Hi everyone, good afternoon and welcome to the Cancer Rehabilitation's Member May. My name is Dr. Kelly Chaviano and I'm the Co-Secretary of the Cancer Rehabilitation Committee. Our session today will be focusing on steroid myopathy and muscle wasting in pediatric and adult cancer patients. We have three wonderful speakers today. We have Vera Cetlina from New York Presbyterian Columbia Irving Medical Center. She is a pediatric rehabilitation fellow. We have Dr. Engel, who is an assistant professor of physical medicine and rehab and oncology at John Hopkins School of Medicine. We also have Dr. Heather Nauman, who is a cancer rehabilitation fellow at UTMD Anderson Cancer Center. Please submit your questions in the chat box. We would absolutely love to hear from you. And now without further ado, let's go ahead and begin our session today. Hi everyone, my name is Vera Cetlina and I will be talking about steroid myopathy today. This is a particular interest of mine. Let me just get rid of all the unnecessary stuff. So this has been a particular interest of mine. I actually have background working as a pediatric oncologist back in Russia. And I did see, and I continue seeing so many patients who are severely debilitated due to this condition that I feel like is a little bit understudied and I wish we knew more about it. So I've been doing a little bit of research on it and we wrote a literature review paper on steroid myopathy together with Ray Stanford and Dr. Ibanez and Dr. Serkin at the Myoslom And I will be presenting basically kind of like an overview of the topic with particular emphasis on exercise treatment and medication treatment for this condition. I have nothing to disclose and objectives of my talk today will be to define steroid myopathy, to list indications for steroid use in oncology and describe pathology and pathophysiology of the disease, as well as review disease presentation and diagnosis and go into more details about therapeutic modalities for it. So what do we know about steroid myopathy? We know that this is a disease that is a result of endogenous or endogenous hypercortisolism or endogenous glucocorticoid steroid intake. We know that it affects lower limbs more than the upper limbs and usually proximal parts more than the distal parts with the caveat that we don't have much proof of actually muscles, proximal muscles being more affected than distal muscles. It's more that the proximal musculature is easier to test and it's more apparent clinically that it's weaker. On the pathology, based on the pathology results, I don't think there is any evidence to think that distal musculature is less affected by steroid myopathy than proximal. It's more clinical picture. We know that steroid myopathy can affect respiratory musculature and it's quite frequent. It affects type 2 muscle fibers a little bit more to a bigger extent than type 1. There are no accepted guidelines for the diagnosis and treatment of this disease as of now. And specifically applicable to cancer population, we know that it's associated with the risk of chemotherapy treatment intolerance. In regards to why do we use steroids in oncology this much, so this is a very common chemotherapeutic agent in the treatment of leukemias and lymphomas and myeloma. It is used for brain tumors to reduce the peritumoral edema and neurological deficits associated with it. Steroids decrease permeability of brain capillaries and also restore blood-brain barrier and that's why they help in this particular situation. And then it's also used in brain tumors to minimize side effects of the radiation therapy and to reduce encephalopathy. It is also a treatment for acute and chronic GVHD after the stem cell transplant and I'll talk in more details about it. In terms of the GVHD specifically, so there are some numbers that I do know. There are some numbers that still we need to know more about. So basically about 50% of patients who receive stem cell transplant, it depends a little bit on the type of stem cell transplant, not a little bit, quite a bit, but in general roughly about 50% develop GVHD and unless it's a very light form of GVHD, they usually require systemic glucocorticoid steroids and that's an accepted first-line therapy for acute and chronic GVHD. Out of the patients who end up receiving high-dose steroids or prolonged steroids for GVHD, about 41% have this data in the adult population, develop steroid myopathy. I don't have data for in pediatric population. And steroid myopathy not directly leads but definitely is connected to overall functional decline of this patient, decline in quality of life, increased obesity and osteoporosis as well. One thing to keep in mind is that oftentimes, especially in the cancer population, there are conditions that are characterized by endogenous glucocorticoid steroid access and myopathy on itself. Among those things to remember is sepsis, cachexia, starvation, and metabolic acidosis. And a lot of our patients, while going through the treatments, they have those conditions in one way or another. And it's important to keep in mind that this adds to their condition. So this is basically, they're already preconditioned to have kind of like worse status in a way. And then in terms of the mechanisms of steroid myopathy, so this actually has been studied quite a bit. So this slide is not too detailed, but I have much more information about this and can talk in more details. The mechanisms are known. So basically, steroids activate muscle proteolysis, and this is their catabolic action. That's what's called catabolic action of glucocorticoid steroids. They basically activate multiple proteolytic systems on the cellular level, and that's how muscle cells get damaged. And then they also have blunt muscle protein syndromes. So this is anti-anabolic effect of glucocorticoid steroids. And it acts on multiple levels, but basically there are certain factors such as myogenin and insulin growth factor one that steroids inhibit. Those are factors that help to build musculature, and it also activates myostatin, and myostatin is a factor that inhibits synthesis of the new muscle cells. So those two together basically lead to reduced myofibrillar protein content, which in turn leads to decreased muscle mass and reduced muscle strength. In terms of the functional assessments and diagnostic tools that we have in our toolbox, overall, this is a clinical diagnosis, however, there are things that we can use in order to assist us in making this diagnosis. So we know muscle testing is what we do clinically, and we know well. Dynamometry is used in membrane muscle encountering, we use it quite a bit. We use kind of like the hand-grip dynamometer, we also use hand dynamometer that with that one you can use the muscles, you can assess the muscles other than hand grip. So that is also possible. There are different ways of dynamometry and how it can be used, but it's definitely a good tool to assess for the muscle strength. And then there are imaging modalities. So things that have been described in the literature is using CAT scan to