Betsy Post 0:27
Welcome everyone to this evening’s DocTalk. We’re really excited to have Dr. Kevin Burns with us. A lot of you in the LIVER LOVERS group requested him, and you talked about how much you respect his work in histotripsy. So I reached out to him and asked him if he could present to us on this DocTalk. And he said, “Sure”. So we feel very fortunate to have him with us this evening to talk to us about histotripsy. I’m going to go over just a little bit about how this is going to work in just a second. But I also wanted Dr. Burns to see a few anonymous comments about him. These are just three that I pulled just so you could see what your patients are saying about you. So I hope that the positive feedback is something that is encouraging to you. You’re very well respected and we’re really excited to have you here, just so everyone knows. If you’ve not attended a DocTalk with me before, or if you’ve forgotten, I’ll ask politely that you stay muted throughout the presentation and put questions for Dr. Burns in the chat. Use the chat feature to ask questions, and then at the end, we will answer questions as much as we have time for. I will go over those questions at the end with him. So without further ado, I will turn it over to you. I will stop sharing and let you share. And again, we really thank you so much for being here with us tonight. We’re excited to learn from you.

Dr. Kevin Burns 1:51
Thank you for having me. I’m Dr. Kevin Burns. Thank you for having me. This will just be like an informational thing. I’m not going to show any cases necessarily, of how this is used, but kind of just what is the technology; How does this compare to any other sort of technology that’s out there; And I think one of the important things to know is, obviously, this is a new procedure. There are a lot of things we’re going to be learning over time. And, we learned something from every case. There’s probably been almost 2000 procedures now performed worldwide. So, people are learning things as we go. We had our first international historipsy summit, it was actually about six weeks ago, that was held in Minnesota. We had doctors from all over the US, and then as well, some of the international sites. So there’s physicians from Hong Kong, some from Europe, that were all there, and we were discussing how we all do these cases differently, and how we can learn from each other. So I think there’s a lot to learn, and this procedure is going to get better and better over time, as you can see here on this slide. So this on the right, is the Edison machine. So this is the, basically, the machine that currently delivers histotripsy. So histotripsy is basically a mechanism, and this company, HistoSonics, makes this machine called Edison. I will disclose I am a consultant for this company, but in this regard, I’m speaking as myself, and I don’t represent the company during this talk, so anything I say will just be my personal opinion. So they’re the only ones that commercially make a platform for this. On the other side of the screen here is what we call the ‘bubble cloud’. This is what is happening inside, just a pictorial, and so histotripsy creates this bubble cloud which can go in and dissolve tissue. So hisotripsy, so it’s a novel mechanism of action. That means it’s a new way to destroy tissue compared to anything we had before, and it’s a mechanical disruption.

Dr. Kevin Burns 4:13
As you can see in this depiction over on the right, this is a kind of a phantom, and histotripsy is happening. And you see it really just completely takes out the center of this phantom here. And you can see how precise the margins are. It’s very, very, very very precise, meaning you can get right up to a critical structure without entering it. And so this causes instant tissue liquefaction and cell death. And it’s very precise and controlled. And I think important too is you can see that there’s no damage in the tissue, around this lesion. This is what a treatment head would look like. And so this would be positioned inside of the water bath on you, and we’d use this to localize the tumor. There’s an ultrasound probe built in, so we can use live imaging to see and then just think about this like a satellite dish and setting all these beams, and it’s only where they meet at this one focal point. Think about it like the size of a grain of rice, where this histotripsy happens, and if there’s not enough power, histotripsy doesn’t happen. Also importantly, as you can see, that histotripsy doesn’t happen on any of the way into the tissue. And so that means that we can treat through structures and it doesn’t damage them. So we could treat through the gallbladder, through the ribs, potentially through the stomach, but as long as the lesion is safe, then we’re able to treat it.

Dr. Kevin Burns 1:51
This is just another depiction. It’s what would be happening on a microscopic level. And this is that bubble cloud. Basically the histotripsy creates this intense negative pressure, it rapidly expands and contracts all the air that is present in the cells, and it uses this to instantly destroy the cell. So as you’ll note, too, histotripsy either is on or off. There’s no gradient. So when we talk about other therapies like microwave ablation, cryoablation, other therapies like that, there’s different levels of ablation, so the center of the lesion will generally get to a hotter temperature or colder temperature, depending on the device. And then as you spread out, there’ll be areas that may not be completely dead, but when you look with histotripsy, it’s all histotripsy or it’s not and so that’s another differentiating factor as well. There’s going to be some videos that we’re going to play here. So this is a demonstration video. I’ll let this play through, and this will simulate what would happen during a procedure if you were there.

