Histotripsy for mCRC liver mets: Dr. Hernandez (2023)

This transcript is automatically generated.

Betsy Post 0:00
Thank you so much for being here to educate all of us tonight.

Dr. Roberto Hernandez-Alejandro 0:32
Wow. This is impressive. Thank you to all these organizers for the I don’t know if it’s executive committee on COLONTOWN. It’s a pleasure, and it’s amazing what you guys do for all the patients that look and follow for advice and a support group, and for the families as well. It’s very impressive, all the things that you do and special. Thank you for Betsy Post, for giving this opportunity. So I’ll if some of you who have seen my previous presentations a lot of times, maybe I prolong too much, maybe it’s too much and it’s difficult to keep the people focus on what I’m presenting. This area of histotripsy is new. So there is not tons of new things that I will have to share. Actually, there was a moment that I said, Well, I think I need to share a little bit more. And I think I was lucky that I had the opportunity of getting three cases of during this week. So I have, I can share a little bit of that, which is, like the first three cases in in this country or internationally, outside the trial, let me tell you. What is a trial important that trial is when there’s something that is not completely proof that they are offering for patients, which is not the standard of care. And patients accept to go after something is finished, a trial, then the results are recovered, and they are sent for FDA, and the FDA goes very deeply in the analysis to see if it’s going to be a proof. And this was a long process for this company, and I’m going to be talking about that. So I’m going to start sharing my screen. So why we should be warrior, and what is important about treatment of cancer and evolution is because many of us here already have been diagnosed with cancer, but many others we’re going to be diagnosed with cancer at some moment, perhaps close to 50% of the people at some moment will develop some type of cancer. I’m not talking only about liver, but also other type of organ cancers. There’s a lot of of research that is happening behind and a lot of institutions working very hard, but it’s very difficult to be able to make huge progresses in other areas, we have been able to make a lot of progress an interesting area, and a lot of progress has been done. It has been in colorectal cancer, breast cancer as well, but colorectal cancer, we have been able to make a lot of progress. But probably in the last few years, we have been a little bit stagnant. And what is interesting in this particular presentation of histosonics is I definitely think that if these start working, and you know, if there are resources for this company, that they will be evolving the way that they deliver this in this interesting energy with that is ultrasound energy to other tumors, I think they will be able to control prostate cancer, much better, I think so they they are doing trials. They’re starting trials kidney cancer. They’re thinking about pancreas. I want to leave it very clear, this is not the answer for destroying the cancer, kidney the cancer for being cured. No, no, no. It’s a tool, a way to probably be cure some patients, very few, maybe, but also a way of trying to get where we gonna go when you’re diagnosed with cancer, and I’m gonna concentrate in liver, because so far has been the only organ where it has been FDA approved is the they are not opening it yet in Europe, it’s only for the United States. And I got some questions that pre questions that I will try to answer during my talk. This, everybody knows what is this. This is one of the most beautiful cities that’s the Arc de Triomphe. And you. Know that it’s every visitor in Paris, they try to go and visit this beautiful place. What? Why did I talk about this? So if you see here, there are around 13 avenues that comes to this place, 13 avenues you can reach this beautiful place through 13 ways, all right? And for me, that is what the patients should be trying to concentrate resection, or, in very few particular cases, transplantation. And I’m talking about transplantation because this is something new that has been happening over the last four and a half years in the United States, in very small population. Okay, I’m not saying that transplantation is going to remove resection, no surgery is the gold standard of liver, cancer of liver, colorectal liver metastases. That is the gold standard. So all the patient wants to get here, wants to get to that opportunity. The problem is, how do we get there? That’s why it’s the example here. The analogy that I’m bringing is there are different avenues. There are 13 ways or more ways of trying to come here. And this is what I’m talking about. You know, we have Y-90 histotripsy now, systemic chemotherapy, hepatic artery fusion, immunotherapy. That is an area that is working on growing resections, microwave ablation. Y-90, as I mentioned, but this is not one way. Sometimes you’re driving here, you want to reach here, and there’s a traffic or there’s an accident, or there might be, you know, group of people blocking the street. And then you have to take other little streets and go from resection to ablation, and maybe, if this is blocked, because there’s other problem there, and then you have to go to the Y-90 Avenue. It’s going to take you longer to get here, but the objective is to try to get into here resection or transplant, because that is what is going to give the patients the best opportunity. So it’s one of the new avenues to get here. I think we need to prove that also could cure some patients, and I’m going to tell you, why do I think it might be able, but but for a particular patients, but more importantly, to be the CEA, to be able to get in here. Now, there are some patients that we cannot attempt curative resections or curative transplant because they have disease outside the criteria, because they have metastasis, unfortunately, in other organs, and they cannot be candidates for resection or transplantation. We need to prove that these two trips he might be able to bring a benefit for these patients. And I think what we have to do here is to start doing some trials. So a little bit of the history of the of It started in 2001 University of Michigan, and they started doing a lot of investigations on this in the lab. And it took them nine years while they were doing a lot of work to develop a company that is called HistoSonics. I have no connection, or I don’t get paid by HistoSonics. I want you to know zero, okay, theyare super nice people. They’re working with us. We have them, a lot of them here during this last three days, because we were doing the first cases, and we have a lot of support. But that is different. I have nothing to do with them. And this HistoSonic, the company started developing, I recall, and I learned from these people that they started doing this with hearts. They were trying that with this ultrasound in babies, creating a hole between the atriums, between the two chambers of the upper part of the heart to connect with some babies who have some problems in the heart. But I don’t know. I don’t think they went too far. And they start developing more things in the lab, and they start concentrating on, focusing on liver therapy and prostate therapy. That’s what they started doing. And then in 2019 they started with a study that it went to the FDA, or they show a eight patients successfully treated. And this is feasibility. Feasibility means that is a study that they treated some patients with tumors, they use these , and the patients didn’t have complications, didn’t do worse. It’s just to show it’s not affecting this treatment. For getting into this area, they they already went to a lot of animals models, a lot of animal models. And I will show you some animal models, because it’s pretty interesting. And then, you know, the companies are getting