Chapters Transcript Video Exercise Therapy to Attenuate the Physiological Impact of Cancer Therapy Lee Jones, Ph.D. presents at the Johns Hopkins Department of PM&R’s Grand Rounds on November 16, 2021 great. Um So, good afternoon everyone. Thank you so much for joining us at this very special. Grand round in honor of our esteemed colleague. Dr Tom Finley. We are very grateful to be joined today by Patricia Finley Tom's wife, his family and many, many friends this afternoon. Thank you so much for being with us today. Dr Finlay was a psychiatrist and a researcher. He was in the department of Physical Medicine and rehabilitation at Rutgers New Jersey Medical School for many, many years and served as the director of research. I got to know Dr Finlay in about 2000 and 10 when I first invited him to give grand rounds in new york city, he gave a phenomenal lecture on his incredible work on Fascia and the extra cellular matrix and its effects on movement. Movement. I have to tell you that I still remember that lecture vividly as it changed the course of my own thinking and research. What struck me then was how he was unafraid to explore new territories. Few people then knew very much about fashion. When DR Finlay approached us to do research on exercise therapy in cancer, he brought that same spirit of exploration. He had brilliant ideas. I needed a team to execute on them. We are so honored and humbled that he chose us. Dr Findlay has given us the greatest gift of all and that is the gift of the spirit of exploration and a very clear mission to follow. We thank the Findlay family for sharing term with us. He is forever part of our own rehab family. We hope that you will stay connected and we will be sure to update you on our progress. It was Dr Finley's wish that we invite Dr lee jones to learn about his use of exercise in oncology. Thank you. Dr jones for joining us today. Dr jones did his training in sport and exercise science at Brighton University in England. Then he did a Masters in health psychology, exercise behavior and cardiac rehabilitation at Lakehead University in Ontario Ontario Canada, followed by a PhD in exercise oncology and health psychology at the University of Alberta in Edmonton Canada. And then a fellowship in exercise oncology at the Cross Cancer Institute, also at the University of Alberta. He is currently at Memorial Sloan Kettering Cancer Center where he serves as the chief of the exercise oncology service at the Department of medicine in the division of Solid tumor oncology. Without further ado dr lee jones. Okay, okay, thank you so much. I'll just pull up my screen. Yeah, mm. And everybody see that. Okay, Hopefully. So. Uh well, well, first of all, it's a it's an absolute pleasure to be here. And and I'm very honored and humbled actually to give this lecture um in honor of tom I really am. It's it's pretty incredible for me to be, to be here. Unfortunately. Met tom once. Um but it's similar to you. My my experience of tom was very, very memories. We had a zoom call of course during Covid about a year ago in, we're on a call for about an hour and tom just grilled me actually for about an hour about our studies, what we're doing, how we're doing it. Um and I remember coming away from the coal. It was and I just I just felt invigorated actually because it was really somebody who was, you could tell just how deeply excited he wasn't intrigued about research and really find it out. Um you know, get into the, get into the true answers of how we can help individuals with cancer and exercise being one of those one of those avenues. So it was a great conversation that just stuck with me and I was deeply saddened to hear of his passing and again, deeply humbled that I get the opportunity to to still present today uh in his honor. So thank you again for the invitation. Um so over the next 45 minutes or so I'll just set my timer. So I stay, I stay on track here. Um I'm gonna talk about about some of the work that we've been doing, I would guess over the past 20 years or so, believe it or not, we've been in this field of of what we now call exercise oncology and so hopefully um this is this is new information to to some of you. And I'm also going to present some some some new data today. Hopefully that will will be of interest. And I'm happy to answer any questions at the end. So I have no relevant conflict of interests. Um so today I'm basically gonna divide the talk into into three compartments. The first I will I will briefly describe about characterization of physiological toxicity in individuals with cancer. I think this is very important before we think about exercise is how do we first characterize what I consider to be physiological toxicity In the second part. Then I'll talk about the evidence from our group as well from other groups about how about supporting the role of exercise both to mitigate and prevent physiological toxicity in individuals that are either initiating, going through or completed cancer therapy. And then briefly in the final section, I will touch upon where I think um I think exercise rehabilitation in cancer may go and just give us some of my, if you will, my blue sky vision of where I think rehab might go. So just part one characterization of physiological toxicity. So I'll just I'll just start with this and and this is going to be well known to the audience. But when I when I first got introduced to oncology again, this was this was over 15 years ago when I started my PhD in Edmonton Alberta Canada. Um I would be recruiting individuals with cancer to our to our exercise studies and I became pretty fascinated by the fact that the way that physiological function impairments were really characterized in individuals with cancer. Um and really it came down to single organ assessment. For example, if individuals were going to go on to certain forms of chemotherapy, they'd be arresting measure of cardiac function. Individuals who might be going on to the thoracic radiation might receive arrested measure of lung function using permanent function tests. Um, but this this was really this is really like single organ assessment in patients that were in the resting state. And so, coming from an exercise physiology background and certainly my background in cardiac rehab, I was kind of fascinated how additional assessments weren't used in individuals with cancer. And so it became pretty clear to our group that although cancer is is a little bit different of course, than car nervous disease, it appeared that individuals that were going through cancer treatment were experiencing a lot of the same impairments that individuals with with cardiac disease also might be incurring. We know that individuals with cancer are typically a little bit older. So, of course, they present with a lot of co morbid conditions. Their cancer diagnosis. There's then a direct hit if you will from the different therapies that individuals might be receiving. We know that different types of therapies can cause damage to the different components of the cardiovascular system, be it that the heart, the lungs, the vasculature or even the skeletal muscle and at the same time, of course, as individuals go through therapy, we know there's also effects that are secondary to treatment. Things like de conditioning or in activity patients become more in active of course, during their treatment They gain weight, body composition changes. So we wrote a paper back in 2007 that we deemed we call this a multiple hit. As individuals go through therapy, they get a series of hits to the cardiovascular system that can cause impairments across the entire system. So instead, and rather than thinking about this from the perspective of single organ assessment, um, what is the what is the the integrative damage that might be happening or occurring across the entire cardiovascular system? So from my exercise physiology background, this is the way that we started to think about individuals in going through cancer therapy. Had these treatments that had might go through this, this multiple hit. So instead of just thinking about single organ assessment, we started to think about how can you look at integrative organ function, cardiovascular function in these individuals. And arguably one of the best ways to do that is through exercise testing. Now, this is not use exercise as an intervention. This is the use of exercise to basically to perturb the cardiovascular system. So, you can measure how well that system functions. And so with these tests you can put individuals on a bike or a treadmill. These are probably well known to the audience. I the gold standard assessment of integrative cardiovascular function is using something called the cardiopulmonary exercise test that you can measure something called Vo two peak or the volume of auction consumed per kilogram of body mass in an individual who's going through exercise. So essentially you can put individuals on the treadmill, you make them walk up a steeper and steeper hill at the same time, you're you're measuring their heart to make sure it's