 So, our last couple of talks are a little bit of a shift of gear. Are you going to do it all together? Or are you going to do it up here? What are you going to do? So, one of the things that's changed in cancer care over the last decade is the recognition that managing the whole patient is critical to the outcome that we would want to see. What does that mean? It means that providing supportive care during the cancer journey is critical. What is supportive care? It could be things like pain management, chaplaincy, understanding the genetics of kidney cancer. And what I thought would be helpful for all of you would be to see here and learn about the supportive care programs. Not that we only have here, but how to think about supportive care as a partner in your kidney cancer care. And we've invited Eve Makoff, who's co-director of our supportive care service. Nancy, who's the nursing director of our kidney cancer program. And John Lee, who's a genetic counselor who deals with families and risk associated with kidney cancer. So you guys have the table. Thank you. We're just going to be a little bit more informal toward the end of the day. And so you can look at us as another team within this huge team that you've heard about all day today. Hi, I'm Eve. Most of you know me as that. I'm an internist, but I work in the supportive care department at the Samuel Ocean Cancer Center Institute. And I wanted to just tell you a little bit about supportive care and how it intersects with oncology. So what is supportive care? This is specialized medical care for people with serious illnesses. It focuses on providing patients with relief from the symptoms, pain, and stress of serious illness, whatever the diagnosis. The goal is to improve quality of life for both the patient and the family. And this comes from the center to advance palliative care. In some institutions, this is called palliative care. In our institution and a lot of other institutions, we change the name to supportive care. Because people associate palliative care with hospice. And what I do and what my colleagues do does not necessarily have to do with the end of life. What is oncology supportive care? Cancer and its treatment, as you know, often causes a variety of symptoms and side effects. An important part of cancer care, no matter what the diagnosis is, is to relieve these symptoms and these side effects. This is called palliative care symptom management or supportive care. This kind of care is more than receiving a drug, any kind of medication. It's also focusing on your emotional state, your spiritual state, and any kind of needs that you have at home or with respect to your symptoms. So again, what is oncology supportive care? It's a kind of support that includes carefully considering your prognosis, your goals for your medical care, what your needs are at home, any kind of physical, psychological, or other symptoms that you have that we can help you with. So who provides this kind of care? We have an interdisciplinary team. In our cancer center, we have myself, we have another supportive care physician, we have a rehab physician, we have a psychiatrist, we have a team of social workers, we have a chaplain, and we have dieticians, and we all comprise the supportive care team. So the research, and I didn't, unlike everybody else who spoke today, I didn't really focus on research, but we do have research and more and more is being done in terms of how supportive care or palliative care is affecting patients and family members. In 2010, there was a sort of the most important initial study to describe how in particular lung cancer patients benefited from supportive care. They were shown to have fewer symptoms, to have less distress, to have better quality of life. Subsequent studies have actually shown that they may actually live longer, and many more studies are underway and have been showing across the board that this kind of care on top of your usual oncology care is actually improving your quality of life and potentially prolonging your life. So I'm quick and sweet, and if anybody has any questions, feel free to call my office. You can ask Dr. Figlin or any of the other doctors up here, all of whom I work with. I work with all of the doctors at the Cancer Center. If you have any questions or think that you need help with any pain or symptom management or any more coordination of care or questions, you know, social work questions, spiritual care questions, dietician questions, you can always reach our supportive care department. Thank you. Thank you. Before I get started, and I think my observation of the day is that with all the speakers that we've had thus far, no one has really talked about side effects. I find that kind of interesting. But anyway, I'm going to cover that a little bit, and I will be available afterwards if you have specific questions. We have a lot of information you can imagine to review. But can you show me, just by raising your hand, how many of you have not been on any targeted therapies to date in... Okay. How many have had immunotherapy? How many have had more than one targeted therapy and more than two? All right. Well, with that information, we're going to get started. And the title of my talk is Taking Your Anti-Cancer Medication Is Not As Easy As You Think. And that's a pretty true statement. And I like to think that it's not as easy as we think because we are a team, meaning you and the audience, the patient, and your healthcare provider, because we do this together. So some of the guiding principles, and I'm going to try to give you some concepts as you kind of go through your treatment plan with your physician. And the first thing is that the treatment that you're going to be receiving, and we get asked this question all the time, is that the treatment for the most part will be chronic administration. Dose reductions will indeed be made. Dosing