Exercise Interventions for Patients with Prostate Cancer
SESSION 8: Exercise Interventions for Patients with Prostate Cancer
Moderators: June Chan (University of California, San Fracisco)
Christina Dieli-Conwright (Harvard: Dana-Farber Cancer Institute)
Better Together: The Benefits of Team-based Exercise for Couples Coping with Prostate Cancer
Kerri Winters-Stone (Oregon Health & Science University)
Prescriptive Exercise as the World’s Best Drug to Enhance Prostate Cancer Survivorship
Christina Dieli-Conwright (Harvard: Dana-Farber Cancer Institute)
View the Transcript Below:
Exercise Interventions for Patients with Prostate Cancer
June Chan, ScD [00:00:09] Good morning. So, I’m June Chan. I’m professor of epidemiology and biostatistics and urology at UCSF. I’m a cancer epidemiologist. Most of my work focuses on diet, physical activity, and prostate cancer survivorship. I want to thank Howard, Andrea, and PCF in general for always being such a strong proponent of studying diet and exercise and prostate cancer survivorship. I was a YI in the CaP CURE days, date myself here, but thank you for all the support for our work over the years. So, I’m gonna do, oh, actually, I invite anybody to stand up and stretch or move around in the spirit of the topic of this next session. I know some people have been sitting here a long time. You guys can start to stand up. You know, move around, at least while I’m doing introductions. I might tell you to sit down at some point, but okay. The way we’re gonna do it today is I actually have a co-moderator, who is Christina Dieli-Conwright, unfortunately doing a scheduling conflict, she can’t actually be here live. So, I’m gonna introduce all the speakers here at the beginning. We’re gonna come up in sequence, and she’s gonna close it out at the end. So, there is a co-moderator for the session. So, feel free to walk in place on the side, do some stretching, anything like that. We’re gonna be joined up here by Dr. Kerri Winters-Stone. Who is the Penny and Phil Knight Endowed Professor in Cancer Research Innovation from Oregon Health and Sciences University. She’s an exercise scientist who studies the combined effects of cancer treatment and aging on musculoskeletal health and cancer recurrence risk and the ability of exercise to intervene and improve health and longevity in cancer survivors. And then, as mentioned, co-moderator for this session, we worked together in the planning of this, but she’ll be joining us virtually is Dr. Christina Dieli-Conwright from Harvard Medical School and the Dana Farber Cancer Institute. She is an associate professor in the Department of Medical Oncology at DFCI, and she studies mechanisms by which post diagnostic exercise impacts cancer prognosis. She conducts randomized control trials to test how prescriptive exercise can improve cancer outcomes in patients across the lifespan.
Kerri Winters-Stone, PhD [00:02:45] Okay. I’m happy to be here and put a bit of a twist on the talks that we’ve heard so far, and even a little bit of a twist on the line of research that June described that I do. And I’ll make that point with a story about one of my participants in one of the first studies that I ever exercise trials that I ever conducted in men with prostate cancer, where I had a gentleman who was a participant in that study, and he was a recently retired medical oncologist who was diagnosed with metastatic prostate cancer four days after he retired. And after he did his performance testing, he asked to come in and talk to me. And when he came into my office, he said, You are asking me all the wrong questions. Said, My wife and I are grieving my death, and you should be asking me about that. And it really made an impression on me that to think about the context in which people are experiencing their prostate cancer, and that it’s having an effect on their loved ones, on their relationships, and the plans for the rest of their life. So, we know that men with prostate cancer face threats to their physical and their mental health as a result of their disease and the treatments that they go through. But what I think we don’t appreciate as much is that their partners also experience threats to their physical and mental health. And caregivers of people with a chronic illness have poorer physical and mental health than people who are not caring for an ill loved one. And the health of the couple is really intertwined. So, the health of one partner influences the health of the other. And as someone who just took care of a brother with stage four esophageal cancer, I can tell you that caregiver strain is very real. And if my health was not well as a carer for my brother, I don’t think that I would have been able to care for him as well through his experience. So, we really need to be thinking about this concept of dyadic health or the health of both people in a relationship. And that the health of each partner also influences the quality of their relationship, which can also be strained during a chronic illness. And each one of those factors independently can affect a patient’s mortality and their quality of life. And we actually looked at this this kind of link, biopsychosocial link in a sample of prostate and breast cancer dyads. So, these are patients and their intimate partners, where we looked at the potential influence of perceptions of relationship health