involved. There’s, you can imagine, there’s a lot of resources that needs to create to grow a company like this. I think these guys, Johnson and Johnson went and tried taking part of this, that there’s a fire. All of this is when they started deliver study. And they started in 14 sites, and this is the area of COVID. So they couldn’t go to a very big institutions to try to do these studies, because it was very difficult to be traveling. There were some people with special permissions to travel to Europe from the US for doing these studies. And then later on, they got financial approval from FDA, after they proved that it was good their trial. And I will explain what happened in that trial. And this is the 2023, the end. And there it this machine. One of these machines is here. I think they already have eight centers who have bought the machine. They are delivering two in this year, one to here in University of Rochester, another one in Cleveland, Michigan is going to get their machine, despite they are the ones the initiators of this in the research they do not the owners are HistoSonic, and the machine that they have before, it was experimental. And now this is a new model, so they cannot use that one. They have to return it, and they will get a new one. And then this is, you know, the hospitals. It’s very expensive, and the hospital needs to deal with this. This is not in our hands as physicians. Now, what does what is this? So hopefully this work. So this machine developed, the deploys through this robot head ultrasound to their body. They don’t need to open the abdomen. We don’t need to open the abdomen. There’s no needles. This is the liver, like if we’re magnifying the tissue of the liver, these are the ultrasound waves that are coming across the abdomen and getting into the liver. And if we pretend that this is a tumor. There’s bubbles that are created with with the ultrasound that is going to be destroying that unwanted tissue, that unwanted tissue, particular we’re talking about, what is tumors, cancer? So that is the objective of this, and they were able to prove it in animals, that they were able to create tumors. And they they treated these animals, and they show that it works. What does this create? It liquefies the cancer. It liquefies the solid tumor, and then that gets reabsorbed. They look at this with imaging for many months to those patients who they deploy the energy, and when it was well deployed, those that substance of fluid was getting absorbed and the liver create a scar tissue, and it disappeared the tumor. Now this was exactly what it was happening in animals. And this is an example of this mouse. It is not my computer, sorry for that, but this is a portion of ice clean spleen that they created cancer in in a peak, and then they treat it with HistoSonics to the these tumor in the they removed the piece of tumor, and they wanted to look how it looks. Sorry that I’m showing this this cancel. There’s a little bit of blood. I hope nobody. You can close your eyes if you don’t like it. But well, you can see here. You can see they cut the piece. This is a spin. You can see that hole that’s like a crater. The tumor was there, and now there’s no tumor. It’s all liquefied. It created that crater. And of course, with time, if they wouldn’t remove it, they will create this. The spleen will create a scar tissue. They analyze these, the pathologies, I think, and they couldn’t find in this specimen of animal any tumors. Now what do I find? Very exciting. When I was when they told me about this, I said, this is hard to believe. I don’t think this is true. These are liver that was treated from animals with HistoSonics, and there was a tumor here in the liver. You can this tissue that you see here, these membranes that looks like like a spider web here and here as well. Those are bile docs. Those are veins and arteries. So this energy destroy the two more. But if there are veins and arteries or bile ducts around, it doesn’t destroy those ones. And I was like, wow, this is hard to believe. I think they just want us to buy the machine. And how come is this happening? And I think it’s the content of collagen of this structure that does. Not take the ultrasound wave and only the tissue around it is going to be destroyed. And we need to calculate and focus our area of treatment so we can target. I don’t know it feels like like military people when they go and shoot a missile and they do the all their calculations. I feel like we’re doing that when during this couple of days that I’ve been working and doing this in some patients. So this is pretty interesting. They did other studies in animals. And you You know, I know that this is very medical and very scientific, but it’s very easy to understand these three slides here in the bottom part are livers from animals in the microscope where they deployed chemotherapy to certain cancers. And there are the cancer, and the more shiny red is the penetration of the chemotherapy in the tumors. So these tumors didn’t receive any these tumors only received chemotherapy. Look at these ones in the top. They received five pulses. That means five sessions of 50 or 100 so what is this telling us that also if, perhaps, if this is in animals, perhaps, if we treat patients with this , and we are treating them with some other immunotherapy or chemotherapy, most likely the penetration of the of the chemo or immunotherapy will get stronger in that tissue. So that is also pretty impressive. Again, remember, I’m not saying this is the answer for everything. We need to prove a lot of things, but this is exciting. This is a very interesting effect that was described since 1950s with with radiation therapy, and it’s called the absocopal effect. What is an abscopal effect? Is when they were treating in animals, and then in the trial, in humans, some of the tumors, okay, they said, Okay, this patient has three tumors in the left side, in the liver, and has, I don’t know, 15 in the right side, a patient who has a lot of tumors. And they were considered that patient, they were considering perhaps palliative and they were saying, there’s nothing we can do for you. And the patient say, Okay, I’ll, I’ll join this trial. Maybe I will get some benefit, or maybe I will help some people in the future. So they treated those two or three tumors in the left side, and they left the other ones not non treated because they couldn’t reach with the energy those tumors. And interestingly, in some patients with the follow up CT scans that sometimes the non treated tumors got smaller. That is what is called abscopal effect. What I think is happening, and I want to do this in my research in my lab, is that what is happening is that liquefied tissue that I was telling you, it gets it shows some RNA or DNA, and then your immune system is going to go and identify it, and then it will have memory and identify other sites of tumors, and it might go and attack this is my theory, and some of the other people as well. We need to prove that he’s not saying, Okay, let’s treat one two more, and the other 20 are going to get smaller. No, but this is so interesting, because what is making me think is, wow, what about if we do this and maybe we give immunotherapy to the patient, because that will enhance the immuno treatment to the patient. So there’s a lot of questions that we don’t have, and I feel that I’m this is the first time that I’m talking big time in HistoSonics. I haven’t talked about this in any medical field, so I think I want to be cautious with with my with with my message here. What it’s interesting is there are a lot of local, regional therapies. As I mentioned in that slide of Paris, France. You know, we have Y-90, we have microwave ablation. We have the hepatic artery infusion pump. There’s a lot of other things that. But what is interesting of this one is that the effect is, immediately, we have, apparently, when we treat it, and then if we, if I will go and