schedules may be altered, and I'd like to spend a little bit more time on that topic as we get further through the slides. To us, your quality of life is definitely a priority. Communication with your healthcare team will improve outcomes. All the side effects can be managed. And please keep your schedule appointments with your healthcare team. And again, these are guiding principles that you need to follow for a better outcome. So you need to ask these questions, and I think you probably have already started formulating these as you listened to the lectures earlier today. Is this the right drug for me? What is the evidence supporting the use of this drug? Are there treatment guidelines? What do I need to know about this medication before I start taking it? What are the side effects? What are the advantages of an oral drug versus intravenous? What resources are going to be available to me? How will success be measured? And by that, I mean everybody asks the question, okay, so if I start taking this medication, how are you going to know if it's working? And generally, the response that we give is that we're going to be doing CAT scans. It might be eight weeks, it might be 12 weeks, but rest assured, we will always be wanting to evaluate the success of these medications. And then again, the question number eight, how long will I be taking this medication? And our response to that is as long as they are helping you and you are tolerating the drug well. So some of these questions are titled here is what patients need to know. We've already reviewed today. What is angiogenesis? You heard from several lectures earlier that it's the formation of new blood cells to tumors. And what we're trying to do is to, but these medications break that process from occurring. Am I getting targeted therapy versus chemotherapy? Most of you probably know that most of the treatments that you're going to get for kidney cancer are going to be either targeted therapy or some type of immunotherapy. What are the side effects? That's what I'm here for in our practice here. I talk a lot about the side effects, management. I do a lot of phone call triaging. So to make sure that you always have somebody available to talk to. And even recently, I have had patients send me pictures of a side effect that they're experiencing. And when that occurs, we can really get on the management of it, because I have a clear picture of what's going on, and then we know how to intervene rather quickly. You need to discuss with your health care team any elective medical procedures that you're going to, or that you might have, because these drugs need to be stopped before you undergo any type of surgical procedure. And then there's a waiting period before you can restart. It's important that we know what other medications you're taking because of drug-drug interactions and what your past medical history is in terms of the potential side effects that you might have. When should you take the medication? What are some of the foods that you shouldn't have? And also, keep a diary. It's hard when you come back for your monthly appointments to kind of always recall some of the side effects that you had in the past 28 days. Well, two of the major classifications of drug that we use, the VEGF inhibitors and the MTOR inhibitors, and they have very distinct side effects. With the VEGF, you're going to see a lot of skin toxicity, fatigue, hypertension, some mouth soreness. The MTOR inhibitors, drugs like affinity and temporolimus can cause some changes in your blood glucose, lipids, so also some skin rashes, and for the temporolimus that is given intravenously, there's a risk of infusion reactions, although quite low. So just to start with some of the side effects, dry skin, a rash, what we call hand-foot syndrome, can occur with these medications. And it's just important that, number one, you know about them ahead of time, that you employ some of the interventions that you're going to learn about, and that you report them to your healthcare provider if they occur. And these are some side effects, not meaning to be too graphic, but it's important that you see this so you can look at your feet and your hands throughout the course of your therapy to see what was happening. And some of these can be quite painful, and that's why it's important that you inspect your feet on a daily basis. And this is what can happen on the hands. It's very common with these targeted therapies, the VEGF inhibitors, and it's what we call hand-foot syndrome. We treat this by a variety of moisturizers, and I like to use the word cream as opposed to lotion, because creams are generally thicker, and what you want is a very thick moisturizer. All of these are over-the-counter, although there are some prescription moisturizers that we can give, but the important thing is not what you use, it's the frequency with which you use it. Some of the GI toxices that you might experience, what about some mouse sores, some heartburn, taste changes, a drop in your appetite, and diarrhea, and even some constipation from these medications. So we do a lot of dietary interventions, and that's why, as Dr. Makov mentioned, if anybody in our practice wants to see a dietician, we can make that happen. They can really be very helpful with food choices when they're having some of the GI toxicities. We have a lot of interventions, sometimes you just have to change your diet and what you would normally eat, and it can really make a huge difference in the outcome of some of the side effects. We recommend, prior to starting these medications, that you start with some over-the-counter meds that can help with heartburn. Again, your physician is going to tell you some of the medications that he or she thinks would be suitable, but the important thing is you need to ask your doctor, should I be taking something like this, and for us, the answer would