Treatment Options for Liver Cancer
March 8, 2009
Welcome to Yale Cancer Center Answers with Dr. Ed Chu and Francine Foss, I am Bruce Barber. Dr. Chu is Deputy Director and Chief of Medical Oncology at Yale Cancer Center and an internationally recognized expert on colorectal cancer. Dr. Foss is a Professor of Medical Oncology and Dermatology and she is an expert in the treatment of lymphomas. If you would like to join the discussion you can contact the doctors directly. The address is canceranswers@yale.edu andthe phone number is 1888-234-4YCC. This evening Ed and Francine welcome Dr. Wasif Saif. Dr. Saif is an Associate Professor of Medical Oncology and an expert in the treatment of gastrointestinal cancers at Yale Cancer Center.
Chu
Our topic for this evenings show is liver cancer. Could you start
off by telling us what liver cancer is?
Saif
This is a great time to talk about liver cancer because after the
last two decades we are now able to develop new drugs for liver
cancer. Liver cancer, basically, is cancer of the liver
tissue, which in general is a very heterogeneous disease, meaning
that it can be caused by many things in different parts of the
world. In simple words, it is a cancer of the liver itself,
not the ducts passing through the liver.
Chu
A lot of times when patients are given a diagnosis of cancer, they
are told that the cancer has spread to the liver coming from say
the colon, the breast, the lung, or pancreas, but what we are
talking about today is cancer that comes primarily from the liver
itself.
Saif
That is a very important distinction that should be made in these
patients; whether the cells which are giving origin to the cancer
are coming from the liver itself, or from other sites such as the
colon or pancreas.
Chu
Is there another name for that, a fancier term?
Saif
A hepatocellular carcinoma, in simple abbreviation you will also
see the term HCC, which is commonly used for this cancer.
Foss
What are the major causes of liver cancer and how do patients know
whether they are at risk for this?
Saif
The causes for liver cancer can be divided into different
groups. One is acquired causes, the second is inherited
causes, and the third is environmental causes. The acquired
causes are the ones which are caused by the infection with
hepatitis B or hepatitis C virus. People who are obese can
also develop cirrhosis of liver, which can lead to liver cancer as
well. The inherited causes
2:35 into mp3 file
http://www.yalecancercenter.org/podcast/Answers_Mar-08-09.mp3
include Wilson's disease, which is a disease of the metabolism
with the disturbance of copper. In addition, people could
also have another disease called hemochromatosis. This is a
disease where the patient has abnormal genetic formation that
mishandles the iron deposition in the body. There is another
syndrome, alpha-1 antitrypsin deficiency as well.
Environmental factors are betel eating in the Asian countries and
also use of aflatoxin, which is a poison, which can lead to HCC or
liver cancer in Africa, where people are eating raw
peanuts.
Chu
Wasif, here in the United States what is thought to be the most
common cause of liver cancer?
Saif
Right now the top cause of liver cancer, in about 60% to 70% of
cases, is due to hepatitis C, followed by hepatitis B, and alcohol
abuse. Unfortunately, with today's dietary habits, NASH,
which is Nonalcoholic Steatohepatitis, or obesity-induced liver
disease, is at a higher increasing incidence in the United States,
which is a nightmare for us because this can cause liver cancer in
the future.
Foss
A lot of people have hepatitis, or fatty liver, how do patients
know whether they are at risk for liver cancer? What are the major
symptoms that a patient would have?
Saif
The main thing is that, unfortunately, patients with hepatitis B
have a hundred fold increased risk of developing liver
cancer. At the same time, for patients who have hepatitis C,
about 30% to 50% of those cases develop cirrhosis, and one-third of
those develop liver cancer. When these people have cirrhosis
of the liver they develop liver dysfunction, which can manifest in
different ways. These patients could have swelling of the
body, a decrease in appetite, and sometimes they can develop high
levels of hemoglobin, called polycythemia. But when these
symptoms start changing, that is a sign that something is
happening. In these patients it can take about 10 years or more to
lead to development of cancer.
Foss
How is the disease diagnosed?
