I am Julian Schink and I have the privilege today to share with you some of my experiences treating women with ovarian cancer and Gynecologic cancer. I have to let you know that I've taken some artistic license here and have included some other Gynecologic cancers as examples of women winning this battle against cancer. I'm not going to spend this whole time talking about just typical ovarian cancer. I'm also going to talk about some unusual cases and I'm going to talk about some examples of just wonderful human spirits overcoming this disease. The reason for this title is that I'm going to tell you about women who are winning this battle. One of my biggest frustrations as a Gyn oncologist is that there are so many negative messages suggesting that we can't win this battle. We can win this battle. I acknowledge we don't win it every time. But there is hope, and we are going to talk about why there is hope and what some of the key ingredients are, from my side of the battle as a warrior in this battle with you, to succeeding. So, if you talk about my heroes, and you all are my heroes, I know that you, everyday, manifest courage and brave deeds. If you look at the definition of courage it is in fact what you face. The quality of mind or spirit that enables one to face difficulty, pain, danger and do that fearlessly. At this time when there is a lot of rhetoric about brave deeds, and we recognize that there are brave men running into burning buildings and risking their lives, from my side of the world I see a huge number of brave women taking on these battles and doing it with more courage than anyone could ever describe. Believe me this young woman is waving her own flag.

Who are the ovarian cancer victims? I know most of you don't want to be characterized as victims, and maybe that isn't the right word, but there are a lot of losses that go along with this disease. I want you to know that we as Gyn oncologists are trying to recognize that and trying to appreciate that and realize the impact of this disease. And, it isn't while the patients are suffering. I can't tell you how often when I see a woman newly diagnosed with ovarian cancer, and her daughter is sitting next to her, which is so often the case, I can tell that right then, even before we've started down this road, she is more concerned about her daughter sitting next to her. She's asking that question. Is she going to follow me down this road? So, certainly, families and all of the upset that happens to families during this battle is a consideration. Siblings, parents, it's very difficult. This is a disease of women in their 40's and 50's who still have mothers alive in their 70's and 80's who have to deal with what's going on, and that is very difficult. In communities, and I'm going to show you today some examples of incredible community spirit. I live in Wisconsin and one of the wonderful things about living in a place like Wisconsin where there are 2,000 little towns is like there are 2,000 little families all caring for each other. So I will show you some examples of that.

What are some of the key ingredients? This isn't meant to be entirely a spiritual discussion, although spirituality and faith are critical components. Each of these key elements is not mandatory. It's not requisite. You can overcome this battle without any of these elements, but each one may make the fight easier and give you better odds of winning. So, faith in a higher power, yourself, and your health care team. That is critically important, that you believe in your health care team. When I see a new patient with ovarian cancer, newly diagnosed ovarian cancer, I share with her right up front that this is a battle that we are going to wage together. I'm in it for her and that I'm very aggressive, and it will come out as we go along that I'm very aggressive about my battle against ovarian cancer. We are going to work together. If she or her family doesn't want to be really aggressive and be in this together, then we ought to look at other strategies or other people to do that.

It takes courage. There is no question it takes courage to face death and press on. It takes courage to except adversity, which in our case adversity really means toxicity, and know and accept that it is often along the path to recovery. I wish that wasn't so and I think that over the last decade we've made strides to decrease the adversity, but it's still there. It takes great courage to accept the indignities and depersonalization that our health care system has. I heard, as you were asking questions, there was sort of this wave building of, why is it that with some of the resources like clinical trials, we keep going back to the major medical centers, back to the teaching hospitals, and that's great. One of the great things is that you have better access to clinical trials in those teaching hospitals, and you have medical students and residents, and you say the same thing twenty-five times over and over and over again. There is a depersonalization that comes with this. I have to thank you for putting up with it, but to let you know in my mind that is part of the courage.

Motivation is a factor and there is no question that you have to want to do this. You have to have a reason to live and a reason to thrive. I will share with you some examples of that as we go along. And support is so important. Whether it be from your friends, your family, your spouse, partner, or your community. This journey can seem incredibly long and difficult without someone there to help.

I'm going to start by showing some slides for a few minutes and this is a tough. If you have a queasy stomach or whatever, and you don't want to look at nasty pictures, don't look. If it's pink up there, don't look if you don't want to see what ovarian cancer looks like. I have found that it helps some people to visualize the enemy.

What is the enemy? The most common type of ovarian cancer is what we call epithelial. It is a silly name and it doesn't have any thing to do with epithelial as it relates to skin. It's just the class that we put the most common ovarian cancer in.

The types. The most common type is serous or papillary serous. There is also mucinous, and endometrioid and clear cell. That is what you hear about most often. There are some other types of ovarian cancer and I will show you examples of one of those called germ cell tumors and these occur in younger women. Between the age of 10 and 30. They are generally quite curable and in one study 93 percent of the women treated for germ cell tumors were cured. That of course leaves 7 percent of the women not getting the best outcome, which is unfortunate. Lance Armstrong had the male version of a germ cell tumor. And as those of you who may have read his book know he even had brain metastasis but he was cured.

