Anyway to get started, my name is Kathleen Hynes-Kadish, and I am a patient at Dr. Meyers at the NYU Cancer Center. And I am here today to tell my experience of living with Metastatic Breast Cancer. Can you hear me? Okay. Firstly, I would like to address some of the myths of Stage-IV Breast Cancer. Namely, the earlier detection is the answer and that if you have Breast Cancer in your liver, you are a goner. In my case, neither one is true. Ten years ago, I was diagnosed with Stage-I Breast Cancer. I followed all of my doctor's recommendations I had a Lumpectomy, Radiation and Chemotherapy and took Tamoxifen. Statistically my chances for occurrence were small, and I believed I would be well. Afterward, my Breast Cancer was detected early, but Breast Cancer is like a terrorist, it strikes when you are least expected. So two years after my initial diagnosis, when I had symptoms, I thought I was just working too hard and getting older. It wasn't until I fainted in the gym and had several dreams about Breast Cancer that I went to my internist for a check up. While leaving his office as an afterthought, I asked him to draw blood for Tumor markers. He thought I was over reacting, but appeased me and did the blood work. When my internist called me at my office, I had a bad feeling, the news wasn't good, it wasn't, my Tumor markers were elevated. I immediately called my Oncologist just made an appointment. After my Oncologist examined me, she informed my husband and me that the cancer had indeed returned. We were shocked and speechless, the Cancer was back, it had been testified and it wasn't curable. A world as we knew would fell apart. It was too much to comprehend. The Breast Cancer had spread to my limb nodes, my abdomen and my liver. So I quit my job, because I thought I had only a few years to live. Fortunately, the FTA had licensed Herceptin a year before my Stage-IV diagnosis. Herceptin was actually pushed through clinical trials quicker than most medications, because of its wonderful results and because Breast Cancer advocates worth for its speedy approval. So I began a weekly dose of Herceptin and Taxol and within approximately three years I had no evidence of disease. For the past three and a half years, I have been on Herceptin alone. Six months ago, I was taken off the Herceptin due to heart complication. So far I am okay. I am fine to be of all medications, but I remind myself everyday that there are many new treatments available that are improving quality of a life and extending our lives. And I believe strongly that we must advocate for additional treatments for Stage IV Breast Cancer. Treatments that will work for all of us and make Stage-IV Breast Cancer a truly chronic disease, and thankfully because of Herceptin, I am here today. It is eight years, yes eight years since my Stage-IV diagnosis, and I have no evidence of disease. Here she is okay and now I would like to introduce Dr. Stella Lymberis who will be speaking about the use of radiation therapy for Metastatic Breast Cancer. Dr. Lymberis is an Assistant Professor at NYU Medical Center, Department of Radiation Oncology. She completed her internship at St. Luke's-Roosevelt Hospital and her residency at New York University College of Medicine in Radiation Oncology. She has been published in numerous publications and has many lectures and has many lectures to Radiation Oncology Residence, Neural Oncology Fellows and Radiotherapy Students. She worked for two years as attending at Memorial Sloan-Kettering treating Brain Metastasis, however since last year she returned to the Breast Radio Therapy team at NYU with Dr. Formenti and she is happy to be here with you today after her maternity leave its be back in professional life, Dr. Stella Lymberis. Thank you. I want to speak here tonight - today I guess getting a little bit later behind the schedule, so hopefully we will pickup the tape and you are not too tired you can hear. So today I am speaking about Radiation Therapy for Metastatic Breast Cancer and most of you I just want to show hands what how many of you have had Metastatic Disease or after in the past having had you know, your primary tumor deliberately to what Kathy was describing. Now that it was common I mean if you we don't have to openly discuss these things but usually in in many cases that's what we are dealing with these are the patients that we are seeing. The other side of the story is what Deborah Axelrod was describing describing upfront Metastatic Breast Cancer and they way different, think if different different diseases in different different we use different tools to address them. You can't hear, I am sorry it it's not high now is that what it is I am sorry okay. So we - most of you are familiar with Radiation Therapy because of having a treatment with - with Breast Conserving Therapy in the time of the initial diagnosis after lumpectomy radiation place an iatrical role so that women can conserve their breast. So the tools of radiation are very similar but I wanted to discuss in detail and describe better what we how we treat with Radiation Metastatic Disease and the new ones of that which you may not be aware of and now point out