Dr. Thomas Lynch, New Advances and Innovations in Lung
Cancer Treatment
November 7, 2010
Welcome to Yale Cancer Center Answers with Dr. Francine Foss and Dr. Lynn Wilson. I am Bruce Barber. Dr. Foss is a Professor of Medical Oncology and Dermatology specializing in the treatment of lymphomas. Dr. Wilson is a Professor of Therapeutic Radiology and an expert in the use of radiation to treat lung cancers and cutaneous 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 and Lynn are pleased to welcome Dr. Thomas Lynch. Dr. Lynch is Director of Yale Cancer Center and Physician-in-Chief of Smilow Cancer Hospital at Yale-New Haven. Here is Francine Foss.
Foss
I would like to start off by having you tell our audience what it
is that got you interested
in the study of lung cancer?
Lynch
I was interested in lung cancer from very early on in my career,
principally because of the impact that it makes on patients and
families. In the United States, lung cancer is the leading
cause of cancer-related death. This year, 180,000 people will
be diagnosed with lung cancer and about 145,000 people will die
from lung cancer, making it the leading cause of cancer death in
men and women.
Foss
Can you tell us how common lung cancer is around the world?
It is very high in prevalence in the United States, but I
understand that it is also a major problem in developing countries
like China.
Lynch
Absolutely true, we are seeing much more lung cancer in the
developing world. Overall, we expect there will be about
500,000 to 600,000 deaths globally from lung cancer and more than a
million cases, and those numbers will continue to go up. Lung
cancer mortality and death follows cigarette smoking very
carefully. So, in countries where cigarette smoking is
increasing, and those include China and India, we are seeing much
more lung cancer and therefore, more lung cancer death.
Wilson
Tom, what sort of symptoms do you see with a patient who has lung
cancer?
Lynch
What is interesting, Lynn, is that lung cancer often presents
fairly late in the game. We know that when people have colon
cancer they often develop bowel symptoms, or they develop bleeding
relatively early before the cancer has had a chance to
spread. When a woman has a breast cancer, either a mammogram
can pick up an early lesion or the woman may feel a lump when the
breast cancer is still very early, but for lung cancer often we do
not get symptoms until the cancer has spread and that is what makes
it, I think, very difficult to treat. In terms of symptoms,
we think shortness of breath is probably the most common symptom in
lung cancer patients. Sometimes cough can occur, sometimes
blood with that cough, shortness of breath, coughing up blood, and
pain can also be a problem, either chest pain or pain in other
parts of the body.
Wilson
What are some of the risk factors for lung cancer? Is it just
smoking, or are there other things?
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Lynch
It really is mostly smoking, 85% of the lung cancer in the United
States is related to tobacco. What we do know is that there
are some less common causes of lung cancer, and asbestos exposure
is one of them. Hexavalent chromium, for those people who
remember Julia Roberts in Erin Brockovich, hexavalent chromium was
the major concern of that movie and then radon is also another
cause of lung cancer, but if you take asbestos, hexavalent
chromium, and radon and lump them together, they are still
dramatically less than the impact that tobacco makes.
Foss
Can you talk a little bit about passive smoking exposure, and also
about the increasing risk of lung cancer in women?
Lynch
Two things, passive smoking is clearly a risk for lung cancer.
I think it is hard for us to know in any one patient whether
passive smoking was a factor in developing lung cancer, but I think
one of the most positive things we have seen over the past fifteen
years has been the rapid development of smoke-free workplaces and
smoke-free bars, restaurants, hotels, and modes of travel, and that
is really a reflection of the fact that we recognize that tobacco
smoke just does not harm the smoker, but it can harm their family
members and people who are with them. There is no doubt that
second hand smoke is dangerous and something we should
reduce. The second issue is that there is an increased rate
of lung cancer in women, two factors there. The first is that
women began smoking in very large numbers in the late fifties to
early sixties and so we started seeing a spike in cases in the late
eighties or nineties with cases for people who started smoking in
the sixties. The second is that we believe women can develop
lung cancer with slightly less tobacco exposure, so if a man and
woman are exposed to the same amount of tobacco smoke, the woman
will have a higher rate of developing lung cancer. Lung
cancer went from a disease in the fifties that was predominantly a
disease of men, to a disease now which is almost 50-50 in terms of
its incidence.