Saif
The disease is diagnosed in different ways. The first is a
clinical picture. Patients can develop weight loss, fever,
and lack of appetite. The second is the picture we see in the
blood. Of course these patients have liver dysfunction, which
means there could be jaundice, or they could have liver enzymes
going up. In addition to that, there is a special test called
alpha-fetoprotein, which is abbreviated as AFP. This is a
tumor marker that can rise in patients with liver cancer. Of
course, as with other cancers, we have imaging modalities
available. MRI, which is Magnetic Resonance Imaging, is very
similar to the CAT scan and is the standard therapy used to
diagnose liver cancer on imaging. Finally, the diagnosis has
to be made with a histological diagnosis by doing a biopsy of the
liver cancer cells and looking at them under the microscope.
5:28 into mp3 file
http://www.yalecancercenter.org/podcast/Answers_Mar-08-09.mp3
Chu
You mentioned a moment ago that hepatitis C and hepatitis B are
the two most common risk factors for developing liver cancer in
this country. If someone has a diagnosis, as Francine
suggested, obviously they are going to look out for symptoms, but
would you want to screen for those patients to see if they might
have early stages or early forms of liver cancer?
Saif
That is exactly true Ed. We have standardized guidelines for
those patients. We always like to vaccinate patients with
hepatitis C to make them immune against hepatitis B. At the
same time, these patients need to have regular follow ups with
their physicians where they should have serial ultrasounds as well
as look in the blood for the alpha-fetoprotein, the blood test I
mentioned earlier. We have guidelines to move forward as we see the
increase in the size of those lesions, starting
from less than 1 cm to go beyond 1 cm.
Foss
Can you talk about the patients who have cirrhosis, or are using
alcohol, and patients who have fatty liver? To what degree can they
influence their chance of getting liver cancer in the future by
modifying some of these factors now?
Saif
This is really a disease that I always say is to some extent
preventable. We have to understand that this is a disease
that alcohol abuse can lead to; at the same time, if everybody gets
vaccinated for hepatitis B, it can also prevent this disease.
Unfortunately, right now for hepatitis C we do not have a
preventive vaccine available. However, there are many other
reasons people get this infection such as a blood transfusion that
is not screened for hepatitis C or B, or a patient getting an organ
transplant in another part of the world. Luckily in the
United States, most of these procedures are performed before
getting those transplantations or transfusions. Definitely by
modifying our dietary habits, trying to cut down the intake of fat,
and regular exercise, we can prevent and decrease the incidence of
this monster disease.
Chu
Can anyone in this country get vaccinated against hepatitis B?
Saif
It is really based on the awareness. We definitely need to
bring more public awareness. I can tell you that among all
the people in the medical field, in general, they are required to
have the hepatitis B vaccination. I believe that now it is
becoming a more common trend to give the hepatitis B vaccine when
kids are first born. I am hoping that with this new trend it
will lead to decreased incidence of this cancer in the future.
Chu
What is really fascinating to me is that in Taiwan, liver cancer
has been one of the major cancers and cancer killer for many, many
years. About 15-20 years or so ago they instituted hepatitis B
vaccination for kids and it's amazing. They have already seen
the incidence of liver cancer fall dramatically.
8:30 into mp3 file
http://www.yalecancercenter.org/podcast/Answers_Mar-08-09.mp3
Saif
I think it is a very positive lesson for all of us to learn that
by having the vaccination it will prevent a lot of cost in the
treatment of this cancer and we will save many lives.
Foss
Wasif, can you just comment on hepatitis C? I understand that
there is not a vaccine for it. What can we do about that as a risk
factor?
Saif
That is a very interesting question. Right now there are a couple
of things that we can do for these people. There is an
immunotherapy called interferon. The interferon is an
injection that has been tested and used and can delay and prevent
the development of cancer and cirrhosis in these patients. At
the same time, some antiviral antibiotics, which also have been
used for the treatment of HIV, have been under exploration to help
this disease, to prevent the development into cirrhosis and liver
cancer.