as well as their behaviors like physical activity and their weight on biomarkers of chronic illness. And we found a significant positive influence of the perception of relationship quality in breast and prostate cancer survivors on the levels of HSCRP, an inflammatory marker in the partner. And then when we looked at the reciprocal, we found that better perceptions of a relationship were also influencing a biological marker like HOMA-IR in the partner. So, these were really kind of some good hard data showing that there may be a biopsychosocial link between the quality of our relationships and the health of our partners. And we already probably recognize that behaviors of couples are intertwined because they share the same environment, the same values, the same types of activities. And these are data linking actigraphy within couples. So, looking at amount of time spent in sedentary behaviors, and how if you regressed one partner’s sedentary behavior time on the other, you can see that they’re very strongly and positively linked to one another, right? But if you flip that, right, there’s a potential positive that their participation in levels of moderate to vigorous physical activity are also strongly linked. So, we might be able to leverage this relationship in order to improve the health of someone with a chronic illness. So that conversation that I had with my participant really made me start to think about, you know, whether or not we should be including partners when we are looking at the benefits of exercise in men with prostate cancer. So, a lot of my research focused on, you know, how do we use exercise to improve outcomes for men with prostate cancer who were prescribed ADT. But we did start to think there’s no reason why we can’t extend that to a care partner. So, then we started a line of research looking at the potential benefits of exercise in men with prostate cancer and their intimate partners. With really the idea or the kind of beginning hypothesis that there might be benefits of exercising with the partner, right? The couple engages in a shared activity, and they can start working toward a common goal toward one another so they can support each other’s positive health behavior change. This is going to improve the health of each member of the dyad, so the patient and the partner’s health. It could potentially improve the health of their relationship. And if you think about that three-legged stool that I showed you, changing any one of those is going to improve the outcomes for the patient. And then if we have the couple train as a team. So, I come from a sports background, that’s how I got into this business, right? Training as a team, I know that there are benefits of training as a team and working as a team. You work harder, you collaborate together, you communicate with one another. So why can’t we have the couple train as a team? And if they train as a team, then that could amplify the benefits of exercise for them, right? So more likely to adhere to exercise when you have accountability of an exercise partner, right? And then also potentially a higher work rate because your person’s pushing you. Lee talked about training for a marathon, and when you train or you go out running with someone, you probably find that you run a little bit faster than when you’re running on your own, right? So, including that partner can amplify the exercise outcomes. So, our hypothesis was that if done together, exercising as a team could result in better outcomes for the patient, for the partner, and for the health of their relationship. So, this led us to our first pilot trial of a program that we called exercising together. There was no playbook for this, no roadmap, no other exercise program where couples trained as a team. So, we really came up with this program on our own, looking at what are the features of a strong team, what are the elements of teamwork that we could incorporate into exercise? And we did a pilot trial in men with prostate cancer and their co residing partners, usually their spouse. And compared this program to usual care over a six-month time period. And we used resistance training as our modality because that’s the modality that I had used already to look at exercise benefits as a countermeasure to ADT toxicities. And resistance training is one of the few modalities where you could have two people exercising together even though they’re independently working at a different work rate. You can’t do that with dance, which is another potential partnered activity or many other types of aerobic activity because one person has to titrate their effort to the other person. So, one person’s either under training or someone’s over training. But in resistance training, you can actually have them exercise at the same time. So, this is what exercise our program we call it exercising together look like. It started with kind of traditional strengthening exercises that were functionally based, we’re trying to improve functional outcomes. Where this was like having your partner be your personal trainer. So, one person in the couple was the coach and the other person was the client, right? And then they would switch. We had them perform different kinds of teamwork actions so that we, you know, within their role, right, they would be coaching the other person, or they would have to receive the