The Healthcare Triage podcast is sponsored by Indiana University School of Medicine whose mission is to advance health in the state of Indiana and beyond by promoting innovation and excellence in education, research and patient care.
IU School of Medicine is leading Indiana University's first grand challenge, the Precision Health Initiative, with bold goals to cure multiple myeloma, triple negative breast cancer and childhood sarcoma and prevent type 2 diabetes and Alzheimer's disease.
Dr. Aaron Carroll: Welcome back to the Healthcare Triage Podcast. We are continuing this year to focus on clinical issues and talk about how they might impact you, and doing that with our clinical partner in this, Indiana University School of Medicine. And this and future Healthcare Triage Podcasts are sponsored in part by Indiana University School of Medicine, whose mission is to advance health in Indiana and beyond by promoting innovation and excellence in education, research and patient care.
Today we're going to focus on childhood sarcoma, which is actually one of the foci of Indiana University's Precision Health Initiative, which is aiming to cure a number of issues like multiple myeloma, triple-negative breast cancer and childhood sarcoma, and to prevent other diseases like type 2 diabetes and Alzheimer's disease. Today's guest is going to be Dr. Jamie Renbarger, who is a pediatric hematologist/oncologist, who also focuses with her research on childhood sarcoma. So our guest today, again, is Dr. Jamie Renbarger, who is a pediatric hematologist/oncologist. And just like last time, I'm going to let her introduce herself because I can never remember everyone's title. So please tell us a little about yourself.
Dr. Jamie Renbarger: Sure. So I am a pediatric oncologist at Indiana University. I'm the division chief for the group, which means basically that I lead our academic operations, and then also leading a precision health focused sarcoma research program.
Dr. Aaron Carroll: All right. So what is sarcoma?
Dr. Jamie Renbarger: So sarcoma is a kind of pediatric cancer. It's a solid tumor that can originate either in bones or in soft tissues.
Dr. Aaron Carroll: So I want to back up way far, because as I asked that question, I realized we probably need to start way back at the beginning. So we hear the word cancer all the time, but it feels I think, to most people like this huge black box that it's obviously terrible, but nobody ... I think a lot of people just don't even know exactly where it is. So what is cancer?
Dr. Jamie Renbarger: So cancer is really a growth of a population of bad cells, abnormal cells. And as you alluded to, there are a lot of different kinds of cancer, it's sort of this catch all term for a whole bunch of different diseases.
Dr. Aaron Carroll: I mean, even that definition, where it's a collection of bad cells instinctively like, well, just get them out. So why is it so bad?
Dr. Jamie Renbarger: The problem with this group of bad cells is that they grow out of control. So frankly, your body is producing abnormal cells all the time. And your immune system is really trained to get rid of those. And for some reason, in some people, this bad population of cells is not picked up by the immune system. And so then is allowed to grow unchecked.
Dr. Aaron Carroll: So is it something that's happening all the time and the body is always getting rid of the bad stuff? And so therefore, it's a failure of the body's ability to get rid of the bad stuff that is failing? Or is it that this is something that is growing that shouldn't be there? I'm coming in from two angles. One could be that there's too much growth when there shouldn't be, the other is that there's a failure of sort of the policing system? Is it both? Is it one? Is it the other?
Dr. Jamie Renbarger: Yeah, it's both. So we know that the building blocks of cells, DNA which provides the message that tells ourselves sort of what to do is damaged by all kinds of things, exposures in the environment, the sun, and a variety of other things all the time. And our bodies do a really great job of either fixing that DNA damage, the damage to that cellular machinery, or getting rid of those cells, killing the bad cells that pop up. In the case of cancer, essentially what's happening is, one, that damage which we know happens all the time occurs, and for whatever reason, the body doesn't recognize it, or doesn't single that group of cells out as bad as foreign, and so they are allowed to begin to grow unchecked.
Dr. Aaron Carroll: Why is it so problematic? Why is it so life-threatening so often?
Dr. Jamie Renbarger: I would step back a little bit from that and think about cancers in kids versus cancers in adults.
Dr. Aaron Carroll: Okay.
Dr. Jamie Renbarger: So, cancers in kids are quite different from many of the cancers that we commonly see in adults, particularly the cancers we see in older adults. And probably a big part of that difference is that cancers and children grow really quickly, whereas in adults, those cancers are often the result of a lifetime of exposures that sort of culminate over time in these more slowly growing solid tumors. Leukemias in adults can be rapidly progressive-
Dr. Aaron Carroll: Don't mean to stop you there. Tell us the leukemias. No, no, no. Keep talking, but what is leukemia?
