advances in the treatment of eye cancer webcast april 20, 2010...

Advances in the Treatment of Eye Cancer Webcast April 20, 2010 Bita Esmaeli, M.D. Jerald Wood Please remember the opinions expressed on Patient Power are not necessarily the views of MD Anderson Cancer

Center, its medical staff or Patient Power. Our discussions are not a substitute for seeking medical advice or care

from your own doctor. That’s how you’ll get care that’s most appropriate for you. Introduction Andrew Schorr: Although rare, eye cancer can affect people of all ages, and there are many different types that can affect your eye or your eyelid or surrounding skin, the orbit around your eye. Fortunately, there are leading experts that are finding ways to treat and beat this disease in many cases. Coming up you'll hear from an ophthalmologist and a patient that she's treated as they discuss how to identify and treat eye cancer. It's all coming up on Patient Power. Hello and welcome to Patient Power sponsored by MD Anderson Cancer Center. I'm Andrew Schorr. Today we're talking about a cancer that may not come to mind right away when you're thinking about cancer, it's less common, but certainly for the people who have it they want to get expert care, and that's what we're going to talk about today. Eye cancer. Now, when we say eye cancer what do we mean? Certainly we mean, could be, cancer right in your eye, but it also could be cancerous cells on the eyelid or in the orbit, the area that holds the eye. Now, this is pretty personal for me. My mother many years ago was diagnosed with cancer inside her eye, and we'll hear a little more about the different types, and she actually was in a clinical trial, and we will talk about clinical trials today, and she actually had a radiation plaque put right on the cancer, and it worked, and that saved her from losing her eye. Of course, if that can be avoided you do want to avoid that, losing your eye, and you want to preserve your sight. Jerald’s Story Well, let's meet someone who really things have worked out very well for, and that's Jerald Wood. Jerald Wood lives just north of Austin Texas. He's 84 years old. He's been married to LaVerne for just about 64 years, so you can imagine he's got a big family of children and grandchildren and great-grandchildren. He did have a health issue that many people have had, diabetes, lived with that, managing that with an insulin pump, but then about four years ago or so something else happened. Now you were going, Jerald, for regular eye checkups as you should for someone with diabetes. We all should get our eyes checked, but somebody with diabetes obviously you're watching that carefully. You went for that visit. What did the Austin eye doctor say?

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Jerald: The doctor was Thomas Chandler, and he because of the diabetes looked at my eyes every three months, and he noticed the irregularity in the eye, and he actually biopsied it and discovered that it was a melanoma type cancer and referred me to another ophthalmologist in Austin, Dr. Todd Shepler, and he immediately said that I needed to get to MD Anderson because he could not handle that type of case. Andrew Schorr: Now, one other point we might make right off the bat, Jerald, these two doctors, what did they fear would happen as far as treating that cancer? What did they think might happen? Jerald: They thought I might lose that eye completely. Andrew Schorr: Well, I'm happy to report that you didn't, and we're going to hear how. Now, that's your right eye. So you were referred to MD Anderson, made the trip to Houston which was well worthwhile, and you get connected with one of the leaders there, and that's Dr. Bita Esmaeli. Dr. Esmaeli is a professor of ophthalmology, and she's been at MD Anderson for well over a decade and is very involved in clinical research. Dr. Esmaeli, what type of cancer did you find with Jerald? Dr. Esmaeli: Jerald had what we call a conjunctival melanoma. Conjunctiva is the surface covering of the eye, and he had a melanoma located just above his cornea and it was just overlapping onto his cornea. It had already been biopsied, but we needed to surgically remove it. Surgery Andrew Schorr: Now, why would some eye doctors think that maybe you have to take the whole eye, and how are you able to not? Dr. Esmaeli: The decision to preserve the eye or not really depends on the extent of melanoma. I think in the majority of patients that we see we are able to with using reconstructive surgical techniques and also sometimes with judicious use of radiation therapy or topical chemotherapy to help in addition to surgery. In the majority of patients, I'm happy to say, we are able to preserve the eye and useful visual function.

