The Vetrospective
Host Dr. Michael Kent explains + breaks down the Science behind the research about our Domestic Companion Animals.
The Vetrospective
Osteosarcoma
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Dr. Michael Kent sits with Dr. Robert Rebhun to discuss Osteosarcomas in Veterinary Medicine.
The Vetrospective Podcast S01 E09: Osteosarcoma
Transcript
Dr. Robert Rebhun: While we can't tell which ones are going to respond, and it's a very few, I think it gives us hope that we can make this happen.
Dr. Michael Kent: Hello, and welcome to The Vetrospective Podcast. This is your host, Dr. Michael Kent. I'm a radiation oncologist at the UC Davis School of Veterinary Medicine, an animal lover, and like I said, your host. On today's episode, we're going to be talking about osteosarcoma. So, osteosarcoma is the most common type of primary bone tumor that we see and meaning a tumor that arises from bone. For those of you who enjoy etymology, osteo comes from the Greek word for bone, sarcoma comes from the Greek word for flesh, and oma means morbid growth or tumor. Put it together and we have osteosarcoma. But of course, if you, your child, your dog, or your cat are faced with learning what this word really means, it can be life-altering. This is one of the cancers that we look at as having a true One Health approach. In other words, what we learn about this disease in people help us treat our patients, and what we learn in dogs can in turn help advance human treatments. We'll talk more about this during this episode.
So, to speak to you about this today, I have invited Dr. Robert Rebhun, who has worked on this tumor for much of his career. Dr. Rebhun is a professor and the Maxine Adler Endowed Chair in Medical Oncology here at the UC Davis School of Veterinary Medicine. Dr. Rebhun did his undergraduate work and his DVM. at Cornell University. They then earned a PhD in cancer biology from the University of Texas Health Science Center at Houston and MD Anderson. Before joining me at UC Davis, Dr. Rebhun completed his medical oncology residency at Colorado State. He works with me at our Center for Companion Animal Health, where he is our Associate Director for Cancer Research, and he is also Director of the Veterinary Center for Clinical Trials. Thank you, Dr. Rebhun, for joining us today, and welcome to The Vetrospective.
Dr. Robert Rebhun: Thank you.
Dr. Michael Kent: Okay, I wanted to ask you before we got started on osteosarcoma, what made you decide on veterinary medicine, and then why cancer?
Dr. Robert Rebhun: Yeah, so vet med was easy for me. My dad was a vet.
Dr. Michael Kent: At Cornell, right?
Dr. Robert Rebhun: Yeah, he was a professor at Cornell. He was boarded in ophthalmology and large animal internal medicine. So, I thought I wanted to be a dairy vet growing up in upstate New York.
Dr. Michael Kent: Lots of cows.
Dr. Robert Rebhun: And then through, I actually was interested in, I wasn't sure if I wanted to go to vet school or med school. And ultimately, I did some research work for a couple of years and decided that One Health was One Health and decided to go to vet school.
Dr. Michael Kent: And then cancer. What drew you to cancer?
Dr. Robert Rebhun: Yeah, I mean, cancer touched me in many ways. I think my father was actually diagnosed with a brain tumor my first year of vet school, which got me even more interested in cancer. And through the basic sciences and through vet school, I decided I wanted to do cancer instead of dairy cows.
Dr. Michael Kent: Fair. So, moving on to the topic we're going to be talking today, can you explain to everyone and even me, why not? I can always learn. What is osteosarcoma?
Dr. Robert Rebhun: Yeah, so I mean, as you mentioned, osteosarcoma is a primary bone tumor that affects usually large breed dogs and also kind of affects people, usually younger age adolescents, but occasionally older people do get osteosarpoma as well.
Dr. Michael Kent: So how common is this disease in dogs?
Dr. Robert Rebhun: Well, interesting in dogs, we estimate that there might be around 30,000 cases in the US per year. So, it's pretty, you know, it's one of the more common tumor types that we see in large breed dogs. as opposed to in people, there's only about 800 to 1000 osteosarcoma diagnoses a year in the US.
Dr. Michael Kent: What about cats? Do we know about cats and osteosarcoma at all?
Dr. Robert Rebhun: Not A lot. It's a pretty rare tumor in cats. And when we see it, they're usually, the ones I've seen is only a handful over 15, 20 years, and they're usually old cats.