Stromal cell tumors have names, such as granulosa cell tumor and Sertoli-Leydig cell tumor. They are rare and usually less aggressive, and I'm not going to spend a lot of time talking about this.

So here's the enemy that we are talking about. This is a picture of ovarian cancer from the surgeon's view. So this is what the surgeon sees when the abdomen is open. The feet are this way, the head is this way. That's the uterus right there with a fallopian tube coming this way and a fallopian tube going that way and these are what we call implants. So if your doctor ever talked about implants, these are implants on the bladder, sort of gluing the bladder there to the uterus. And here is a portion of the ovarian tumor on the rectum right there, the white material that looks like cauliflower growing. Now, I acknowledge this may look a little crude but when we do a hysterectomy we actually grab onto the uterus, on each corner like this with these clamps and lift the uterus up. But we grasp the uterus and lift it up and here now you see what we call, cul-de-sac with implants back here on the corner of the uterus. This ovary is pretty normal in this patient. That's a normal small white ovary and fallopian tube there and on this side, there's actually, you can't see if very well, but this is all a big tumor kind of coming off the side of this ovary here. You hear about omental cakes and tumors in the upper abdomen. So this is now turned around looking towards the patient's head. Her head is up here. This is all the small intestine, which is fairly normal in this patient, and this is, that's the colon right there, and this is an omental cake. A big white chunk of tumor right there. That's what we are fighting against.

If you talk about ovarian cancer in the United States there are in the range of 27,000 cases each year. Unfortunately, almost three-fourths of women with ovarian cancer present with Stage III or IV disease. Now one of the dogmas, and this is sort of my own personal bias in this, there is a lot of talk about how we have to move from here to there and will improve survival, because in this group of women the survival is around 85 percent. For women in the long-term who never have it come back, for this group of women it use to be 20 percent but I'm going to say it is closer to 30 percent to 35 percent of women never have it come back, but we still have a long way to go. I personally don't believe that our best strategy is to insist on moving from here to here. I think our best strategy is to prevent all of this. And the reason I say that is that a large number of these women start with a tumor on their ovary. When it's very small it already has spread to the omentum and other places. I personally believe that most of these are a different disease than the women who have it start in their ovary. That is why we have not succeeded in using Ca-125 as a marker, because if it started on the surface, Ca-125 is not going to help you. There may be a place for markers. The markers that are going to eliminate these diseases are the ones that tell us when there is a precancerous change or such an early change on the surface of the ovary that we can take it out before it spreads all over the abdomen. Those are the markers that we need, and there are colleagues that are working hard on finding those. But when they find them we aren't going to talk about going from here to here, we are going to talk about preventing the whole disease.

Does ovarian cancer debulking play an important role? Absolutely. There's terms we use like bulky disease and optimal disease which now people call less than 1 ½ centimeters, no visible residual disease and how long people are likely to live is really closely tied to which one of these groups you end up in. And which one you end up in is very closely tied to whether or not the person operating on your cancer is going to push to take it out. Now it is true that there are some people that no matter what you do you can't get that cancer out. But in most expert centers where you have Gyn oncologists, 85 percent of women can be at least optimal. And in many centers this number is running at least 50 percent. So, our goal as Gyn oncologists has to be to get all the visible cancer out. And your goal, if you're a patient is to end up at a place where someone has that attitude, because it is the only thing that we can affect. The chemotherapy people are given in the United States is pretty much the same wherever you go. It is the same drugs made by the same company. But the human factor here is how hard you work to get that cancer out. If you go to someone who isn't committed to it then it's not going to happen, and it makes a difference.

Here is what we call a survival curve. So in this study done by SWOG 100 percent of the people are alive here and here at six to seven years, in this study 65 percent of women were still alive five, six, seven years later. I know that those aren't the numbers that you generally have been hearing, and this ties back to a question that someone asked in the last group. What is the role of consolidation therapy? Well, in this SWOG study these are the women who finished, had aggressive surgery. They went on to clinical trials. When they finished their clinical trials they had no evidence of cancer on a CAT scan, they had normal Ca-125s, and then they participated in a SWOG trial where they were given six months. In this study it was twelve months of altretamine. In the other study it's twelve months of Taxol. In both of those studies though it is impressive it begins to make a difference. I personally believe that we will find a place for consolidation therapy. We haven't figured out what the right drugs are and what the right strategies are and who benefits most. What I do know when we look at this is that it's starting to get exciting now. When I started in this business fifteen years ago there were no survival curves that had 50 percent, 60 percent, 70 percent of the people living. Now I acknowledge that we've got to push that up higher, but we are beginning to make some in roads. Now it's a highly selective group of people, but it's beginning to look like we are making a difference.