the differences. Okay so at NYU so as I mention radiation is an intrical part of Breast Conserving Therapy and at NYU we have many active protocols that in partial Breast Radiation prone and supine treatment and very advanced on board image on board imaging and cloning imaging which might not mean a lot to any of you but what that means is very sophisticated technology that we use, so we can really target the radiation just to either the tumor bed or the breast itself and spare normal tissues and minimize toxicity for our patients and this is not only important for our patients who are newly diagnosed Breast Cancer who have - lets say earlier stages of disease but these same tools and the same advanced technology enables us to treat optimally patients with Metastatic Disease. So let me let me explain let me explain what what I am talking about. So hear this is an example of Supine Breast Treatment so you see that these angles here this yellow angles are out of the breast - I am sorry the linear accelerator treats the breast from one side and other side, and in our department we also have an ability to treat in the prone position with the belly down to eliminate side-effects as well and eliminate thus to the heart and lung. As you see here on the left hand side the breast is falling through an opening in a manor that you can beam basically amuse X-ray beams to target only the breast and not treat to the heart and the lung, which here so basically the beams the beams of radiation would be in this plain and not be treating the heart - I am sorry the heart or the lung and only be treating the breast. Now in Metastatic Disease we use the same tool again to spare normal tissues from exposure to radiation and that's very important because as we are treating and trying to palliate someone's symptoms that's when they have a breast recurrence in or progression disease in the breast you know, you don't want to subject their lung to any more radiation and you don't want to subject their heart, so all these tools that we use are very important in the treatment of advanced disease when it is in the breast. So what other sites are involved with Metastatic Breast Cancer, what other sites do we treat with radiation, in addition to what I mentioned another another site is usually a very big problem site is the skin and soft-tissue and the chest wall many patients have had mastectomy upfront or at some sometime along the way. And then later on, are presenting with a chest wall recurrence. Now, some times that's the only sign of disease in their body. They have had PET scans and there is surely no disease elsewhere, but there is a small nodule of painful and sometimes bleeding you know, disease that can't be in the chest wall that is very hard to control. And Radiation Therapy can play a very important role to completely eliminate that that disease, heal that tissue and and is very effective in addressing disease in that area. Another site is also the bone and as Dr Axelrod mentioned the pelvis or spine, the lung as well and the brain. So Chest-wall Recurrence, I just wanted to return to this, because it's very it's not so common, so many centers have not really provided other treatments that are effective in treating Chest-wall Recurrence or have I guess has expanded the resources to do so. Chest-wall Recurrence is a big problem because most women have already had radiation, they have maxed out in terms of the radiation that they have received to their chest wall and to that side to begin with. So now this Chest wall Recurrence, if in many times either can be addressed surgically as Dr Axelrod mentioned but sometimes, if it's very progressive or large you know, that's not an option either or it would really, it would really interrupt the patients, schedule on chemotherapy and we don't want that because the biggest fear Metastatic Disease is really controlling Systemic Disease, so it really becomes a very difficult disease to manage because you don't want to interrupt with - you don't want to give the take the patient on chemotherapy for the time that you are addressing their Chest-wall disease. So one treatment that is very effective actually and and has is a very old treatment, 20 30 years ago it was used much more was Hyperthermia and then it's sort of in mostly in Europe and it sort of came I don't know, got out of vogue and people were not using it so much, but is now returning actually and there is many reports in ASCO and with about effectiveness of Hyperthermia. The only place that does that does this treatment is Duke and they have published actually and had presented some work last year at ASCO and New York and NYU here in New York. So this is and I have been lucky and very fortunate with Dr. Matthew you have many patients over the last five years that we have treated. It's a very rare problem, but this is a very effective treatment that I think that you know, people should have more awareness and publicized more that there are options of treatment, because most women, basically I have told by their doctors that there is nothing they can do because they can't have radiation and they live with this problem and there is effective