Cancer Answers: New Options to Treat Brain Tumors, November 9, 2008

Dr. Joachim Baehring, New Options to Treat Brain
Tumors November 9, 2008Welcome to Yale Cancer Center Answers with Dr. Ed Chu and
Dr. Ken Miller.  I am Bruce Barber.  Dr. Chu is Deputy
Director and Chief of Medical Oncology at Yale Cancer Center. 
Dr. Miller is a medical oncologist specializing in supportive care
and is the author of Choices in Breast Cancer Treatment.  If
you would like to join the discussion, you can contact the doctors
directly at canceranswers@yale.edu
or1-888-234-4YCC.  This evening, Dr. Ken Miller sits
down for a conversation about the treatment of brain tumors with
Dr. Joachim Baehring.  Dr. Baehring is an Associate Professor
of Neurooncology at Yale and he is Director of the Yale Cancer
Center Brain Tumor Program.Miller
Let's start by talking about some basic information.  When
people talk about a brain tumor, what are they referring to?Baehring
 The two major categories of brain tumors are those that primarily
affect the brain, meaning that they start in the brain, and
metastatic brain tumors.  Patients who have cancer in the lung
and the breast can develop metastases, seeding of the tumor to the
brain.  Those are the two major categories.Miller
What is more common?Baehring
 More common are the metastatic tumors, probably by about five
fold, maybe even 10 fold.Miller
So there are a group of people who unfortunately develop a cancer
that starts in the brain itself?Baehring
 Yes.Miller
In broad categories, what are the different types of cancer that
arise in the brain?Baehring
 There is a large variety of primary brain tumors.  The
largest group of brain tumors is called gliomas. That term is
derived from a normal type of cell that exists in the brain and
that cell type is called the glial cell.  Tumors that resemble
those cells, and likely are derived from those cells, are called
gliomas, and amongst those tumors there are benign variants and
malignant variants, or cancerous variants.  The most common
tumor, unfortunately, is a malignant one and it is called
glioblastoma.Miller
So there is a glioma, which is a low-grade one, and a glioblastoma,
which you were just referring to.  What are the differences,
do they look alike under the microscope, or do they behave
differently?2:24 into mp3 file 
http://www.yalecancercenter.org/podcast/Answers_Nov-09-08.mp3Baehring          
 Again, there is a large group and some of the low-grade tumors are
quite different from the high-grade ones; those tumors may even be
curable by taking them out.  However, there is an overlap
between the "low-grade" ones and the malignant ones.  Those
tumor groups are called astrocytoma, or oligodendroglioma, and they
can be diagnosed at a stage where they look very benign, but over
the years they can transform into a higher grade tumor and then
behave more aggressively.  There is an overlap between the two
groups and one can transform into the other, unfortunately.Miller
Let me ask a question that I think a lot of people are wondering
about, what goes wrong with a normal cell to make it become
malignant, and what are the risk factors?Baehring
 There are many very well-established risk factors for various
types of systemic cancer.  However, for brain cancer, we have
not really identified major risk factors.  The only one where
there is a clear correlation between exposure and later development
of brain cancer is with radiation.  Patients who in their
childhood had a tumor affecting the brain, let's say patients with
leukemia who require radiation to the brain because the leukemia
had spread there, later in life they have a risk of developing a
brain tumor in the area that was radiated.  Other risk factors
really have not been consistently linked to brain cancer. 
Very small subsets of patients with brain cancer have a genetic
predisposition. I would say at a center like ours, we may see one
or two cases a year amongst over 100 newly diagnosed cancers. 
So, that is quite rare.Miller
A million dollar question, but a common question people ask, do
cellphones cause brain cancer?Baehring
 I don't think at this point there is any evidence that they
do.  There are many studies across the world, most of which
seem to suggest there is no correlation between the use of
cellphones and the risk of developing brain cancer.  However,
as with many other exposure risks, many times they are ruled on
decades after the exposure was initiated, so there may be a slight
increase in risk, but again, there is absolutely no evidence,
neither from animal experiments nor from studies in humans, that
cellphone use increases the risk of brain cancer. Cellphones have
been around for a long time, so I think the likelihood that we will
ever establish a link is quite low.Miller
Which absolutely is reassuring because you see almost everybody
with cellphones in their hands. Typically, what are the symptoms
someone would have? You see a large number of new patients here,
what do they tell you?5:24 into mp3 file 
http://www.yalecancercenter.org/podcast/Answers_Nov-09-08.mpBaehring
 The two most common symptoms that patients presents with, that are
later found to have a brain tumor, are headaches and
seizures.  A headache is obviously a very common symptom, and
probably one of the most common symptoms that people seek medical
advice for. One does not have to be concerned about developing a
brain tumor with every headache, obviously.  Headaches are
stress related, migraines are another stress related, very common,
form of headaches, and there are various other types of headaches
that are not caused by brain tumors.  There are a couple of
features that should alert somebody who has a chronic headache that
they should have it checked out.  The typical brain tumor
headache is worst upon awakening in the morning. Patients even wake
up in the middle of the night, and they may feel nauseated. 