assess for muscle volume loss and ultrasound actually to assess for change in echo intensity and thickness of the muscles. There are a few studies, a few papers that we found utilizing ultrasound. It's mostly for research, but it could be actually a good tool for us to use in the future to track progress of the treatment in general. And then muscle biopsy is not used usually. I mean, unless you're suspecting some other disorder, but muscle biopsy is not needed to diagnose steroid myopathy. But if you're suspecting something, another condition, then muscle biopsy can be of use. And usually it's type 2 muscle fibers affected more than type 1, as I mentioned prior. And then in terms of the EMG studies, also it's a little bit on the research side, but it does show that there is a decrease in muscle fiber conduction velocity. It's either related to the suppressive effect of glucocorticoid steroids on circular excitability, or it is related to the decreased diameter of muscle fibers themselves. So if the diameter is decreased, then it makes sense that the velocity will be a little bit slower. Again, this is not the tool that is used on a regular basis, but it's just good to know that this is what's happening. And this is just some pictures from the paper that I was using CAT scan in order to measure the muscle volume. So here they were actually measuring the ESOS over here. And they did prove that they have a myositis group and the control group of patients who were taking steroids for other indications. And they were basically comparing pre- and post-steroid use, and they showed that there was significant change in the volume of the ESOS muscle. They basically were checking cross-sectional size of the muscle. For the ultrasound, I actually don't have the picture from that paper that was using the ultrasound, but they were using the gray scale. So basically different shades of gray to assess the echo intensity. There is a similar scale that's used for spasticity. Maybe that scale could be used in the future if we do decide to use ultrasound for tracking progress, because CAT scan is hard to use. All right. So this presentation and the course. So roughly half of the patients on high-dose steroids develop clinically detectable proximal muscle weakness. The high-dose steroids overall, that varies quite a bit in different papers, but overall high-dose steroids is more than 30, 40 milligram of prednisone per day, if you're talking about adults. Incidence is significantly related to cumulative dose of steroids and increases with prolonged exposure to steroids. And proximal muscle weakness develops within the 15 days of initiation of treatment. So data on when does the onset of disease happen varies quite a bit, and it varies also in the prospective and retrospective studies. So prospective studies tend to have numbers, smaller numbers, and retrospective studies tend to have larger numbers of the days after the beginning of the steroid treatment until the steroid myopathy was developing. But this is roughly the number that I could get for you. And there is an increase in muscle strength observed within three to four weeks after discontinuation of the group corticosteroids. This is the study in patients with CNS metastasis. That was done by a neurology team at Memorial Sloan Kettering and was published in 1997. They had 15 patients that they followed, and nine patients out of 15, so about 60%, developed proximal muscle weakness. That weakness correlated to the cumulative dose of steroids, but not the average daily dose. The onset was about 15 days in most of the patients that developed steroid myopathy, and they actually had quite a high rate of respiratory decline in those patients. So they had 10 patients out of 15 with respiratory decline. There was not all the patients that had also proximal muscle weakness. Two patients had respiratory decline, but no proximal muscle weakness, but still that's a high number. And three patients who could be followed for more than three months off steroids were noted to have either improvement or resolution of the weakness and respiratory impairment. And then this is the only study that we were able to find in stem cell transplant patients. So this is coming from University of Buffalo, and it's published in 2006. And this was in retrospective analysis of the 17 outpatients who developed acute GVHD more than grade two after the stem cell transplant, and they were treated with at least two milligrams per kilo of metoproteinazolone. And the paper says that steroid myopathy was identified in 41% of the patients, and 38% had moderate severity, and 3% had severe steroid myopathy. So what do we know about treatment? We know that if we lower the dose of steroids, as I said, usually it helps. We don't fully know the trajectory of the disease and how much do you need to lower the steroid. And the numbers are very, that's very vague. I couldn't find much information about it. We know that if we could use non-fluorinated glucocorticoid steroids, such as hydrocortisone or prednisone, it's better than fluorinated ones. We, and I will talk about this a little bit more, know that moderate intensity exercise or physical therapy is beneficial for those patients and help with improving muscle strength in those patients. Protein enriched diet and diet rich with branched chain amino acids is something that is talked a lot about in the literature. However, there are no studies in this patient population. It makes sense that if you were to provide patients with protein enriched diet, hopefully there will be more amino acids that would be digested and hopefully their muscle bulk will be better. However, there is no literature published on this yet. And another thing to remember is that actually steroids somehow managed to decrease the amino acids intake of muscle cells. So basically how muscle cells are, yeah, kind of like getting the amino acids in, sorry, I couldn't find the word, but that could be on the way of implementing this, but still sounds like an easy and correct approach from the logical standpoint. And then creatine supplementation also talked about in the literature. However, there was no literature that I could find studies in steroid myopathy population. And then anabolic steroids. So anabolic steroids, specifically oxandrolone is a medication that has been approved by the FDA for the treatment of catabolic effects of steroids. It is not very commonly used, possibly because of the fear of the side effects. I'm not sure why, but we have a study right now at Memorial Sloan Kettering trying to look more into that. So I will report once we have more information. In terms of the exercise therapy, so this is part of the literature review that Dr. Stanford and I did. We found 25 studies in the animal models and humans studying the effect of exercise, different exercise programs on the patients or animal models with steroid myopathy. And basically across the studies, the exercise was shown to reduce the rate of atrophy caused by steroids, both fluorinated ones and non-fluorinated. And the participants