Focused Ultrasound: Breaking Barriers, Changing Lives

00:00 Music (under) Host: Hello and welcome to this edition of Cook Children's Doc Talk. Today we're talking about focused ultrasound. No physician ever wants to tell a parent that their child has cancer or a neurological disorder, especially when that disorder is a brain tumor. Even more difficult is being told that it's a diffuse intrinsic pontine glioma, or DIPG. These are highly aggressive and devastating brain tumors that are typically seen in very young children. Because the tumors are located beneath the blood brain barrier in critical areas of the brain, surgical removal is impossible, and there have been no curative treatments for DIPGs with very few children surviving beyond two years after diagnosis. Until now. Enter focused ultrasound therapy, non-invasive, incisionless treatment that is now being offered as a clinical trial in only a handful of pediatric healthcare systems nationwide. In this episode, we're going to be talking about this groundbreaking technology and its impact on pediatric neuro-oncology and neurosurgery and most importantly, bringing life changing outcomes to children. 00:01:11 Host: Cook Children's is honored to be the first pediatric healthcare system to bring this clinical trial to Texas, and joining us today to talk about it, are pediatric neuro oncologist Sibo Zhao, MD, and pediatric neurosurgeon John Honeycutt, MD, and here's a little bit about our guests. 00:01:29 Host: Dr. Zhao earned her medical degree in pediatric hematology oncology from Texas Children's Hospital Baylor College of Medicine, and completed her residency at the University of Texas Health Science Center, School of Medicine. As a neuro oncologist, Dr. Zhao is the medical director of neuro-oncology at Cook Children's and specializes in brain and spinal cord tumors, neurofibromatosis and retinoblastoma. 00:01:54 Host: Dr. Honeycutt earned his medical degree at the University of Arkansas medical school. He completed his residency at the University of Oklahoma, his pediatric neurosurgery fellowship at the University of Tennessee, Le Bonheur Children's Hospital, St. Jude's. He is passionate about new neurosurgical technologies that continually improve outcomes for pediatric patients, and has been instrumental in establishing and growing the IMRI and deep brain stimulation programs at Cook Children's to be among the largest in the world. Welcome and thank you both for taking time out of your busy schedules to be here. 00:02:30 John Honeycutt: Glad to be here. 00:02:31 Dr. Zhao: Yay. 00:02:34 Host: So, Dr. Zhao, you were recently awarded an endowed chair at Cook Children's to start the focused ultrasound therapy program. This is a great opportunity and a huge undertaking. Can you start by telling us a little about the program, and no pun intended, its main focus. 00:02:52 Dr. Zhao: Hi. Thanks for having me today, and that is a great question to start our conversation today. The endow chair program is pretty unique. Physicians who work here at Cook Children's are very busy taking care of patients, and even though a lot of us involve ourselves in clinical research, and especially all of us who are in oncology, we do this just to make sure we bring the best and the latest treatments to patients. But it is very hard to find a significant amount of time to dedicate our efforts to do anything more, or beyond taking care of patients. So the Endowed Chair program allow those of us who have that little bit of extra drive to give us some protected time to do some cool things here in the hospital. So for me, I applied a few years ago, after having lunch with Dr. James Marshall, and he kind of joked about it, and he said, you should consider applying for endowed chair. So that's how it all got started. I initially read up a little bit about focused ultrasound, and the more I read about it, the more, and pretty quickly, I was convinced that we needed to have this here at our hospital, and the only way for us to do it, probably the best way, is through this Endowed Chair program that will give me kind of some leverage and time and resources to really bring the focused ultrasound here to Cook Children's. And really my main goal is not just bring focused ultrasound technology to my patients with brain or spinal cord tumors, but also hopefully over the next several years, as we get to do more with it, expand its use into other departments: neurology, anesthesia, cardiology. I mean, there's a long list of potential subspecialties and fields ... endocrinology. I mean, these are people that I look forward to engage and invite them to also get excited about focused ultrasound. So that's really the main goal, is to bring this almost like a new service line to our hospital, to potentially do some pretty cutting-edge research in various diseases in children. 