coaching. So, think about that in couple dynamics, right? When your partner is telling you what to do, how you usually respond to that is not as favorable as if it was your paid personal trainer. Who was telling you what to do, but we’re trying to get couples to practice this and do this in a more beneficial way. And then we also included tandem exercises or more collaborative exercises where they had to work together as a team to complete an exercise. So again, think about sports and doing a drill within a team. You’ve got to talk to one another, you’ve got to communicate with one another, collaborate, figure out how to do that drill effectively. And it’s also more fun. So, we wanted to have a way to make sure that this was an enjoyable activity for them to do as partners. And we, you know, this was a pilot study, so we were looking at feasibility. We didn’t even know if couples would sign up for a program like this. We quickly accrued to this trial. We had no trouble filling that, and we had 100% retention in our group. And so, I just saw Jim go, what? Which is what we thought. I mean, this is practically unheard of to have everybody who started a program finish it. And this was a twice-weekly program. OHSU is up on a hill, it’s hard to drive to. We had it two times a week on person. This is way pre-COVID, right? And nobody dropped out. Whereas we had dropout in the control group and we had strong adherence, no adverse events as expected. And then from outcomes, men got leaner and more active. Again, this is what we would expect. Both partners improved their physical functioning, which means they are remaining independent. Potentially longer and requiring less help from one another. And then partners increase their levels of affectionate behavior and reduce their depression, potentially helping them become better care partners. So, this was enough for us to think we need to interrogate this a little bit more, but does it really matter if they train as a team? And we couldn’t tell that because in our original intervention, all couples exercise in a group with other couples. So maybe that’s the driver. Maybe the driver is that they both decided to get active and more healthy together, and that was the driver. So we designed a trial called exercising together that was a three-arm randomized controlled trial trying to tease out the unique benefits of training as a team by comparing people who were randomized to an exercising together arm, exercising with other couples, to arms where survivors were exercising in a group with other survivors and spouses with other spouses, or to a home-based unsupervised group that or program that wasn’t getting any group benefit. So, it’s a 12-month RCT in couples coping with prostate. Now we extended to other types of cancer, including breast and colorectal cancer. Our primary input was an outcome called symptom congruence. That’s how much do partners agree with one another about the patient’s symptomology like pain, fatigue, and functioning. As well as relationship quality. And then we also looked at biological and physiologic endpoints to see if there’s any difference in outcomes when couples train differently with one another. And we’re right in the middle of analyzing all those data, so I can’t share that with you today, but I can show you from a retention standpoint, again, in the partner group, we’re seeing the highest retention, it’s 96%. This was a much longer study. And adherence rates that are also very high. I can show you some preliminary data. So, we did look at symptom congruence. This is for pain ratings. And if couples are in perfect agreement, that score would be zero. And you can see that all the couples start off disagreeing about what their partners, the person with cancer, what the survivor’s pain was. And when they exercised together as a team, they became more and more congruent, right, about what the level of pain was, potentially indicating that they’re gonna better manage his symptoms and his cancer together as they go through treatment. So, all of the trials so far have been in the post-treatment setting, and what we really think is if we can move this program closer to the point of care and the beginning of treatment, we can use it as a way to prevent changes, right, that happen as people go through treatment. One of our radiation oncologists, as we were doing the other trial, reached out to me and said, you know, Couples are coming to OHSU from Alaska and Idaho and different states, and they live in an apartment here and they go to radiation therapy one hour a day, and then they have nothing else to do. Can they come to your exercise facility? And I said, sure. And let’s do a pilot trial at the same time. So, we decided to do a pilot trial of exercising together, now starting at the point of radiation treatment. So, this was a very small trial. 