remove the two more, I will see the effect immediately. So we need to prove it, because we need tissue in the humans to to show that, and we’re working on that here. This technology is addressing the concerns that could represent a major clinical advancement in this treatment. These are, these are slides, these ones that I’m showing here from the sonic group that I asked them if I can share it with you. So this is their, their trial, and I want to explain you this. I don’t want to go too much into detail. There were several patients it. The trial was called hope for liver United States and hope for liver international these are the countries where that participated. And if we look at these the criteria, you don’t have to go into this detail. There were different type of tumors, patients who have primary tumors in the liver, HCC, which is very common. It’s more common in patients who have cirrhosis, there were they didn’t treat any tumor more than three centimeters. Why? It’s not because they don’t think they can do it, because they wanted to be sure that they can demonstrate to the FDA, this works. If you have a tumor that is 15 centimeters, most likely you won’t have a very good outcome, right? But how do you demonstrate? Okay, let’s go for to the low hanging fruit. We need to prove that it works. And then from there you start expanding. One of the tumors that I treated on Monday, it was four centimeters. So we went bigger, and I think it worked. What they were looking at that trial, they look at the efficacy endpoint, and that was, they follow the patients with CT scans, and then they wanted to see that the tumors were not growing back, the one that were treated, and they were also looking at the that the patient didn’t develop complications. Those were the main objectives. And as I mentioned, during the US, there were 25 patients. In Europe, there were 23 and in the UK as well. And then those 44 patients in total, they have 49 tumors that were treated, and the patients were look after several months, weeks. And the interesting part, let me show you. These are patients who have cancer of the primary cancer that has cirrhosis. And there were 18 of them, and 26 they have metastatic cancer, not HCC. So here there’s a group of patients who have colon cancer or other metastases from other primary cancer, could be from pancreas, could be from breast cancer, could be narrow endocrine tumors, so but two more that we’re going to deliver. This is an important slide that I want you to remember, or just to have my message here is, many of you have seen pictures or cartoons of a liver. This is a liver that is kind of divided in the segments the liver have eight segments here. The number one is behind. Is a very little one that is behind. Number two, number is like a clock, 2345678, so a clock that run this way, but the number one is behind. So these are the number of tumors that they treated. What happened here in the right side, segment seven and segment eight, they didn’t treat any tumors. And here in the right side, in the bottom part, only three and three. Why they treated 24 here? Why did three and six and eight? So if you see the left side is from this vein to here, a lot of treatments in the left side and minimal treatments in the right side. The main one of the main obstacles of this technique are the ribs, the margin ribs, the coastal ribs. They don’t allow the ultrasound waves to go, so the liver, as you know, is covered by the ribs in the right side and the left side is more kind of in the middle. So if you see the picture that me here, is the left side, the right side is here in the ribs. So it’s very difficult, unless they are very low in the right side. And you can treat it because they go below the coastal margin. So that is one of the limitations these people. Needs to create some way that we can penetrate or pass those ribs. And they should be doing that. And I think they have impressive engineers and software people. Hopefully they do that. I already told them you have to do also, you know, to be able to open the patient. I can move the ribs away with my retractors, and then with a hand piece, if you give me the HistoSonic treated. I The patient would have cancer. – They don’t care if you open or not open. You know that what they want to have is a treatment that that could help them for going to resections or getting cured. Yeah, so I think the future is promising, and hopefully these people start developing more advanced This is, I don’t want to bore you with these, but the results of the two things that I told you about, safety and efficacy, they got 95% of efficacy. What does that mean? That out of 44 tumors, 42 responded the way that they wanted. And you can see here, this is before the procedure, there was a little tumor here in the left side of the liver was treated and create a cavity here, and that cavity weeks later, months later, it disappear and it heals completely. And in the other point, which is the complications. They minimal complications. Three patients out of the 44 patients have some complications. The complications were one patient have infection, but this patient had a previous pancreas cancer surgery and have 20 metastasis later on, the patient has some problems in the bile ducts. I think I don’t know this, and I’m not protecting them, but I think probably this complication is more related to the pancreatic surgery than the HistoSonics. Another patient has pleuretic pain. I think probably that what I can understand now is if you treat something in the left side that is very high, the ultrasounds can hit the pleura, which is in the lungs and and can create some inflammation. Probably, patients apparently don’t need too much medication of pain. After that, the patients were kept in the hospital for one day in the trial. Many of them, they wanted to leave a hospital. Our first patient left the next day. We were talking and joking and talking about life and I think, minimal pain, one of our patients that is really now on in the hospital that we treated this morning before I started the surgery that I’m doing right now. I went to see him, and he is doing very well. He told me that he feels like he doesn’t to be he doesn’t need to be here. I want to be cautious. I think in the future, probably maybe we can do this early in the morning, and maybe the patient can be discharged in the in the late afternoon or early evening. But while this is not the the objective is not to do that. I think the objective is to understand much more, because there are some limitations, and it’s clear tumors in the right side. There are not our friends for these things. But of course, we need to find a way of of being using this. They concluded that this trial was good. FDA approved. It took them a lot of time for getting the FDA approved. The FDA went back and forward, back and forward, asking for some things. And everything worked very well. I did this – This is my slide that I put. What are the limitations, the rights, the right side, the rib cage. They only treated three centimeters tumors. Can we treat bigger? I think so. And one of the pros is within a four centimeters. I was planning to do another one that is a little bit bigger. We don’t have pathology result in humans, but we will have them soon. Um, uh, there’s a learning curve, right? It’s taking us a lot of time to be taking some more time for preparing the patient. The patient has to be under anesthesia because the patient gets to the or no surgeries, no needles, the patient is intubated, so the patient is not moving while we do this procedure, we have to do an ultrasound identify the tumors. One of the problems will be, if we do a ultrasound and we cannot identify the tumors, that will be a big limitation, and that will be a problem because we cannot deploy this thing. So what I’m thinking is if, if I have patients here that could be candidates for these I want to do an ultrasound before they come