Diagnosis and Treatment of Mesothelioma Webcast June 9, 2009 Anne Tsao, M.D. Kathy s Story

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1 Diagnosis and Treatment of Mesothelioma Webcast June 9, 2009 Anne Tsao, M.D. Please remember the opinions expressed on Patient Power are not necessarily the views of M. D. 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. Kathy s Story Mesothelioma is a rare form of cancer that affects the lining around the lungs. It can be around the heart, around the abdomen. Typically, it's caused by exposure to asbestos, and the incidence of this type of cancer is rare, but it's also on the rise. We're going to hear from a leading expert from M. D. Anderson and an inspiring patient next on Patient Power. Hello and welcome to Patient Power. I'm Andrew Schorr. This program is sponsored, like so many we've done, by M. D. Anderson Cancer Center, where we connect with you leading, often world-renowned experts. We're going to do that today as we learn about a condition that some of us just see advertised in legal ads on television, and that is mesothelioma. It's a rare form of cancer. It affects the lining around the lungs, sometimes around the heart and in the abdomen, and it's typically caused by exposure to asbestos that may have been 40, 50 years, decades earlier, and then it develops, and people have a variety of symptoms that we'll learn about. One person who found herself affected by this is Kathy. Kathy is 54, she lives in Lumberton, Texas, down the road from Houston to the east. And she was having breathing problems, really beginning in February of 2008, and then June it got really bad. Kathy, tell us, how bad did your breathing become? It became so bad that I could barely walk across a room without having to sit down. Oh, my. It was very bad. And I did have some pains in my chest. But you were gasping for breath.

2 I was gasping for breath. All right. Now, you'd been going to the doctor for months, your primary care doctor. Right. And you were being treated by antibiotics and cough medicine, but it kept getting worse. So finally, I understand, you were admitted to the hospital in Beaumont, Texas, and they do the various exams, biopsy, including the lining of your lungs, and it comes back with this disease I mentioned. Had you ever heard of mesothelioma before? Only on TV. Like the legal ads we were talking about. So you knew it was something that maybe you needed to go to a major cancer center for. What did you tell them in Beaumont? I told them that I just wanted to go to M. D. Anderson, that that's where I needed to go, and my doctors in Beaumont agreed. So you got to M. D. Anderson and they saw you right away? Yes, they did. So you I end up being given a clinical trial medicine. Did that help? You know, there was some still of the gasping. Right. I can understand. Well, you eventually had surgery, major surgery, which we'll learn about. And it took a while to recover. I know you were in the hospital a couple weeks. So here we are now, months down the road. How are you doing today? 2

3 So much better. So very much better. I still sometimes overdo, I still have problems breathing, but it's just, you know, I have to sit down and recover. But I just feel much better. Going to M. D. Anderson I've learned so much, and I know what to look for. You think it was a good choice? Yes. Oh, definitely. Often the prognosis, if you will, when someone is diagnosed with a condition as serious as mesothelioma is not good. Do you feel like you're with us in part today and doing as well as you are because of M. D. Anderson? Yes. Yes, most definitely. And they were honest with me, you know, about mesothelioma, and that it very likely would come back. And I know that, I realize that, but I'm fighting as hard as I can. Incidence and Causes of Mesothelioma Well, good for you, Kathy. We're delighted you're with us. Let's meet your key physician now, and that is Dr. Anne Tsao, and she is an assistant professor of thoracic, head and neck medical oncology at M. D. Anderson, and she's known really around the world as a leading expert in this condition. Dr. Tsao, thank you for being with us. Let's help people understand. We say this condition is rare. How rare is it? Yes, Andrew. Thank you so much for having me on the program. So the incidence of mesothelioma is about 3,000 new cases per year in the United States alone. Out in other areas of the world is incidence is even higher. And we talked about asbestos. So what is it about asbestos which had been used so much in construction, the automotive industry, in older buildings. What is it about asbestos that would cause this condition? And then why does it take decades to show up? Well, that is actually a million-dollar question that we would all like to know. The exact molecular mechanisms are still as of yet not elucidated. The problem is that over time the asbestos fibers, when you inhale it, stay in your body. It causes 3