So how can that be? This is a very difficult slide. I show this to medical students and they all start getting sick. For medical students this is like chemotherapy. It makes them upset and they get sick. Bare with me. It might surprise you to know 10 to the 9th cells. That is, a billion cells is our clinical limit of detection. And a billion cells are only the size of 1 centimeter in circumference. So when we are giving chemotherapy and trying to eliminate this tumor we do a great job of getting rid of the drug sensitive tumor, but we don't do a good job of getting rid of the drug resistant tumor. There are tumors that are still there. And the part of this whole business that we as Gyn oncologists and as scientists have not yet figured out is what is the part of that drug resistant tumor that survives when the chemotherapy is done, that flips the switch and says it's okay to grow again. Because if it grows fast, then you have three months before your cancer comes back. If it grows slow you have three years before it comes back. And we don't know what that switch is. But we do know it's different in different people, and we have to find the drugs that work on that little switch.

Now, people talk about consolidation therapy and they say, "Oh, well maybe it works because it's suppression. It's just a way of holding that tumor down." So in the Taxol consolidation trial the curve is shifted over seven months, they got nine months of treatment to move that curve over seven months. Well. Is that good, bad? If it's a well tolerated therapy it's not the end of the world. For other therapies though the consolidation therapy, and this is the goal, is to either completely eliminate the tumor or alter it's growth so it takes fifty years to come back, so that basically it takes longer to come back than you're going to live, which hopefully is 50, 60, 70 years. That's one strategy that people are looking at. We have a long ways to go before we figure that out.

Now I'm going to switch gears. This is what I came to talk about. Stories of faith, courage, motivation, support. These are my patients. These patients have all given me permission to tell these stories. I asked them. I tell them that, "I'm going to tell a whole bunch of people about you," and they are all for it. They want to spread this message. I'm very close to these patients and sometimes it's very hard for me to talk about. If it's too hard I will just stop.

The first person I want to tell you about is a person named Ann. She was 46 years old in 1994 when she was diagnosed with a high-grade metastatic endometrial stromal sarcoma. Ann was a 5th grade teacher with three of her own children. One child was in college and the others were in high school at the time. Her daughter was very traumatized by this. Actually her oldest daughter was in college but she dropped out during this. She had twenty-five of our children that she was also taking care of-including my own children. She is a teacher in my son's school. So, they were all counting on her to come back, but Ann didn't come back. Because Ann never left the school. She worked throughout her chemotherapy. She was on a regimen that's call MAID and it's one of the hardest treatment regimens that we give. She would come to the hospital at night and get this treatment and go back to school. She would come in on the weekends and she'd go back to school. She'd lost all her hair and she just kept going to school.

Along the way the school supported her, her friends supported her. She had faith. There was no question. She relayed that to me many times over. She had incredible courage. Her family was there with her. As I said her daughter dropped out of school to just be there and help around the house and look after her dad and all that stuff. People don't believe that these treatments work. I am here to tell you that they do. This is a CAT scan of Ann's lung in February of 1994. I want you to look at that. That is a big old tumor in her chest. This is her CAT scan a few months ago. The same place, it's gone. Not only do the treatments work, but they last.

This was even more difficult for us. Here is Ann's liver, and this again. This is the liver right there, that's the heart. It is all dark because that's the lungs. This is the liver sticking up sort of towards the lungs. That big black ugly spot in her liver is a tumor. It is gone. It is still gone. Nine years later Ann is alive and well. She moved up from the fifth grade to the sixth grade. It has been a battle. Ann had four surgeries to get there. She had thirty radiotherapy treatments, twelve different cycles of chemotherapy, and I noticed when I was making this slide the other day that she has had twenty-six CAT scans. That is a lot of CAT scans. Her faith is clearly stronger than ever, and so is mine by the way. She is and serves as a beacon of hope and courage, because since she went through this, three other teachers in that school have been diagnosed with cancer. Two of them with breast cancer and they have had to undergo chemotherapy, and she has become, in our community, a critical source of support. Her three children are grown now and starting their own families. They got on with their lives as well. Any time I need someone to come talk to a patient that has metastatic carcinoma and can't believe treatments work, she comes on a moments notice and visits with those patients.

Switch gears here. Kelly came to see me. She is tragically a single mother. It's hard to be a guy when you hear stories about what happened to Kelly. When she was seven months pregnant her husband came home. This was her first pregnancy. Her husband comes home one day and says, "I don't like being married anymore," and boom he is gone. So in her seventh month of pregnancy she moved from northern Wisconsin back to her hometown close to Madison. She had her baby and she started raising her baby and she needed a job. When her baby was about nine months old, and she had not been working very long at all, maybe six months at the most, she was having really irregular bleeding. She went to her family doctor. He did a pregnancy test and the pregnancy test was positive. The doctor said you're pregnant or you're having a miscarriage or something.