Foss
If you are on one of these treatments for hepatitis C, and your
virus is silent, are you still at risk for liver cancer?
Saif
As long as we keep the virus at the low risk and we are not letting
the liver become more damaged, we definitely can delay, and in some
cases prevent, the development of liver cancer.
Foss
You mention that toxins or chemicals might also be a risk
factor. There are lots of people out there that may have
worked in factories or been exposed to various chemicals at
different points in their lives, should they be worried about liver
cancer?
Saif
There are a multitude of toxins thought to cause liver cancer.
A few years ago there was a concern about people using
anabolic steroids, which can cause liver cancer. Some chemical
exposure such as ethylene glycol can also cause damage. In
addition, there was some concern about using oral contraceptives,
but none of those studies have shown a statistical association of
these exposures to the development of liver cancer. However,
the use of raw peanuts that can lead to the poisoning of aflatoxin
is the only environmental factor that has been well established to
cause liver cancer.
Foss
We are going through this peanut scare in the United States, can
you talk about that? Should we worry about our peanut butter
and our peanut products right now?
Saif
I think right now the only concern, as you know from the news, is
Salmonella. We really need to know from where these peanuts are
coming from, keeping in mind that there are three major sources of
peanuts coming to United States. One is of course Africa, but
most commonly we get from South America, and the third source is
China. I think it is also based on where they were cultured,
where they were grown, but I think right now there is no
scare. Acute use, one
11:04 into mp3 file
http://www.yalecancercenter.org/podcast/Answers_Mar-08-09.mp3
or two times, of those peanuts will not lead to liver cancer. It
is the chronic use of those things that can accumulate and cause
liver damage.
Chu
Once the diagnosis of liver cancer is made, who should that
individual seek for medical attention?
Saif
This is a stepwise pattern that involves a lot of physicians.
This starts from the primary medical physician, or the PMD, or the
clinician that has been seeing the patient for a long time.
When these patients are diagnosed with hepatitis C or B, sometimes
they end up having the involvement of a hepatologist. A
hepatologist is the gastroenterologist physician who specializes in
liver disease. When it comes to the diagnosis, of course,
that includes the involvement of a medical oncologist. In
addition, we need a radiologist who will be looking at the MRI or
other CAT scan reports, and we also need a pathologist who will be
confirming the diagnosis. It requires the involvement of many
people, as we want to make sure before we make the decision for
this patient's treatment, that we confirm the diagnosis.
Foss
How do you do a biopsy on a patient with liver cancer?
Saif
That is a very, very challenging situation. Unfortunately,
most of the patients with liver cancer have coagulopathy.
Coagulopathy, in simple terms, means that these patients have
thinned-out blood due to the lack of proteins produced in the
liver, and they can bleed. At the same time, if these
patients have cirrhosis, which is the fibrotic development of the
liver tissue which can also lead to the enlargement of the spleen,
and unfortunately, the enlarged spleen also squeezes their
platelets and they have low platelets, which is a cell component
that reduces the risk of bleeding. That is the reason we have
to be very careful doing a biopsy on those patients, which is
mostly done by a fine-needle aspiration. However, we have
guidelines that can prevent a biopsy on those patients if we have
certain criteria fulfilled.
Foss
Do patients with liver cancer develop metastasis like with other
cancers?
Saif
That is true. Liver cancer can metastasize to many areas. It
can go to the belly and cause fluid in the belly, it can go to
lymph nodes, it can go to lungs, and it can even go to bones; in
very rare cases it can go to the brain.
Chu
Do you typically do CAT scans, or other x-ray imaging studies, to
make sure that the liver cancer has not spread beyond the local
area of the liver?
Saif
That is exactly correct Ed, and if we are concerned about bones we
also do a bone scan, which is a nuclear medicine test.
13:32 into mp3 file
http://www.yalecancercenter.org/podcast/Answers_Mar-08-09.mp3
Foss
Thank you very much Wasif. We are going to take a break
now. You are listening to Yale Cancer Center Answers and we
are discussing the treatment of liver cancer with Dr. Wasif
Saif.
