CHALLENGE Trial: Dr. Gill (2025)

Manju George 0:00
Hello everyone. Welcome to DocTalks. I’m Dr Manju George, the Scientific Director at PALTOWN Development Foundation, the non profit that supports COLONTOWN. And today we have with us Dr. Sharlene Gill and she’s going to talk to us about the challenge trial. And you know, as far as I’ve seen, everyone diagnosed with cancer, they want to know how physical activity impacts everything. So this is so great that you’re here today to tell us more about the challenge trial. And I really applaud the Canadian team to have pulled a trial like this off so and then, before starting with the actual trial results, my question for you, Dr Gill, is, if you could first introduce yourself and then tell us a little bit about how you got involved in GI oncology.

Dr. Sharlene Gill 0:52
Oh, yeah, well, for sure. So thank you so much. Dr George, for the introduction. I’m really delighted to speak to this group and to speak about exercise and cancer, I think it’s, it’s, it’s the novel treatment we didn’t think we were looking for, but we’ve now kind of identified so, so it’s an interesting question. So you know, my entry into oncology actually came about because I was a oncology pharmacist. And then while in medical school, I continued to work, and I thought, this is really medical oncology for me is really where I wanted to be. For GIOncology at the time–we’re talking about like, 25 years ago, when I did my fellowship, there was such a diversity within GI oncology, like, if we think about upper GI, lower GI, hepatobiliary at the time, it was typically an older population. Not that that was my draw, but just to highlight how much things have shifted in that space, and I just thought that there was lots of opportunity in GI and so that’s kind of what drew me to it. And just, you know, what we’ve all kind of seen in the last 20 years, especially in the last 10 years, I’m just very grateful that I’m in this space and have an opportunity to care for patients. I’ve never looked back. It’s been the what was that the best decision I made.

Manju George 2:27
Okay, thank you so much. And then I would recommend everyone watch Dr. Gill’s TED Talk.

Dr. Sharlene Gill 2:27
Thank you. Yes, from 2 years ago, thanks so much.

Manju George 2:31
Okay, let’s, let’s get on with the talk?

Dr. Sharlene Gill 2:40
Okay, for sure. So I’ve called this From advice to action, and I hope over the next sort of half an hour or so, as we go through the data, that the reason for that title will be apparent. So we’re going to be talking about the CHALLENGE trial. And the CHALLENGE trial is a randomized control trial that demonstrated with level one evidence that exercise improves survival after colon cancer. And so I’m a medical oncologist. I’m based out of BC Cancer in Vancouver, Canada, and I also have the privilege of serving as the Chair for the GI disease site for the Canadian cancer trials group, or CCTG, which was the cooperative group that led this trial. So there’ll be some coming in and out of the presentation that shared this data at ASCO 2025 and I’ve left time for sort of questions and discussion, because I think you’ll find that the evidence is fairly self explanatory. It’s kind of more the execution and implementation that we’re kind of trying to figure out as next steps, moving forward. So the CHALLENGE trial is a phase three trial looking at the impact of a physical activity program on survival outcomes. So the primary endpoint was disease free survival in patients with high risk, stage two or stage three colon cancer who had completed adjuvant chemotherapy. Dr Christopher booth, who presented this and was the first author, was a fellow at CCTG 17, years ago. At the time this trial was conceived, and I was a relatively junior member of the CCTG GI disease site at the time, and he kind of came to me with this idea, and to the group about doing a randomized trial of exercise. And it didn’t seem like it would be possible, but I think this is one of the things that only a cooperative group can take on. So over the course of the trial, we partnered with the Australasian GI tumor group, AGITG, so the Australia New Zealand group and Jeanette Vardy was the lead investigator for that group. And then later on in the trial, UK also came on board. And so about 10% of the patients came from from the UK, so over the trajectory of the trial– it was a multinational trial.

Dr. Sharlene Gill 5:16
And so at the time, Chris came to us with this idea as a very fresh faced fellow, it was really on the basis of retrospective epidemiologic data that was consistently showing an association between physical activity and risk of recurrence after treatment of colon cancer. And Dr Jeff Meyerhardt from the Dana Farber, led a lot of this early work in terms of the demonstrating this association between following patients over time after they’vecompleted adjuvant treatment, and then looking at self reported physical activity as measured by MET hours per week, and demonstrating that those patients who are more active had experienced better outcomes, betterlong term outcomes. Now, as we know, the nature of retrospective data is that it can certainly help generate hypotheses. It can tell us a story. And there are sort of– there’s biologic possibility, there’s a dose response. The more people exercise, the better their outcomes. And so many things that kind of led us, would lead one to believe this is probably something real, but we know that there’s lots of confounders there. And the criticism was always that in a non randomized setting, how do you know that there isn’t something about people who exercise that’s just different and and so that was kind of the crux of the argument from the biologic plausibility piece.