were able to regain strength loss from steroid administration. In terms of the exercise modality, so that is a little bit different. So basically, we were trying to compare endurance versus resistance training. And due to different methodology of the studies, and that there was multiple studies in rats and very few in humans, we were unable to come to a conclusion whether one is superior, but definitely both show positive effects. And moderate versus strenuous exercise. There is some data that suggests that strenuous exercise might be actually worsening atrophy. So we're thinking that light and moderate exercise would be better. And then in terms of length of therapy, it's very hard to extrapolate the data from animal models into the human models. But basically, one study we had compared length of exercise versus strength of exercise. Compared length of exercise versus and showed that higher improvement in the group that had exercised for more weeks. And then in terms of the anabolic steroids use, so it's an official, as I said, FDA indication for the, it says to indication for offset of the protein catabolism associated with a prolonged administration of corticosteroids. And there is one study available on anabolic steroids use in steroid myopathy, and I will talk a little bit more about it on the next slide. There has been several pediatric patients that were treated that we know of with Exandrolone at Memorial Sloan Kettering, patients with steroid myopathy due to steroids administered for GVHD. So far, there is no published data available in pediatric population. We're going to try to analyze the results of their treatments and report further. And in terms of how Exandrolone is helping, so it started to act through stimulating insulin growth factor one expression. So that's the factor that steroids are actually inhibiting. So steroids are inhibiting, and that's the main reason why the catabolic action is happening. And Exandrolone is overriding that. So that's the idea why it's helping. Oh, sorry. So I guess I didn't have the slide on anabolic steroids use, but I guess I took it out for the time sake. But what I wanted to point out is that that study was only, the participants were only men. They had specific reasons why they used only men in that study, but I don't have any data on women with steroid myopathy treated with Exandrolone. At least I didn't find any. And then just a few of the final thoughts. So there is a study that was actually using ultrasound on trying to detect steroid myopathy early on prior to clinical symptoms. And based on that study, it seems that the patients who are getting steroids might be manifesting with ultrasonographic features that could be related to steroid myopathy prior to them developing clinical symptoms. So they haven't yet developed clinical weakness, but on the ultrasound, it seemed that the muscles have already changed. Thinking of that, I am considering this would make sense to me that maybe we should start targeted moderate intensity exercise therapy for those patients getting steroids earlier than them developing clinical symptoms. And of course, when they do develop clinical symptoms, obviously they have to start exercising. And then my thought process is once the clinical symptoms are there, then we definitely need to act. So either we need to consider lowering the steroid dose or at least have a discussion about it. And if that's not possible, then we definitely have to act in one way or another, including possibly starting Exandrolone treatment for them. And yes, another thing that I wanted to mention, but I think I already emphasized that is about a possibility of using ultrasound to track the progress. Because right now, it's difficult to have kind of like an objective. There is no objective assessment of those patients, except for manual muscle testing. So it's either dynamometry, that would be the muscle strength. And if we want to assess volume, ultrasound could be used. OK. And in terms of the future directions of the research regarding steroid myopathy, so things that I would like to have answers about is steroid dose needed to cause steroid myopathy, especially in children. I don't have good numbers on that. And also the progression curve. So progression curve is not described generally as of now. So I think it would be good to have a study either with just dynamometry and manual muscle testing or something, but to describe progression curve of the disease on the certain dose of steroids and the recovery curve once all steroids or once the steroid dose is decreased. And also, how early should the physical therapy be started? And then what is the best monitoring strategy? What should we use? Dynamometry only, or do we need something else? And are anabolic steroids safe? There are some side effects that should be considered with using those medications. As I said, they are not used commonly as of now. So there is a lot to learn. And this is it. Thank you so much for your time. And I wanted to give a special thank you to Dr. Ibanez, Dr. Stanford, and Dr. Serkin for support and collaboration. And just overall, thanks for having me here at New York Presbyterian and at McConnell Sloan Kettering. All right. Thank you. Now we can move on to our next speaker. Sorry, my room, the lights keep going off. So if I get up and jump around, I'm just getting the lights back on. If anyone needs a quick stretch, feel free to get a quick stretch in and we can get started. My name is Heather Nauman, I'm a fellow at MD Anderson Cancer Center, and I'm going to talk about cachexia in our cancer patients. So no disclosures. And the objectives for this lecture, I'm just really want to go over kind of the definition, the stages, diagnosis, and the available treatment options for cachexia. So what is it? So it's a complex metabolic syndrome that's associated with an underlying illness, which in our case for our patients, cancer, and it's characterized by a loss of muscle mass with or without the loss of fat mass. The pathophysiology is related to having systemic inflammation. So cancer cachexia occurs in about 50% of all patients with neoplastic disease, and it is a poor prognosticator. More than 20% of patients who are diagnosed with cancer will die from cancer cachexia. So it's very important to be able to recognize it and intervene. So the prominent clinical features in adults is weight loss and in children, growth failure. And again, making sure we account for any fluid retentions or endocrine disorders in these patients. Anorexia, inflammation, insulin resistance, and increased muscle protein breakdown are all frequently associated with any wasting disease. And this is distinct from starvation, age-related loss of muscle mass, depression, malabsorption, and hyperthyroidism, and it's associated with increased morbidity. So there's three kind of stages. I kind of think of it like a spectrum. You have the pre-cachexia phase, cachexia, and then the refractory. So in pre-cachexia, these are like very early signs. You start noticing the anorexia, maybe impaired glucose tolerance. Usually