Understanding Stomach Cancers

Dr. Jill Lacy, Understanding Stomach
Cancers
July 25, 2010Welcome to Yale Cancer Center Answers with Dr. Ed Chu and
Dr. Francine Foss, I am Bruce Barber.  Dr. Chu is Deputy
Director and Chief of Medical Oncology at Yale Cancer Center and
Dr. Foss is a Professor of Medical Oncology and Dermatology
specializing in the treatment of lymphomas.  If you would like
to join the conversation, you can contact the doctors
directly.  The address is canceranswers@yale.edu and
the phone number is 1888-234-4YCC.  This evening Francine is
joined by Dr. Jill Lacy.  Dr. Lacy is an Associate Professor
of Medical Oncology at Yale School of Medicine and she is an expert
in the diagnosis and treatment of gastric cancers.  Here is
Francine Foss.Foss
Let us start off by having you define what gastric cancer is?Lacy
Gastric cancer is a malignancy that grows in the stomach, and
actually there are a few different types of stomach cancers. 
There are some rare types, including gastric lymphomas, and these
are tumors of lymph tissue often caused by bacteria and
interestingly, can often be treated with an antibiotic.  There
are endocrine tumors, called carcinoids, and they are often very
slow growing, almost benign tumors, that we often can ignore, but
when we talk about gastric cancer or stomach cancer we are most
often referring to the most common type of stomach cancer called
adenocarcinoma of the stomach. These are very common cancers
worldwide.  They grow in the inner most superficial lining of
the stomach wall.  Worldwide, their incidence is about a
million and gastric cancer is actually the number two cause of
cancer related deaths after lung cancer.  I would mention that
there are some interesting epidemiologic features in the United
States, the incidence of gastric cancer, adenocarcinoma, has been
steadily declining since about the 1930s, so we are now down to
about 22,000 cases a year with about 12,000 deaths per
year.   But what's of some concern is that in the past
two decades or so there has been a spike in stomach cancers that
are located close to the esophagus.  We call these proximal
gastric cancers or cardia cancers and unfortunately these tend to
be a little bit more aggressive and have a worse prognosis than the
gastric cancers that are further down in the stomach.  We do
not know why we are seeing this mini epidemic in these proximal
gastric cancers, but we know that the risk factors appear to be
similar to those for esophagus cancer; obesity, high BMI (body mass
index), acid reflux disease, and preponderance in males over
females, and again tobacco is a risk factor.Foss
Jill, we hear a lot about antacid and there are a lot of
advertisements in commercials on TV and in magazines about acid
reflux disease and the use of antacids. I am wondering, is that
really happening because of this increased risk in reflux and
gastric cancer and does that actually help to prevent gastric
cancer?Lacy
I think it's very unclear as to whether acid reducing therapy
influences the incidence of these proximal gastric cancers I think
that's an area of active investigation.3:33 into mp3 file 
http://yalecancercenter.org/podcast/july2510-cancer-answers-lacy.mp3Foss
Can you talk a little bit about differences in terms of age and
race, are there certain predispositions for gastric cancer other
than the ones you mentioned?Lacy
As I mentioned, in the United States there is preponderance in
males, it is a disease of the older, middle aged and elderly. The
median age is around 65 to 70 for gastric cancer, a little bit
younger for the proximal gastric cancers. There is tremendous
geographic variability in the incidence of gastric cancer
worldwide, so for example, there are very high incidence areas in
East Asia, in particular Japan, in areas of South America in the
region of the Andes Mountains and in Eastern Europe, so some of
this may be ethnic, some may be environmental, we do not fully
understand those marked geographic differences in incidence.Foss
You mentioned alcohol and tobacco as being risk factors.  Are
there other dietary risk factors?Lacy
There have been a large number of epidemiologic studies looking at
the relationship between diet and gastric cancer and so the weight
of evidence supports an increased risk of gastric cancer in areas
of the world where the diets are high in salted foods, cured and
smoked foods, and pickled foods. Conversely, diets high in fresh
fruits and vegetables appear to be associated with a decreased risk
of gastric cancer; that data is pretty solid in terms of those
relationships.  What is probably much more important than diet
in terms of risk factors for gastric cancer is infection with the
bacteria called Helicobacter pylori or H. pylori.  H. pylori
is a bacteria that's very common in our environment and it tends to
infect the lining of the stomach and it can cause a number of
stomach diseases including peptic ulcer disease, gastric ulcers,
inflammation of the lining of the stomach or gastritis.  We
mentioned lymphoma before, it is a causative agent of stomach
lymphomas and importantly, it is a major cause worldwide of gastric
adenocarcinoma.  Probably 40 to 50% of gastric cancers
worldwide are related to H. pylori infection.Foss
How does one actually know if they have H. pylori?Lacy
Most people who have H. pylori have no symptoms.  They do not
know they have it and it will cause no problems, so that is the
good news.  There is really a very low incidence of gastric
cancer in individuals who harbor H. pylori, but some of the
symptoms that can be associated with H. pylori are stomach symptoms
of indigestion, dyspepsia, high acid feeling, abdominal pain and
obviously if one is experiencing symptoms like that, that should be
discussed with ones primary care provider or one should see a
gastroenterologist.Foss
I know that in the case of gastric lymphoma just treating the H.