safe for them to exercise. And you're also measuring gas exchange information. And so you can measure how much oxygen they're consuming during exercise. And this is something called Vo two peak, sometimes also called Vo two max. So this gives you an idea of how efficient this individual is bringing in oxygen from the environment and delivering that action down to the muslim mitochondria. And we can measure this and this gives us a very good measure of the cardiovascular function of an individual. So just to put this into context. View to PICO cardiovascular function in humans can range from anywhere from from tim miller to the auction per kilogram of body mass. That this might be an individual say, with heart failure all the way up to the olympic athletes which are literally off the chart. They could have vo two peaks of 80 85 and even above. So this is the range of view to peek in humans. This is age here on the X axis. And what you can see right away is as we get older, our fitness declines. Um So that's just a job it gets to all of us. So your your fitness is determined basically by two things. One is your genetics. The second thing is your level of exercise behavior or physical activity. So individuals who are endurance trained. These have the highest level of fitness across the entire age continuum. These are individuals who are active and these are individuals who are the sedentary individuals. So these individuals have the lowest fitness across the entire age continuum. I'm just referencing here, a view to peak of 15. This is considered to be the lowest view to peak for independent living, which is really important. Landmark of course. And I'll talk about this a little bit later. So this has been our measure of how we can assess the impact of cancer therapy in individuals who are going through cancer therapy. So, when we first got into this field, we started with the hypothesis and because we were very interested how how fitness might change as an individual is diagnosed with cancer or certain types of cancer and how that might change as individuals then progressed through their through their cancer journey. So under the Y axis here we have cardiovascular reserve capacity or if you will, a person's vo two peak. And this is essentially time along the X axis. The blue line represents what we, what we know is the normal age related decline in someone's fitness level as they get older. The young lady depicts what we thought might happen an individual who has been diagnosed with cancer. So at first there isn't much difference, of course, at the point of diagnosis between individual individual that cancer versus ones one of those whose with cancer and then it's section B. This is when treatment hits. And at that point we hypothesize there'd be a significant decline in someone's cardiovascular reserve capacity. Moon's treatment was finished. The common notion was that, well, of course, treatment is finished Now, fitness spontaneously recovers and then continues on the normal age related decline. But is this true? Or does fitness not recover at all? It just actually flatlines and then continues on the normal age related decline or individuals with cancer due to the decline during treatment. And then does this continue to decline even after therapy? Of course, if if individuals, if you look at the normal age related decline, um, individuals who have been through cancer therapy, you might have experienced this significant decline or which we thought there might be a significant klein. These individuals would hit these hit these important milestones, such as over clinical dysfunction a lot earlier if they've been through cancer therapy compared to individuals who had not been through cancer therapy. So, we thought there might be a big hit and this big hit would have clinical consequences in individuals who have been through cancer therapy. So, we then started to test this model and find out whether this model is actually true or not. So I'm going to summarize a lot of data in just one slide, but essentially over the past 10 to 15 years or so, there's now been multiple studies that have been reported showing that there's this accelerated significant decline in someone's cardiovascular reserve capacity or their fitness level as they go through cancer therapy. And in fact, If you look at 3-6 months of cancer therapy and this could be chemotherapy could be hormone therapy could be radiation therapy. The degree of decline depends a little bit on on the type of therapy and the intensity of therapy. But in general, there's anywhere from 10 to 20% decline in someone's fitness level in about 3-6 months of therapy. And people would say, well, well, Lee, of course this, this is going to happen. These individuals are getting pretty heavy duty aggressive therapy. Of course you're going to see this decline. But I think what's important to keep in context is typically we see a 10% decline of fitness, Normally over 10 years of aging and an individual who's not going through cancer therapy. So in other words, 3-6 months of cancer therapy was the equivalent to 10 years of normal aging. And if you speak to individuals who have been through cancer therapy, they will tell you this, they will tell you that they feel 10 years older than they did before they before they started on their cancer journey. And so we and other groups have now quantified this using these objective measures to actually prove that that is the case. So the next question is if indeed you do see this, this rapid decline during treatment, what happens after the completion of treatment? Does it spontaneous recover what happens? So we've also done several studies in that space as well. I'm just going to summarize two of those very, very quickly. So the first study was was from our group which we published now a few years ago, almost a decade ago, I guess. Um And this was a very simple study. That's This was 140 women with early stage breast cancer who completed that their chemotherapy or radiotherapy. Um at least three years prior to them coming to the study. So very simply we brought these women into our lab, we put them, we put them on a bike to test there to test their fitness. And then we compare compare their fitness levels two Women of the same age Who had not been diagnosed with breast cancer and not been through breast cancer therapy. And these were the data and I think I think that that that they're pretty informative. So this is vo two peak range from 10 to 30 that was measured. And then we looted vo two peak Per decade of light. So this is an individual who are age 50, 60 and 70. The red represents the women with breast cancer, blue represents that age matched women or the healthy controls. And I think what you can see right away is compared to the women with breast cancer where we measured their fitness levels. The women who had not been through breast cancer therapy across all age decade of all decades of life had a significantly higher level of fitness. Um I think what's what's kind of telling about this, if you look at the median or the mean vo two peak for a woman who has been diagnosed with breast cancer, who on average is age 50 you can see their vo two peak is around about 20 the same Vo two peak and a woman who has not been diagnosed with breast cancer occurs on average at age 70. So, from a physiological perspective, our breast cancer survivors are operating actually 20 years older from a physiological perspective than women who have not been through cancer therapy. Another study published about seven years after hours and this is in adult survivors of childhood cancer. So, these are individuals who were diagnosed with cancer as Children treated as Children and then they've been in long term follow up. This is them bringing these individuals into a laboratory for testing a fitness 26 years following the completion of their therapy. So, this is again, view to ranging from 10 to 35. This is the group whether these individuals were treated with chemotherapy that included a type of chemotherapy calls a dream is in these are individuals got got chemotherapy that did not contain this particular type of chemotherapy and this is the healthy controls. And again, you can see the results very clearly. Those these individuals, even though they're almost 30 years following the completion of their therapy, still have a fitness level. That on average is about 21% below individuals of the same age, the same sex who have not been through cancer treatment. So not only do you see this rapid decline june treatment, but it doesn't appear to recover at least in the context of these studies. So the next thing we wanted to look at is, what does this mean? We know that low fitness is associated with, with outcomes such as patients might report lower quality of life. They might feel more fatigued and low fitness is is important for many other disease conditions. But we wanted to know is this clinically important in individuals with cancer? And there's a couple of studies that have looked at that. So this is the first study we