She said, "Well you know the guy left when I was seven months pregnant and there is no other guy. I don't think this is divine intervention and I'm not pregnant." So low and behold she had a very rare cancer called choriocarcinoma, which is a consequence of pregnancy, and she had metastatic disease in her chest. She came to see me alone in my office while her family was watching the baby at home. I told her that I thought she was going to be all right when she came in. She looked me right in my eyes and told me, "I know I'm going to be alright. I have to be alright for my little girl." She clearly had the motivation to do well. She had courage and she had strength. She faced chemotherapy every weekend alone. She would come into the hospital on Friday. She too worked while on chemotherapy. Her family would watch her baby girl. She was such a delightful person. The nurses would fight for the opportunity to take care of her. They would say, "Is Kelly coming in, is Kelly coming in." Amazingly, the employees at the factory that she worked at, and she'd only been there a short time, all donated their sick leave so she could keep getting a full paycheck. True community support. She is alive and well. And so is her little girl.

Now some of you who have been to some of these ovarian cancer programs before have heard Meg speak. Meg is a dear friend of mine. I want to share with you her odyssey, which is particularly a compelling story. This is a picture of Meg with the quilt that her family made for her in the background. You will notice on that quilt those are the hands of her family that she wore during her treatment. At age 38, Meg, then a law professor at UW with two small children, was told that she had a dermoid cyst in her ovary. So the supposedly benign cyst was taken out by her well-meaning Gynecologist in a bunch of pieces through the laparoscope, but to the surprise of everybody, including Meg, it was found to be an ovarian cancer. That's not the way you are supposed to take it out. Not in a bunch of pieces, not a Stage I tumor. That increases the risk of it coming back.

So with the support of her family, Meg went all over the country asking people what to do. That was her first odyssey. The people around the country said the same thing. You're done having kids, take the ovaries and the uterus, get staged and dah, dah, dah. She did all of that, but despite that, nine months later Meg showed up in the hospital with a blood clot in her leg which had traveled to her lung, what we call a pulmonary embolus. A CAT scan that was done to evaluate why that happened revealed an 8 centimeter tumor in her liver. A biopsy of that tumor in her liver showed recurrent ovarian cancer and it looked just like the tumor that had been taken out.

She had six cycles of three different chemotherapies after that. She had a clear cell carcinoma. Clear cell carcinomas are bad actors. They cause blood clots in the legs and they don't respond very well to chemotherapy. She still had the tumor in her liver. Here is Meg's CAT scan after all this chemotherapy, and that black spot right there is her tumor that would not go away. Her odyssey continues. Meg wants a new liver. She's a pretty compelling person for those of you who have had the privilege of meeting her. The problem was that about two months before this Mickey Mantel had gotten a new liver. Now he needed a new liver because he had too many Budweisers, but at the same time he also had cancer, and I don't think he even got out of the hospital from his liver transplant.

So, our transplant team was not interested in finding Meg a new liver. One of Meg's friends, a well-meaning supportive friend from California sent her a newspaper clipping, and it says, "Cryosurgery Cures Liver Tumors." She shows up in my office with this little clipping. We look at it and talk about it and I said we've never done this. We looked at how to get it done. Our surgical oncologist was actually willing to do this because it was an evolving therapy then, and it's much more of a standard treatment now for people with colon cancer. In 1994 it was really quite new. Meg's response was, "The chemo's not working, so what in the world do I have to lose." I even said to her, "You could die during this surgery," and she said, "That's not so bad. I can't stand the thought of sitting here knowing this thing is in my liver and growing and you don't have a treatment that works. I have nothing to lose." At that time our program couldn't quite figure out how to take care of her, so she just continued her odyssey. She flew out to L.A., met the guy who the newspaper article was written about and a week later she had her liver frozen. Not like Ted Williams. She had her liver frozen just a little bit.

Who do we do this to? Who benefits? I'm cautious, I don't want to impart false hope here. Who benefits from what we call secondary cytoreduction? Another surgery to get rid of cancer. First of all, there is no benefit if you do it right after your first chemotherapy, if the chemotherapy didn't work very well. That's what Dr. Miller showed us many years ago. But, if you have had a long period of time, like twelve months of progression free interval, and you have an isolated site of disease, and we know you can get rid of all of the tumor, people benefit. The other group of people who benefit are people who have very slow growing tumors. I could stand up here all day and tell you about people who have slow growing tumors that we go in periodically and take out. They also benefit.

Now Meg didn't quite fit the rules though. She had an isolated site of disease, although we didn't know that for sure, and we didn't know for sure if it could be completely removed. She didn't meet this criteria, and in fact she met this criteria, so there was some question if this was the right thing to do. But, she's 38 and she kept saying to me over and over and over again, "What have I got to lose?" So here is her liver tumor, 2.8 centimeters in diameter at the upper part of the liver. Now, here it is. That says right there, June 13, 1995. A big hole in her liver. When I saw her at this visit I was very upset. I said, it's back and it's bigger. So we stuck a needle in this thing and all it had was a bunch of dead old cells in it, no cancer. Amazing. Here is Meg's liver, September 22, 2000. The hole filled in, Meg's still around.