4 irritation of the lining of either of the lung, the lining around the heart, or the in the lining around in the abdomen. And what it does is it induces genetic changes, the whole sequence of events. But because this spans decades, for instance, the median time from exposure to the time this disease presents is about 32 years, but it can actually range anywhere between 15 years to even 50, 60 years. So because the time frame takes so long we still don't know what the exact genetic changes that occur and what sequence of events happen in order for us to be able to specifically target those changes by therapy. Symptoms and Diagnosis What are the typical symptoms, and how can they be confused with other things? It is actually a very confusing disease when a patient first presents because symptoms are very nonspecific. Oftentimes they are fatigue, shortness of breath. Also some patients describe weakness and lack of appetite. But when you actually do a chest x-ray many times patients who have an earlier stage of the tumor have just fluid around the lung, what we call a pleural effusion. And this can be mistaken for pneumonia, other types of lung cancer or metastatic cancer from other sites of the body. So how do you get an accurate diagnosis? Well, it's very important for physicians to be very aware that this is in the differential for a patient like this and that they would refer then if there is any concern that this could be a cancer and it's not an infection to a major cancer center that does specialize, not only in thoracic malignancies but especially in mesothelioma. All right. So we heard how Kathy came there. Good idea. And I say time and time again, I mean for my leukemia that I was treated for I found out M. D. Anderson, I'd never been to Houston before, I live in Seattle, was the largest leukemia clinic with specialists for my leukemia, CLL, so I went there, and I'm glad I did. When people are typically treated, I understand, and in Kathy's case, I just want to check with Kathy. Kathy, you were told in Beaumont first that with mesothelioma that there wasn't much they could do for you. How long did they say you had to live? They told me around six months. 4

5 Okay. So you said, I want to go to M. D. Anderson, then the oncologist who was brought in agreed. Doctor, so that's what people are told around the country. What can you do at M. D. Anderson that maybe is not done typically everywhere else? Part of the issue of bringing awareness is that there is hope for patients with mesothelioma. There are clinical studies now in every single setting being offered in mesothelioma at M. D. Anderson as well as a very large translational program that is actively investigating new targets for therapy. We have over 30 physicians from all the different multidisciplinary groups, by that I mean surgery, radiation oncology, pulmonary, thoracic medical oncology, as well as radiology, that all specialize in mesothelioma. And we take a team approach to every patient that comes in through the door. We also have research nurses as well as LVNs, as well as mid level providers that are all very familiar with this disease, and in fact often support our mesothelioma program. So on top of the clinical research effort we also have the clinical expertise at M. D. Anderson. And certainly for a patient with mesothelioma because this disease tends to be more rare, I believe that out in the community they don't have the resources that we have to treat it. And so for us we definitely do believe that patients with mesothelioma can certainly exceed the median survival of six months. Treatment Options Now, Kathy mentioned that she had surgery, and we've had her surgeon, one of your colleagues, Dr. David Rice, on a program related to lung cancer as well. So surgery is usually a key part, but it takes a whole multidisciplinary team. And there are different types of surgery, and I would imagine surgeons like Dr. Rice are more experienced at doing them as well, so that comes into play. Without a doubt, yes. Help us understand the type of surgery. I know in Kathy's case, Kathy, I think you have one lung, right, now? One lung was removed, correct? Right. Help us understand what's done with the surgery, when a patient is up to it, Doctor. 5