pylori is often enough to eradicate the lymphoma, is that true for
the other kinds of gastric cancer if you treat the H. pylori?Lacy
For adenocarcinoma, caused by H. pylori, once you have carcinoma
treating the H. pylori will not7:27 into mp3 file 
http://yalecancercenter.org/podcast/july2510-cancer-answers-lacy.mp3
 reverse that process.  It is not an effective treatment for
adenocarcinoma as it is in lymphoma, so that is a major
difference.Foss
Can we talk a little bit now about the diagnosis of gastric
cancer?Lacy
Patients are generally going to be diagnosed by a procedure called
endoscopy and a directed biopsy of an area of abnormality on the
inside in the stomach. Endoscopy is done by a gastroenterologist
and it involves putting a flexible tube down the esophagus into the
stomach.  There is a bright light and a little camera on the
end of the tube and the gastroenterologist is able to visualize the
inside of the stomach with pictures that are projected on a TV
monitor, and then if there is an abnormality that is visualized,
the gastroenterologist can easily take a directed biopsy through
the endoscope of that area and  in general that's how we get
the diagnosis of stomach cancers.Foss
Is there any specific blood test that can be used?Lacy
Not really.  There is nothing specific that gives us a
definitive diagnosis of gastric cancer.  You need to get a
biopsy and that is generally done via endoscopy.Foss
And once you have a diagnosis through endoscopy and biopsy, what
are the next steps?Lacy
In terms of the treatment of gastric cancer, treatment is going to
be dictated by the extent of disease, whether it's localized to the
stomach and surrounding structures, or whether it has spread to
distant sites such as liver, the lung, or other areas in the
abdomen, and so the initial evaluation involves determining the
extent of disease and we in oncology call that staging the
patient.  Staging always involves a CAT scan, which gives
pictures of the entire body and allows us to see whether there is
distant spread. What is also very important in staging gastric
cancer is a procedure called endoscopic ultrasound, or EUS, and
again this is a procedure that involves putting an endoscope down
into the stomach and in this case there is an ultrasound transducer
around the end and one can generate very, very detailed pictures
from ultrasound of the layers of the stomach and it allows one to
see how deeply into the wall of the stomach the cancer has
penetrated.  That gives us some information about stage. 
Endoscopic ultrasound also allows us to look at the lymph nodes
around the stomach and to see whether those lymph nodes or lymph
glands may be involved with cancer as well.Foss
Just to reassure our audience, when a patient undergoes this kind
of endoscopy or ultrasound procedure, are they awake or are they
sedated?10:24 into mp3 file 
http://yalecancercenter.org/podcast/july2510-cancer-answers-lacy.mp3Lacy
They are minimally sedated, this is a minimally invasive procedure,
so there is some mild sedation and patients are likely sleeping
through this procedure.Foss
After getting the scans and determining how extensive the disease
is, how do you make the next decision about how to treat a
patient?Lacy
Again, treatment of gastric cancer, like many cancers, is driven
and dictated by the stage, so the extent of disease and how far it
has spread, and that is determined by those staging procedures that
we just went through, a CAT scan and an endoscopic ultrasound.
