Cancer Answers: Gamma Knife for Cancer Treatment, January 23, 2011

Dr. Veronica Chiang and Dr. Jonathan Knisely, Gamma
Knife for Cancer Treatment
January 23, 2011Welcome to Yale Cancer Center Answers with doctors Francine
Foss and 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 1-888-234-4YCC.  This evening, Francine
and Lynn welcome doctors Jonathan Knisely and Veronica
Chiang.  Dr. Knisely is an Associate Professor of Therapeutic
Radiology and Co-Director of the Yale-New Haven Gamma
Knife Center, and Dr.Chiang is an Associate
Professor of Neurosurgery and of Therapeutic Radiology, Director of
Stereotactic Radiosurgery, and Medical Director of the Yale-New
Haven Hospital Gamma Knife Center.  Here is Francine Foss.Foss
I would like to start off by having you tell our listeners a little
bit about your backgrounds and how you became involved in your
respective fields.Knisely
 I will go first.  My realization that radiation oncology was
the field I wanted to go into, was predicated upon the realization
that there would be CAT scans and MRI scans available
ubiquitously.  It was not something where people had to
debate, gee; do you think we should get a scan?  And that was
concurrent with the availability of digital desktop computers,
which would be able to figure out exactly where things were in
three-dimensional space and be able to aim the radiation where the
problem was and avoid the stuff that did not need to be
treated.  The transition from that to radiosurgery was very,
very simple because neurosurgery was a field in which everything
got pinned down with a stereotactic frame for a biopsy or a
procedure and there was no issue with movement, and the
availability of MR Imaging allowed us to see exactly where things
were in the brain with a much higher degree of accuracy than
elsewhere in the body.Chiang
From my perspective, I was a young neurosurgeon, looking for a
career, and radiosurgery was a developing field particularly in the
area of metastatic tumors.  I think that, certainly, over the
last 10 years, this field has moved from something that was
considered relatively novel to something that has now become pretty
much standard of care, and what was required was emerging between
the medical oncology field, the radiation oncology field, and the
neurosurgeon to allow comprehensive management of these lesions,
and so this was good for me.Wilson
Jonathan, can you tell us exactly what gamma knife is? We hear the
word "knife" and I think some people assume that there is a
surgical aspect to this.  Tell us the details about this and
when it was first developed.Knisely
 The gamma knife's original concept dates back to the early 1950s.
 Brain surgeons trying to do operations back then had the same
challenges that we have currently with identifying exactly where
the target is, the thing you are going after.  A neurosurgeon
named Lars Leksell in 1949 developed a stereotactic frame system to
allow biopsies to be done. About two years after that, he realized
that the trauma associated with conventional neurosurgery in going
in and getting the thing out might be able to be avoided by using
convergent beams of radiation that were highly focused, directed at
the site of what was going to be removed, directed at the tumor,
and that led to
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a number of prototypes that they tried in Sweden.  The first
working model of the gamma knife was in 1968 in Stockholm, and
again, it took some time, really until you had good high-speed
computers and good three-dimensional imaging that would allow you
to see exactly where the thing you wanted to hit was, to be able to
target the radiation as accurately as we can currently.  The
gamma knife uses about 200 very highly focused radiation beams that
come from all different directions, not just in one plane but in
many planes simultaneously to aim radiation at what you are trying
to destroy or stop the growth of and by having, for example, 200
radiation beams coming altogether, each of the individual beams is
only delivering 1/200th of the dose of radiation that the tumor
gets so that the dose to the normal brain cells is much, much
lower, and more likely to be very well tolerated.Foss
Can you tell us, Veronica, about stereotactic surgery and also
about the impact of the gamma knife on what you do as a
surgeon?Chiang
I think that for neurosurgeons, stereotactic surgery has been
around for a long time.  Typically we will put patients to
sleep and this is a technique that has been practiced on animals
previous to this to make sure that the technique was safe.  We
have used it a long time, as Dr. Knisely suggested, targeting
things that are deep in the brain.  It started particularly
with the treatment of pain and movement disorders, and in fact,
when Lars Leksell started, that was really the goal of offering
radiation to that area.  This has then translated in the
operating room now to modern day where we use it to guide where a
craniotomy is made to make the smallest incision possible, but it
also allows us to resect lesions more completely, and obviously,
there are still places that we cannot go and so what we cannot
achieve from a surgical perspective we can now achieve with the
radiosurgical treatment. We can aim radiation at places where we
cannot go surgically or we do not want to go because patients are
inappropriate for surgery.Wilson
Jonathan, what are some of the primary indications for gamma knife?
