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Tripawd Talk: Histotripsy for Osteosarcoma Dogs, a Non-Surgical Bone Tumor Treatment

Today we have exciting news about histotripsy for osteosarcoma dogs. This is futuristic therapy is a non-invasive cancer treatment being studied as a possible alternative to amputation. It might also have pain relief benefits too. Today on Tripawd Talk Radio we’re thrilled to have assistant professor and board certified surgical oncologist Dr. Joanne Tuohy, DVM, PhD, DACVS tell us all about it.

histotripsy for osteosarcoma dogs

Among other things, here’s what you’ll learn on Tripawd Talk Radio

  • What is Histotripsy for Osteosarcoma Dogs?
  • Does Histotripsy for Osteosarcoma Dogs Have Immune Upregulation Benefits, Too?
  • What Does Histotripsy do to the Body?
  • Does Removing the Primary Osteosarcoma Tumor Speed Metastasis?
  • Can Histotripsy Replace Chemotherapy for Dogs?
  • What is the Future of Histotripsy Treatment in Dogs??
  • Where to Find Histotripsy Clinical Trials for Dogs

Dr. Joanne Tuohy is a board-certified surgical oncology vet with a background in integrative cancer care and translational research. She holds a Ph.D. in comparative biomedical sciences (immunology) and is an assistant professor of surgical oncology at the Animal Cancer Care and Research Center in Roanoake at the Virginia-Maryland College of Veterinary Medicine.

Dr. Tuohy is a groundbreaking oncologist studying histotripsy for osteosarcoma dogs, those with brain tumors, and other cancer-related illness. Listen to the podcast or watch the video to to learn about the treatment, and histotripsy clinical trials at the Virginia-Maryland College of Veterinary Medicine.

What is Histotripsy for Osteosarcoma Dogs?

histotripsy ultrasound tool for dogs
This is the histotripsy ultrasound tool for dogs

Histotripsy is an exciting new tumor oblation technique that uses ultrasound technology, but does not require any heat or open surgery procedures. What makes it really exciting is that it’s non-invasive and precisely targets cancer tumors without destroying surrounding tissues. Histotripsy is being tested in humans with good results, and now histotripsy for osteosarcoma dogs is being studied by veterinary oncology research experts like Dr. Tuohy. This is exciting stuff, so tune in and learn with all of us!

Download the Tripawd Talk Radio podcast and listen to the audio file on the go!

Or watch the Tripawds YouTube Channel video interview with Dr. Tuohy.

Where To Find Clinical Trials of Histotripsy for Osteosarcoma Dogs

Histotripsy for osteosarcoma dogs and those with brain tumors is currently available in the clinical trials listed below.

Read about histotripsy for osteosarcoma dogs in deep detail! Our transcript with Dr. Tuohy is below. Thanks for tuning in.

More Information About Histotripsy in Veterinary Medicine

Study: Histotripsy Ablation of Bone Tumors: Feasibility Study in Excised Canine Osteosarcoma Tumors

Study: Immunological Effects of Histotripsy for Cancer Therapy

Study: Histotripsy: the first noninvasive, non-ionizing, non-thermal ablation technique based on ultrasound

Virginia Tech Magazine: Transdisciplinary collaborations essential to tackling cancer

Tripawd Talk Radio Transcript Follows

Tripawd Talk Radio Podcast
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Histotripsy For Canine Appendicular Osteosarcoma

TRIPAWDS: Can you give us a little bit of background about the current state of canine osteosarcoma treatments, both for pets and people? 

I know that there hasn’t been a lot of breakthroughs lately other than immunotherapy. But if you could tell us how close we’re getting to a treatment that actually might be able to stop it, that would be great. I’d love to hear all about it.

