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Aerobic Exercise Relieves Pain for Ovarian Cancer Survivors

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  • 00:00 --> 00:02Funding for Yale Cancer Answers is
  • 00:02 --> 00:04provided by Smilow Cancer Hospital.
  • 00:06 --> 00:08Welcome to Yale Cancer Answers
  • 00:08 --> 00:10with Doctor Anees Chagpar.
  • 00:10 --> 00:12Yale Cancer Answers features the latest
  • 00:12 --> 00:14information on cancer care by welcoming
  • 00:14 --> 00:17oncologists and specialists who are on the
  • 00:17 --> 00:19forefront of the battle to fight cancer.
  • 00:19 --> 00:21This week, it's a conversation about the
  • 00:21 --> 00:23role of aerobic exercise in relieving
  • 00:23 --> 00:26pain for ovarian cancer survivors with
  • 00:26 --> 00:28Doctor Leah Ferrucci and Anlan Cao.
  • 00:28 --> 00:30Doctor Ferrucci is an assistant professor
  • 00:30 --> 00:32of epidemiology and chronic diseases
  • 00:32 --> 00:34at the Yale School of Public Health,
  • 00:34 --> 00:37where Miss Cao is a graduate student.
  • 00:37 --> 00:39Doctor Chagpar is a professor of surgical
  • 00:39 --> 00:41oncology at the Yale School of Medicine.
  • 00:42 --> 00:44Maybe we can start
  • 00:44 --> 00:45off with each of you telling us
  • 00:45 --> 00:47a little bit more about yourself
  • 00:47 --> 00:48and what it is you do.
  • 00:48 --> 00:50Leah, maybe we'll start with you.
  • 00:50 --> 00:54Sure. So I am a nutritional epidemiologist,
  • 00:54 --> 00:55and I actually trained here at
  • 00:55 --> 00:57the Yale School of Public Health
  • 00:57 --> 00:59for both my masters and my PhD.
  • 00:59 --> 01:01And as part of my PhD,
  • 01:01 --> 01:03I was able to also be a part of research
  • 01:03 --> 01:05at the National Cancer Institute.
  • 01:05 --> 01:07So I had that unique ability to
  • 01:07 --> 01:09work with strong investigators
  • 01:09 --> 01:12here at Yale as well as at the NCI.
  • 01:12 --> 01:14And so my work has really focused
  • 01:14 --> 01:16on thinking about diet as a risk
  • 01:16 --> 01:18factor for cancer incidence,
  • 01:18 --> 01:18risk of cancer.
  • 01:18 --> 01:21And then in the last few years,
  • 01:21 --> 01:23I have taken that to think about diet in
  • 01:23 --> 01:26the context of cancer survivorship and how
  • 01:26 --> 01:29we can think about not only diet itself,
  • 01:29 --> 01:31but also energy balance as well
  • 01:31 --> 01:32as physical activity.
  • 01:32 --> 01:34Another lifestyle factor in the
  • 01:34 --> 01:37context of thinking through how we can
  • 01:37 --> 01:38improve outcomes in cancer survivors,
  • 01:38 --> 01:41whether it be quality of life or
  • 01:41 --> 01:43perhaps even ultimately survival.
  • 01:44 --> 01:46Fantastic, and how
  • 01:46 --> 01:48about you, Anlan?
  • 01:48 --> 01:51I'm a fourth year PhD candidate and I'm also
  • 01:51 --> 01:52Cancer Prevention and Control
  • 01:52 --> 01:54fellow at Yale Cancer Center.
  • 01:54 --> 01:56Professor Ferrucci is
  • 01:56 --> 01:57my mentor and I'm also mentored
  • 01:57 --> 01:59by Professor Melinda Irwin.
  • 01:59 --> 02:00Before coming to Yale,
  • 02:00 --> 02:03I was a preventive medicine major in college,
  • 02:03 --> 02:05and I received my Bachelor
  • 02:05 --> 02:06of Medicine in China.
  • 02:06 --> 02:08My current research centers around
  • 02:08 --> 02:10cancer and nutritional epidemiology,
  • 02:10 --> 02:13with a special focus on lifestyle
  • 02:13 --> 02:15factors and ovarian cancer.
  • 02:15 --> 02:17And I entered this program
  • 02:17 --> 02:19because I just loved epidemiology.
  • 02:19 --> 02:20And I'm not saying this because
  • 02:20 --> 02:22my professor is here and she
  • 02:22 --> 02:23teaches epidemiology.
  • 02:23 --> 02:27But in my first interaction with API,
  • 02:27 --> 02:29the study designs and the
  • 02:29 --> 02:31philosophy behind them amazed me.
  • 02:31 --> 02:32And I was like,
  • 02:32 --> 02:33I definitely want to get
  • 02:33 --> 02:34additional training in this.
  • 02:34 --> 02:37So I entered this program and I
  • 02:37 --> 02:39specifically focus on cancer and
  • 02:39 --> 02:40lifestyle because we've all been
  • 02:40 --> 02:42hearing about the compromised
  • 02:42 --> 02:44quality of life of cancer survivors
  • 02:44 --> 02:45and how researchers and physicians
  • 02:45 --> 02:47should pay more attention to it.
  • 02:47 --> 02:50So I'm paying attention and lifestyle
  • 02:50 --> 02:52factors to me are really powerful
  • 02:52 --> 02:54because they are highly modifiable.
  • 02:54 --> 02:56And if we found that lifestyle
  • 02:56 --> 02:58interventions like what we do here
  • 02:58 --> 03:00can actually improve quality of life,
  • 03:00 --> 03:02prevent recurrence and improve
  • 03:02 --> 03:04survival for cancer survivors,
  • 03:04 --> 03:05then this lifestyle interventions
  • 03:05 --> 03:07could be valuable additions to the
  • 03:08 --> 03:09current standard of oncology care.