looked at and this was in, in almost 400 individuals with lung cancer. And we measured fitness levels in these individuals. Um we basically split these these individuals into whether they had high fitness, moderate fitness or low fitness. And then we looked at the longevity in these individuals. Long story short compared to those individuals that are high or moderate fitness. Those of low fitness had the shortest survival time. And this is active for controlling for things like age, cancer treatment and other prognostic markers in individuals and lung cancer. So this was I think one of the first of these showing that fitness was had prognostic importance in individuals with lung cancer. Like since that time, we were also published a second study. This was published just a year ago. This was in 1600 individuals with various forms of cancer. We didn't measure view to peak in these individuals, but we estimated there this was exercise capacity on a treadmill with indirect measurement of their view to peak. So this is a peak met about five years of follow up again. We we did, we we split these individuals either into low fitness, moderate fitness or high fitness. And of course, I think the data is self explanatory here compared to those individuals of high and moderate fitness. Really not too much difference between them. The high fitness groups lives the longest, but you can see the high risk of premature mortality in the individuals of low fitness showing again that those of modern high fitness, it appears to be protective. So that hit to the system appears to be very clinically significant for many reasons, including poor survival rates in individuals who have been diagnosed with cancer. So just to summarize this first part, if you go back to our conceptual model, I think we we and others have now shown that you get this rapid decline in someone's cardiff Castle reserve capacity as they go through cancer therapy. This has really led to the notion of cancer therapy being associated with accelerated aging or accelerated uh accelerated physiologic aging or the other aging, female types such as cognition and other things have also been linked to this phenomenon and at least appear to our data. It doesn't it doesn't appear to continue decline. I would argue that it appears to flatline but doesn't spontaneous recover, which I think is very important. And we've also shown of course when if your fitness stays low, that also might predict for for poorer longevity in these individuals. So this now brings us on to the second part is what can we do about it? So if that's the bad news, what can you do about it to either prevent or mitigate the effects of cancer therapy on things like cardio, respiratory fitness Cordova. So, reserve capacity and in this respect, we we really thought about this from from a Nasa approach to spaceflight approach, you might find it's a little bit strange to be thinking about space flight and what's Nasa and space flight got to do with oncology. But there's actually a lot of parallels between these two disciplines when when an asteroid is preparing for spaceflight, they will go through an exercise training program both before um they go on their mission during space flight, they also will perform exercise training in space, believe it or not, and as soon as they come back to Earth, they also will engage in post flight exercise training. So we thought this was very analogous. What what might happen with an individual going through cancer? Can you think about it in a similar kind of fashion? Could you think about exercise training before an individual starts cancer therapy? Can you think about exercise training during their cancer therapy to try and offset some of the potential effects of of cancer therapy on on the on the on the cardiovascular system. And even after the following the completion of therapy, can you think about exercise training there to help recover these individuals? So, this is the way that we've been thinking about it. So, over the next little bit, I'm gonna split my talk up into studies that have looked at exercise before cancer treatment, those during cancer treatment and those after cancer treatment. Now, there's been a lot of studies that have been published over the past 15-20 years, so, I'm not going to be able to summarize all those studies of course, but I'll just hopefully just give you a flavor of some of the work in in these areas. So, what about rehabilitation? So, to confess this is this is an area that I really followed too much, but there's been an explosion of interest in the role of preh ab in individuals of cancer, particularly those who are going for a pretty major surgeries to see if we can lower complication rate. And so um to look at to do this talk, I actually pulled up a couple of recent papers just to get a sense of of of this data. And so these are two recent studies. I'm not going to go through these studies in any great detail just to say that these were both in these both studies where individuals would call rectal cancer, which is a pretty major surgery and this is short term physical activity, exercise advice in the period before these individuals were going through cancer surgery. Again, I'm not going to go through these studies in any great detail only to say that both of these studies were negative. The role of rehabilitation in both. These studies failed to improve surgical recovery in both. Um, and so and you know, this this study here is in I mean, this is a large randomized control trial 761. And it seems to be that that's that's really the this status and hopefully maybe somebody can correct me. But in pre op I think there's been a lot of efforts here, but the studies to date have been a little bit disappointed. I think one of the major reasons for that of course is we've got a very short window of time between diagnosis, the surgery in which to intervene and so these studies are doing, you know, asking individuals to do a little bit more physical activity. But the impact has been minimal to date at least. That's been my read of it. So, we've been doing a study here at M. S. K. That I think is it might be might be relevant to the setting. Now this study actually is not designed to look at the impact of exercise on surgical complications is designed to look at the impact of exercise on tumor biology in in in men with prostate cancer. But I think again, I think these findings might be relevant to the preoperative setting. So this is this is a Phase One A Phase one B study. It's essentially a dose escalation of exercise in the preoperative window of opportunity. So we're taking about 40 men with prostate cancer, all of which have to be inactive to get into our study in the first place these men get then assigned to one of six different escalated doses of exercise. So the lowest dose is 90 minutes of exercise. The highest dose, believe it or not, is 450 minutes of exercise per week. And this ranges anywhere from from 12 from 3 to 12 weeks, depending on how long the individual has before their surgical intervention. As I mentioned, this is that this is a phase one Be study as well. So we're going to identify what we consider to be the maximal feasible dose of exercise in the setting. Will then recruit an independent sample of 20 patients and run them through the same dose and again, this is not designed for surgical complications. But I just wanted to share this with you because I think I think some of the finest might be relevant which I'm going to share with you next, nope. I think importantly, one of the limitations of course if these preoperative rehab studies is having sufficient time to exercise individuals before they go for surgery because it's a short short window of opportunity. Now, most of the approaches to exercise training in the pre have as well as after after cancer treatment. It's been using a facility based approach. This is where we bring individuals into our facility so we can monitor every single exercise session to ensure that they're doing, we prescribe exercise correctly and to actually quantify exactly what individuals did. This is the way that we've done to really make sure that we're delivering high fidelity exercise to individuals with cancer. The problem with this of course, it's highly inconvenient to get individuals traveling to a center even three days a week. Imagine trying to get somebody in five days a week for a standard period of time. It's expensive. This is like a slower cruel which has been absolutely problematic. So with this particular study we knew we had to design an alternative approach. If we're going to be able to do exercise studies at high fidelity that didn't involve the inconvenience of coming into a center. So we designed something called digit X. Which basically puts together a bunch of digital solutions and devices together with advanced analytics. That now allows us I think to address some of the major barriers. We've had to deliver an exercise at high fidelity in all clinical populations including those with cancer. So when individuals come into our