Staging goes from 1 to 4, so for patients who have stage four
disease, that would be disease that has spread to distant sites,
for example, to the liver or lung, and those patients we generally
would treat with palliative chemotherapy.  They would not be a
candidate for a curative surgical procedure; however, patients with
lower stage disease, stages 1, 2, and 3, in general those patients
will be going on to some kind of surgical procedure, which
hopefully will be definitive and curative.Foss
Given that more patients are having endoscopies now for various
reasons, are we picking up more cases of gastric cancer
earlier?Lacy
Certainly in Japan, where they have a national screening program
that involves actually looking at the lining of the stomach with
Barium and X-rays, 40% of patients are diagnosed with what we call
early stage gastric cancer.  In the United States, we don't
recommend any kind of routine screening as we do for colon cancer,
for example, with colonoscopy, so most endoscopies are done in the
setting of someone having some type of symptom. Therefore, we are
not picking up gastric cancer at early stages as much as we would
like. Most patients present with stage 2, stage 3 and stage 4
disease as opposed to stage 1 disease.Foss
We have talked in the context of colon cancer about the virtual
colonoscopy.  Is there a virtual endoscopy yet?Lacy
Not yet, not for gastric cancer.  Now one has to go through
that procedure.Foss
In patients say who are smokers and drinkers are those the kinds of
patients who perhaps should think about getting screening
procedures done?Lacy
Again, there is no recommended mass screening for gastric
cancer.  Screening, however, can be individualized so if you
have a patient that is at particularly high risk, and risk factors
would be someone who has had documented H. pylori infection and
abnormalities on endoscopy, someone who has a strong family history
of gastric cancer, someone who has previously had gastric polyps
removed that are premalignant, or someone who has known long
standing inflammation of the13:48 into mp3 file 
http://yalecancercenter.org/podcast/july2510-cancer-answers-lacy.mp3
 lining of the stomach, gastritis, that's a risk factor. 
Those patients perhaps should be regularly screened with
endoscopy.Foss
I am glad you brought that issue up about family history.  Are
there genetic syndromes that are associated with gastric
cancer?Lacy
Most cases of gastric cancer are not genetic, but there are a few
genetic syndromes that are associated with a marked increase of
gastric cancer.  There is a familial gastric cancer syndrome
where generations after generations of patients are afflicted with
gastric cancer.  We actually think that Napoleon was part of a
gastric cancer family.  He died of gastric cancer as did one
of his parents and grandparents.  So those patients obviously
are very high risk and not only should they be screened, but if the
diagnosis is made and it's made through genetic testing,
consideration of a prophylactic total gastrectomy should be
made.  A familial cancer syndrome that is associated with
colon cancer is called the Lynch syndrome and in those families,
there is also an increased risk of gastric cancer. Those family
members probably should be screened not only with colonoscopy for
colon cancer, but also upper endoscopy for gastric cancer.Foss
This has been very informative.  We are going to take a short
break now for a medical minute.  Stay tuned to learn more
about therapies for gastric cancer with Dr. Jill Lacy.Foss
Welcome back to Yale Cancer Center Answers.  This is Dr.