Dr. Michael Kent: Yeah. So, you had mentioned large breed dogs. Is there a reason why we think they happen more commonly in large breed dogs than in our small breeds?
Dr. Robert Rebhun: I mean, we see a bunch of different cancers in large breed dogs, but osteosarcoma, I mean, it tends to be associated with taller dogs. We think that there are some genetic differences between large breed dogs that may predispose them to osteosarcoma, but we haven't nailed that down yet.
Dr. Michael Kent: Something else to work on. So how old and... Are dogs in general? You mentioned this is something that hits young adults, kids, and humans, but what about dogs? What age range do we see?
Dr. Robert Rebhun: Yeah, so there's what we call a bimodal distribution, which just means there's kind of two high points of when this can occur. It's usually, there's a subgroup that's between one and three years of age and then there's most of the cases that we see are probably between 7 and 9.
Dr. Michael Kent: So yeah, the ones that one and two, those are pretty uncommon, but do occur, right?
Dr. Robert Rebhun: Yeah.
Dr. Michael Kent: So, and when we're thinking about osteosarcoma in dogs, what bones do we see this develop in most commonly?
Dr. Robert Rebhun: Yeah, so most commonly we talk about appendicular, which just means the legs. So can be forelimbs, can be hindlimbs, but there are certain locations that is pretty common within the bone. So if we see x-rays and we see a lesion in a certain area and a certain breed, that unfortunately fits with osteosarcoma a lot of times.
Dr. Michael Kent: What about front legs versus back legs? Is there a predilection or a particular bone or a particular site?
Dr. Robert Rebhun: Yeah, I mean, I think it's a little bit more front legs than back legs in most of the studies. We have an expression away from the elbow and towards the knee.
Dr. Michael Kent: I never liked the, on the back end, the towards the knee.
Dr. Robert Rebhun: Yeah.
Dr. Michael Kent: But yes.
Dr. Robert Rebhun: Yeah, the forelimb, the away from the elbow usually works pretty well is what we tell the students. But the other one, you know, towards the knee is, they can be anywhere in long bones. Yeah.
Dr. Michael Kent: So I always think of it more kind of either up at the shoulder or down and what we would, commonly refer to us in the wrist and kind of in those bones there and the like. So do we know what causes this disease at all? What causes osteosarcoma?
Dr. Robert Rebhun: No. Again, I mean, we're looking at, you know, a variety of groups are looking at genetics. You know, there's certainly a breed predisposition that we see in certain large breed dogs, even more than other large breed dogs. And really the only other thing that has been known to be associated with sometimes surgery implants like TPLO, if they get their cruciates fixed surgically and put in implants, sometimes they've been associated with osteosarcoma. But it's really hard to nail that down as well.
Dr. Michael Kent: Yeah, it's hard to prove, right? Because if you have a lot of dogs getting this particular type of surgery, were they going to develop it anyway?
Dr. Robert Rebhun: Yeah. And I said, the predilection seems to be towards the knee and that's where the implants are for knee surgery.
Dr. Michael Kent: Yeah.
Dr. Robert Rebhun: It's hard to say.
Dr. Michael Kent: Yeah. And so where else do we see this, you know, besides in the long bones? You mentioned our appendicular skeleton or which means our long bones, our, you know, radius and humerus and the like. But where else do we see these pop up in dogs?
Dr. Robert Rebhun: We can see these just about anywhere, honestly. I mean, we can see them in the jaw. We can see them on the head. We can see them in the hips or spine sometimes. But most commonly it's in the legs.
Dr. Michael Kent: Yeah, most commonly. And then I know as a radiation oncologist, I often treat the ones in the nose also. So, we see them intranasally too. And so really, because it's a tumor that arises from bone, it could be anywhere bone starts, right? Anywhere we have bone.
Dr. Robert Rebhun: Yep.
Dr. Michael Kent: And so how is an owner going to know? What are the clinical signs? You know, we can't really say symptoms because symptoms are self-reported. So, what is an owner going to notice if their dog has osteosarcoma?
Dr. Robert Rebhun: Yeah, I mean, clinically, a lot of times what we'll hear from owners is that there was some incident. You know, we were jumping out of the car, we were chasing a squirrel, we did something, we were playing ball, and we noticed a lameness, so a limp. But a lot of times it's just kind of that little activity that kind of puts it over the edge, so to speak, because these are pretty painful. There's a loss of bone that's there. It can be quite painful for these dogs. So usually it's going to be a limp. Some dogs, you know, may start acting off, may not eat as much, but most times it's just, “oh, my dog's got a limp”. And it's hard to tell if that's a soft tissue injury or if they may have, hurt their ligaments or something?