Then once patients get up and walk around it gets better, and gets
better during the day; at the end of the day they may not even have
it.  A headache that is chronic and gets worse week after
week, month after month, that becomes more frequent, in general
that is the type of headache that you don't just want to treat with
over-the-counter medication, but see a doctor for.Miller
That is important advice, but just to reassure people, as you were
saying, headaches are very common, and thankfully, most of the time
are not related to a cancer but to a benign cause.  How do you
detect a cancer in the brain?Baehring
 Once you have taken a history from the patient, examined the
patient, and found a concern for a tumor, the next step is usually
obtaining an imaging study of the brain. Nowadays, at least here in
the US, the most commonly used diagnostic test is an MRI scan of
the brain with contrast dye.  It is the most sensitive and
specific noninvasive test that we have, and that usually can rule
out the presence or absence of a brain tumor.Miller
There has been a lot of talk about newer ways to image the brain
and understand how the area where a tumor is relates to the
functional parts of the brain that control speech and vision. If
you are contemplating having a patient have surgery, and you want
to relate it to what they may lose in terms of function, how do you
do that using imaging studies?Baehring
 There are a couple of new very interesting techniques, and the
ones that I use nowadays are all MRI based, so for the patient
there is not much of a difference having a regular MRI scan or one
of these specialized MRI scans.  If surgery is needed in an
area that carries very important function like speech or strength
on one side of the body, an MRI scan called a functional MRI is
obtained where the patient is asked, while lying in the MRI
scanner, to perform a certain task, either read from a text or
listen to a verbal command or simply squeeze a soft ball in one
hand, and the MRI8:41 into mp3 file 
http://www.yalecancercenter.org/podcast/Answers_Nov-09-08.mp3
 can actually pick up differences of blood perfusion on the surface
of the brain and areas that are activated generally require an
increased oxygen demand and blood supply.  That relative
difference is picked up by the scan and then a computer program can
generate a color-coded map where the activated area is highlighted
in relationship to the tumor, and that provides very important
information to the neurosurgeon in determining whether this tumor
can be safely removed, or if removal would likely result in a
neurologic deficit, then only a biopsy be performed.Miller
             
 This sounds fascinating.Baehring
 It is.Miller
I have heard for a long period of time, of having a neurologist or
a specially trained person in the OR doing an EEG or doing other
studies.  Can you tell us a little bit about that, the
intraoperative part of things?Baehring
 Yeah, tests like that are still indispensable.  The
preoperative imaging capabilities have dramatically improved. 
However, in the very end when it comes down to making a decision as
to whether a piece of the tumor can be safely resected or not, the
neurosurgeon still does some intraoperative testing and there are
various options such as simply stimulating the surface of the brain
with an electrode, and if a tumor is located very close to the
language area, sometimes patients are only lightly sedated for the
surgery, and then in the operating room, the medication is briefly
withdrawn.  The patient is asked to read something before and
after stimulation, and if there is a change in language function
after stimulation, the surgeon knows that they cannot remove that
part of the brain.  Also, stimulation in a patient who is
sedated off the strength control area, the brain results in
contraction of muscles on the opposite side of the body.  So,
if a surgeon elicits that kind of response with stimulation, he
knows this is an area where they cannot go.Miller
Fortunately it sounds like that aside from the physical exam and
your expertise, you also have a lot of tools available to you to
help make those decisions.Baehring
 Yeah, the technology has evolved quite dramatically, and while
there are a lot of tumors still that we cannot cure, the outcome
from surgery has improved simply based on the fact that we can
determine the relation of the tumor to the normal brain much
better.Miller
How is a biopsy done?11:28 into mp3 file 
http://www.yalecancercenter.org/podcast/Answers_Nov-09-08.mp3Baehring 
         
 A biopsy can be done one of two ways, either the skull is opened
like for regular surgery and then a small piece of the tumor is
taken out, or a way that is less invasive, is what you call a
stereotactic biopsy.  A patient is taken to the operating
room, a small bur hole is drilled into the skull, and then a fine
needle is inserted into the area of interest into the tumor and
then a very small tissue cylinder, it is only about a millimeter
thick and about a third of an inch long, is retrieved and then the
pathologist looks at the tissue.Miller
Are there ever times where you are unsuccessful in getting a biopsy
and you have to just decide to treat someone?Baehring
 Sure, that does happen.  If a brain tumor is in a very
critical area of brain function, if it is very deep in the brain,
or if it is in the lower part of the brain in what is called the
brainstem, there are a lot of vital functions like breathing
located there.  Sometimes either a biopsy cannot be performed
because it would be unsafe for the patient, or only a very small
piece can be retrieved, on which a diagnosis is not possible. 