therapy that can tried. So hyperthermia is basically heat treatment. It's just it's applied superficially, it's applied in the body by a like a heat applicator, it's not painful, it's you have to stay still while it's being done and it's usually involves a physicist as well in a room with the patient and the nurse and it takes about an hour, an hour and a half of heat application directly to the disease. Over multiple sessions and combined with radiation or combined with chemotherapy, it's it is very effective and I think Dr. Tiersten had mentioned to you all about Doxil and why it work so well because it's encapsulated in liposomes the reason the Hyperthermia synergizes so well with chemotherapy is what it does is by elevating the temperature of the tumor. It allows that the medication the drug that encapsulated in the liposome tube preferentially go to that site, so you are basically eliminate its if there is there is a biological rational on combining Doxil with Hyperthermia or radiation with Hyperthermia because you are basically you are heating is preferentially the area that - that you want the response and you can what you know link it with radiation or the chemotherapy and they use lower doses of chemotherapy and got it and even better response at that is at that site. I don't know if that everyone is everyone is clear on that you know because of you are basically delivering better the chemotherapy at the tumor and it will even works and it works better because its also at a higher temperature. So that's hyperthermia that's and then general general principles of palliating with radiation well you know, nowadays and I don't you know want to be get too technical, but we really use physics and computer modeling and prior I am an engineer in my background. And that's why I was interested in this field and it is a very exciting exciting thing to be able use computers in treatment planning to be able to treat you know, organs and specifically Metastatic Disease or other other or primary Breast Cancer in such a way that you can limit the doss to normal normal structures and reduce side-effects for our patients. And another principle guiding principle is that we have to work together with our Medical Oncologists. So when we give radiation we don't want to recruit too much bone marrow or really do damage to the patient so that when they cannot tolerate their chemotherapy, because we have treated too much of their bone marrow and then you know their blood counts are low. So these are all that's why like as everyone has said before its so important and critically important no one is working in a vacuum and what the patients and the treatments that I and the people in the breast program think about for our patients we always discuss them with the Medical Oncologists and the surgeon to make sure that we are not missing something and then we make sure that the overall treatment plan for the patient is optimal. So let me you an example so for lung. This patient had other sites of disease and was on chemotherapy but the main you know one threatening area that we were concerned about was a lesion that was near the Hilum, so this is bronchus that leads to the trachea and disease that is more central, it can be very problematic if its not not controlled for if it cannot be controlled with chemotherapy that can lead with with the collapse of the lung and impair breathing and also impair functioning to the patient. So it was it was felt that we needed to intervene with you know, with radiation therapy to help prolong the time, I am sorry to to basically treat this get it get the lesion under control, so the patient can not have that problem and then continue on chemotherapy and the treatment here was was effective, and now its it didn't near the other sites of disease elsewhere that the chemotherapy addressed. And that why it's again important to work together with the Medical Oncologist but this would become a pressing issue that was treated with radiation this specific lesion. In the pelvis if it is a weight bearing site for instance in the femur it was decide you know its that's in the air that's in area that if there is a lesion there it can basically impair the patients walking and take up up person whose has you know has very good functional status to some one who would be bed bound or required surgery so again at that you know, in those instances radiation therapy is indicated to treat a specific lesion. Again chemotherapy is even more important because it treats generally but there are specific situations where radiation would be used to prevent and to and basically used to control and and restore somebody's functioning and get rid of the pain and allow somebody's mobility. And this can be done in two two to three weeks, a patient who has pain and cannot walk and he is requiring a walker or a cane within two weeks. We will require less pain medication feel much better and not have that problem so if there is it is effective. The other thing is in the spine. Spine metes now can be can be treated very conformably with without subjecting the kidneys, liver, lungs to radiation and can be treated over a shorter period of time