  • 03:09 --> 03:11And I think that's where I'm working towards.
  • 03:13 --> 03:15I mean, if we can
  • 03:15 --> 03:17really hone in
  • 03:17 --> 03:18on lifestyle modifications,
  • 03:18 --> 03:22not only might that be a benefit
  • 03:22 --> 03:24to cancer survivors or cancer
  • 03:24 --> 03:26patients or even preventing cancer,
  • 03:26 --> 03:28but could have offshoots of reducing
  • 03:28 --> 03:31heart disease and stroke and all kinds
  • 03:31 --> 03:35of other ailments and it might be a
  • 03:35 --> 03:37really cost effective intervention too.
  • 03:37 --> 03:39So let's dive into your research
  • 03:39 --> 03:41a little bit more.
  • 03:41 --> 03:42Leah, do you want to tell us
  • 03:42 --> 03:43a little bit more about your
  • 03:43 --> 03:45current studies and what
  • 03:45 --> 03:46you're doing and what you're finding?
  • 03:47 --> 03:49Sure. So the most recent study
  • 03:49 --> 03:51that we are working on is
  • 03:53 --> 03:56we are looking at an exercise
  • 03:56 --> 03:58intervention among ovarian cancer survivors
  • 03:58 --> 04:00who had already completed chemotherapy.
  • 04:00 --> 04:03And were sort of described as a little
  • 04:03 --> 04:04bit low in their physical activity.
  • 04:04 --> 04:07So they couldn't have been doing more than
  • 04:07 --> 04:0990 minutes of physical activity a week.
  • 04:09 --> 04:10And what we were trying to look
  • 04:10 --> 04:13at here is if we were able to
  • 04:13 --> 04:14increase their physical activity,
  • 04:14 --> 04:17would we see an impact on a very
  • 04:17 --> 04:19common symptom that's related to
  • 04:19 --> 04:21chemotherapy and this is known as
  • 04:21 --> 04:23chemotherapy induced peripheral
  • 04:23 --> 04:26neuropathy or CIPN. So here again we had
  • 04:26 --> 04:28this exercise intervention in place.
  • 04:28 --> 04:30It was six months long and it
  • 04:30 --> 04:33was home based aerobic exercise.
  • 04:33 --> 04:34We'll probably go into a little bit more,
  • 04:34 --> 04:37but mainly the women in our study were
  • 04:37 --> 04:39able to do this by doing just brisk walking,
  • 04:39 --> 04:41something that is accessible
  • 04:41 --> 04:43to many individuals.
  • 04:43 --> 04:45And so over the intervention time period,
  • 04:45 --> 04:47we had one group receiving this
  • 04:47 --> 04:49exercise program and another group
  • 04:49 --> 04:51receiving just information about
  • 04:51 --> 04:52ovarian cancer survivorship.
  • 04:52 --> 04:54So that comparison group we call
  • 04:54 --> 04:56an attention control group.
  • 04:56 --> 04:58So we're giving them the same contact
  • 04:58 --> 05:00with our research staff and really
  • 05:00 --> 05:02trying to isolate is it the exercise
  • 05:02 --> 05:03or is it the attention that someone
  • 05:03 --> 05:06is giving that might have an impact
  • 05:06 --> 05:07on our outcome.
  • 05:07 --> 05:09It's also important to keep in mind
  • 05:09 --> 05:11for this particular analysis that
  • 05:11 --> 05:13we were looking at what's known as a
  • 05:13 --> 05:15secondary outcome of the original study.
  • 05:15 --> 05:17So this study is known as the walk
  • 05:17 --> 05:19trial and the primary outcome for
  • 05:19 --> 05:22that had actually just been health
  • 05:22 --> 05:24related quality of life overall.
  • 05:24 --> 05:26And we did see benefits for the
  • 05:26 --> 05:28exercise intervention for that primary
  • 05:28 --> 05:30outcome specifically with physical
  • 05:30 --> 05:32related health related quality of life.
  • 05:32 --> 05:35But in this analysis we got to
  • 05:35 --> 05:38relook at our data and see is the
  • 05:38 --> 05:39intervention specifically also impacting
  • 05:39 --> 05:42this key symptom that we know about.
  • 05:42 --> 05:44Our key side effect that we know
  • 05:44 --> 05:45about related to chemotherapy.
  • 05:45 --> 05:48So when we evaluated this,
  • 05:48 --> 05:49this CIPN which was self reported by
  • 05:49 --> 05:52the women in our study before they
  • 05:52 --> 05:53started the exercise intervention
  • 05:53 --> 05:55and then after the six months we
  • 05:55 --> 05:57saw that there was an improvement
  • 05:57 --> 06:00in this self reported chemotherapy
  • 06:00 --> 06:02induced peripheral neuropathy.
  • 06:02 --> 06:04And those who had completed our
  • 06:04 --> 06:06exercise intervention and those who
  • 06:06 --> 06:08had been in the attention control group
  • 06:08 --> 06:10actually saw a slight worsening of
  • 06:10 --> 06:11their symptoms as they were reporting
  • 06:11 --> 06:13it to us at the end of the study.
  • 06:13 --> 06:16So this was really indicating to us
  • 06:16 --> 06:19that among those who have completed
  • 06:19 --> 06:21chemotherapy and potentially have
  • 06:21 --> 06:23these symptoms at the start of an
  • 06:23 --> 06:24exercise intervention that the exercise
  • 06:24 --> 06:27intervention can be helpful in reducing
  • 06:27 --> 06:28the symptoms that they are having.