Dr. Sharlene Gill 6:59
And these are slides, and I’m sorry the acknowledgement fell off my screen here, but that were presented by Dr Meyerhardt at ASCO when he introduced the challenge presentation, the biologic rationale. It kind of relates to the fact that we know exercise has plays many roles in things like a metabolic growth function. So if we think about IGF, one, insulin like growth factors and their potential role in carcinogenesis, it plays a role in controlling inflammation and pro inflammatory cytokines that also then have a role in carcinogenesis, as well, asprogression of cancer. So we’re thinking about cell proliferation, angiogenesis, and it has a role in immune function as well, particularly we think about immune surveillance, both from a prevention and a recurrence lens. I think that biological plausibility is fairly robust. I think it’s wanting to understand what particular aspect of that is driving it is still ongoing work, but it certainly made sense that exercise would be beneficial, but because it was observational data, it was felt that a randomized control trial was needed. And I will say that, I work in a public health system, so in Canada and one of the drivers for us within the CCTG to support this trial was that if we are ever going to be able to ask for public funding to support patients with cancer receiving an exercise program, we had to have level one evidence. So the strength of the observational data would not be enough for us to go to our provincial ministries and say, Look, we need public dollars to support this. So that that was the Canadian angle. We knew our health system was going to demand this level of evidence.

Dr. Sharlene Gill 8:41
And so this is the schema. For those of you who’ve seen, this trial schema is fairly straightforward. It’s again patients who’ve completed adjuvant treatment, high risk stage two or stage three colon cancer, 5FU based chemotherapy, and then within two to six months of completion of adjuvant chemotherapy, they underwent baseline fitness testing to determine eligibility. So in the trial, on average, it was about four months after completion of adjuvant chemotherapy that patients were randomized. And the purpose of the baseline fitness testing was, as you can imagine, there are some people who are already coming into this quite fit. And so in a very fit population, to demonstrate a difference with an incremental improvement is going to be harder, right? So, and that’s small proportion, but some people were too fit. And then there are some people who don’t have the fitness capacity to be able to engage in the structured exercise program. And so that this did not exclude a significant number of patients, but it was trying to make sure that this was targeted to the patient population that was most likely to benefit, and then patients were randomized in a one to one fashion to receive health education materials alone. So I’m going to highlight this, because it’s really important, this question of advice to action. So all patients who were randomized were advised, even in the standard arm, that exercise is good for you. And the difference in the experimental arm was that they were also advised exercise is good for you and given health education materials, but then they were also enrolled in a structured exercise program that I’m going to explain to you, and it was a three year intervention.

Dr. Sharlene Gill 11:48
And so this is sort of an example of, this is actually the health education material that was provided to patients, but it’s a 34 pager. I don’t have all 34 pages, but you can see, it’s a bit dated. So different thing about 2007, pre AI and fancy graphics. And it was developed by Kerry Courneya, who was the other co lead for the trial. He’s a kinesiologist, a physical activity consultant based out of the University of Alberta in Edmonton, very widely recognized in Canada for his work in promoting exercise science in cancer, and actually recognized last year with an Order of Canada citation, because he’s really been an amazing, tremendous champion. And so as a step up to the challenge, is what we called it. And in this 34 page document, it was kind of why exercise is good for you, kind of a lay summary of the epidemiologic data, the other benefits of exercise, and even a program that was laid out for people about how much they can walk. And so everyone received this, and then even people like me, and you can see how dated this is by my picture, provided little quotes to say, yes, please exercise. You should exercise. And so the control arm got this and the experimental arm got it. For the experimental arm that was enrolled in the structured exercise program, the target for the trial was to increase physical activity by 10 MET hours over their baseline. And so a MET is a unit of energy expended by sitting for one hour. So all of us sitting here for this one hour session will have expended one MET.

Dr. Sharlene Gill 12:36
An hour of brisk walking burns, expends four MET hours. So to increase your MET hour increase by 10 MET hours per week would mean an additional two and a half hours of brisk walking per week. That’s kind of the equivalent metric. And brisk walking, as Dr. Courneya describes it, is you look like if someone saw you, they’re like, Oh, wow. Manju looks like she’s late for an appointment. Like it is intentional walking. It’s not strolling. And Physical Activity Consultants at all the participating sites across Canada, Australia and UK, worked with the patients. So the medical oncologist referred them, but it’s really the PACs who did the work to create an exercise prescription. And so this was sort of the the framework. And, changing behavior is really hard. And this is, again, kind of this idea of, advice is often not enough in this exercise science space. And so most people don’t, may not receive that and and we know that a cancer diagnosis, and I don’t have to tell you, is sometimes an opportunity where people really are rethinking, what’s in their control. How can they feel more empowered? And so it is a much more motivated, I would say, potential setting. But we still know that this is really hard. And so the structured exercise program, was not just about exercise. It was a behavior change intervention, and it was a three year intervention split into three phases.