to the to the procedure, to see if I can visualize them. Because otherwise we bring them here, we try to do it, and we don’t find it. And then, you know the patient, they go, it’s, it’s, maybe it’s just the anesthesia, like a colonoscopy, very briefly, but well, it’s better and it will be safer to avoid the anesthesia, to have an ultrasound early. That’s what we’re learning now, what are the diagnosis and what are the indications? So for example, if I have a patient with pancreatic cancer, right that we know, and probably you all know, that pancreatic cancer is not very – It has a pretty bad outcome, unfortunately, majority of the time, and if the patient has metastasis in the liver. Are we going to do histotripsy? If I would be doing a trial for them, for those patients, I will try to do it, but I know that that patient won’t have a benefit most likely. Right? I prefer to try to keep that room for that patient that has the capacity from colon cancer or a primary liver cancer, that I know that that patient most likely have a benefit, right? If, if my groups, we start doing feel comfortable with this technology, and then we have more access. We will be opening for other diagnosing, for more and more and more for for patients. But at this moment, we are limiting for the diagnosis of colorectal cancer, perhaps some narrow endocrine tumors, the primary liver cancer, collangercarcinoma, HCC. And you know that a lot of my work is based on colorectal liver metastasis. Let me share some of my experience. And I don’t know if our super patient is here, but this is what our patient number one, and I asked permission if I can share some of her images. And this is here. You can see there are tumors in the right side of the liver right in the left side as well. You can see this one here, and a lot of here. Initially, when I met this patient, I said, I think I might be able to do an ALPS. Why is that? Because I need to remove a lot of tissue in the liver in the right side, the left side also has cancer. So the only part that there was no cancer, it was in the in the center, in the segment four of the liver. And let me remind you what is an ALPS. For example, in this cartoon that I have here, I put some metastases in all of this area, and then the first stage, we go and remove the tumors, for example, in the left side. Then now the left side is clear, but it’s very small. If I remove now all the right side, this patient won’t survive because it’s too small. So the idea was to remove that ligate. These veins here, all the blood flow from the portal vein will go to the left side. The liver will grow in seven days, this little part with no cancer, will grow very big, and now I can come back in a second surgery and remove the right side, and the patient won’t have liver failure and will end like this. So I have the opportunity of being pioneer on this technique. And I think it work, but I think we have to be more cautious, because, you know, these are the results of patients. A lot, majority of them, they will have recurrence, most likely, but, but there will be a big opportunity for doing other things. So what I thought about? Okay, look at these patients. This patient has colon cancer, and the primary tumor is in the sigmoid. Patient received 10 cycle treatments of FOLFOX, there’s a mutation of KRAS. The CEA was extremely high, but then by November, it came down, responding very well to chemotherapy. Should I do an ALPS? And that’s what I initially thought. Look at this amount of tumors here in the right side, the right side, a lot of tumors. And these two, this big tumor in the left side, and another small, very superficial here in the left side. So the only area where there’s no cancer is here in the center. That’s segment four. So I thought, okay, I should be doing an ALPS. And then when I start getting more involved with this , I said, wait a moment. I started thinking. And this, I don’t know it came one day, while I was taking a shower, and say, What about if I do this? What about if I use here, right? Because this is a tricky one, and my plan was to do in those tumors in the left side, in the left side. Now, hopefully that that left side of the liver is clear, give more chemotherapy, wait to see that there’s no cancer back in the left side, and then I can safely come and do surgery in the right side and do a right hepatectomy. Can I do that? So we’re halfway there, and this is where we’re going. So that’s we did this. We developed this technique of histoSonic in our patients. It creates that microbubbles that we can see with the ultrasound and it creates a very interesting sound. It’s a little bit hurts the ears, but that is good when you’re awkward when you’re doing this procedure. So my goal is, okay, let’s target this tumor here, and remember what I told you about, that it preserved the vessels. You see these white structures here. Those are veins that she needs to survive if I do a right hepatectomy later on, so with other type of ablation, I wouldn’t be able to preserve those. And this is another patient. This is a picture from today. This is not our first patient. This is our third patient. And here is Dr Tommyama, which is my colleague, my super colleague. Big here. He’s here. I’m here as well. I know that it’s a little bit blurry picture. It was a, not the best cell phone. All of these are the people from HistoSonics that they came from, Minneapolis, from California, to support us in the or engineers that they deployed the machine. This is the machine here. This is a robot arm. This is a bubble of water that is hanging from the robot arm that has the ultrasound. The patient is anesthetized, and this is the ultrasound machine. So this ultrasound is helping us to see the two more. It sent the images to this other machine. And here we managed to deploy the energy. And this is how we do it. You have, we have on in our hospital, we have other monitors where we can see CT scan for for fusion of the images, and be able to see things much better. So this is the case of our first page. This is tumor here. You might say, Okay, this is the same. No, it’s not true. This is not the same. There’s no tumor anymore. This is a cavity, and you see the shape is different. And why does it goes like, like elliptical, like an egg, I think is because the patient is moving up and down, up and down during the breathing, so the treatment moves a little bit. Now here, this is the area the bottom part where the tumor was located, and then the treatment extension went a little bit beyond into this area. But what is important thing now our patient all these left side of the liver and the segment four, hopefully there’s no two more that one that was in the surface that was very small. My plan is to go in the operating room, hopefully in February, after some chemotherapy, remove it, take it out and do the right path, and the primary tumor will remove it in the first day in that stage. Now the patient doesn’t need two operations. Now the patient needs only one operation. Hopefully, if this works, we need to prove that it works. But I think this is this is this is exciting. We have to be cautious, as I mentioned. And I think one of the things that I learned from a surgeon who I love, all surgeons who I they teach me, and they I learned from them, from what they were pioneers, many, many years ago. And one was Dr Blumgard. And here he is. I was in New York City with him. He passed away one year ago. He was from Memorial Sloan Kettering Center. He is one of the persons who came from South Africa and started what is called HPV surgery in the United States, a part of pancreatic opioid surgery. And one day I was asking him, when I was doing these ALPS, and then I was starting liver transfer for colorectal metastasis. I asked him, Dr Blumgard what advice do you have for me in my life? And he told me, Festina Lente, and I was I didn’t understand very well, what does that mean? And this is what he means.