6 Yes. So there are two main types of surgery to remove the tumor. There are other lesser surgeries but these are the two main ones that are utilized. One is called the pleurectomy/decortication, which is not what Mrs. Evans had. The pleurectomy/decortication just essentially debulks the tumor. It sort of tries to peel it off of the lung. And as you can imagine, this tumor, it grows all around the entire lung and can often invade into the diaphragm and the pericardium. The diaphragm separates the chest cavity to the abdominal cavity, and the pericardium is the lining around the heart. Now, surgeons often throughout the United States are familiar with this because this is a procedure that's also done for lung cancer, not just mesothelioma. The other surgery, which does I believe require extensive expertise and certainly should only be done in the hands of surgeons who are familiar with doing this procedure for mesothelioma, is called the extra pleural pneumonectomy, or the abbreviation that we use is EPP, and this is what Mrs. Evans had. Now, this is a huge surgery that can take up to ten hours, so again you want to be in very, very experienced hands. And what they do is not only do they remove the tumor but they also remove the lung as well as the lining around the heart and also portions of the diaphragm. And then they reconstruct everything. And after the surgery it's also very important to have a radiation oncologist who is familiar with mesothelioma treating you because surgery needs to be done with adjuvant radiation in many cases. Now, it was a little bit different for Mrs. Evans, which I think we can get to a little bit later, but for many patients radiation is very crucial to their treatment. Yeah, Kathy was saying that she's been told, I guess by Dr. Rice, that she might have radiation later, and that personalized approach I understand is so key. Help us understand where drug therapy comes in. It used to be that mesothelioma was not treated with systemic therapy or drugs, and the reason for that is that it was very resistant to many agents. Now, this was with chemotherapy in the past. And then in the early 2000 era, 2003, there was an agent that was used with an old chemotherapy, cisplatin, and this agent was called pemetrexed, and what it showed is that there were patients who were sensitive to this drug. So it taught us that chemotherapy can be utilized in this tumor type and can achieve benefit. And with that said now there is a huge movement to try to find targeted agents or novel therapies to try to use it against this tumor type. And I do believe that eventually we will be able to find targeted agents that will work for treating this disease and make it into a chronic illness and then ultimately find a cure for it. 6

7 Clinical Trials But, as you mentioned, you have many research studies going on, including one that I guess Kathy has been in, studying all that, but hopefully maybe giving some people a short at tomorrow's medicine today. Absolutely. And that's why I can't emphasize enough that I believe if you have a diagnosis of mesothelioma you should be evaluated for a clinical trial that provides not only the standard treatment, whether it's chemotherapy or if it's surgery and radiation but something on top of that with one of these new targeted agents. These targeted agents are being designed to try to hit protein pathways in the cancer cell that the mesothelioma tumor cells rely on in order to grow, divide, invade and travel to other parts of the body. Now, you're at ground zero, and one of the astronauts, if you will, of really the leading edge of science in this disease. Do you feel there's a gap then in what you know and what your team know at M. D. Anderson and what someone might be told at a small hospital or doctor's office around the country or maybe even what they look up on the internet? Oh, I've been told by so many patients that come here that they were given no hope whatsoever back at home, and this is why I think it's critical that all patients with mesothelioma be seen at a major cancer center that specializes in this disease. Now, we do have a very large program at M. D. Anderson, in fact, it's one of the largest in the United States, that specializes in this rare tumor type. And what makes us even more unique is not only do we have the clinical research program but we have a very active laboratory-based program as well because we're trying to find a cure for this tumor. That sounds good to you, doesn't it, Kathy, find a cure? Oh, definitely. All right. We're going to take a quick break, and when we come back we'll hear more from Dr. Tsao, more from Kathy. This is all part of our program understanding this rare cancer but also giving people a lot of hope. More from Patient Power and our M. D. Anderson sponsored program right after this. 7