That is rare, but it does happen.  If the patient's symptoms
progress, we are bound to treat based on imaging appearance and
other test results, we simply have to treat for the most likely
diagnosis.Miller
Those must be very difficult situations.  Before taking a
break, let me ask you, what is the primary form of treatment for
people with a cancer that arises in the brain?Baehring
 For most cancers of the brain, for most malignant brain tumors,
the treatment approach requires several specialties. 
Typically, the surgeon is the first involved either for a biopsy or
removal of the tumor.  Secondly, the radiation oncologist
provides radiation to whatever of the tumor is left and possibly
also to some degree of normal-appearing brain around the
tumor.  Thirdly, chemotherapy is a tool for many different
types of brain tumors.  There are variations.  There are
particular tumors that can be cured by surgery.  There are
other tumors that are very sensitive to radiation and other tumors
that go away with chemotherapy alone, but as a general rule for the
most common tumors like glioblastoma, all three treatment
modalities are required.Miller
You are listening to Yale Cancer Center Answers.  We are here
discussing the latest in treatment options for brain tumors with
Dr. Joachim Baehring who is an expert in the treatment of these
types of tumors at Yale Cancer Center.  We are going to take a
break for a medical minute and will be right back with you.14:21 into mp3 file 
http://www.yalecancercenter.org/podcast/Answers_Nov-09-08.mp3Miller
Welcome back to Yale Cancer Center Answers.  This is Dr. Ken
Miller and I am joined today by Dr. Joachim Baehring who is an
Associate Professor at Yale Cancer Center and an expert on the
treatment of malignant tumors of the brain. Joachim, we started
talking about treatment of cancers that arise in the glial cells,
glioblastoma and tumors like that.  I also know that you are
an expert in the treatment of patients with lymphoma of the brain.
Can you tell us a little bit about that, I mean we typically think
of lymphomas and the lymph nodes, how does it arise in the
brain?Baehring
 Brain lymphoma is quite a rare tumor.  There are only about
1000, maybe 1400, cases a year in the United States altogether.
Just for comparison, for colon cancer and prostate cancer, there
are over 200,000 cases a year in the US.  So it is in order of
magnitude less frequent.  Lymphoma, you are right, typically
affects lymph nodes, but also other organs of the body can be
affected like the liver, spleen, heart, lungs or the brain. 
Of all lymphomas that arise in the United States, only 1 in 50
affects the brain alone, and it is a rather peculiar tumor in that
it seems to affect only the brain.  Only at the very last or
late stage when the tumor relapses after initially successful
treatment, does it leave the brain and spread into other parts of
the body.  There is a unique predilection for the brain with
these tumor cells, and we believe that these tumors arise from
cells that at some point during the patient's lifetime were primed
to attack some intruder, bacterium or virus in the brain, and that
is why they later seek out the brain again, but that is a
hypothesis and has not been proven yet, but it seems to be true for
other types of lymphoma.Miller
If a patient has a central nervous system lymphoma, is the
treatment in that case surgery, chemotherapy, or radiation?17:15 into mp3 file 
http://www.yalecancercenter.org/podcast/Answers_Nov-09-08.mp3Baehring          
 Lymphoma happens to be exquisitely sensitive to chemotherapy, so
it has a rather typical appearance on MRI.  If we suspect a
lymphoma, typically the surgical procedure is limited to a
stereotactic biopsy, meaning biopsy through a small bur hole. 