What types of patients do you see and manage with this technique,
which has obviously evolved tremendously over the last 40
years?Knisely
 We are seeing approximately 60% of our cases having metastatic
disease to the brain.  The common tumors that spread to the
brain include lung cancer, breast cancer, and melanoma.  We
also see many patients with other types of tumors.  Tumors
that spread to the brain are very commonly referred for treatment
on the gamma knife.  We see a number of other tumors that
start in the brain; tumors such as meningiomas, pituitary
adenomas.  We treat vascular malformations, arteriovenous
malformations, and vascular tumors.  We treat conditions such
as trigeminal neuralgia, which is a very painful condition
affecting the face.  We have treated skull based tumors,
tumors arising in the paranasal sinuses that have spread to the
orbits.  As Veronica indicated, this technique was originally
developed for movement disorders and pain syndromes so we have done
that in the past but we do not have a current active program with
movement disorders.  We have actually even treated somebody
with epilepsy.7:43 into mp3 file 
http://yalecancercenter.org/podcast/jan2311cancer-answers-knisely-chiang.mp3Foss             
 Can I ask both of you how you determine that a patient is eligible
for gamma knife? Do you have a combined modality clinic or do the
referrals come in and one of you sees them?Chiang
What has made it most efficient for us, and this has really just
evolved over time, is that the consultations predominantly come
through one coordinating center and for now that is most
effectively coordinated through the neurosurgical services, the
main reason for that being that the neurosurgeons have been
subdivided somewhat into their sub-subspecialties.  So, if you
had metastatic disease, you would be referred to my office. 
If you had a vascular malformation, you would come through Dr.
Gunel's office, etc., and it is that office's responsibility to
make sure that there is a consultation both with the neurosurgeon
and with the radiation oncologist.  We have made a concerted
effort for those consultations to be either performed at the same
time or at least on the same day, so it makes for a single day
visit, and then what we have been able to achieve, certainly with
metastatic disease because of the urgency with which these patients
need to be treated, is for their treatment to most often occur
within the same week.Knisely
 Francine, the way I explain it, or I think of it is like a Venn
diagram where surgeons can either use conventional microsurgical
techniques or radiosurgery, and I as a radiation oncologist can use
fractionated radiation therapy or radiosurgery.  We have to
concur that radiosurgery is a good option for that patient and make
sure the patient understands the risks and benefits of the
different approaches that might be applicable, and it is common for
us to also recommend observation for patients because many of the
tumors that we might treat with the gamma knife are benign and we
want to make sure that the patient actually has a tumor that is
causing some loss of function before we recommend an
intervention.Foss
Would there be a situation where you may do surgery and use the
gamma knife?Chiang
Yes, certainly.  I think that there are some situations where
the tumor may either be too large for its location or just too
large overall, or where there are multiple lesions, and so some of
them may need to be addressed surgically and then the rest of them
could be addressed with radiosurgery.Knisely
 We also use radiosurgery with radiation therapy.  It depends
on the clinical situation.Wilson
Jonathan, can you talk us through the actual procedure? Obviously
our listeners may think of traditional surgery, neurosurgery, it is
a hospital stay, general anesthesia, very long procedure that may
take most of the day for Veronica and her colleagues? What is
involved in the gamma knife procedure itself?Knisely
 Once the decision has been made to offer radiosurgery and the
patient understands the procedure is scheduled and that usually
means the patient comes to the hospital early in the morning, and
once they have been confirmed to have a heart that is beating and
they have got an IV started, then local anesthetic is administered
by Dr. Chiang to four spots on the scalp so that a stereotactic
frame can be put on the patient's head.  This is basically a
temporary guidance system, literally a frame of11:18 into mp3 file 
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reference that will be used for determining exactly where the
radiation should be aimed.  Once that frame has been put on,
the MRI scan and/or CAT scan that is used to obtain the
three-dimensional coordinate system for the procedure is
done.  That takes about 20 minutes.  The patient will
come back to the Gamma Knife Center and we will then review the
imaging, come up with a plan and that can take sometimes 20
minutes, sometimes an hour or more.  Once that plan has been
generated, reviewed by Dr. Chiang and myself together with a PhD
physicist, we take the plan that has been created in virtual
reality and transfer it to the computer system that will control
the treatment, we bring the patient in, hook the patient up to the
machine that will control the positioning of their head so the
radiation is aimed with submillimeter precision, and the treatment
is then delivered.  Very simple treatments might only take a
half hour of time in the machine.  More complex treatments
where many different spots might need to be treated, might take
several hours, but generally it is an outpatient procedure. 