How Canine Bone Cancer Research Led to Histotripsy for Osteosarcoma Dogs

DR. TUOHY: Unfortunately, there haven’t been major developments in osteosarcoma treatments that extended survival in a significant way for a long time. Of course, as you mentioned, there are things on the horizon, say for dogs. So in immunotherapies, I think that’s very exciting. And for either for a long time now, for both people and dogs, the traditional treatments have been twofold.

The approaches are to [A] resect the primary tumor, and then [B] having to slow down metastatic disease, or eradicate it.

Unfortunately, as with most solid tumors in both our vet patients and in humans, metastatic cancer is often unfortunately, the cause of death. That’s a very large area of research. And that’s an obstacle that if we can overcome, would provide great benefits for extending survival. That’s what’s the immunotherapeutics, a lot of them we are targeting is to be able to control metastatic disease.

Controlling Metastatic Disease in Dogs with Osteosarcoma

In osteosarcoma, we’ve got a unique situation, especially in our canine patients, where a lot of these dogs that suffer from the disease are large breed dogs and giant breed dogs. Historically, we have had limb salvage surgery options that are available for our canine patients. But they are limited in, first of all, the location where the tumor is. So they’re only amenable for patients usually with tumors in the distal radius.

If a patient has got a tumor elsewhere, then limb salvage option, surgical limb salvage options don’t tend to be possible. Or, unless there is some very individual unique custom-made implants that get designed, but not in general, not a standard of care.
In people, limb salvage is a very common surgery and so it is often undertaken. But in some human patients as well, amputation is still necessitated. Especially in areas of the world where perhaps amputation may be more of a realistic option for patients versus limb salvage surgeries.

Improving Survival Time for All Dogs with Bone Cancer

For our canine patients who are large and giant breed dogs, they, even though they are still very amenable to removal of their tumor in canines, specifically by limb amputation, it would be lovely if we can get to a point where we have limb salvage options that are more generally applicable to our dogs who are suffering from this cancer.

There are a subset of dogs with very severe neurologic orthopedic disease, who may not be appropriate candidates for limb amputation. Those certainly would benefit from a good option as well. I think all of these things combined really speak for the need for advances in therapy for osteosarcoma. Not only for the primary tumor, but also for metastatic disease.

That’s how we can improve the treatment options we have for our patients, but also extend the survival.

Can Histotripsy for Osteosarcoma Dogs Help Them Beat the Odds?

TRIPAWDS: I know that you’re working on a treatment called, histotripsy, and I would love for you to give us some background on it because I had never heard of it before. You have this clinical trial going on, so I’d love to spread the word and be able to tell more people about it.

DR. TUOHY: Histotripsy is a very, very new technique. It is a technique that is what we call a tumor ablation technique. And it uses these highly specialized focus ultrasound waves to essentially disintegrate the tumor cells. So it’s a mechanical disintegration.

There are ablative techniques out there that have been explored for a long time for various cancers. And a lot of these techniques, so far, have been dependent on heat ablation.

A Non-Invasive Way to Treat Certain Cancer Tumors

Killing tumor cells with heat, versus histotripsy is one of the kind of the newer generation of tumor ablation techniques that do not require heat to kill tumor cells, which has its advantages. Because the heat can sometimes potentially also be a limiting factor in that we have to preserve some critical structures that shouldn’t be destroyed by heat in the region.

The unique thing about histotripsy is that [A] it doesn’t require heat, and [B] it also is a noninvasive way to treat these tumors. Just like when you and I go in for an ultrasound, and we have an ultrasound probe that’s placed on us. In a similar fashion, histotripsy relies on delivery of these ultrasound waves with an ultrasound probe. Except this ultrasound probe is highly specialized and very customized to deliver these ultrasound waves that create these, we call them “little bubble clouds” in the tissue.

It’s because of the mechanics of having these ultrasound waves, these bubble clouds get, these little bubbles get produced and then they coalesce into a big bubble cloud. Ultimately, they disintegrate into themselves. They mechanically destroy the tissue.

TRIPAWDS: This is able to target the tumor and do that sort of action without damaging surrounding bone?