8 Welcome back to Patient Power as we continue our program on mesothelioma. It's kind of like tomato and tomato, you can pronounce it a couple of different ways. But no matter what, it is a serious condition, and as we're hearing, you want to get to really a leading research center where they have a multidisciplinary team and also give you the chance, if you want, and I would recommend it, to participate a research trial because we're trying to have a much better outcome. And Kathy Evans who joins us from Lumberton, Texas has been doing well. She had major surgery, which we just learned about, and she has been in a clinical trial and doing better. Kathy, you were saying you kind of thank your lucky stars that you really did push as a powerful patient to get to such a center, in your case M. D. Anderson. Yes, I am. And I feel like if I had not pushed it that I would not have found out what it was. And I landed over there with two of the best doctors at M. D. Anderson. My surgeon, Dr. Rice, and Dr. Tsao is just wonderful. Asbestos Concerns Now, there is still a lot of investigation going on, but in your case I know you've worked in the school district around the Beaumont area for many years, maybe 30 years, and you're retired now. Do you look back on working in the school district maybe many decades ago and you're pretty sure there was asbestos that you were exposed to? Oh, definitely, because when they came back, I don't really remember exactly how it was done, but they came back and said that all this asbestos had to be either removed or taken care of. The school district, they just went in and covered it back up. It was not removed. Dr. Tsao, so if somebody maybe felt they worked in a field or were in facilities or homes, and, Kathy, I think you had told me you grew up in a home where you think there was siding made with asbestos, right? Yes. Okay. So if somebody was in that situation, Doctor, what could they do proactively to be followed by their primary care doctor or whoever their provider is to try to spot it early? Now, you can tell us whether early diagnosis makes a difference, but we certainly know that getting an accurate diagnosis makes a difference. 8

9 Well, absolutely, early diagnosis and accurate are critical for a patient's chances at beating this disease. Now, the problem with mesothelioma is we don't have a blood test yet that is FDA approved that will tell us whether or not you have mesothelioma. And chest x-rays and chest CT scans done on patients who do not have the disease have never been shown to help prevent this or improve on the survival of people who end up developing the disease. Now, there are in development some blood tests that are being looked at right now, but they aren't available for commercial use right now. They are currently in research studies. So it may be that eventually we will have something that can be used. What a patient can do right now is stay healthy. Have a very healthy lifestyle. Get their yearly checkups with their primary care physician. If they develop symptoms such as shortness of breath, a cough that doesn't go away, or if they've got chest pain, such as on the chest wall pain, that does not go away, they need to see their primary care physician. They need to be evaluated, and that may require a chest x-ray. If they have fluid in their chest they will require what's called a thoracentesis, which is removal of the fluid, and an evaluation for either cancer cells or bacteria for infection. If there is any hint at all that this could be a potential cancer they need to just come right away to one of the major cancer centers for an evaluation. Great specific advice. Now, we've received some questions by , and I wanted to pose some to you, Doctor. Gerald from Cypress, Texas tells us that back I guess over the last few years his wife, they've been renovating and remodeling a home that was built in 1960, and they've been sure that it had asbestos. He says, "My exposure has been somewhat limited. I'm very concerned. I cut four to five pieces of asbestos siding, drilled about 20 holes in the siding and shutters, tore off about 18 to 20 pieces of siding and replaced it with new non-asbestos siding." And his question is, "What sort of exposure can cause damage that leads to this disease?" Do we have any knowledge? We don't have any specific knowledge that we can say whether or not his exposure was relevant to him because it isn't just the amount of exposure. It is also the person. For instance, some people may be more susceptible to developing mesothelioma because of their genetic makeup. We know, for instance, that there are several villages in Turkey as well as in China where patients often develop mesothelioma at a much higher instance that even lung cancer because there is a genetic predisposition towards developing the tumor. Now, this is just specific in those specific ethnic populations, but I wouldn't be surprised if later on we were to discover certain genes that might make you more susceptible to asbestos. Now, Kathy, you have a brother, right? 9