At the end of the procedure, the head frame is removed, bandages
are put on where the head frame had been attached, and we discharge
the patient from the hospital.Foss
Is this done in a special Gamma Knife Center or is it done within
your department?Chiang
We actually have a small area that has been designated for gamma
knife patients and the procedure.  We are, however, part of
the radiation oncology department and so we are one of the, I
think, six or so vaults down there.Knisely
 In the basement of Smilow Cancer Hospital.Chiang
Yeah.Foss
We have talked a lot about brain tumors and I am wondering, do you
use this technique for other kinds of spinal cord tumors or other
areas that might be difficult to get to?Knisely
 The gamma knife was developed by a brain surgeon for use in the
brain and there are some limitations in its design that preclude it
from being used for tumors too far below the bottom of the
skull.  We have other technological platforms that we can use
to address tumors that occur lower down in the neck or down in the
spine.Wilson
Is gamma knife available, Jonathan, in other centers around the
United States or in Connecticut?Knisely
 There are no other gamma knifes in Connecticut.  There is a
gamma knife in Providence.  There are a couple in New York
City and its immediate environs.  There is one in
Boston.  It is a technology that has been recognized as being
very valuable and many other platforms have been developed to try
and duplicate what the gamma knife can do using other approaches to
focus radiation very precisely on very small volumes of tissue.Wilson
Let's address that when we get back from our break.  We are
going to take a short break for a14:19 into mp3 file 
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medical minute.  Please stay tuned to learn more information
about gamma knife with doctors Knisely and Chiang.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 doctors Jonathan Knisely and Veronica
Chiang and we are discussing gamma knife.  Veronica, could you
talk to the listeners a little bit about both short- and long-term
side effects, if there are any, related to the gamma knife and
review some of the expected benefits of the treatment?Chiang
One of the reasons why gamma knife has become so popular as a tool
is that there really are not too many side effects from the gamma
knife treatment itself.  The advantage of the gamma knife is
that compared to other radiation tools that have been used in the
past, the amount of normal brain that receives radiation is
relatively small compared to tools such as external beam radiation
or even IMRT, and certainly compared to surgery, many of the
approaches that we use surgically require entry through normal
brain to get to deeper tissues and tumors and so there is very
little of that involved.  As Dr. Knisely had discussed before,
there is obviously no knife cutting and no opening of the skull and
things like that and so these are all clearly benefits of
undergoing gamma knife.  Gamma knife, in addition, is a
one-day procedure, so there is no admission to the hospital, there
is no general anesthesia, and all of these things, particularly for
patients with metastatic disease who have a lot of other disease
going on in the rest of their bodies it is clearly an
advantage.  The side effects of radiosurgery mainly depend on
the size and the location of the lesions themselves.  In
general, with lesions smaller than a centimeter in size,
radiosurgery rarely causes a problem.  As the lesions start to
increase slightly, larger than that up to about 3 cm, which is the
limit of gamma knife, there can be some swelling from the single
dose of radiation, but this can usually be treated with a dose of
something called Decadron, which is a medical steroid that we use
and those effects are transient.  Unfortunately, radiosurgery
can sometimes bring on seizures.  What we have done in our
center is we have treated people with a pretreatment dose of
anti-seizure medicine and that in general has averted seizures from
occurring.  Down the line, what we have been seeing is
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some people unfortunately, as with other forms of radiation that
have been delivered, the tumors can start to re-grow again, but
obviously, this is possible with any tool that we use, and I think