Dr. Jamie Renbarger: I tend to group cancers and we tend to group cancers into two groups. So the liquid tumors or blood based tumors are leukemias, and solid tumors are just that a more solid mass that can be anywhere in the body, anything from breast cancer to a brain tumor to a sarcoma, these solid tumors that originate in bone and soft tissue. As a general rule, many solid tumors, particularly in the early stages in adults grow more slowly and progress over time. And contrast in kids, many of the solid tumors that we see most commonly in children actually grow and progress quite quickly.
So one, that can make them a problem, whether they originate in a bone and quickly cause pain and disfigurement, dysfunction, or in a brain and cause increased pressure in your head. They can quickly become problematic and life-threatening. Life-threatening part often comes with later stage cancers, where they are maybe not present just in the original spot, but can be disseminated throughout the body, and cause a variety of different kinds of problems from again, disease going to the brain, and ultimately leading to a lot of pressure in the brain and badness to tumor being in the lung, in the abdomen that again, can all result in a variety of different kinds of life threatening consequences.
Dr. Aaron Carroll: I mean, it's a hard, broad question. But how do we broadly treat cancer right now?
Dr. Jamie Renbarger: We're in a really interesting spot with how we treat cancer because there's so much change going on and so much development around really smarter approaches to how we treat cancers. But historically, we treat cancer with poison. Chemotherapy is poison. Or I guess I should say, traditional cytotoxic chemotherapy. It really capitalizes on this idea that this is a population of cells that are growing quickly and more quickly than the normal non-cancer cells in the body. And so it attacks any cells that are growing really fast through a whole bunch of different mechanisms or approaches, but that's kind of the gist. And that's why we see the kinds of side effects that we do with chemotherapy with standard cytotoxic chemotherapy. People lose their hair because hair is actually rapidly growing.
Chemotherapy can cause mouth sores or irritation to the GI tract, because that lining of your mouth and intestinal tract and stomach are fragile and are constantly being repopulated with new and healthy cells. And so that's really the traditional approach. And in fact, in children, because their cancers do tend to be these cells that grow most quickly, kids cancers overall respond quite well to standard traditional chemotherapy. Adult cancers are not as successfully treated with cytotoxic chemotherapy, while there is a subset of adult cancers for which that chemo works pretty well, we know outcomes with it for adults with cancers aren't that great.
And so that's really led to this evolution of thinking more carefully and really diving into what's driving these abnormal populations of cells to grow within that cellular machinery. And how do we target very specific points in that cell growth pathway to stop the exact factor that's making that engine rev too much, if that makes sense?
Dr. Aaron Carroll: So is it a factor that's only in the cancer cells or it's a factor in all cells but just is not performing correctly in the normal cells?
Dr. Jamie Renbarger: It's really the latter. It's often these are proteins or they are growth factors or other proteins in the cells that you find in many different cells throughout the body. But in fact, often they're much more active in the cancer cells, which is what makes those cells susceptible to that more targeted approach.
Dr. Aaron Carroll: So that still sounds like it's cytotoxic unless I'm misunderstanding. Is it still the same theory, it's just more targeted? Or is it something completely different?
Dr. Jamie Renbarger: It is a very similar theory, you're right. I kind of look at standard traditional chemotherapy as using a big hammer. You're using a big hammer to go after anything that's moving fast. And this more targeted approach certainly goes after the subset of cells for which whatever growth factor is important, including often the cancer cells. And so the newer, more targeted agents aren't without side effects, they exist, it's just they tend to be not as broad and not as widespread.
Dr. Aaron Carroll: And are these still like very experimental or are these therapies that have been approved and we're pretty much using them now?
Dr. Jamie Renbarger: Many of the newer targeted chemotherapy drugs are approved for adult cancers. They're not at a point where they're approved for pediatric cancers. And so we end up using, frankly, the vast majority of drugs that we use to treat pediatric cancers, we use off-label. The vast majority of drugs that are of interest right now within that targeted group of drugs, we can get access to something that's already FDA approved.
Dr. Aaron Carroll: So that seems interesting given that we just talked about how the fast growing cancers tend to happen more in kids, why are they studying these types of therapies more in adult cancers?
Dr. Jamie Renbarger: Yeah. So again, if you think about going after or targeting very specific proteins or growth pathways, it's not that it actually is logical in adult cancers, because it's not that those tumors aren't growing, or the cancer populations aren't growing. It's just that there may be populations or groups of cells that are growing just even faster than the cancer in adults. And so you have to be a little more creative or smarter about exactly how to target the population that you want to get rid of, if that makes sense. The big hammer approach doesn't work as well in adults because so many other cells are growing as fast or faster than the cancer, whereas this more targeted approach actually tends to be more successful. Still not the magic bullet but-
Dr. Aaron Carroll: What about focusing on the other side is, as we sort of alluded to before sort of the cells that are acting abnormally, and then the policing system, which perhaps isn't able to catch up. What about goosing the police system? What about trying to make the immunological system work better to kill whatever's going on?
