Charles Ryan: Hello everybody, I'm happy to join you today. We're going to talk about the PCF Global Health Equity Challenge Awards and today we're going to talk with Christina Dieli-Conwright from Harvard Medical School. Dr. Conwright is a associate professor in the Department of Medicine and an expert in exercise oncology and is bringing a lot of the ideas of exercise science to the care of men with prostate cancer and our understanding of the disease, and how activity and exercise can interface with the progress of the disease and with the progress against the disease, let's put it that way. So Christina, great to see you. We're going to have you do a little presentation and then we'll have a conversation.

Christina Dieli-Conwright: Great. Thank you so much and thank you so much for the opportunity to discuss this topic. I am always happy to share more about exercise oncology, particularly with prostate cancer. Broadly the field that this has really expanded into has been commonly referred to as exercise oncology. Really in recent years, that term was coined about 10 years ago by actually a colleague of mine, Kerry Courneya, up at University of Alberta. And what this field of research is centered around is the utilization of exercise or physical fitness to enhance the lives of people diagnosed with cancer or at risk of developing cancer. So really what we do is study how exercise can improve various health aspects of an individual with cancer, at risk for cancer. And it's been a really exciting field to be involved in, especially as it's really blossomed over the last 10 to 15 years with an explosion of research that's taken place.

And a lot of that has really come from a number of clinical intervention trials that have focused on features related to health status, primarily rooted in psychosocial health. So we know that engagement and regular exercise elicits multifaceted benefits among prostate cancer survivors, many of which are shown here on this slide, looking from the top left going down reduces features of chemo brain, can improve mood and sense of control, improving aerobic fitness, potentially improving efficacy of treatment, enhancing immune function, pelvic floor function, balance, reducing recurrence, looking over on the right hand side, improving fatigue, joint range of motion, improving treatment tolerance, muscle conditioning, bone density, reversing deconditioning particularly at the level of the muscle, increasing chance of survival and improving quality of life. And we could probably go on and on. The two features that you see there with an asterisk are up and coming. There's minimal evidence to date that exercise can improve treatment efficacy and treatment tolerance.

However, this is really a growing field because we all want to know, can exercise during treatment actually allow the treatment to work better? But as you can see, this is a fairly robust list. So hopefully it's very clear that exercise has many benefits. So if we take a quick step back, what is really the problem that we see with patients diagnosed with prostate cancer and other cancers? And that's really this phenomenon of accelerated aging, particularly spurred on by cancer treatments and also risk factors that lead up to a diagnosis, treatment side effects during, and then of course all the milieu that can follow after. And that's really just what this graph is showing. If you look in on the turquoise line, that's the natural decline in general health with age. And if you look at the red line, you can see that's accelerated where health can decline at a more rapid rate.

So what we try to do is think about windows of opportunity to intervene, to get those two lines closer together using exercise. So the solution, as you can imagine, is to utilize exercise in various ways before, during and after treatment. However, the body of literature that actually exists out there these days is really focused on after treatment. So we really try to think about pushing the envelope a little bit. But just from a more historical perspective, the root of this field actually was inspired by epidemiology. As we know there's strong risk factors, particularly health behaviors associated with cancer risk. And so physical activity has been one of those features that's clearly come out. And so that started to really inspire intervention work. Then if you coagulate all of that intervention work via various types of systematic reviews, meta analyses, you can come up with this review here, this overview of exercise recommendations. And that's on this particular slide here.

So the current American College of Sports Medicine recommendations are aerobic exercise three times per week for 30 minutes at a moderate intensity and resistance exercise two to three times a week, about 30 minutes focusing on large muscle groups. Particularly why it's these parameters is what you see on the left hand side. There's very hard concrete evidence that these types of exercises programmed this way can improve quality of life, reduce anxiety, depression, fatigue, and also enhance physical function and fitness.

And I will wrap up with what we're very proud to share here today, which is the POWER trial, which is supported by the grant mechanism that you mentioned, which is exercise to enhance cardiovascular health among Black prostate cancer patients with androgen deprivation therapy. Thought leading into the name the POWER trial there. We're really excited about this trial. If you look at the literature, there's huge disparities that we know that exist with prostate cancer outcomes, health outcomes, particularly on cardiovascular health among Black men compared to non-Black counterparts. And that was really the inspiration for this particular project. In addition, if you look at exercise oncology research as a whole, there's well over 200 plus exercise trials in prostate cancer. There's one to date in Black men with prostate cancer. So this particular grant and this project will fill a huge gap in the literature and will really give us an opportunity to study a vulnerable population that's at high risk, not only for cancer related outcomes but also for cardiovascular health outcomes.

And so what we're going to do, what we're currently doing recruiting patients for, is utilizing a virtually supervised aerobic and resistance exercise program. So they could do it at home. They receive a bike and dumbbells as well as a wifi enabled tablet. And they have somebody from my lab on the other end of the Zoom link supervising them real time, three times a week for 16 weeks. And we are looking at whether or not this type of exercise can reduce the risk for cardiovascular disease. We'll also look at fitness, quality of life and potentially longer term outcomes with a long follow up. And we're hoping to use this preliminary data for a larger scale phase three trial to really test the efficacy of exercise on these endpoints related specifically to cardiovascular events and cancer outcomes, which as we know needs a larger POWER trial in order to do so.

