Dr. Miguel Materin, Diagnosing and Treating Eye Cancers
Welcome to Yale Cancer Center Answers with Dr. Ed Chu and Dr. Francine Foss. I am Bruce Barber. Dr. Chu is Deputy Director and Chief of Medical Oncology at Yale Cancer Center and Dr. Foss is a Professor of Medical Oncology and Dermatology specializing in the treatment of lymphomas. If you would like to join the conversation, you can contact the doctors directly. The address is canceranswers@yale.edu and the phone number is 1888-234-4YCC. This evening Ed and Francine welcome Dr. Miguel Materin, an Assistant Professor of Ophthalmology at Yale School of Medicine. Here is Ed Chu.
Chu
Let's start off with two questions, one is how common is a
diagnosis of eye cancer, and what different types of eye cancers
are there?
Materin
I am happy that you are asking that question because eye cancer is
a rare disease. I want to emphasize for the listeners of this
program that eye cancer is not common. Having said that, it
is important to know that eye cancer can affect any person at any
age.
Foss
What are the different types of eye cancer?
Materin
We can divide eye cancer into primary tumors, which means that the
cancer is from the eye, and secondary tumors, which means a cancer
somewhere in the body metastasized to the eye.
Chu
Are the types of eye cancer the same for say younger kids as
opposed to adults? Do we see the same spectra of eye cancers?
Materin
No, the most common intraocular cancer primary in kids is
retinoblastoma. The most common intraocular primary cancer in
adults is melanoma.
Chu
For this evening we are going to be focusing primarily on ocular
melanoma, but perhaps Miguel, you could tell us a little about what
retinoblastoma is, who gets it, and what age group?
Materin
Retinoblastoma basically has 2 types of presentation, it can affect
one eye or it can affect both eyes in kids. The average age
is about 1 year for kids with bilateral disease, which means that
both eyes are affected, and about 2 years for unilateral disease,
meaning affecting only one eye.
Foss
Miguel, how would a parent know that their child may have this
kind of cancer?
Materin
Thank you for asking that question. The most common
presentation is the white reflex in the center of the eye, either
with a flash or like from regular photography, or sometimes a
person notices that the pupil looks different or funny compared to
the other eye. I would say that white reflex in the pupil,
which is the black circle in the center of the eye, is the most
common presentation, and the second most common presentation is
strabismus.
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Foss
Is this picked up by the pediatrician in most instances?
Materin
A paper that was recently published said that the first person that
most frequently notes this is the mother, second the pediatrician,
third a grandparent, and fourth a father.
Chu
Typically then, the pediatrician gets the signals from the family
members and they would then refer the patient to an
ophthalmologist?
Materin
Yes, in general they will refer the patient to a pediatric
ophthalmologist because white reflex in the eye does not mean
absolutely it is a cancer, but it is very important to rule out
cancer because there are other conditions that can present with a
white pupil like cataracts, retinal detachment, and infections in
the eye or congenital anomaly, but the most important thing is to
rule out retinoblastoma because the patient's life is at risk. I
want to emphasize that in the United States 95% to 98% of these
kids survive this cancer.
Foss
Can you talk to us a little about how you treat it?
Materin
There are different modalities of treatment for
retinoblastoma. I am going to mention them not in order of
how often we use them, as all of them are important. Removing
the eye is always an option. Systemic chemotherapy is another
option. Sometimes we need to combine the chemotherapy with
laser or cryotherapy. There are new methods of treatment and one of
them is to provide chemotherapy through the ophthalmic artery so
that the child will receive less chemotherapy.
Chu
Miguel, you had mentioned there are other benign conditions that
can lead to this white reflex. I am just curious, are there
are any benign eye conditions that could potentially lead to
retinoblastoma or other eye cancers?
Materin
No, the retinoblastoma develops because there is a mutation in the
cells and this is extremely important and why kids with unilateral
disease, 90% of them only had the mutation in the cells in the
retina. When the retinoblastoma affects both eyes, that means
the mutation is present in every single cell of the body of the
patient and that puts the patient at higher risk to develop other
problems in the future.
Foss
Is this a genetically inherited condition, bilateral
retinoblastoma?
Materin
Yes, and it is dominant and the penetrance is about 80% to 90%.
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Foss
So, that means that other children in the same family need to be
screened carefully?