Dr. Jamie Renbarger: Exactly. That's the second really common approach that's being developed now. And that is really using that policing system or an individual's own immune system to really attack the cancer cells. And that can be done either through a kind of tumor vaccine, where again, you're exposing the individual's immune system to a little bit of some cells that are similar to the cancer but really to say, hey, this is something you want to go after because it doesn't belong.
Dr. Aaron Carroll: And is that theoretical or are we actually doing that?
Dr. Jamie Renbarger: So within kids tumor vaccines are really used now in the setting of clinical trials. But certainly there are some really promising results.
Dr. Aaron Carroll: When they create a vaccine for cancer, even in pediatric cancer, is it a vaccine that is broadly for, hey, this is a vaccine for leukemia? Or do they actually have to create an individualized vaccine for each individual child?
Dr. Jamie Renbarger: Yeah. So it really is cancer cells and cancers, while they can fall into or be categorized as pediatric sarcoma or a specific kind of a pediatric brain tumor, every cancer is different. And so it really is a matter of creating a custom vaccine in many cases, for a child or an individual's specific tumor.
Dr. Aaron Carroll: So I'm going to have to ask more questions about this because I'm not getting it. But the antigen for the cancer is already in their body. So how does then putting it into a vaccine and injecting it into their body cause any kind of more of an immunological response than the fact that the cancer is there already?
Dr. Jamie Renbarger: Yeah. The theory, and I'm not a tumor vaccine expert, but really the theory is that for whatever reason, the immune system isn't going after those cells at all, or isn't able to mount a response that's adequate to really ... And we're not talking about using vaccines to get rid of giant solid tumors. We're talking about using vaccines as an adjunct to other therapies. We know that if a cancer comes back, then it comes back because there were some cells that we couldn't see that were still there. And so vaccines really are created to go after those few remaining cells, not to shrink a big, solid tumor. The idea is that you're really kind of reminding the immune system that, hey, these guys are bad, and providing a memory for them to say, okay, anytime you come across one of these cells, you need to make more white blood cells that are specifically going to go after these abnormal cancer cells, if that makes sense.
Dr. Aaron Carroll: You have cancer in the body, I mean, I'm thinking this maybe perhaps this more applies to adults, but cancer grows, it gets bigger, we cut it out, or we attack it with chemotherapy, and then it comes back. What eventually kills people? I mean, it just seems like you could stay on this. I mean, what is it that eventually leads to death in so many people?
Dr. Jamie Renbarger: Before we get to that, I just want to back up to something that you commented on. And that is, why doesn't it just keep sort of hanging out? Why can't we just keep going through this process? One thing that we're finding, and this might be a little side note more than anything, but one thing that we're finding is, in children, particularly with more these newer targeted drugs, there is certainly a population of kids for which these work really, really well, just one drug at a time. Which is pretty incredible when you think about how abnormal these cells are. But we are kind of turning cancer into a more chronic disease in that setting.
Because what's happening is these targeted drugs are really shrinking the tumor down, maybe not making it go away altogether. And so then it just kind of sits there. It doesn't grow, it doesn't completely disappear. But people can get back to a very normal, healthy life, which is particularly important. If you think about a six-year-old, for whom this maybe works for two or three, a single drug may work for two or three years, allow them to grow and develop and participate in school like a normal child. Maybe not make that go away, but certainly can can greatly improve their quality of life, but also their quality of life.
Dr. Aaron Carroll: That seems the kind of thing where it's like, well, if we can get a single drug which gets you three years, and then we have another drug which can get to another three years, then it's very likely in that six-year time period, we'll develop another drug which can give you another ... Is that sort of the long term plan?
Dr. Jamie Renbarger: No. Certainly, I think there are individuals for whom that approach might work really well. Our long term vision is that by beginning, particularly in the pediatric population, by beginning to introduce newer targeted therapies, and immune based therapies, these treatments that train the immune system, in kids who have high risk disease or disease that comes back or relapses after that initial treatment that we can learn about, which are the most effective in children. So that we're not waiting until the disease comes back, but we're actually modifying our upfront treatment approaches in kids with the highest risk disease initially. And then hopefully, all children with the idea that we can use safer, more effective treatments up front and decrease the overall chance that their cancers ever going to come back. So we don't want really ideally want to get to that point where it comes back.
Dr. Aaron Carroll: But still, even if it does, this gets back to my broader question, it seems that again, you do your surgery, you try to get as much as you can, and then it comes back. What kills people? Why can't we just keep doing what we do?
Dr. Jamie Renbarger: Yeah. So ultimately, as those cancer cells are exposed to more and more different treatment options more and more different treatments, cytotoxic chemotherapy, immune therapies, targeted therapies, they're really smart. And they continually change and evolve to try to get around whatever we're throwing at them. Right?
