Dr. Daniel Morgensztern, The Evolution of
ONTAK
February 20, 2011
Welcome to Yale Cancer Center Answers with Dr. Francine Foss and D.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 chemotherapeutic radiology and he is an expert in the use of radiation to treat lung cancer and cutaneous lymphomas. If you would like to join the conversation, you can contact the doctors directly. The address is canceranswers@yale.edu andthe phone number is 1888-234-4YCC. This eveningFrancinewelcomes Dr. Daniel Morgensztern. Dr. Morgensztern is anAssistant Professor of Medicine at the Yale School of Medicine and he specializes in the treatment and care of patients with lung cancer. Here is Francine Foss.
Foss
Let's start learning a little bit about you because you are new
here to New Haven. Can you tell us how long you have been here and
what your role is?
Morgensztern
That's correct. I am new to Yale-New Haven and just came here
in December 2010. I graduated from medical school in Brazil
and I trained in internal medicine in Hematology/Oncology in
Miami. In 2004, I moved to Barnes-Jewish Hospital in Saint
Louis and now I am here at Yale.
Foss
Well, welcome to New Haven.
Morgensztern
Thank you.
Foss
Can we talk a little bit about lung cancer, can you tell us a
little about it?
Morgensztern
Lung cancer is the most lethal malignancy in the world and also in
the United States. That means it
is the most common cause of cancer deaths. It is also the
second most common cause of cancer in both men and women. The
American Cancer Society estimates that for the year 2010, there
were approximately 220,000 cases of lung cancer in the United
States. In the proportion of men and women, it is still more
prevalent in men, although the incidences are increasing in
women. So, for the year 2010, there were approximately
115,000 male patients with lung cancer as opposed to 105, 000
women, so the trend for the incidence will be about the same for
men and women in the next few years.
Foss
Can you tell us a little bit about the age distribution, are we
seeing it in younger people?
Morgensztern
The median age at presentation that we see the most is the patient
between 60 years to 70 years, yet we are seeing an increase in the
number of younger patients diagnosed with lung cancer, particularly
non-small cell lung cancer.
Foss
That segues into my next question, which is, are there a number of
different types of lung cancer?
2:58 into mp3 file
http://yalecancercenter.org/podcast/feb2011-cancer-answers-morgenstzern.mp3
Morgensztern
Yes.
Foss
Can you tell us a little bit about the different types?
Morgensztern
This is a very interesting question. In the past, we used to
subdivide them into two main subtypes, non-small cell lung cancer
and small cell lung cancer. Now, non-small cell lung cancer
has its main subtypes, which are adenocarcinoma, large cell
carcinomas, squamous cell carcinoma, and undifferentiated
carcinoma. We are now moving towards the subdivision of
adenocarcinomas as well, depending on the genetic material in each
of the tumors, so we are moving towards more of a subdivision of
the lung cancer subtypes.
Foss
Are any of these types better or worse than the others?
Morgensztern
Unfortunately, the survival for lung cancer is not very good, yet
we have seen multiple advances in the treatment and most of them
seem to be restricted to patients with non-small cell lung cancer
of the non-squamous variant. That means patients with non-small
cell lung cancer, other than squamous cell carcinoma, which
includes adenocarcinoma and large cell carcinomas mainly,
particularly for adenocarcinoma, survival is improving
significantly recently.
Foss
Are there any genetic predispositions to lung cancer?
Morgensztern
Yeah, there have been studies showing genetic predisposition for
non-small cell lung cancer. The studies are still very early,
but we know there must be some predispositions since there is a
higher number of patients that smoke, and not all of them develop
lung cancer. There are some recent studies showing some genes
that predispose for lung cancer and also genes that predispose for
development of lung cancer. We have a smaller amount of
cigarette smoking, particularly in woman.
Foss
Are these genes, genes that we are screening patients for now, or
is this all research?
Morgensztern
No, it is all research so far.
Foss
Can you talk a little bit about whether there is a propensity for
lung cancer in specific ethnic groups?
Morgensztern
No, there does not appear to be a propensity for non-small cell
lung cancer in ethnic groups. The reason we are seeing an increase
in lung cancer in women, is because the percentage of women that
smoke has been increasing since the 70s and decreasing in men that
smoke, so this is the only recent trend that we
have seen recently.