and this way this was this specific lesion is of the vertebrate body and it was in danger of impinging the spinal chord and caught in time with an MRI imaging we were able to determine that it was only one specific area of the vertebrate body that had this problem and this patient doesn't not did not even have any other sites of Metastatic Disease, they just had one area of their spinal one you know, with wonderful very small region of their spine. But left untreated, this can cause spinal chord compression and paralysis. I mean these are huge you know, it's very serious and thank god that the patient have a little bit of numbness and tingling and brought it to the attention of their oncologist and an MRI was done, so we could find - we could realize that that she had this lesion and with new with our techniques nowadays were able to treat very conformably with Stereotactic Body Radiosurgery which is like surgery basically in the sense that you are not treating the whole level of the spine, you can protect the spinal cord, it's very fancy radiation planning that you see that is like a circle around here so that the spinal cord in the middle does not get radiation and is protected from radiation damage and and this treatment - and these was given just with five five fractions and on subsequent MRIs the spine is looking looking very good and the patient it will not have is not risking paralysis or any problem and the the Metastases is completely controlled. Brain Metastases - this is a big topic you know itself but for Brain Metastases, surgery plays an important role, whole Brain radiation therapy plays an important role and there is also focused treatments that also are very effective that protect the rest of the brain so you can treat just one lesion and not subject the brain to radiation and this is an area I worked in for a while and it's a very tough disease and it's a painful process for patients to go through because just thinking that your brain or your head is is receiving radiation, that alone is so frightening and horrifying to most people and to get to the point to understand that that in certain cases, you know, they will be helped by it, you know, it takes a lot of time and a lot of discussion with your doctor to understand that and actually as a physician working in this area specifically I found it most difficult myself because I have tried to you know, tried to think as an intelligent person and who uses their head like you know, me I think everyday hopefully, you know, seeing patient in front of me would say I just can't, just the thought of it. the thought of undergoing radiation and subjecting my brain to radiation I would rather die than to do that. And it took a lot of work to talk with them and tell them the medical truth which is that your your mental thinking and your clarity and your intelligence will be preserved better if you if you undergo it. but how but it's a very it's a very tough discussion and it's and it's certain you know, if anyone wants to talk about with me on personally, we can we can go through it because for most people it's just to too difficult to even think about that they you know, could have Brain Metastases and that would something they can happen in their life. So let's let's try to do this as easily as possible, for single or few metes we do have the techniques where we do not subject the whole brain to radiation, okay. And with radio surgery we can treat nowadays just the lesion and protect all the rest of the brain. So there are some good news; and that can be done either with Gamma Knife or it can be done with LINAC Radiosurgery. And I had done the LINAC Radiosurgery for you know, for a few years and and the Gamma Knife is another way that its done; and they are equivalent in their efficacy, but I can tell you a little bit on which is sort of better because of other reasons, not because the outcome is any different. Brain metastases are common in all patients with cancer 30 percent. And both of them do present with a single lesion; that's the good news. And the good news is that can be easily treated with a very conformal treatment; that with radiation and and actually the control rates of that therapy are very high, 80 percent of those single lesions can be controlled if they are caught early and not present a problem to that patient. But it's all about you know, getting it you know, catching that early and getting and then being treated with LINAC or Gamma Knife Radiosurgery. And the most common sight; actually this is a much bigger problem for lung cancer. For breast thankfully it's a much lower percentage of breast cancer disease overall that's metastatic that will go to the brain. So those are the good news. So the treatment would be the Whole-Brain Radiation or Radiosurgery. This is an example of what we how we treat with the whole-brain, and unfortunately we cannot spare the scalp and this way preserve the woman's hair you know hair hair loss. Alopecia does come with the Whole-Brain Radiotherapy treatment. But one the common misconception is that all patients they get Whole-Brain therapy will become vegetables and they won't you know they will you know you