Dr. Aaron Carroll: Right.
Dr. Jamie Renbarger: And so over time, you get to a point where there's nothing that's safe for the patient that's also effective in treating the cancer, and/or it's a solid tumor if it's in a location that you can get to. Or it's so disseminated, it's in so many different areas of the body, so many different bones, lungs, bone marrow, which is where the blood-making cells are located, that a patient has a tumor that starts in their femur bone, their thigh bone that eventually leads to needing to either excise that tumor or amputate their leg, but by that time the cancers may already be in their lungs, the most common location for sarcomas to go. You can resect lung nodules or lung tumors only for so long before you don't have enough healthy lung tissue left or those tumors grow enough that that patients are unable to breathe appropriately. I mean, there are [crosstalk 00:20:21] bad things.
Dr. Aaron Carroll: That makes a lot of sense. If the cancer metastasizes to a part where we can't really operate anymore, and it's going to grow and [inaudible 00:20:26], I would imagine your brain would be bad as well. Okay, that makes sense. It seems that, in my impression, we keep getting better and better at treating childhood cancers that it doesn't seem to be as bad as even I thought it was when I was training, and even when I was training the doctors kept telling me how much better it was than when they were ... So have we made significant strides? Is this a disease where we seem to be doing much better than we used to be? Or is it a constant struggle?
Dr. Jamie Renbarger: Absolutely. We're doing much better than we were even in the 70s, 80s. Overall survival in kids who are diagnosed with cancer is extraordinarily high. And that's why I'm a pediatric oncologist and not an adult oncologist.
Dr. Aaron Carroll: So when you say extraordinarily high, though, what are we talking about?
Dr. Jamie Renbarger: So kids live. So we're talking about 75% of kids with cancer are alive at five years post-diagnosis, and that number is inching up all the time. I would say it's in the 75 to 80% range. The challenge is and the reason that this kind of research is so important, it's really two reasons. So one, there is a subset of kids with aggressive sarcomas, myeloid leukemias, they're very high risk lymphoblastic leukemia. There's a subset of cancers where we haven't really made any progress over the last 25 years.
Dr. Aaron Carroll: And why is that? What makes those different?
Dr. Jamie Renbarger: Yeah, that's a great question. And it really is very disease specific. But in the case of some of the sarcomas, for example, often it's that, again, that they're able to evolve and change in response to treatment. The cells start out much more screwed up than other pediatric cancer cells. And they are very quick to evolve and change in response to treatment. And that probably is part of what's at the foundation for why we haven't been able to keep up with the change in those cells or the evolution of the cells to really find effective treatments.
Dr. Aaron Carroll: So with sarcomas, we're talking about bone cancer. So this is again, now you get a totally naive question, have they often moved outside of the bone by the time you find them?
Dr. Jamie Renbarger: A subset of the cancers have moved away from wherever they start? And again, if we're talking about osteosarcoma, osteo was bone. So it's a bone cancer in kids. And a subset of them 20% or so have moved outside the bone. Those are easy to say, all right, that's a higher risk tumor, and we need to be more aggressive in how we treat that. It's the tumors that haven't moved outside the bone that we really aren't good at predicting which ones are going to come back.
Dr. Aaron Carroll: I mean, granted, if it's happening to my child, I'm sure I would have a completely different question. But given that we believe it's localized, and we have an incredibly hard time treating it and it's one of the most ... Do we not amputate enough? Do we not just cut it out immediately enough? What is the-
Dr. Jamie Renbarger: Yeah. So the approach to treating something like osteosarcoma, this bone cancer in kids, is we do a biopsy to establish a diagnosis. And then we do what's called neoadjuvant chemotherapy. So neo basically means that before we resect the tumor, we give chemotherapy to shrink it.
Dr. Aaron Carroll: Sure.
Dr. Jamie Renbarger: So again, if you can imagine a kid who's growing and you're going to take out a part of their thigh bone, which is the most common location for osteosarcoma, one, you want to minimize the amount of bone that you have to resect as much as possible. Already, we know that, and in fact the historical approach 30 years ago, kids did have their legs amputated. And actually research has shown that whether you do an amputation or what we call a limb sparing procedure, so essentially these kids end up ... If it's in the end part or the lower part of their thigh bone, end up getting a knee replacement at a young age.
Dr. Aaron Carroll: Sure.
Dr. Jamie Renbarger: And so research has shown that there's no difference in overall survival between doing an amputation at that time versus doing a more conservative limb, what we call limb sparing approach. So they still have their leg, they've just have had a knee replacement. And sometimes they need another knee replacement after they've finished growing. But in terms of them leading a normal active life, having that limb sparing procedure tends to-
Dr. Aaron Carroll: Of course, yeah.