Foss
Welcome back to Yale Cancer Center Answers. This is Dr.
Francine Foss
and I am joined by my co-host Dr. Ed Chu and Dr.
Wasif Saif, a medical oncologist at Yale Cancer Center.
Wasif, we talked a little bit about liver cancer, let's focus our
discussion on the treatment options for this disease. Can you
talk a little bit about the treatment for liver cancer?
Saif
The treatment options can be divided into many groups. The reason I
bring up the group is because it is very important to understand
that bringing the different groups together will help us know how
many people are involved in the treatment of liver cancer. Of
course, surgical dissection is the gold standard and the only
curative potential for these patients. Patients can also be
given local therapy which can include modifying the temperature
delivered to the cancer cells causing the damage. There is
also something called TACE, that we will discuss, chemotherapy, and
finally liver transplantation.
Chu
The surgery that you talk about, is that performed by a general
surgeon or someone who specializes in gastrointestinal cancers, or
liver cancers specifically?
Saif
That is an extremely important question Ed, and it is really
important for my listeners, and my patients and their families, to
know that this is a surgery where you want to go to a specialized
person who is well trained and well experienced at performing liver
surgeries in patient with liver cancer. Patients must go to a
liver specialist who is specialized to do those things because of
the complexities in the liver structure due to the cancer and
underlying liver disease.
Foss
What if a patient cannot have surgery, what if the tumor is
inoperable?
16:13 into mp3 file
http://www.yalecancercenter.org/podcast/Answers_Mar-08-09.mp3
Saif
That is a big question that I would like to piece into different
portions. The first thing is that if somebody cannot go for liver
surgery, because they have multiple areas of disease and cirrhosis,
then those patients are candidates for liver transplantation, if
they have no disease outside the liver. If the patient has
localized disease, but are not surgical resection patients due to
cirrhosis, and the disease is limited to one or two lobes or
different areas, those patients can go for a local therapy that can
include radiofrequency ablation or transarterial
chemoembolization.
Chu
What is radiofrequency ablation?
Saif
Radiofrequency ablation is trying to heat up the tissue cells in
the cancer part of the liver by using single, or multiple,
electrodes. By virtue of that you can kill the cancer cells.
Chu
So that would be good if you had isolated tumors within the
liver?
Saif
That is exactly true. For patients that have isolated tumors,
in particular patients that are not amenable to surgery, or
patients with cirrhosis where we think that surgery may not be
amenable, radiofrequency can bring out good results. To bring
some historical perspective of radiofrequency ablation, going back
a few years ago this was not a very common procedure. In
Japan, they did an ethanol injection procedure, which was able to
reduce the cancer in about 40% to 50% of the cases. This is a
recent technology that is a great alternative to ethanol injection
into the liver cancer.
Foss
You mentioned radiofrequency ablation, and also a procedure called
TACE, or embolization of the tumor. Can you tell us how those
are different and what is TACE?
Saif
TACE stands for Transarterial Chemoembolization. The liver
has two blood supplies, one is the portal vein that supplies the
liver parenchyma, or liver cells, and the second is the hepatic
artery infusion that supplies blood to the tumor. By
obstructing the hepatic artery, we can lead to the necrosis of
vascularized liver tissue. We can do this procedure with two
technologies. Most commonly, we use gelatin-like foam that
obstructs the artery and leads to the death of the cancer
cells. In some cases, we also include chemotherapy, which is
given through the artery after blocking it so that we not only
cause damage to the tumor by depriving it of the blood supply, but
leaving behind chemotherapy will cause further damage to that
cancer cell.
Foss
That sounds fairly complicated. How long does the patient
have to stay in the hospital for that kind of a procedure?
Saif
It is based on the experience of the center. At a tertiary
cancer center like Yale Cancer Center, we do this procedure very
commonly. It is done by intervention radiology after we
discuss the case in a multidisciplinary tumor board. This procedure
can be done where the patient may only have to
19:04 into mp3 file
http://www.yalecancercenter.org/podcast/Answers_Mar-08-09.mp3
stay for couple of days. This procedure is getting much
easier with the expertise we have in our hands here.