Dr. Sharlene Gill 14:24
And for those of you who are really interested in knowing the details of it, I will say that in the New England journal publication, the supplementary appendix, in great detail, describes what was done at each of these sessions, including what the behavior change component was. So let me kind of lay it out for you. So at in phase one, so if I’m in Vancouver, I would refer a patient. Doctor Kristen Campbell was our physical activity consultant based out at the University of BC, and the patient would be asked to participate in 12 mandatory sessions every two weeks over the first six months. And these were in person, and during that session, they would be going through a supervised exercise program, but also engaging in a discussion around behavior change theory, so really asking motivating questions. What are the drivers of decision making? What are your barriers to change? And then when patients would come back, there would be an element of accountability for, these were the goals, what were you able to do like your homework? And if not, if you weren’t able to achieve it, how can we modify things? And even simple things, like telling people, what if you leave your runners at your bedside before you go to bed, and then when you wake up in the morning, they’re there? And so those really practical suggestions, in addition to the mandated sessions every two weeks, they were also encouraged to do additional.. they were offered the opportunity to do an additional 12 sessions. So it could have been weekly if they chose to do that. And the goal in that phase was to reach that 10 MET hours per week increment. The second phase, which was month six to 12, the sessions continued every two weeks. They were mandatory attendance, but now they could be done in person or virtual. And one of the, if I can call it, a silver lining of covid, but one of the things that we learned by executing this trial during covid was really honing in on the virtual platform, and that as we are thinking about the knowledge translation piece and implementing this in practice, that data is very helpful to kind of know how that’s feasible to do this virtually.

Dr. Sharlene Gill 16:48
Canada, as many of you know, is geographically very vast. And so we have a number we have patients living in very remote communities up north. So from an equity and accessibility lens, this was, this is, was a really good learning. And then for the last two years, month 12 to 36 mandated, 24 mandated monthly sessions, again, could be in person or virtual. And so this, I hope this, you see this and you realize two things. One is that this was not a prescription of going to the gym and working with a trainer every day. This was really about providing that support, providing a program and a prescription. But most of the patients who participated in the trial were doing this on their own right. This was they’re kind of, it’s either every two weeks or once a month, but it’s being it being accountable and getting that guidance along the way that was critical to change the behavior. And the second was that it was intense. I think a lot of the biological plausibility piece around why exercise is beneficial in cancer is related to cardiovascular exercise. Not so much like strength training and pumping iron and so this was, most of the activities were cardiovascular activities, so brisk walking or whatever worked in people’s lifestyle. But it was cardiovascular activity. And so the primary endpoint I mentioned was disease free survival. We know that in the adjuvant setting of colon cancer, this is a validated surrogate for overall survival. And then the secondary endpoints were overall survival. Patient reported outcomes measures of physical fitness, which we’ll talk about, safety, adherence, and then biomarkers, as well as the health economic piece the last two are..still work ongoing that wasn’t reported at ASCO, but they did report some of the other secondary endpoints.

Dr. Sharlene Gill 18:57
So over 15 years, actually come back to the power calculation, and then I’ll tell you. But the original power calculation was 962 patients for 380 events to detect a hazard ratio of 0.75 or a 25% proportional reduction in risk of recurrence or death or new primary– hazard ratio of 0.75 for disease free survival, so that would have translated into a 6% absolute improvement in three year disease free survival, and it was an Intent To Treat analysis (ITT), meaning patients were analyzed in the arms to which they were randomized, as opposed to what’s sometimes called a per protocol analysis, Which for something like this would have been very confusing. People who actually did the intervention, right? So this was about an intent to treat. But we hit a lot of roadblocks along the way. I think when Drs. Courneya and Booth called it the CHALLENGE trial, I didn’t think they did it– it was kind of like stepping up to the challenge, but not that it would be challenging, but it was really challenging. Accrual Was slower. Part of it was for the centers that are used to doing oncology trials, getting infrastructure for physical activity consultants to be a part of the team with work, that took time. We slowly engaged our international partners. That took time, and then the event rate was lower than expected, which is good for patients, but the estimated recurrence rate was higher than what actually was observed. And so that took time. So our data safety monitoring committee approved a cut off at the end of December, end of 2024, so with 200 events at that time, that gave the trial 80% power to detect a much bigger Delta hazard ratio of 0.67. So the risk with that approach would have been that maybe we would have missed a smaller benefit. But it had gone on a long time, and we felt that this was really the appropriate time point to close the accrual and close the data set.