Dr. Jamie Renbarger: The reason for doing that chemo before the tumor resection is one, we want to try to shrink it and minimize the amount of bone that we have to resect as much as possible. But two, we use the response of that tumor to the chemo that they get up front to say, okay, how many living cells are still left in this cancer? And that's a really important prognostic factor. So how sensitive are these malignant cells or cancerous cells to chemotherapy allows us to at least make an educated guess at how aggressive the cancer is and how well it's going to respond to chemo.
Dr. Aaron Carroll: So logic would just in my head seems to me like, okay, if we can shrink the tumor, and then we can either cut it off or like, okay, great cure. Is it the problem that it just metast and moves away in ways we can't get? Or is it that kids who have cells which are more likely to turn into sarcoma already are therefore to have more likely to have other cells which are going to turn into the sarcoma already?
Dr. Jamie Renbarger: Right. So it's really the former. And that is that more than likely what's happening is that there is residual microscopic disease. So there are a few cells hanging out that we can't see. If you can imagine having a big tumor, that then you're sticking a needle into or you're cutting open, and then you're doing a big surgery with even a few still some viable cells, the opportunity for those to get into the circulation or to be even in that local tumor area and to not get every single little cell is quite high. Quite high.
Dr. Aaron Carroll: Which is why I guess I was asking at the beginning, like if we had one in the lower thigh, I mean, as hard as it is to imagine why it's like, what if we just amputated immediately every single time? And that just doesn't seem to catch it all still.
Dr. Jamie Renbarger: Yeah, exactly. Exactly. And so because the other important thing is, in order for an aggressive solid tumor to grow, it has to make blood vessels. And so there's a decent blood supply to the tumor itself. And so the opportunity for the cancer cells to get into the circulation as that tumor grows is there as well. The other thing that we do, so kids get a little chemo, then they have their surgery, and then they have a number of additional cycles of chemotherapy to get any cells that are still hanging out. And that works great in 60% of the kids, 65% of the kids. It's that 35 to 40% where it still comes back?
Dr. Aaron Carroll: So given that this is your area of interest, what are the sort of new things or things we're trying for sarcoma? Like what can we do differently that we're not doing now?
Dr. Jamie Renbarger: We're using in individual patients what we call molecular profile or understanding what's deriving cells in an individual to try to customize combination treatments. So pick specific combination treatments that we think could be effective based on what's deriving that abnormal population of cells, if that makes sense.
Dr. Aaron Carroll: Yes. So you're trying to actually figure out ... You have a theory that did specific drugs might be better for specific patients out of the many options that we might have to treat?
Dr. Jamie Renbarger: Right. Exactly. And we're developing those theories or hypotheses based on really rapid DNA sequencing, DNA and RNA sequencing that we're doing in every child's individual-
Dr. Aaron Carroll: So we should be clear, this is what I think we've referred to in previous, precision medicine. So this is the idea that we can tailor treatments to people based upon DNA?
Dr. Jamie Renbarger: DNA in some cases for kids, the DNA changes in pediatric tumors tend to be a lot less common than in adult tumors. And so often, we'll find more changes further down that cell growth path in what we call RNA or proteins. So more the growth factors or the genes that are causing those growth factors to get revved up-
Dr. Aaron Carroll: Is this theory or is it working?
Dr. Jamie Renbarger: Yeah. So we're seeing some pretty dramatic responses. It's really variable. And so certainly, we're seeing some kids where we use this information to customize a treatment and they have a great response. And other kids for whom it doesn't work as well. And so we're really in a learning phase of why does it work for some and not others? And how and we're doing a lot of investigation in animal models as well. So taking tumor from the specific patients that we're seeing who have disease that's come back, putting that into animals so that we can evaluate a whole bunch of different new combinations.
One, to inform how we treat those kids at the time that the tumor comes back, and two, so we can begin to think about how do we change what we're doing up front so we never get to this point. Thinking about changes we can make across the board in our kids with sarcomas. But the third thing is, how do we do a better job of predicting the kids who have disease that's going to come back?
Dr. Aaron Carroll: So I got to go down this road, because I want to make sure I get this. And also, because it's fascinating to me. So you're taking cancer out of active patients, and then you're giving it to rats, I'm assuming?
Dr. Jamie Renbarger: To mice. Yes.
Dr. Aaron Carroll: Okay. So we're putting into mice. And then testing different combinations of therapies on those mice to see which works best and then you go back to that child and treat them? Or is this more like, we're just trying to do research in general on these types of cancer?
Dr. Jamie Renbarger: Yeah. So at this point, it's not to go back and treat that child.
Dr. Aaron Carroll: Okay.
Dr. Jamie Renbarger: Although, it can be really interesting to know what we've given to that child, what's actually worked well, and to look at the different responses that we see in the mice who have that tumor in them, similar combinations to what we gave the child and others. But no, we're not using it at this point to go back to that specific child, but more to inform the future kids that retreat. But I will say that we're not randomly picking combinations, but the combinations that we're evaluating are really informed by what we're learning based on doing that comprehensive DNA and RNA sequencing in those specific tumors.