10 That's right. Okay. But his breathing has been fine. Right. But he grew up in the same house, didn't work for the school district though, right? No, he didn't. Okay. So, Doctor, let's say the house was a factor that they grew up in, should he be followed more closely? So if you have a first-degree relative, I guess my question is, does that make a difference, or is it more that you think you had direct exposure? How does someone know whether they should be followed more closely or disclose that to their doctor? What I would say is that he should definitely have yearly checkups with his primary care physician, and he should disclose to his physician that his relative, immediate family member, in his case, Mrs. Evans, does have mesothelioma. And that way his physicians will be more alert to look for any specific signs or symptoms that are concerning. Cutting-Edge Research and New Treatments Okay. Good point. Now, we've gotten some other questions, but I think you've mentioned them. Jeff from Kansas City, Missouri, asked about clinical trials for this condition, and the answer is definitely yes. There are a bunch of them, right? Yes. We actually have clinical trials in every single clinical setting for mesothelioma, and some of the clinical studies that we have done have been directly grown out of laboratory discoveries that we've made at M. D. Anderson. For instance, we identified that there is a protein called SRC kinase that is up-regulated in this tumor and can regulate making the tumor cells more aggressive. So we have a drug called dasatinib, which Mrs. Evans was on for a short period of time, that actually targets SRC kinase, and we give this in the surgical setting before to test sensitivity of the tumor, and in patients that are sensitive to the drug they then get it for two years for free after their surgery. 10

11 Wow. And that's just one trial. That's just one study. Yes, we have several others. So the idea, so when somebody comes to M. D. Anderson, and as Kathy said, she was seen in two days and saw the whole team and Dr. Rice and eventually had surgery. Tell us what goes on behind the scenes in your group assessing what are the individual needs, kind of the plan that you would recommend for a patient. Because everyone is different, right? Absolutely. So when they first come in through the door we usually are alerted, the mesothelioma focus group, which consists of close to 30, 33 physicians. We're alerted that a mesothelioma patient is new to our institution and, we usually have one of our research members, whether an LVN or an RN, speak to the patient to find out if they would be willing to provide a sample of blood for us for research purposes, because, again, we're trying to look for that cure. So we will ask every single patient that walks in through the door with mesothelioma whether or not they would give us a very small tube of blood while we check their baseline laboratory values for them. And so that is actually archived away for research purposes. Now, after that the patients will either go first to either surgery or to medical oncology, and it doesn't really matter which way they go. It's first available. Now, if a patient obviously has very limited disease they'll probably go to surgery first, but because we are very closely connected, we always communicate with each other. We have three different research nurses that all specialize in mesothelioma clinical research trials that just get called on the phone, and then they'll bring all of the appropriate studies that the physician feels would be relevant to discuss with the patient in the clinic that first day that they're here. Now, sometimes a patient does need to have additional studies before we can offer them a clinical trial, and that will require radiographic evaluation, blood work, as well as potentially a pulmonary evaluation with one of our lung specialists. And once that's been done some patients may require an additional biopsy, in which case that may be done either through our surgery group or through our interventional radiology group, which is also very familiar with mesothelioma. And then once those studies are completed we get a final team approach. And usually a patient has also been seen by medical oncology, surgery and radiation oncology all at the same time then during that period of time. We put our heads together and we decide on the best course of treatment for the individual patient. And then depending on what setting, whether it's a surgical setting or whether it's a nonsurgical setting, the patients will then be offered either the clinical studies that 11