studies we send them a study kit. This this includes a treadmill. So we send individuals a treadmill. This comes with an ipad healthwatch, bluetooth scale blood pressure cuff and also a glucose monitor. So we send these two to our to our individual participants. All this data all the apps are connected to the iPad. All this data flows through something called political cloud. It comes in all passively so we can collect information on individuals basically 24/7 that they're in the study. And then we can use this information. It comes into M. S. K. We can real time visualize whether individuals are wearing the device is not what these devices are. Talent us. And of course we can monitor these individuals now in real time while they're doing their exercise sessions. So this is what it looks like. So to get down the issue of convenience everything is done remotely in our trials including the informed consent. We can do that remotely because we send them a tremble. We can do a fitness assessment in their home. This is a sub maximal exercise assessment. Every single exercise session is also done remotely in the person's home with one on one real time monitoring by your exercise physiologist that are sitting here in Manhattan in new york city we collect a lot of bio specimens in our protocols. But instead of asking individuals to come into M. S. K. To to give us bio specimens or blood draw, we send a company to their home also to collect the samples. So in other words, an individual never needs to leave their home to do all the study procedures. Um because we send them all these different devices were now able to I think characterize the physiological impact of exercise in a manner that's never been previously possible. For example with with with the health watch that we've given. We now get a heart rate reading every 10 minutes 24 7 we get a blood pressure reading every day. We get a body composition every day. Which is obviously a lot different than just getting a reading. Maybe just during exercise session or baseline and post intervention. This comes into our systems were able to analyze it. And some of our studies were also getting, as I mentioned, bio specimens. Not really going to talk too much about that today, but just just telling you what we're doing in the context of some of our studies. So get to get back to the preoperative study in preh ab again was not designed to look at surgical complications. But I just wanted to share with you some of the fitness data that we've collected understood again. I think it's instructive um to maybe the future of of sump rehab studies. So in these individuals we measured sub maximal exercise both at the beginning of the intervention again at the end. And this is just some of the data. This is not this has not been peer reviewed yet. So you can take this with a pinch of sold. This is percent change of delta change in fitness. And this is the individuals who did 90 minutes a week, 150 minutes of exercise a week, 375 and 450. Each line represents an individual patient. As you can see, we've got 26 patients who have been through this study to date those who did 90 minutes got about 6% improvement of fitness, 17% with 150 minutes, 19% 375 and almost a 50% improvement in fitness with those individuals that did 450 minutes of exercise. Now, I'm not suggesting that you told your patients to do 450 minutes of exercise per week before going for a surgery. My point is that it does appear to be dose dependent if you can get a greater dose of exercise into these individuals, even in a very short period of time, you can get some significant improvements in fitness. Now, whether those fitness improvements then translate into improvements in surgical complications and recovery, we don't know. We haven't looked at that yet. But again, I think I'd be happy to discuss maybe the future of where this could go. So that's pre hab what about during treatment? What is some of the studies that have been done there? So, I'm just going to talk about two. I think exemplar studies that have been done actually, both by my former supervisor, Carrie Kania, use in Edmonton Alberto. This is the first study which is now 15 or so years old, but I think it's an importance that it's talked about. This was a multi site randomized controlled trial three on randomized controlled trial. In 242 patients with early stage breast cancer initiating chemotherapy. Um, patients could be doing any level of exercise before they come into the study. I think that's important to emphasize just there's lots of endpoints in the study. I'm just going to talk about the changes in fitness and this was measured vo two peak. So, in the patients who didn't get any exercise, this is the control patients, As you tend to expect, there was a significant decline about a 5% decline in fitness in about 17 weeks of chemotherapy. This is the group that did resistance training during that time. And what you can see right away is resistance training did not mitigate at all the significant klein in Vo two peak observed with with control. So basically, resistance training was ineffective, preventing decline in Vo two peak a robot training. Those individuals who got a robot training, it did appear to completely mitigate decline that you saw in the other two groups. In fact, there was a slight increase in fitness in the individuals who got a robot training. This is a robot training three days a week. But from this study you would argue that really aerobic training is the way to go to prevent declines in fitness during chemotherapy and early stage breast cancer. However, there was also a second trial that that Dr. Turner did and his colleagues a few years later. This time it was in 301 women with breast cancer initiating chemotherapy this time, what they did, they did a standard dose of exercise training which was equivalent to the aerobic train dose. In the first study, hi basically, they doubled the dose of of of aerobic training. Or they also looked at the combination combination group. So this is the combination of aerobic and resistance training to see if that was more efficacious. These are the data and you don't need me to tell you, I think it's pretty self explanatory in all the groups, there was a significant decline in fitness. It didn't they did not replicate the protection against the decline with a robot trainer and all groups. There was significant decline. Now, this was slightly mitigated by the group that did high high doses, but again, this was not statistically significant. So from these studies, I think you could potentially argue that this exercise might mitigate decline, but there doesn't appear to be different between these different modalities. So what about after therapy? What what is it? Some of the data we know there again, there's been lots of studies that have looked at exercise training for the completion of cancer therapy. I'm not gonna be able to talk about all the studies. I'm just gonna give you, I'm just going to focus on on a couple of our studies again, because I think I think they're informative. So this is a study that we recently finished. This was in 174 women have completed breast cancer Therapy um at least 1-5 years following the completion of their therapy, all these women had to be inactive, defined as performing less than 90 minutes of exercise per week to get into our study in the first place. And all had to be unfit to its own studies. So we measured their fitness levels before they came to the study. If they were to fit, they were ineligible. We only took individuals, but at a fitness level below the age, much cemetery value. So these women were randomized to one of three conditions, either a control group that got stretching or two different types of exercise training regimens. Either something called a linear aerobic training program or a nonlinear aerobic training program. So, I'll just describe to you what I mean by these. Mhm. So, linear training program is essentially the approach we take with most exercise interventions. There is progressive If you will escalated period in the 4th, 1st 4 weeks of the trial, where we increase both the intensity in the duration of the exercise sessions. Thereafter, every exercise session is roughly about 75% of a person's baseline exercise capacity in each one of these sessions is about 45 minutes in duration. So this is the classic approach to exercise training would call that linear approach. What we what we want to do is test something called the nonlinear approach. So this is the way that you're basically train if you're running for a marathon Again, just in the interest of time, I'll just quickly describe it essentially. Now, each one of the exercise sessions is of a little bit different intensities. Exercise sessions range from anywhere from 50, at baseline exercise capacity. This would be a session in black all the way up to Kind of the red bars here, which represents an exercise session at about 95% as someone's baseline exercise capacity. All these other lines represent somewhere in between. So basically you've