  • 06:31 --> 06:33You know that's really interesting
  • 06:33 --> 06:35because we can imagine
  • 06:35 --> 06:38that exercise does a lot in terms
  • 06:38 --> 06:40of improving quality of life, right.
  • 06:40 --> 06:42It releases endorphins,
  • 06:42 --> 06:44it makes you feel better.
  • 06:44 --> 06:49But this idea of the fact that
  • 06:49 --> 06:51walking,simple walking, could
  • 06:51 --> 06:53actually improve peripheral
  • 06:53 --> 06:56neuropathy might not be as intuitive.
  • 06:56 --> 06:58So Anlan, can you talk a little bit
  • 06:58 --> 07:01more about why it was that at the
  • 07:01 --> 07:03beginning of this whole study you
  • 07:03 --> 07:05hypothesized that there might have been
  • 07:05 --> 07:08a link and and maybe talk a little
  • 07:08 --> 07:11bit more about the intervention itself
  • 07:11 --> 07:14and how you measured peripheral neuropathy.
  • 07:14 --> 07:17It sounds like it was self reported,
  • 07:17 --> 07:18but can you talk about why,
  • 07:18 --> 07:20you would think at the outset
  • 07:20 --> 07:22that these two would be linked?
  • 07:22 --> 07:23That's just not intuitive.
  • 07:24 --> 07:24Yeah, sure.
  • 07:25 --> 07:28So actually we hypothesize not specifically
  • 07:28 --> 07:31walk but aerobic exercise overall.
  • 07:31 --> 07:34And there were some potential mechanisms
  • 07:34 --> 07:36that we hypothesize like exercise overall
  • 07:36 --> 07:39can just make the patients feel better,
  • 07:39 --> 07:43so subjectively if they are feeling more fit,
  • 07:43 --> 07:45in that case, they probably will perceive
  • 07:45 --> 07:48less pain or better quality of life.
  • 07:48 --> 07:51And because as Professor Ferrucci mentioned,
  • 07:51 --> 07:52the primary outcome of this
  • 07:52 --> 07:54study was quality of life.
  • 07:54 --> 07:57So we hypothesize neuropathy as one of the
  • 07:57 --> 08:00mediators on this pathway of how aerobic
  • 08:00 --> 08:03exercise can improve quality of life.
  • 08:03 --> 08:04And biologically speaking,
  • 08:04 --> 08:07there are some molecules and some biomarkers
  • 08:07 --> 08:10that can be increased by exercise and
  • 08:10 --> 08:14that may have an effect on neuropathy.
  • 08:14 --> 08:17But I think currently there is no
  • 08:17 --> 08:19solid biological evidence suggesting
  • 08:19 --> 08:21any clear pathway this way.
  • 08:21 --> 08:24So I guess our study also calls for
  • 08:24 --> 08:26more studies like basic science
  • 08:26 --> 08:29studies to help review the mechanism
  • 08:29 --> 08:31of how exercise actually improved
  • 08:31 --> 08:32peripheral neuropathy.
  • 08:32 --> 08:35And the other way that we can develop
  • 08:35 --> 08:37other drugs or others forms of exercise
  • 08:37 --> 08:40that can achieve the same or even
  • 08:40 --> 08:43better effect of improving neuropathy.
  • 08:43 --> 08:45And about the specific exercise
  • 08:45 --> 08:47form that we were looking at,
  • 08:47 --> 08:48as we mentioned,
  • 08:48 --> 08:50we focus on home based moderate and
  • 08:50 --> 08:53moderate intensity aerobic exercise,
  • 08:53 --> 08:56but most of the women chose to do
  • 08:56 --> 08:58brisk walking and that's actually
  • 08:58 --> 08:59more than 95% of women.
  • 08:59 --> 09:01And it maybe makes sense because
  • 09:01 --> 09:03we call ourselves the walk study.
  • 09:03 --> 09:05So it may sort of leave some
  • 09:05 --> 09:06impression on them,
  • 09:06 --> 09:09but some women also chose to do hiking,
  • 09:09 --> 09:11biking, swimming or yoga.
  • 09:11 --> 09:14And as professor Ferrucci mentioned,
  • 09:14 --> 09:16we have an American College of
  • 09:16 --> 09:18Sports Medicine certified Cancer
  • 09:18 --> 09:20Access Trainer that guides them
  • 09:20 --> 09:22through weekly phone calls to how
  • 09:22 --> 09:24to improve their physical activity.
  • 09:24 --> 09:27And we also have this 26 chapter
  • 09:27 --> 09:28book on exercise and ovarian
  • 09:28 --> 09:30cancer survivorship that can serve
  • 09:30 --> 09:32as an additional resource.
  • 09:32 --> 09:36Leah, I mean, was there a
  • 09:36 --> 09:39particular dose that was significant?
  • 09:39 --> 09:43So you mentioned that these were women who
  • 09:43 --> 09:46in general had what you call low rates of
  • 09:46 --> 09:49of activity 90 minutes a week or less.
  • 09:49 --> 09:51Some might think that 90
  • 09:51 --> 09:52minutes is actually quite a bit,
  • 09:52 --> 09:55but we'll leave that aside.
  • 09:55 --> 09:57Was there a certain dose,
  • 09:57 --> 09:59like for example, if you did 91 minutes,
  • 09:59 --> 10:01it wasn't as effective,
  • 10:01 --> 10:04but if you did 150 minutes,
  • 10:04 --> 10:05it really was.
  • 10:05 --> 10:06Did you look at that and
  • 10:06 --> 10:09did you find that that was impactful?