they've only lost like less than 5% of their total weight loss. So you may not notice like a huge, but it's the beginning of it. Excuse me. The risk of progression varies, and it depends on the patient's stage and type of cancer and how aggressive that cancer is. The presence of systemic inflammation, how much food intake they're currently doing, and the lack of response of their anti-cancer therapies. So then once we enter the cachexia phase, these are patients who have more than 5% loss of their stable body weight over the past six months, or if you're unable to figure that out, if you don't have the information to determine that weight loss, if they had a BMI less than 20. If they have ongoing weight loss of more than 2% or sarcopenia, or if they've ongoing weight loss of more than 2% and have not entered the refractory stage, they're classified as having cachexia. Then we reach the refractory stage, and that's a result, usually a very advanced cancer and rapidly progressive, unresponsive to treatments. And this is usually associated with active catabolism. Usually there's a lot of heavy inflammation going on. So if you're looking at labs, you would see a lot of inflammatory markers elevated. And this was really when it's management of weight loss becomes very difficult at this time. And so refractory cachexia is characterized by a low performance status. So the World Health Organization, a score of a three or four, and a life expectancy of less than three months. And just for those who aren't aware the WHO grade three is the definition of that is they're capable of limited self-care, confined to bed or chair, more than 50% of their waking hours. And a WHO grade four is they're completely disabled. They cannot carry on self-care and they are totally confined. And just for reference, the next stage would be a grade five, which is when they are deceased. So there's a scoring system called the cachexia score, CASCO, to be able to give some quantitative staging to cachexia in our cancer patients. And these range from zero to a hundred. And within that, there's certain ranges, mild, moderate to severe to terminal. And there's a bunch of factors that go into creating the score, but there's main five categories. There's the body weight loss and composition out of 40 points. There's inflammation, metabolic disturbances. And that's a lot of laboratory work looking at their IL-6 levels, CRP and et cetera. We can go into that more in detail in the Q&A if you're interested. And then there's physical performance, anorexia and quality of life. And those three are determined more, there's questionnaires that are given to the patients to fill out. And then total the scores obtained, and then you're kind of able to define their level of cachexia. And the diagnostic criteria in adults is weight loss of at least 5% in 12 months or less in the presence of an underlying illness, plus three of the following, decreased muscle strength, fatigue, anorexia, low fat-free body mass and abnormal biochemistry, as mentioned earlier, like elevated CRP, IL-6, patients with anemia and low serum albumin. So the key components for any patient with cachexia is really knowing that it's that fat, is that at least 5% loss of body weight, excluding changes with water weight. And the timeframe may be disease-specific. In cancer patients, it's usually shorter compared to patients with chronic kidney disease or COPD. So in our patients, it's usually within like a three to six month period versus the chronic diseases, it's more like a 12 month to kind of get the idea of how much quicker it comes. In cases where there's a history of weight loss and you can't document it, I think I already had mentioned this, but just to reemphasize, if you can't get that 5% loss, as long as they have a BMI under 20, that is still considered a diagnosis of cachexia. So clinically, this is a clinical diagnosis. We have to take into account their body weight, their skeletal muscle mass is really important because if they've lost, most of these patients, when they lose weight, they're not losing fat, they're losing muscle, their food intake, their fatigue, range of motion is important to assess, quality of life surveys, performance scales, getting their serum, like inflammatory markers, fibrinogen, hematocrit, and albumin. And again, a lot of the inflammatory markers will be elevated, whereas your hematocrit, albumin, the iron panels will be low, decreased. So what do we do? Like once we have the diagnosis, what are we, what's next for these patients? There's really the big three, and of the big three, really, I think diet and exercise have been shown to be the most effective. I'll go into some of the pharmacologic, pharmacologics that have been studied, but I would just want to emphasize that even though they have been shown to help with some of the symptoms, they really provide more of a quality of life improvement, not necessarily improvement in their skeletal, in their lean muscle mass. So for the diet modifications, these patients usually have caloric deficit in cachexia, usually they have at least like a 200 to 400 a day deficit. And so adding additional supplementation of at least one calorie per ml can improve their nutritional status, especially for these patients who are receiving chemotherapy. Our usual goal, I think, we always try and tell patients to try and take in around one to 1.5 grams per kilogram per day, excuse me. And again, so some of this can be challenging for patients with decreased appetite, and that's where some of those pharmacologics will come into play. And overall, they really just need to increase their calorie intake per day by three to 400 calories. So for exercise, so we all, I think, know that exercises help increase our insulin sensitivity, protein synthesis, and helps with the antioxidative enzyme activity, and that it can help suppress maybe some of those, that inflammatory response that our patients are going through, especially when they're undergoing chemotherapy. So there is, you know, there's actually a lot of evidence to showing that endurance exercises, so doing high reps under a certain time, you know, extended time periods, kind of low resistance, can also really improve the cancer-related fatigue. So combining the resistance and the aerobic exercise training really helps these patients with cachexia try to at least to maintain the muscle mass that they have, even if they can't gain it, usually at least shows that it at least slows the loss. So pharmacologics, I'm gonna go over these pretty quickly, mostly because, again, they are with limitations. So, you know, steroids, I think we just had to talk about steroid myopathy, so there's always a risk with using steroids that we have to keep into consideration. There have been multiple studies done using prednisolone and dexamethasone at low doses daily, mostly to try and increase these patients' appetite and give them a little more energy to do the exercises. Again, there's, you know, you have to, they're very short-lived because they only can be used for a short period