be yes, because heartburn can be a bother when you're on these medications. Another medication, because diarrhea can occur, things like over-the-counter amodium, if you need a prescription medication, these are all things that you should know about before they happen so that you're prepared if and when they do occur. We have a lot of oral side effects. Your mouth may feel like it has a burning sensation. It may or may not have some isolated sores in the mouth. There's really not any one great intervention that we can recommend, except for good old-fashioned mouth care, warm water rinses with or without salt water or baking soda, and again, the frequency at which you do this can change the outcome. These are just some examples of products that we use. Many times, we tell patients to change their toothpaste to children's toothpaste because they're more fruit-flavored and they don't have the spicy minty flavors. One of the most common side effects is fatigue. The first thing is, let's figure out sometimes what is causing the fatigue together. We can do that with the patients, but ways to manage it. I know it may sound a little unusual, but to exercise. I mean, don't lie around all day because you're tired. Even if you take a five-minute walk in the morning and a five-minute walk in the afternoon, that could help. Set priorities for yourself when you want to do something. Many patients tell me that if they take a 20 to 30-minute nap in the afternoon, when they wake up, they feel much more refreshed and they can carry on. But don't ever hesitate to let your physician know if you are feeling this way. Just because you're having these side effects does not mean that the treatment is going to be stopped. We may have to make some adjustments, but it's important that you tell us what you're feeling. Another common side effect is hypertension. This is something that we anticipate very frequently with these medications. If you have a baseline history of hypertension, chances are your blood pressure is going to increase while you're on the treatment. We always require that you take your blood pressure once a day, keep a log, and bring that log with you when you come to your visits. And if we see your blood pressure start creeping up, we'll start either with a medication if you've never been on one. We like to coordinate most of this care with your primary care physician or cardiologist. And a lot of times having that appointment with these other physicians prior to starting is very helpful so that your whole team is aware of the type of medications that you're on. And what's interesting is that the development of hypertension can be what we call these biomarkers that perhaps the medication is actually working. So developing hypertension can be seen as a positive effect. Now some of the medications, synitinib, everlimus, excitinib, it doesn't really matter what time of the day you take it, although we recommend that you take it the same time every day. And it can be taken with or without food. Synitinib is generally taken on a schedule of four weeks on, two weeks off. But one of the most exciting things that we have come across is changing the dosing schedule of the drug synitinib. So what we do now for patients is we start them on four weeks on, two weeks off. And if they can't tolerate that, what we do is administer the synitinib, two weeks on followed by one week of rest, go for another two weeks and then another week of rest, which equals six weeks, which is a cycle of therapy. And we're able to do that without decreasing the dose. And what you should be asking your physicians and what your goal should be is trying to maintain the dose of these medications. Because the higher the dose that you can maintain, the better outcome, the better effect, anti-tumor effect that you can achieve. Now, drugs like seraphinib and pisopinib, they're a little bit more challenging in terms of dosing because they have to be taken on an empty stomach. So you have to either take it at least one hour or two hours after a meal. The drug Temserolimus is IV-given weekly, and then the drug Bevacitamin is also intravenous. So it doesn't really matter whether or not you've taken food or have not taken food. And then many of these drugs, you cannot take grapefruit or grapefruit juice. That's probably the only food contraindication. And any questions for me or we can address some of these questions? Oh, sure. Go ahead. Because of a drug-drug interaction between the grapefruit and the medication. It's like an enzyme that the grapefruit has and it interferes with the medications. You can have a regular orange. There's some oranges that you're not recommended that you have, but the main drug is grapefruit. Civil oranges are one that you sometimes will hear about not to be taken with the targeted therapies. Anything else? Anybody else? Thank you. Hi, my name is John Lee. I'm a genetic counselor here at Cedars, and I just wanted to take some time to talk to everyone about the genetics behind kidney cancer. It's a little bit different than the genetics that has been previously alluded to in some of the other talks today, but I will differentiate that. Some common questions are, is my specific type of kidney cancer genetic? And are any of my other family members, such as my brothers and sisters and children, are they at risk as well? So these are some of the points that I want to address today. So when we talk about genetic testing, when I've talked with various patients about this, you'll see all sorts of different opinions regarding genetic testing itself. None of which are right or wrong. Everyone has their own opinion. Some people feel as though knowledge is power, and it will help them make decisions moving forward. Others say, you know, why would I want to know of them at an increased risk of developing a different type of cancer? I don't think I would do anything. It would