After that Meg vowed to dedicate her life to helping patients. There is no question about this. She said, "I'm not doing that lawyer stuff as a lawyer teaching the law students." She was the Associate Dean in law school for a while. In 2001 she started a program at UW called The Center for Patient Partnerships, and she works as a patient advocate in our hospital. She speaks to ovarian support groups. She's truly a beacon of hope and she will go see anyone of my patients who is questioning why in the world we are doing chemotherapy, or whatever other treatment, just to remind them that you can overcome this battle.

The last person I want to tell you about is Amanda. If I can, this is hard for me. Eighteen-year-old Amanda is facing a very difficult battle with Stage IV dysgerminoma. In the last seven months she's had thirty-two days of chemotherapy. She has been in the hospital more than 50 days. She is not giving up. She's not giving up at all, and neither is a town in northern Illinois that she lives in called Pecatonia. Her community just gave her a check for $25,000 that they raised to help her with her medical bills. They did a fundraiser where somebody donated a car, a new car, and sold raffle tickets for $10.00 each. That's Amanda in front of the car. Here is a picture in the paper of Amanda getting a check for $24,590.00. You might be able to tell, she's crying. She has a twin sister and that brings along with it some difficult sibling issues I assure you. On Super Bowl Sunday she was in the hospital. I took this picture of her. She clearly has faith, courage. She's motivated. She has an incredible support system to wage this battle. I'm not positive I'm going to win this battle, but I have all the help I can ask for in waging this battle to see if we can help Amanda.

I want to finish by just thanking you all for your courage and support, which inspires those of us on the treatment side to do everything we can to win this battle. Thank you.

David Mutch: Thanks Skip. We are going to have two short talks on quality of life. Dr. Bethan Powell, University of California - San Francisco, and then Vivian von Gruenigen from Case Western. Then we will get some lunch, which will be out here, and then I figure we can come in here and ask questions while we eat. That would probably be the smartest way to do this, and then we will just answer questions until we get tired. If you're too tired we can go. The guys from Canada have a whole list of questions so it may take awhile.

We have to go study before we can answer them. By preface of my talk I just wanted to say two things. First is, if you felt very overwhelmed by the first session you should be. I actually came to listen because as a Gyn oncologist we don't get to have these people as our captive audience altogether in that kind of format. It was really an opportunity for me to hear them. I think it is also a tribute to the sophistication of many people that are here that this was what you asked for last year, kind of not the puff and the icing, but really to struggle with novel therapies and vaccine and what's available and really to have very important questions.

The second thing I wanted to say, and I think Skip Schink alluded to this-somebody also asked the question about, their wife had symptoms and why didn't the doctors hear. There was a study done where one of the Gynecologic oncologist went out and submitted a survey to patients with ovarian cancer, and it's always been our belief that ovarian cancer was a silent killer. What they found out when they submitted that survey to the patients is that it was not silent. Patients did complain before their diagnosis. So the message is, "listen to the patient." Unfortunately some of the symptoms are vague.

"Listen to the patient" became a theme of mine in this research. Not only that, but I had the opportunity to participate in a clinical trial as a patient which was a randomized trial between participating in an intensive twelve week long, six hours a week complimentary medicine program during chemotherapy versus the randomized arm which was to do nothing. I randomized to the intensive complimentary medicine arm, and that is where my interest started. I found that other patients were doing incredible things with complimentary medicine. They were doing just massive amounts of stuff. Trying to figure out what stuff was worthwhile to do, what wasn't worthwhile to do? The expense of all this stuff was overwhelming. As a way to start as a scientist to investigate these ideas, I thought these patients really needed to know some science, and there was very little. As a scientist the first thing I did was to ask the patients. So, we formed a group, and this is kind of an unusual group, but it is a group of myself, as a Gyn oncology surgeon, a Ph.D. in nursing, Sue Dibble, who has been very active in breast cancer research and in complimentary medicine research, Joe was a student at the time, and Isaac Cohen is the Director of Acupuncture and Herbal Medicine in Berkley in northern California.

Interestingly enough we started with the idea, we are going to ask all of these people what they are doing for complimentary medicine. We had a pilot and a survey that we had made up, and in order to test the survey we had to ask a small group of patients to take the survey. What we found was there was a belief in medicine that patients wouldn't tell their doctors what they were doing on the side that they wanted to keep a secret. We believed this. Well what we found when we asked these five patients-we were exhausted. We couldn't get off the phone, we were there for hours. Some of my patients were calling to volunteer, and other people heard about it and they wanted an appointment. They were mad that they couldn't get to tell us everything they were doing. Because we were becoming exhausted we didn't think it would be a very feasible survey. So, we decided to focus just on herbal medication. The purpose of the study was to explore which herb medicines patients with ovarian cancer were using.