How the University of Michigan Became Histotripsy Pioneers

DR. TUOHY: Yeah. So you know, again, it’s very new and we, that’s why we’re investigating it. It actually, the technology started at the University of Michigan, I believe. To demonstrate the precision of how they can target lesions with histotripsy, there is a short little video that was released by the investigators to demonstrate that by showing how the histotripsy could draw out an M for Michigan and be very precise.

TRIPAWDS: I want to be able to see that! 

DR. TUOHY: Yeah, to create an area of ablation that in the form of a letter M. So, that’s how precise this technology can be. That’s why it’s exciting because we potentially could really target only treating the tumor, much like very highly specialized ablation techniques as well. For example, radiation treatment has advanced to that level as well, where they can be very precise. Our hope is to be able to develop histotripsy to that point where it’s precisely kills these tumor cells.

Also, we are starting studies to investigate how structurally affected the bone is by the ablation because there’s always the risk of fracture occurring after we ablate a tumor. Say, even with radiation, when we treat, say, some of these osteosarcomas can be treated with radiation. And if they get treated with radiation therapy, there can be a risk of fracture occurring afterwards because of the decrease in the integrity of the bone in that region.

Does Histotripsy for Osteosarcoma Dogs Have Immune Upregulation Benefits, Too?

We’ve got several avenues of investigation into this very new technique, with the hopes of being able to use it. Not only to have a noninvasive way to treat the primary tumor in osteosarcoma, but also with immune upregulation with the treatment as well.
There has been a strong suggestion that the histotripsy treatment itself can potentially help to activate the immune system such that it can recognize the tumor, and also act as a form of immunotherapeutic, and so that’s been very exciting.

In Spain, currently, there– it’s, I believe it’s the first of its kind, histotripsy clinical trial and people. And that is to treat liver cancers in people using histotripsy. They’ve got some very promising preliminary results, not only for ablating the tumor itself in the liver, but also in how it affects other liver tumors in the same person that got the ablation, but the other tumors weren’t ablated.

In one of these patients, one of the tumors had started to regress. But these are very early results, you know, but that’s where the premise that this potentially could be an immunotherapeutic, would be really exciting. Because it can then can target both avenues of treatment, treating the primary tumor and treating metastatic disease.

How Does Histotripsy for Osteosarcoma Dogs Affect the Body?

TRIPAWDS: Where do the cancer cells go when they’re ablated?

DR. TUOHY: They’re no longer structurally intact. So it’s cellular debris at that point. And so, they remain in the site and then the body’s own mechanisms were eventually kind of “clean up that area.”

TRIPAWDS: Just absorb them and circulate them, and ablate them? That is pretty cool! So the ultrasound, what does the device look like? Does it just lay on a skin like a normal ultrasound machine? There’s no surgery and it’s just an exterior device?

DR. TUOHY: Yes, exactly. So you’re right. It’s like a probe like we… you see the ultrasound probe on our skin. This is a little bit different because it is, because of the way it’s a very specialized probe in order to allow the ultrasound waves. The probe itself can’t quite sit on the skin directly. In order to allow the ultrasound waves to travel to the skin, we actually have this water that acts as an interface for the– where there’s this highly specialized ultrasound probe. It delivers all its ultrasound waves through the water.

The water actually has been degassed, so the gas, the air has been taken out of it. Because ultrasound waves don’t travel well through air. So, the water is degassed, the ultrasound waves travel through the water, and the water is what sits right next to the skin.

That allows the ultrasound waves to travel through the water and then travel, and then hit the skin and go to the tumor. Because if you just put it in the air, ultrasound waves just don’t travel well through air.

How Else Can Histotripsy for Osteosarcoma Dogs Help Treat the Cancer?

TRIPAWDS: For tumors that have really integrated with the bone and degraded some of that bone, could this technology be used in conjunction with the new bone cements that are out there, and/or traditional plating?