will lose all your thinking and your reasoning. And that's not true. For the first nine months, you know, most patients would notice no difference in their thinking, calculating or other functions. Its just much later one to two years later that they might notice a little bit of a forgetfulness, like I don't know where I put my glasses down and and that sort of thing which which, sort of that most women under anxiety will do; which is not something to disregard though. I mean that you know, again it's easy to laugh about; but if you were the patient you know, when you are the patient, it's very scary. But if they didn't have the Whole-Brain Radiation therapy, they will lose basically, there are very few treatments that are effective for widely metastatic small disease in the brain and and you know, it's much worse not to get the treatment. Hopefully some day we will just get some you know, we will have some better options for our patients. In terms of radiosurgery like I said for small lesions or small multiple lesions, Stereotactic Radiosurgery is the treatment. And this is the barbaric part of it is that that a small little frame is attached to the head for about for a few hours that the therapy is done. Now this again there was a lot of research in radiation, trying to figure out a way to do it so that they does not those does not have to be a fixation mechanism that is attached to the patient's head. But we don't know how to do that yet. So it's under it's under investigation. But currently the current protocol is that and with numbing medicine it's amazing. The patients have the frame on and and they are smiling and they are okay. But you just have to work with them very carefully and very slowly when you attach and and when you touch the frame, it's painful. It's like going to the dentist. And then this is the Gamma Knife. The Gamma Knife is faster. So you wear the frame for a much shorter time. It's not that either of the two procedures; one is better than the other. But for treatment of solitary or small brain metastasis, if I had a choice or if it was my relative, the Linear Accelerator treatment, it takes much more time. They have to plan plan the treatment and then they have the physicist has to prepare and triage the machine. So the whole process the time that the patient has the frame on their head is unacceptably long. It's not like that in all centers but its something that one should inquire if if a relative or yourself is undergoing treatment. But the Gamma Knife, it's usually for a very short period of time and the treatment planning is much faster; so that makes it easier. The outcomes are the same for both procedures. It's just you know what you actually go through as a patient that you should find out about. Now in terms of treatment of metastatic disease the current paradigm in treatment of metastasis disease is addressing tumor cell proliferations. So we want to attack tumors with chemotherapy, we want to reduce the tumor burden. And we have mentioned surgery, we have mentioned targeted radiation therapy like I like I described a little bit. But there is a new paradigm that I wanted to discuss with you and then leave you with as ideas of what we are trying to do to make a difference and to try to impact on progression and seeding; because we there is not much this is the area that more of the biology is centered on. And and we really are trying to address and trying to impair any future seeding of the metastatic of metastatic disease. So we have an in-house protocol here at NYU NYU-0258; this is a chemo-radiation study. So it it uses the best chemotherapy that works for the patient as as thought of by their medical oncologist. As and it uses an agent GM-CSF which basically what that does is try to boost the immune response of the body of the patient to number one, prevents you know to prevent the development of new metasis and also you know to keep at bay or to attack the existing sites that are metastatic. So we have this safety mechanism in our body already. The only problem is we don't understand it fully and there is a lot of research in immunity to try to understand this process. And if we could understand it well that would be the end of metastatic breast cancer or the end of melanoma or the end of you know it would be it would be revolutionary. And unfortunately we don't you know, we don't know all the key players. But we do know some things. We do know what? We do know that that there is an immune response that can be elicited against tumor. Does that make sense? We we know that that our body can mount a response against a tumor cell. And that has been proven in mice, it has been proven you know there is models that we can that have been published that that tell us that and also clinically. So what that we are trying to do is in this study is to induce an immune mediated tumor response outside of the area that we treated with radiation. So because radiation causes cell death. It kills the cells. Those cells then; because they are dying, then the immune system tries just scavenge and clean up and do the basic clean up of the area. And by doing that process hopefully, you will have primed