Dr. Kevin Burns 1:51
This is the machine that the physician would be controlling, and this is how the procedure room setup is. Generally, this is going to be done in an operating type of room. It’s the procedure, I think, importantly, it’s not sterile. So there’s no incisions. Nothing breaks your skin anywhere. We are doing these under anesthesia in almost all situations now, and so that’s why, most commonly it’s going to be done in a procedure room. But I think as we learn more and more, I think this is going to move to the outpatient setting, where we can do this in a surgery center so we can get you in and out faster because of this procedure, it’s non invasive. So this would be to set up. There’s an ultrasound here that we can use to ultrasound you as well as provide the signal of the ultrasound. This is the water bath that sits on you. This is put on after you’re asleep, and the treatment head goes inside of this water. So if you think about ultrasound waves, if you ever had an ultrasound, they put that ultrasound gel on that’s to get rid of any air that’s between the ultrasound probe and your skin, because the sound waves don’t really transmit through air. And so this water bath will create a consistent water from the treatment head all the way to your skin. And so the treatment can successfully be delivered. This water bath can be positioned in different ways. In this example, the patient is lying face up, but we can put people on their side to move things around, or get to tumors that are in other locations. We’ve got many liters of water in here. So this is actually quite heavy, and so it takes a couple people to get this all positioned for you. – I’ll continue this video. – and so this is, again, what the treatment head would look like. And so this was going to simulate a procedure of treating one tumor inside of a patient. Here’s the treatment head inside of the water bath and here’s the simulated ultrasound waves coming down. And then at the center, this is the targeted tumor. And so the doctor can basically decide how big in all of the dimensions we wanted to do this. This is showing some fusion imaging. So in certain situations, we can take your pre-existing CT or MRI, and we can try to fuse it with the ultrasound, so that can help us find locations that maybe are hard to see or we’re not confident we’re in the correct location. So this fusion can help us localize more difficult to reach tumors and then after we program everything out, we basically set all the voltages. That just means, how much power does it take to kill your tumor? And that’s personal to every patient. Then we start this process. The robotic arm will move the treatment head through our pre program path in order to deliver that histotripsy throughout the tumor, including a margin. Next, we’re going to see what this would look like internally. So again, this is a simulation of what this will look like. This bubble cloud is going to go through, and it’s really liquefying everything in the treatment field.

Dr. Kevin Burns 9:21
And so if you had one tumor that was small that we are going after, this procedure can be fairly quick. I would say it’s pretty common that we’re going to be treating multiple tumors, and multiple tumors can be treated in one session. So that’s just kind of an overall of what the procedure would look like while you’re asleep, if this was something you were going to go through. Again, this was another demonstration here. I’ll pause this here. This is just more about how this works. So this is the treatment head again, and in the bottom corner, you can see there’s a number turning up. That’s the physician dialing the voltage up. Once you hit the critical voltage for your tissue and your body, histotripsy will happen. And then you could keep turning it up and nothing else happens. So we try to calibrate that for every patient to use the least amount of power in order to enable histotripsy to happen. And then if we look at what happens here, this would be what the physician would be doing. This is a simulation, again, of what would be happening. I think it’s helpful to actually see what would be happening inside, to visualize this. This is a piece of animal liver that’s sitting in this phantom, and this is very sped up, but this is what would be happening to the tissue internally. And I think it’s also important to know that there’s no damage anywhere else in the structure. It’s only in this treatment volume and where the histotripsy is happening. And then we’ll see that we’re actually going to cut this open, and you can see that this liver tissue is actually turned into a liquid, so basically, completely liquefied. So inside of your body, your body’s natural repair processes and lymphatic system would go through and reabsorb this and the cavity would decrease over time.

Dr. Kevin Burns 11:26
Now, if you did histotripsy, and then you immediately removed a tumor, and then you gave it to a pathologist, they would be able to do the staining. This would be similar to any biopsy you would have, and they would see that the histotripsy area is this acellular lysate, meaning that on the outside, we can see all these cells. They’re perfectly preserved, not damaged at all. So, very thin margin here, but you can see that it’s completely killed and then completely alive. So you can get very close to critical structures without damaging them. And you can also preserve more liver parenchyma than other therapies, potentially. And so this is that acellular lysate. This is something where the pathologist can’t actually tell what tissue this is from, and that means this is basically completely destroyed. Another important feature of histotripsy is kind of some tissue selectivity. So if the type of tissue has a lot of collagen in it, it’ll be resistant to the damage from histotripsy. In the liver, that would be the bile ducts, the portal vein, the hepatic arteries. You can see these are examples inside of animals where you can see histotripsy was performed, and then the liquid was washed out. And you can see that these vessels still run completely through the treatment zone. And in this video here, you can see that they’re actually washing everything out. And you can see the stroma and the structure of the liver remains, but all of the tissue is completely destroyed. This allows us to treat potentially in some more dangerous areas, in the hilum or the center of the liver, maybe a tumor that’s right on a vein or right on a bile duct. And we can maybe do this a little bit more safety than other therapies could, compared to microwave ablation or radiation.

Dr. Kevin Burns 12:50
This would be an example of a preserved vessel. This patient was treated with histotripsy and then they had an MRI. And this big black cavity is the histotripsy zone, and then this is a portal vein branch running through. You can see that this vessel is still open, even though it was completely inside of the treatment zone. If this patient had a microwave ablation here, likely this whole area would get scarred down, or potentially there could be a recurrence, because the vein would keep flowing in blood, and it wouldn’t allow enough temperature here to destroy the tumor right along the vein. And so histotripsy gives us a way to instantaneously and completely destroy a tumor so it’s a for a lesion that’s an appropriate size this is a one-time procedure to go in to try to kill it. We can potentially alter the microenvironment and immune system, we’ll touch on this in a moment. In certain patients, we can reduce the disease burden, and we can improve patient’s quality of life. If you have a tumor, let’s say you have many tumors, and we know that the chemotherapy is not working anymore, if you have a lot of pain, we’ve been able to treat tumors in patient that have pain, and that’s reduced their pain, or maybe it’s pressing on a bile duct, and you need to have a drain placed. So there can be ways to use histotripsy, even if we’re not curing the disease, in order to make you have a better quality of life with very minimal side effects related to the procedure.