Dr. Roberto Hernandez-Alejandro 38:12
You know, we have to make haste, slowly. And he was telling me, you have to be like a rabbit, but like a snail, as same moment, and I kind of understand his message. And I was asked to write the paper in in the American Journal of Transplantation, a critic of a paper, and I call it that, Festina Lente, because I think that paper, particular, they were kind of rushing on, trying to do things. And so I just want to share that with you, not, not, not that paper that I talk about liver transplant for colorectal metastasis. But I try to, I love innovation. I think we have to be cautious. Is not going reckless, doing things. I think we have to go slowly. And at the end, I want you to remember this, what I mentioned at the beginning. The important thing is trying to get there. It doesn’t matter if you one side, the other side, the other side, or you have to go one, one and two, and you, hopefully you are able to get here right. This is the important thing. And how do you do that? You need to have a lot of courage. And I think you need to have a team and a group of physicians, a surgeon or surgeon who reached the goals for you and to help you driving that part. And with that, I finish my presentation and I will stop sharing.

Betsy Post 39:34
Thank you so much. I know we don’t have a lot of time with you, but there are some questions. So I thought we could take some of these questions.

Dr. Roberto Hernandez-Alejandro 39:51
I will try to answer, hopefully short yes and clear

Betsy Post 39:57
So if a patient does have a few small lung mets, would that rule out this procedure if there’s only one liver lesion?

Dr. Roberto Hernandez-Alejandro 40:12
I don’t know if the patient comes and it’s in the left side right, as I mentioned to you, if it’s in the right side, I would say this patient, we won’t be able to treat it. But if it’s in the left side and those, yeah, I think it will depend. I will I think it will depend if the patient is telling me, okay, I have 20 tumors in the lungs and one in the liver. I think there’s not going to be a benefit for that. I don’t think there’s going to be a benefit okay, if the patient has two small lesions in the lungs, and they have been stable, and they have been there for six months, one year. Wait a moment, and there has one lesion in the left side. I said, wait a moment. I can go do it and but also I will tell the patient. Maybe I can get one of my thoracic surgeons here and get the two long metastases out. So, um, as I mentioned in my slides, we need to think sometimes a little bit outside the box. We have to go festine lente – not go crazy, right? But I think it will depend on the characteristics of the of these patients. So if the patient is not responding, and it’s progressing, probably we know that the outcome would not be good, but I wouldn’t be closing the door, but I will have to analyze very carefully the diagnosis if the patient is responding or not to chemotherapy.

Betsy Post 41:33
The next question is just about, do you know what other facilities outside of URMC, have the machine right now, and you may or may not know that.

Dr. Roberto Hernandez-Alejandro 41:42
So I asked them, because I know I was going to get that questionBetsy. Cleveland Clinic got the machine, I think they are planning to do next week their first case. That’s what my understanding. Nobody else will start cases in this 2023 but I think in January, Wisconsin is starting. They have put out eight machines in total by early next year, to my understanding, also, Michigan is getting their machine. NYU is getting a machine. I think Hopkins is trying to get it, but they having conclude and close the deal. But there has been eight, I think they will, they will. I think by the end of 2024, probably there will be around the 10 to 12 machines out there. And the important thing is to to be able, you know, it’s very interesting, because as as a surgeon, we we, normally, as a surgeons, we try to go with a mentality of saying, Okay, let’s go. Let’s resect, let’s do a transplant, let’s do a reception. Let’s help the patient, and trying to be smart in the way we do it. But with this is a very different mentality of about, you know, calculating, I don’t get scrubbed, right? It’s very strange for me. I don’t get scrubbed. I’m not wearing or gloves and all my gowns. It’s different. But I think as a surgeon, what it makes me feel very comfortable is because I know where the patient needs to go, and I know what surgeries the patient probably will and this is I see many times as a bridge, as a path to get into that resection, to get into that transfer. I think this is giving opportunity for patients.

Betsy Post 43:44
Great. The next one, I think, is a quick answer. Does getting this still leave the option of surgery and perhaps an HAI pump later?