of time, and then during that short period of time, they may help, but there's really no data showing that it's like a long-lasting effect, and it does not overall increase their body weight at the end of the day. There's also use of, there's studies that have shown the use of progestogens, and it's very similar. It's kind of, you know, the thought is if we can help improve these, the appetite, caloric intake, that maybe we can help, you know, slow down or ameliorate the cachexia syndrome. And there are studies that have shown that, you know, like migestrol acetate did help with appetite and caloric intake on a low dose, but also you have to take into account, you know, some of our patients with, you know, with certain cancers, they would not be candidates for certain, you know, hormone medications. And you also have to be careful because like, especially in the MPA and a certain dose, it actually became, there were actually really pretty serious side effects. So they had, they were able to figure out the safe dose between 500 and 4,000 milligrams daily, but there are also other side effects we have to consider when using hormones. And I think anyone who works in the cancer world knows about cannabinoids. And again, the thought is if we can help with the anti-medic, you know, stimulate the appetite, that we can help improve. But again, the data doesn't really show an improvement. They may be, even if the appetite has improved, there's no correlation to improve body and overall body weight, especially lean body mass. Ghrelin has been also studied. Again, same thought, except for ghrelin, there also has the ability to suppress some of the pro-inflammatory cytokines. So the thought was maybe if we can not only stimulate the appetite, but also kind of suppress some of the pro-inflammatory cytokines, maybe that would actually really have a bigger effect on these patients. And there was a study done by Garcia that was phased to placebo-controlled double-blind study, and they gave ghrelin to these patients to try and improve their lean body mass. And it actually, the results did show they did have an improvement in their lean body mass, their total body mass, and their hand grip strength. And they actually did use just strictly cancer patients. And then there's also, thalidomide has been studied more on the angle of trying to reduce anti-inflammatory properties, thinking since that's the overall pathogenesis of cachexia. And I did find a study that was done in cancer patients that it did show it was very well tolerated, and it did help attenuate their weight loss and lean body mass in pancreatic cancer patients. However, there was, they also didn't, it kind of, again, kept it as stagnant, stagnant, it didn't help their overall weight, it did not increase as a result of taking the thalidomide. But again, it was also a short-term, they didn't do a long-term follow-up, or at least I wasn't able to find that information. And then there's also, I think, omega-3 fatty acids, that's kind of the simple thing we could do over the counter for patients. And this one also is for the thought, again, not only to produce pro-inflammatory, I'm sorry, down-regulate pro-inflammatory cytokines, thinking, again, if we can get rid of the cause, the pathogenesis of the cachexia, which is the systemic inflammation, maybe we would have improvement in these patients. And so there are studies that have been done that just showed the use of polysaturated fatty acids, especially like EPA, that have been used to try and decrease the amount of proteolysis-induced factor and it has actually shown that EPA does help inhibit those factors that do promote for protein breakdown. So in conclusion for my portion here, patients with cancer are at high risk for developing cachexia, not only after chemo, but also before, just due to the systemic inflammation that usually comes with neoplastic disease. The weight loss that happens during chemotherapy as well just makes for a worse prognosis for these patients and it can worsen their chemotherapy toxicity. So a cachexia diagnosis needs a full evaluation of their body weight, get their food intake, body composition, and again, some of those labs that we're talking about, the inflammatory labs. Dietary modifications and physical exercise so far has been shown to be the best strategy for these patients to improve their overall outcome. And some medications that really can help stimulate appetite and decrease inflammatory cytokines, we think overall can help improve these patients' quality of life. So thank you. And Dr. Engel is going to cover more on cachexia. Okay, am I muted. Sorry. Can you hear me now. Everyone hear me. Are we good. Yes. Awesome. Thank you. So I just wanted to thank the other panelists for speaking. They did a great job, and honestly, they presented so well on this short time that we have that they really did a great job and it didn't leave much more work for me to do, although there's a lot of research that can be done on this topic. So I'm talking about the adult portion of muscle wasting and cachexian patients with cancer. So I don't have any disclosures or financial issues to disclose. And so I just wanted to bring to the forefront that we're talking about muscle wasting and cachexia in adults with cancer and skeletal muscle wasting is a poor prognostic factor, and this can be seen regardless of what someone's starting body weight is and folks that are obese as well and should keep that in mind. And I was also going to talk about the NCI division of NIH future research, as well as ASCO's recommendations, the American College of Clinical Oncology. And I just wanted to also remind everyone that maltrition and cachexia are technically distinct entities, although they can be found in the same patient. So this is part of the ASCO guideline, and basically it's on the management of cachexia. This was a group that was put together, and they released these guidelines back in 2020 in the Clinical Journal of Clinical Oncology. And again, they said cachexia is multifactorial and correlated with decreased survival, decreased quality of life, and increased treatment toxicity and fatigue. And as physiatrists, we have it within our scope of practice to help improve quality of life and help patients that have cancer and have various side effects and various treatment toxicities improve their quality of life and improve their functions. So this is something we should be very, very cognizant of. And the numbers are in the chart to help determine how much weight someone's lost. And then we can also ask them these other symptoms. Because we're looking at weight loss, as well as loss of appetite and decreased skeletal muscle. Unfortunately, some of the treatments can have various impact on their appetite. Some people can have what's called dysgeusia, or yucky taste to things, or something they used to love, a meal they used to love now tastes awful, and they won't want to eat it anymore. And then there's the other challenge also of making all their appointments that can pose a problem into getting the