Dr. Michael Kent: So yeah, this isn't really specific to a bone tumor, what you're describing, right? I mean, things like you said, like an injury or even arthritis, the dog is getting older because we're, you know, most of the dogs are older dogs who get this. So how would like you clinically approach this if you were, let's say, bring your dog into your local vet, are you immediately thinking bone tumor when the dog becomes lame after playing ball?
Dr. Robert Rebhun: Well, I am because I'm an oncologist,
Dr. Michael Kent: But we see a stilted.
Dr. Robert Rebhun: That shouldn't be the case. A lot of soft tissue injuries, again, knees, all sorts of things can cause lameness. So, I mean, I think just heading to the vet and looking at, having them look and do an examination. Usually if we see like deep bone pain on physical exam, that will be something that makes us want to do an x-ray. But if it seems like it's just a routine injury, a lot of these, it's reasonable. Majority of time, it's going to be, oh, let's get some rest and maybe start some pain medication and we'll recheck it in a week or two.
Dr. Michael Kent: And then if it comes back or it's still persistent, then it's probably worth getting an x-ray to try to investigate this further. So how else do we go about diagnosing this? Like how do we actually decide this is a bone tumor? How do we decide it's potentially an osteosarcoma?
Dr. Robert Rebhun: Yeah, so some of that depends on where in the country you are. So here in California, we don't have a lot of fungal diseases.
Dr. Michael Kent: Fortunately, yes.
Dr. Robert Rebhun: They can look a lot like this on x-ray. So that can be, painful lesion on palpation, on physical exam. And, if you're in the Ohio River Valley and, you do x-rays and you see a lesion that looks typical of osteosarcoma, you may also have fungal disease on there. And so getting a sample of that would then be the next step.
Dr. Michael Kent: So, can we just use the x-ray and the changes we see on an x-ray or a radiograph, a radiograph being the technical term for an x-ray to diagnose this, or you mentioned we might have to do more?
Dr. Robert Rebhun: Yeah, I mean, depends on where you are, but I mean, a typical x-ray here, we may be about 90%, but it's not 100%. And again, that's if it's a typical location, typical breed, typical everything, we can be pretty confident on an x-ray. But it's always best to try and get a sample to confirm that.
Dr. Michael Kent: Yeah. So, if we're looking at x-ray and we see this destructive and even productive type lesion on the x-ray, and I know this is audio, so I can't really show you a picture or one, but they're pretty striking, right? And so now that we see this, and what would be the next steps that we would take with the owner to decide on how to proceed.
Dr. Robert Rebhun: Yeah, I mean, if it's reasonable, we try and get a sample of it to see if we can confirm. Sometimes we can confirm tumor versus infection. That may be as far as we go, but once we know it's a tumor in the bone, then we know to address the pain and to address the tumor itself. And then we're probably heading towards surgery. And so, once we kind of know that, we will do what we call staging, is just searching everywhere else in the body to make sure it hasn't already spread somewhere.
Dr. Michael Kent: So staging is kind of assessing the tumor locally and then seeing where it may have spread or may not have spread, at least to a best ability we have, right? So
Dr. Robert Rebhun: Yeah.
Dr. Michael Kent: How do we go about staging it? What are the tests we use for that? and where are we looking? Where is it most commonly spread?
Dr. Robert Rebhun: Yeah, I mean, everything, it depends on the dog and the client in the situation, but most times we're concerned that it's going to spread to the lungs or other bones. It doesn't spread very commonly through the lymphatics. So, if we're looking at the lungs, we can do x-rays. We can also do a CT scan. And if we're looking in other bones, I mean, we want to do a good physical exam, see if we can pick up any pain anywhere else. If we do suspect some pain somewhere else, then we can do x-rays of that area or a CT scan or a few other tests. But those are the ones we usually use.
Dr. Michael Kent: Okay. And so let's say we have to advise an owner if we're going to do an x-ray or a CT scan to look for the lungs. What's kind of the advantages of each? or why would you choose one over the other?