12 are appropriate, or if they wish to go home we will always work with the patients and their local medical oncologist. So oftentimes we will actually fax the treatment recommendation to their physician at home if they don't wish to stay for a clinical trial. Kathy, it sounds like you have quite an extensive team on your side, doesn't it? Yes, I do. I feel very safe with them. Doctor, so it sounds like then if this condition is suspected for somebody, and as you said even lung cancers are of course common and very serious, too, people want to get with the right team and have it evaluated. It seems like having the right treatment plan right from the start is important. You don't want to get off on the wrong foot. Without a doubt. And with mesothelioma there are three different histology subtypes which I didn't mention before, but we're learning now from the laboratory that each of these subtypes is unique and should be treated differently, potentially with different targeted agents. So it's also critical that you have a pathologist who is very familiar with this tumor type who can make the distinction between the three different sub groups of mesothelioma. So that's also what's offered at a multidisciplinary, large cancer center program. Right. I often talk on our programs about the art of medicine as well as the science. So we have all the science you're learning, but then we have the experience of people like you, like the specialized pathologists you were just mentioning, and I don't think we patients often understand that, that it's not just about the numbers or what's on an x-ray or CT scan, but it's also on the opinion. It makes so much difference. So a rural or even a community hospital or a non maybe major NCI cancer center might not see this very often. How often do you see patients with this condition? Quite often, actually, now. We see a couple hundred patients at M. D. Anderson per year, and certainly we know that out in the community they may, for instance, see only one patient a year, if that. Wow. It makes so much difference. Doctor, so I just want to wrap up with you. It sounds like while the typical information that somebody might be given is, You may just have months to live. With the work that you and your team are doing and your 12

13 colleagues at major centers around the world you're obviously trying to cure it but also give people hope of a longer life and a higher quality of life like Kathy is having and that that's becoming real for people. Absolutely. And perhaps one of the biggest points that I really would like to emphasize is that if a patient has a suspected mesothelioma please send them right to us. Because oftentimes out in the community they'll attempt to treat but their treatments then make the patients ineligible for clinical studies. Or they'll do a procedure called a talc pleurodesis in a patient that may have been able to get a surgery, but by them doing the talc pleurodesis they may make them no longer able to do a surgery, specifically the pleurectomy/decortication, and thereby they can't get on to some of these clinical trials. So it's very important to just send the patient directly. Don't try to treat them at home. There is hope for these patients, and that's going to involve enrollment on the clinical studies. Obviously there are people listening to us around the world and they say, gee, but Houston. You know, for Kathy it wasn't too far, but other people say it's a long way. I've never been to Houston. I'd never been to Houston before, but yet this is the fight of somebody's life, and you want to bring the best expertise and research to bear. Absolutely. And we actually have a social worker that works with us for mesothelioma patients, and if you are interested in a clinical trial we certainly work with you to get Angel Flight. We try to help with accommodations as well as with your travel to try to make it easier for you so that we can help you. Right. Because if you're having trouble or gasping for breath the idea of just going far afield at all seems daunting, but it could be lifesaving. And it can certainly be expensive as well, and we are very cognizant of that. Our social work team is fabulous, and we try to help you with that. Dr. Anne Tsao, thank you so much for being with us and bringing your expertise out here where we can spread the word worldwide on Patient Power. I want to get a last word from Kathy. Kathy, so what's your hope for the future? I know you're obviously still living with the condition. You know it's not cured at this point. There may be radiation in your future, and certainly you're making your trips to M. D. Anderson but it sounds like with a great team. How do you look towards the future? 13

14 I think that my cancer right now is in remission. I don't know that, as far as being told that. Hopefully we'll find that out in July. But I'm going to live and work with this disease and fight it as long as I can. And I do have a couple of spots that they have found on my right lung, but they have not grown or changed in size or anything like that since last October. But they do watch that carefully. Well, Kathy, I wish you all the best. It sounds like you're pretty hopeful but also thankful. I am. Very much so. Very, very so. M. D. Anderson is the place to go. I say that, too. I say that, too. Kathy Evans from Lumberton, Texas, thank you so very much. Dr. Anne Tsao from M. D. Anderson, thank you for being with us, too. Thank you. This is what we do on Patient Power time after time. I'm so delighted to connect with experts like Dr. Tsao and inspiring, truly inspiring people who are powerful patients, like Kathy Evans, who said, I'm going to M. D. Anderson, and I want to go where there's expertise in what I've got, and you've heard how it has made a difference for her, and it's making a difference for others, too. Thank you so much for joining us. 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 M. D. 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. 14

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