got a you've got a mix of high intensity sessions together with lower intensity and modern intensity sessions that gradually progress across the course of the intervention and they're all mixed. Excuse me. So, this is called the nonlinear training program. So we basically wanted to test which one of these was more effective at improving fitness in individuals that have completed their therapy for early stage breast cancer. So here's the data. So this is this is the stretching group. This is the linear training group. This is a nonlinear training group. This is fitness here on the Y axis. As you can see in the stretching group, there's really no difference at all from from baseline to post intervention, you wouldn't expect them to this. These individuals are not going through any form of therapy. The linear group, there was a nice improvement in fitness as we know from prior trials, there was also improvement when only a training. But actually this was no better than than the linear training group. So both of these regimens were effective, but non linear was really no better than the linear training group I also mentioned actually, which is important. The nonlinear training group actually was the adherence rate was actually higher in this group. So, individuals that are doing higher intensity sessions, you might expect that to be associated with lower adherence. That's associated with higher adherence, which was an interesting finding also of interest actually was the individual patient response in this study. So we're not only interested in what the mean response in terms of all the patients put together. But what was the individual patient response? And I think what came through on this, which was pretty surprising to us actually Is that the majority of individuals, whether they got linear training or nonlinear training didn't have a clinically meaningful response in their view to peak level, like 65% had had an improvement of fitness. That was below that. What we would be considered to be clinically important. And this is classically what you don't hear about exercise study. We think that exercise works for everyone and it works very well well. It turns out that maybe that's not the case. So based on that, we actually have now a new study that's underway that's looking to see if we can identify what the optimal dose and exposure of exercise training is in these individuals to minimize that non response to exercise. This is the same algae bility criteria as our prior study. Now, individuals are randomized added to standard exercise, which is 100 and 50 minutes for 16 weeks. They either get a great dose of exercise so they either get 300 minutes for 16 weeks or they get higher exposure. So that's 100 and 50 minutes to double the length of time. So 32 weeks Or they both get intensity and exposure. So 300 minutes for 32 weeks. So this study is currently ongoing. And I think I think, well, I hope the results are going to be pretty interesting. Just one study I want to mention, just to say that this is not all about about breast cancer. We also just completed a study in about 90 individuals who completed treatment for early stage lung cancer. Again, all these individuals had to be enacted to go to our studies and unfit. We took individuals anywhere from 1 to 10 years from the completion of their therapy with a four on randomized control trial randomized out there to stretch and control aerobic training only resistance training only all the combination of aerobic and resistance training here are the data. This is the control group, aerobic resistance and the combination, this is vo two peak. You can you can see in the control group, nothing happens. None of these patients were undergoing therapy at the time. So you wouldn't expect there to be any decline or increase in their fitness. The aerobic training group, we saw a nice improvement in fitness resistance training. We saw no improvement whatsoever. We actually hypothesized that we would see an improvement in fitness with resistance training because these individuals tend to be a little bit more frail and we thought resistance training might improve fitness. It didn't um the combination of aerobic resistance training was also effective, but I think you could argue that was probably primarily due to the aerobic training component of this combination because resistance training by itself didn't have any impact. Um So again, the take home message from this study, at least if you're looking to improve fitness and an individual who's been diagnosed with lung cancer and finished therapy is maybe aerobic training is the way to go. But of course other studies are of course needed. Now. Just as Justin my final study I'll talk about, I think an important question literature and in clinical practice is if you have an individual who has been newly diagnosed with any form of cancer, the question might arise. When should I start exercise training? We know that we have we have data to support the role of exercise training during therapy. There's also evidence of course to support the role of exercise training after therapy. But I think often we we hear that if individuals are going to go through therapy, if you're going to continue to exercise program or thinking about starting a new exercise program, maybe you should wait until your cancer treatment is finished to start a new exercise training program. You've got a lot going on. Maybe a starting next program at that time might be not the best idea. We thought that was an interesting question because we know the detrimental effects of what can happen in individuals who go through therapy but don't exercise during you get that significant client. So the question is if you do have a new individual for diagnosing cancer, when should you advise them to start exercising. So we designed a trial to answer that question. This again, has not been peer reviewed. This data literally is now just finish it. So please don't share this data, but I just wanted to share some initial findings. So this was a randomized controlled trial of what we consider to be the optimal sequencing of data from the individual has been newly diagnosed with breast cancer. Sorry for the type of here, this should be breast cancer. So these these women were randomized to one of four conditions either aerobic training during their chemotherapy. They then transitioned to a control group After the completion at that chemotherapy, the second group either got their chemotherapy without any exercise training insurance. They finish their chemotherapy then transitioned to anaerobic training group. The third group got exercise training all the way through way through. And then the final group which is neural care got their chemotherapy as per standard of care. And then after the following the completion of their chemotherapy, they also just got got usual care. No exercise training. And these are the data. So I'll just walk you through this. Um So the blue is the group that got exercise trained during chemotherapy. The navy blue here or the light, the darker blue if you will is the group exercise training after that chemotherapy. Green is the continuous group exercise training both during and after chemotherapy. The orange is the usual care group. So this is from baseline to midpoint which essentially is the time during chemotherapy As you can see consistent with the data from all the groups have a decline in fitness, but the decline of fitness is mitigated in those groups that perform exercise training during their treatment. This is the concurrent group and also the continuous group. Now, in the second comparison here we have we have the change from midpoint. So this is going from after the completion to chemotherapy to 16 weeks after the completion of chemotherapy. As you can see, all groups spontaneously recovered their fitness. But the groups that were performing exercise training during that period sequential and the continuous group, their improvement in fitness was better than those that went, switched back to new york care. I know no exercise training, Just just of interest. We're interested. What is the change of fitness across all the groups from baseline to post intervention. So that 16 weeks from the completion of chemotherapy in the continuous exercise training group was the only group that had a significant improvement in fitness. All the other groups actually return to their baseline or pre chemotherapy level, but only the continuous exercise training group at a at a significant improvement in fitness. So, again, I think the message here is at least from my perspective, is for an individual starting their treatment is you start exercise early and you continue exercise even after that treatment is finished. These are the individuals who are going to recover the fastest. So just to summarize the second part, I think we've shown that without exercise you get the significant decline during therapy, this might continue to recover in certain individuals but certainly exercise training I think can really accelerate or