Dr. Robert Rebhun: Yeah, I mean, our standard is usually x-rays. dogs may sit still for x-rays or they may need a light sedation or something like that. CT scans are great. You can see smaller lesions on them, so they're more sensitive. The problem in dogs, we don't have a long history of doing CT scans for chest and so when we see little things, even if we see what we're convinced are small growths in there, we're not really sure what that means long-term for the dogs.
Dr. Michael Kent: So they may or may not be the tumor. They could be even just like an old infection, like what we might call a granuloma or something, right?
Dr. Robert Rebhun: Yeah. So they're very sensitive. They're not as specific.
Dr. Michael Kent: Got it. So sensitive meaning we can find lesions more, but specific meaning we don't know if that's tumor or is that something else?
Dr. Robert Rebhun: Yeah, in some cases. And we know if we take X-rays and we see a tumor there or what looks like growths, that's a pretty poor prognosis and it's going to guide potentially what we decide to do.
Dr. Michael Kent: So how often have they already spread by the time a dogs diagnosed with this or that we have a high suspicion.
Dr. Robert Rebhun: The number that we say here or anywhere in academia is about 10%. I think there may be a higher percentage out there in the real world with general practitioners that take films and then take x-rays. If they already have spread to the lungs, they may not choose to come see us because the prognosis is poor.
Dr. Michael Kent: So, how do we go about treating this? You know, we have a dog who presents for lameness. The local vet maybe has put him on a non-steroidal anti-inflammatory drug for a little while. They rest him, doesn't get better. So, they take an x-ray and they're suspicious. They send him to us. So how do we talk to owners? What are our options for treating it?
Dr. Robert Rebhun: Yeah, I mean, so the biggest problem with osteosarcoma, I mean, we like to get a diagnosis, so oftentimes we will try and do fine needle aspirate under ultrasound guidance.
Dr. Michael Kent: That's where we put a needle into the tumor and try to get cells out, right.
Dr. Robert Rebhun: Exactly, yeah. And, or, you know, we could do biopsy, but most times we can get our answer with that needle into the lesion itself. Once we are confirmed that it is osteosarcoma or that it is a tumor, unfortunately the problem with osteosarcoma is that almost all of them have already spread by the time they're diagnosed.
Dr. Michael Kent: So spread meaning we can see the disease or spread.
Dr. Robert Rebhun: Yeah, so like I said, when we look on x-rays, the number is only 10% that we can see that have spread. Those are big tumors that have to be, they have to be bigger tumors to be seen on x-ray, but... We know this tumor sends out a bunch of cells. We call it microscopic disease. So, we know that the cells themselves have spread. And it's estimated that we need to see, in order to see a tumor, you probably need a billion or more cells.
Dr. Michael Kent: And a billion cells is what, going to be just a few millimeters or like a portion of an inch, right?
Dr. Robert Rebhun: Yep.Yeah. And so, you know, there could be a million cells there and we can't see it on x-rays. We can't pick it up even on CT scan. So that's the problem with this disease is at the time of diagnosis, in people and in dogs, probably 95 plus percent have already spread. We just don't see it.
Dr. Michael Kent: Okay, so I'm going to break it out a little bit then. So, we have a dog who comes in and it's got a suspected bone tumor in, let's say, above its wrist, its distal radius, most common, one of the most common sites we see. We aspirate it, It looks like tumor, not infection. We're in California, so that's unlikely. And we take chest x-rays and they're clean. What's our next step for treatment? What do we offer to the owners?
Dr. Robert Rebhun: I mean, that's where things differ a little bit in vet med versus human medicine. So, what we try and do is we try and match what the goals of the owner are, what the dog, it may depend on the owner, it may depend on the dog. but we have, five or six different treatment options that we can approach this with.
Dr. Michael Kent: Yeah. So, we're taking in the dog in the family and kind of holistically looking at that and trying to advise the owner on what to do. So, what would be our most commonly offered treatments? I know we don't like to use the term standard of care when we don't really have a standard.
Dr. Robert Rebhun: Yeah. So the, I mean, the most aggressive option, the, it's called, which I don't love either, curative intent option is to remove the primary tumor and then follow that up with some sort of therapy, usually chemotherapy. So, we get rid of the primary tumor. That can be most times, that's amputation, to get rid of the entire tumor. Occasionally we can do limb spare, but only in certain locations and in certain dogs.
Dr. Michael Kent: And those are with higher risks of complication too, right? So, you always have to weigh the benefit versus the potential complications and risks.
