Lucy Denly speaks to Dr Christina Dieli-Conwright about her research into personalized exercise interventions.
Ox Pers Med J 2021; 1(1): 8-10
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When one mentions the role of personalised medicine in cancer therapy, it is usually the tailoring of medication to patient factors that is thought of. However, Dr Christina Dieli-Conwright takes a different approach. Dr Dieli-Conwright is faculty at the Dana-Farber Cancer Institute and Harvard Medical School, and her research is centred on testing personalized exercise interventions to improve cancer outcomes in patients. Increased physical activity has been shown to reduce the risk of developing a primary tumour, improve the responsiveness and tolerance to chemotherapy, and expedite patient recovery following surgery or chemotherapy. Dr Dieli-Conwright kindly agreed to be interviewed by the Oxford Personalised Medicine Journal on her work.
OPMJ: Could you begin by briefly telling me about your research?
Dr DC: The focus of my lab is designing and implementing exercise interventions to target various health and treatment outcomes of cancer survivors. This includes everything from reducing co-morbid disease risk, improving body composition, and cognition outcomes, all the way to improving the way patients tolerate their chemotherapy and how they recover from surgery. We are beginning to think about how we can intervene in the prevention stage, but the primary bulk of my work so-far has been in the survivorship phase.
OPMJ: What does a personalised exercise programme entail?
Dr DC: We need to do research with a set protocol of exercises that we want to deliver in order to really determine if that exercise is impactful. However, we do need to tailor these exercises to each individual’s needs, so we do a battery of baseline fitness tests in order to assess where an individual is at before they start an exercise programme to better tailor our exercise protocol to what they need and to their own physiological baseline. These baseline fitness tests include their cardiorespiratory fitness through a VO2 max test, as well as the 6-minute walk test, Margaria stair climb test, gait speed, grip strength, and one-repetition maximum strength. Using results from these tests, patients are prescribed a set of standard exercises at a difficulty or repetition number personalized to them. The relative intensity of the exercises as calculated from baseline tests is the same across the trial population, but the absolute intensity differs between patients.
OPMJ: Is that mainly aerobic training or resistance training?
Dr DC: It really depends on the primary endpoint that we are investigating in the trial. So long as there is enough research to promote utilizing both aerobic and resistance then I would prefer to do so. However, if there is lack of that evidence, primarily in the resistance exercise framework, then we will rely on aerobic exercise only. We need to have the study rational to justify what we are doing, and we cannot just pick and choose what we like or what we prefer! We review the literature extensively to figure out what is the best exercise modality that is going to target a specific outcome, then we build from there.
OPMJ: Your research involves carrying out randomized controlled trials to test whether various types of prescriptive exercise improve cancer outcomes in individuals. What are the biggest challenges you face in carrying out this type of research?
Dr DC: I think some of the biggest challenges are not actually unique to exercise research. I think it is probably just clinical research in general, with the biggest challenge being recruitment. We are asking patients to do something that will almost certainly have some sort of benefit. However it takes their time, and it takes their effort, especially if we are doing a study where the patients are still receiving chemotherapy. We are asking patients to take on an additional task, an additional commitment. Finding individuals who are willing and interested to do this is a challenge. Along with this comes a recruitment bias. We are often getting individuals who are motivated to come and exercise, so that of course lends to a certain population who by means of that motivation will often be likely to comply with what we are asking them to do.
I think overall once we get the patients on, they enjoy the studies. They have a great time, they get to meet lots of great staff members of mine that help to run the exercise programme which are always very fun for them to do. I have some very engaging individuals on my team who really care about this area of research and the patients can feel that. So they really feel like they are in part contributing to science. We have had a very high adherence rate to our studies (well over 90%), and once the patients sign up they come to a majority of the sessions.
We really want a well-rounded population that is more generalizable to the greater nation. It is really hard to do that, especially in a major cancer centre where patients often come for secondary or tertiary opinions, or they have the financial resources to go to a major cancer centre. We are concertedly making efforts to recruit more participants from underserved populations, so they have the opportunity to participate in personalised exercise trials as well.
OPMJ: One of the commonest criticisms of personalised medicine is that it is very difficult to implement research findings into clinical practice due to expense and other hurdles. Have you found this to be true with personalised exercise therapies?
Dr DC: Our research is focused on efficacy trials, and we are still trying to show that while we know that there are so many benefits of exercise, there is still more to be discovered. We have the resources and the experience to test the physiological outcomes of exercise interventions in a specific trial population. The bigger question is how we can really disseminate these interventions beyond research, and that is a really difficult question that is not within my area of expertise. There are whole fields of implementation and dissemination scientists who would be better positioned to attempt to answer this question. Exercise is not easy and fast. It takes time, it takes resources and it takes motivation.