Dr. Sharlene Gill 21:17
So over that 15 years, 889 patients were randomized, one to one to structured exercise program versus health education materials alone. 55 sites were participating, mostly in Canada and Australia. As I mentioned, the median age is 61 so but the range was 19 to 84 but a slightly younger population, I guess, compared to, if you look at medians, half female, 90% were stage three, and 80% received oxaliplatin containing chemotherapy, and otherwise, there were no big differences in terms of the two groups in terms of adherence with those three phases. So 83% of participants completed the mandated sessions, the every two week sessions in the first six months. 68% of patients completed the mandated sessions in the phase two the second six months, and then by end of phase three, like 63% of participants completed the whole three years of mandated sessions. So that’s actually in exercise science, pretty good adherence to the program. From a safety lens. The only adverse event that was different was musculoskeletal events. So 7% more people in the exercise program reported things like sore muscles. You can call that an on target effect, or on target side effect, but that was really, that was really it. Five years into the accrual of the trial, we published, sort of just a feasibility, like at one year from patients being randomized on the trial, we wanted to recognize that we were seeing a signal that this was feasible. And what we reported at that time, and at that point, about a third of patients had been enrolled on the trial, was that by self reported physical activity, there was an increase in both–that’s the first row– in both the the control arm, health education material alone, or the exercise program arm. So that brochure maybe made a bit of a difference early on, but the delta was 10 MET hours for the experimental arm. And then the other metric, that’s a very objective metric is a predicted VO2 max. And I like to exercise, but I’m not a kinesiologist, but my understanding is that that is a very good index of physical functioning and aerobic capacity. And so at that one year mark, there was an improvement seen in predicted VO2 max in those patients who are on this not super rigorous, but prescribed exercise program.

Dr. Sharlene Gill 24:08
When we reported this at ASCO, and Chris presented it, these were the physiologic fitness metrics over time, and so self reported physical activity, the six minute walk test, so how many meters they complete in six minutes? The VO2 max in terms of aerobic capacity. And then the questionnaire, the short form 36 on physical function and a change from baseline. So for this one, the the lower the score, the better, meaning you’re reporting less of an negative impact, on physical function. The important thing to highlight here is that the x axis here is time. So over, it’s over seven years, but over the three years in the intervention this was maintained, these were sustained differences. Which, kind of the hope is that this was not just a three year program, that there was true behavior change that is long lasting for the participants. So to the primary endpoint of disease free survival, and why we’re talking about it. The CHALLENGE met its primary endpoint for disease free survival, so a hazard ratio of point seven two, which translated into a 6.4% absolute difference at five years in disease free survival, 74% to 80% and if we look at it from sort of a number needed to treat framework, that absolute difference means that for every 16 people who exercised, one person was prevented from having a recurrence or a new cancer, which is a clinically meaningful number needed to treat. And if we look at the pattern of recurrences that were observed, the major impact seemed to be a reduction in recurrences in the liver, so distant metastatic relapse for those patients who were enrolled in the structured exercise. And interestingly, though, not big numbers, but there was this observation that there were reduced new primaries, which biologically makes sense, because we’re talking, thinking back to the things we’re talking about in terms of metabolic growth factors and pro inflammatory milieu and those things, and for hormone driven cancers like breast and prostate, we also know exercise has a role in androgen/ estrogen regulation, and So this is kind of been, was not totally expected, but an interesting observation, and reduction in new colorectal primaries, kind of speaking to a secondary prevention effect as well. Overall survival was a secondary endpoint that was also positive, so a hazard ratio of 0.63, which can think of it inversely, the sort of that translates into a 37% proportional reduction in risk of recurrence over time. And you see those curves, as with most adjuvant trials, they start to separate sort of at the four or five year mark. And so the at eight years, the difference in overall survival was 7% so from 83% to 90% for those unstructured exercise and that was primarily driven by colon cancer related deaths. And again, from an NNT like a number needed to treat, you could say, for every 14 people who participated in the exercise program for three years, exercise prevented one person from dying, which, again, is very clinically meaningful.

Dr. Sharlene Gill 27:46
When Dr Booth presented at ASCO, he put this up as kind of a benchmark, this against other drug interventions that have been become standard of care in the adjuvant space, not just in colon cancer, but in lung. If you think of osimertinib and durvalumab, in breast trastuzumab, and pembrolizumab and pertuzumab, and that 7% absolute improvement at eight years falls well within what has been deemed to be clinically meaningful to change standard of care when we talk about drug treatments, but without the toxicity and at a fraction of the cost. And so the conclusions were that a structured exercise program–so we’ve tried not to just say exercise, because, again, the intent is really to try to build capacity for cancer rehab physical activity consultants as part of a patient’s cancer treatment team. And I think while this data is in the adjuvant setting for colon cancer, it’s going to be hard not to extrapolate it to other settings. And because biologically, I don’t think, and most people don’t think, this is something unique to colon cancer, but that would be an extrapolation. It’s a first in class anti cancer effect demonstrated in a randomized control trial. And there is ongoing work within CCTG to look at sort of the secondary endpoints of biomarkers, health economics, and also predictors of adherence, trying to identify what were the barriers for those 1/3 of patients who were unable to complete, the mandated sessions over the three year program.