Dr. Aaron Carroll: So are you looking for specific genes or mutations in the DNA? Or is this just a let's just see what's there kind of thing?
Dr. Jamie Renbarger: Yeah. So in many cases, when we have a pediatric cancer that comes back, we do what we call a really comprehensive look for changes in DNA, RNA and proteins. So we're not looking at very specific known changes, necessarily. Certainly, we look to see if those are there. But we're really looking broadly to, one, identifying novel changes, new changes that maybe haven't been identified before. But to get a better idea of the whole landscape of bad tumors really, aggressive tumors.
Dr. Aaron Carroll: The number of combinations and permutations that would just seem to be in that kind of information, it even seemed like ... I mean, do you need massive numbers of children to do this type of research or is it-
Dr. Jamie Renbarger: While in fact, there are a massive number of permutations there, when we think about the different growth pathways, there are some commonalities among those different growth pathways. And in fact, many of the newer what we call more targeted drugs don't just target one pathway, but might target four or five different cell growth pathways. And so while there are a massive number of very specific profiles that we might find from tumor to tumor, we see a lot of commonalities.
Dr. Aaron Carroll: So how far down the line are we? I mean, is this like, okay, now we're finding out stuff that we can actually start using to treat children or is a lot of this still early stage and we don't know where it's going?
Dr. Jamie Renbarger: Yeah. We are definitely using this information to make informed decisions, more informed decisions about treatments that we use in kids when their cancer comes back. I would say that this isn't in pediatrics, really isn't at the point of upfront therapy as much, although there are some clinical trials in that arena. The other place that we're specifically interested, if you think about the idea that you have a pediatric sarcoma, starts in the femur, maybe we know a patient is at higher risk, because when they first come in at the time of diagnosis, they have some spots in their lungs as well. We take care of all that with our standard traditional chemotherapy. We know because the tumor was already in more than one spot when they came in, that they're at much higher risk for relapsing for that cancer coming back.
So what we're doing in that subset of kids in preparing to launch a clinical trial in is taking that comprehensive look at what's driving those cells. So sequencing their tumors to say, okay, after we're done with traditional chemo, we don't want to just stop. We know stopping is really high risk. It's kind of like sitting on a ticking time bomb waiting for it to start to grow again. But yet, we don't want to expose these kids to more cytotoxic chemo because that probably isn't of benefit either. But would it be helpful, and so the question for this upcoming trial is, would it be helpful to take the individual patient, what's driving their tumor at the time of diagnosis, and starting them on a more targeted or a very targeted drug after they're done with chemo similar to like using tamoxifen or a maintenance therapy and somebody with breast cancer after they get radiation.
To try to get rid of any cells that are hanging out that we can't see and decrease their risk for relapse and improve overall survival and outcomes. And so that's something that, while it's not right at the time of diagnosis, is an approach that we're really interested in kids with who we know have more aggressive disease at the time of diagnosis.
Dr. Aaron Carroll: What do you think are the most sort of cutting-edge of promising therapies in general that are brand new, that we just haven't tried before?
Dr. Jamie Renbarger: So for sarcomas or for cancers in general?
Dr. Aaron Carroll: I would say both. Sarcomas [crosstalk 00:35:37] cancer.
Dr. Jamie Renbarger: Overall as a field, I think we're really excited about certainly about more targeted agents, immune based therapies. So the idea of harnessing the immune system, either by using cell infusions or tumor vaccines, together with potentially more traditional approaches. We haven't even talked about more novel radiation therapy approaches that are less toxic. But I think thinking about targeted therapies together with immunotherapy or cellular therapy is really the future of where we're going to go.
Dr. Aaron Carroll: Well, I'm always fascinated because I hear people say, we need a cure for cancer. And it doesn't seem like there's going to be a cure for cancer. It's going to be many, many, many, many, many different cures for cancer.
Dr. Jamie Renbarger: Yes.
Dr. Aaron Carroll: Some people view this as one big disease, but clearly it is not. Is that correct?
Dr. Jamie Renbarger: That's completely correct. Yeah. Again, cancer is this big general term for a whole bunch of different diseases, and the approach to treating all of those different diseases is quite unique. And so you're right, it is finding a lot of different approaches to a whole bunch of different diseases.
Dr. Aaron Carroll: So when we talked about before and you said about 75% of kids have a 5-year survival rate, what percent of kids are cured? I don't want to cure. I want will live a normal life expectancy. Because clearly, if we turn it into a chronic disease, they may live a long, long time.
Dr. Jamie Renbarger: Yeah.