Dr. Robert Rebhun: So removal of the tumor, amputation is the most common, most aggressive way to treat this. We get rid of the primary tumor and then we need to talk about slowing down those cells that have already snuck out to other places in the body.
Dr. Michael Kent: So how do we, how do dogs do after you take a leg off most of the time? How do we expect them to respond?
Dr. Robert Rebhun: Yeah, I mean, our not so funny joke is that, you know, dogs have three legs and a spare. Most dogs do very well with amputation. It depends a little bit on the breed. I mean, really giant breed dogs, Forelimbs hold about 60% of the weight. And so, and it's more dramatic when we have a forelimb amputation because they have to hop and their head goes up and down.
Dr. Michael Kent: And with a giant breed dog your going to see that, their face is almost in yours.
Dr. Robert Rebhun: Yeah. So, you know, we say, you know, forelimbs are a little bit tougher. The hind legs, you know, may also depend like things like if we have severe osteoarthritis, if we had bad knees, something like that. But, In most cases, the dogs do very well.
Dr. Michael Kent: And they're getting up really within a day of surgery usually and just learning their new center of gravity so they don't topple a little bit, right?
Dr. Robert Rebhun: Yeah, I mean, depends on, like I said, if we get a... seven-year-old lab that's a hunting lab that the bone pain hurts so much, usually you're right. They get up from surgery, they feel so much better. And it's like trying to, how do you keep them in the hospital for a day? You know, big St. Bernards or something with a forelimb, they may actually take a few days to get up, get around. They might need a lot more help.
Dr. Michael Kent: So now you've already alluded to that we have to do more now after we've taken off the limb and that we have to, basically, we usually offer chemotherapy, right? So how effective is the chemotherapy? When do we start it?
Dr. Robert Rebhun: Yeah, so I'll kind of throw in a little comparative note here. I mean, when people, the standard is to actually start chemotherapy before you remove the bone tumor.
Dr. Michael Kent: What we would call neoadjuvant.
Dr. Robert Rebhun: Yeah. And then they typically get chemotherapy after the surgery as well. In people, chemotherapy is, it's a much more toxic protocol, which just means it's toxicity is, you can handle toxicity a little bit different in people. But chemo's actually much more successful in people. So probably 60 to 70% five-year survival and there can be long-term cures. In the dog, we typically just do the amputation or the surgery to get rid of the bone pain, and then we follow up with chemotherapy. And so can be anywhere from 4 to 6 doses of chemotherapy usually.
Dr. Michael Kent: And they're about every three weeks or so, right? So you're looking at a commitment and we're monitoring the lungs and and the like. How effective is it though? How, what, you said 60 to 70% effective at long-term control, at least for humans. What do we consider control and how long does it last?
Dr. Robert Rebhun: I mean, there's a variety of different studies. I would say the largest prospective clinical trial that's ever been done in dogs with surgery followed by chemotherapy. The median survival is listed as 280 days, which just means half the dogs live longer than 280 days and half the dogs live less than 280 days.
Dr. Michael Kent: So what, 10 months or something? And there's a huge range around a median though.
Dr. Robert Rebhun: So yeah, and the other way to put that is there's about a 40% survival at one year. And at two years, about 24, 25% of dogs are alive at two years.
Dr. Michael Kent: So it's pretty tough. So, what can we do then if, let's say a dog comes to us and they already have lung mets or spread to the lungs, sorry, using vernacular, or if they've gone through chemotherapy and it's in the lungs, where do we have really effective treatments for that?
Dr. Robert Rebhun: No, I mean, that's something that researchers have been working on for now 40 plus years. Human and dog, once it's spread to the lungs, there's not a lot that has been shown to work.
Dr. Michael Kent: So, you already alluded to a little bit of this disease in people. And you know, it's not as common. 800, 1000, you know, young adults, kids get this a year. And 30,000, and I've seen numbers even saying higher sometimes in dogs in the US getting this a year. How similar are they to each other? How similar is the disease in us, people, versus disease in dogs?
Dr. Robert Rebhun: Yeah, I mean, it is one of the cancers that we see that is quite similar. So, we talked about the age differences a little bit. But, if you look at these under a microscope, they're almost indistinguishable. If you look at them molecularly and genetically, they have a lot of similarities. Certain genes are upregulated and downregulated. There's a lot of similarity. And then clinically, like we mentioned, usually happens in the legs or the arms. And it usually spreads to the same places in both species.