Dr. Sharlene Gill 29:33
This is a picture of Dr Christopher booth when he was presenting at ASCO. And on the second picture below, that’s Dr Kerry Courneya, who was the physical activity co lead for the CHALLENGE trial, and it was a simultaneous publication in the New England Journal of Medicine. And at the time when it was presented at ASCO in June, it did receive a lot of press internationally and in the Canadian Press. Which are some of the headlines on the on your left and in the US press as well, really highlighting that this is of interest, I think, to the public to see that you can actually, scientifically, demonstrate a survival benefit with an exercise intervention. I may be biased, but this really does set a new standard of care. Historically, we’ve thought about exercise in oncology as a quality of life intervention, right? And it is a quality of life intervention that is a very meaningful value, but it is also a treatment, right? And and should be viewed as such, and should be made available to patients and from again, our advocacy lens, we’re trying to work to get this to be a funded facility for patients, not just a please go out and exercise if you can.

Dr. Sharlene Gill 31:00
Knowledge alone will not change patient behavior outcomes, and health systems need to invest in behavior support, really, to move the move the needle on this in a population based manner. It’s empowering for patients. This is what patients have told us. It’s achievable for patients. This is what we’ve seen in the trial. It’s sustainable for health systems like we’ve done some back of the napkin calculations and some more sophisticated calculations within my provincial health system. And this is quite literally, like less than 1/10th of the cost without a lot of the other health resource implications, and, of course, without the toxicity of a lot of other trials. So this really is has value. And I think it also reminds us of the power of academic cooperative trials groups to answer this question that matters to patients. So we have patient representatives in our cooperative group trials. And really, like most cooperative group settings, try to make sure that we don’t get boxed in and, oh, this is, could be really scientifically interesting, but really are looking big picture. Does this matter to patients? And I just think of the patients who chose to participate in the trial that I enrolled in Vancouver, and they were just so excited at this opportunity. They just completed their adjuvant chemotherapy, and it was but the barriers were, were really about they felt they weren’t sure they would have the time, and how would they manage this and I think that’s where it really highlighted that we need to provide that support as a program. Again, not just telling people to please go exercise. When it came out, just in locally, I was trying in our efforts to try to advocate for health system change, I published this in our local newspaper at the Vancouver Sun. But it’s this idea of of embedding exercise into survivorship care and simply telling people to exercise is not enough, and I think we saw that because I think we could have been criticized if the control arm was surveillance only, but because there was this active education component to it. And despite that, you see this improvement, you realize that it’s really the the exercise program intervention that made the change, and we need to, sort of build capacity and also eliminate structural barriers that for patients to participate. This is the just are some members of our CCTG group, some of them you may be familiar with, and this was the picture on your left was the “Bum run” which our CCRAN, the colorectal cancer research advocacy network, one of our Canadian colorectal cancer advocacy groups had held at our CCTG meeting in the spring, so a bunch of us went and joined.

Dr. Sharlene Gill 34:05
And then, when you mentioned this earlier, I feel always very privileged to have opportunities to engage with patient groups and speak to patients, A, because I learn a lot, and B because I think it’s really important for us to remember that empowering patients to take control of their cancer journey is so important. And so when I did this TED talk, it’s been like three years ago, but it was just on the heels of covid, and I was feeling a bit, I don’t know kind of like many people lost during covid, about what’s finding my purpose and and working towards doing this talk really helped remind me why I do what I do, and even today, I’ll patients who will see me for the first time, and they’ll be like, I saw your talk, and that really helped me to prepare for this consult, even so, and that means a lot to me, and so I’m really grateful for that. So that’s all my I won’t keep speaking here, but I would be happy to take any questions. Thank you very much. Yeah.

Manju George 35:21
Dr Gill, thank you so much. That was really very informative. And thank you for, you know, telling us about your TED talk. I think one of the questions that I have for you is I’m really curious about the behavioral intervention part, because I think that from COLONTOWN, we know that, we have a Healthy Habit Highway kind of group, because there are already, there are a lot of people who have been exercising, and then they have called colorectal cancer diagnosis, and they’re like, Okay, we need to do this more. But like you said, you know, the moment of diagnosis is like really a point in many people’s lives where they think they have to recalibrate their life. They have to stop living the way they did. Then they want to make changes. So a lot of people look at exercise as a means for that. So I mean my question to you, it is, like, from your experience with this 800+ that’s a large number of people, what has been some of the common things that people came up with why they couldn’t exercise, or why they miss sessions?