Francine Foss and I am here today with my guest with Dr. Jill Lacy
who joins us to talk about gastrointestinal cancer.  Jill, we
talked a lot about the epidemiology and the diagnosis of gastric
cancer.  Can you tell us, once a patient is
 diagnosed and comes into the system, say into Yale Cancer Center,
is there a multimodality approach for this disease?16:52 into mp3 file 
http://yalecancercenter.org/podcast/july2510-cancer-answers-lacy.mp3Lacy
Yes, that's really been one of the major advances in the
field.  Up until about 10 years ago gastric cancer that was
non metastatic and localized to the stomach and surrounding
structures was treated with removal of the stomach, or part of the
stomach, and in many cases that was definitive and curative
therapy, but unfortunately even with the most optimum surgery in
the United States more than 50% of patients who had undergone
surgery for gastric cancer would have a recurrence, and when
gastric cancer does recur, in most cases, it is fatal.  What
has changed has been the appreciation that the use of so called
adjuvant therapies in addition to surgical resection can markedly
improve the prognosis and cure rate for patients with gastric
cancer.  There have been several studies conducted here and in
Europe and Asia that have shown that the administration of
chemotherapy either before or after, or simply after surgical
resection, or the use of radiation with chemotherapy after surgical
resection, or in some cases prior to surgery, can increase the
overall cure rate by about 10% to 20%.  The management of
gastric cancer that is localized has really evolved from being
exclusively a surgical disease to being a disease where
multimodality therapy is critically important in maximizing the
chances for cure.  When we are faced with the patient who does
not appear to have metastatic disease and is going to be a
candidate for surgical resection, it's critically important that
all the physicians that are going to be involved meet together and
discuss the optimum management for the patient. That would be the
gastroenterologist who has done the staging with endoscopy, the
surgeon obviously, the medical oncologist, and radiation
oncologist.  At Yale we have a tumor board that meets once a
week and we discuss all new cases of gastric cancer and come up
with a treatment strategy that will involve multiple treatment
modalities and there is often a lot of discussion about the most
appropriate sequencing of surgery, chemotherapy, and radiation.Foss
Can you just let us know, on a national level, the NCCN guidelines
for the treatment of gastric cancer in the resectable setting? What
are the recommendations?Lacy
 There actually is more than one recommendation. For patients with
what we call resectable disease, a disease that has not spread to
distant sites, one option is for patients to receive chemotherapy
before surgery then go on to resection and receive additional
chemotherapy after surgery.  Second option is for patients who
underwent an initial resection of their tumor upfront, gastrectomy,
those patients should receive post operative adjuvant therapy and
generally that's going to be radiation with chemotherapy, and then
in patients who have gastric tumors that are very close to the
esophagus or growing into the esophagus, those patients can be
managed with one of the prior two approaches, or alternatively with
radiation and chemotherapy prior to surgery, so it is a little bit
complicated.  There are a couple of different options and
sequences and that's why a discussion in a tumor board format can
be very helpful in optimizing management for patients.21:00 into mp3 file 
http://yalecancercenter.org/podcast/july2510-cancer-answers-lacy.mp3Foss
Would you ever do surgery on a patient who has metastatic gastric
cancer?Lacy
Generally when we are dealing with metastatic gastric cancer and we
know that upfront from the staging evaluation, from the CAT scan or
the endoscopic ultrasound, we would not do a gastrectomy, it's a
big operation and it would potentially delay the time to starting
chemotherapy; however, there are some settings where we do need to
do surgery and that would be someone who presents with sort of
catastrophic pictures such as perforation of the stomach or massive
bleeding, those patients would go to surgery for palliative
gastrectomy even in the metastatic setting.Foss
Can you tell us a little bit about the standard chemotherapy for
gastric cancer?Lacy
This is a work in progress, I would say.  There are a number
of multi-drug regimens usually at least two drugs, in some cases
three drugs, that appear to have approximately equivalent efficacy
in controlling the disease and so one chooses the regimen based on
the side effects and whether or not we think a patient would
tolerate one drug over another.Foss
How long does the adjuvant chemotherapy go on for, how many
months?Lacy
When we are using adjuvant chemotherapy in patients who are
candidates for surgery, the protocol is 9 weeks of chemotherapy
with a three drug regimen prior to surgery, then surgery, then
recovery from surgery and then an additional nine weeks, so it's 18
weeks of chemotherapy.Foss
At the end of that is a patient essentially disease free for a long
period of time?Lacy
In the United States the overall cure rate with that kind of
approach, taking everyone into account, is about 40%, so we
certainly still have room for improvement.Foss
It sounds like we have room to develop additional therapies in
gastric cancer as well and I know Jill that you have been on the
forefront in your research in looking at novel approaches for
gastric cancer, can you tell us what's happening?Lacy
There have been some very exciting developments in recent years in
gastric cancer, and this is coming from lots of science that is now
defining what the mutations and the molecular lesions or molecular
abnormalities are that are causing gastric cancer, and so the hope
is that by identifying these mutations and these molecular lesions
that we will be able to use so called targeted therapies, therapies
that specifically target these molecular abnormalities.  We
will be able to incorporate these targeted therapies into the
treatment of gastric cancer.  We are already doing this in
some other cancers, in colon cancer, lung cancer, and breast
cancer, and now I think we are beginning to see that we are going
to be able to apply this type of approach to gastric cancer.24:21 into mp3 file 
http://yalecancercenter.org/podcast/july2510-cancer-answers-lacy.mp3Foss
 One of the drugs that you are using for gastric cancer is a drug
that we use in breast cancer, Herceptin?Lacy
This is very recent, and very exciting data. In gastric cancer
about 25% of tumors will express or over express a large amount of
a protein on the surface of the tumor cell called HER2 or HER2/neu
and this protein has been a target in breast cancer for an antibody
called Herceptin and Herceptin has been widely used in a subset of
breast cancer patients for many, many years with great
efficacy.  And what we learned within the last year is
patients with gastric cancers, again it is about 25% who express
this protein HER2/neu, if you add Herceptin to their chemotherapy
regimen you get much greater efficacy, a higher response rate, and
most importantly longer survival.  So this study that showed
this really is practice changing.  We are now recommending
that all patients with metastatic gastric cancer have their tumor
tested in the pathology lab for the presence of this protein
HER2/neu and if that test is positive, we are recommending that
those patients should receive Herceptin, this targeted antibody, in
combination with chemotherapy as a part of their treatment. 