  • 10:09 --> 10:11So we didn't look specifically at dose,
  • 10:11 --> 10:13but I will say what our goal for women to
  • 10:13 --> 10:16achieve was that 150 minutes per week,
  • 10:16 --> 10:18which is the general recommendation
  • 10:18 --> 10:20out there for all individuals in
  • 10:20 --> 10:23the population and also has been
  • 10:23 --> 10:24translated specifically to cancer
  • 10:24 --> 10:27survivors as being an important
  • 10:27 --> 10:28kind of threshold to be thinking
  • 10:28 --> 10:30about for physical activity levels.
  • 10:30 --> 10:32And these women were actually very,
  • 10:32 --> 10:34very successful in increasing
  • 10:34 --> 10:35their aerobic activities.
  • 10:35 --> 10:37So I believe it's on average they
  • 10:37 --> 10:40had about 160 minutes per week of
  • 10:40 --> 10:42this moderate to vigorous activity
  • 10:42 --> 10:44by the end of our intervention.
  • 10:44 --> 10:45So this was actually very,
  • 10:45 --> 10:47very exciting to see, right.
  • 10:47 --> 10:50This is a group that potentially was
  • 10:50 --> 10:52not doing activity as you had mentioned
  • 10:52 --> 10:54at the start and yet we're able to
  • 10:54 --> 10:56attain that goal quite early on.
  • 10:56 --> 10:58And actually we had very little variation.
  • 10:58 --> 11:00So most women got up to that high level.
  • 11:00 --> 11:02So looking at the dose response was
  • 11:02 --> 11:04actually not even really that possible
  • 11:04 --> 11:06because everyone was just so successful
  • 11:06 --> 11:09in attaining that goal in this study.
  • 11:09 --> 11:09So unfortunately,
  • 11:09 --> 11:11I can't say if just a small increase
  • 11:11 --> 11:13would have also seen the same effect
  • 11:13 --> 11:14because we were seeing such strong
  • 11:14 --> 11:16increases overall in the women.
  • 11:16 --> 11:18How exactly did women do that?
  • 11:18 --> 11:20I mean there might be
  • 11:20 --> 11:22a lot of people who are sitting
  • 11:22 --> 11:24listening to the show and saying
  • 11:24 --> 11:26to themselves, that's fabulous.
  • 11:26 --> 11:29I mean these cancer survivors
  • 11:29 --> 11:31magically got themselves up
  • 11:31 --> 11:34to over 160 minutes a week.
  • 11:34 --> 11:37Now was that due to this
  • 11:37 --> 11:39trainer that you had?
  • 11:39 --> 11:41I mean is that the advice that you
  • 11:41 --> 11:44would have for people is to get a
  • 11:44 --> 11:47trainer or what were some of
  • 11:47 --> 11:49the perhaps techniques or skills
  • 11:49 --> 11:51or bits of knowledge that really
  • 11:51 --> 11:54helped these women to achieve
  • 11:54 --> 11:56that outcome that perhaps the rest
  • 11:56 --> 11:58of our listeners in our audience
  • 11:58 --> 12:01might be able to behoove themselves of.
  • 12:01 --> 12:03Well, I'm not an interventionist,
  • 12:03 --> 12:05so I cannot say much about this.
  • 12:05 --> 12:07But what I can say is that brisk
  • 12:07 --> 12:10walking is likely accessible to the
  • 12:10 --> 12:12vast majority of patients diagnosed
  • 12:12 --> 12:14with ovarian cancer because it
  • 12:14 --> 12:16does not require any equipment.
  • 12:16 --> 12:19And if the patients wanted to do this,
  • 12:19 --> 12:20they could initiate this form
  • 12:20 --> 12:22of exercise on their own,
  • 12:22 --> 12:24well after obtaining a clearance
  • 12:24 --> 12:25from their doctors too.
  • 12:25 --> 12:28But if they need additional resources to
  • 12:28 --> 12:30help them to motivate them of actually
  • 12:30 --> 12:32initiating this form of exercise,
  • 12:32 --> 12:35then many cancer centers have physical
  • 12:35 --> 12:37therapists that could be a resource for them.
  • 12:38 --> 12:41And some also have the certified
  • 12:41 --> 12:43cancer exercise trainers like the
  • 12:43 --> 12:46interventionists in our study could also
  • 12:46 --> 12:48help them to start aerobic exercise.
  • 12:48 --> 12:50And for some women if they prefer
  • 12:50 --> 12:53to go to the facility instead of
  • 12:53 --> 12:55doing some home based exercise,
  • 12:55 --> 12:59theres the LIVESTRONG program at YMCA,
  • 12:59 --> 13:01which is a program specific to cancer
  • 13:01 --> 13:02survivors that incorporate both
  • 13:02 --> 13:04aerobic and resistance training.
  • 13:04 --> 13:06So those are all the resources that
  • 13:06 --> 13:08could be useful to the cancer survivors.
  • 13:08 --> 13:10We're going to take
  • 13:10 --> 13:12a short break for a medical minute,
  • 13:12 --> 13:13but when we come back,
  • 13:13 --> 13:15we'll learn more about the role of
  • 13:15 --> 13:18aerobic exercise in relieving pain for
  • 13:18 --> 13:20ovarian cancer survivors with my guests,
  • 13:20 --> 13:24Leah Ferrucci and Anlan Cao.
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  • 13:30 --> 13:31provides coordinated state-of-the-art
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  • 13:35 --> 13:38Learn more at smilowcancerhospital.org.
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  • 13:42 --> 13:44estimates that more than 65,000
  • 13:44 --> 13:46Americans will be diagnosed with
  • 13:46 --> 13:48head and neck cancer this year,
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  • 14:08 --> 14:11treatments for head and neck cancers.
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  • 14:30 --> 14:32DNA damaging and targeted therapy.
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  • 14:36 --> 14:39You're listening to Connecticut Public Radio.