Dr. Roberto Hernandez-Alejandro 43:56
I don’t see why not. I would say the answer, yes. I think that, as I was mentioning, remember those little streets that I wrote in the map? Right? If you have one, you can go to the other one. There’s some things that you cannot so if you have an ALPS, for example, a resection of an alt, and then you’re saying, I’m going to get a pump. I haven’t seen anybody in the world doing that, right? And I think it will be very dangerous. So I think if sometimes when you go to one path, you won’t have the other one. And I, I like to be very honest and clear with my patients, right? My first patient was saying, Can I still have a pump if the HistoSonic fails? Right? Now, yes, if I go and I do an alt, you won’t have an opportunity of getting this right, a hepatic artery pump. That’s clearly but, you know, we, I we have to be very clear with patients. I know they come with a lot of education nowadays, seeing especially those ones who have advanced metastatic disease in their liver. And we need to provide opportunity and an education. And then I answer that question, can I answer that question that is right? Now there that I saw about the insurance. You know, insurance is difficult. I want to be polite. Insurance are difficult.They’re very difficult. But we already, we were fighting with them, and I talked to them peer to peer, and I explained them, what is we’re doing, and when we didn’t have problems, I think, for example, patients will go for transplant, for colorectal metastasis, transplant, that’s very difficult because it’s huge and they don’t see they some of them, they go for experimental, but this they see like an ablation. So it’s less difficult for patients, and the cost to the insurance is not huge compared to, you know, a big transplant or big reduction. Of course, I wouldn’t say this is better than transplant or this is better than resection. No, every, each is different streets, different avenues. Remember, we’re going to get to the center and get into there, but that’s it.

Betsy Post 46:02
So this one is: can this be used on just one tumor if others exist? For example, if there’s a tumor at the top where all the veins and arteries meet?

Dr. Roberto Hernandez-Alejandro 46:12
So can this be used on one tumors If the tumor is located more towards the left. So it’s not necessary to be the left if the ultrasound has access to the liver, and if the liver is not, if the ribs are not blocking, the ribs are like I was a little bit frustrated this morning with our second case. The ribs were obstructing us, and we couldn’t, and I have to be honest, we couldn’t treat two of the tumors that I was trying to treat in that patient, and it’s because of the ribs, the ribs were blocking. So I need to come and to bring the patient a plan B, and I already talked to a patient. We woke up the patient, and I told the patient, I’m doing on January five a left hepatectomy. It’s going to be a more aggressive treatment, but I think we’re trying to find answer for patients. But there’s limitations. I want to be clear, this is not the answer for everything, right?

Betsy Post 47:19
So if a patient has surgery to remove the primary colon tumor and additional mets to lymph nodes, could they be a candidate for this to do the rest of the job and stay on systemic chemo?

Dr. Roberto Hernandez-Alejandro 47:31
Okay, so if a patient has the primary tumor removed and lymph nodes, but if those lymph nodes remember, if those lymph nodes are around the primary tumor and there are metastases, the problem is when there are lymph nodes not around, not only around the primary tumor, when they are lymph nodes in the retroperitoneum, which is in the back part, and if they are lymph nodes around the liver, and if those are malignant lymph nodes, the prognosis is worse, and sometimes it’s not, we have to be very cautious. So I wouldn’t do surgery or something big in those patients. I will be waiting, because the time is going to tell me if I should be aggressive or not later on. So what I do is to Sonics in because the patient have lymph nodes, but then the patient receives treatment, and then I cannot see those lymph nodes. Well, I will do all and do HistoSonics or even do surgery, right? Perhaps not transplant, because, you know, we give immunosuppression, and those lymph nodes might come back within suppression, and the cancer can come back and spread to other places. But I think it depends on each patient. I wouldn’t say no, but if there are multiple lymph nodes around the liver, and then probably the benefit will be remote.

Betsy Post 49:00
Does the number of existing tumors factor into eligibility for this procedure?

Dr. Roberto Hernandez-Alejandro 49:09
Does the number of liver tumors? I think with time, we’ll be learning more, and I think we’ll gonna get smarter and how we do these things, I will feel comfortable with just what I have learned in the training, and what we have been seeing that we can treat maybe two or three tumors in one session. It takes more time, it takes it takes, like, I don’t know, like, close to two hours or hour and a half to prep, to make the measurements, to make the fusion, to develop your plan of attack. And then when you, when you have all your your lines drawn, and then you just press the button, and then you just wait. And then you have to be standing beside the machine listening how that is working well. And that treatment could be, I don’t know, 10 – 12 minutes, or it could go to 40 minutes, but I will be able to treat two or three tumors in one session. Now, of course, if a liver is full of tumors, that means that there’s some in the right side, so I wouldn’t be doing but I think if I’m able to treat the left side with HistoSonics and clear those cancers, then I can go and do surgery in the right side, correct and probably the patient can be no evidence of disease. We know that there’s a chance of of recurrence, but we will follow that patient close, and that will be the best prognosis for those patients.

Betsy Post 50:41
How will you get pathology results if the tumors are liquefied in the process?

Dr. Roberto Hernandez-Alejandro 50:46
Great question. Great question. So my patient from today, I treated two little tumors that were in the bottom of the right side, close to the gall bladder. So they were hanging, like not hanging, but just beside it, below the the costal margin below I treat them. And there’s another very big that I have to go and do resection in the right side above so I cannot do histotripsy so that patient is going to go to the operating room. You know that, because I have to go and remove it, and I will have those other two little tumors over there that that have been treated, it will take me five minutes to scoop them out. I’m going to do that, and I will be able to answer a question for that question soon. And nobody has that answer yet, so hopefully we can bring good news soon.

Betsy Post 51:47
Awesome. Someone’s asking, What about a tumor 11 centimeters? Could you explain? Like, would that be something that would be possible or not?

Dr. Roberto Hernandez-Alejandro 51:58
I don’t think anybody has tried that, I will be afraid of doing it. If it’s tumor of 11 centimeters, not sure if it’s in the left side, probably will be more into the center of the left side, because, you know, the amount of tissue of the of the liver. But even if it was in the left side, I I would think about other options. I will offer surgery. I will offer Y-90 and then surgery, depending on what type of tumor it is.