Now, I would add that Herceptin of course has been FDA approved in
breast cancer for many, many years.  It's not yet FDA approved
in gastric cancer, but we expect that, and hope that it will be
within the year.  Fortunately we were able to get approval to
use the drug in patients who are testing positive for this protein
HER2/neu.  So this has been a very important and exciting
breakthrough in the field.Foss
Is it now standard practice to test all tumors for HER2? Lacy
It is evolving, and this is relatively new, so people are just
beginning to incorporate this into their practice, but yes,
pathologists are on alert and they are now beginning to do this
routinely.Foss
There was another really exciting advance that was actually
reported this year at the American Society of Clinical Oncology,
and that involved the use of the drug Avastin, which is an
antiangiogenic factors in gastric cancer.Lacy
Avastin has been a very exciting antibody, a targeted therapy,
which was approved about 6 years ago now in metastatic colon cancer
and it was an enormous breakthrough in the field.  The study
showed that Avastin in combination with chemotherapy in colon
cancer improves the efficacy of chemotherapy and again, extends
survival.  Since that time, Avastin has also been approved for
use in combination with chemotherapy in lung cancer and in breast
cancer and more recently it has been approved also in brain tumors
and kidney cancer, so this has been really a Blockbuster drug in
the field. We think it works by interfering with blood flow to the
tumor and what is very exciting is that this year, two weeks ago,
at the National Cancer Meeting in Chicago, the data was presented
from a large clinical trial in gastric cancer.  This trial was
conducted largely in Asia and Europe, to a lesser extent in the
United States, and the patients were given either chemotherapy28:06 into mp3 file 
http://yalecancercenter.org/podcast/july2510-cancer-answers-lacy.mp3
 alone or chemotherapy with Avastin and what the study showed was
that again Avastin improved the efficacy of chemotherapy, the
response rates were higher, and the time to progression of disease
was higher and the survival was also better by about two months,
although it was not quite statistically significant.  What was
also quite interesting is that when they looked just specifically
at the American patient population, the benefits of Avastin seemed
to be much more dramatic with an increase in survival of about four
months, which is very impressive. There was a lot of buzz at the
meetings about Avastin and gastric cancer.  We will certainly
be seeing more studies with Avastin. We actually have a clinical
trial open here at Yale for patients with metastatic gastric cancer
with chemotherapy and Avastin and I think this is going to be an
ongoing and exciting story in the field.Foss
Jill, it sounds like a lot has changed over the last 10 years or so
in the treatment and management of gastric cancer.Lacy
It has, and thank you Francine.Foss
It has been really great to have you here as our guest today on
Yale Cancer Center Answers to talk about new advances in gastric
cancer.  Until next week, this is Dr. Francine Foss from Yale
Cancer Center wishing you a safe and healthy week.If you have questions or would like to share your comments,
visit yalecancercenter.org, where you can also subscribe to our
podcast and find written transcripts of past programs.  I am
Bruce Barber and you are listening to the WNPR Health Forum on the
Connecticut Public Broadcasting Network.