10 couples training three times a week, this was at our facility again pre-COVID, but again, 100% retention. This is during treatment, very high adherence rates, very high ratings of the class among participants. And if you look at the data, I don’t know how well you can see these, but improvements in functional outcomes among patients, improvement in functional outcomes among partners, increases in physical activity levels in both partners, reduction in anxiety in both partners, and depressive symptoms among spouses. This is during treatment. And improvement in active engagement or the degree to which the couples are collaborating and communicating with one another. So right now, we’ve moved to R01 trying to, this is a type one hybrid effectiveness implementation trial. So, we’re now doing a fully powered trial in prostate and breast cancer to see whether or not our preliminary findings hold up, and we’re adding an implementation arm so that if this program is effective, we have already learned about how to swiftly implement it into the clinical setting. Our target goal is 200 prostate and breast cancer dyads. We’ve accrued 73 so far. And again, the retention, 95%, right? And I just wanted to share a quote from one of the partners of our participants, a man with prostate cancer, she said, I’m listening more to things my husband is saying, I’m watching and aware of different things that might happen or changes, or when we’re doing our exercise, making sure he’s not too tired. I’m benefiting too because I’m feeling a lot better. I think when we leave here, we’ll be better than when we came, right? And that’s what we want. If people are going through treatment, they’re coming out better after treatment because they’ve gone through an exercise program together, then I think we’ve found something really positive. I do want to acknowledge, because one question I get that I might have gotten on try to get in front of it is, you know, what about the guys who aren’t married? Not everyone is married, some men never marry, some men are widowed or you know, not partnered any longer. I think social support can also come from other carers, friends, siblings, adult children, peers, other men with prostate cancer, and that’s gonna foster accountability, enjoyment, socializing that might also lead to better retention. I became very interested in a construct called cancer loneliness during the pandemic. This is a mismatch between the amount of social support that somebody wants or needs and the amount that they’re getting specific to cancer. It is very high in people with cancer. And in men with prostate cancer, about 75% of men report experiencing some level of cancer loneliness, even when they’re married. And construct of cancer loneliness is linked to poorer physical and mental health. We found in a different set of studies where we’re only training men with prostate cancer, but doing it in a group setting, that exercising with other men in a group reduces feelings of cancer loneliness. And you can even do this and kind of create this online. So, like Lee said, everyone in the exercise world had to innovate hard during COVID because we were one of the biggest groups disrupted. So, we moved all our group interventions over to Zoom. Men exercise just like they would in a room, and we see a very positive social benefit. So just to wrap it up, hopefully I’ve grown your awareness about the importance of spousal in a relationship on the health and potential outcomes of patients. Exercise potentially could be a vehicle to optimize dyadic health, the health of both the patient and the partner, and potentially their relationship, and all of those are going to potentially positively impact patient outcomes. If couples exercise together, it may help patients stick to an exercise program longer and derive more benefit than if they exercised on their own. But even if they’re not exercising with their partner, exercising with other prostate cancer patients can also be beneficial and provide some missing social support and improve quality of life. And I’m gonna end with a shameless plug for two trials that we have going on. iLIVE is a diet and exercise trial in men with prostate cancer. We do group online resistance training classes in that trial and then eMBRACE is our couples-based trial. Like Lee’s trials, these are all decentralized. We do everything online so people can enroll from anywhere across the country. Yeah. Okay, thank you. I think I have like one minute for questions.
[00:21:16] Yes, really quick. Two things. Did you assess differences in the length of time couples were together? So, a couple five years versus thirty years and then also are there differences in same sex?
Kerri Winters-Stone, PhD [00:21:27] Yeah. Both great questions. The first one in our first pilot, you know, most couples have been in a relationship for a long time. And our sample size was too small to be able to look at the influence of relationship length. In our second study, we shortened that because we think, you know, time sense diagnosis, but we’re looking at potential moderator effects of relationship length. So the program might be more or less effective depending on how long you’ve been in a relationship because the strain is higher in people who’ve been married for a shorter period of time than when they’ve been married longer, and they’ve usually already been through, you know, adverse events in their life and they’re able to buffer those a little bit better. And then for same-sex couples, I can’t answer that question right now, but we do are going to be able to do a sub-sample analysis in our exercising together trial to be able to look at that.
Unknown [00:22:27] Hi Kerri, glad to have you in Portland. What are the prostate cancer specific outcomes or have you looked at that? Like do people getting exercise do better from a prostate cancer perspective?