just cause me anxiety, and I would worry a lot about that. Others say, certainly they have different motivations for the testing. They don't care themselves necessarily whether it's genetic, but they want to know specifically are their children at increased risks of developing this cancer. Others have concerns about insurance discrimination for either themselves or family members saying, I'm concerned if I am positive I'm going to be discriminated against based on health insurance, life insurance, things like that. And other people say, I want to be tested for everything. I want to know as much as possible, you know, not even just cancer. I want to know, you know, what am I potentially at risk for? Cardiovascular disease, other things. I want to know, you know, how to prepare best for the future. So I think in terms of talking about genetic testing, it's important to talk about some of the basics and science behind this. So to begin with the human genome, it consists of about three billion base pairs, and everyone has about 26,000 different genes. You have two copies of every single gene. You get one from your mother and one from your father. So you get half the material from either side of the family. Everyone's sequence varies roughly about every 300 to 1,000 bases, and these are what we call SNPs. The large majority of our DNA is actually the same, so over 99.9% of it. However, there certainly are key differences between all of us. It's what makes us different from each other. Most of these variations lead to trait differences, but some of them can lead to disease as well, such as cancer. It's expected that everyone has about four to five deleterious or harmful mutations, and a larger number of these SNPs as well, so variants that could also potentially lead to disease. So within different types of diseases and genetics, there's a couple different categories that you can see. So some are what we call chromosomal disorders, so these are either having an extra copy of a gene, a missing copy of an entire chromosome. These are things like Down syndrome, Fragile X. There's also single gene disorders, so this is having a particular mutation in one particular gene. So if you've heard of BRCA1 and BRCA2, these are the hereditary breast and ovarian cancer genes. A lot of other genetic syndromes such as Tasex, cystic fibrosis, hemophilia and sickle cell are also tied to one gene in particular. And then there's a lot more complex disease that we categorize as genomics. So these are sporadic versions of cancer, cardiovascular disease, diabetes, Alzheimer's, where we think that there certainly is a genetic interaction, but it may be multiple genes that are causing these and also a gene in an environmental interaction. And we haven't gotten a good handle on these specifically in terms of being able to offer specific testing for them. And it's certainly an active area of research. So all cancer is actually genetic, but only about 10% is inherited, and the number within kidney cancer is probably actually closer to about 5%. So the reason for this discrepancy is it's important to understand there's actually two different types of genetic mutations that someone can have. The first of which, which is my area, is what we call germline mutations. So these are the mutations that you are born with. You inherit these from either your mother or your father. So the person has these throughout the entirety of their lifetime. They're actually present in the egg or the sperm. Again, they can be passed on from generation to generation. And these are the ones that affect these cancer syndromes that, again, can run within families. The other types of mutations that you can have are what we call somatic mutations. So these are mutations that we think are acquired over someone's lifetime. They occur only in the cancer's tissue. More importantly, they're not inherited. So these somatic mutations cannot be passed on from generation to generation. However, these are certainly very helpful within both prognosis and treatment. And these are the type of mutations that were alluded to in the previous talks in terms of how can we now characterize cancers in terms of individualizing treatment for patients. So the somatic mutations certainly play a very, very large role within treatment. But again, the germline mutations also can have an important role as well, but a separate role there. So within genetics, family history is very, very important. You know, whenever we try to assess whether a type of cancer is genetic, we try to look further into the family history to see what kind of patterns can we see, either individuals with the multiple same types of cancers within a family or different types of cancers that form a pattern within a specific type of syndrome. Most of these conditions are inherited in what we call a dominant pattern. So that means that, again, everyone has two copies of a single gene, one from mom, one from dad. Within a dominant condition, all it takes is having one changed copy to be at a higher risk of disease, or in this case, cancer. But it also displays a phenomenon that we call incomplete penetrance. So really what this means is, when someone has a genetic change, they certainly may be at an increased risk of developing cancer, but it's not necessarily a 100% chance to develop cancer. So you can see people with these genetic mutations that never develop a cancer. So it can kind of appear to skip a generation within a family. So in this particular example, you see starting up here with grandmother, she has the mutation, she also has the cancer, which is indicated by this orange shading. She had a couple of children here. This daughter over here has the mutation and also had cancer. This daughter over here did inherit the mutation, but never developed cancer. You can see that she had five children, three of whom ended up developing cancer. But when