  • 14:39 --> 14:40Welcome
  • 14:40 --> 14:41back to Yale Cancer Answers.
  • 14:41 --> 14:43This is Doctor Anees Chagpar,
  • 14:43 --> 14:45and I'm joined tonight by my guests,
  • 14:45 --> 14:48Doctor Leah Ferrucci and Anlan Cao.
  • 14:48 --> 14:50We're talking about the role of
  • 14:50 --> 14:52aerobic exercise in relieving pain
  • 14:52 --> 14:54for ovarian cancer survivors.
  • 14:54 --> 14:57And right before the break we were
  • 14:57 --> 14:59talking about a recent study that
  • 14:59 --> 15:02they've done looking at a walking
  • 15:02 --> 15:04intervention basically home based
  • 15:04 --> 15:06exercise primarily walking that
  • 15:06 --> 15:09actually reduced cancer induced
  • 15:09 --> 15:12peripheral neuropathy and Anlan,
  • 15:12 --> 15:14maybe you can tell us a little bit
  • 15:14 --> 15:17more about what exactly is this
  • 15:17 --> 15:19neuropathy that cancer survivors get.
  • 15:19 --> 15:20Yeah, sure.
  • 15:20 --> 15:22So chemotherapy induced peripheral
  • 15:22 --> 15:25neuropathy or CIPN biologically speaking
  • 15:25 --> 15:28is the damage to neurons that leads
  • 15:28 --> 15:30to alter perception of touch, pain,
  • 15:30 --> 15:34sense of position and vibration or damage
  • 15:34 --> 15:37voluntary movement and coordination.
  • 15:37 --> 15:38So that being said,
  • 15:38 --> 15:41some typical symptoms of CIPN include
  • 15:41 --> 15:43like a tingling sensation in hands
  • 15:43 --> 15:46and feet or some patients may describe
  • 15:46 --> 15:49that as pins and needles feeling.
  • 15:49 --> 15:51Some patients may also experience
  • 15:51 --> 15:53burning or warm feeling, numbness,
  • 15:53 --> 15:57weakness or discomfort or pain.
  • 15:57 --> 16:01And some may also have less ability to
  • 16:01 --> 16:04feel hot and cold and cramps in feet.
  • 16:04 --> 16:05And it's actually highly prevalent
  • 16:05 --> 16:08for cancer patients who receive
  • 16:08 --> 16:10chemotherapy to experience neuropathy.
  • 16:10 --> 16:13And it's actually dependent on the chemotherapy
  • 16:13 --> 16:16regimen because some drugs are more
  • 16:16 --> 16:18likely to cause CIP and than others.
  • 16:18 --> 16:22And so what we are testing is exercise
  • 16:22 --> 16:25and how exercise can improve CIPN and
  • 16:25 --> 16:27that's because so far we only have
  • 16:27 --> 16:30limited options for how to manage CIPN.
  • 16:30 --> 16:32We do have one drug,
  • 16:32 --> 16:33Duluxetine,
  • 16:33 --> 16:35that is the only drug that had
  • 16:35 --> 16:37enough supportive evidence to be
  • 16:37 --> 16:39a part of the current guidelines
  • 16:39 --> 16:41for CIPN management from ASCO,
  • 16:41 --> 16:44which is a large clinical oncology organization.
  • 16:44 --> 16:46But it's developed specifically for
  • 16:46 --> 16:48CIPN and the evidence
  • 16:48 --> 16:50indicates it only has limited benefits.
  • 16:50 --> 16:53So it's not a solution to all and
  • 16:53 --> 16:56some patients may also use patches,
  • 16:56 --> 16:59creams, or cooling gloves to help with
  • 16:59 --> 17:02numbness and tingling in hands and in feet,
  • 17:02 --> 17:04but there's not enough evidence so far
  • 17:04 --> 17:06to support a recommendation on those.
  • 17:06 --> 17:07And clinically,
  • 17:07 --> 17:09there is a pretty common approach
  • 17:09 --> 17:10to reduce CIPN,
  • 17:10 --> 17:13which is to reduce or delay the
  • 17:13 --> 17:14chemotherapy that causes CIPN,
  • 17:14 --> 17:17like paclitaxel in ovarian cancer.
  • 17:17 --> 17:19So this is pretty effective because you
  • 17:19 --> 17:22are targeting directly to the cause of CIPN,
  • 17:22 --> 17:24but this will lead to the patients
  • 17:24 --> 17:26receiving less than the original
  • 17:26 --> 17:29chemo prescription or
  • 17:29 --> 17:31delayed original prescription which
  • 17:31 --> 17:33may negatively impact survival.
  • 17:33 --> 17:35So this is like the last resort
  • 17:35 --> 17:37that we don't want to go into if
  • 17:37 --> 17:38we have other options.
  • 17:38 --> 17:41And exercise was proven to be
  • 17:41 --> 17:43effective in improving quality of
  • 17:43 --> 17:46life in our study and also in other
  • 17:46 --> 17:48aspects of cancer survivorship.
  • 17:48 --> 17:51So we were hoping that maybe exercise
  • 17:51 --> 17:53could also help us to manage CIP.
  • 17:53 --> 17:56And as Professor Ferrucci mentioned,
  • 17:56 --> 18:00we used a self report questionnaire
  • 18:00 --> 18:03to measure CIPN that is called the
  • 18:03 --> 18:05FACT GOG Neurotoxicity Questionnaire
  • 18:05 --> 18:09and it has 11 questions basically
  • 18:09 --> 18:11asking about the symptoms of CIPN
  • 18:11 --> 18:14and how the patients feel about
  • 18:14 --> 18:16pain or overall weakness.
  • 18:16 --> 18:19And the overall range of this
  • 18:19 --> 18:21questionnaire is from zero to 44.