5:36 into mp3 file
http://yalecancercenter.org/podcast/feb2011-cancer-answers-morgenstzern.mp3
Foss
One of the issues with lung cancer, is that like
other cancers if you pick them up early enough, you might be able
to do better in terms of caring for patients, is this true?
Morgensztern
That's correct. That's very important because the earlier you
catch it, the higher the chance is of cure, especially if the
cancer is in early stage, or early enough for the patients to be
treated with surgery, which offers the best hope for cure.
Foss
What should we be doing to screen patients?
Morgensztern
That's a difficult question that became even more difficult
recently. We have seen lots of trials looking at screening,
doing imaging tests in patients before the development of lung
cancer to find out the where the cancer could be diagnosed at
earlier stage, most of the studies have been negative, but in
November there was a study, from which we have only preliminary
results showing a 20% improvement in survival for patients screened
with CT scan compared to chest radiograph. So, obviously we
will have to wait for the final results, but it is
intriguing. Perhaps a better option in the future would be to
do predicted molecules, either in the sputa or in
the blood, which will have less side effects and less radiation
from the CT scan, and probably more reliable.
Foss
Can you talk a little bit about which patients should be screened;
obviously somebody who has smoked for a long time should be
screened, but what about other people? Say people exposed to
passive smoke because their spouse smokes?
Morgensztern
The national lung cancer threat includes only patients that were
heavy smokers or patients that quit smoking less than 15 years ago,
so this is the only data that we have. It is a little bit
harder to quantify passive smoking, but I think that as I said, if
we develop predicative markers, so instead of doing x-rays, CT
scan, or PET scans, we can just do a blood test once a year in
people that we think are high risk. Also for patients that
have mutations, some of them we think may be a risk factor for the
development of lung cancer, but in the future will have a better
group of molecules to test that will probably be more reliable than
just the history of smoking itself.
Foss
You are talking about molecules that we can find potentially in
the blood that we would use to screen?
Morgensztern
That's right.
Foss
Are there clinical trials now that patients could get involved
with to look for those molecules or is that available say at Yale
Cancer Center?
Morgensztern
It is not available yet, but I hope it will be available soon.
8:23 into mp3 file
http://yalecancercenter.org/podcast/feb2011-cancer-answers-morgenstzern.mp3
Foss
When a patient is diagnosed with lung cancer, that often times is
based with a biopsy?
Morgensztern
That's correct.
Foss
Can you tell us what the next steps would be as far as what kind
of a work-up the patient would get?
Morgensztern
Ideally when the patient has a diagnosis of lung cancer we should
look at the staging, which means how far the disease has spread.
That would basically guide the way we would treat the
patient. In the Yale Thoracic Oncology Program we have a
group of specialists from all specialties; pulmonary, radiation
therapy, surgeons, radiologists, and medical oncologists and we try
to make the decision together. Usually when a patient has a
diagnosis of lung cancer, they undergo a CT scan of the chest and
abdomen to get an initial idea of if the cancer has spread to other
parts of the lung or liver. It is usually followed by a PET
scan which looks at the whole body. In some patients what we
find is that they may need imaging of the brain, such as a CT scan
or MRI and then we are ready to decide how to treat them.
Foss
Are all patients seen in the multimodality clinic?
Morgensztern
Yes, we see all new patients in the multimodality clinic. It
is very important for all the specialties to give an opinion in a
meeting, so by the time we finish the meeting, we know exactly what
everybody thinks and we are sure and confident that we are giving
the best treatment possible.
Foss
Let's go back a minute to the presentation of lung cancer, are
many of your patients asymptomatic? What are the most common
symptoms that they come in with?
Morgensztern
Unfortunately a small percentage of patients are asymptomatic and
have the diagnosis for other reasons such as they fall or have a
car accident and the x-ray will show us that. Most commonly,
patients present with shortness of breath, chest pain, or worsening
cough, or sometimes coughing blood. Occasionally, the
patients present with symptoms of spreading of the disease that
could be bone pain or headaches, and that is usually a poor sign, a
bad sign when they present with distant spreading.
Foss
So, if you are out there listening to the show and you are a
smoker, what are the signs that you should look out for that would
make you want to go to the doctor?