People find motivation particularly challenging, and regardless of what I discover in my trials of the physiology of exercise interventions, this will not change. In this way, exercise is so different from a drug trial, with even the shortest exercise regime of 15-30 minutes taking far more time and motivation than it does to swallow a pill. It is a choice to adapt an active lifestyle.
A challenge with our work is that patients participate in the trials and then the study ends. What do they do next? We do have follow-up periods and track patients for a small amount of time afterwards, but our work is completely dependent on funding and funding does not go on for ever, so unfortunately we can only do so much in that realm. How can you really get people to continue to exercise once they have finished these trials? I don’t know that you can to be honest. We can’t get the general population of the United States to exercise, so how are we going to get people with cancer who are dealing with long-term detrimental side effects to exercise? I think it is a bigger question that goes beyond cancer survivors.
OPMJ: I believe that the issue of time and motivation in exercise interventions really is global. I have observed similar issues in clinic as my role as a medical student here in Oxford, with cancer patients struggling to make the lifestyle changes required to be deemed fit enough for their operations to remove the cancers.
Dr DC: Yes. I think this is going to be a continual societal problem. There are numerous things we can do, but I think one of the most important is to continue eliciting the benefits with research and demonstrating some of the unique aspects that exercise can actually target. We can also figure out from the cancer perspective how we can provide resources for patients. One resource we provide in the United States is a registry of exercise resources for cancer survivors on the American College of Sports Medicine Website. If you put in your ZIP code and the city you live in, then it outputs a list of free resources in the community. This registry has been started to be built over the past couple of years, and it is a great resource for physicians to refer their patients to.
OPMJ: We have a similar resource here in the UK, called Moving Medicine. This is an initiative created by the Faculty of Sports and Exercise Medicine UK that provides health professionals with accessible and evidence-based advice on physical activity for patients with different conditions. One of the biggest questions at the moment in the field of exercise medicine is whether there is an optimal amount of physical activity to improve cancer survival or treatment-specific side effects. Do you think there is an upper-limit to the benefits that physical activity can provide to cancer outcomes?
Dr DC: The patients we work with are so sedentary and deconditioned that it would be challenging to test that upper limit. To find people that are motivated enough to test that upper limit would be difficult, as I think that the amount of physical activity required to become detrimental would be quite high. I imagine that triathlon and marathon runners could overtrain for an event to the detriment of their therapy, however I have treated marathon runners who are undergoing chemotherapy while training for an event and this training has not been detrimental. If a patient with pre-existing health conditions and cancer pushed themselves too hard, they could develop injuries or immunocompromise which may prove to be detrimental dependent on the situation. However, I am not sure that there is a level of physical activity at which exercise becomes detrimental to cancer outcomes.
The question of optimal dosing is an important one, as it would allow us to say “Do this much exercise and this is what will happen”, but I think that the bigger question is how we can make exercise more efficient and still effective. We don’t want to tell people to exercise for 5 hours a week as it sounds very daunting. If we are trying to help cancer survivors, we need to design interventions that give them most benefit for the effort required. We have increasingly been studying High Intensity Interval Training, where you can do 20-30 minutes of exercise with some pretty significant gains. Patients like it as it is fun and quick and makes them feel good. Time is a huge barrier for not just patients but for anybody to exercise, so it is crucial we find ways of making exercise both effective and efficient.
OPMJ: Is there a particular aspect of your research that you are most hopeful for in the future?
Dr DC: I would say there are two areas that I am most hopeful for. Keeping it in the wheelhouse of efficacy, I really think we are going to see a greater volume of investigation looking at how exercise can improve treatment toxicity and treatment efficacy. If we can make people strong with exercise, then I think they will be able to better sustain their treatments. If this is the case there will be less withholding of chemotherapy, as well as less modification of doses of chemotherapy or immunotherapy due to reduced toxicity so that hopefully treatment will be more effective.
The other area that I think will be interesting in the future will be the targeting of sedentary behaviour. If we can reduce sedentary behaviour throughout treatment, then we can alter both treatment outcomes and the development of comorbid conditions. We know that interrupting sedentary time could be a strong regulatory factor of fasting blood glucose. Lots of patient develop pre-diabetes during the course of their treatments, so if we can give advice to patients as simple as “get up for 5 minutes” then that may have a lot of impact on patient outcomes. We plan to use ecological movement assessment technology to prompt patients to stand up. However technology is not for everyone, and as many cancer patients tend to be older adults it is not suitable for a large number of our study participants. I therefore think it is complimentary where appropriate for the population.
The Oxford Personalised Medicine Journal would like to thank Dr Dieli-Conwright for her time, and for her honest and interesting answers to our questions.