  • 18:21 --> 18:25And what we found was that exercise
  • 18:25 --> 18:29significantly improved the score by 1.6 point,
  • 18:29 --> 18:301.6 points,
  • 18:30 --> 18:31yes.
  • 18:31 --> 18:34And that could translate to a moderate
  • 18:34 --> 18:37improvement in one symptom or just
  • 18:37 --> 18:40slightly improvement in a couple of symptoms.
  • 18:40 --> 18:42So what we think about that outcome is
  • 18:42 --> 18:44that it's pretty clinically effective
  • 18:44 --> 18:47and it's also statistically effective.
  • 18:47 --> 18:49So that's why we concluded that
  • 18:49 --> 18:51aerobic exercise actually can
  • 18:51 --> 18:53help improve CIP and symptoms.
  • 18:54 --> 18:55And so, Leah, you know,
  • 18:55 --> 18:57kind of expanding on that, right.
  • 18:57 --> 19:01So if we think that exercise could you
  • 19:01 --> 19:04know reduce peripheral neuropathy,
  • 19:04 --> 19:07potentially allow patients to continue
  • 19:07 --> 19:11on a chemotherapy regimen that they
  • 19:11 --> 19:14may have been intolerant to before.
  • 19:14 --> 19:17And I know that this was this
  • 19:17 --> 19:20study was done in people who had
  • 19:20 --> 19:22completed chemotherapy who may
  • 19:22 --> 19:24have had residual neuropathy.
  • 19:24 --> 19:27But can you talk a little bit about
  • 19:27 --> 19:29other studies that you might have
  • 19:29 --> 19:32done that have looked at you know
  • 19:32 --> 19:33whether exercise really allows
  • 19:33 --> 19:36patients to be more adherent to
  • 19:36 --> 19:39their their chemotherapeutic regimen,
  • 19:39 --> 19:42whether in fact we do have any
  • 19:42 --> 19:44data suggesting that there is an
  • 19:44 --> 19:47improvement in survival or recurrence
  • 19:47 --> 19:50free survival with exercise.
  • 19:50 --> 19:52So I think this is sort of
  • 19:52 --> 19:53a story of more to come.
  • 19:53 --> 19:56I would say we have recently along
  • 19:56 --> 19:58with Doctor Melinda Irwin who had
  • 19:58 --> 20:00led the walk study originally and has
  • 20:00 --> 20:03recently completed a study in breast
  • 20:03 --> 20:05cancer patients during chemotherapy
  • 20:05 --> 20:07along with doctor Tara Sant here
  • 20:07 --> 20:10at Yale where they were looking at
  • 20:10 --> 20:12exercise and diet intervention in
  • 20:12 --> 20:14breast cancer survivors at the time
  • 20:14 --> 20:16that they were receiving chemotherapy.
  • 20:16 --> 20:17Unfortunately,
  • 20:17 --> 20:19they did not see that it looked
  • 20:19 --> 20:22like the exercise component or the
  • 20:22 --> 20:24diet component of the intervention
  • 20:24 --> 20:26positively impacted the amount
  • 20:26 --> 20:27of chemotherapy that individuals
  • 20:27 --> 20:29were able to receive.
  • 20:29 --> 20:30So that was a question that
  • 20:30 --> 20:31we were trying to think about.
  • 20:31 --> 20:33But surprisingly, in that study,
  • 20:33 --> 20:35we actually had very,
  • 20:35 --> 20:38very high adherence to chemotherapy overall,
  • 20:38 --> 20:40which is not what we would have expected
  • 20:40 --> 20:42kind of looking at historical data.
  • 20:42 --> 20:44So that's a little bit up in the air
  • 20:44 --> 20:45if perhaps we ended up enrolling
  • 20:45 --> 20:47this really adherent group.
  • 20:47 --> 20:49They were all motivated to kind of
  • 20:49 --> 20:51be involved in a research study
  • 20:51 --> 20:53and perhaps had higher chemotherapy
  • 20:53 --> 20:55adherence than what we would have
  • 20:55 --> 20:57expected in a wider population.
  • 20:57 --> 20:59So that was for breast.
  • 20:59 --> 21:01But in tandem with that work,
  • 21:01 --> 21:03Doctor Irwin has recently begun to
  • 21:03 --> 21:05study in ovarian cancer survivors,
  • 21:05 --> 21:06where again,
  • 21:06 --> 21:08she's testing a lifestyle intervention
  • 21:08 --> 21:11that combines both diet and exercise
  • 21:11 --> 21:13during chemotherapy to see if we can
  • 21:13 --> 21:15impact that chemotherapy adherence
  • 21:15 --> 21:18or how well women are able to
  • 21:18 --> 21:20adhere to their prescription.
  • 21:20 --> 21:22So that one has just actually started
  • 21:22 --> 21:24enrollment and this is actually
  • 21:24 --> 21:26an exciting one as well to think
  • 21:26 --> 21:28about CIPN because this will be
  • 21:28 --> 21:31a group in which we can see is
  • 21:31 --> 21:33exercise potentially also able to
  • 21:33 --> 21:36prevent that symptom from beginning.
  • 21:36 --> 21:37So in our current trial,
  • 21:37 --> 21:40we had women who had already completed
  • 21:40 --> 21:42chemotherapy, already had CIPN at baseline,
  • 21:42 --> 21:45they were reporting these symptoms to us.
  • 21:45 --> 21:46But in this new study,
  • 21:46 --> 21:47we're hoping that we can take a
  • 21:47 --> 21:50look and see again as a secondary outcome,
  • 21:50 --> 21:52but an important one to think through
  • 21:52 --> 21:52for hypothesis,
  • 21:52 --> 21:54can we actually prevent CIPN
  • 21:54 --> 21:56if they are having exercise
  • 21:56 --> 21:59during their active treatment phase?