Dr. Kevin Burns 14:16
There’s a lot of literature, again, this is all in animals on “immune modulation”. That means that doing histotripsy is doing something to alter the immunologic response to the tumor. This does not happen in most patients. This happens in some patients but obviously we study things in animals, so there’s many animal models kind of showing that this does happen. And so I think with all the data we’re collecting now, especially in the BOOMBOX study and other studies, we’re trying to learn who is benefiting from this the most, which tumor types, which mutations, and which therapies may augment this because I think this will be an important part of histotripsy’s future. So, this would just be an example of immune infiltration. So, if you look at a control animal versus a tumor that was treated with histotripsy, you can see that there’s a lot more immune cell infiltration into this non-targeted tumor. Looking at other modalities, so external beam radiation, radio frequency, those weren’t really much different than controls, but a mouse model treated with histotripsy had a much higher percentage of tumor infiltrating lymphocytes, and that’s one of this markers of having an immune response. And then looking at the tertiary lymphoid structures, or tumor infiltrating cells in other models, you can see that again, more papers show that in non-treated tumors, there’s some immune cell infiltration which does not exist in the controls. And again, a lot of this data is available if it’s something that you want to do further research on. And then in humans, hopefully we have some more answers for this in the next coming years.

Dr. Kevin Burns 15:54
So again, the procedure is non-invasive, and so that’s one of the hallmarks here. We are generally putting everyone under general anesthesia, so it’s non-invasive, but we’re still getting put to sleep so there are some risks related to anesthesia. I would say most patients have mild pain. There are some patients who have more severe pain, and that’s going to be based on the tumor location, and generally, your physician will be able to tell you that ahead of time. So if I’m going to treat something on the edge of the liver or right under one of the ribs, I’m going to let the patient know ahead of time that that that lesion is probably likely going to hurt afterwards, just so when you wake up, you don’t think something’s wrong because you’re having pain. So I would say, “You know what? The maximum pain can go up to a five or six, usually that’s right after the procedure, and then it can die down after that”. There are definitely some people who have no pain. They walk out of the procedure like nothing happened. It is again, a single session procedure for an appropriate lead, and that means one that we can completely cover at one time. Again, here’s just another setup of what the room would look like if you were there.

Dr. Kevin Burns 16:52
These are just some general things, in case you want to come back and reference a video. So, just some things about the procedure. Oftentimes, we will give you some dietary restrictions prior that helps reduce the amount of gas that’s in the abdomen. As you can imagine, you can have gas in the colon and the small bowel, and if that moves around or gets near the liver, that may eliminate a window in order to see some of the tumor. So oftentimes, we will do a bowel preparation, and you usually will be provided instructions on that by your physician that’s performing the procedure. A closer look up here, so you can see that this is a simulated patient here. There is some kind of oil on the patient, you actually get castor oil rubbed on your skin, and that helps, again, create this contact between this membrane here. This is a very pliable surface, we fill this with water, and this conforms to your body well, and then the treatment sits right in here. So this is really all that contacts you, and this is a disposable part, it gets changed out with each patient here. So this would be a simulation of what the physician would be seeing during the procedure. So again, this is in a phantom, but during the therapy we can monitor this live. Once we turn it on, we can monitor live if something changes, if the breathing changes, or the tumor moves in location, we’ll see that live. We can pause the therapy. We can replan and move things out. We’re monitoring this live here. And so this little crosshairs here is the histotripsy happening. You can see on ultrasound, we can already see that this tumor area is much more dark than the surrounding area. And so that we can see that we gave histotripsy into that area. So this is just an overview of what the console looks like when your physician is performing the procedure.

Dr. Kevin Burns 18:30
After the procedure, you can definitely have some pain. Most patients, at least in my practice, are discharged the same day, a couple hours after the procedure. Some patients may stay overnight for certain reasons, but I would say, 95% of patients will go home the same day. And there’s definitely normal things that happen after this. The following day, it’s fairly common that you would have a fever, a flu-like illness. If you’ve had other therapies like microwave ablation or an embolization, they can be very similar to that. And you can also have some fatigue, and that can last for several days. Looking at some of the data that helped get this procedure accepted, and the first was the THERESA trial. This was conducted in Barcelona, Spain, and this was a safety study, to make sure this works and make sure it’s safe. And so just an example of a tumor that would have been treated in there. This is an MRI showing this white spot here. This is a tumor that they did histotripsy on it, one week afterwards. You can see it’s larger, that’s very important to note, if you have histotripsy or any therapy, and then you get an image a week two weeks later, most likely it’ll be much larger than it was, because oftentimes we treat a tumor, plus a margin, that means we’re treating the tumor plus some of the normal liver around it to make sure there’s no cell that’s trying to escape already, to make sure we encompass all of that. And then in this patient, for example, once you get out to eight weeks, you can see that it really has a dramatic size decrease compared to that one month imaging.