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I think also it's important to note that conjunctival melanomas are really quite rare, so I think for most ophthalmologists they may just see one or two in their entire career, so the comfort level with being able to save the eye and doing less radical surgery may just be lack of comfort, may be a function of lack of familiarity in most cases. Andrew Schorr: Right. Good point, but so many cases like that of rare cancers are referred to MD Anderson, so just by definition you see more of it. Dr. Esmaeli: Yes, that's true. That's absolutely true. Because we have the multidisciplinary environment at MD Anderson I am able to more readily engage additional colleagues. If we feel like a conjunctival melanoma is too thick or too advanced and we may be worried about future occurrences we may be able to use radiation as a form of adjuvant therapy. And it helps to have other practitioners that are familiar with again this rare cancer, and we can put our expertise together and deliver the best care. Other disciplines that are important particularly for conjunctival melanoma are pathologists, expert pathologists that can evaluate the surgical specimen. That's really, really important because we get so much prognostic information from that surgical specimen. Andrew Schorr: Right. That's a good point for people. So one is the skill of the eye doctor, the surgeon, but also guidance from pathologists who have seen this before so that you can have a plan. Jerald, just for you, so in Austin you were being told you might lose the eye, you go to Houston, you see this expert team. They're able to not just save your eye but also save most of your vision, right? Jerald: Yes. I would like to make a little side note here because I feel that I was a lucky person because Dr. Chandler discovered the spot. He worked in the same office with Dr. Shepler's wife, who is also a doctor. So he and Chandler recommended I see her husband, Dr. Shepler, and Dr. Shepler knew Dr. Esmaeli personally, and he personally arranged for me to get the appointment with Dr. Esmaeli. And as I said I think she hung the moon, so that made me the luckiest guy on the street. Andrew Schorr: Dr. Esmaeli, you've got a boyfriend there in Austin. Dr. Esmaeli: Thank you, very much, yes.

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Andrew Schorr: So for our audience listening on the internet, obviously it helps, their personal relationships, but MD Anderson will take all comers and try to give you the best care. Dr. Esmaeli: Absolutely. And also I can perhaps clarify that I thought you were kidding me saying Mr. Wood is my boyfriend. He's actually one of my absolute favorite patients because I know how difficult it is sometimes it may appear for him to return to see me every three months because I want to keep a very close eye on his eye and aftermath of the surgery, but I think that Dr. Shepler, as a side note, was one of our former fellows. He did part of his fellowship training at MD Anderson as a rotation with me, and I think he got a firsthand look of what we do, the kind of the extent of disease and the types of melanomas and other eye cancers that we treat, and I think that is why he felt he was familiar enough to refer Mr. Wood to me. So I'm very pleased that it turned out that way. Andrew Schorr: It worked out. And we should mention, Jerald, you ended up, as so many people do, some at MD Anderson but sometimes in their own community, might have sort of cosmetic surgery to their eyelid that's sometimes beneficial after you've been treated, and of course Dr. Esmaeli does that for many patients, but you ended up having that in Austin and that worked out fine, right? Jerald: Yes. Actually, Dr. Shepler did that, but the eyelid actually drooped down over the cornea to the extent that it interfered with my vision. So I didn't call it-- Andrew Schorr: It wasn't cosmetic. It was functional. Dr. Esmaeli: Functional eyelid surgery, yes. Andrew Schorr: That's an important point. Dr. Esmaeli: Maybe I can explain what we do after removal of conjunctival melanoma. We actually replace the bare area with amniotic membrane grafts, which is really borrowed from placenta. But still that doesn't quite replace the normal conjunctiva, so there's sometimes scar tissue that may lead to droopiness of the upper eyelid, which I think is what happened in Gerald's case. But it was then corrected later by elevating the eyelid to restore the position of the upper eyelid after the conjunctival melanoma surgery.