that the rate of re-growth with radiosurgery has been inordinately
low compared to some of the other tools out there that we have
available to us.Foss
Veronica, is there a limit to the number of lesions that can be
radiated at any one given time?Chiang
Actually there used to be.  It depends on the machine that you
have.  We, very fortunately, have been able to upgrade
recently to the latest version of the gamma knife known as the
Perfexion and this machine was specifically designed to treat
multiple metastatic disease, and so while we used to have a limit
of around 10 or 15 lesions because it just took a long time to
treat those people, we actually have been able to treat up into the
30 to 40 lesion range per sitting with this machine.Foss
Jonathan, I had another question about side effects.  If you
compare your patients who have had whole brain radiation to those
who have gamma knife, the whole brain patients oftentimes complain
of fatigue and then they have these kind of memory changes that are
transient, do you see that with gamma knife?Knisely
 It is much less frequent with gamma knife.  The dose to
normal brain structures is much lower.  There actually was a
randomized control trial, a scientific study that looked at
radiosurgery alone versus radiosurgery plus whole brain radiation
therapy for patients with between one and three brain
metastases.  This was a study conducted at MD Anderson Cancer
Center in Houston.  They found that with detailed
neuropsychological testing evaluating patient's short-term memory
and quality of life that at four months' time, which is a relevant
point in time for anybody who unfortunately has developed brain
metastasis, patients who had had a whole brain radiation therapy
had worse problems with their memory, which would affect such
important things as remembering to take medicines and obviously
where did I put my cell phone, and they had a poorer quality of
life than patients who had been treated with radiosurgery
alone.Foss
So would not all patients want to go for the radiosurgery?Knisely
 We think that it is a superior option.  When we think about
whole brain radiation therapy, that is a treatment technique that
was developed in the 1960s and was used to treat patients who had
developed large and symptomatic brain metastases, also that was
developed at a time when we did not have effective systemic therapy
for cancer.  We now have the ability with MRI scanning and CAT
scan to detect lesions when they are very small and we have a
treatment technology that has made it very easy to pick off these
very small marble and smaller sized spots in a single
setting.  We think we do a very good job at it, and we think
it is a better option for treating patients.Wilson
Jonathan, with the accuracy that you are able to provide, does the
gamma knife provide a higher21:27 into mp3 file 
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dose of radiation to a lesion that a non-stereotactic, more
traditional technique would be able to safely offer?Knisely
 Yes, it does, because we are not including very much normal brain
in the high-dose area, literally only a millimeter around the spot,
maybe 2 mm, we are able to increase the dose significantly in that
single setting.  I have heard people refer to it as being
radiocautery as opposed to radiotherapy, but if we are only
treating the tumor, I think that we have very little downside to
doing it that way.Foss
If a patient has had gamma knife, can they then go on to have whole
brain radiation?Knisely
 Yes, they can.  The focal high-dose radiation does not
preclude somebody receiving a whole brain radiation therapy in the
future if that were required.Wilson
A question for both of you, can you discuss with our listeners what
goes into the treatment planning process because obviously that is
where the actual treatment plan is developed and is essential for
the success of the treatment?  What is involved with
that?  Jonathan, you had mentioned a PhD physicist as part of
your team, how does it actually work?Knisely
 The imaging studies that have been obtained on the patient on
their morning of treatment are brought into a specialized computer
workstation and we review those images with the physicist,
identifying exactly where the lesions are we want to treat and
setting up things that are called dose calculation matrices. 