DR. TUOHY: That’s a great question. So, I think what you’re referring to is cementoplasty, is that what you’re talking about?

TRIPAWDS: Yes. Yes.

DR. TUOHY: That is definitely an avenue of investigation that I foresee as a potential avenue. As we get further along in this whole evaluation of histotripsy is, first, at this point, at this stage of our evaluations, we are evaluating just some, answering some basic questions.

What does the histotripsy do to the osteosarcoma tumor cells? What does it do to the immune system?

As we are advancing more in our investigations, we will be starting some biomechanical studies to investigate what it does to affect the integrity of the bone that gets ablated. Then eventually, some kinds of bone replacement techniques or the space replacement techniques. One of these would be cementoplasty, where there’s bone cement being added to the area to help it be more structurally sound.

You mentioned implants, so that could be on the horizon typically. It may be an area that is interesting to investigate. There have been some studies in the past, exploring, supporting these limbs that have been radiated, you know, the legs with osteosarcoma.

Radiation was performed that killed the osteosarcoma cells but then rendered the limb quite weak. There have been clinicians who have looked at prophylactically placing implants. But that has been challenging insofar as there appears to be more complications. That is currently not the standard of care. We don’t place implants after we radiate a site typically. Of course, there are always exceptions in medicine, but in general, that’s not something we advocate for, at least, I wouldn’t advocate for. But perhaps, one never knows.

You know, keeping an open mind in research and trying to forge new ways, I think that’s always key.

TRIPAWDS: That’s good to know. Listeners can check the show notes for a link to our recent episode with BIOCERA-VET to learn more about cementoplasty.

What is the Future of Histotripsy Treatment in Dogs?

TRIPAWDS: When a dog is receiving the (histotripsy) treatment, do they get any other treatments concurrently, like a bisphosphonate or anything like that?

DR. TUOHY: Yes. So if histotripsy does become, as I hoped, to be a standard of care therapy in the future, then most certainly, I think that adjuvant treatments like bisphosphonates can be used at the same time.

Of course, everything has to be evaluated first. Because any new treatment that comes out, we have to make sure there are no adverse interactions and things like that. But I definitely foresee it.

I think cancer, in general, I would never say never. You know, that’s usually, it doesn’t hold true, but I think that cancer is in general a disease that requires multimodal treatment. I don’t think that there can foreseeably, at least right now, be a one silver bullet that, you know, we’re going to do this to treat the cancer. And that’s the only treatment.

I think that there are always going to be multiple adjunctive therapies that can be used at the same time, and in cancer. That scenario where perhaps histotripsy can be a limb salvage option, certainly, bisphosphonates can be considered in that setting as well.

Dr. Tuohy and Virginia Tech Team Up to Study Histotripsy Treatment in Dogs 

TRIPAWDS: I’m curious if you could tell me how you got interested in this therapy?

DR. TUOHY: As I’ve gone through my training and my clinical time, I’ve always been interested in ways to ablate tumors. And hoping for a way to be able to spare patients from needing to have surgeries.

Prior to coming to Virginia Tech, I had been interested in other forms of ablative techniques. And then when I came to Virginia Tech, I was very fortunate to have established a great collaboration with bioengineering colleagues, to explore some very novel ablation techniques, such as histotripsy.

What captures my interest with histotripsy is that it is noninvasive, and it’s also nonthermal, and it’s not radiation.
As we know, radiation can have side effects, just like surgery can have side effects. Of course, will histotripsy have side effects? We don’t know yet. It could very well.

But you know, it’s very promising. All of those features of histotripsy really captured my attention, and also the fact that it could potentially stimulate the immune system.

Can Histotripsy Replace Chemotherapy for Dogs?

TRIPAWDS: With this technique, would you hope to replace chemotherapy? Or would it be used in conjunction with it?