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Types of Eye Cancer Andrew Schorr: Okay. Well, we're going to talk about other types of cancer. Let's go on because we said many of them are rare, but this is particularly rare. Maybe we should start with the eyelid. What shows up on the eyelid that would be cancerous? What would those cancers be? Dr. Esmaeli: So any cancer of the skin can essentially occur right at the eyelid margin. The eyelid is made of skin and muscle layer, and then the inside layer is made of conjunctiva and what we call tarsus that has lots of oil glands in it. So any cancer that can occur on the skin or on the oil glands of the tarsal plate can essentially be seen on the eyelid. So the most common ones would be basal cell carcinomas, followed by squamous cell carcinomas, and then in terms of incidence sebaceous carcinomas and melanomas. Of course basal cell carcinomas are the most common cancers in humans in general, and they can occur in the eyelid frequently because it's a sun exposed area, so we see that quite often. Andrew Schorr: And we've done programs on skin cancers, and it sounds like that's sort of what we're talking about here, skin cancers that are in the eyelid? Dr. Esmaeli: Correct, except that in this case it really presents unique challenges and also considerations in the sense that by removing the eyelid we essentially threaten the function and well-being of the eye and vision, so it's really important to not only try to achieve good surgical margins perhaps, as we do for skin cancer anywhere throughout the body, but it's also important to be able to reconstruct the defect in such a way that the eye is still functional. So it does present unique considerations and challenges when these cancers happen on the eyelid. Andrew Schorr: Doctor, let's talk about the next part of eye cancer. I guess you'd call it the periorbital location, so this is within the kind of bony area where our eyeball sits back. What kinds of cancers would these be? Dr. Esmaeli: Sure, this can be referred to as orbital or periorbital. So there are cancers that happen in the lacrimal gland, that is the tear producing gland that is located sort of on the top and outside corner of the eye, just adjacent to the eye, actually, just underneath the eyebrow. And cancers that happen in that area include lymphomas, adenocystic carcinomas, adenocarcinomas, and lymphomas are fairly low grade and treatable. There are lots of treatment options available, and usually

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the role that we play is establishing the diagnosis of lymphoma via biopsy and then patients go on to get radiation therapy or chemotherapy in collaboration with the lymphoma experts we have at MD Anderson. For other lacrimal gland tumors it really requires a multidisciplinary surgical team including ophthalmologists, neurosurgeons and sometimes plastic surgeons together to do a multidisciplinary surgical removal of the lacrimal gland. Sometimes we can preserve the eye and sometimes we do not. And then of course there are all kinds of cancers that happen in the paranasal sinuses that are surrounding structures around the orbit and then they secondarily involve the orbit. So in those situations probably the critical role we play is to try to be the guard for the eye. So we help other surgeons remove those tumors while we hope to still preserve the eye and the function of the eye. Andrew Schorr: Good point. Yeah, the guard to the eye and trying to protect that. Now, what about when the cancer, like in Jerald Wood's case, is in the eye itself? We talked about one type, his type of melanoma. What are other types? Dr. Esmaeli: The most common intraocular tumor in adults is a uveal melanoma. That's a melanoma that happens in the vascular plexus layer inside the eye. Andrew Schorr: And I think that's what my mother had. Dr. Esmaeli: I think so. It sounds like it from with what you described to me. So that's a melanoma. So the uveal track is made of the iris, which is sort of the colored part of the eye that you can see through the cornea. Like some people have blue eyes or green eyes, that's the iris. So it can happen on that structure, or it can happen on the continuation of the iris which goes inside the eye wall covering underneath the retina. And that type of melanoma again usually is discovered during a routine eye exam, or if it is really large it can actually present with visual loss or symptoms such as flashes of light or other, retinal detachment perhaps can be can be secondary to a uveal melanoma. For that tumor in particular, there are really three different treatment options. One is to remove the eye. The other is to do brachytherapy or plaque radiotherapy, which I believe is what your mom had. Andrew Schorr: Yes, she did, many years ago. Dr. Esmaeli: And then a third option is to use proton beam radiotherapy, and that is available at several centers including ours for uveal melanoma.