Dr. Michael Kent: So really similar. Are there big differences besides the age distribution that we see? between people where it's younger people and older dogs most of the time? Are there other major differences that, we've found at this point?
Dr. Robert Rebhun: I can't really think of any, but maybe you can.
Dr. Michael Kent: Not off hand. That's why I was asking you. But so you, what we're saying in a sense is what we learn in people, we can apply to our patients and what we learn in dogs, we can hopefully apply to people, largely young adults. So, this is actually a really good tumor to study in humans and in dogs then.
Dr. Robert Rebhun: Yeah, I mean, I think, we talked a little bit about the variety of things that can, the variety of treatment options that we can do with dogs. So, I mentioned the most aggressive way, amputation followed by chemotherapy. But sometimes, if you've got an old dog or maybe a dog that already has severe osteoarthritis or something, we do have palliative options as well.
Dr. Michael Kent: Yeah, and I do some of those.
Dr. Robert Rebhun: Yes, you do.
Dr. Michael Kent: Yes. So you want to run through those for people?
Dr. Robert Rebhun: I mean, we talk about amputation alone just to relieve the pain. Like dogs may actually come in with a fracture where this bone is weakened and they're so painful. We, unfortunately the options are euthanasia or we remove the leg.
Dr. Michael Kent: Right then, yeah.
Dr. Robert Rebhun: And so some owners may just want to get a few more months and not want to do chemotherapy for their dog. Maybe they're, have somebody at home that's pregnant or trying to get pregnant and the secondary chemo exposure might be a concern for them. Maybe the dog, like I said, has got bad osteoarthritis or other orthopedic disease, and we just want to palliate. So, we can talk about palliative radiation. We come see you and give them radiation. Almost all of these dogs, we're going to be putting on pain medication.
Dr. Michael Kent: In addition, even to the radiation, I know we tell people we can usually get somewhere in three to six month kind of range of decent pain control. At least about 75% of dogs we treat begin to control it.
Dr. Robert Rebhun: I think that's the goal. With palliative, you know, we're looking at three to six months, like you said. Radiation works great. Some other medications may be helpful, but there are most cases options to palliate if they don't want to be aggressive.
Dr. Michael Kent: So, I wanted to bring us back to talking a little bit about people. In a sense, you've talked about how we've maximized the dose of chemotherapy and despite the toxicity. And in dogs, we use chemotherapy and we've also kind of maxed out what we feel is acceptable, even though we dose a little bit lighter and we still fail. and we fail 60 to 70%, if it's your kid, that's not where we want to be. That's heartbreaking. And so where do we go from here? How do we move this forward?
Dr. Robert Rebhun: Yeah, I mean, that's where opinion comes in.
Dr. Michael Kent: Of course, that’s what I want from you.
Dr. Robert Rebhun: That's where we sit right now. I mean, I think in people, like you mentioned, they've maxed out chemotherapy. They've tried even more aggressive protocols and it doesn't seem to add anything. Once it's spread to the lungs, chemotherapy doesn't seem to do much.
Dr. Michael Kent: No, it's too much disease, right? And it's maybe resistant because you've already had seen the chemo and the tumor in an evil Darwinian way has figured out how to get around it.
Dr. Robert Rebhun: Yeah, and dogs, the chemotherapy helps. Like you mentioned, when we just do palliative, we're looking at three to six months. We're looking at more like 10 months with chemo. So, but again, there are a subset, 25% alive at two years that do respond to chemo.
Dr. Michael Kent: Yeah. So worth doing.
Dr. Robert Rebhun: For us anyway, I think, their chemo does work. It works in a subset of dogs. Wouldn't it be great if we could know which dogs that it actually worked for? Which dogs, the tumor doesn't respond to chemotherapy.
Dr. Michael Kent: Because we have some fail early, even at a couple months, right?
Dr. Robert Rebhun: Yeah, actually about 1/3 of dogs fail right when, before they, or right at the time when they finish chemotherapy.
Dr. Michael Kent: And this is kind of new, this research you've been working on, I know.
Dr. Robert Rebhun: Yeah, we've been doing it for a couple years.
Dr. Michael Kent: So how do we move it forward? I'm going to throw out the word immunotherapy to you and ask you to kind of talk about that, because I know that's something you've been working on, we've been working on together also.
Dr. Robert Rebhun: Yeah, I mean, I will add that in addition to chemotherapy, there's other approaches, receptor tyrosine kinase, targeted, personalized therapies that for other cancers have worked great. They haven't done much for osteosarcoma.