Materin
When we see a patient with retinoblastoma, we have to evaluate the
entire family, both parents and siblings.
Chu
Presumably you could also do a blood test to see whether or not
there is an alteration of the retinoblastoma gene.
Materin
Yes, the gene that we usually evaluate is chromosome 13 and it is
through a blood test. If we can have some tissue, which means the
patients eye has been removed, then we send that for analysis
too.
Foss
Are there other kinds of cancer associated with this retinoblastoma
gene?
Materin
Yes, and that is why I mentioned the germline mutation, which means
that all the cells are affected by these mutations and these
patients have a higher risk to develop second cancers or even third
cancers down the line.
Foss
How common is this familial retinoblastoma?
Materin
It is not common fortunately. It is about 1 in 15,000 or
20,000 live births.
Foss
We talked a little bit about the treatment for
retinoblastoma. How many kids are actually cured?
Materin
In the United States, or in developed countries, about 95% to 98%
of them can be cured.
Chu
Terrific, why don't we shift gears a little from retinoblastoma in
the pediatric population and discuss ocular melanoma. I guess
we always think about melanoma as being a very aggressive form of
skin cancer, but can you describe for us what ocular melanoma
is?
Materin
Well, the first point that we need to make is that melanoma of the
eye and melanoma of the skin act as different diseases. At
this point it has not been proven that melanoma of the eye is
related to sun exposure. However, melanoma in the eye is more
frequently present in the white population, with blue eyes, and
they are at high risk. That does not mean that every person with
blue eyes will have a melanoma in the eye. Again, this is a
rare condition. The incidence is about 6 persons in 6 million
that will have this cancer.
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Chu
Again, is the incidence of ocular melanoma highest in highly
exposed sun areas, regions of the United States and high sun
exposure areas around the world?
Materin
Eye melanoma can affect different structures of the eye. The
most common one is in the choroid, which is in the back of the eye,
and that area does not have a lot of exposure to the sun. If
we consider the eye melanoma also in the eyelid, or in the
conjunctiva, well the eyelids are part of the skin and that could
be related. The conjunctiva is less common and we have seen
melanomas present even in African Americans and Hispanics, even in
Asians.
Foss
Miguel we are now starting to see skin melanomas in younger and
younger people. Can you talk about the age distribution for
ocular melanoma?
Materin
That's an important question. Ocular oncologists all around
the world are working and trying to improve the patient's survival
for these cancers. It is a very difficult goal to be made
because we don't know how the melanoma will react. What we
have learned is that the eye melanoma is a systemic disease.
We think of the eyes as a different part of the body, but the eyes
belong to the body. I am saying this because we don't know
exactly when the metastasis, mainly to the liver, will
happen. We don't know at which point of the disease this is
happening. We are focusing, when I say we, all the ocular
oncologists, in trying to learn who is at higher risk to develop
metastasis. That is why it is becoming standard of care to
perform a biopsy from that little tiny tumor in the back of the
eye. With that biopsy, we send tissue for analysis, but this
analysis is not to study the cells, it is to study the DNA or the
RNA of that tumor, which will tell us how aggressive the tumor
is. Regarding the age population, it's more frequent in the
early 50s, late 60s, but again, whoever is in this field has seen
much older people and much younger people, we actually treated a
30-year-old lady last week.
Foss
How does an ophthalmologist notice this? What does the
ophthalmologist see during an exam that would make him or her
suspicious?
Materin
When we say ophthalmologist, we are talking about a general
ophthalmologist, and this is with the full eye exam. Some
patients have symptoms which are common symptoms like blurry
vision, floaters, and decreased visual acuity. Sometimes
patients don't have any symptoms and this is found in a routine eye
examination. So with a fundus exam, the ophthalmologist can
make or suspect a diagnosis and refer to a specialist.
Foss
In general terms, a patient would expect if they have a routine
ophthalmologic evaluation by a general ophthalmologist that this
should be picked up if it is present?
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Materin
If it is present, it is most likely going to be picked up.
Foss
Great. We would like to talk more about ocular melanoma when
we come back from our break. You are listening to Yale Cancer
Center Answers, I am Dr. Francine Foss and my co-host Dr. Ed Chu is
with me and we are joined by Dr. Miguel Materin, Professor of
Opthalmology at Yale School of Medicine.