nutrition they need. And they might take longer to eat. For example, someone that has a head and neck cancer, for example, and it's harder for them to swallow when it takes a lot longer for them to eat. They can't just, you know, shove a sandwich in their face in between appointments or in the car. So the guidelines that looked at randomized control trials and systemic reviews, they tried looking at a lot to begin with, and a lot of them didn't really fit their criteria. And they looked at 33 total from 66 to 2019. And they wanted to also remind people to think about caregivers and to think about caregiver distress. Because caregivers, it's very, very, we have ingrained within us, in the United States at least, to, and in many other countries, that food means a lot to us and food is associated with various holidays and family events, be them happy or sad. And they have connections and things like that. And if you don't know what to do for someone that's been through, maybe lost a loved one, or you might bring over a food item, for example. And so they're reminding us of how there are all these close ties that we have, these complicated societal and cultural wars that are around food. For caregivers, maybe it's a significant other that for years has made their meatloaf for their loved one, for example. And the loved one doesn't want it anymore and they feel like they're failing. They feel like that's something that they can do to help their loved one. And when they can't provide them the food or they're not eating what they used to, or they don't like what's served to them, they can feel like they're failing. And it's something that I thought was very interesting that the ASCO guidelines pointed out. And really keep in mind that there's limited access to care for several folks that have health disparities and minorities and at-risk populations that can further complicate the matter. So, just to talk about a little bit as well, just some research that's coming down the pipeline. The National Institutes of Health, the National Cancer Center, sorry, the National Cancer Institute talked about cachexia and they said for years we were in this desert of no advances, no progress. And they talked about what's called crosstalk. And there are cancer cells releasing these cytokines, these chemicals, talking to the fat and the bone and the muscle and basically corrupting them so that the machinery doesn't work as well as it used to. So that you can give someone that has cancer, that's being treated for cancer even, the right amount of nutrition and water and the machinery won't process it the same way as they used to. The machine that is the body won't process it the same way. And it's being corrupted by these cytokines and this crosstalk. And now there's a lot, a lot of inflammatory markers between the host cells or the body and the cancer cells. And this disturbs the normal metabolism, the normal factory that we have within our body. And immune cells are taught to release these cytokines, such as IL-6 was one of the big ones and there's a lot of other ones as well. They also talked about GDF-15 and being studied as it determines a desire for appetite, and it binds to something called GFRAL in the brain. Previously there were no medications at all in the world. I'm sorry to say 2021 that were approved for, for cachexia, but in 2021 in Japan, this anamorellin was approved and it mimics ghrelin, an appetite stimulant. However, ghrelin does not appear to actually be low in a lot of patients that have cachexia, and there's trials that are currently ongoing with this medication that started being used in Japan, just about two years ago. So back to some of the management of cachexia and ASCO guidelines. They talked about the different things that you can do for someone that has cachexia and the type of recommendation and the evidence behind it and the strength of the recommendation. So these are some things that sometimes our oncologist collaborators like to see. So the nutritional referral for counseling of nutrient-dense, high-calorie and high-protein diets was an informal consensus. The evidence quality, however, unfortunately is low, but the strength of the recommendation is moderate. They cautioned against, this is very important, they cautioned against the use of parenteral and tube feedings and said that they should only be used if there's like a reversible cause. For example, someone has a first-time bowel obstruction and it's going to be, have surgery and it looks like it's reversible. And this is an informal consensus again. This was low evidence quality, however, they thought the strength of recommendation was moderate to avoid tube feeding and parenteral nutrition in long-term use, and I thought that was very important. And then they did reinforce that in the United States, there's no current FDA-approved medication for cachexia. And so it is okay, actually, even according to their set standards, not to offer medication. And that was evidence-based. The quality, though, was low and moderate strength of recommendation. They did, however, as just illustrated, point out that steroids used in the short-term and progesterone analogs potential to improve appetite and your body weight, and that was evidence-based, intermediate quality, and moderate strength of recommendation was moderate. And I just want to remind everyone again that we're using this interdisciplinary approach. We're working with the whole team, so we have our great colleagues in counseling, in palliative care, as well as in nutrition, physical occupational speech therapy that can help us as well, because cachexia does not occur in a vacuum, and it's impacted by so many things, and to look at the whole picture. And that also a lot of cancers, unfortunately, when the person is diagnosed, it is because of a weight loss. It is because the person might be already considered cachexic at the time of diagnosis, and pancreatic cancer, for example, is one of those cancers. So by employing something like rehabilitation, and this is the definition here, or trying to see the patient as close to diagnosis as possible, as close to when they're diagnosed prior to having any interventions, can allow us as physiatrists who see patients with cancer to jump in and make a change. We can allow for those nutrition referrals. We can allow time to discuss physical activity, and how that can help improve the patient, and help improve their quality of life, and help improve their fatigue, and help improve their skeletal muscle, and help them become more independent and maintain independence. So I just wanted to leave that here, and then there's some more information about cancer rehabilitation here. I'm just going to go through that so we have some more time for questions. And then Dr. Gould had cancer cachexia prevention via physical medicine, a physical exercise molecular mechanisms article that was published in 2013. And they illustrated that cachexia can occur, like I said, in early or late stages of cancer. Sometimes people have this weight loss, this unexplained weight loss, for