Dr. Kevin Burns 20:02
Next was the HOPE4LIVER trial. Up. So again, this was basically a technical success and safety trial, and this had a total of 44 subjects that were both in the in the EU and in the US, and looking at the breakdown of tumors that were treated. Most of them were not primary liver cancer so the most common would be metastasis from the colon, rectum, breast and pancreas, and then the others were hepatocellular carcinoma. So really, in all comers to compare this, and this is really a safety trial and efficacy and the one year data was just published from this, and this showed that the success rate was about 95%, meaning that in 95% of the patients, the tumor was correctly targeted and treated. And this is based on the immediate imaging, and the safety showed that there was only about 7% of patients who had any sort of complication- related – and one patient had pain. There was one patient of note, that did have liver failure after this procedure. So this is just something to note, and your doctor would likely discuss this with you if they thought you were at risk for this. This patient had greater than 20 tumors, and this patient unfortunately passed away about one month after the procedure, likely due to just the progression of the remaining tumors in the liver.

Dr. Kevin Burns 9:21
And so again, looking at some example images. This top image would be a small tumor here that was treated. So you can see on the first day afterwards, tumor is much larger, but you see it’s kind of black now, so it doesn’t take up any of the contrast dye. And then at one month, you see it’s getting smaller. And then by six months, one year and two years, you really see that you can barely tell anything was there. So that’s another powerful attribute of histotripsy, is that we get reabsorption of the cavity, so over time, they shrink down a lot. If we were to treat this with a microwave ablation, you would just see a big area of scar tissue, of all dead tissue around it, and that would pretty much just stay the same size forever. Sometimes that can be similar with radiation so it can be helpful with histotripsy that this really gets reabsorbed. And so it can be helpful for follow up because if we see that it’s getting smaller, and then maybe you’re out two, three years, it starts growing again, then we can be concerned that there could be a recurrence, and we may need to address that. Looking at the one year data, they showed that there was basically a 90% local tumor control at one year. So in 90% of the tumors that were treated at one year, there was no evidence of recurrence. So this is pretty comparable to other local therapies, and this is considered a very good effect. And again, in these, 96% of these had complete tumor coverage immediately post procedure. Again, very overall safe procedure.

Dr. Kevin Burns 22:41
And then if you look at the survival rates here, so about 73% of the patients with primary liver cancer were still alive at one year, which is very favorable with current data. And then in liver metastatic disease, about half the patients at one year were still alive. Again, this is a very sick patient population that was in this trial. These patients had to progress through all lines of systemic therapy, and so these are much sicker patients than somebody who’s still able to get chemotherapy or still has other options. We also published as part of this, this study of some of the first nine centers that came online. We looked at the first 230 cases treated clinically. So this means not part of a trial, this is a real-world user. So we participated, and you can see the other sites that participated here. We, overall, showed that this was a very safe procedure. That was the the point of this. We’re doing something new. We need to make sure that it’s safe. And so this looked at a total of 230 patients again, across these nine centers. Looking at these, almost half were colorectal liver metastasis. So that’s a very common patient population that we’re treating. And then you look at these, 95% of these patients had no complications. That means 5% of patients had some minor complications and there was one major complication in this as well, again, that was a patient who, unfortunately did pass away from progressive disease elsewhere, outside of the treatment zone, but overall, a very safe procedure. And so whenever you have a new procedure, we need to prove that it works, and so this is the hardest part.

Dr. Kevin Burns 9:21
The company is sponsoring a study, and you may be asked to participate in some studies. When you get your procedure done, there are a lot of individual doctors looking at very specific things, and there’s a lot, I think, that we’re going to learn over the next coming year. One of the ones is called BOOMBOX. This is a study that we’re just going to collate the results from multiple sites in order to get a large number of patients with each kind of tumor type and see how patients are progressing over time. So when we talk about liver-directed therapies, there are a lot of options for colorectal liver metastasis. One of them is surgery, which I didn’t put on this slide, but surgery is definitely an option if you have all your disease confined to one lobe of the liver, potentially, you could have that lobe removed. You can even get liver transplants now. You can have hepatic arterial infusion pumps. And so those are some of the things I won’t mention here, because I’m just talking about some targeted therapy. So we have histotripsy. We have Y-90, which I’m sure you guys are familiar with as well. We have microwave ablation and SBRT. We can also mention chemoembolization on here as well. And so if you kind of compare the mechanism of these – so histotripsy is non-invasive, and it’s ultrasound based, and it mechanically lyses the tissue. Y-90 uses radioactive beads that emit this very strong radiation in order to kill the tumor with radiation, microwave ablation uses intense heat in order to coagulate the tissue and kill it, and then SBRT, or external mean radiation, again, uses highly focused external radiation that can be delivered over the course of many sessions in order to give critical radiation to kill a tumor. So some of the benefits of these procedures, histotripsy and external beam radiation are both non invasive. Histotripsy generally will require anesthesia, whereas SBRT will not. Histotripsy in general is a single session procedure, whereas SBRT has multiple procedures that you would have to come back for. Another benefit, histotripsy doesn’t damage any of the tissue on the way in or the way out. When you get treated with radiation, although it’s very precise now, and it’s much more tolerated than it was before, there is some radiation that is affecting the organs on the way in and so that can be of a concern in lesions that are in a certain location.