Morgensztern
Most smokers, especially heavy smokers, have a disease called COPD
(chronic obstructive pulmonary disease), so they usually have cough
and shortness of breath, but you should be careful
11:00 into mp3 file
http://yalecancercenter.org/podcast/feb2011-cancer-answers-morgenstzern.mp3
if the cough gets worse, or the shortness of breath gets worse,
especially if there is a new pain or you are coughing blood, you
should seek your doctor immediately.
Foss
Can you talk about the actual diagnostic biopsy, are patients
mostly getting needle biopsies or are they having surgical
biopsies?
Morgensztern
The place of biopsy would depend on the presentation, the location
of the tumor. If it looks like from the CT scans that the
tumor has spread to the liver, for example, it is easier to do a
biopsy of the liver, which would not only diagnose the cancer, but
also evaluate whether it has spread or not, but for the patient
that has the disease localized to the lung, it all depends how
close they are, either to the chest wall or the main airways. If
facing close to the main airways, we typically do a bronchoscopy or
needle biopsy, and if it is closer to the chest wall, we would try
to do a CT-guided needle biopsy. The patient goes to the CT
scan machine, and that would help the radiologist guide where the
biopsy should be, which is over the skin.
Foss
How often does a patient with lung cancer actually go to the
operating room to have part of the lung taken out, is that a common
procedure now?
Morgensztern
No, this is not common. Nowadays, it is not very common for a
patient to require that. Sometimes when the tumor is very
small, the service may elect to remove it, so they will be doing a
treatment and diagnosis at the same, but for most of the cases
either a needle biopsy or a bronchoscopy with biopsy.
Bronchoscopy is when we put a camera down the throat and the camera
will guide where the biopsy will be, and that is usually enough for
the initial diagnosis.
Foss
Dan, now that we are doing a lot of chest x-rays on patients, we
have been seeing these pulmonary nodules coming up and the
controversy has always been, what you do with these pulmonary
nodules and how often do those actually represent lung
cancer. There has been a lot of controversy about how to
handle that. Can you let our listeners know what the
recommendation is now?
Morgensztern
What you are describing is what we call the single pulmonary nodule
and it is hard to know on the first imaging test whether they
represent a malignancy or not. There are some characteristics
that we look for in that. The first characteristic is whether
they have a previous x-ray which showed the nodule to be the same
size, so this is usually a good sign, where another nodule, larger
than 3 cm, or they are rapidly enlarging, would be a red flag that
something must be done about it, usually a biopsy, but it is not
known what percentage of nodules represent cancer or not. This
should be taken very seriously, at least in the first imaging
studies.
Foss
We are going to have to take a break for medical minute right now,
when we come back we will
14:08 into mp3 file
http://yalecancercenter.org/podcast/feb2011-cancer-answers-morgenstzern.mp3
talk a little bit more specifically about some other new treatments
for lung cancer. This is Dr. Foss with Dr. Daniel
Morgensztern.
Foss
Welcome back to Yale Cancer Center Answers. This is Dr.
Francine Foss and I am joined today by my guest Dr. Dan
Morgensztern and we were discussing the topic of lung cancer.
We talked a little about how lung cancers present in the fact that
many patients will have a biopsy and staging studies, from that
point, what happens next and what are the treatments for lung
cancer?
Morgensztern
Once the diagnosis and staging are made, the treatment would depend
on the type of cancer and the stage. So, for a small cell lung
cancer, which represents only about 15% of the total number of lung
cancers diagnosed in the U.S, we have a very simple staging
classification, either they have spread or they do not have spread.
If the cancer is localized to the chest, we typically give a
combination of chemotherapy and radiation, and this is a curable
disease. Unfortunately, once the disease has spread beyond
the chest or the thorax, the disease is incurable, so we would try
to give chemotherapy which usually is effective and improves
survival and quality of life of the patient, so we will try to
offer that to the majority of patients. For non small cell
lung cancer, the staging is a little more complicated since we have
a four stage classifications, but in general, for the patient that
has stage I or II which are early stages, we tend to offer
surgery. If surgery is not possible, we have new techniques
of radiation therapy that are very effective, such as stereotactic
body radiation therapy which is a specific type of radiation that
focuses on a small section of the lung, so it encompasses all of
the cancer and very little of the adjacent lung, and this has been
very successful for tumors that are smaller.