We've really integrated some unique features in this study. We're working with support groups specifically for Black men that patients receive newsletters every month, specifically geared towards Black community and the Black culture. And we also are engaging specific patient advocates who self identify as Black and who have had prostate cancer themselves as well. And so we're really excited to see this study as it progresses through to full accrual and we're incredibly thankful for the opportunity to have the funding to execute such a trial. Thank you so much.

Charles Ryan: Well congratulations on receiving that funding. It's an outstanding design and a great hypothesis and a really important area. I talk to my patients about exercise. I put a lot of patients on androgen deprivation therapy as an oncologist. And I always try to figure out where are they on the exercise spectrum already. So I'm going to give you three scenarios and I want you to tell me, what would be the one thing you would tell a patient in this scenario? So this would be a person who has essentially never exercised and they're about to start androgen deprivation therapy. If you could give them one instruction, what would it be?

Christina Dieli-Conwright: The one instruction that I would give them would be to move more, sit less.

Charles Ryan: Okay. Perfect. I love it. Somebody who already exercises a couple times a week, not intense, but they're active and they're not in terrible physical shape and they're starting androgen deprivation therapy, what would you tell that person?

Christina Dieli-Conwright:

Simple. To keep it up and to not stop.

Charles Ryan: So three times a week, just stick with what they're doing. And then we see a lot of people who are very fit and even before they get to me, they've read a lot about exercise and these are people who are almost exercising every day and they're concerned about things and they're already in good shape. What do you tell them to do?

Christina Dieli-Conwright: Similar to scenario B, consistency is going to be key. You can start getting into the prescriptive parameters. Should they challenge themselves more? Should they back off? Should they start doing what we call periodization where it's really rigorous programming of the exercise variables. But to be honest, I think what really matters, especially as we get older, is consistency and keeping up that motivation. If what motivates individuals in scenario B and C is to take it to the next level and really dig in or find a really challenging fitness goal like some event to channel or to participate in, then that's great. But I think keeping up that motivation, consistency goes such a long way because that's the part of exercise that it's often missing in people in scenario A who haven't yet started exercising at all.

Charles Ryan: My scenario A patients who don't exercise, I say, try to take a 30 minute walk three times a week, start there and let's talk next time. But I also wonder, and what I'm getting at also is, is there an ideal exercise that is specifically if you will, a targeted approach for the cancer patient? Is it doing leg presses because that's the biggest muscle in the body. Or is it that 30 minute walk. Or is it something that we just don't know but we think there is something or we just don't know because it's individualized to every individual?

Christina Dieli-Conwright: Yeah, I think it's the latter. I don't necessarily think it's that we don't know. I just think that exercise is not a one size fits all model. And if you look at the guidelines I threw up there, those are simply just from a meta analysis that looked at all the literature that had exercise intervention trials, pulled all the parameters together and spit out that algorithm, if you will. But it's really not a one size fits all model. If it were then patient in scenario C may never have gotten cancer in the first place perhaps.

Then exercise may be this all powerful thing. So I think that's what makes exercise a little bit... It does make it complicated, especially because the body physiologically only responds to so much and then it gets bored and then you do need to adapt and maneuver things a little bit. And that's the piece of exercise that's hard to translate because we want something simple like going out and walking three times a week to be the be all, end all. But it does get a little bit tricky, especially for people in the bucket scenario B you mentioned who are already doing something and they're probably really comfortable and enjoying that something and that's great, but maybe it's not enough physiologically to have a more impactful benefit. But if they're motivated and they're doing it, it's really hard to say, oh, you need to go do a lot more at a really high intensity that gets really discouraging.

Charles Ryan: Okay. So that gets to something that I think about when I'm seeing patients, which is I don't want to tell somebody they need to be doing high intensity interval training three times a week and for them to come back and say, I've failed at you're a recommendations doctor, and then they feel like they are failing themselves. While we want them to do that, if they could, we really don't know where the line is for an individual patient. And so this gets a little bit to the psychology of cancer patients and how much they have under their control. And I guess this gets to my scenarios. If you don't exercise, you have a lot that you can gain from doing this one other thing.

If you already exercise a lot, then you're probably not in that group of patients in whom exercise is going to move the needle, as you pointed out. They probably wouldn't have gotten the cancer in the first place if they're already really fit. So I think about this a lot as I'm talking to patients because it directly feeds into what I want them to do and how I want them to deal with this scenario and the various levels that one would take on exercise.