  • 22:00 --> 22:02I mean, so important
  • 22:02 --> 22:04when we think about
  • 22:04 --> 22:06the massive amount of money
  • 22:06 --> 22:08that we spend on these drugs,
  • 22:08 --> 22:11the toxicity of the drugs,
  • 22:11 --> 22:15to think that something like exercise or
  • 22:15 --> 22:19diet might actually be able to improve
  • 22:19 --> 22:22outcomes independently is just so enticing.
  • 22:22 --> 22:25But it is difficult I
  • 22:25 --> 22:29think for people to embrace lifestyle
  • 22:29 --> 22:32interventions, nonetheless,
  • 22:32 --> 22:34I think these studies are really laudable.
  • 22:34 --> 22:37So, Anlan, maybe you can talk
  • 22:37 --> 22:39a little bit about,
  • 22:39 --> 22:41what does it take to do studies like this?
  • 22:41 --> 22:44I mean, it sounds like this
  • 22:44 --> 22:46is quite the endeavor.
  • 22:46 --> 22:48Can you talk a little bit more about
  • 22:48 --> 22:50kind of how you set up a study like this,
  • 22:50 --> 22:52the team that's involved,
  • 22:52 --> 22:54the patients that are involved and
  • 22:54 --> 22:57for patients who are coming down the Pike
  • 22:57 --> 23:00who might be listening to this show,
  • 23:00 --> 23:01who might think, jeez,
  • 23:02 --> 23:05I really wish there was a study
  • 23:05 --> 23:07like that near me.
  • 23:07 --> 23:09Can you talk a little bit about
  • 23:09 --> 23:11how patients get involved
  • 23:11 --> 23:12in clinical trials in general?
  • 23:13 --> 23:15Yeah, that is definitely
  • 23:15 --> 23:17a very important question,
  • 23:17 --> 23:18but I'm only a PhD
  • 23:18 --> 23:21student and I'm more of a research
  • 23:21 --> 23:23assistant in this sort of study.
  • 23:23 --> 23:24So I think maybe Professor
  • 23:24 --> 23:25Ferrucci might be the better
  • 23:25 --> 23:27person to answer this question.
  • 23:27 --> 23:29Sure, I can take that on.
  • 23:29 --> 23:31So these are known as our
  • 23:31 --> 23:32randomized controlled trials,
  • 23:32 --> 23:33which many people are familiar with
  • 23:33 --> 23:35more in the context of testing
  • 23:35 --> 23:37a new treatment or new drug.
  • 23:37 --> 23:39But we use this same design for
  • 23:39 --> 23:40testing these lifestyle interventions
  • 23:40 --> 23:43where we're trying to enroll a group
  • 23:43 --> 23:45of individuals who are willing to
  • 23:45 --> 23:46essentially randomly be assigned
  • 23:46 --> 23:48to either the intervention or
  • 23:48 --> 23:50educational program that we are
  • 23:50 --> 23:52testing and then our comparison group.
  • 23:52 --> 23:53So in the walk study,
  • 23:53 --> 23:55it had been the exercise was the
  • 23:55 --> 23:57education and the sort of lifestyle
  • 23:57 --> 23:59component that we wanted to
  • 23:59 --> 24:01evaluate and then we had that in
  • 24:01 --> 24:03comparison to the attention control.
  • 24:03 --> 24:05So this is an important thing that
  • 24:05 --> 24:07we have to describe to potential
  • 24:07 --> 24:09participants is that they might
  • 24:09 --> 24:11get that control condition.
  • 24:11 --> 24:12But this is a really important
  • 24:12 --> 24:14piece to understand, right?
  • 24:14 --> 24:16Is exercise going to improve the outcomes
  • 24:16 --> 24:18that we're hoping that they improve.
  • 24:18 --> 24:20So our staff get really well
  • 24:20 --> 24:22trained in trying to convey the
  • 24:22 --> 24:24importance of the research,
  • 24:24 --> 24:25the importance that individuals
  • 24:25 --> 24:27understand that random chance
  • 24:27 --> 24:28of being in either group.
  • 24:28 --> 24:31And then particularly with the walk study,
  • 24:31 --> 24:33they also had this benefit even in
  • 24:33 --> 24:35the control condition of having
  • 24:35 --> 24:37contact with our study staff
  • 24:37 --> 24:38through weekly telephone calls.
  • 24:38 --> 24:40So they were getting this extra
  • 24:40 --> 24:43layer of support in a way not tied
  • 24:43 --> 24:45specifically to exercise content.
  • 24:45 --> 24:47So that also might have been helpful
  • 24:47 --> 24:49for this particular study and bringing
  • 24:49 --> 24:51people into the research component.
  • 24:51 --> 24:52But as Anlan said,
  • 24:52 --> 24:54this is a very complicated thing
  • 24:54 --> 24:55to sort of get off the ground.
  • 24:55 --> 24:57We have a large research staff
  • 24:57 --> 24:59for this particular study.
  • 24:59 --> 25:01We had about 144 women who
  • 25:01 --> 25:03enrolled in the study itself,
  • 25:03 --> 25:05but we had actually screened over 700
  • 25:05 --> 25:07individuals to find those people who
  • 25:07 --> 25:09were not only willing to participate,
  • 25:09 --> 25:12but also eligible based on some of those
  • 25:12 --> 25:14criteria we had had mentioned before,
  • 25:14 --> 25:16like having completed their chemotherapy,
  • 25:16 --> 25:18having that lower level of
  • 25:18 --> 25:20physical activity at the start.
  • 25:20 --> 25:21So to just enroll for this one study,
  • 25:21 --> 25:24it actually took over four years.