The patients that have stage II usually means involvement in one of
the lymph nodes close to the lung, and we tend to offer
chemotherapy after the surgery; we call this adjuvant
chemotherapy. Patients with stage III, that usually means
that there is an involvement of a lymph node between the lungs, or
a mediastinal lymph node. We tend to offer chemotherapy and
radiation also with curative intent, we try to cure those patients,
although the cure rate is about 20%, there are some cures, and we
try to give them this opportunity. For patients
17:47 into mp3 file
http://yalecancercenter.org/podcast/feb2011-cancer-answers-morgenstzern.mp3
with stage IV, it means that the tumor has already spread.
There are some exceptions where we can try to do surgery, for
example, if there is only a small lesion in the adrenal glands or
in the brain or in the other lung, we can still try to perform
surgery of curative intent and we are trying to cure them, but if
the disease spread beyond that, where there are multiple lesions,
we would tend to give chemotherapy. Just like a small cell
that has already spread, the chemotherapy is given with the intent
of improving the survival and improving symptoms so patients may
live longer and better.
Foss
Can you talk a little bit about the side effects of the
chemotherapy that you are using?
Morgensztern
This has improved significantly since the 1990s. The
chemotherapy that we are using now are as effective, if not more
effective, and they cause less side effects, especially now that we
have better medicines for side effects as well. Most of the
medicines will cause nausea, the majority of them will cause hair
loss, which we call alopecia, and one of the most serious side
effects is a drop in the blood cell counts, so patients may
unfortunately be at risk of infection if the white cells go too
low, but we do have medicines now that can prevent it, not 100%,
but it decreases the chance of those complications from
happening. We also have very good new medicines to help for
nausea and vomiting, so we have improved significantly
recently.
Foss
Are there complications associated with the radiation therapy?
Morgensztern
Radiation therapies are also improving, but we still see
complications. For patients that have, for example, involvement of
the lymph nodes in the mediastinum, when they undergo radiation,
they also involve the esophagus, so they can have trouble
swallowing in the beginning of the treatment or towards the end of
the treatment. After two weeks, the majority of patients
improve without problems after that. It can also cause what
we call pneumonitis, which is the inflammation in the lungs, but
all those complications have improved. The probability of
having those is decreasing overtime with better techniques.
Foss
Do you think, overall, that the chance of a patient with lung
cancer living today is better than say it was ten or fifteen years
ago?
Morgensztern
The probability of a patient for any stage to be living now,
compared to 10 to 15 years ago, is much higher, although for
patients with early disease that are treated with surgery, the
difference is not that great, but for patients with more advanced
stage, there is a clear improvement in survival.
Foss
For many years, there really was no good news in the story of lung
cancer, but recently we have had a number of new and exciting drugs
and targeted therapies, could you talk a little bit about that?
20:58 into mp3 file
http://yalecancercenter.org/podcast/feb2011-cancer-answers-morgenstzern.mp3
Morgensztern
With pleasure, we always like to give good news. And even
before that, we conducted a study with 130,000 patients diagnosed
with non-small cell lung cancer in the United States, outpatients
with stage IV, which means that it has already spread to other
organs, and we have seen that there were no improvements in the mid
90s to the late 90s, yet in the beginning of 2000, there has been a
significant improvement in survival especially for patients of
adenocarcinoma for which most of the new treatments work. We
have been very fortunate to have medicines approved by the FDA in
the mid 90s such as paclitaxel, docetaxel, vinorelbine,
gemcitabine, and this was very significant for the care of
patients. They improved the response rate, they were less toxic so
they cause fewer side effects than the previous medicines, and then
in 2000, we have seen the development of targeted therapies.
We have seen the EGFR tyrosine kinase inhibitors, erlotinib,
and gefitinib. We still use erlotinib now, which has a brand
name of Tarceva, which is just a pill that helps some patients
significantly. We have seen the development and approval of a
drug which improves survival when added to chemotherapy compared to
chemotherapy alone. In the last year we have this brand new
medicine called Crizotinib, which works only for patients if they
have a specific mutation called ALK mutation. This mutation
is present in about 4% of the patients with non-small cell lung
cancer, usually patients with adenocarcinoma subtype, and all
patients should be tested for it because if they have the mutation,
they may derive significant benefit from it.