Dr. Michael Kent: Yeah, because I mean, even some of the targeted therapies I have, I know if we give in the face of gross disease, i.e. we see lung spread already, lung masses or lung mets, it doesn't do anything.
Dr. Robert Rebhun: Yeah.
Dr. Michael Kent: So, how do we do better?
Dr. Robert Rebhun: Well, immunotherapy has also been kind of a swing and a miss on osteosarcoma on the human side. There have been trials looking at checkpoint inhibitors, which have revolutionized cancer treatment in people.
Dr. Michael Kent: So, for those of you who want to learn more about checkpoint inhibitors, we have an episode with Dr. Rachel Brady talking about immunotherapy. But briefly, a checkpoint inhibitor is something to try to reactivate the immune system, reactivate our T-cells so they're able to recognize and attack a tumor. Sorry to interrupt, but…
Dr. Robert Rebhun: Yeah. They haven't really, for sarcomas and osteosarcoma in particular, they haven't really been shown to be a benefit.
Dr. Michael Kent: So how do we move this forward? Because these are what we sometimes refer to as immunologically cold tumors, i.e. the immune system can't find them as opposed to, let's say, a melanoma which has lots of changes on it that and causes an inflammatory response. We've checkpoint inhibitors have worked well on their own there. What do we what do we try to do with osteo now? How do you tackle this?
Dr. Robert Rebhun: It's I think there's excitement over immunotherapy and the approach to immunotherapy. We just haven't found the right one yet. And so as you mentioned, yes, these are considered colder tumors. The immune system isn't recognizing them, but there may still be ways to get the immune system to recognize them. So, it may just be a tougher ask. We've got to figure out a way for the immune system not only to recognize them, but then release the brakes and make sure that they're attacking these tumors.
Dr. Michael Kent: So combination therapies. I always like to think radioimmunotherapy is going to be the key, but we will see. So, another kind of question I have is, how do you find this earlier? Like, we find this pretty late in disease. Is there anything that we can think of or anything we can do to maybe try to diagnose this earlier?
Dr. Robert Rebhun: It's really hard, honestly. I mean, sure, if you've got a giant breed dog and it has a wimp, you can rush in and take x-rays. The problem is, if you catch it super early, we may not be able to see it on x-rays yet.
Dr. Michael Kent: Yeah, this is a tough one. And so maybe down the road, we'll have more molecular tests and or could find gene signatures, but we just haven't been able to do that as of yet.
Dr. Robert Rebhun: Yeah, I mean, there are several groups that are working on blood tests to try and pick up, you know, what they call liquid biopsies that may be able to pick up circulating DNA from released from the tumor. But.
Dr. Michael Kent: It's not ready for prime time yet.
Dr. Robert Rebhun: Stay tuned. Stay tuned.
Dr. Michael Kent: All right, well, anything I should have asked you, anything I forgot to ask? Before I wrap up here, I want to just make sure if there's something we should talk about.
Dr. Robert Rebhun: No, I mean, I will say that I wanted to add with the immunotherapies that there are several studies in people and in dogs that look like, even though they're cold tumors, that there may be an immune response. And so there are certainly cases where we've seen things like, for example, when patients get an infection post-operatively, both in people and in dogs, it's been reported that they have a better outcome. So, stimulating the immune system in this tumor. And we've seen in clinical trials, I mean, we're still, we're trying immunotherapy here for metastatic tumors that are in the lungs. And we've seen some responses to immunotherapy. So, I think it gives us, while we don't, we can't tell which ones are going to respond and it's a very few, I think it gives us hope that we can make this happen.
Dr. Michael Kent: Hope and we have to figure out how to make more of them respond.
Dr. Robert Rebhun: Yeah.
Dr. Michael Kent: So, I really appreciate you coming here today to speak with me on the Vetrospective. So, thank you, Dr. Rebhun.
Dr. Robert Rebhun: Thank you.
Dr. Michael Kent: The Vetrospective, as with life, takes a village. I want to thank those who suggested I start this project and everyone who has encouraged and supported me along the way. Particularly, I want to thank our producer and director, Danae Blythe-Unti, Nancy Bei, who is our program coordinator, our sound mixer, Andy Cowett, and theme music was composed and produced by Tim Gahagan. Thank you all, and we'll see you next time.