you look at this family tree, it appears to skip a generation because this individual never developed a cancer. But if you were actually to genetically test these individuals, you would see the mutation consistent within all of them. So it's an important distinction to make there, just because you don't see it within every single generation doesn't necessarily mean that it's not genetic within a family. So what are the types of cancers that we can see that are more commonly associated with genetic syndrome? So certainly on the left side, some of the more common ones, breast cancer, ovarian, prostate, uterine, and pancreatic. But certainly we can see renal cancers, pheochromocytomas, periglanguomas, gastric cancer, thyroid cancer, colon cancer, and melanoma as well. So there's a wide variety of different cancers that can be hereditary and run within families. There are also some other cancers that are very common, and you can see clustering within a family, but we don't think that they have a large hereditary basis to them. These are things like lung cancer, Hodgkin's disease, leukemia, lymphoma, liver cancer, and also skin cancers. So over here, this slide, it's a little bit hard to read, but the point of this really is that there are a large number of different genes over here that can be associated specifically with hereditary renal cancers. Genetic testing from the germline side has really taken a large advance within the past few years. Historically, we would need to do single gene testing looking at one or two of these genes at a time, trying to find what is the most likely gene here. It was very costly, very time consuming as well. Within the past few years, there was a breakthrough in technology, and there's a new technology available. It's called Next Generation Genetic Testing. It allows us to actually screen for the large majority of these genes all at once for very similar prices as single gene testing, and actually at the same time as it used to sequence a single gene now. So the diagnostic rate of genetic testing is going up because previously where we were missing some of these genetic conditions, we're not missing them like we were before because the testing is more readily available. So what are some things to look out for a person or a family history that makes it a little bit more or less likely to have a genetic condition? So if someone has a kidney cancer, these are some of the other things to look out within, again, a personal or a family history that can be things that could potentially indicate that this could have a genetic basis to it. So things like spontaneous pneumothorax, fibrophiliculomas, a history of seizures, retinal angiomas, hemangioblastomas, liomyoma, oncocytoma, and then certainly other types of cancers within the family specifically, again, pheochromocytomas, paragoniomas, colon and uterine cancer, and then also very importantly, again, multiple types of kidney cancer within a family. So also when we look at the family history, it's also important to realize that the family history does include more than what we sometimes consider to be closely related individuals, so more than just first degree individuals. You can certainly see patterns within a family extending out to great aunts, great uncles, distant cousins as well. So when you look at your family history, again, it's important to look beyond just parents, siblings, and children. You can see atypical presentations within families where there's very distantly related individuals that have the same types of cancers and it's actually due to the same heritable cause. Some other red flags for kidney cancer itself that can make it more likely to be hereditary, certainly the age of onset of the kidney cancer. Any cancer before the age of 50 has a higher chance of being hereditary. If there's bilateral involvement, so if both kidneys have cancer, that's more likely to be genetic. Any cancers that are multifocal, one tumor and one kidney. And then certainly, again, a family history of kidney cancer and also neuroendocrine tumors. There's also another offshoot of hereditary kidney cancer that we call familial kidney cancer. It's classically defined as families that have two or more renal cancers, but no genetic mutation has been found within this family. Again, the diagnostic yield has improved with our newer genetic testing panels, as we call them, but still, certainly there's families with multiple kidney cancers that where we can't find a genetic mutation. We think that the explanation is likely within some other genes that we don't know about yet. Again, as I mentioned earlier, we have about 26,000 genes. We're doing cancer testing for about 40 of those genes at this point, so there's certainly lots of genes that we haven't characterized yet that may play a role within hereditary renal cancer. So within these families, it's currently recommended that first-screw relatives undergo screening, but the exact risks and the frequency of the imaging isn't quite clear. Certainly more research needs to be done there. There was an NCI study that kind of underscores the importance of this that showed that 2 out of 141 family members who had this screening were actually found to have tumors on their screening. So it's very important, again, even when there's not a genetic mutation that's able to be identified within these families that have familial kidney cancer that family members know about this so they can get the appropriate screening. So overall, genetic testing can play a role within patients' care in terms of figuring out, potentially, why did their cancer develop? Are they at risk of either a different type of cancer or any other malignancies? And how can we best screen them moving forward? And then certainly for other family members, if there is a genetic mutation that's identified, it doesn't mean that everyone in the family has the same mutation.