We identified 113 patients in three years of my practice. Fifty patients ended up being eligible and 41 of these 50 agreed to participate. This is a big slide, but basically the only differences between patients who used herbs and didn't use herbs, and you'll notice 51 percent of patients did use herbs, but the only differences in characteristics was they were younger, and this was significant. They also had higher Ca-125 most recently. That would be something worth exploring but perhaps patients who are using herbs are patients who, maybe, have a more serious battle with cancer, and that explains why their Ca-125 was up. Their Ca-125 at diagnosis was not different. As I mentioned, 21 patients or 51 percent reported using, now these are medicinal herbs. We asked about 35 herbs. The total number of herbs reported were 31 different herbs. The average number used per user was 6, and the range was 1 to 24. So some people were using 24 herbs simultaneous, at quite a cost per month. Only one patient used herbs instead of chemotherapy and there was only one harmful effect or side effect and that was a very minor one that somebody reported, and that was an increase in hot flashes.

This is a list of the herbs used. The most common was Gensing. Other frequent ones were garlic, ginger and also soy. We asked about medicinal soy, not just increasing the soy in your diet.

They used it for different reasons, cure. There are a number of herb uses. So, some of the herbs were used for a cure. Most were used for the immune system or symptom management, which is probably a pretty appropriate way to use herbs. However, we did find that 30 percent of the uses that patients said was, "I used Gensing for cure," and "I used garlic for energy." 30 percent of these uses didn't correlate with the known or accepted use that the herbalist or acupuncturist published in the lay literature. So patients weren't always using it in an accurate way. When we looked at the timing you'll see 41 of the uses was both during and after the chemo, and another 27 was during chemo. The point here is there was a lot of use during chemo, and there is very little study done on the interaction between medicinal herbs and chemotherapy. There have been some recent reports of side effects of herbs contributing to bleeding in surgery, affects on the liver, and it may actually be, it works better with chemotherapy or could harm chemotherapy. We have no idea. Patients are using it with chemo.

Now 5 out of the 41 patients reported using an herbalist or any health practitioner, an acupuncturist, a Chinese medicine doctor, somebody who had some credentials. Only one patient used a medical doctor and that was a psychiatrist who ordered St. John's Warts for depression. But, this is consistent with other national studies which say that patients do not consult any quote, "expert," and I think that that explains why a lot of the uses of these herbs didn't correlate with any known use. It also raises the question of what doses were being used, and if the expert wasn't somebody who knew about this stuff, the expert was usually somebody in the health food store or in the grocery store, or wherever.

About half told their oncologist. Of those, almost all of them initiated the conversation. The reasons why they wanted to know were very rational. They wanted to insure that the herbs didn't interfere with the chemotherapy. They wanted to know the affects of the herbs. They wanted to have more information about the herb. All the patients who informed their oncologists reported being dissatisfied with the response from the oncologist.

So, the conclusion from this first study was that the majority of ovarian cancer patients from the bay area do use herbs. That many do not consult a health practitioner. That medicinal herbs were commonly used during chemo, and that the medical oncologists were not documenting the uses. I think that's very important, because as we learn more about these uses, there very well could be interactions. And finally, it was very clear that oncologists were not viewed as particularly open and helpful in this area.

So having concluded that patients used this stuff we then went into the lab. And again, with a collaborative group who are working in complimentary medicine, we began to study the affects of herbs on ovarian cancer cell lines. So this is in a dish, it's not in vivo, it's called in vitro.

We tested 16 herbs, and our laboratory looked like some sort of marijuana manufacturing factory, which is great for pictures at national meetings. We had all these jars with twigs and leaves and we smushed them all up and made teas. Each of the herbs had been given to us by an herbalist who is an expert in Chinese medicine. He had gone over with a panel of Chinese herbalist and picked the ones that they thought were most appropriate, that would be recommended concoctions to their patients. Now, one of the things that we wanted to do was take complimentary medicine and try to apply scientific method to it. One of the problems and the weaknesses in this study is the way Chinese doctors use herbal teas. It's used over time, so it's a three month long term effect, and it's used usually using multiple herbs at once. That's very hard to study scientifically because one of the scientific methods is you change one variable at once. It is also individualized. Acupuncture points are checked, and this is added to this and so on. This was the best that we started with.

The herbal tea was prepared using water extraction, just like a tea. We tested cell survival using a fluorescent assay where the more it lights up it represents the more alive cells. And we looked at cell death. There is a feeling that the way that chemotherapy works is by exploding the nuclear DNA and causing fragmentation.