Dr. Kevin Burns 9:21
Y-90 or radioembolization is very minimally invasive, all done through a small catheter that’s in the artery. It’s very effective if you have a larger tumor or you have multiple tumors all in the same area of the liver. And again, this is also an outpatient procedure. And microwave ablation is also a very fast procedure. So microwaves can be very fast. It’s well established. It’s been around for over a decade, and so we have a lot of evidence showing for microwave ablation that it’s equivalent to surgery, based on a trial called the COLLISION trial that came out for lesions under under three centimeters. Histotripsy is new, so there is still some limited availability. There’s spotty insurance coverage so that’s one of the other things we deal with and the ideal candidates for these procedures. So histotripsy kind of opens up… There’s some more patients who can be treated but in general, we’re thinking about someone who has oligometastatic disease. That means you can count the number of lesions, and you think there’s a chance you might be able to get all of them. In some cases, we’re just debulking patients, so let’s say you’re trying to get to a transplant, and your CEA has to be under a certain level. Histotripsy could be beneficial to start debulking some of the tumor to see if we can get the CEA level down, or if you’re having pain, or if there’s a tumor in one location that’s causing a problem, that may be a reason to go after that one as well. Again, once we get more data on the immune effects of this, this could get into more widespread practice as well. So these are just the different therapies, and if there’s questions about these later, we can talk about these.

Dr. Kevin Burns 15:46
When we talk about histotripsy, when people ask, can my tumor be treated with histotripsy it’s a very complex question, because we have to, one – be able to see the location of the liver. And so this is just a depiction of what the liver segments are. The liver is divided into eight segments based on their blood supply. And the liver is also different in every patient. Some people’s livers are bigger, some are smaller, some are higher in the chest. And so if you tell me you have a tumor in segment four, that’s one centimeter, can you treat it with histotripsy, you still need to see the pictures, but pictures, because everybody is different, really, on the inside. If you’ve had surgery before, that will also alter where your liver is and so it’s really important to review these images to make sure that it’s something that can be treated. If you consult with someone who does histotripsy, and I don’t think it’s good for histotripsy, we’re going to let you know what some of the other options are, in case you haven’t been told about them. But I think point of the slide is that every segment is currently being treated. At the beginning, we were not treating segment eight, segment seven, and now those are much more common for us to be able to treat.

Dr. Kevin Burns 15:46
And so some of the strengths of histotripsy really, is that it preserves the liver parenchyma. It can preserve the hepatic veins, the portal veins, the bile ducts. This means that we can treat the more dangerous tumor locations. We have good radiologic results. That means over time, the tumors get smaller, and so they can be easy to follow on imaging. It’s also non-invasive, and you get immediate results. The tumor is dead before you wake up from the procedure. So looking at histotripsy in general right now, we’re really focused on the liver, but this is a technology that will probably come to a lot of other organs in the future. The kidney trial called HOPE4KIDNEY, that one just closed, so we’re waiting on the results for that, and that would be to treat primary kidney cancer. The trial to treat pancreas tumors is underway. A safety trial is underway in Europe, and so that will hopefully come to the US soon. And then, as you can imagine, this technology may be able to be adapted to other areas throughout the body. So I will stop here, and if anyone has questions, I can check the chat as well.

Betsy Post 30:22
Yes, we have a lot of questions. Okay, I can read these off. And if any of these regarding insurance are not something that you can speak to, that’s fine. So just let me know because we do have a couple about that. If you have knowledge if histotripsy is covered by the VA, and if not, do you have any idea on the timeline to getting it covered?

Dr. Kevin Burns 30:46
Sure, yeah we have treated VA patients, and we’ve had referrals from the VA directly. I can’t say it would be covered 100% of the time, but I know that I think the VA is supportive of this technology now. So I would say that I would go to your doctor at the VA and see if they can get a referral to try to get a review approved, because I know we have treated patients with VA insurance. That wasn’t the case at the beginning, but I would say, since this year, we have been able to do that. I don’t know the specifics of that, but, but we have treated VA patients or with VA insurance.

Betsy Post 31:18
Well that’s great. Now this question I’m really interested in, too, so I’m glad someone asked it: what was the biggest breakthrough or learning that happened at the recent conference you mentioned?

Dr. Kevin Burns 31:33
I think it’s just that there’s so much people have come up with a technology and then doctors will figure out the best way to use it. So there’s a lot of different use cases. So, when this first came out, we were just going to treat tumors that are in the left liver that are very easy to see. And you’ll see that now we’re doing using different anesthesia tricks. We can get the liver to move around, and we can treat these very tough locations that maybe when this technology was thought of, that wasn’t really something that was thought to be possible. And so as doctors are doing more and more cases, they’re getting more experience in how this works. And so I think that’s one of the things, and it’s also to see that a doctor in Hong Kong learned to do the same thing, and we’re all doing the same thing. And so it’s nice to see that the worldwide community is really participating in this.

Betsy Post 32:31
Great and I know you talked about this a little bit, but we have a big following of histotripsy, a lot of interest in it. We did have a prior talk, but that was a while ago. So if you could speak to this question, it sounds like you can go through ribs safely now, so the right side is on the table, because we did have a prior talk on that, and they said that would be sort of a no go. So I’d love to hear more about that.