Chu
Wasif, you mentioned liver transplantation. Many, many years ago,
for those sports fans out there, Mickey Mantle unfortunately had
liver cancer. There was a lot of publicity about him getting
a liver transplantation, that unfortunately, did not help him, but
who are the types of patients that are most appropriate for liver
transplantation?
Saif
The patients that can qualify for liver transplantation are
patients who are surgical candidates, except they have cirrhosis of
the liver. These are the patients who do not have any
extrahepatic disease, or macroscopic involvement of the blood
vessels.
Foss
Does it make any difference whether you have hepatitis B or C, as
to whether you are a candidate for liver transplant?
Saif
Not really. The concept of liver transplant is a very neat
one. In reality, liver cancer is the only tumor, the only
solid tumor, where we have a very reasonable rationale and success
for doing transplantation by replacing the liver with a donor
liver. Not only are we are able to cure the cancer, but we
are also able to improve dysfunction, which was the reason causing
the cancer in that patient.
Foss
We hear a lot about the shortage of organs for donation, can you
tell us how long it usually takes to get a liver transplant?
Saif
There are a lot of issues. First of all, it is a supply basis
issue, and second it is also cultural differences. In the
United States, the average time for a patient to get a donor liver
could be from 8 months to 2 years time, and unfortunately, right
now, the current dropout incidence is about 20%. Keep in mind
that there are two kinds of liver transplants which are done in
different parts of the world. One is the cadaveric, which is
from a dead person, and second is the living donor. Keep in
mind that there are some cultures, some religions, where patients
do not want to get a cadaveric liver transplant. Right now it
is really a challenging situation to get the right patient at the
right time, and of course a patient has to be on the waiting list
that reminds us that we have to create some kind of intermittent
treatment procedures for these patients to control the cancer.
Chu
What has the experience been at Yale Cancer Center with respect to
liver transplantation?
Saif
As you know, we have outstanding folks who joined Yale Cancer
Center a few years ago. Dr. Sukru Emre came here from the New
York area, and we also got Dr. Mario Strazzabosco from
21:34 into mp3 file
http://www.yalecancercenter.org/podcast/Answers_Mar-08-09.mp3
Italy. We have a very robust team and are launching an
outstanding program. We are hoping that we will be one of the most
recognized, world-renowned centers for liver transplant.
Chu
One of the real breakthroughs is that a new target therapy was
recently approved to treat liver cancer. Can you tell us a
little bit about that?
Saif
That is exactly where I started my first discussion today, that
this is an exciting time, and the right time to talk about liver
cancer. The reason is that we now have Nexavar, which is also
called Sorafenib. It is a small molecule target drug, which
is approved by FDA for the treatment of liver cancer. This is
a pill form drug, so patients take it by mouth, and this is a drug
that works by working on two targets. It decreases the blood
supply to the tumor. At the same time, there is a growth factor
pathway in the cancer cells, Raf pathway, and this drug also
inhibits that growth factor pathway and decreases the tumor
growth. This drug was used in an international study called
SHARP, and that study showed that patients who received this drug
have a 44% increase of survival compared to no drug.
Foss
Would a patient get this drug first as part of their initial
therapy for liver cancer, or would they get it later on?
Saif
This is an extremely important question, what is the best treatment
for a patient? This is, again, decided by a multidisciplinary tumor
board, because we always want to the give the best to the patient.
We know that surgical resection and liver transplant are the best
treatment options for those patients. If those patients have
unresectable localized disease, or advanced disease, and if those
patients are not candidates for local therapy, surgery, or liver
transplant, then Sorafenib is the drug of choice for these
patients.
Foss
What about patients that do not have outpatient prescription
coverage? This is a big problem nowadays and I am wondering
about some of these new drugs that are very expensive.
Saif
This is a very difficult situation and I think that now, with the
current situation, it is going to be even more challenging.
As this drug has been approved after working hard with our folks at
the cancer center, we have multiple folks who are involved just in
helping with this, fighting with insurance companies and asking for
different resources. So far we have been quite lucky getting
this drug out to most of our patient at Yale Cancer Center.