example, before they're diagnosed with cancer, and it's often seen in pancreatic cancer. And they also show us that exercise is extremely beneficial because there's so many cytokines and interleukins and tumor necrosis factors that are affected, and it inhibits inflammatory cytokines, and also, among other things, decreases oxidative stress. With repeat exercise, you have more superoxide and various other factors from exercise also protect against cell damage. And again, as illustrated in one of my favorite articles, the American College of Sports Medicine Roundtable articles, the three articles that came out a couple years ago, report on physical activity, sedentary behavior, and cancer prevention and control by Patel. Being physically active is one of the most important steps for people of all ages and abilities. They can take for cancer prevention, treatment, and control. So that's one thing I want to remind people as well. And also, exercise can be very helpful because some people have to be so careful about side effects that occur in medications, as just illustrated, such as Magestrol can have side effects, and almost all medications can have side effects. So that's just something I want to illustrate. And I think that's it, and that's my email, and I'll stop sharing, and I think we might be up to questions. Awesome. Thank you guys all so much for such incredible talks. I learned so much. For those that are listening, do we have any questions for our amazing speakers? And if you do, you're welcome to just like unmute yourself and shout out or you can type your question in the chat. I have a question. Can you hear me. Yes. Hi, I'm Leslie big a I'm at JFK john rehab. So my question was, in your practices like in your outpatient practices, how do you go about kind of following patients when you're evaluating them for kink axia totally followed you know how you guys die, you know the diagnosis and the since this is kind of a long process for these patients, how do you follow up with them like how do you kind of stay on top of, you know, are they doing the exercise are they following the nutritional recommendations what have you found beneficial in your experience. I think what I tend to do is try to see the patients if I can. I'm going to be honest with you, I don't have a formal kink axia program I know some other places do like Dr. Roy is very very involved with it and has an excellent program and Dr. Hunter does as well. I actually try to see them fairly frequently because I think that those are some of the biggest issues. And it might just be like talking with someone about what they can eat and what they can what's portable and, you know, because it's a huge change in their life and it's just another thing to think about as far as the nutrition x aspect, but I do at least every month at the schedule allows and even I think this is a good opportunity to increase access to care, and sometimes increase access to care through virtual medicine. So just trying to even the caveat to that is that we might not have a weight on that day. But it's very likely that within the recent past they have been seen in the clinic and there is a weight that you know on the day that they had to have their infusion or something like that. So I do try to see them at least every month and see how things are going as far as their nutrition as far as, you know, you know how they're eating how their fatigue level is how are there things are able to do now they weren't able to do before and whether having more side effects from their treatment and things of that nature I wish I had a better like screening tool, better program, but at the state and time. I don't but hopefully in the near future I will. Does that help. Thank you. Thanks. I just wanted to add to. We also at MD Anderson don't have an actual cachexia clinic, but we do have a pre habilitation program, and part of that is, you know, we would hopefully I guess if the oncologist get them in early enough. We get some time to be like to get a basic measure so we have like a to need a machine to give us a good idea of their body fat body composition to see how much fat, and how much lean muscle mass they have go, I can start. We also have them meet with a physical therapist to get a good, like, actual plan for their therapy and their home, like a home exercise program, and then we always make sure that they have not yet been seen by nutritionists that they are seen by a dietitian, and we also give our spiel about making sure they have adequate protein intake. And then we try we also have offer them. We have our nurses usually call these patients. They're not in line and, of course, but we will offer the nurse can check in after like four to six weeks to see how things are going, what's been challenging, are they able to do the exercises have they had issues with nutrition and see if anything's changed or if the need is be seen by us sooner rather than later. And then after they have surgery or their, whatever the intervention is by oncology, we follow up again, like, after like you know six to eight weeks afterwards, and we do another to need a measurement and we kind of see what has changed, and we do it again in like nine months to kind of see overall, how are they doing, kind of get an idea they are they quickly losing their muscle mass, are they maintaining. So those are things that we've we've done for the prehab program and MD Anderson. All right, guys. One question that came in, if there's one thing you would emphasize to patients with steroid myopathy, what would it be. I'll take this one. I had a, I had a young patient who was like 18 or 19 Oh, he must be 19 because he's like first year in college and he was I think a baseball player and he was so so so and he had like every lapse of his cancer and was started on steroids and he was asking me a lot of questions about what will happen he was so worried he knew about myopathy, a lot, because he actually did his research. And then when I came and it just happened that I also knew something about it, we had a talk for half an hour. So I told him to stay active and to exercise, I told him not to go crazy because he was doing a lot of weights, and I told him that I, there is some data suggesting that overdoing it might be actually the commental for the muscles that are being affected by steroids. So I actually made sure to explain to him that I want him to do. And maintain his activity level to the best ability. I mean he was pre, you know, he was very active and doing a lot of sports before so for him it was easy, because I just told him to try as much to stay active as possible for someone who is not as active prior of course it will have to be discussion of what exercises we would like them to do but I would definitely want them to do some aerobic activity some resistance training, but not big weights and not nothing strenuous to make sure to not damage the muscles that are already at risk for being damaged. That's what I would do. Nutrition I actually think, I mean, again, as I said there is no like there is no perfect