Kerri Winters-Stone, PhD [00:22:39] Yeah, so in those trials we’re not look because they are including multiple cancer types. So, we’re not looking at prostate cancer specific. We’re looking at inflammation with HSCRP and insulin family protein. So, we’ll look across the board, but we are dividing that sample out to be able to see whether or not the program is more or less beneficial depending on the type of cancer that you have. Yeah. Okay, thank you.
Unknown [00:23:08] Can I ask a quick question? Very fascinating study. Just curious, in your upcoming studies, are you thinking of including like couples who do not exercise as a control arm?
Kerri Winters-Stone, PhD [00:23:21] Well in our current trial in radiation oncology, first of all for eligibility they can’t be currently exercising and then we have a usual care control arm, so they won’t be training. Okay, thank you. Okay. Okay, now it’s my pleasure to introduce Christina Dieli-Conwright, who is online. I think her slides will pop up in a minute. Thank you.
Christina Dieli-Conwright, PhD, MPH [00:23:56] Hi there, everyone. Thank you so much for the opportunity to present virtually today. I greatly appreciate it. I’m so sorry that I couldn’t be there. Could probably tell by how I’m dressed that I’m still in the Boston colds. I have the great honor of co-chairing this session with June, and I’m gonna wrap us up and close us out. I know a few of our speakers have to leave promptly at 11:30, so I’ll do my best to stay on time here. Thank you to PCF for highlighting this area of research and for all the support over the years with exercise and nutritional oncology research. It’s been such an honor to get to know this organization. I get to sort of keep hammering the nail into this topic and hopefully convince you by the end of this hour plus long session that prescriptive exercise and exercise is the best drug out there and particularly in enhancing prostate cancer survivorship. So, in order to continue, sorry, I’m trying to advance my slides here. Here we go. In light of the short amount of time that I have here, I’m gonna give an overview of my approach and my lab’s approach to prescriptive exercise oncology. I’ll then talk about some of the published and soon to be published data on the outcomes that we focused on, and then I’ll wrap up with three ongoing trials that are going to help to continue to push this field forward. My disclaimer, which has no conflict with pharma, et cetera, is that I am a clinical exercise physiologist by training and I love supervised exercise. I also have a strong bias to resistance exercise, but that’s a story for a different day. Thanks to my colleagues and for wrapping up this session, I don’t have to go too much into the detail about the benefits of exercise. We know that engaging in regular exercise elicits many benefits among prostate cancer survivors. There’s been quite a breadth of work in this particular disease group area. This is shown in this overview, everything from reducing fatigue, improving fitness, range of motion, muscle condition, bone health, potentially chances of survival, quality of life, on and on and on. We’re starting to dig into additional evidence as to whether exercise can actually improve treatment tolerance and treatment efficacy. And that’s where you see those two gold stars. And there’s a great group funded by NIH called the ENICTO Consortium that’s trying to dig further at that. So, we’ve got quite a bit of evidence already to suggest the benefits are multifaceted there. So, what I actually do in my laboratory, also from a sports science background like Kerri, is I like to translate what we know in sports science to exercise medicine and apply those training principles to individuals diagnosed with cancer. I’m a native to Los Angeles. I’m not going to talk about the Dodger game last night. We’re going to come over that later on this evening. But inspired by the some of my favorite LA athletes there, we can draw a lot from athletics. Athletes train with a goal in mind. There’s performance testing to determine how we’re going to know if athletes are improving. There’s periodization, excuse me, or systematic progression that Lee was mentioning earlier. And there’s of course going to be oversight by qualified trainers. And so, we apply all of those same principles to individuals diagnosed with cancer through the design of our trials. And this is the approach that we like to stand by, if you will. We also know from the basics of exercise science that there’s principles that exist that help to guide exercise prescription. The main common principle is the FITT principle, whereby we’re prescribing exercise by touching upon the frequency or how often somebody is exercising, the intensity, the time, the type of exercise, and the volume and the progression of exercise as well. So, we can get quite detailed on how we’re actually prescribing exercise. And this would apply for cancer survivors as well. We also believe that documentation of this prescription is going to be vital. It helps from both an exercise design and programming