Betsy Post 52:32
Okay. So someone’s asking, the location of the tumor on the left side and away from the biliary tree and blood vessels is needed for this to be used. So the utility would be a subset of liver mets.

Dr. Roberto Hernandez-Alejandro 52:48
I would say the applicability, the utility of these would be, hopefully they are in the right side, in the sorry, again, repeated, not right side, okay, left side. Hopefully they are in the left side. But what is impressive is even if they are beside the bile ducts, or beside the arteries or veins, we can preserve with this technology, with this ultrasound, and we can preserve that tissue. So it’s not a it’s not a problem with other ablative therapies, we cannot use it because we will destroy what grade bleeding or or bile leaks.

Betsy Post 53:32
Okay, I’m just going to take, there are a lot of questions, and I don’t know that we’re going to get to them also, just carry on: is the procedure available if you currently have a hepatic pump?

Dr. Roberto Hernandez-Alejandro 53:46
Good question. I don’t know. I I think so. Why not? I think it wouldn’t affect. It wouldn’t affect, I don’t think it will affect. Now, sometimes, some patients with a pump, sometimes some of them can have biliary complications. So if there are bile duct are very dilated, probably I will be very cautious with that. But if the patient doesn’t have those complications, and no, no bile duct dilations, and if it’s in the left side, and we can see it in the ultrasound. I think I might do it. I will do it.

Betsy Post 54:28
Is this an option if liver function levels such as alt, AST, ALK, phos are high and bilirubin is stable?

Dr. Roberto Hernandez-Alejandro 54:37
Wow. Well, great question. So Koji Tomiyama, we both work together, and we think, we always think that, you know, two brains for eyes, for hands, we can do more for patients. And we have other surgeons. I don’t want to minimize the work that two of the other surgeons are right now taking my patient. To operating, and I will join them soon. So I what I think is what he says, Doctor Tomiyama, is that the interesting part of this technique is that it doesn’t affect the parenchyma the parenchymal is the tissue of the liver, because the waves where they are traveling through the liver to get into the tumor, the waves do not injure the liver. They only injure the tissue when they collide the two the forces for three or four areas that are coming. But what they are traveling and go through different tissue, they don’t affect it. So they for the question of patients who got, for example, cirrhosis and they have or hepatitis and they have inflammation of the liver, then this could be an option of treatment for them.

Betsy Post 56:01
This one is about if the patient has already had a liver resection and also ablation, but they are getting a few, one centimeter, you know, small liver mets back in the liver. Is this something on the left side, those mets kind of continue to recur. Would this be something that could be an option?

Dr. Roberto Hernandez-Alejandro 56:26
If we can see them with the ultrasound, I think so. Yeah. Why not?

Betsy Post 56:34
Awesome in other centers outside of URMC, would this typically be within the surgical department or surgery, or IR or another specialty?

Dr. Roberto Hernandez-Alejandro 56:43
That’s a very smart question. I think someone that question, that someone is in the medical field, you know, this is a very smart question, because I think, you know, I’m biased in this answer, right? I’m a surgeon, but I think IR thinks one way, surgeons woud see other way. But normally ablation therapies, you know, microwave ablation, or when we do Y-90, they’re my friends, my colleagues who are in IR, and I need them a lot here. But the way of thinking is kind of they’re not seeing the patient, and the follow up continuously and treating the cancer, right? So it’s just a passage through them for for a period of time, or a short period of time. And I think when the surgeon has this device, the way of thinking is different, trying to create that bridge, right? Because otherwise the patient normally is referred from the oncologist or the surgeon to the intervention or radiologist for having, you know, SBRT or having a microwave ablation. So definitely, I think I asked to the histosonic people if there are more surgeons or more interventional radiologists, and they said that at the beginning, the interest was more from interventional radiologists. But now, who has been buying it are departments of surgery. And they said that it’s around 70 to 30%: 70 surgeons, 30% interventional radiologist.

Betsy Post 58:23
Awesome. Is a met in segment one, an option for for this procedure?

Dr. Roberto Hernandez-Alejandro 58:31
It’s pretty deep. Segment one is very back, probably, if it’s a little bit large and we can see it well, you know what I will do with a patient like that? If a patient has a segment one, two more, I will try to see the ultrasound, if we could see any ultrasound, but otherwise I will go and resect it, right? So again, we need to think this is not the only option. There are other options. And I will go and say, Okay, I can go and recite it. I knew they tell me, well, cannot resect because he’s beside the IBC. Well, right now I finish this and I have to go and replace an IBC in a liver transplant. So I’m a liver transplant surgeon, that’s my business.

Betsy Post 59:18
Would someone that had a failed PVE be a candidate given that they have less liver volume,

Dr. Roberto Hernandez-Alejandro 59:26
Yes. So this helps for those patients who have less liver volume, because it preserves more liver volume. We don’t have to one resect much, okay, if the tumors are more in the left side, right? I know I’m repeating this too much, and hopefully I don’t know, in two or three or four years, this group comes with an idea of saying, okay, you know what? Now we’re dealing with the right side. That will be phenomenal.

Betsy Post 59:55
Is this something can innumerable mets to the liver be addressed if they’re small, but tiny.

Dr. Roberto Hernandez-Alejandro 1:00:02
I will have to see the images. I wouldn’t be able to answer that. I will need to see the images. If there are little, little, little, probably not. You need to have at least some size. One, one and a half, two, three centimeters. Okay, one that are little ones, it will be very difficult.

Betsy Post 1:00:22
Is there information on the complication rate of this versus ablation?