Dr. Kevin Burns 32:55
Yeah, that was at the beginning where they thought that this was all going to have to do what’s called subcostal, meaning under the rib cage, and so that really limits the liver. I would say, pretty quickly into treating – so all the trial patients, those are all subcostal treatments. All the initial treatments were generally subcostal. Pretty early into our experience, we started doing transcostal treatments, meaning that we put you on your side, so you generally your left side down, and we could treat through the ribs. And so as an I’m an interventional radiologist, we do a lot of procedures in the liver, transcostal, meaning between the ribs. That’s how we put in biliary drains. That’s how we do microwave ablations, that’s how we do biopsy. So that’s a very common way for us to access the liver. And so we’re really familiar with that anatomy. And so now I would say most of our treatments are probably right sided and through the ribs now, so that’s probably the most common things that we treat now the there’s a newer histotripsy machine, and so anyone that gets a machine now gets the new one, and all the other ones are being replaced, so everyone’s going to have the same one, and it does allow maybe some deeper lesions to get treated. There’s some subtle differences between it. histotripsy still happens on either one, but I think the point of that is treatment times are faster now. Treatments are about 40% faster than they were a year ago, and that’s through software improvements as well as hardware improvements. At the beginning, when we were treating transcostal, it was through the ribs. There’s a lot of pain associated with that. I think there’s a little bit, potentially some less pain now with this new treatment, and just because the procedure time is a little bit faster.

Betsy Post 32:41
In the portal vein picture that you showed, how long does it take for the liver to repair itself?

Dr. Kevin Burns 34:16
So generally, when we have a patient and we’re out one month from the procedure, the tumor will likely be around the same size, but it’ll be hopefully dead as long as we are able to deliver effective histotripsy. But once you get out to three months, that cavity is a lot smaller. And then at six months, sometimes it’s just a little speck. So the liver can repair pretty quickly and process that dead tissue in there.

Betsy Post 34:58
We do serve an international community in COLONTOWN so I was happy to see some of that information. And we do have a question here. I’m curious if any Canadian doctors joined the international conference you mentioned earlier, or maybe if you know of anyone in Canada that’s doing this now, or any information on that? This patient had had ALPS, so an aggressive extended in 2020, recently, facing recurrence. And would histo be something worth exploring?

Dr. Kevin Burns 35:26
Yeah. So currently, there’s no one practicing this in Canada. I know there’s a lot of interest in bringing it there, and I think every country has its own regulatory bodies that have to approve these things. So I think it will get there soon. I don’t have any knowledge of when that would actually happen, and I’m sure it will get adopted there as well. But there are many Canadian patients who seek medical care in the US, and many of them travel down to have this procedure. I would say, in a patient who’s had a liver resection hisotripsy, for an appropriate lesion would be a very good technology, because you’ve had surgery before. That means that likely, you’re probably not going to go through surgery again. And so you’re looking at probably microwave ablation, potentially, Y-90 or TAS radiation. So I think histotripsy does offer a unique advantage. You’ve been through surgery, so we can avoid needles to go through. And since you have probably less liver, although the liver is probably hypertrophy, we can, we can not damage as much liver as you could in another procedure. So I would say recurrence after a resection is a very common indication for histotripsy currently.

Betsy Post 36:37
Thank you. How long is one under general anesthesia?

Dr. Kevin Burns 36:41
I would say, depending on the number of lesions and the size the procedure it can take anywhere from one to three hours.

Betsy Post 36:50
How many tumors can be treated in one session?

Dr. Kevin Burns 36:53
There’s not realy a limit on number of tumors, more of some volume limitation. So if you think that there’s going to be a lot of tissue getting destroyed, your body has to process that. We didn’t speak to this earlier, but it’s very rare, some patients can have some kidney issues after this procedure. That’s extremely uncommon, and we think that may be due to potentially high volume treatment. So it’s also going to be a lot for your body to process. You probably have very severe side effects as well. And so if you had five small tumors, those could be all treated at the same time. But if you had one large tumor, that may be all that the physician or myself would be comfortable going after at one time just due to the volume of the lesion.

Betsy Post 37:34
What about histotripsy triggers an immune response? I think you spoke a little to this that.

Dr. Kevin Burns 37:39
Yeah. So again, in humans, we still have a lot more to learn on this. There are definitely case reports. That means it’s not a peer reviewed study, but case reports of patients who have had this response. That means that, because this is not thermal and not radiation it doesn’t just necose everything, and so the cells are completely destroyed, but there may be some protein or antigen that is left in the acellular lysate, and as your body cleans that up, it may learn to recognize something that was hidden from the body. So cancer generally progresses because it can escape the body’s natural processes. So if we can show it some antigen or some way to recognize the tumor, then potentially, I say potential, because we still need to prove this out in humans, that you could help stabilize disease elsewhere in the liver.

Betsy Post 38:28
What would be some of the more common things that would disqualify a patient from being able to receive histotripsy?

Dr. Kevin Burns 38:35
I’d say most common would be size and location of the tumor. A tumor that’s on the liver dome, if you’ve heard that, it’s probably not a great location to treat, because there are some better options; and size, if you had a single six centimeter tumor, this is probably not the best option for you. This could be combined with other things. And so I think those are the most common things. If you have very bad liver function, that would be another discussion we do. There are people who we do treat with poor liver function, but and there are people who get better after this procedure. So it’s a case by case basis with that. So I would say those are the most common things. Or if for some reason, you can’t have anesthesia, that would be one of the other disqualifying factors. There have been cases done not under general anesthesia. But I would just say in general, the reason we use general anesthesia is so that we can control your breathing. So if you imagine, the liver is going to move, it’s right under the diaphragm, so it moves every time you take a breath. So if we put you under anesthesia, we can augment that, make it less or more and we can make it predictable, meaning it’s the same every single time we take a breath. And so that we can make sure we can treat a tumor that might be right next to the stomach or right next to the pancreas, and nothing’s going to move and injure any other organ.