If the diagnosis is confirmed, then chemotherapy is
administered.  There are different types of chemotherapy
regimens, all of them include a drug called methotrexate that is
given by vein every two to four weeks over the course of 6 to 12
months. There is about a 60% to 70% chance that the tumor will go
away with that treatment.Miller
Which is excellent and probably a lot better than it was years
ago.Baehring
 The treatment paradigms have changed.  In the old days these
tumors too were treated with surgery and then radiation and the
patients either had severe side effects from those treatments down
the line, anywhere 6 months or 12 months down the line, or the
tumors relapsed fairy quickly.  About 15 years ago there was a
change in the treatment paradigm and that has improved the outcome
of patients with these tumors dramatically.Miller
I want to switch to a different topic.  We have talked some
about surgery, we have talked about chemotherapy, but you and the
team you work with are also experts in the use of gamma knife
radiation, what is that?Baehring
 A gamma knife is a device that provides a radiation boost to a
defined area within the brain.  The core feature of a gamma
knife is actually a large shielding device and the radiation source
surrounds this shielding device.  There are over 100 bur holes
in that shielding device and they can be focused on an area within
the brain that is abnormal, may that be a tumor.  There are
other indications for this procedure as well.  The advantage
is, if the x-ray beam comes from different directions and all the
beams meet in one target, the exposure of normal brain surrounding
the problem is minimized, whereas the tumor exposure is
maximized.  That is in contrast to standard radiation where
the x-ray beam may be from three or four directions and that
exposes normal brain much more than gamma knife does.  Gamma
knife is not for everybody and tumors that are not very well
circumscribed, and unfortunately most of the primary brain tumors
are not, are not good targets for gamma knife simply because the
treatment then only focuses on the very core of the tumor, but it
does not address less obvious tumor surrounding this lesion.Miller
Let's stroll down a little bit further on this, your description of
the gamma knife has been very helpful to me. For patients with a
glioblastoma, which you were saying is the most common type of
brain tumor, who has surgery, would you want to give them external
radiation, or the typical20:34 into mp3 file 
http://www.yalecancercenter.org/podcast/Answers_Nov-09-08.mp3
 radiation, or would you want to use gamma knife?Baehring
 The standard treatment protocol for a glioblastoma consists of a
standard radiation protocol, meaning "involved field radiation"
where not only the tumor and whatever is left after surgery is
exposed to radiation, but also a safety margin of about two thirds
of an inch to one inch that surrounds the tumor, and that simply
addresses the nature of the tumor.  The tumor is not
circumscribed, it is not surrounded by a capsule, it is not sharply
separate from the brain, but it has very fuzzy edges.  There
are tumor cells that infiltrate the brain surrounding the tumor
that is visible on MRI scan.  A gamma knife is used for
patients with glioblastoma; however; there are very selective
indications for it.  If a patient after surgery has a very
small residual, or after initially successful treatment has a very
small recurrence, that may be an inappropriate target for a gamma
knife, but gamma knife has been studied formally for glioblastoma
in addition to a standard radiation, and unfortunately, that did
not lead to a survival advantage.Miller
I think people sometimes have the impression that hi-tech is
better. You hear about gamma knife or cyber knife, and I think this
assumption is that they are better, but in this case it is not.Baehring
 That's right. There is a select small group of patients that would
benefit from additional radiation boosts, but one really has to
select these very carefully.Miller
What does adjuvant therapy mean? And how is it applied to people
with brain tumors?Baehring
 Adjuvant really means additional therapy after surgery, that's
what we mean with adjuvant.  So, in a way, radiation treatment
is an adjuvant treatment and so is chemotherapy. For patients with
primary brain tumors, as I mentioned, most patients do need both
the primary treatment, which is surgical removal of as much of the
tumor as we can, and adjuvant treatment such as radiation and
chemotherapy.Miller
What type of chemotherapy is used for patients like these?Baehring
 For the most common primary brain tumor, the standard of care now
includes a drug that is called temozolomide.  It is a drug
that is given by mouth and it alters the molecule, the DNA
molecule, within the cancer cell that carries the genetic
information, and by doing so, it interferes with the ability of the
cancer cell to divide, which is ultimately the basis for tumor
growth.23:21 into mp3 file 
http://www.yalecancercenter.org/podcast/Answers_Nov-09-08.mp3Miller 
             
 What are some options for patients with brain tumors, and in
particular, are there any clinical trials that are available?Baehring
 There is a large number of clinical trials available.  Over
the last 10 years we have seen numerous new drugs enter the field