Foss
Welcome back to Yale Cancer Center Answers. This is Dr.
Francine Foss and I am joined by my co-host Dr. Ed Chu and Dr.
Miguel Materin, Assistant Professor of Opthalmology at Yale School
of Medicine. We have been talking about ocular melanoma and we
talked a little bit about the diagnosis. You mentioned surgically
biopsying these tumors. Can you talk a little bit about how
that's actually done?
Materin
Yes. We plan a treatment, once the diagnosis is made, most of
the time clinically in the office. We take the patient to the
operating room with the plan already set for this tumor. The
different options of treatment again, if the tumor is too big or if
there are no chances for future vision, we remove the eye, which
means anucleation of the affected eye. Then we send the tissue for
analysis. The most common treatment that is performed is the
application of the radioactive plaque, and that is placed on the
surface of the eye wall in the operating room. That plaque, which
to give you an idea has a diameter of a penny, is placed using 2
sutures to hold that plaque and that will stay on the eye for about
4 or 5 days. Immediately before placing the plaque, we do the
biopsy using a very thin, tiny needle. What we send for
analysis may be 4 or 5 cells, and then the patient will stay in the
hospital for 4 or 5 days until the plaque is removed.
Chu
Miguel, can you clarify a little bit, does this plaque contain
radioactivity that's being emitted to treat the ocular
melanoma?
Materin
Yes. The plaque is made of gold, and within the plaque the
group from radiation oncology, they
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design the radiation dose and they place a couple of seeds with
radioactivity that will kill the cancer.
Chu
Okay.
Materin
Having said this, all these patients need future follow-up
examinations by general oncologists to have all the tests done to
rule out any spreading of that tumor, mainly to the liver or
lungs.
Chu
10 to 15 years ago, one of the treatment options was to give
external beam radiation therapy. It sounds like that's no longer a
favorite treatment option.
Materin
Some centers in the United States use what is called a proton beam
radiation. The response from the tumor is similar to the
radioactive plaque. There are some advantages and some
disadvantages of one over the other, and that depends on the
doctor's choice.
Foss
Are there frequent centers around the country that use proton beam
as opposed to this plaque therapy? Is it more common to
receive the plaque?
Materin
In the United States and worldwide the plaque is the most common
treatment, and there are, to my knowledge, 2 or 3 centers in the
United States that still use a proton beam.
Chu
And Miguel, is there a risk for loss of vision if one uses this eye
plaque or proton beam radiation therapy?
Materin
With any treatment that we perform to the eye that has a melanoma
in it, there is always a risk for vision loss. But I want to make
this important point, which is that in ocular oncology, we have
different goals. The number 1 goal is to save the patient's
life. Number 2 goal is to save the patient's eye, and vision
comes 3rd. Yes, we want to keep as much vision as possible
but our goal is to kill that cancer.
Foss
If patients have metastasis elsewhere in the body and they receive
chemotherapy, is that chemotherapy as likely to penetrate the eye
and to help to treat the disease there as well, or does
chemotherapy not get into the eye itself?
Materin
Chemotherapy for melanoma is a different topic because the
radiation will kill the cancer in the eye with or without
combination of some lasers that we use. If the metastasis is
already clinically observed by the general oncologist, that is a
different story, and there are different trials in the United
States and worldwide trying to extend the survival of these
patients. It is a very difficult situation.
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Foss
Even if a patient has metastasis, they are going to receive direct
treatment to the eye in addition to whatever chemotherapy they
would receive?
Materin
There are two points. Point number one is that at the time of the
diagnosis of ocular melanoma, less than 2% of patients will have
metastasis, clinical diagnosed metastasis. Point number two is what
I mentioned before, these days we consider a uveal melanoma as
systemic disease. So, together with medical oncology we are
trying to find ways to keep these metastasis under control if
we think, and if we agree, that they are subclinical, or already
there. We do not know what happens that triggers those
metastases to become clinically active and put the patient's life
at risk.
Chu
In general, if a patient presents with ocular melanoma, would you
recommend CT scanning evaluation to look at potential involvement
at other sites throughout the body?