Those are areas that we want to know the dose very accurately
within.  We will instruct the physicist, saying this is an
area that we want to be very careful about, or if these are
structures we do not want the radiation to hit to any significant
degree, important things such as the optic nerves important for
vision, or the cochlea, which is very important for helping you
hear if we are treating a tumor very close to or involving the 8th
cranial nerve, the hearing part of your cranial nerves, we will
then let the physicist sit there and do his work, saying you are
not doing it right, move it a little bit to the left, move it a
little bit to the right, change it this way or that way.  Once
we have all agreed that we have achieved an optimized plan, then we
print it out, we sign it, and push it on over to the treatment
computer.  It is relatively straightforward.  This is,
however, where I think the experience that we have allows us to be
very comfortable with doing this because we do this literally five
or six times a week.  It is something that we do all the time
and represents a major part of Dr. Chiang's and my practice. 
It is not something that we fire up once or twice a month, it is
part of what we do to provide comprehensive services.  We are
fairly subspecialized.Chiang
I think that what comes with the Perfexion also is incredibly
sophisticated software that was developed over the last 20 years
that really allows the calculation for the doses that are required
to be done in an almost seamless fashion.  I certainly
remember about 15 years ago when I was a resident that a lot of the
calculations were part done by hand and all of that has really
changed now and allows us to pretty much in real time do the
calculations to what we need it to be.24:57 into mp3 file 
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You have both seen advantages in terms of efficiency and for the
patients with the upgrade of the equipment.Chiang
Very clearly, this is much more user friendly.  It is much
more comfortable from the patient perspective and the planning and
treatment times have significantly decreased.Knisely
 One of the things that is important is that this machine has an
increased, I guess, robotocization of the positioning that is
required.  If you had three spots in your head, for example,
that we needed to move from the front left to the back right and
then over all the way to the right above your right ear, we would
need to go into the room and change your position manually with the
previous version of the gamma knife, and perhaps change the
diameters of the equipment that focuses the radiation on those
spots, all that can be controlled automatically by a computer now,
making it a lot more efficient for us to be able to offer treatment
that is more complex to patients without having any time
penalty.  Everybody can still get out in time for dinner.Foss
And the patient is awake through this procedure?Knisely
 Yes, no anesthesia, well, local anesthesia and a bit of sedation,
but that is generally more for the MRI scan than for the actual
treatment itself.Foss
Do you see any advances in terms of thinking about combining other
therapies with gamma knife, like what we talk about the use of
radiation sensitizers in radiation oncology, do you foresee that
there would be any direction that we might combine gamma knife with
other agents or other therapies?Chiang
From my perspective, what I have really seen more than the use of
radiosensitizers or radioprotective agents, is how our tool can be
used in combination in an interdisciplinary way.  One of the
groups that we work particularly closely with is the Melanoma Group
and just our ability to understand how what we do interacts with
the systemic agents that they administer and how far we can push
the envelope as far as how long after radiosurgery these agents can
be given and what would be helpful, I think, in the long run, would
be to be able to look at each of the agents that each of the these
interdisciplinary groups uses and say you know what, it is safe to
start this three days afterwards so you do not have to wait four or
six weeks before you start chemotherapy or systemic therapy, and so
those are the  things that are starting to be developed as far
as studies going forward.Wilson
Jonathan, just jumping back to side effects for a minute, obviously
with the whole brain treatment, I know patients can have hair loss
with that, do you see hair loss with the gamma knife technique?Knisely
 We generally do not.  Occasionally, if we are treating a
lesion that is very close to the scalp, a very superficial
meningioma, there might be a temporary focal loss of hair right
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meningioma is located, but the high-dose radiation generally does
not hit the skull or scalp, so there is no hair loss.Foss
And what kind of monitoring does a patient require after the
therapy?Chiang
Once the head frame is taken off and vital signs, so blood pressure
and heart rate are checked, and oxygen levels, if necessary, then
there is actually very little monitoring that is required, it is
the reason why it is an outpatient procedure, and people literally
go right home once they get changed after their frame is
removed.Dr. Veronica Chiang is an Associate Professor of
Neurosurgery and of Therapeutic Radiology, Director of Stereotactic
Radiosurgery, and Medical Director of the Yale-New Haven Hospital
Gamma Knife Center.  Dr. Jonathan Knisely is an Associate
Professor of Therapeutic Radiology and Co-Director of the
Yale-NewHaven Gamma Knife Center. 
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.