Dr. Sharlene Gill 36:36
So I think a combination of things, I think that it’s interesting, you made the comment about like, what at the time of diagnosis,? And this is true in medicine across, disease types, but that that moment of reflection. And so on the one hand, I will say, I have some, I have patients who are very active, and then they get diagnosed, and they’re like, what the.. like I’ve been doing everything, and this still happened. And I can understand how that’s really demoralizing, and for them, it’s the work is really trying to say that there may be other aspects of how your cancer presented that were changed because you exercised? Or maybe or the biology of your cancer may be different. So we try to pivot a bit to encourage them to continue to not lose faith and stay active. And we know also the mental health benefits of exercise. There are also many ancillary benefits and but, but the majority of people honestly, many of our patients are still in their 60s and 70s and are not used to being engaged in a routine exercise program. We see that a lot actually, in our less urban centers, where, like sometimes in Vancouver, when Vancouver’s West Coast is kind of a West Coast lifestyle, people are outdoors. We had more than a few screen fails, meaning people were too active. But that was not the case in our smaller sites, because in those communities, people were not as active often and were able to participate.

Dr. Sharlene Gill 38:20
So the main barriers were the in person sessions and, for many people, even though they finished their adjuvant chemo so the intensity of their medical visit is finished, they’re trying to get on with their life and get back to work and all their family responsibilities that have been put on hold for the last year because of their diagnosis and surgery and chemo. So that was a big one. Was that I just can’t go. And so you’ll see that the initial drop off in the adherence was in that first phase, and then those who made it through that were actually pretty stable through phase two and three, especially when it allowed that virtual component. And then the second was, you know, I think that, we didn’t see, for example, we didn’t see weight loss. That was not something. And so some people were maybe a little bit skeptical about would this really change my risk of recurrence and I actually am, to be honest, I’m grateful that we didn’t see weight loss because it because of two reasons. One was that this isn’t, this isn’t about weight loss. And it also tells us, reminds us, that this is not, you don’t have to do that kind of a change in your lifestyle, in terms of diet, and you’re exercising every day, that this is something that hopefully is very achievable for the majority of the public.

Manju George 39:55
Okay, okay, that’s, that’s really good to know. I think we have some questions in chat. Let’s look at those. Oh, wow. So this person says the PREHAB trial similarly found that supervised training was more effective than self directed exercise in improving functional outcomes following colorectal cancer surgery, the supervised program involved one hour sessions of aerobic and strength training performed three times per week, with rest days in between, I have two questions about this. How important is it for the exercise program to be scientifically tailored? Or can any varied and consistent exercise routine be just as beneficial? More importantly, if someone is highly self motivated and adhere strictly to their self developed exercise program or regimen. Is it possible to achieve the same level of success as patients who receive private or supervised training, if not, where can we find hope that exercise, regardless of format, can still contribute meaningfully to survival and functional recovery?

Dr. Sharlene Gill 40:56
Yeah, wow. Very thoughtful question. Okay, so the PREHAB trial, I think again, a really, a much more finite time period, because it really was kind of as the lead up to surgery, but really demonstrated the importance of that structured, that supervised component. I think we have to, from a generalizability and pragmatic lens, have to kind of not be too prescriptive about the physical activity. And that’s why, in a lot of the discussions around the challenge intervention, even though patients came in, had a baseline assessment, then the physical activity consultant crafted it, we’ve tried to say it could be as simple as like walking briskly for 30 minutes five times a week, right? To make it so that it doesn’t land in a way that people feel like it has to be a scientifically structured program. That being said, I feel very strongly that it’s my responsibility as a advocate for my patients to pound the door as it was and say, well, we should have capacity for patients to be referred to a physical activity consultant. So there’s working always pushing for that ideal. But right now, what am I telling patients in clinic, just that is that whatever behavior changes about that motivation, but also you have to enjoy the activity you’re doing. So if there are physical activities that you enjoy, you don’t have to necessarily change them. But maybe we’ll do more. We’ll talk a little bit about kind of escalating that and really trying to be nimble and flexible with that. So people don’t feel overwhelmed by “oh my god, I love playing pickleball. That’s my whole thing. And now you’re telling me I have to do this”, and we don’t want to do that. So for I don’t know how well to answer your question based on the CHALLENGE trial. So for people who were already very motivated, like, I would have people, they’re like weekend warriors, biking and everything that they weren’t eligible for the trial. Really high fitness, functioning folks who were not part of the CHALLENGE trial. But that being said so, what we don’t know is, what is that? Do we tell them to exercise more? Does an increment from of 10 MET hours for someone who’s already maybe doing this very high level of activity, achieve the same benefit? I don’t know, but I think people who are self motivated are engaging in exercise for a multitude of reasons. Often it is kind of that empowerment, physical functioning, your sense of well being. Our mental health, we know how we manage stress. So it’s interesting. Someone asked me once they said, well, if the trial is negative, are you going to tell people not to exercise? And I thought, Well, no, because we know that there are all these additional other benefits for exercise, but the value of it being positive was really trying to, I think patients get it, but for health systems to understand that this requires a commitment and infrastructure. I hope that answers your question,