Materin
I prefer the medial oncologist to make that final decision because
sometimes the patients are not from the town where we are
working. They are coming from some other distance, but in
general, what they need is a liver function test which is blood
work. They need liver MRI and they need a chest x-ray two
times or three times a year depending on the results of the biopsy
as I mentioned before.
Foss
Are there any blood tests, molecular tests, which could be done in
the blood that would help us to know whether a patient has
metastasis?
Materin
There is a lot of research about that, and what I can tell you, and
again this is changing almost every year, but the biopsy we take is
the main predictor. Again, in January 2010 the main important
predictor for metastatic disease is coming from the result of the
biopsy we perform in the operating room. Recently it was the
chromosome number 3, again within that tumor these days, there are
other tests like RNA analysis classifying these tumors into class 1
and class 2; class 1 being the better prognosis, and class 2 having
the worst prognosis.
Chu
Miguel, we have been talking about the eye melanoma spreading to
other parts of the body and we mentioned that the liver seems to be
one of the preferred target sites, but does the reverse
happen? Does skin melanoma ever metastasize and spread to the
eye?
Materin
The answer is yes. It is not the most common place for a
metastasis of skin cancer, and there are other cancers like breast
cancer or lung cancer that spread to the eye much more often than
skin melanoma, but the answer is yes.
Foss
In some cases, a skin melanoma may have completely regressed and
you find a patient who has
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metastasis. Could there potentially be a situation where an
ocular melanoma could have arisen from the skin? Can you tell that
with the molecular test you are doing on the tumor? You
talked about chromosome 3, for instance. Are there specific tests
to tell you that this came from the eye and not from the skin
originally?
Materin
Most of the time, I can say more than 90% of the time, when the
patient has skin melanoma giving metastasis to the eye the patient
already knows, or the doctor knows, that there is a metastasis
somewhere else. So it is very unlikely that the skin melanoma
will give metastasis to the eye only, or being the ophthalmologist,
the first one to make the diagnosis of metastasis from skin
melanoma; can that happen? Yes, but I think it is less than
5%, or 2% of the cases.
Chu
If a patient presents with an eye melanoma, what is the risk of
spread to the other eye?
Materin
It is very unlikely. There are publications and there are a
few, very, very uncommon syndromes that can put patients at higher
risk for uveal melanoma in both eyes, but it is published and there
are papers, I have seen them, but it is very, very unlikely. That
is a very common question that we answer for patients and their
family, and another important point to be clear about is that the
melanoma is not a hereditary condition. It is very unlikely
that somebody in the family will have melanoma in the eye.
Foss
If a patient is successfully treated for a uveal, or an intraocular
melanoma, are they at risk over the next couple of years? Are they
at risk for recurrence or are they at risk for complications from
the radiation treatment that they received?
Materin
The incidence of recurrences, which means the tumor coming back
after the treatment, is about 5% depending on the treatment that
were are using. When we combine the radioactive plaque with
laser, the chances are 3%. If only a plaque is used the
chances are about 10% for the tumor to come back. This means
that with the radiation, we can control a tumor within the
eye. The problem is that we do not know when these metastases
occur.
Foss
Effectively, patients are always at risk for recurrence?
Materin
When we see a patient with an eye melanoma, that is a patient with
us forever, or with the local doctor, or with whomever they
decide. Regarding your question about the side effects from
the treatment, yes they have a 50% chance more or less, depending
on location, size of the tumor, and amount of radiation received,
to have decreased visual acuity in the affected eye between 1 to 3
years. We have seen decreased vision before that, after that,
and we have seen patients who kept good vision forever.
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Chu
And Miguel, if the decision is made for surgical removal of the eye
melanoma, what is the role of eye implants after surgery has been
performed?
Materin
For resection of that melanoma we have 2 different ways. One
is to resect only the tumor and the other one is to remove the
eye. If we remove the eye, there is a profession called
ocularist and they can make an artificial eye that looks exactly
like the opposite eye.
Chu
Miguel, it has been great having you on the show this evening to
share your experience on eye cancers.
Materin
Thank you. Thank you for the invitation.
Chu
You have been listening to Yale Cancer Center Answers and we would
like to thank our guest expert Dr. Miguel Materin for joining us
this evening. Until next week, this is Ed Chu from Yale
Cancer Center wishing you a safe and healthy week.
If you have any questions or would like to share your comments, go to 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 from Connecticut Public Radio.