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Andrew Schorr: We're going to get more into treatments and tie it back to some of these cancers when we continue our discussion about eye cancer. We'll hear more from Jerald Wood, who is doing really well having been treated for his rare type of eye cancer, and we'll hear more from Dr. Bita Esmaeli, who is professor of ophthalmology at MD Anderson. It's all coming up as we continue Patient Power right after this. Treatment Andrew Schorr: Welcome back to Patient Power. Andrew Schorr here. This program sponsored by MD Anderson as we're talking about eye cancer with really a renowned expert, Dr. Bita Esmaeli, who is professor of ophthalmology at MD Anderson. We're going to talk about her research in a minute, which certainly people around the world have been hearing about, but we're also going to revisit in a minute with one of her patients who has done so well, Jerald Wood. He's from Georgetown Texas, just north of Austin. First, back to Dr. Esmaeli. So, Dr. Esmaeli, we kind of went through a number of cancers, of the eyelid, of the area around the eye, of the orbit, and of the eye itself. Help us understand the tools you have. Obviously, in extreme cases would be surgery and remove the eye. We hope that wouldn't happen for people. We heard about surgery with Jerald where you could take away some of the eye and in many cases replace it with some tissue. So surgery, would that be typical? Is that what happens most of the time, is some cutting of something, cutting it out? Dr. Esmaeli: Yes, I think that in a way we are very lucky that we can diagnose most eye tumors early enough to hope for a cure, and most cures are rendered by surgical removal or brachytherapy, in the case with uveal melanoma with plaque radiotherapy or brachytherapy. So in a way I think that our discipline is really quite neat as an oncologic discipline in that we can render a cure to the majority of our patients, and I think that's really exciting. But in addition to surgery in terms of different surgical options the challenge is to be able to do surgery, remove the tumors, bring cure but also have a functional and useful eye. So I think that's the challenge, and I think we are able to achieve that in the majority of our patients. But in addition to surgery we use of course radiation therapy and chemotherapy, which are the other two broad categories of treatment options for cancer patients. Andrew Schorr: Let me ask you about radiation for a minute. So we talked about one approach, which you referred to as brachytherapy. Some men may be familiar with it where there are seeds put in the prostate. So that's one form. Some women now have it for breast cancer where there's radiation put down in place sort of in a catheter for

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radiation there. So that's one way, with plaques put on where the cancer is in the eye. Then there's traditional radiation, external beam radiation. Now, that can still be used safely with the eye? Dr. Esmaeli: Yes, it is used in many instances for orbital tumors, orbital lymphomas, for meningiomas, which is a benign tumor of the orbit but it can cause quite a bit of visual morbidity in the eye, and it is also used for adjuvant treatment for advanced cancers of the eyelid and conjunctiva. It does have some toxicity associated with it, but in situations where the alternative is removal of the eye or removal of the orbital contents, which is even more than just the eye, the eyelids and the surrounding tissues, then if we can avoid that but offer radiation therapy with some toxicity to the eye that certainly is a very attractive option. And that is sort of a complicated multidisciplinary effort that really requires very close association between the orbital and oculoplastic surgeon for example and the radiation therapist. And I'm very proud of our multidisciplinary team especially for situations like that because it is unique to MD Anderson or places like this, essentially cancer hospitals where you have this opportunity for specialists to work together on individual treatment. Andrew Schorr: It helped me. I know it's so important. Let's talk about one other form of radiation which MD Anderson has been one of the early adopters of. It's at few places around the country. That's proton therapy. My understanding of proton, and you mentioned it along the way, is that the radiation kind of gets to a point and it stops. It doesn't like keep going, and I would think around the brain and around the eye that would be very helpful. Dr. Esmaeli: Yes, it is. It's exactly as you say. There is less of a toxic effect to the surrounding structures, so it's a more focused delivery of radiation therapy. IMRT is another focused delivery of radiation, but protons in particular is one that is useful for orbital tumors particularly in pediatric patients or young adults because there will be less of a scatter effect to the important endocrine structures in the brain and also less of a toxic effect to the eye itself, so it is a very useful additional radiation technique to have available. We currently use it for orbital tumors, and we are very close to being able to also use it for uveal melanoma, which is the intraocular form of melanoma. Andrew Schorr: Right. Let me ask you just about uveal melanomas. I understand there's a risk for people that even if it's successfully treated in the eye there's a risk that cancer may show up somewhere else, and you mentioned for instance even in Mr. Wood's case and his cancer, about coming back. Why do you need to monitor people so closely?