Chu
I have heard that the sponsor of the company that makes Sorafenib,
which is Bayer Pharmaceuticals, has some type of reimbursement
program.
24:07 into mp3 file
http://www.yalecancercenter.org/podcast/Answers_Mar-08-09.mp3
Saif
They have sponsored programs for patients who cannot afford it,
and they are willing to help those patients get treated for liver
cancer.
Chu
You have been very active in developing new treatment regimens for
colon cancer, pancreatic cancer, and also liver cancer. Can
you tell us a little bit about the types of studies that you have
done, and are planning to conduct in the future?
Saif
We are trying to create a robust state of the art cancer center,
and the GI program is having a lot of challenges. Why
challenges? Because GI cancers, together,
are the most common cancers worldwide and we have to work on many
cancers; we cannot leave any cancer behind. That is the reason
liver cancer is another enemy that we have been fighting. At
Yale Cancer Center, we have performed a clinical trial using a
Chinese herb medication called PHY-906. This clinical study
also used another drug called Capecitabine, or Xeloda, which is a
commonly used chemotherapy for many cancers including colon,
pancreas, and breast cancer. We combined the two drugs in
liver cancer and we presented this clinical data at our
international meeting last year and it was very promising to see
that the median survival was approaching almost 36 weeks
time. In addition to that, we also have conducted clinical
studies with other drug such as S-1. S-1 is another oral
medication that we have seen very interesting results for with
liver cancer, and now we are opening another clinical trial with a
drug called TAC-101, which is another drug that works on a cancer
receptor antagonist that will be given to patients who have failed
Sorafenib.
Foss
It sounds like there is a lot more hope for patients with liver
cancer today.
Saif
That is exactly true, and I think that goes to the understanding of
the cancer itself. As you know, multiple clinical trials are
looking at drugs such as Erlotinib, Sutent, Avastin, or
bevacizumab, and other chemotherapies, so after we have realized
that we can conquer this disease, we are getting more robust and
more targeted in treating this cancer.
Chu
It is quite remarkable because when all of us started our careers
in oncology, when we heard about liver cancer, the feeling was that
the prognosis was pretty dismal, but I think we have come a long
way in a very short period of time.
Saif
This is an exciting time for us, to know that things that were
unsuccessful in the past, which were the reason of our failure, now
are the reason of our excitement because we have a hope, and this
hope is strengthened by what we see in our patients; living longer
and having a better quality of life.
26:49 into mp3 file http://www.yalecancercenter.org/podcast/Answers_Mar-08-09.mp3
Foss
Can you talk from the point of view of a patient, what resources
are out there? Is there a foundation for liver cancer, or other
resources that you direct patients toward?
Saif
Right now there are a lot of resources around here. We need
to recognize them and try to make them interconnected to each
other. As you know, American Liver Foundation also has a
chapter in Connecticut. Last year, myself, Dr. Salem, Dr. Mario
Strazzabosco, Dr. Sukru Emre, and Dr. Jeff Hollick
all gave lectures in the State of
Connecticut. We had people statewide come here to talk.
People can also go to yalecancercenter.org and that will be
able to provide information to patients and patient care
providers.
Chu
In the last 30 seconds, Wasif, any last minute messages that you
would like to convey to our listeners out there?
Saif
The one thing is to keep in mind that this is a preventable
cancer, and we want to prevent it. Do not lose your hope, we
are here to help you at Yale Cancer Center and together we can
fight this disease.
Chu
Thanks so much for joining Francine and me on the show this
evening. You have been listening to Yale Cancer Center
Answers. I would like to thank our guest expert Dr. Wasif Saif for
joining us. Until next time, I am Ed Chu from the Yale Cancer
Center wishing you a safe and healthy week.
If you have questions or would like to share your comments, go to yalecancercenter.org where you can also subscribe to our podcast and find written transcripts of past program. I am Bruce Barber and you are listening to the WNPR Health Forum for Connecticut Public Radio.