Foss
Is there an increased incidence of smoking in younger people now,
and is that pushing the age of onset of lung cancer back to a
younger age?
Lynch
The age of onset seems pretty well established, it is about 67
years old and we have not seen much change in it. People have
always started smoking relatively young. If you look at
people who start smoking, the typical person starts between the
ages of 13 and about 18 years of age and that has not changed much
over the past several years. What is disturbing, and it
depends upon what survey you look at and what data sets, but
frequently studies of the earliest smoking groups suggest that
there are increasing rates of smoker in the 15-to 16-year-old age
range. Again, some of that may just reflect that we sometimes
lose our momentum toward delivering the tobacco message to young
people.
Wilson
What about asbestos, is that a factor?
Lynch
Asbestos is a factor primarily for people who have occupational
exposure, but asbestos causes two types of cancer, mesothelioma
which is a cancer of the lining of the lung and that can be a very
difficult cancer to treat, and then probably more than mesothelioma
it causes non-small cell lung
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cancer, particularly in people who are exposed to asbestos who also
smokes cigarettes; if you happen to work at a shipyard, for
example, building Destroyers, or building ships, or perhaps in a
brake factory where they use a lot of asbestos for brake linings.
Remember most of those industry applications occurred in the 50s
and by the mid to late 60s and early 70s they were pretty much
phased out, but we still do see some people whose asbestos exposure
can be traced to very heavy occupational exposure and they get
either mesothelioma or lung cancer.
Wilson
Since these patients sometimes have limited symptoms and present
with later stage disease, tell us about how you actually make the
diagnosis.
Lynch
A lung cancer diagnosis always requires a tissue biopsy, it always
requires a biopsy of some abnormal area. Sometimes we can
biopsy the lung itself and often we use a CAT scan or sometimes a
specialist called a pulmonologist will put a bronchoscope down the
airway which is a small, thin, very pliable, scope that allows the
doctor, after putting the patient asleep slightly, to go down and
examine the airway and biopsy the cancer if they see it down in the
airway. We now have a new technique where you can biopsy
cancer even if you cannot see it in the area. So between that
and CT or CAT scan-guided fine needle biopsy, those are the two
ways we diagnose most lung cancers. Sometimes people have
lung cancer that spreads to the liver or the brain and sometimes it
is through biopsy areas there that we make the diagnosis, but most
often it is made by a lung biopsy.
Foss
That brings up the question of using a chest x-ray to screen
patients for lung cancer. There has been a lot of controversy
about the use of chest x-rays in patients who are chronic smokers
for detecting lesions that may or may not be cancer, and patients
undergoing procedures that are unnecessary. Can you talk to
us about the role of the chest x-ray and also whether there are any
other new screening technologies available for smokers?
Lynch
That is a great question Francine. In my opinion, chest
x-rays clearly do not save lives from lung cancer. By the
time you see in it on a chest x-ray, almost always the cancer has
spread to other parts of the body and so we are pretty confident
now that doing screening or routine chest x-rays without symptoms
in smokers does not make sense. There is some controversy
about CAT scans in this area and there are some people who argue
that people who are smokers should have a CAT scan to look for
early changes of lung cancer and if you find a spot or lesion on a
CAT scan, that's something that you can follow-up with and maybe if
you find it early, you can make a difference in how people
do. I must say, at this point, we have never proven that and
it may well be that we are just picking up early cancers that we
would have picked up otherwise and there is a lot of controversy
surrounding what you refer to as, cost to patients, in terms of
biopsy of things that turn out not to be cancer, meaning people
have to go through difficult biopsies and painful biopsies when it
turns out to be benign. Unlike a breast biopsy or colon
biopsy, lung biopsies carry with them a certain amount of risk, so
it makes us a little bit less enthusiastic about biopsying lesions
of
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the lung unless we are very, very worried there may be cancer. I would say at this point there is no hard and fast data that will support doing screening CAT scans for people who are smokers.