being tested in clinical trials.  There are a couple of drugs
that are of particular interest to patients with primary brain
tumors.  One I want to highlight is a group of drugs that
targets the tumor's ability to grow new blood vessels when tissue
grows at a high rate like in cancer.  Tumor cells and tumor
growth is dependent on oxygen supply, a nutrient supply, that
requires growth of blood vessels.  So, there are drugs that
can specifically target the tumor's ability to do that.  There
are different mechanisms.  Some of these drugs are given by
vein, others by mouth.  For some drugs we already have some
clinical trial data that is quite encouraging.  There is a
drug called bevacizumab that has gone through the first phases of
clinical trial.  There are other drugs that are a little
earlier in the development.  However, we do not have
definitive trial results yet that would tell us why all of these
drugs need to be included in the standard of care, but we are
probably getting close to at least identifying one or two more
drugs that may be added to what we have been doing so far;
radiation and standard chemotherapy.Miller
It makes me think back to the situation with lung cancer and colon
cancer where bevacizumab, or Avastin, seemed to work
synergistically together with chemotherapy. Might that apply to
treatment of people with brain tumors?Baehring
 There is certainly evidence from experiments that there may be a
synergism between bevacizumab, or other drugs that attack the
ability of the tumor to grow blood vessels, and standard forms of
chemotherapy.  There is a drug called irinotecan that in
experiments, at least, has been shown to have a greater effect on
tumor cells if it is given in addition to bevacizumab.Miller
And some of the research that is going on at Yale is very exciting,
for example the use of viruses to attack the brain, and new methods
of delivering therapy, can you tell us some about those?Baehring
 There are several groups at Yale with an interest in brain tumors,
and the two different topics you mentioned are probably the hottest
that are currently ongoing.  One group in our department, led
by Anthony van den Pol and Guido Wallman, is trying to identify
viruses that not only have the ability to specifically infect tumor
cells, but also then kill them. They have been successful and have
shown in animal experiments that tumors that26:27 into mp3 file 
http://www.yalecancercenter.org/podcast/Answers_Nov-09-08.mp3
 are growing in the brain can be successfully treated with
this.  However, there is still a long way to now transfer this
knowledge into a clinical trial where patients are actually
treated.  There are examples of different viruses that have
already been used in clinical trials in humans.  This would be
a refined origin of those viruses and I am hopeful that over the
course of a few years we will get there and can use some of these
new tools.  There is another group at Yale that is led by Dr.
Saltzman, the director of the Department of Biomedical Engineering,
and he is developing "micro vehicles" with which we can administer
drugs, or other treatments, directly to the brain.  Those
vehicles are called nanoparticles and they are microscopic
particles that can be coated with certain molecules that renders
them specific for brain cancer cells.  They can be loaded with
different agents that can attack brain cancer. This is quite an
exciting field of research and I think that is a little closer to
clinical use in the viral treatment.Miller
Sitting here with you, I have to share with the listening audience,
I can see your eyes light up when you are talking about these; it's
exciting isn't it?Baehring
 You know, these are exciting times.Miller
That's terrific.  How can a patient access help from the brain
tumor center?Baehring
 We can both evaluate patients, as in a primary consultation, and
then treat them, or we also provide second opinions. If a patient
is interested in simply coming in or sending us material, we will
review the case in our multidisciplinary tumor board and then
provide an opinion as to how we would approach the case. But for
anything general, we have a clinic coordinator, Elizabeth
D'Andrea.  She can be reached at Yale at 203-737-1671. She is
the first contact person through which patients enter the system,
and she makes the decision if that patient should be seen first by
a surgeon, a radiation doctor, by myself, or one of our other
medical oncologists.Miller
Terrific, you have been listening to Yale Cancer Center Answers. I
want to thank our guest, Dr. Joachim Baehring, for what has been a
really interesting session for me, and I hope for all of you as
well.  Joachim, thank you.Baehring
 Thank you for having me.29:08 into mp3 file 
http://www.yalecancercenter.org/podcast/Answers_Nov-09-08.mp3Miller
 Until next week, I am Dr. Ken Miller from the Yale Cancer Center
wishing you a safe and healthy week.If you have questions for the doctors or would like to share
your comments, go to www.yalecancercenter.org
where you can also subscribe to our podcast and find written
transcripts to past programs.  Next week, you will meet Dr.
Melinda Irwin who joins Dr. Ken Miller to talk about exercise and
cancer prevention.  I am Bruce Barber, and you are listening
to the WNPR Health Forum from Connecticut Public Radio.