standpoint and also helps to push the field forward as well so that we’re transparent with what exercises we’re having individuals do. It’s been long established that exercise safety is prominent. We know that exercise is safe and effective throughout the cancer continuum. While most of the data resides in the traditional survivorship window, we know that cancer survivors can exercise safely even during chemotherapy, before surgery, soon after surgery or transplant, et cetera. We know that there’s certain types of battery of tests that we can also do to integrate safety throughout this. This is quite a small table, so I don’t expect you to read it all, but I’ll highlight different types of safety checks we put into place. CPETs or equivalent testing like cardiopulmonary exercise tests or stress tests, if you will. We take a pretty heavy intake of baseline symptoms that could be treatment related or just general health related. We, of course, track ongoing cancer-related complications. And then we do a pretty comprehensive intake of what is that individual’s knowledge of exercise and experience with exercise so that we understand the person as a whole that we’re trying to work with, if you will. And this has been published quite extensively, especially in the cardiotoxicity field as well. We also think it’s critically important to know the patient. Exercise can be precisely manipulated for each person. And so, we want to ensure that we’re doing just such. That also helps with long-term engagement, with adherence. Exercises we know is work. Some people, many people don’t always like to engage in exercise. So, really taking more of a precision approach and moving a bit more away from that one size fits all model is important as well. So, I’m going to move into some of the outcomes that we’ve looked at. This is a particular study I’m gonna start with, it was actually led by a graduate student of mine. So, where my entry point actually it was with exercise oncology with prostate cancer is actually around problems related to androgen deprivation therapy and various health outcomes that can arise as a result of ADT use, particularly around body composition. And so, one of my first queries in this field was actually around targeting lean mass. But we also know from individuals that have tracked different treatment toxicities with prostate cancer that cardiovascular disease is quite problematic and does remain the main cause of mortality among men with prostate cancer. As noted in this figure, on the left side are a number of different therapies that are often prescribed during the prostate cancer trajectory. And on the right side is the different side effects. I’ll share with you first a small study we did that targeted muscle, but then also highlight some of our work focused on cardiovascular disease. So, the first study we did, as I mentioned, was led by a graduate student of mine, Jackie Dawson, who’s actually now an associate professor at Long Beach State there in California. What was really cool about this trial was that it was funded by the National Strength and Conditioning Association. Which, for those of you who may be more familiar with exercise work, that’s actually one of the governing bodies of strength and conditioning and weightlifting. So, it was great that they saw an interest in funding this type of work. This is actually just a schematic to show the periodization scheme that we used over the course of the 12-week study. These were individuals who were diagnosed with prostate cancer and subsequently on ADT, who were not actively engaged in resistance exercise. And so, we prescribed the exercise in a way that focused on hypertrophy in order to determine if we were actually able to alter lean mass. This was an in-clinic pre-COVID study. And this study was really fantastic in the sense that we had 99% adherence to exercise. This was actually conducted in Los Angeles when I was back at USC before I moved over to Dana Farber. But really exciting about this trial was what we did find that with just 12 weeks of exercise; we actually were able to improve lean mass. These gentlemen, again, were highly adherent and also were moving quite a bit of mass. So, they were adhering not only to coming to the sessions, but actually to the prescription that we were prescribing. So, it’s not shocking that we actually saw increases in lean mass in that sense. However, also for those of you who know how difficult it is to change muscle mass, we were actually pleasantly surprised that we saw these changes here. And that’s what you see in the middle graph here was a positive improvement in sarcopenic index change. And on the right hand is the lean mass change data with that significant change of 1.1 kilos. On the left-hand side there, you’ll see the prevalence of sarcopenia. This was again from DEXA whole body scan, whereby the beginning of the study, it was about 38% in the exercise group who had sarcopenia. And by the end of the 12 weeks, that had reduced down to 15%. And the control group worsened, if you will, they lost muscle during that time frame