Foss
That would mean that if a patient is a smoker and has no symptoms
at all, that you would not recommend going forward with the CAT
scan?
Lynch
I would not recommend at this point going forward with a CAT
scan. We just do not have any evidence yet that these have
been shown to save lives and there are two large randomized trials
which are now going on to try to ask that question and give us some
help in terms of telling us whether or not these scans can actually
pick up early lesions that can improve survival. What we do
know is a CAT scan can find a nodule better than a chest x-ray can,
that is not debated, but what we do not know is whether finding
those nodules improves survival of patients. That is very
much an open debate in medicine.
Foss
What about blood tests and looking at the sputum? I know
there are lots of molecular tests available now to detect other
cancers in the blood and I am wondering if any of those are
available for lung cancer?
Lynch
That's a great question and something which I think we are very
eager to see in the next five to ten years. In lung cancer we
have made some real strides in understanding the molecular basis of
lung cancer, particularly for a never smoker. Yet those
understandings have not yet transferred into any early detection
test. Our hope is that one day we will be able to do either a
sputum test, which means examine some of the phlegm molecularly to
see if there are changes within genes of some cancer cells that may
be coughed into the phlegm, or even a blood test to look for early
changes that could be consistent with lung cancer. There is
some work that was done by several groups to look at what are
called circulating tumor cells, or cells that are in the blood
themselves that are cancer cells, taking those cells out and
looking at them and seeing if they are lung cancer cells, sometimes
that may turn to be a technology that is interesting down the
road.
Wilson
I know this is a large topic, but let us start to discuss some of
the different treatments that are available for lung cancer and
what you feel are the advantages to a multidisciplinary approach?
Tell our listeners a little bit about personalized medicine.
Lynch
Lynn, I will break it into two parts, first is a multidisciplinary
approach and you are someone who in your own career has made a huge
difference for people by advocating strongly for the role of a
multidisciplinary approach. What we mean by a
multidisciplinary approach is that a patient with lung cancer sees
more than one type of doctor. They see a medical oncologist,
they see a radiation oncologist, they see a surgeon, they may see a
pulmonary specialist if necessary, but they see a team of doctors
and it helps them make a decision about what the right treatment
for that patient is. For some patients the right treatment
might be to do surgery and take the tumor out. For other
patients the right treatment might be chemotherapy, so I think it
is very important that before a treatment starts patients have the
opportunity to consult with a multidisciplinary team. This
has
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made a huge difference in breast cancer and breast cancer really
led the way in the multidisciplinary approach. In prostate
cancer it makes a big difference and I think we are seeing in lung
cancer, certainly in my experience, and I suspect that in yours as
well, that it has made a big difference in lung cancer.
Wilson
Give us some more details about some of the treatment that you
do.
Lynch
Personalized medicine is one of the things you talked about.
Personalized medicine can mean a lot of different things, one thing
people mean when they talk about personalized medicines is exactly
what we just talked about, it is the idea of bringing together a
team of doctors that look specifically at a given patient's
condition and focus treatment on that given patient, so that is one
form of personalized medicine. The second form of
personalized medicine is using a molecular understanding of the
cancer to be able to inform treatment decisions. One of the things
we are working on is taking patient's cancers, once we have done a
biopsy, taking a piece of the biopsy, and analyzing that biopsy for
the presence of genetic changes that help predict appropriate
therapies. What we have learned over the past several years is that
there are several unique genetic changes to lung cancer, something
called the EGFR mutation that we look for, there is the ALK
translocation, there is the RAS mutation, and all three of those
can help us guide therapy and give patients better options.
Wilson
That is fantastic information Tom. We are going to take a
short break for a medical minute. Please stay tuned to learn
more information about lung cancer with Dr. Thomas Lynch.
