Dr. Singal: You’re right, we have to start disseminating these models. Talking to people, getting the word out is critical. It’s not just improving care at UT Southwestern or in Dallas; its about improving care across the United States. That’s one of the things that I’m trying to do now, go out and share our data so people can do this to help patients across the country. However, at the same time, I’m hoping we can find a way to do even a better job. We’ve created a good model but we have to create an amazing model.
You’re going global.
Dr. Singal: Yes, yes we’re going global. Well, we’re going national and maybe then global.
And that feels good right?
Dr. Singal: Yes, it feels great. Sometimes my wife will ask me why I am still working at 9 or 10 pm… It’s because I come to work the next day and I can see that it truly makes a difference. I think that positive feedback of seeing things change excites me, it keeps me going. It really keeps our team going. This isn’t just a one-person effort, it says a lot about our Liver Tumor program and team at UT Southwestern.
Since these issues are nationwide how is it going in terms of spreading the word to other prominent institutions and getting other groups on board that this is a worthwhile endeavor?
Dr. Singal: Yeah, I’ve talked with doctors about our work at several institutions across the country and we’ve started to see increased interest in our interventions from other large health systems.
What can you do to make this screening more effective and a better screening process, how can you improve that?
Dr. Singal: As we discussed, our work isn’t only focused on increasing liver cancer screening. We are also working on finding better screening tools – both new imaging tests and new biomarkers. If we can find a blood test that’s able to find most liver cancers at an early stage, that would make liver cancer screening much easier. That means when a patient sees his or her doctor, the doctor orders that blood test out the door and the liver cancer screening test is done. And so we’ve been very active in not only trying to find new blood tests but also evaluating any blood tests that have been proposed. We’re hoping that over the next couple years, we can get some of these blood tests to prime time.
So that means identifying something that you haven’t identified yet?
Dr. Singal: It’s not only identifying new blood tests that can do this but also rigorously testing blood tests that have previously been proposed.
How close are you?
Dr. Singal: I’d like to say it’s around the corner but we’re probably still a couple years away. We’re should hopefully have data coming out in the next two to three years.
What else might you want to say that we haven’t touched on yet, anything?
Dr. Singal: We’ve really focused on liver cancer screening but of course it’s critical to get patients in for appropriate treatment once they are diagnosed. One of the other aspects that is important for improving survival is getting patients to the right center. We and others have shown that referring patients with liver cancer to multidisciplinary programs, such as the one we have established, is the best thing for patients. It’s not just seeing a single doctor with a single specialty but it’s coming to a health system that offers all specialties that can treat liver cancer. Liver cancer is not just cared for by a surgeon or an oncologist. The best care comes from a team of doctors from different specialties that is communicating on a regular basis. At UT Southwestern, we have created a multidisciplinary program including a multidisciplinary clinic and tumor board. Our multidisciplinary clinic is arranged so patients come in and they can see any or all necessary providers as a one-stop shop. So a patient can come in and can see the surgeon, interventional radiologist, medical oncologist, and/or hepatologist all in the same day. We believe that set-up not only makes it more patient friendly but has been shown to improve outcomes, most notably it improves patient survival.
When you’re doing your screenings and in your clinic you’re seeing patients too?
Dr. Singal: Yes, I not only do research to improve liver cancer care but I also see patients in clinic. I love both aspects of my job, particularly the fact that I get to do both on a regular basis. I’m actually a Gastroenterologist and Transplant Hepatologist by training. However, given my role as Medical Director of our Liver Tumor program, most of my clinical effort is currently focused on patients with liver masses including suspected or known liver cancer.
END OF INTERVIEW
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