Dr. Aaron Carroll: But do we get to the point where we get most of these kids were like, it was a terrible disease, but we've done a good job, and now you can go about your life?
Dr. Jamie Renbarger: So you're edging into my other area of great interest. So you said, how many of these kids actually live a normal life and have a normal life expectancy? And in fact, the other opportunity, I think, for some of these more targeted drugs is in the kids who we already cure, but we leave with a lifetime of irreversible side effects. Or of this what seems like an early aging kind of picture, if you will. And so that is when you're little, when you're a child, and you get exposed to toxins that that damage all kinds of cells, that has a lot of downstream effects. While we're focusing our efforts on kids with really aggressive disease for these newer therapies, I think ultimately, when you think about the goal of optimizing therapeutic approaches by maximizing efficacy, but also minimizing side effects.
But for acute side effects and long term side effects, we've got a lot of work to do in the kids who we already cure. Because the reality is that among survivors of childhood cancer, close to 70% of them have at least one significant chronic illness that's associated either with having cancer or receiving treatment for cancer at a young age. And beyond that, on the order of 40 to 50%, have at least two significant chronic illnesses as a result of this primary disease that they had. And that includes things like heart disease, diabetes, obesity, metabolic syndrome. They're at very high risk for strokes and heart attacks.
We know that because they have weakness that actually was established at the time that they had their cancer, that really in many kids really never gets back to normal. That they're less active than their siblings, than their peers, and that sets them up for a whole host of things. And we haven't even touched on the fact that when you can't keep up with your classmates when you're back in school, you may feel more isolated. And so may not go as far in your education as you otherwise would have or have the same kind of job that you would have if you hadn't developed cancer. And so I feel this ethical obligation to figure out how do we do a better job, both in our upfront treatment of those kids who we know maybe have really low risk disease, fine. So how do we do a better job of using less toxic therapies? There's a ton of work to do there.
Dr. Aaron Carroll: So the health services researcher me is obsessed with that end of the spectrum. Because I'm interested in like how do we improve sort of globally, everyone, and of course, trying to figure out those issues for a host of kids with chronic disease is massively important. You're right. In fact, look, I've been as guilty as everybody else, even though that's where my inclinations lie. I've spent most of this time talking about how do we cure? How do we cure? Focused on the benefits and ignoring the harm. So what do we do about that?
I mean, I would imagine, first of all, it's hard to study in the sense that we've spent so much time getting these kids to be healthy, and then we have to follow them for decades in order to see what actually happens to them in the long term. So I'd imagine, one, it's hard to do. I mean, keeping cohorts of kids together just to study the efficacy is hard, let alone the decades of following we would need to do to see what are the long term implications. How much do we know about that? And sort of what are we doing about it?
Dr. Jamie Renbarger: Yeah. So there is a large national effort called The Childhood Cancer Survivor Study that is based at St. Jude, but actually includes a large cohort of childhood cancer survivors that they're following longitudinally, really with survey based tools to capture long term outcomes. In addition, I should say, in addition to the surveys, they're also linked with the medical centers where they're followed, so that we can provide as ... Children's hospitals can provide more detailed information maybe about complications that they develop long term. And so that's really where a lot of probably the biggest effort in childhood cancer survivors lies at the moment. And that's really the cohort that we've learned most from in terms of risk for things like cardiovascular disease and obesity and diabetes. And we could go on and on. It's a hard thing to think about a kid of vulnerable population of patients for whom the big hammer works, right?
Dr. Aaron Carroll: Right.
Dr. Jamie Renbarger: How do you mess with that? How much data do you need to say, all right, yeah, we can cure this population, but we know we cause harm at the same time? What is that balance? And what's the level of evidence required for an alternative treatment to mess with that, the big hammer, traditional chemotherapy, that maybe cures 98% of a population?
Dr. Aaron Carroll: Especially since I imagined that you can mess with the front end, and maybe we could see it's slightly less powerful, but we might have to wait 20, 30, 40 years to see if that's actually making a difference on the other side. How do you even do that? Because it's like, we will be tinkering with something we know that works and we're not even sure. It'll take us decades to see if it actually makes a difference on the other end. Before you were talking about it, my inclination was to be ... The cynical part of me is that there's probably gazillions of dollars spent on the front end of like, how do we develop drugs? And how do we develop techniques that will make all of this stuff better and relatively much less money?
Because there's very little money to be made in preventing side effect 40 years later. So, one, I bet there's much less research in general on that back end than I wish there was. But I'm thinking even now like, how would you even do that? Because to try to tinker with this stuff, how much of a decrease in efficacy are you willing to take for knowing we got to wait decades to see if there's a difference in the other end?