Manju George 44:27
Yeah. Thank you so much for that. The next question is, so I just wanted to make a comment, so it’s really interesting that you did not see weight loss. So that, I mean, I so basically what that says is that any amount of improvement, right? Even if you did that, minimum, though, 10 MET hours increase seems like a lot, but maybe not, right? For someone who’s not doing anything even that, so even if you don’t see a difference in your weight, you might still be benefiting from the exercise.

Dr. Sharlene Gill 45:00
Right, yeah. And that wasn’t the goal, and the other reason why I said we were kind of if we saw weight loss, it’s hard to see that just from this measure of exercise. So then it would be, oh, did people change their diet significantly? And is that what’s driving it? And to some respect, if starting to exercise helps you to adopt other healthy lifestyle changes, that’s great. It doesn’t have to be related to the exercise, but it’s not. It was not like running 10k every week or something like that, because, again, most of these patients are in their 60s who are on the trial.

Speaker 1 45:00
Yeah, so we can go to the next question. Is there any evidence that the type or amount of cardio exercise makes a difference? The study looked at brisk walking. But do you think doing more of that or doing higher intensity exercise would have more of a benefit?

Dr. Sharlene Gill 46:01
I think there is a dose response. I think that the study goal was 10 MET hours per week. But patients over the course of three years, many increased it by up to 25-30 MET hours per week. So, and we know from the epidemiologic data that that there is a dose response, the more people exercised that their risk of recurrence was lower. So I do think if it’s practical, it’s part of your lifestyle, and you you think it’s something sustainable, then by all means, there probably is more benefit over time. But I think the key is trying to for people who don’t exercise that much, really making it achievable, so I try to tell people, you don’t have to be doing that level of activity to see the benefit, but I do think there is probably a dose response to a point, right? It’s everything’s gonna be to a point.

Manju George 47:01
Yeah, okay, thank you. This question, this person says I was running at least five times a week before diagnosis. Diagnosed stage 2A 2/24, low risk, surgical treatment only. I continue to brisk walk six times per week, at least four to six miles, not only for physical activity, but mental benefit, I hope it decreases my chances of recurrence. I do not attend supervised exercise. It’s on my own.

Dr. Sharlene Gill 47:32
Yeah, thank you for sharing that. That’s perfect, you’ve already engaged in the behavior change component, which I think, as I said was the biggest part of this supervision. It wasn’t so much the exercise because you’re already doing it, but it was the behavior change. So again, by no means am I saying we all have to have supervised exercise, but many of us do need that support for the behavior change component.

Manju George 48:05
Okay, okay. I just want to share what happened with me. So here, when I was diagnosed, there was a program at the YMCA, and somebody in COLONTOWN told me about it. It was called Live Strong. It was 12 weeks of exercise. But it is like any cancers would all go in there, and then they would tell us about the benefits, and then it was more like a structured exercise program, but not the part that you were talking about, the barriers. So then during that 12 week time, we didn’t have to pay for membership. And then after that, they encouraged us. So during that 12 week time, apart from this particular one and a half hours twice a week, you are free to attend as many classes at the YMCA and whether you wanted to do a lot more, lot less. I felt that I used to be always an active person. I did not run. I did yoga. I did like follow a YouTube video and do some 30 minutes of activity, something like that. But this was really good for me, because then that exposed me to strength training, to Zumba, to so many other things that I had not done. And I got my family to come with me to the YMCA, and then we did it. So this was in 2018 when I started, and we did it till covid in 2020 and after that as well. Then we stopped going to the Y. So then, we were talking about, like, access to all of these. And there was some discussion in a couple of groups in COLONTOWN where we were saying, it’d be so good if, during the survivorship–what you’re actually trying to do– is that the oncologist could, discharge us from their care and say, here is a year that you can be this place, yeah, something like that would have been awesome, right? Because it’s not available in many places.