Dr. Roberto Hernandez-Alejandro 1:00:28
So you know, in good places, when they do when they do ablation, the complication rate is low in good centers, people who are talented, of course, if the tumor is located in the segment one, right, if you know it’s more complex, or if it’s very high, then very close to the lungs, it’s more complex, and they have more complication rate. But normally, you know the complications would be, for example, bleeding or an injury of a small bile duct, which is not common with normal ablation, with microwave ablation or or radio frequency ablation, but with this, of course, the HistoSonics. There’s not too much data on those patients were treated. Only three have some complications, as I mentioned, and they were, one was infection because of the pancreatic surgery. Another one was pain in the chest. And the third one, I don’t remember, but it was something that with Thailand, only disappeared. So minimal. Hopefully we will have more patients who will be able to share their their outcomes.

Betsy Post 1:01:43
How does this differ from SBRT?

Dr. Roberto Hernandez-Alejandro 1:01:47
I think it’s very different. So SBRT, you know, it’s, it’s a very different, different technique. Where are they going to go and deploy some microspheres? And and it will have some radiation. And then this will be a different it will you have to wait for three to six months to have the peak of the treatment, and you will have it. It works very well in patients who have certain type of tumors, specifically, for example, colonic carcinoma, HCC, because this is where we started using this technology, and nowadays we have started using in colorectal liver metastasis. It’s not our first line, it’s not our preference immediately, but it’s an option that we can use. It’s not the main street that you use for trying to get to resection. It’s not the main street to try to get used for transplantation, but I use it few times when there is some complexity and and, you know, you cannot get there very easily. Then I change streets and and use it in our patients.

Betsy Post 1:02:59
Someone said the use in conjunction with immunotherapy is intriguing. Can you explain how this makes sense with immunotherapy?

Dr. Roberto Hernandez-Alejandro 1:03:10
Because, but what it’s believed that it’s happening is when you would liquefy the tissue your immune system, the patient’s immune system, because there must be some RNA exposed or something like that, your immune system identified that, and then immune system, your lymphocytes and your antibodies, are going to go and attack that. And probably they identify all their other tumors. They now they are enemy tumors, and they will go on and attack them, and maybe they will start reducing in size. Now, if you give immunotherapy, then you’re enhancing the immune response. So that immune response, the abscopal effect that you started with by with histotripsy might get enhanced with immunotherapy. This is just thoughts, okay, don’t take this. This is not we haven’t been able to prove this. We need to prove there’s a lot of research that we have to do in the lab, right? But this, I’m just trying to, to see, to to help patients. There’s things that are going to come in the future. There’s there’s hope that we have to do a lot of work in the lab and help those patients.

Betsy Post 1:04:34
Is a patient with positive CT DNA eligible?

Dr. Roberto Hernandez-Alejandro 1:04:39
Yes, yes.

Betsy Post 1:04:40
Okay, what if I don’t have a left sided tumor? I only have one big right sided tumor because I had a liver resection. Now I have a recurrence.

Dr. Roberto Hernandez-Alejandro 1:04:52
I see – cholorectal metastasis, I would say, Yes, probably, well if, if there’s no – – I don’t know, just thinking very clear. So this patient, for example, has a left a left hepatectomy. Now has recurrence in the right side, but the patient is responding to chemotherapy and the primary has been removed, and there’s no evidence of disease outside the liver. You know, what I’m going to say, right? Why not? Why not transplant? You know? Okay, why not transplant? Right? Patient might be cured with transplant might be – so changing the streets.

Betsy Post 1:05:33
So from what you’ve described, it seems multiple beams have to converge in a spot for this to happen and work. Is that why the tumors have to be a certain size?

Dr. Roberto Hernandez-Alejandro 1:05:46
Yes, and I think they did it from three centimeter tumors because they want to show that it was good visible. And as I mentioned, the low hanging fruit. And now it’s time for start pushing the envelope cautiously and and then do those, those tumors that are a little bit bigger,

Betsy Post 1:06:06
I think we only have one last question, if a patient is accepted for this treatment and lives out of state, what is the frequency of follow up required at your location?

Dr. Roberto Hernandez-Alejandro 1:06:19
I will do with you know, follow up by imaging, and we do a lot of teleconference. I do a lot of telemedicine with our patients. We have a lot of patients from outside the state, and we communicate with their oncology team or their cancer team and give our recommendations, right? And we, you know, we see them every three months, or as often as it’s needed.

Betsy Post 1:06:50
I’m going to ask one last question, just so that I’m super clear, what is the maximum size like with ablation? I know we hear, generally speaking, five centimeters or less. Is that something that’s similar with this? Or did you, did you say, I can’t remember?

Dr. Roberto Hernandez-Alejandro 1:07:07
It was three centimeters in the trials. And, you know, Monday, we did one that it was around four centimeters, or a little bit more than four centimeters, the one that I show you in the pictures, right? If I have a five centimeters, I won’t do it. Probably I will do it in two sessions, because the bubble that creates that bubble of of of the bubbles, the cloud. It’s called the cloud of bubbles. I think it generates around three, three and a half centimeters. So I will do one session of maybe half of tumor, and then the other half of tumor with another session. That’s what I will do. I you know, we have to come with enough innovation and be creative here, because there’s not too much data. So we need to generate that. But I think it will be safer if, if, if it’s in the left side, we can reach it. And if it’s five centimeters, I think you will be if you tell me, if it’s a 20 centimeters, if you know, about 12 centimeters probably wouldn’t I be the preference. I think we’re not there yet.

Betsy Post 1:08:07
Okay, all right. Well, I just wanted to thank you so much for all of your time. Thank you for educating us on this, and I know that we’ll follow up with you again soon, and you’ll have updates, and you’ll continue to keep us all informed. We wish you a happy night, a successful night in the OR.

Dr. Roberto Hernandez-Alejandro 1:08:44
Thank you again to everybody from the group of COLONTOWN. Thank you, Betsy, for this opportunity to all the patients and their families. It’s amazing what you guys do for for your beloves, and I wish you happy holidays, to each one of you and and and a happy life.