DR. TUOHY: Yeah. So I think that, in my mind, I think that there, well, there’s always going to be room for multiple therapies. Even though, say, if we’re successful at stimulating the immune system, and having histotripsy act as an immunotherapeutic, I think that… I’m not sure if just a sole therapy would be sufficient.

I think that being able to target a cancer from various aspects, probably would be, at least in the near future, the way that we continue to treat these cancers.

I probably wouldn’t guess that it would totally replace chemotherapy. But that perhaps there can be synergistic effects with chemotherapy, such that maybe we don’t have to give us much, potentially. You know, these are all guesses on my part, but, and hopes and dreams. But yes, any way to reduce treatment in one area, I think is beneficial, in general, to patients.

Just like multimodal pain therapy, where if we use one pain medication, and we, and it has to be given in these doses, X doses, and it’s got its side effects versus if we use multimodal analgesia, multiple different drugs that target different parts of the pain pathway, and it can result in more effective pain management. And also, reduction in the doses of each drug that gets used.

Who Designed the Veterinary Histotripsy Treatment Tools?

TRIPAWDS: Well, we know all about multimodal pain management in this community. So you’re speaking our audiences’ language. You mentioned your colleagues at the Department of Biomedical Engineering, did they actually create and design the device that you’re using as the probe for this technique?

DR. TUOHY: Yeah, our biomedical engineers, they’re really wonderful group of people. My primary collaborator for histotripsy, my faculty collaborator, he actually came from Michigan and had trained at Michigan, and was one of the, I think the people involved very early on with development of histotripsy.

And so, here, he got his lab, and so the transducer that gets used for our veterinary studies. For example, these are transducers often that are custom designed in his lab, and manufactured in that sense, so that they’re kind of customized for each application.

TRIPAWDS: Oh, that’s really cool. I just love that he, your colleagues in that department went across the country to Virginia. So now, I mean, there can be another option for people if they don’t live next to Michigan or in Michigan. You know, it’s nice to know that the treatment is going around, so to speak.

Where to Find Histotripsy Clinical Trials for Dogs

DR. TUOHY: Oh, yeah. It certainly is. Yes, it is relatively limited at this time with regards to the availability, because it’s still in its developmental stages. It’s really only available, I believe, through clinical trial options. I’m very fortunate to be supported by a number of funding agencies to carry out these clinical trials, and so be able to have these clinical trials be available for our patients as well, so.

TRIPAWDS: So we’re almost out of time. I would love for you to give our listeners and viewers the scoop on the clinical trial. How can they get involved?

DR. TUOHY: Yeah, thank you. Currently, we have a clinical trial for dogs with suspected osteosarcoma. And this particular trial is for owners who have already elected for a limb amputation for their dog. The purposes of these early studies that we’ve been doing are to ablate a portion of the tumor. Then assess our area of ablation to see how accurate we’ve been, and to make sure that the histotripsy does indeed destroy the tumor cells.

Then, also, we draw blood samples from our clinical trial dogs over time to monitor their immune response as well. We’ve got that trial currently open, and it is for dogs without any evidence of metastatic disease at the time of diagnosis. This is at the minimum based on three-view chest radiographs.

Coming Soon: Clinical Trial for Histotripsy as Osteosarcoma Pain Management

Then we’ve got another clinical trial that actually will be opening soon. It’s not quite open yet. But it will be a clinical trial that is a very, very, very early pilot study for owners who have elected to not have any standard of care therapy for their dogs. So they’ve chosen not to do any amputation, no radiation, and instead they’re just going to keep their dog at home on palliative care.

And so for those, for that subset of owners, this clinical trial may be of interest to them where we are going to ablate the tumor with histotripsy. There will not be an amputation afterwards. So with the hope of being able to reduce some of the pain through histotripsy, so that was something I didn’t mention before. But that is, of course, an area that’s very important for any limbs salvage option is that it also reduces the pain or removes the pain.