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Dr. Esmaeli: We need to monitor them for two reasons. One is the risk of what we call local recurrence, which is the potential for recurrence on the surface of the eye or inside the eye. That's true for uveal melanomas and also for conjunctival melanomas because when you think about it we do conservative surgery because we're trying to save the eye. For a disease as potentially aggressive as melanoma we really are in a way cheating by preserving the eyeball, by not removing the eye, so it is really important to do very close monitoring. I typically monitor conjunctival melanoma patients for at least five years. The same is true for uveal melanomas. Now, what is particularly challenging with uveal melanomas is that there is really no way to do early detection of metastasis, unlike for conjunctival melanomas. I'll get back to this in a moment because we have a clinical trial for that. But for uveal melanomas, since you asked that first, we essentially deliver treatment to the eye, whether it's removal of the eye or plaque radiotherapy, and then we are essentially in this wait and watch pattern until such time that the patient has really overt massive metastatic disease and usually in the liver. This is a unique pattern of metastasis for uveal melanomas, and at that point of course the treatment options are quite limited. So what we'd like to do some day is to find good targets for treatment of uveal melanoma and identify the high-risk patients and be able to in fact offer some type of adjuvant treatment after they get the eye treated rather than waiting until it becomes metastatic. So that's a situation unique to uveal melanoma. Andrew Schorr: Let's come back to conjunctival because I understand you have a trial and you've been leading research on that. Dr. Esmaeli: Yes. We can talk about that for conjunctival melanomas and really more broadly for any eyelid or conjunctival cancer that has the potential for lymph node metastasis, which is really the most common way these cancers spread is through the regional lymph nodes. For any of the cancers that do that, which is the overwhelming majority of the cancers of the eyelid or conjunctiva, we have trials that look for microscopic metastasis in the regional lymph nodes. In fact Jerald Wood had this done. It's called sentinel lymph node biopsy, and we have a clinical trial for this and for the last decade I've been very interested in studying this for eye tumors, and it's a way to map the first or the first few lymph nodes that drain the tumor, the cancer, and then we biopsy those and we look at them very carefully under the microscope to look for subclinical, really microscopic metastasis. That way we are able to offer treatment early on rather than again waiting until such time that the patient present with massive metastasis in their regional lymph nodes. And I really should give credit to several colleagues, and again this is just to emphasize the multidisciplinary nature of MD Anderson. I have been able to offer

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sentinel lymph node biopsy for our conjunctival and eyelid cancer patients because I work very closely with a surgical oncology colleague, Dr. Merrick Ross. And head and neck surgeons, I'm going to mention Jeff Myers, Dr. Jeff Myers in head and neck surgery. And then of course folks in nuclear medicine that help us map the sentinel nodes prior to surgery. So it's really an attempt to find early microscopic metastasis, very analogous to when sentinel node biopsy is done for breast cancer or other more common cancers. Andrew Schorr: Now, one area of treatment that maybe comes in here but with or without showing in the sentinel node would be chemotherapy. So I know you can give cancer-fighting drug in eye drops and then I would guess particularly if it shows up in sentinel node, the question is should you have systemic therapy, like I had for leukemia, where I had it through an IV and it went all around my body. So chemotherapy is an approach as well, right? Dr. Esmaeli: Yes. For ocular surface cancers we use chemotherapy drops in the form of an eye drop, and this is especially compounded for our patients and it's usually a couple of different drugs, mitomycin C or 5-fluorouracil. They are mixed in an eye drop, and we use it usually for conjunctival tumors, and this again would be an attempt to avoid more drastic measures such as removal of the eye or even sometimes as a step before we do radiation treatment. Again, all of these efforts are to try to preserve the eye and its visual function. But for certain cancers, for example lymphoma, lymphoma of the lacrimal gland or orbit, which is in fact the most common primary orbital tumor in adults, chemotherapy often is used, either standard cytotoxic chemotherapy or monoclonal antibodies, rituximab and drugs like that that are targeting B cell lymphomas. Those are used then for orbital and eye tumors similarly to when it happens in other locations. Andrew Schorr: Now, you used a word I just want to follow up on, and that is "targeting" the tumor. So we're entering more and more the age of what we all call personalized medicine, certainly in cancer care, trying to understand the exact genomics, I guess it might be, of one person's particular cancer. Where do you see that headed related to some of these cancers that have been difficult? Like the uveal one you mentioned, I know the survival has been tough to move the needle on that. Where can genomics play a role, and what's MD Anderson doing? Dr. Esmaeli: Yes, I think that is the one eye cancer that really deserves a lot of attention in that area. Historically, uveal melanoma patients gets their eye treated, whether it's by removal of the eye or radiation therapy, and regardless of what we do for their eye tumor about 50 percent of the time they get liver metastasis, and that's very, very difficult to treat. To what we really need to do is find out, number one, who is