The cell lines that we tested, and this is the dilution at which 50 percent of the cells were killed as compared to the control. So there was 50 percent less lighting up. And the dilution of the tea means that if you had really strong tea, where it was like all herb, really concentrated, it might be 1 to 10-so 1 herb to 10 parts water-so these were working with just 1 part herb in 450 parts of water. The more activity of the herb, the weaker the dilution it's effective at. This was a specific herb tested. It was 1 out of the 16. It is called Scutellaria barbata. It worked. It was cytotoxic in 11 of the 11 ovarian cancer cells, and 50 percent of breast cell lines. So, oops, that was Camomile. I'm probably short on time so I will summarize this graph.

This graph is a control. As you can see, up here is 80 percent cell survival and you always lose some cells in the Petri dish from the beginning. This is increasing dilution, weaker and weaker tea, and a control should be flat. So this is the control in red, and this is an ovarian cancer cell line, which is treated with Scutellaria barbata. You can see with stronger teas you get a lot of killing, but even as you weaken or dilute the tea you still get killing up until a very weak tea. So, that says this is active in a Petri dish to kill ovarian cancer.

So here what we showed is that with increasing boiling time there was increased activity. So here this represents new activity or cell death, and the longer we boiled the tea the better it came.

So in summary from this work, what I basically want to tell you is that some of the herbs, Scutellaria barbata, did have activity in cell lines. It's important that it was only active in dividing cells, because cancer is a dividing cell, where as a lot of the normal cells in the body are not dividing. We were able to begin the extraction process of what the active agent in this tea is. We do know that it is activated by heat, that it's not a protein, and that's bigger than a certain size. We are trying to identify what exactly it is.

For our future direction with this work, what we are going to try to do is standardize, one of the problems with herbs is, you know, you take your weeds and your sticks and your leaves and you smush them all together, so potentially the sticks could be stronger than the leaves. It's not very scientific. It would be nice to know what the active agent is and then we could purify it and then we could give it to people. The most immediate thing we are looking at now is looking at cytotoxicity with Taxol and carboplatinum. So what might it be like for the patient who is drinking tea with chemotherapy, and then we need to start doing it in mice, and eventually, hopefully, as you heard today, with clinical trials. We would like to take this to a clinical trial. One of our other problems, it's really hard to drink this tea. It's really nasty. Thank you.

Bethan Powell: There is very little out there. I think it reduced the toxicity of Taxol. I can't remember what the herb was. Most definitely we all need to become more sophisticated. People ask me in San Francisco, "Couldn't I do natural, something natural," well, Taxol is natural, but herbs aren't. I honestly don't know if they are good or bad. My point, instead of putting several millions of dollars in this stuff, it would be really nice to take that money and put it into a clinical trial that might work, or put it into an herb that might work. Let's find out.

Good afternoon. My name is Vivian von Gruenigen. I am a Gynecologic oncologist at University Hospitals of Cleveland, Case Western Reserve University. This afternoon I'm going to correlate a little bit of information on quality of life, nutrition and lifestyle issues in women with a Gynecologic malignancy. I'm going to start very broad, but at the end of the talk you'll see why I'm starting so broad. It is amazing how women with cancer aren't necessarily taking an active process with their nutrition, and they are not changing bad nutritional habits. They're not even eating what the American Heart Association and the American Cancer Society recommends for five servings of fruits and vegetables a day.

We know that cancer is a multistep process. But the question is, what does diet have to do in the role as a promoter of cancer? Of course the obvious factor that we went over this morning is genetics. Other factors include geographical and environmental. We all know that tobacco increases the risk of lung cancer. So, what about ovarian cancer? Is there any correlation between nutrition and ovarian cancer?

Approximately one-third of the half million of cancer deaths that occur in the U.S. may be due to dietary factors. Of course this can be related to environmental, such as tobacco. There have been dietary correlations with pancreatic disease and colon cancer. So the question is, what about ovarian cancer?

What has been observed in the literature is that there are geographical variations in the rates of ovarian cancer between Europe, Japan and the United States. What some of this research has shown, not just in ovarian cancer, in other cancers, is when certain ethnic populations immigrate to a westernized society, then they adopt the same risk or a similar risk for the development of certain cancers. The question is, why does this happen? There are worldwide differences in ovarian cancer rates between countries. As other countries are becoming more developed , their incidences of ovarian cancer are also on the rise.

The research in Gyn malignancies and nutrition is sparse. Some of the epidemiological studies suggest that milk may be a component; however, others have isolated this out to enzymes and others believe that milk may just be related to the fat product. Others have suggested saturated fats increase the risk of ovarian cancer. And there is some epidemiological research that suggests that when you increase your intake of vegetables and fruit that your risk may decrease.

There are also case control studies. Daniel Cramer has studied the fat component of milk the most and has shown that there is a possible modest association between the saturated fat and ovarian cancer. This is of debate and was actually presented at the GOG last year when Dr. Cramer spoke. There are some case control studies indicating there may be a protective affect of increased intake of vegetables, more so than fruit. And that a diet low in saturated fat may reduce the risk. However, there has been no proof of cause and effect.