attenuate and accelerate that recovery. We're still interested in if you will a space flight approach where we do exercise training in the same cohort of patients before, during and after therapy, we haven't been able to pull that off yet. But hopefully that's something we do in the future. Now, just in the last couple of minutes, I'm just gonna talk briefly about where I think this might all go or where I might might hope it might go. I think if you look at the current status of exercise guidelines for cancer survivors, they're pretty generic. It's typically one side fit all approach same exercise recommendation 150 minutes and all patients will benefit equally from this dose of exercise. I think our data shows that that is that might not be the case. So what will a potential future vision look like? Well, I'm hoping that we can really leverage new technologies and innovation in digital technology to better personalize not only monitoring the patient but also the delivery of exercise prescription to patients. So I think we can we can use digital devices, we can integrate this with EMR to really help predict and identify those those individuals that are high risk for maybe physiological impairments in those individuals. We can then prescribe personalized exercise prescription. So the conceptual vision that I have. So how does this look if we if we die down a little bit, it's as you know, we've got lots of lots of individuals now wearing I have wearable devices whether that's in in their phone or because they've got I watch or a smartwatch from these devices. We can measure a lot of interesting outcomes and metrics, be it something as simplistic as steps per day, but also things like walking speed. These functional outcomes that I think can be very important with and I watch. You can also look at heart rate. You can also get estimated view to peak in these watches as well, which I think could be very informative. You can imagine if you had this type of invasion, would be able to monitor patients very, very closely in a way that's never been possible before. You can imagine if you're monitoring say somebody's mobility steps or viewer to peak. You know that treatment has been initiated as individual. You could then monitor where a decline might happen and you would then be able to do something about that and be able to monitor in a fashion that we currently are not able to do. You imagine that each patient's trajectory might be a little bit different when they're initiate initiate treatment right now we don't see these patients as often as we might like. So this will give us I think real time feedback of how these individuals might be doing during their treatment. We can then modern to these patients in such a fashion. That will give insights of and then we can predict maybe when when a patient might be experiencing toxicity from treatment. So we can intervene earlier to offset that toxicity happening. If we're able to monitor these patients, I think with with high resolution data in a way, um there's not been previously possible, then I think this will inform the way that we can intervene. You can imagine a scenario where we've got three different types of patients, all of which are going through a trajectory as they go through cancer therapy. Each one of these patients, you can see their experience is very different. So therefore the types of intervention or the types of exercise intervention this individual needs you expect might be very different with individual number one, this is the individual that seems to be very well and then crashes quite quickly. This individual might need more intensive exercise intervention and monitoring might require a little, you know, actual one on one support to get exercising because they're not doing so well. Individual # two seems to be flatlining. They seem to be very well not experienced in toxicity, but this kind of individual probably don't need as intensive monitoring. Maybe just monitoring threat by their phone. Maybe the occasional checking to make sure they're doing okay. Individual number three again appears to crash a little bit stabilize it a little bit. Maybe this is an individual doesn't need as intense exercise training and prescription. And maybe they're also going through something like hormone therapy where glucose monitoring might be actually more indicated. So you can personalize the types of surveillance that you might need depending on the type of treatment the individuals going through and the type of anticipated toxicity this individual might get. Then your course you can then monitor these individuals in a longitudinal fashion. Again, this will give you information or they're responding to the exercise training program that I give. Do I need to modify it? Do I need to discontinue it and so forth? So obviously this is obviously very much a blue sky vision, but I wanted to put it back. I think it might be an interesting point of discussion. So just to conclude, um, I think the current progress in exercise oncology, exercise rehab in cancer. I think we've made incredible progress over the past 15 years. This is a field that really didn't exist Over 20 years ago and I really do think we have we have a reasonable evidence-based right now. The guidelines we currently have a genetic generic but they're always probably will be generic because I think guidelines are like that. I think it's going to be really up to the clinicians to personalize the information that we have from these studies to to really do the best job that we can for the individual, we have that in in front of you when they come to clinic, obviously we're gonna we're going to gather more information as it as we do more studies. But I think really personalization is going to be the key and maybe there's a future for integration of digital solutions and technology into rehab. I really think this is the way that it needs to go. But of course a lot needs to happen before we can do that. But again, I think that would be very interesting to discuss. So with that I'd just like to thank you so much again for the honor and privilege of presenting today. It's been a huge honor. I'd just like to thank my team or my collaborators and the funding agencies that that support I work. Thank you very much. I'm happy to take any questions. Yeah, I have a question. Um Hi dr jones I'm Cathy marshall um prostate cancer medical oncologist here at Hopkins Kathy. How are you? Good. Thank you so much for that talk and and thank you to tom's family um for for supporting this work. Um I've had the opportunity to talk to him many times to try and develop an exercise protocol in prostate cancer with dr Jessica angle from P. M. And R. So um that is that's the work that we're, you know part of what he's helping to support um which we're doing in prostate cancer. Um So I wanted to ask you and get some insight from you one on recruitment challenges and how it's been accepted by patients. And if you've noticed differences, especially um with regards to tumor type or where people are on the cancer journey, for example, if they've completed all of their therapy and, you know, considered cure versus um people who maybe are like right around the time of diagnosis or or changes in treatment. Um and then also, um the uh if you've looked at any of the tumor markers, um like, for example, in the prostate cancer, um, exercise trial that you mentioned. Yeah. So, yeah, great, great questions. I'll answer your first question first and then um then we can go from that. So yeah, you know, recruitment to these types of studies is always a massive, massive challenge. You know, I mean, recruitment to any clinical trial is a massive challenge. Of course, I think to these trials are not being biased, but I think it's even even harder. You know, you're asking individuals to come in four or five days a week for extended period of time in that was basically the impetus for why we designed this this digital approach when I moved from Duke to SK. I'm like, oh, I live in the city of 1.8 million people. You know, I'm gonna have no problem recruited to our studies that didn't turn out to be the case. People wouldn't even come from the west side to the opposite side to come out of us. That is and you know the reality is that 70% of our individuals that M. S. K. Come from outside of Manhattan, right? So we it was fine if we wanted to recruit a few people people who lived on the Upper East side but that that wasn't going to do it. So the trick was that we needed an approach that we can maintain delivery of exercise at high fidelity but also leveraged the convenience of being at home. So one of the approaches that of course is given individual fitbits and things like that. But we we really felt that we need to be able to quantify exactly what individuals are doing. So we designed that approach. So to answer your question, When we had our first model of individuals coming into our center that was that was a real challenge. You know, less than probably 5% of eligible patients were able to convert to get into our