the immune system to be able to go attack the tumor sites elsewhere that are so that the lesions that are elsewhere in that in that patient's body. I don't know if you get it. We are going to review it, you know kind of go through it again; because it's a little confusing. But, what what this is called is "Abscopal" and the basic punch line you know the basic thing is that we are tying to use immunity to fight metastatic disease. So the Abscopal effect has been described in the literature in you know in medicine, in 1953, as a remote effect of ionizing radiation on malignancy outside of the field. So you treat with radiation, let's say lesion A, but then when you you know you find that there is effects elsewhere, but then you don't even treat. So you know trying to so that was that was actually this was written and and as a concept its not you know it's not the first time it has been thought of and people were talking about it in the 50's. So was called "Abscopal" from the Latin, "ab" "away from" and "scope" is "away from the target". So you are aiming at one target that you are you know, you are basically your effect to somewhere there. So what we are trying to do what we are hoping in this clinical trial is that since we have at NYU many preclinical models using flat Flip Three that's that's in mice, this has worked, okay. So in people the stimulant of the immune system is a different drug. It's GM-CSF, okay. So that's why GM CSF is used to stimulate the immune system. And we know that the GM-CSF is a growth factor of the immune cells; that the dendrite cells are immune cells, and we know that vaccination with the radiated tumor cells that can secrete GM-CSF the GM-CSF can stimulate a potent anti-tumor immunity. So this has been published and this has been you know it has been has been shown in people. So what is the study? The study basically allows enrolls patients that have are progressing; on their chemotherapy they are progressing, or they are stable. But most of them are progressing. They have to have at least three sides of metastatic disease; okay. And those three sides have to be known either on PET Scan or etc. The treatment would be GM-CSF at that dosage daily for 14 days and radiation to one of their targets one of their sites, I am sorry. And then after a few weeks they do it again; the cycle of GM-CSF and radiation to another of their targets. And meanwhile they are on their chemotherapy without adjustments. So you know you don't you are not you don't as a patient you are not dropping all your guns that you know, you are working hard, then you think that you your need for an experimental phase one study that tells you that you shouldn't be on chemotherapy. So that's not how this is done, because the concept of this of this protocol is to in addition to the chemotherapy, try to elicit and elicit an immune response and radiation is used as a tool to cause cell death so that then the body has those dead cells to try to process and then in response elicit an immune response. So that's that's sort of that's what it is is doing. And we do have many patients enrolled probably already five or six and unfortunately this is a this is the PI on the Dr. Formenti. She is the Chairman of Radiation Oncology and its really on her ideas and it's you know, very novel way to think about using radiation and also in trying to advance treatment and trying to think to understand more to understand more the body's immune system which we really are not we have not synergized that currently with them with existing therapy. So this is an example of a treatment of a patient. This is a very small lesion, very targeted radiation. The radiation itself would cause very no side effects because this is a small targeted conformal treatment. So you know we pick areas that you know the last thing you want to do in a clinical trial is actually cause harm, because the truth is that we don't know that this is going to work and we need to at least in all the steps that we make, do it in the safest way as possible. I mean that's just you know our philosophy and my philosophy as a physician, trying to decide how to approach this, because you are caught in the middle, you want to do the best thing for the patient that is in front of you who is in front of you, but on the other hand we will never advance medicine if we never do any clinical trails. So it's a very hard ethical dilemma that we need to work together; all of us on how to best in the safest manner, try to come up with trials that we can generate more data and have better options to be giving our patients with metastatic breast cancer in 10 years. And that's a very you know difficult problem. So the take home message is we have you know by forming the proper medical team, medical oncologist surgeon and radiation oncologist patients with metastatic breast cancers can be treated, allowing them to lead normal lives and live with the disease such that the disease does not control them and but more importantly new research and frontiers in biology will help us find novel methods so we can impact on metastatic spread, seeding and treatment of metastatic breast cancer. Thank you.
member. 