Christina Dieli-Conwright: Sure, absolutely. And I will say something that goes a really long way from what we see with the patients, especially that we were enrolled in our exercise trials is what you mentioned. The fact that you are having conversations with your patients about exercise, already impacts their potential adoption of exercise. And we actually looked at this recently in a survey we did through ASCO. We surveyed patients and inquired about whether or not they'd had these types of conversations with their providers. And it goes such a long way because it means something to them. They hear it from you, and they say, okay, I need to think about this. Whether it be because they trust and respect the information you're giving them, or whether it be because they don't want to disappoint you as their provider, whatever that motivation might be, it really does go a long way. So it always makes me so happy when I hear providers mentioning that they have conversations with their patients about exercise.

Charles Ryan: Well that's why we're doing this recording and that's why we at the PCF are funding exercise science, because we believe the epidemiology, we know that there's something there. We're not quite sure exactly what it looks like and you will help us to figure that out. Now, another question that comes up frequently is, is exercise and all of the perceived improvements in outcome and survivorship, is this a survivorship concept? Meaning you're helping their cardiovascular health, you're helping their mental health. Exercise has all these other benefits, maybe even if it doesn't affect the cancer. And that's something that when you go to work every day, you and your team and you're thinking about this, are you thinking that you're developing an anti-cancer therapy, or a survivorship approach, or both?

Christina Dieli-Conwright: We think of both, actually. We think of both. I mean particularly as you saw with the POWER trial, it's more on the survivorship end. However, another population that's incredibly important to us to study is patients with metastatic disease. And in particular looking at the interplay between numerous health factors such as frailty, sarcopenia, et cetera, whereby there could potentially be some impact that exercise might actually have on individuals with advanced disease. So certainly both, certainly both.

Charles Ryan: Yeah. And I will just close my own thoughts and wonder what your thoughts are on this. If you look at the spectrum of prostate cancer and the biology of the disease, there are some people in whom their cancer is going to override any exercise intervention we can do. However, there is a large proportion of the disease in the group of people who get it, who are diagnosed with it, where it's a metabolic disease. And I will talk about this frequently. I will say prostate cancer is a little bit unique among cancers because of its dependence on metabolism and its dependence on hormone status and the ability of activities and diet and activity to mitigate or to strengthen the hormonal status. So do you think of prostate cancer as a unique cancer with regards to your angle from exercise?

Christina Dieli-Conwright: Oh, certainly. Absolutely. And we think about that with the type of exercise that we prescribe. You mentioned walking a little bit earlier, and we have alluded to and have mentioned in this conversation ADT, side effects of ADT. So in combination with that is the impact it has on skeletal muscle, which is a huge metabolic regulator in the body. So what we really like to do, and another part of the reason we included aerobic and resistance exercise in the POWER trial is tap into those two modalities because they do have an impact on metabolic features within the body. And so absolutely for certain, there's so many ways you can manipulate, prescribe types of exercise, et cetera, that you can really throw out there. And we do think about those. You also have to think about it in the context of a clinical trial and what's feasible to disseminate, et cetera. But, I absolutely agree. There's certain things that we like to think about with exercise specific to prostate cancer and getting at those metabolic issues that you're mentioning.

Charles Ryan: And unlike other cancer treatments that have side effects, the drug is given against the cancer and there's some adverse or untoward effect on the body, hair loss, nausea, whatever, swelling, fatigue. Exercise, the side effects are generally considered to be positive in so far as the adverse effects, the other effects, I should say, of the exercise are reduced cardiovascular, reduced blood pressure, better sleep, et cetera, et cetera. And so it's really a very easy thing for me to recommend to my patients because it's a treatment we hope and it's a treatment with only positive side effects, so to speak.

Christina Dieli-Conwright: That's right. That's right. Absolutely. Absolutely. We like to hear that. We like to hear that. As long as it's done safely, it should always be very positive.

Charles Ryan: Well I want to thank you and congratulate you again for receipt of this award. In particular, your focus on Black men with prostate cancer and how exercise may affect their outcomes. Tell us a little bit about how somebody who's listening might be able to get involved in your study.

Christina Dieli-Conwright: Absolutely. So we are actively recruiting at the Dana-Farber Cancer Institute and the Beth Israel and also throughout the greater Boston area. So if anybody listening is interested, they can certainly reach out to me directly. I can provide my email address, lab website, etcetera, and we'd be happy to enroll anyone interested.

Charles Ryan: What if somebody's already started androgen deprivation therapy or is already receiving treatment for their cancer?

Christina Dieli-Conwright: So they are eligible if they're already receiving androgen deprivation therapy. If they are not, but are planning to, then we can certainly stay in contact with them and once they start androgen deprivation therapy, then they would be fully eligible to enroll in the trial.

Charles Ryan: Perfect. Great. Well congratulations on your receipt of this award and taking on this really important area of research in particular in Black men with prostate cancer. We know from many other studies that Black men have a particularly difficult challenge with prostate cancer in terms of outcome and maybe a group that benefit from exercise as well or more than others. So we look forward to your results and congratulations again.

Christina Dieli-Conwright: Thank you so much and huge thank you to Pfizer and PCF for support of this work. We're excited to execute the project.