Wilson
Welcome back to Yale Cancer Center Answers. This is Dr. Lynn
Wilson and I am joined by my co-host Dr. Francine Foss. Today
we are joined by Dr. Tom Lynch and we are discussing lung
cancer. Tom, let us get back to some of the information that
you were discussing before the break about genetic mutations and
how that might impact treatment for patients.
Lynch
Lynn, I think one of the things we are most proud of in lung cancer
is that over the past several
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years we have identified several genetic markers that help explain
why certain patients get lung cancer and we have done most of this
work in people who are nonsmokers and we now know that there are
probably four or five genetic markers that are important. We
have learned about something called an EGFR mutation, something
called an ALK translocation, and the RAS mutation. Also
something called the HER2 mutation. When you have changes in
those molecules, what it allows the doctor to do is pick a
treatment specifically for a patient with that type of mutation.
For example, if you have a patient that has an EGFR mutation,
you may pick a drug like Iressa or Tarceva, which is a drug that
specifically attacks the Epidermal Growth Factor Receptor. If
you have an ALK mutation or ALK translocation, you may go ahead and
try a drug specifically targeted toward ALK, a drug such as
crizotinib, which is not yet in the market but is in clinical
trials. It is an example of how doctors are using molecular
information to guide therapy. Now, what Dr. Foss does in
lymphomas is we have been using molecular information for quite
some time to help guide therapies, and just now in solid
tumors, like lung cancer, we are beginning to really understand how
molecular correlates can drive treatment.
Foss
Is the analysis of tissue for these specific mutations available
yet to the average patient with lung cancer?
Lynch
Yes they are, at Yale we have a program for doing molecular
profiling of patients with solid tumors with lung cancer, colon
cancer, and breast cancer and we are able to molecularly profile
these patients looking for a broad range of mutations that can help
direct therapy. I think what you are going to see in the next
several years is that type of testing platform will become more
available at community hospitals and at smaller centers.
Right now, the places that are doing the molecular profiling tend
to be the larger cancer centers like Yale, Memorial
Sloan-Kettering, MD Anderson; the bigger centers are really
committed to doing it.
Foss
If a patient were at a smaller center, a community hospital, say
here in Connecticut, and they wanted their tumor to be analyzed, is
there a process by which they could get that done?
Lynch
There are two ways, their doctor could contact us here at Yale and
arrange for the sample to be sent and we could run the specimen
here or the patient could be referred by the doctor here to be
seen. Either way we'd be delighted to work with doctors
around the state to try to increase the number of patients who are
molecularly profiled. It is the kind of thing that right now
we're at the very beginning of the use of these new tests, but they
can have great promise as we go forward.
Wilson
What sort of thoughts do you have about how the treatment of lung
cancer has changed, say over the last decade, aside from what you
have just talked about with the genetic evaluation?
Lynch
A couple things, one is we've become more innovative with targeted
therapies, which we just talked about, the genetic based therapies,
and the second thing is we are becoming aggressive about using
targeted local therapies like radiation and radiofrequency ablation
to target early lesions. So we have more choices now for
treating early stage cancers and I think the third
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big change has been that histology plays a role again. When I
was training, it did not really matter if you had adenocarcinoma or
squamous cell. What we now know is lung cancers break down
into two big types, small cell and non-small cell, and then
non-small cells breaks down into three big types, adenocarcinoma,
squamous cell carcinoma, and large cell carcinomas. We now know
that patients who have adenocarcinoma will do better with certain
types of drug treatment and people with squamous cell will do
better with slightly different types of drug treatment. So
again, I think what we are doing is learning how to get the right
drug to the right patient and that is something that is different
than it was five to ten years ago.
Foss
Tom, in the future do you think patients with lung cancer will not
be treated with conventional chemotherapy drugs, the way we know
them, or do you think there is always going to be a role for
chemotherapy in addition to these other new agents?