Dr. Jamie Renbarger: Now, it's a really challenging area. And the reality is even within the state of Indiana, where we are, there are close to half a million cancer survivors. Now, this is all ages prosper, across board. It's a large population. In the United States, we're approaching 20 million cancer survivors. And so when you think about the impact, if you will, of improving health and wellness in that population, on their cost of care, on their life expectancy, on their ability to contribute to their communities and to society, I think that the cost savings and benefit to actually optimizing their health and wellness could be huge, significant. So that's my new direction that we should-
Dr. Aaron Carroll: Totally. I'm sold. I don't need to be [crosstalk 00:44:37]. That would be so complicated to try to get at.
Dr. Jamie Renbarger: Right.
Dr. Aaron Carroll: Especially, I think, and that's part of I think we've seen with a lot of pediatric diseases, as we get better and better at prolonging people's lives out of childhood, all of a sudden, there are all these adult implications that we've never dealt with before because nobody lived. And now they do. It's a whole new area we need to figure it out.
Dr. Jamie Renbarger: Yeah. Absolutely.
Dr. Aaron Carroll: We've spent a lot of time talking about pediatric cancer. I mean, I'm sure we could spend an equal amount of time talking about adult cancer. But are there any sort of broad strokes about what would make that different in sort of how we go about treatment? Are they more likely to use surgery or radiation as opposed to chemotherapy?
Dr. Jamie Renbarger: Yeah. Overall, one of the big differences is that across the board, if you look at adult cancers as a whole population, so it's a really diverse or heterogeneous population of diseases, but overall outcomes are not nearly as good as they are in pediatrics. Certainly, there are subsets of adult cancers that we do really well. And that's certain breast cancer, some prostate cancers and things like that. Because overall survival and disease outcomes are not as good in adult cancers, it is ripe for new discovery. And so it is an area where looking for alternative approaches, because that traditional cytotoxic chemotherapy for many of those diseases is not as effective. It's an area we're thinking about, what are better more effective approaches to this disease?
Dr. Aaron Carroll: Are we not as good at it because they're different cancers that are harder to cure? Or is it partially because a lot of it occurs in older people who already have worn down systems in other areas that therefore they can't take the side effects? Or is it just that if an 80-year-old man gets cancer, his five-year survival rate wasn't as good as a child's to begin with anyway?
Dr. Jamie Renbarger: Yeah. It's really a combination of all of those things. The reality is, yes, many adult cancers, because they are more slowly growing, are more advanced by the time they're diagnosed. They're more likely to be metastatic or to be located in more places beyond their original spot, or certainly to be locally, what we call locally invasive. So if you think about pancreatic cancer, for example, number one, it grows more quickly than some other adult cancers, but often is much more locally invasive, and is in the liver and other locations by the time it's even diagnosed. And some of them are in locations that are more difficult to surgically resect. And you're right, the tolerance to treatment is much different in adults than in kids, particularly in older adults.
Dr. Aaron Carroll: What are you most excited about with respect to sort of the future of where we're going with pediatric cancer? And what do you think is the big thing that you're most excited about? Is it something we've already discussed or is it something else?
Dr. Jamie Renbarger: I really think in pediatric cancers, the future of immune based therapies, cell and immune based therapies and targeted therapies, using those together with, initially, together with standard chemotherapy, I think we'll continue to see improvements in and survival. And also, I think, in some cases, we will see for kids with more aggressive cancers, newer, less toxic therapies being introduced much earlier on. And so our overall outcomes will be much better.
Dr. Aaron Carroll: Seems like that would be a real plus. Because given that 75% or more get [inaudible 00:48:25], that's a much better diagnosis, I think, than most people think cancer is. But I think what also most people panic about, especially parents, is that I know what my child's going to have to go through to get that 75% shot. So I would imagine the idea that we could have less cytotoxic or therapies with fewer side effects that were easier to take would probably be a real leap forward.
Dr. Jamie Renbarger: Absolutely. Absolutely. I think, particularly if it's without having to compromise on survival response.
Dr. Aaron Carroll: Yeah. Depending upon when they get it, it's such a hard to lose a couple years. At 60, if you have to go to the hospital, and you're not as active for a couple years, terrible. But if we cure you, wonderful. But if you're 9, 9 to 12 is a big deal. Yeah, I can imagine that there's a lot more angst there.
Dr. Jamie Renbarger: Absolutely. For sure.
Dr. Aaron Carroll: Jamie, I can't thank you enough for joining us. This has been fascinating. Absolutely, I'm going to try to convince you to come back again, because I'd love to spend a whole other hour talking about the wellness aspects and what we need to do for people after we've finished treating them. But thank you so much for joining us.
Dr. Jamie Renbarger: Sure. Thanks for having me.
Dr. Aaron Carroll: If you like this podcast, we'd really appreciate it if you might think about writing review on iTunes or wherever you get your podcasts, every little bit helps. And of course, subscribe so you don't miss any of our future episodes.