there. So exciting study. It was a great study to get our feet wet in this particular population. And that same trial on the left-hand graph there, you’ll see the significant improvement in quality of life. And we saw a trend for improvements in fatigue and depression. Circling back to cardiovascular disease, we often look at metabolic syndrome in our lab. Metabolic syndrome is a cluster of features, if you will. When an individual has metabolic syndrome, there’s significantly higher risk of developing cardiovascular disease and diabetes. These features include a high waist circumference, high triglycerides, elevated glucose, high blood pressure, and low levels of HDL. While this was resistance exercise only, we weren’t hypothesizing that there would be a profound change in metabolic syndrome because we really felt that we would need that aerobic stimuli as well. So, we were pleasantly surprised to see reductions in both waist circumference and triglycerides with 12 weeks of periodized resistance exercise. So, we then pivoted a bit to look at a different type of prescriptive exercise. And we wanted to look at circuit training and interval training combined, knowing from the exercise science literature that that type of training has a positive effect on everything from body composition to cardiometabolic health. So, we looked at whether, excuse me, we looked at whether or not individuals with breast, prostate, and colorectal cancer could actually elicit improvements in vascular function. I’ll show you those measures in just a bit. But if you look here on the right-hand side, you’ll see the circuit training program that we used. In essence, individuals would cycle through an interval on the treadmill. They would go through a number of weight machines, they would take a minute break, and then they would repeat that two more times. And this also was periodized over the course of 16 weeks. So minimal rest, and they were moving from station to station, hence the circuit interval name there. This is the data from the prostate cancer survivors. We looked at endothelial dysfunction, and we measured that by flow-mediated dilation in order to give us a sense of their vascular health. As you can see in the blue bars, we saw significant increase in flow-mediated dilation. In other words, in essence, the blood was flowing through the vessels at a higher and faster, more efficient rate, if you will. Not shown on this particular graph, but I’ll get to in just a second is the fitness data. But here you’ll see the arterial thickness in we measured by ultrasound, also giving us an indication of vascular health. And we would want this to decrease. Excuse me, my slides are going a little crazy here. We wanted this to decrease, if you will, so that the vessel is less thick. And we saw that in the exercise group. Unfortunately, the control group worsened just slightly. We also saw significant improvements in VO2 peak. That’s just in those boxes there on the side, of about five mls per kg per minute, which is again a marker of cardiorespiratory fitness. From EpiWork, we know that a 1.0 ml per kg per minute increase in VO2 peak is associated with an adjusted 9% reduction in all-cause mortality. Obviously, we didn’t measure risk for mortality here, but you can see the potential impact that improving cardiorespiratory fitness has on overall health. So, I’m going to show three studies that I believe are addressing sort of these call to action or unaddressed areas within prostate cancer and exercise research. As again, I’m being conscientious of the time here. These are three trials that are ongoing. I’m gonna start with the POWER trial, which actually is just about to wrap up, that’s been supported by PCF, Pfizer, and DOD. What I noticed was an obvious gap in the literature with prostate cancer and exercise is a lack of focus on black men. And we know that specifically among black men, there’s quite large health disparities and cardiovascular disease and disease progression. So, we designed a virtually supervised exercise trial for black men. They do the exercise at home. All of the equipment is sent to their home. And we’re specifically targeting cardiovascular risk, which we’re focusing on the Framingham risk score. We’re also looking at fitness outcomes and quality of life and longer-term outcomes through EMR abstraction there. This is a small pilot study. So, we’re actually using this to gather preliminary efficacy data for a larger phase two trial first, which will hopefully then lead into larger phase three trial. This trial has been very well received in the Black community in the Boston area. We’ve spent quite a bit of time building relationships with the NAACP, Zero Prostate Cancer, and other types of organizations in order to really help to support the Black prostate cancer community in our area, and hopefully we’ll be able to do that nationwide. Just preliminary speaking, as I’m not gonna show data for this trial, we have so far seen significant improvements in cardiovascular fitness. So that’s been really great to see. We have about 85% adherence to