  • 25:24 --> 25:26So I would say you know to keep in mind
  • 25:26 --> 25:28that this work while you can generate
  • 25:28 --> 25:30a paper what seems like fairly quickly,
  • 25:30 --> 25:32the actual background work that goes into it,
  • 25:32 --> 25:34that in the field piece
  • 25:34 --> 25:36can take quite a while.
  • 25:36 --> 25:37And as you can imagine,
  • 25:37 --> 25:38as we're enrolling participants,
  • 25:38 --> 25:40we have to have our interventionist
  • 25:40 --> 25:42ready to be counseling them.
  • 25:42 --> 25:44So this is not a process where we
  • 25:44 --> 25:47can enroll all 144 women at one time.
  • 25:47 --> 25:48So in part,
  • 25:48 --> 25:49you have that pool of people
  • 25:49 --> 25:51coming in and sort of a trickle
  • 25:51 --> 25:52or a rolling process so that you
  • 25:52 --> 25:54can provide the actual content to
  • 25:54 --> 25:56them that you're trying to convey,
  • 25:56 --> 25:57in this case,
  • 25:57 --> 25:59the exercise counseling and these
  • 25:59 --> 26:01weekly telephone calls that they received.
  • 26:01 --> 26:03So I hope that answers a little
  • 26:03 --> 26:04bit about the design.
  • 26:04 --> 26:07Yeah, for sure. I mean and Anlan did you
  • 26:07 --> 26:10find that you know if you tell patients
  • 26:10 --> 26:13that we're looking at exercise
  • 26:13 --> 26:16and its potential impact on improving
  • 26:16 --> 26:18quality of life in in cancer survivors,
  • 26:18 --> 26:22would that in and of itself
  • 26:22 --> 26:26even if you were randomized to the non
  • 26:26 --> 26:29intervention arm the attention control,
  • 26:29 --> 26:31where might those women be more
  • 26:31 --> 26:33likely to just try a little bit of
  • 26:33 --> 26:35exercise on their own and how
  • 26:35 --> 26:37would that dilute the results and
  • 26:37 --> 26:39how would you mitigate against that?
  • 26:40 --> 26:44Yeah, definitely. I mean,
  • 26:44 --> 26:46doing randomized controlled trials,
  • 26:46 --> 26:48usually the best way to do this is
  • 26:48 --> 26:50to blind the patients of what kind
  • 26:50 --> 26:52of intervention that they received.
  • 26:52 --> 26:54Like if it's a drug trial,
  • 26:55 --> 26:56methodologically speaking,
  • 26:56 --> 26:59we probably will provide women
  • 26:59 --> 27:01who were randomized to the
  • 27:01 --> 27:02control group with a placebo.
  • 27:02 --> 27:05So in that way they wouldn't know
  • 27:05 --> 27:07which kind of intervention that
  • 27:07 --> 27:09they're getting and that way we can
  • 27:09 --> 27:11help to get a more valid result.
  • 27:11 --> 27:13But this is a lifestyle intervention
  • 27:13 --> 27:15and like you mentioned,
  • 27:15 --> 27:18there's no way that we can stop the
  • 27:18 --> 27:20women from exercising themselves.
  • 27:20 --> 27:22And actually that's what we've seen
  • 27:22 --> 27:25our study that women in the control
  • 27:25 --> 27:28group actually started to elevate their
  • 27:28 --> 27:30exercise level a little bit as well.
  • 27:30 --> 27:34But how we deal with it
  • 27:34 --> 27:36statistically in our analysis is
  • 27:36 --> 27:38that we will consider that this
  • 27:38 --> 27:41sort of crossover as what we call
  • 27:41 --> 27:43in randomized control trial will
  • 27:43 --> 27:45bias our results toward and
  • 27:45 --> 27:49so because control women started
  • 27:49 --> 27:51to exercise that sort of made
  • 27:51 --> 27:52them more similar to women who
  • 27:52 --> 27:54were in the exercise arm.
  • 27:54 --> 27:58So that would make us
  • 27:58 --> 28:00observe generally
  • 28:01 --> 28:03reduced effect size compared
  • 28:03 --> 28:06to what we would actually have if
  • 28:06 --> 28:09they did not start exercising at all.
  • 28:09 --> 28:11So in that case,
  • 28:11 --> 28:13if we observe a fact,
  • 28:13 --> 28:16a very effective result in the end,
  • 28:16 --> 28:19then that would mean if everybody
  • 28:19 --> 28:21adheres to their randomized group,
  • 28:21 --> 28:23we will actually have a even larger
  • 28:23 --> 28:25effect size than what we observed.
  • 28:25 --> 28:27So that's usually how we deal
  • 28:27 --> 28:29with this sort of crossover in
  • 28:29 --> 28:30randomized controlled trials.
  • 28:31 --> 28:33Anlan Cao is a graduate student
  • 28:33 --> 28:35and doctor Leah Ferrucci is an
  • 28:35 --> 28:36assistant professor of epidemiology
  • 28:36 --> 28:39at the Yale School of Public Health.
  • 28:39 --> 28:41If you have questions,
  • 28:41 --> 28:42the address is canceranswers@yale.edu
  • 28:42 --> 28:45and past editions of the program
  • 28:45 --> 28:47are available in audio and written
  • 28:47 --> 28:48form at yalecancercenter.org.
  • 28:48 --> 28:51We hope you'll join us next week to
  • 28:51 --> 28:53learn more about the fight against
  • 28:53 --> 28:55cancer here on Connecticut Public Radio.
  • 28:55 --> 28:57Funding for Yale Cancer Answers is
  • 28:57 --> 29:00provided by Smilow Cancer Hospital.