studies. And this is studies that were on the shorter side because we knew there had to be on the shorter side because there's no way we're going to get somebody to commit to six months of exercise training coming to a center. So now we've got this new approach, we can recruit from anywhere in the tristate area anywhere. So our recruitment rates gone from about 5% to about 30%. So it's not 100%, it never will be. But 30% of all the patient is actually pretty, pretty stellar actually. And I think you're some questions, have we seen any differences by cancer type or stage of where they are across their cancer journey? We hadn't, you know, this preoperative window of opportunity. We thought we were screwed up with that because, you know, it's an intense period. People are stressed because they're going for surgery. The crew has been been amazing, but we've also got a trial in women with metastatic breast cancer, the cruelty that has been amazing. Um So, so we haven't seen those differences. And I think it I think it really leads to the fact I think people are surprised. Like you're gonna send me a treadmill what? And I'm not saying it takes away all excuses, but it really it really helps. Um So I'll just finish with that before I go to your 2nd 1. Do you have any responses to that? Okay, so in terms of markers I actually had to talks prepared. One was on physiological taxes. The other one was on biology. I chose this one. Um But yes, we're that's that's the work that we're doing now is we're interested in not only changes in response to exercise in terms of biology but also due to molecular features, but did tell individual responds to exercise. So in terms of the first part, we, you know, we've done our N. A. C. In all those prostate cancer samples. And we're seeing pretty remarkable changes at the gene expression level which is consistent with the work we've seen in mice where you have to see, I mean one of the findings is increased infiltration of immune natural killer cells into the into the TME into the tumor micro environment which I think is pretty cool. We're also replicating that in our human samples as well. We've got data in mind showing that also mutation status appears to response to exercise. We haven't done that in people yet. Um But that's something we're very very interested in. Thank you so much. Very good. I'd like to ask the question possible. Thank you so much for this. I'm sure thomas smiling down on us. It makes me miss my dinner conversations with him. I was election a lot over dinner. Um And I'm a social scientist so I have always asked me about the role of depression in these studies. Have you been looking at any intervening variables around mental health and depression in particular and how it impacts the willingness to participate and then adhere to the program. Yeah. Great question and thank you so much for being on the call profession. I really appreciate it. Um You know we we have the other studies that have looked at depression using the I think the C. S. D. Um As a as a as a measure we we and ensure that exercise decreases patient reported level of depression using that scale. Although I think the caveat this is not recruiting individuals that might be depressed to begin with. So that that's the caveat if you will. We haven't look at that in our particular studies we have looked at things like anxiety, general quality of life fatigue. They they're measures that typically again on the whole tend to get better in these studies but not not all those measures. And again the caveat with those. We haven't recruited necessarily a patient population that might have high levels of fatigue to begin with, higher levels of anxiety to begin with. And in fact I think across most of the studies at least in exercising cancer. That's also been the case. We report all the time that exercise improves fatigue. But it's an individual who don't really have fatigue to begin with which I think is important. So you know, do those things correlate with with adherence I think maybe maybe not. I you know, my my background actually my PhD was a little bit of social psych as well. So you know we if you look at the behavioral constituents of the way that we go about our intervention, there's a lot of behavioral constructs that are built into that on purpose. Yes we send them a treadmill but every call is one and one we get rapport with the individual, we get to schedule when it's convenient for them all these things that I think ultimately build south efficacy. So, you know, the adherence levels in our studies are Are pretty remarkable, 85%, even over a year of training. Um, you know, this is training five days a week for a year straight. I'm not making this up. You know, I mentioned that We had that one dozing group where men trained 475 minutes of exercise. The adherence rate was 93% 9 individuals. I couldn't if you told me that, I wouldn't have believed it. And yes, that's for a short piece of time. But I think it's because of, you know, we do build, I think a lot of behavioral constructs into our study interventions, I think that really helps with adherence. So fantastic question. I think, well, we do measure patient reports in our points and we will be able to look to see how the change in some of these patient reported endpoints correlate with also with with adherence and other measures. So we'll certainly be looking to do that in a fantastic question. Thank you so much, robert, thurston there has raised a hand. You're gonna ask the questions. Yes, yes. And I'm related to tom through marriage anyway, considering my brother or cousin or something. Um, but I'm a runner. And so it sounds like the things you've explained dr jones kind of Say that that's a good thing to do to keep running. And I run about average 3-5 miles. Not every day, but most days. Um So I guess my I have two questions, one is um does it improve? Oh, I didn't say this, I'm a diagnosed with Stage four prostate cancer, so it's metastasizing. Um Just treating with hormonal therapy, I need to say that. So Is it better to step up and run like 10 miles instead of five miles? The other question is it sounds like you're saying resistance exercises are not nearly as important as fitness exercises, and so I'm I'm a little bit questioning that because I feel like I'm I'm I'm losing weight, I think because muscle muscle mass is kind of seeping away and it seems like exercise would be helpful, so I want to throw those to you. Thank you. Yeah, thank thanks so much for for the for the excellent question. Um If I forget any part of your question, just remind me and I'll try and answer it. So, so great. Great on the running. Yes. You actually wouldn't be eligible for any of our studies because you're already too active, you're you're running already too much, which is which is great. Um So yeah, so in terms of if you're running, I'll answer that first. Yeah, the only thing, I mean it's hard for me to give Mhm specific advice in the context of this call, but what I would say is if with your with your running, I would say if you try and stay away from running the same distance and intensity every time that you run And and so not necessarily going for 10 mile instead of a five miler, but on some of those runs, think about intensity. Some days are going to be a lot easier. The good, but might be a little a bit longer. So you might do six miles but a little bit easier. Other days you might only go two miles, but go a little bit harder if you will. So now you're varying both the duration and the intensity of those stimulus and that will give you more of a physiological bump if you will. Um and if you've trained for a marathon, that's how you were trained, you wouldn't train just doing long, slow distance, you would vary it up. So that would be my advice on the first, on this, The second part of resistance training. Resistance training is incredibly important. And please don't come away from this thinking that resistance training isn't. I really did. It was in that one particular study where we didn't find that it was particularly helpful, but that doesn't mean in general that it isn't particularly you start to get older, you lose some muscle mass. So, resistance training in that context can be very advantageous for maintaining your muscle mass, maintaining your posture and balance. Another thing is particularly important of course for running. So I would encourage you to to maintain your resistance training and also to keep running because I I think it's you look great and I think it's I think whatever you're doing is working. Thank you. Thank you dr jones. Uh this is here, Pablo Zelnick, I'm so some of you who are uh outside the department don't know, maybe I'm the director of the department of Rehab Hopkins. So I just have a couple of comments and um and that I'd like to share 11 is thank you to tom and the family and friends of tom for really provoking these conversations for the support of the department. And I very specially too for joining us here today and asking questions to the group. It's been really a pleasure