Dr. Sharlene Gill 49:58
It’s true, we were talking about barriers. So, cost is a barrier for people to, especially, again, you’ve come through this major life changing event, you haven’t been working, for many people for a period of time, and then this idea of sign up for a membership to a gym. I ‘m again, you know, I’m speaking of our Canadian system, which is the public health system. I think dollar for dollar, the return on that investment to to me, makes so sense. And I think that it does land well with policy makers as well, but just trying to figure out how to make it happen and, Dr. Booth, who’s actually, who I mentioned is the lead author. He’s based at the University of Kingston. He’s doing a lot of work, also for us, for to nationally advocate for this. But exactly that’s what I would love. I i would love to be able to discharge a patient and provide them not just the Okay, go exercise here, but actually send them somewhere where they’re connected with someone who can get them on on track and help them to do that. And bring me back in here. We’ll talk about it. But I think I’m very confident that this is something that will will be a part of our health system.

Manju George 51:25
So the other point that I what one of the things that you mentioned was about sustainability, right? So sorry, I’m getting some messages, but I think for me, that was one of the things like, so my kids would laugh at me, saying, “that’s not running” because I wasn’t running, and then, but then there were some studies which said that, like, to get benefit, you don’t need to run, run. You need to, like, move faster than walking. And so they used laugh at me, saying, “this is, like, old people running, like, where are you going, mommy?”

Dr. Sharlene Gill 51:57
Kids can be harsh, but that’s exactly, yeah, it is, it is. It doesn’t have to be running and in the point of the other thing that I didn’t talk about, what’s gonna make is we’ve seen this before. We’ve seen it in cardiac rehab as well, right where we and the health system does exactly what you’re saying Manju, is they prescribe cardiac rehab, and patients after a cardiac event will go and have supervised exercise. So this is not something that is new in that sense, but, but new for oncology. But I think that if we had said it’s running, that would deter people and thankfully, the benefit was seen with a relatively modest but very diligent, consistent application of exercise. So I don’t want to minimize that this wasn’t work for people. This was definitely work for people, but very achievable,

Manju George 52:58
Yeah. And I also want to say that you had shared that, that booklet with me. So I will post, when we have it in COLONTOWN University. I’ll post a link to that, because there were questions asking, like, why are you not able to exercise? And what can we do? Like, I mean, I think that part is something that would be really of value. And I’m guessing the the physical activity consultant, probably they also helped in figuring out what those things were. So we have three minutes. My last question to you, it is like running such a trial. I mean, 15 years and taking so many centers I don’t think it would have been possible in the US.

Dr. Sharlene Gill 53:35
I think we had our doubts over time. But I’m just grateful that we are in in an environment where we recognize the importance of publicly funded research and, these kinds of questions, we just need that kind of infrastructure, whether, though, so our Canadian cancer trials group is a member partner of the NCCN, so and which is funded by the NIH, and we can in Canada, interestingly, it’s mostly funded by philanthropy, the Canadian Cancer Society. But yeah, this is something that only a cooperative group trial could have done, and, but I think the crux was that patients really wanted it. I think that would have ended the trial if there was no momentum, but our patient advocates within our group, and patients we spoke to, they felt it was a really important trial, and their participation is what made it happen.

Manju George 54:46
Okay. My other question is you said that in person visits were one of the major barriers. So do you think that after covid and everything that we have learned, do you think that if it had more of a virtual component, it would that have been different?

Dr. Sharlene Gill 55:01
I think maybe the adherence would have been different, you know, in 2000 and like nine, when the trial, the idea of virtual training, and so people didn’t quite, you know, covid really changed that. But this idea that, you know, you might have YouTube videos, but those, you know, having a live training session virtually just seemed very foreign. But I do think now what we’re thinking about implementation a virtual component is huge, like especially for, again, not just people who are who have very significant time constraints, and also people who live far away, and it’s and it’s so great that we can be apply that now. So I yeah, I think a virtual component will be key. And the trial was able to kind of confirm, at least demonstrate the feasibility of the virtual component through the second and third phases of the intervention. Okay,

Manju George 55:57
Thank you so much. This was very helpful. Thank you so much for your time. I hope that for everyone in Canada & in the US, I hope this will push people to prescribe exercise for, survivors. And I think that would, and I’m sure that when you look, you might see a general improvement in health as well, right? Which means that for the investment, you’re getting benefits in multiple ways.

Dr. Sharlene Gill 56:24
Yeah, yeah. And even the finding of different reduced primaries in non colorectal related cancers, I think this just is amazing. So yeah, thank you for spreading the word about this. I do like I think, I think this will change how we look at exercise as an active treatment, not just, not only as a survivorship intervention.

Manju George 56:45
Okay, okay. Thank you so much. Thanks to everyone for attending, and the video will be posted in about two weeks with the transcripts on COLONTOWN University.

Dr. Sharlene Gill 56:54
Thank you. Thank you. Bye.