data for us to use for steroid myopathy but it just makes sense for to talk about, you know, protein intake if they're, if they're doing a milkshake and they're all kind of different types of shakes those days especially when they're being treated with chemo and stuff to just tell them to add protein to the shake as opposed to just doing it without protein I think it makes sense even, you know, it wouldn't hurt. One of the biggest things that I tend to talk about with patients is that, unfortunately, that they can be at a greater risk for falls, and to reinforce that they have to be more careful with things like the steps getting on and off the toilet in and out of a chair and things in and out of a car and talk about different strategies in that realm as well. And that could be a good opportunity for an occupational therapy evaluation as well. Absolutely. It sounds, sounds good. The next question we have is psychopenia versus cachexia, what are some of the major differences. So, I'm full disclosure, I haven't talking with with with Dr. in New Orleans, and I think we're going to split hairs with things at that time if that's okay with you to talk about muscle wasting and sarcopenia and cachexia and some of the, the definitions there and talk about that with the panel that was kind of one of our plans if it's okay if I table that until the fall if that's okay. Legit, I like it. Kelly, and panel. This is Sam. Great talk guys. Couple comments but then kind of open up to kind of gauge your, your perspective. Obviously, Dr. Roy, and I kind of work together here, and we've worked with a lot of different people who are in the audience. I think a few things as we talk about muscle I think it's important to pay attention to other organ systems as well. We talked about like steroid myopathy. One of the things we at least we talked about a little bit is bone health as well. And so although we may be talking about exercise and strengthening. We also have to pay attention usually the people who have steroid myopathy, often not able to get off the steroids for whatever reason. And then, so we've got to pay attention to bone health so when we kind of approach, at least from an exercise standpoint, that is part of the discussion of what to do, as well as kind of that weight bearing exercise and to kind of engage with that in the context of safety. I think a lot of these, the challenges that we face and I know you kind of talked about the prehab component, where usually this like secondary referral, that's kind of like people already got a bunch of problems. When they come to us, and the challenge, ideally with a lot of these things is identifying early and preventing progression, similar to, I don't know, graph versus host related complications, right? If you kind of get someone that's contracted and have all those issues, there's only limited progress you're going to be able to make on that secondary effect. And so I think the goal is hopefully to get us more involved within these programs, and I actually don't think a lot of cancer centers have these types of programs, or they get them when like palliative care is kind of in because they've already lost 50 pounds and their skin and bones and you're kind of like, I think this was going on a little bit before. And so this is a little bit more of kind of like advocacy of what we need to do in terms of gauging, because I think we catch people oftentimes, and I know Dr. Roy's been kind of working on that, and I think the mechanism is going to be a lot of what you guys identified early and what are risk factors before you actually see the results to hopefully prevent. So we see a lot of different diagnoses, whether it's the GI cancers or other people who are higher risk, that kind of we know they're higher risk based off what their perspective time course is going to be, or steroid myopathy and potentially think about interventions that we can do to prevent and engage. So that's at least from my clinical experience. I know everyone's had different and I don't know if anyone had any thoughts or ways to kind of help engage where we don't catch people where they're already significantly down the road where you're merely just able to give kind of supportive care for these people versus actually intervening and preventing progression. Thank you so much, Sam. Yeah, I'm, I hesitate to talk about this, but I'm part of a prime for LT clinic as well. Well, that is the, it comes out to the acronym crime, but it's a clinic looking, looking at folks that have frailty that are 75 and older, but it's not all patients that have cancer. It's patients that are that are pre-op. And so I think that we do get patients for more of a pre-op perspective then but it can also be on one hand, it can also be after nothing else has worked, then this is what you know we're doing to try to help with, with, with the And like, like you said, it's the patients that have lost like 50 pounds and things like that and can we get them in a good enough shape for surgery. But no, I think you guys have an awesome, awesome clinic and thank you so much for for commenting. Any other questions from anyone? It doesn't seem like it from the silence. So, um, so what I'm going to do is I'm going to say thank you to everyone for coming today. This was a really fabulous discussion. It's always really great when all of us cancer geeks get together and talk about these really important topics and see what other people are doing and in other different facilities and and I just, I'm so thrilled to be a part of this so thank you to everyone who put in such such hard work into the presentation and thank you to everyone for sharing their perspectives and time today. Thank you. Can I can I just ask one thing does anyone have any suggestions for what we should be doing, other than then Sam because I think that maybe this might be an opportunity to ask that, or other other ideas or places that we should get in and, and, you know, kind of bring our grassroots effort to the table. I'll bring it up again in the fall. I can speak for kind of like pediatric population because I'm now involved in with the children oncology group. And I think some, I mean, ideally we should be involved in the planning of clinical trials and design of the clinical trials and designing of the end goals. So I think I actually can speak for adults just because I wasn't looking into those but I think getting your oncology team on board and doing something together in order to improve the outcomes just makes sense. But I know it's easier said than done. And for children, I think children oncology group is kind of like very umbrella and it involves a lot of institutions around the country. So it's very convenient. I don't know if there is similar, something similar for adults. That's a great idea. Great. Awesome. Thank you for bringing that up. Thanks. Take care, everyone.

steroid myopathy

muscle wasting

pediatric cancer

exercise therapy

medication treatment

cachexia

diagnosing cachexia

ASCO guidelines

medication options

bone health

interdisciplinary approach