There is a focus ultrasound technique that is a thermal ultrasound technique. It’s called HIFU. And that actually is used in people for pain relief for people with bone tumors. And so, I’m hopeful that histotripsy can also offer some pain relief in these patients. And so there will be a clinical trial opening for this subset of dogs to receive histotripsy. We assess their quality of life after and their pain levels.

Does Removing the Primary Osteosarcoma Tumor Speed Metastasis?

TRIPAWDS: We’ll have links to the clinical trials and keep people updated about the new one in time. But this, really quick, this talk of ablation, tumor ablation makes me think of one other concern. We interviewed an oncologist years ago who said removal, he had concerns about removal of the primary tumor spreading, helping spread metastasis faster. So I’m wondering your thoughts on that, and if there’s been any further study there?

DR. TUOHY: There certainly has been this phenomenon that’s being reported that potentially, removal of a primary tumor could actually, as you say, speed up the metastasis. I think it’s definitely an area that we do not understand very well. We need a lot more data to establish what the effects of that really are, in order to be able to make an educated decision. You know, is removing the primary tumor, something that, is that a mindset, we want to readjust?

But for the moment, for our therapy, and especially for tumor like osteosarcoma, the pain in and of itself of the bone tumor, essentially, to me, as a clinician, necessitates removal of that primary tumor. Because leaving the primary tumor in place without any, really any effective way to ameliorate that pain with oral pain medications alone, I think that is not something that I would feel is medically justified, in my book anyway to… in the hopes that maybe it won’t promote the spread.

TRIPAWDS: I think we both agree with that, the effects of pain mediation kind of outweigh the spreading of that disease any quicker.

Who is Eligible for VA Tech Histotripsy Clinical Trials?

TRIPAWDS: One last question about the clinical trials. Do participants have to live in Virginia or a surrounding state?

DR. TUOHY: No, they don’t. We’ve had had patients come from Pennsylvania, New York, Boston. And I even had an owner call me from California, she was totally prepared to bring her dog out here. So no, we don’t, for the current clinical trial that we have, we don’t.
The only follow up time points that we have for the current trial is blood collection.

As long as they have a clinic near them, who’s willing to work with us on collecting the blood and sending it to us, and of course, I pay for all the shipping costs, et cetera, then we do not require for dogs to live in the area so they can come back to us.

TRIPAWDS: But it does sound like the treatment is done at your facility, so they would need to be, to travel where the equipment is.

DR. TUOHY: Yes. Yes.

TRIPAWDS: How many treatments are you doing in the trial? Is it just one and done, and study?

DR. TUOHY: Just one. It’s one treatment before the amputation. They do have to have their amputation with us, so that we can have the tumor afterwards.

TRIPAWDS: I see. OK.

DR. TUOHY: Yes, you’re absolutely correct. I just, in my head, assume that piece of knowledge. They do have to– the patients do have to visit us once for the treatment and then the limb amputation, and then they can go home. For subsequent follow ups, where we collect the blood samples, they can get their blood sample sent to us.

Thank you Dr. Tuohy and Virginia-Maryland College of Veterinary Medicine!

TRIPAWDS: Wonderful. We wish you the best of luck, because the hopes are that this device proves positive and many of them get produced and distributed, and they can eventually enter into the stream of treatments available for osteosarcoma.

TRIPAWDS: This is such an exciting way for people to get in on the ground floor of this treatment and really make a difference in the findings. So, thank you so much for being here today and explaining all this to us. This is fascinating.

DR. TUOHY: Thank you. Thank you for having me. I really appreciate this opportunity. And I really enjoyed meeting both of you. I’ve really loved your website and I think you’re doing great things.

TRIPAWDS: Thank you. That means so much to us coming from doctors like you. So, please keep up the good work and we will keep listeners informed.

DR. TUOHY: Thank you.

TRIPAWDS: Wow, many thanks to Dr. TUOHY and her colleagues for the fascinating work they’re doing. Check the show notes for details about the clinical trials or learn more at tripawds.com.

[End of transcript]

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