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going to get liver metastases, and there has been some progress made in that regard. There are now genetic profiling and chromosomal studies that can pretty well identify who is going to get metastasis, but unfortunately we still don't have any drugs or treatments to offer the high-risk patients. So one of the areas of active research for us is to harvest fresh tissue from patients who are going to have the eye removed anyway because of the tumor characteristics. We study the tissue from patients to do specific mutational analyses to find out if there are targeted drugs that can be used some day for them if they develop metastatic disease. I think this is sort of the general term used is the genomics and the proteomics of specific tumors. So we are doing that by taking their tissue to the laboratory and studying it and also by trying the newer drugs in cell cultures, uveal melanoma cell cultures, to see what drugs might have potential for this. Hope for the Future Andrew Schorr: One thing that's clear to me as I listen to this, Jerald, I'm sure you'd agree. When I listen to Dr. Esmaeli, I hear that she's quite the specialist researcher and that there's a team around her and that if someone is diagnosed with one of these cancers of the eye they might well, if they can, certainly have a consultation or maybe ultimately treatment or participate in research at MD Anderson. It worked for you, right, Jerald? Jerald: Yes, it did. Anyone with cancer should head for MDA. Andrew Schorr: I say that all the time. I did from Seattle. Dr. Esmaeli, you used the C word, and I don't mean cancer, I mean cure, early on. So there are people listening who are diagnosed with cancer of the eye, and they're really scared, and there's not a lot of information always around and certainly not some of the latest that you've been giving us today. Now, I know every case is different, but it sounds like in some of these cases there actually is a hope of a cure. Dr. Esmaeli: Absolutely. And I really feel very lucky to be able to contribute in that way. I think the overwhelming majority of our patients indeed are cured if diagnosed early and if treated appropriately. And I think the overwhelming majority of them also keep their eye. Yes, we have to reluctantly remove the eye sometimes, but I think that in terms of sheer numbers, the overwhelming majority are cured and are able to have a useful, functional eye despite all the treatments that we do. So that's very exciting. I feel very fortunate that if I have to work with cancer patients, which is incredibly gratifying, it's really a privilege to be able to indeed have patients that are cured, whether it it's with surgery or other modalities we talked about.

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Andrew Schorr: Thank you for all you do. Jerald Wood, is there anything you want to say to your doctor here publicly? Jerald: Well, I think I got the best one. Dr. Esmaeli: Thank you. Thank you very much. Andrew Schorr: And you have to say that about LaVerne, your wife of, what, 64 years too. You did that too. Dr. Esmaeli: Absolutely. And I have to say Mr. and Mrs. Wood are just the example of wonderful patients that really put up with our recommendations. I think when you get diagnosed with cancer the first thing that happens is you're shocked and you're traumatized but I think then there comes an acceptance point, and I think they are just a perfect example, despite the travel inconveniences back and forth to Houston from their home town, I have to say this is the win-win situation because they have put up with our recommendations with the close monitoring. And I'm really happy to say that Mr. Wood not only is free of his melanoma but also has a useful, functional eye, and I feel really confident that we've done it right in his case. And I think it takes two. It doesn't just take the doctor but also patient contributions are really key, and I'm really grateful to both of them, to Jerald and LaVerne for being amazing patients. Andrew Schorr: Well said. Well, it does take a team. Dr. Bita Esmaeli, professor of ophthalmology, very devoted of course at MD Anderson, thank you so much for being with us. Dr. Esmaeli: Thank you. Andrew Schorr: And, Jerald Wood, I hope you keep enjoying your yard work and your computer work. It takes vision of course, and really I hope you'll have a lot more years with LaVerne and all the children and grandchildren and great-grandchildren. Thank you so much for being with us, Jerald. Jerald: Thank you for the opportunity.

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Andrew Schorr: This is what we do on Patient Power, and I'm always bowled over by not just the great doctors and inspiring patients but the teamwork among them, and you hear that with Jerald Wood and Dr. Esmaeli today. I'm Andrew Schorr. Remember, knowledge can be the best medicine of all.

Please remember the opinions expressed on Patient Power are not necessarily the views of MD Anderson Cancer

Center, its medical staff or Patient Power. Our discussions are not a substitute for seeking medical advice or care

from your own doctor. That’s how you’ll get care that’s most appropriate for you.

advances in the treatment of eye cancer webcast april 20, 2010...

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