to have you here and the curiosity and asking the questions. Um dr jones I really appreciate your your talk. I think it's really, really enlightening. I just was going to point out, you know, um that you know, your your way of thinking is very similar to a lot of things that we have been doing here in the department. And this idea of doing personalized interventions. We have a center of access in precision rehabilitation. That that is exactly this concept of measuring function of the of the person in the community in the in regular life, taking advantage of all these tools that we have now available for measuring activities and people and very much to the point that Patricia was asking we're not only looking at the physical activity, but we're also looking at the cognitive and psychosocial aspects of function and unfortunately having a right to the space of cancer. We've been doing this in the space of COPD and stroke. But but within that similar concepts really are emerging. So I I really enjoy your conversation on this and maybe maybe in a specific question, comment about the the talk is um It's remarkable that you show and your data points to this individual differences, even your dose escalation study. You see that those who are doing the 450 minutes, some people have the same benefit of doing 90 minutes and so on. And So I think that since I'm pretty lazy to do exercises, if I can do the 19, I will definitely choose that 1 450. But so any any thoughts on how you predict or any thoughts on how you go about understanding who would benefit from the higher versus lower or also on brilliant question to use my english, brilliant, brilliant questions. So it's interesting, Yeah, we talked about the maximal but yeah, it's like what's the minimum I need to do to get the maximum benefit right. Um so the honest answer is we don't know because we book because we don't have the data yet. But this is something that we're very very curious about. We're curious about this from both. An improvement in physiological outcomes and also actually tumor related outcomes. It comes back to the question, I think Kathy answered earlier. Um, So we do see this heterogeneity and response in actually in one of the studies are presented, which is 174 individuals with breast cancer. We are now going deep into that study to try and identify what are the, what are the characteristics of those individuals that had a really incredible response to this to this, You know, uniform delivered exercise versus those who didn't Because maybe in those individuals, the ones that have a really nice response, maybe they don't need 160 minutes, maybe they just need 90 minutes. Maybe. Maybe there's some individuals in there who do need, you know, the greater dose from a from a clinical perspective that data is incredibly, you know, I think it's one of the most important questions we have because right now it's it's everybody gets 150 minutes. And I've always thought that that doesn't make any sense. Doesn't make any sense. You know, what's interesting is you brought up that the study you do see in general, if you look at all the pages, that dose response. Now, if I put in the response, you don't see that, you don't see that normally with, If you look at cardiovascular disease, for example, you normally see this very nice linear response, the more exercise appears to be the better benefit. But if you then replace that with something like risk of recurrence, you don't see that same relationship. You kind of see a plateau. Once you get to a threshold of an exercise dose increases the amount of exercise doesn't give you any additional amount of benefit. I think that's fascinating. And something that we are looking at very carefully. That's all I can tell you. We don't have any data yet. But maybe I can come back when we have that data and we and we can talk about that. Absolutely. I'd love to hear more about this and finding that. Yes. Um What is the critical interaction, I mean, what's driving the critic interaction between exercise and biology of? Yeah. All right. Thank you so much. There may be one or 2 more questions if it's okay with you. All right. Ah All right. We have to robert's here. You're raising your hand. So go ahead. I'm delayed. Ian I'm one of tom's in laws in law. I went through that eye surgery where they, you know, you have to have your head down and all that kind of stuff. And I didn't start taking notes on how my was progressing until like two or three weeks after the process. Do your participants keep a regular log of how they're feeling so that you could have some idea of whether they're keeping up their practice is based on how they're feeling or they just lost it. It just feels like if they had a we're giving you a record of their progress and how they felt that you'd learn a lot. Yeah, great, great question. There's no doubt that we, you know, I I would like to ask people every day how they felt. Um The problem with that is you get you get a little bit of burnout with that. If you're asking individuals same questions every day and your your responses start to become automated, I'm not an expert and psycho metrics, but I believe that that's the case. So in our studies we will ask what we call patient reported endpoints. You know, questionnaires will deliver those at the beginning of the study halfway through and typically to the end not on on greater frequency as we would probably be like because we're a little bit cautious about overburdening our participants to complete too many questionnaires. But this is where this physiologic data comes in. I think it's very nice because it's completely passive what I mean by that they put on the watch and we we get that data whether individuals are thinking about it or not now, that doesn't tell us how they feel. But it does tell us about how they are functioning everyday, how they're going about their normal daily lives. So yes, it's not exactly to the information that you need. Of course if you have both, side by side that would be incredibly powerful. But I think there's a there's a threshold about how much we can ask individuals to do and write down all the time. So we to answer your question. We tried to do it but not as much as we we would like but we are also trying to be a little bit practical if that if that makes sense. Mm Great question. And maybe the last question, maybe robert sleep. Is that how you say sleep? Yeah. Thank you. I'm a colleague of tom in Germany and first of all the brilliant presentation Tom would be delighted. I know him good enough. Yeah, this is perfect. No, but he showed respect um in the last two presentations that he gave in Germany he presented his considerations that that the long method of resistance training which is an unusual way where you build up the the resistance from set to set would be more efficient than conventional resistance training. And he had some early indications but when I asked him how sure he is he don't mean he's not sure. So I I so my question is, do you have any indications on research on that or plans for research or any data about it? We we don't, I you know, I most of our studies have been a robot training based um you know the results we got without resistance training and long quite honestly, we're surprising and disappointing to be honest, we really expected um that resistance training would would be effective in that particular cohort and it and it really wasn't the data. The data. This is why you do the study. This is why you need the studies now. Of course. Now, of course it could have been the fact that the resistance training program that we prescribed wasn't good enough. It wasn't, you know, it was it was it was a pretty standard, but it maybe needs to be more personalized. Maybe it needs to be designed differently like tom was talking about it. So I think that question remains to be open. The problem we've had resistance training is because now we've got this remote approach. It's been challenging to remote delivered resistance training programs in our in our individuals that you can send individuals a bunch of dumbbells. But then to do it properly without injuring I think is is it's gonna be difficult. We haven't cracked that problem yet. So maybe somebody else has and they can and they can tell me um but I think lot, there's more questions than answers as there is in most fields. Great, well, again, thank you for joining us today and having this conversation has been terrific and and also one more time. Thank you for at home and family and friends for joining us here today. I really, I I couldn't agree more with Lawrence comments about having this conversation between the researchers. The clinicians and patients is and you know customers. We are all customers that you know today though, but it's very enlightening. So thank you for joining us today and I hope you enjoy the rest of the day and just continue being in touch. Thank you so much, everyone. It's been a pleasure. Thank you. Have a good afternoon even. Created by
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