Foss
All of these are specific targeted therapies that are targeting
specific pathways or genes in the tumor cells.
Morgensztern
That's correct. All of them are specific targeted therapies.
Those are the ones that have been approved by the FDA.
Now, what we have seen over the last two years is a multitude
of new medicines, most of them are tablets which are easier to take
that target multiple factors and some of them in early studies have
shown results. The main task is to find out which patients
have which characteristics, and predict for the response for
patients with similar characteristics and who should receive this
medicine. There are so many new medicines; we just don't know
right which patients to give which medicine to.
Foss
I guess that is a good problem to have at the end of the day, too
many medicines. Can you talk about issues of looking at tumor
tissues to try to identify personalized medicine or to try to
identify which pathways are activated in which tumors and how you
use that information in the clinic?
Morgensztern
This is the future of medicine, the future of oncology for sure,
and this is the main goal of all treating oncologists
worldwide. We want to be able to look at the tissue, look at
which abnormality each patient has and provide the medicine that
will target the specific pathway. This is what we call
personalized medicine, the right medicine for each individual
patient. Right now we don't have that much information, we have
some mutations that we know could be targeted by specific medicines
and outpatients should be tested for that and there have been
several
24:46 into mp3 file
http://yalecancercenter.org/podcast/feb2011-cancer-answers-morgenstzern.mp3
studies in multiple institutions of what we call a whole genome
sequence, so the whole genome of the patients is being evaluated
and there are mutations being found, the only problem is that we
don't know which mutations are what we call passenger mutations,
they are there but we don't know if they have any consequence, as
opposed to the driver mutations, that are thought to induce
cancer. At some point, we will be able to sort it out not
only in lung cancer or adenocarcinoma, but we will probably call
them non-small cell lung cancer, adenocarcinoma, plus something,
this plus something will be whatever mutation is present and
whatever pathway is abnormal for which we will have a specific
medicine.
Foss
It is interesting because 15 or so years ago, there was pretty
much one formula for lung cancer, everybody got the same two drugs,
and now we are basically developing our strategies as we go along
and treatments are going to be highly individualized.
Morgensztern
We hope so. Obviously, it was much easier to practice a few
years ago because we had only a few chemotherapies to give and we
had been doing this mostly blindly, we just gave it to everybody
and hoped some people would benefit, but this is now changing, and
we have seen from some very basic information, for example,
patients with squamous cell subtype of non-small cell that don't
respond. We know that they do not respond to a very commonly
used medicine called pemetrexed, so negative selection. If we
can avoid giving this medicine to patients that we know would not
respond, that would increase the probability of the patient
responding to other medicines, or preventing them from having this
medicine that would not work, and we did not had this information
before.
Foss
Since there are so many patients out there with lung cancer, the
impact of oral therapies is probably most pronounced in this
setting, can you talk a little bit about how you see the impact of
these oral therapies in terms of the concept of patients say living
a normal life with their cancer and not having to run into their
oncologist's office all the time?
Morgensztern
There are good and bad things about oral therapy. There are
some oral chemotherapies that are very toxic. The fact that
the medicine is oral does not mean it is less toxic, but now with
the development of new oral targeted therapies, it's a different
story because they cause much less side effects, less nausea,
people don't lose their hair, blood counts don't go too low, so we
are not so worried now with these meds about a bad infection which
could be lethal. It is much more convenient as well, though
most of the treatments for non-small cell lung cancer or even small
cell lung cancer are given every three weeks, it is much easier for
the patient to take the tablets and it will be more flexible for
them to schedule appointments to the doctor. It is a very
very good advancement and we are welcoming the news.
27:50 into mp3 file http://yalecancercenter.org/podcast/feb2011-cancer-answers-morgenstzern.mp3
Foss
Can you let us know what you think the important questions are and
areas that should be researched further in lung cancer?
Morgensztern
On one hand it is very encouraging that patients with
adenocarcinoma are having such a significant improvement, and on
the other hand we need to develop better therapies for patients
with small cell lung cancer and also squamous cell. There are
still a large number of patients that we most definitely need to
find treatments that will work for this population as well.
Dr. Daniel Morgensztern is an Assistant Professor of Medical Oncology at Yale School of Medicine 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.