exercise. And again, just a great community of prostate cancer survivors to work with here. The next trial that we have ongoing, also supported by PCF that is really exciting in a number of different ways, addresses the gap of really trying to figure out what’s going on at the level of skeletal muscle tissue. So, this study actually involves, we call it the FIERCE Trial. It involves muscle biopsies, which I’ll come back to in just a bit. And we’re trying to look at the interaction or the interplay between frailty, sarcopenia, and ADT, particularly among men with metastatic prostate cancer where there lies less exercise oncology trials with. We’re doing a multi-component prescriptive exercise intervention again, multi-component here. The individuals receive supervised resistance training, functional and balance training. Those are all in clinic, and then self-directed aerobic exercise on their own. The in-clinic exercise is performed in a circuit fashion. Frailty is our primary aim here. We’re looking at also additional biomarkers of systemic inflammation. Sarcopenia assessed by CT scans and also looking at sarcopenic measurements, specifically hypertrophic and catabolic biomarkers from muscle biopsies of one of the quad muscles. We’ve done this in the past with some of our previous data in prostate cancer, previous trials in prostate cancer. So, we knew that obtaining muscle biopsies from this population was feasible and not burdensome by doing a burden assessment. And then we’ll also look at an exploratory aim of biochemical progression to and assess LNCaP cells. This trial, again, is ongoing, so I’m not going to show preliminary data, but hopefully there’ll be some next year at this time. And then lastly, and I will be quite honest, this is inspired by individuals such as Kerri’s work and others who’ve done dyadic interventions. We have a trial that just started accruing patients, dyads, if you will, this past August in collaboration with Tracy Crane at University of Miami, funded by PCORI. This is a trial for older adult cancer survivors and their support persons, where we’re using our prescriptive exercise in the setting combined with a Mediterranean diet, hence partnership with Dr. Crane, who’s a registered dietitian. And we’re looking at dyads, particularly the cancer survivor who’s been diagnosed with prostate cancer, breast cancer, colorectal, or lung cancer, and their support person, as we’re referring to. Their support person can be over the age of 18, whereas the cancer survivor over the age of 65. And here we’re going to be focusing on cognitive function and physical function as well. It’s a non-inferiority trial. There’s no control group. So, individuals are randomized to either supervised or unsupervised, but they’re still exposed to the same prescriptive intervention. This is a phase three trial of 764 dyads across the two sites. We’ve already enrolled patients to this and it’s been fantastic so far. The dyads have been incredibly fun to work with, very engaged. And so, this trial, as I mentioned, is new and just starting, therefore results won’t be out for quite some time, at least the next four to five years. But very fantastic experience to be able to work with these dyads in this capacity. What’s really fun about working with the prostate cancer community is once they finish one trial, they often want to jump to a next. So, we have a long list of patients who, although hopefully we’ve already made them quite active and they’re not eligible for this, but who are very interested in continuing on with additional trials. On that note, I like to end talks often with this tidbit that I think is quite impactful. As exercise oncologists certainly were focused on very specific outcomes, and I love to focus on prescriptive exercise. But as a reminder, 31% of the world’s adult population is physically inactive. So, it’s about 2 billion people. And as summarized and noted by the CDC and WHO, the economic burden of physical inactivity is about $300 billion, or at least approaching so by the year 2030. So, I think that again, shout out to PCF for allowing us to highlight this work. I think that our squad here with myself, Lee, Kerri, and June looks like we’ve got quite a bit of work to do. To be able to crunch down these numbers but certainly been quite impactful to be able to work with the prostate cancer community to help to impact those lives. As the co-moderator participating virtually, I just wanted to give a shout out to our group here. I think we’ve covered quite the gamut of interventions and different types of work going on in prostate cancer. Again, hoping to excite the prostate cancer and PCF communities and hope to continue to inspire individuals to do this type of work and to get active. So, thank you so much for your time, and I’d be happy to take a question if there’s time for it from the audience.
June Chan, ScD [00:43:38] Christina, I’m still here. I don’t think there’s any questions, so just thanks very much to everybody. Thanks for your attention. Thank you, Christina, for joining virtually. And Lee, if you’re still here.