The etiology and assessment of nutrition is quite complex. I'm moving the talk from potential carcinogenesis to when you as a patient, or family member, might be concerned about malnutrition and having problems eating and drinking. Malnutrition may be caused by weight loss or by specific nutritional deficiencies. For example, anemia. Anemia might not be due to blood loss but there are certain nutritional complexes that can aid in anemia. Of course we know that malnutrition may be induced by cancer or chemotherapy. It may be due to malabsorption due to our therapy. Or it may be a reaction of the immune system. So this is multifocal in nature.

Patients with weight loss greater than ten pounds over a short period of time may likely need a nutritional assessment. This may include blood tests and nutritional counseling. We rarely use TPN (Total Parental Nutrition) in Gynecological malignancies. There are potential complications with TPN. We attempt to avoid this, but of course there are those short-term periods when we need to use TPN. Enteral Nutrition is when, instead of the nutrition going through the vein, it is delivered into the gastrointestinal tract through a tube. This tube can be placed in the nose, stomach or small intestine. Many formulas are available and depending on the patient the supplement is derived for her specific needs. There are also potential complications with enteral feedings along with TPN. Many times physicians and nutritionists recommend oral dietary supplementation. Examples include Ensure, Boost, or whatever the product the hospital carries. Many times these products can be used to boost the nutritional status of the patient. Something to consider are homemade oral supplements. You can blend fruits or vegetables. You can use instant breakfast shakes or ice creams. This may be more cost effective. Foods with high caloric intake, and high protein content are good. Of course when needed we can use medications to boost the appetite.

Overall health may be improved by eating well before, during and after the therapy. The goal is to have good nutritional intake so you can have strength, and are more active. You can exercise during therapy or before and after surgery. There are other nutritional parameters that are improved with diet and exercise such as decreasing the risk of infection and helping the immune system.

Before treatment some recommend to increase fruits and vegetables to at least five or more servings a day. Increase whole grain products if you can tolerate this during therapy. Decrease your intake of fat, alcohol and salt.

During therapy you need to focus on high calorie, high protein foods, for example, dairy products. It has been shown that protein requirements increase during chemotherapy. You can focus on foods such as peanut butter, yogurt, and cheese. If you anticipate you're going to have a problem during surgery, or therapy, you need to get organized and do meal planning ahead of time. For example, you may want to stock up on soups for after surgery.

After treatment, it is recommended to maintain a healthy weight, and increase physical activity. Exercise is important to the nutritional and the immune systems. Exercise can also increase the quality of a woman's life. Obesity increases the risk for other cancers and diseases such as heart disease, diabetes and hypertension. So, we also need to focus on the long-term issues of being of generous weight.

Suggestions for healthy eating and activity in women with cancer and in remission include eating fruits and vegetables, five or more servings a day. In addition, eat whole grains, limit the consumption of red meat, and maintain a low fat diet. These can be processed, and are higher in fat. Drink plenty of fluids, maintain a healthy weight and continue or initiate an exercise regime. Inform your health care team of any complementary/alternative medicines, or supplement use.

I initially started research at NEO UCOM, Northeastern Ohio College of Medicine in Akron and Canton, Ohio and then joined University Hospitals of Cleveland and we looked at some of these areas. We started researching nutrition in women with endometrial cancer. We are also presently enrolling and studying an ovarian cancer group. The reason we started with endometrial is that endometrial is more common than ovarian cancer. We can accrue patients faster. Hopefully a year from now I'll have preliminary data on ovarian cancer patients. In a prospective fashion, we looked at complimentary and alternative medicine use, quality of life, diet and exercise in women with early endometrial cancer and compared these to women who underwent surgery for non-cancer. There was a significant increase in complementary and alternative medicine use by all women, and the most used of these, in the Ohio area, was megavitamins, antioxidants, teas and garlic. This finding is also increased six months out in women without cancer. These women went into surgery thinking they may or may not have cancer. They ended up not having cancer and they underwent a lifestyle increase of their CAM products.

The next finding was the most concerning to us. Women with endometrial cancer usually are of generous weight. Not only were they of generous weight, but they maintained that generous weight after the diagnosis and treatment of cancer. The majority of women with endometrial cancer present with early stage disease, and the majority of these women are cured. So these women are of generous weight and they are maintaining it. Therefore, we cure their cancer, but because they're of generous weight they are at higher incidence for, colon cancer, breast cancer, diabetes, hypertension, and coronary artery disease. As physicians, we are not making an appropriate intervention. Yes, we have cured some women of their cancer; however, there is an intervention that weight loss can decrease your incidence of other cancers and other medical issues.

Women with a non-cancer diagnosis reported an increased exercise frequency at six months compared to women with endometrial cancer who reported no change at all. Again, it's like the CAM result. There are women who ended up not having cancer, but it made such an impact that they actually changed their health habits. Neither group increased their intake of fruits and vegetables over 6 months with 67 percent consuming 5 or more servings a day.

David Mutch: Thank you, Vivian.