Lynch
It is a great question. I think we will see chemotherapy
around for several more years, but unlike in lymphoma where I think
chemotherapy will continue to have a role for quite some time, I
think the days of chemotherapy and lung cancer are somewhat
numbered, and my hope is that within 15 to 20 years we will no
longer be using chemotherapy in lung cancer. I think it will
be unusual for a patient to get chemotherapy as opposed to now,
where that is still a mainstay of treatment.
Foss
Another question I had is, we often times do not focus on the
positive aspects of some of these cancers and certainly in lung
cancer there are patients that are cured with definitive therapy,
although that number is small, could you say a little bit about
that group of patients?
Lynch
We cure approximately one in seven of the patients who come into
our office with lung cancer and by cure we mean that those people
live for 10, 15, 20 years and die of whatever they might have died
of if they never got lung cancer, and that is a misperception
because some people think that you can never be cured from lung
cancer. We do have a chance of curing some patients from lung
cancer, and those are generally patients who present with good lung
function, meaning their lungs are not totally compromised by
tobacco and have a lung cancer which can be either surgically
removed or could be treated with radiation therapy, and some of
those patients also get chemotherapy as part of their treatment.
There are some good news stories and I have been taking care of
lung cancer patients now for more than 20 years and I have had
plenty of patients who are cured who live 15 to 20 years and the
only reason I can't tell you longer than 20 years is because I
haven't been doing it longer than 20 years yet.
Wilson
Thinking of breast cancer for a second just as a model, there is
obviously a lot of publicity, a tremendous amount of fundraising
and research being done, which is terrific, but as you have
mentioned most of the lung cancer cases are actually caused by
smoking and there is some perception that there may be a stigma
associated with that. Since it is a different disease where
most of the cases are caused by smoking itself, has that impacted
potential research funding and the way that perhaps the lay
population thinks about the disease?
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Lynch
I think you are absolutely right Lynn. I think there is a
blame that we see with lung cancer. There is a tendency to
blame the patient for developing the disease and therefore, I think
lung cancer generates less sympathy from the public. I always
have been struck by talking to lung cancer survivors who will very
passionately say that no one deserves to get lung cancer.
People who started cigarette smoking were using a legal product and
they were using a product that has been promoted, encouraged, and
enhanced by our society, and therefore, to turn and blame the
smoker is unfair and cruel to people, particularly at a vulnerable
time in their lives, and so I personally think that is a terrible
thing to do, but I also think it explains why people are very
hesitant to put direct research dollars into lung cancer. One
of the interesting things is that if you go back, and this is not
2010 data but it is 2005 data, if you look at the amount of money
that the National Cancer Institute spends per death of a certain
cancer, what we find in breast cancer and prostate cancer is that
we spend about $15,000 of research spending per death. In
lung cancer, we spend $1,300 dollars of research spending per
death, so big disparities between what's spent per death for lung
cancer and then prostate and breast. Now, with that said, I
am someone who believes that spending money for all cancer research
is good. Meaning, I think that money spent in prostate cancer
research and breast cancer research will pay off for all cancer
research and I think efforts in lung cancer are going to help women
with breast cancer and men with prostate cancer. What I hate to see
is different groups pitted against each other as if this was a
political race and someone is running for congress. It is not
us-or-them. The idea is how we can we fund the research
together to decrease the morbidity for cancer, because whether
somebody dies of lung cancer, melanoma, lymphoma, or breast cancer,
it is the same impact on the patient and family and I think we have
to work hard to eliminate cancer death from all causes.
Foss
Can you talk a little bit about new developments in the treatment
of lung cancer and whether you think that immunotherapies, which
are now being used in other types of cancer, will potentially play
a role?