Betsy Post 39:46
How many procedures have you performed?

Dr. Kevin Burns 39:49
I — hundreds. I don’t know the exact number. One of my practices is myself and my two partners performing it. I think we’re almost 300 cases here. I work at another facility as well, and I know we’re over 100 cases there, yeah. So something like that.

Betsy Post 40:15
Can histotripsy be used for lymph nodes?

Dr. Kevin Burns 40:20
Yes. Speaking not for the company, talking about this, histotripsy is a technology, so think about it like radiation. If you’ve ever had radiation, you might have had, let’s just say you had rectal cancer. You might have radiation to your rectal area. You might have radiation to a lesion in the bone, to the liver. So you can have radiation anywhere in the body, as long as it’s something that’s safe. So histotripsy is a technology that can be applied to other organs in the body. Right now, in practice, it’s in the liver. The kidney trial just ended. The pancreas trial is starting. And so if you fast forward, you can think that this is probably going to move to a lot of other organs throughout the body, and mainly be ‘can the lesion be seen and safely treated without injuring another organ?’. I would say this, treating lymph node now would not be something that’s like an approved therapy, and it wouldn’t have any sort of insurance coverage at this point.

Betsy Post 41:16
Is there any risk of histotripsy causing metastasis via tumor cells not being destroyed and becoming dislodged?

Dr. Kevin Burns 41:23
That’s a common question that we do get and I understand the question. It makes sense. I’ll speak at this histotripsy summit we were just at. The scientists who helped discover this, and this question was brought up, and basically what they had said is, they tried to make this happen in animals, and they couldn’t do it again. Animals may not always apply to humans, but it’s something that hasn’t really been seen. And so that’s all I can say on this right now.

Betsy Post 41:51
Do you have to stop chemotherapy for a certain amount of time before getting this procedure, or can it be done while getting chemotherapy?

Dr. Kevin Burns 42:04
Great question, I usually mention this. I forgot to mention that. In general, we do not stop any systemic therapy for this so that is another advantage for a patient who may have very good control on a systemic therapy and they don’t want to stop. You know, to have surgery is one of the most common ones where you need to stop for quite some time. And so we generally treat patients on their therapy. If you have very severe side effects right after you get your chemotherapy, it’s probably not the best time to schedule your procedure, but it can be done around the therapy. And we like to think this is going to be synergistic, kind of with the chemotherapy. I would say in a future state, we may learn that there are certain immunotherapies that may augment or enhance the effects of this, and that’s something that’ll take years to tease out. But in general, you do not need to stop your chemotherapy. I’ll mention, if you’ve had a hepatic arterial infusion pump, you can still be treated. That’s another question that I commonly get. And we don’t need to stop the pump or anything like that.

Betsy Post 43:02
Can patients with underlying health conditions qualify to receive histotripsy?

Dr. Kevin Burns 43:08
Yeah, I think it’ll be dependent on whether or not you’re a candidate to have any procedure. First, would you be able to have anesthesia? If you have really bad cardiac disease, that may be a disqualifying factor, or whether your liver, we think is healthy enough to take any sort of procedure.

Betsy Post 43:27
I think you probably talked a little bit about this, but can this be done on a patient who has multiple tumors, such as 10 plus?

Dr. Kevin Burns 43:35
Yeah, so if 10 plus tumors, it’d probably be quite hard to get all of them. We have to make sure that the treatment goal is aligned but it definitely can be done on patients with that many tumors. I would classify that was probably going to be a debulking procedure, or, let’s say, maybe you have nine tumors in the right liver, and there’s one on the left. If the left sided one could be treated, maybe you could qualify for some other procedure for the right, and so every patient is different. There are a lot of patients who are seeking this procedure out to see if they can have any immunologic benefit from this, because they know they’re not really a candidate for anything else.

Betsy Post 44:14
I’ve been told Medicare covers histotripsy. Has this been your experience?

Dr. Kevin Burns 44:19
Yes, yeah. Medicare seems to be covering this as far as we’re aware.

Betsy Post 44:28
Are you aware of any centers offering or planning to offer histotripsy in Australia?

Dr. Kevin Burns 44:35
No one currently. I think there’ll be more news to come on that, maybe later in the year. But I know there’s a lot of advocacy trying to bring this to a lot of countries. I think this is very patient driven so if you live in Australia, or if you are in another country trying to bring this, I think it’s going to be very patient driven at this point to bring it up to the appropriate people. Probably get a doctor involved that maybe you think would be a person to advocate for this and then try to bring that into the system. I think it’s going to depend a lot on regulatory bodies in those countries. This is available in Hong Kong, outside of the US, this is available in Hong Kong and in Dubai or in UAE. I think it’s in Abu Dhabi.

Betsy Post 45:19
I don’t know if you can answer this so it’s okay if you can’t, but how much would it cost if you paid out of pocket?

Dr. Kevin Burns 45:29
It changes, I’m not going to answer that on a video, because this changes in every site is going to have different prices. What I’ve learned in this, is medical costs are very complicated, and so this can change frequently, and it can vary by site. So I would say it’s not steep, but it’s cheaper than other things that I know of that can be done as well.