Lynch
It is interesting that you ask that because we presented data just
recently at the European Society of Medical Oncology meeting in
Milan which looked at a study that we did examining the role of a
new immunotherapy, a drug called anti-CTLA-4 against lung cancer,
and really what these approaches are doing is they are trying to
turn the body's immune system into an important weapon in fighting
cancer and what these molecules understand is that the way that the
body mounts an immune defense is extraordinarily complex and if we
can find a way to get these cells, which orchestrate the immune
system, to recognize that it is not normal to have a lung cancer,
we may be able to lead to regressions of lung cancer. This
approach has been proven now in melanoma and we have colleagues
here at Yale, Dr. Kluger and Dr. Sznol that have done some
groundbreaking work with immunotherapy in melanoma, where these
drugs have made huge differences, and this year in our paper at
ESMO, we showed that lung cancer might actually respond as well to
these drugs. It is a very early study, very preliminary data, but
we show that the progression-free survival was longer for patients
who are treated with this. We need more data, we need more
experience to know if this is a fluke or if this is real, but it
was the first time in my experience encouraging that immunotherapy
may play a role.
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Foss
And again, you would direct the immunotherapy primarily for the
earlier stage patients?
Lynch
Most of the immunotherapy trials have been criticized because they
have been done in late stage patients, and we all know that in
late-stage cancer patients the immune system is depressed and so I
keep an open mind. I think some of these trials will be started
initially in late stage patients. I think you are correct
that the potential for them is probably greater after surgery or in
stage II or III patients, but I would not close the door to the
fact that you can have benefit in late stage. You know in
melanoma, Dr. Sznol and Dr. Kluger are seeing great benefits even
in late stage patients, so I am hopeful we might see benefits in
multiple different stages.
Foss
Is there a vaccine yet for lung cancer, and do you think that there
will be one in the future?
Lynch
There are several vaccines under development for lung cancer and
some of those vaccines include taking peptides, or proteins, that
resemble proteins that are made by lung cancers, and trying to use
those to vaccinate the patients so the patient's body fights the
lung cancer. Other vaccines use cells to try to vaccinate the
patient against the lung cancer cells and several of those are in
clinical trials right now, large clinical trials, where half the
people get the vaccine, half do not. And that is an
interesting point for patients, because I think a lot of people do
not like clinical trials like that where half get it and half do
not, but in the vaccine world it's really the only we are going to
know whether or not these treatments work as opposed to some of the
targeted drugs we talked about earlier where you can give them to a
patient with advanced disease and possibly see the disease
shrink. In the vaccine world, where disease is gone and you
are giving it to prevent recurrence, you almost have to have those
treated and untreated groups to be certain.
Wilson
Getting back to causation and cigarettes, if we did not have
cigarettes, at least 80% of the lung cancers would not exist. How
are we doing as a society in getting folks to quit smoking, trying
to manage that problem?
Lynch
The smoking rate in the United States right now is about 27% to 28%
and men and women appear very similar in terms of numbers. I think
that smoking cessation is at the heart of any cancer prevention
strategy. We have talked about lung cancer today, but as you
know and Francine knows very well, smoking causes head and neck
cancer, it causes cancer of the throat and the esophagus, it causes
cancer of the pancreas, it causes cancer of the bladder.
There are a broad number of tumors, not to mention stroke or heart
attack, so a number of health reasons why we should be working to
help patients stop smoking. One of the important quality
metrics we are going to be looking at in cancer care nationally is
do we advise patients to stop smoking when they get admitted to the
hospital? Let's say you get admitted for a broken leg, if you smoke
cigarettes your nurses and doctors should tell you that you really
should not be smoking and they should offer you quit smoke services
and that is one of things we are working on at Smilow and at all
the hospitals around Connecticut to try to increase the resources
our patients have to be able to stop smoking because it is
something which, if you talk to smokers over the age of 20, most
people
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want to stop and people who are thirty or older do not want to be
smoking two packs of cigarette a day, spending that money, they
know how they feel on tobacco. They know it is bad for
them. They love their families. They do not want to
die. They want to stop smoking and our job is to give them
the tools to be able to stop smoking.
Dr. Thomas Lynch is the Director of Yale Cancer Center and Physician-in-Chief of Smilow Cancer Hospital at Yale New Haven.If you have questions for the doctors 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.