Betsy Post 45:56
Yeah, I think that this patient has said she’s tried four different insurance approvals and all of that, and been denied, which is unfortunate.

Dr. Kevin Burns 46:05
Yeah and I would say, just speaking to this there, I’m sure people know who Jenny Stein is. She’s somebody who works trying to get approval. So a lot of hospitals, and we use her. She basically, all she does is try to get histotripsy patients approved. And so just know that if you see somebody for histotripsy and then we submit your stuff, there’s this SWAT team of really good people, really working behind the scenes, trying to get all these approved. And no matter what your insurance is, they’ll try to get everything approved. We’re doing peer to peers. We’re doing appeals. I’ve had to go on, I’ve had to go on a telephone court case to argue my case. So there’s a lot that’s being done for this. It’s a new therapy, and so it is expected, and I think over time, there’ll be more acceptance from this. Main thing is we just need to publish more data and so we can support. I did a peer to peer. They got overturned because I sent the person the new one year HOPE4LIVER data, and she said, that’s long term evidence. I think this is appropriate for the patient. I’ll approve it. So as we get more data, we’re going to get more approvals for patients.

Betsy Post 47:13
Is there a size limit for treating a tumor? I heard you mentioned a six centimeter tumor was too large.

Dr. Kevin Burns 47:20
There’s no size limit for the tumor, but if you had a single tumor, there could be a better option. And so I think that’s why it’s appropriate to speak with a physician. I’m an interventional radiologist. This is done by interventional radiologists as well as liver surgeons. There’s also a radiation oncologist that does this, so they can probably discuss with you what the other options are, and make sure you choose the appropriate thing for your tumor. If you had a six centimeter tumor in the hilum of the liver, and there’s no other option, then, yes, this can be a therapy where we’re going to try to treat as much of the tumor as possible, prevent, and potentially relieve a biliary obstruction. Maybe you have a biliary drain that you’re trying to get out. So there can be other reasons why we would still go after a tumor that’s larger. You know, this is a colon cancer forum, but there’s a lot of patients with cholangiocarcinoma that are these very large, aggressive tumors, and so this can be used to start kind of debulking those tumors, maybe allow a patient to get to another procedure, potentially a resection. So there can be reasons to go after a larger tumor.

Betsy Post 48:17
Are you aware of any ongoing histotripsy trials for lung mets?

Dr. Kevin Burns 48:22
No. The only trial currently enrolling is the pancreas safety trial in Barcelona, Spain. I think lung is going to be a long ways off. As you can imagine, this therapy doesn’t work there. And so you can imagine that that may have a lot of factors that would make this much more complicated to treat something in the lung. So I think that that is going to be probably quite far off into the distance. There are a lot of other procedures for lung mets, so I would say SBRT, or radiation, which we mentioned later, is fairly common for that. And then if you speak with an interventional radiologist, there’s a lot of ablation modalities that can be done for lung mets as well.

Betsy Post 48:58
I should have asked this earlier with the chemo question I knew it was going to be asked, Can this be used with Avastin?

Dr. Kevin Burns 49:04
Yes, we are not stopping Avastin with this. So that is also what differentiates this from from some other therapies. I’ll speak to, kind of related to Avastin. Avastin, we know, impairs wound healing and may mess with vessels. So if you’re having a TAS or a Y-90, that can make the vessels more friable, and obviously it impairs wound healing. So we haven’t seen any issues with Avastin. We talked about this procedure being extremely safe, now that we have done more procedures total, there are some patients who have some very rare complications, so there definitely have now been patients that have had some bleeding related to this, but that’s still going to be very, very small compared to any other therapy that we offer and so far, I haven’t seen that associated with Avastin.

Betsy Post 49:49
That is the last question that I see. So I just wanted to thank you again for being with us this evening, and if there’s anything you’d like to add before we sign off. This has been enormously helpful. I have learned a ton. So I truly appreciate it. And of course, everyone in the comments is agreeing, just saying how helpful it was. So this is truly a huge update from the last DocTalk we had on histotripsy so I really appreciate it, and I’ll turn it over to you to say anything else that you’d like to.

Dr. Kevin Burns 50:19
Yeah if you can still see my screen, this is just the contact information for Mission Hospital, which is one of the sites I operate at, just in case you want to get in contact with our nurse navigator to ask any questions or try to get into our system. This is the contact information, so I’ll leave that there. So I think, in summary, this is a new procedure. This is not magic. It’s still a procedure that requires a lot of skill and learning in order to treat these tumors and first decide, should we treat the tumor? That’s one of the other important things. And so when you consult with either a surgeon, interventional radiologist, or another physician performing this, you can ask, what are the other alternatives? And we can decide, or help you decide, what you think is best for you to do. There’s lots to learn with this. So every patient we treat, we are learning. When we treat a patient, we treat a lot of patients who travel to us. We’re going to want to see you back virtually. We do a lot of virtual consultations. We’re going to want to see you back at one month, three month, potentially six months, depending on how things are going. Because we want to see what is happening to these lesions over time so that we can learn, we can improve our techniques, and we can offer even better therapies over the course of years.

Betsy Post 51:33
Thank you so much, and thanks for everyone for attending and all of your great questions and participation. So have a great night. Thank you, bye, bye.

Dr. Kevin Burns 51:40
All right. Thank you, everyone, bye.