00:05:14 Host: What are the current challenges or barriers in diagnosing and treating these gliomas? What makes this type of tumor so difficult to treat? 00:05:24 Dr. Zhao: So I think there's different kind of challenges in treating different kinds of gliomas, right? So when we talk about gliomas, and Dr. Honeycutt and I, we know that it's not just one diagnosis. There are the low grade and the slow growing, there are the high grade that are very fast growing. So I think specifically the population that we are focusing on today are those patients with very aggressive type of gliomas, specifically diffuse intrinsic hunting glioma, or DIPG, or a very similar entity called diffuse midline glioma. These are extra challenging for lots of reasons. I think to start with the tumor locations being very centrally located, like the brain stem, the thalamus, these are areas that make resection or to remove the tumor, not possible. So that's a huge challenge to start with. And also, I mean, even though we are learning about these tumors, we have learned more over the last decade about mutations and genetic changes and different things. We truly have just continued to have no good medications or drugs or anything that's effective against these aggressive types of gliomas. They're resistant to chemo, resistant to radiation. We just don't have any good options for them. 00:06:56 John Honeycutt: It's always heartbreaking to us to see one of these when they come in. It's terrible outcomes, and we know what these kids and families have in front of them. So for the longest time, we ... was nothing being done for these and about 15 years ago, oncology and neurosurgery both recognized that we were just spinning our wheels. Weren't doing anything new, and so we have sort of turned a corner and much more interested in being more aggressive and trying to find solutions for these patients and their families. 00:07:32 Host: How does focused ultrasound therapy work from diagnosis to treatment? 00:07:36 Dr. Zhao: Well, focused ultrasound is not meant for diagnostic purpose. It's not an ultrasound because we think of ultrasound as using it to diagnose different conditions. So it's not for diagnosis. So Focused Ultrasound is actually only for therapeutic indication. So it works through several different kind of mechanisms and broadly kind of categorized into five different areas of how they work, and then from there, once it hits the body, it kind of leads to different effects. So it's a huge field, and not just in pediatric there's a lot more that's going on in adult population using focused ultrasound. So the list of how things work, probably somewhere in the range of 60, 70, 80 different ways of how these focused ultrasound technology affect the body to treat different conditions. But I think simply put is that focused ultrasound utilizes sound waves, or ultrasound waves, and it kind of manipulate these sound waves so that the sound waves produce different kinds of energy. And where the sound waves kind of converge and meet on the body itself it delivers its effect. And it's very precise, because we can define where the sound wave goes and where the treatment focus goes, and it goes ... earlier you mentioned it's incisionless, and that's really how it works, is that it's just sound waves kind of penetrating through the skin and get directly deep in the part of the brain, or deep inside the body. Yeah. 00:09:17 Host: One of the greatest difficulties of targeting these gliomas is the blood brain barrier, which is there to protect the brain from risk of infection. So how exactly does this technology allow an infusion into the tumor? 00:09:31 Dr. Zhao: Focused ultrasound has been shown to be able to do that, to open up the blood brain barrier transiently, which is important for us understand. It's not gonna open it permanently or irreversibly. So what happens is that patients will receive an IV dose of a medication, it's called micro bubbles, which are tiny, tiny, like spheres that are gas filled. So these are injected through an IV. And once it's circulating the body, we turn on our focused ultrasound device. And the device, or the machine, has its own like parameters that we dial in to a certain setting and we turn it on, and then that produce this kind of a very mild mechanical force that interacts the sound waves with the micro bubbles, literally just kind of open up the blood brain barrier. But it only opens it up where the tumor is, because we also set where within the brain we want the blood brain barrier to be open. So we can define what we want to do, how we want to do it. So when the blood brain barrier is open, we can give medication through the IV again, so normal chemotherapy that wouldn't go through into the brain now can transient. Hopefully that's the expected outcome, that it can go through an IV, get to the tumor directly, kind of infuse into a tumor, and then what we know is that within a few hours, the blood brain barrier then closes on its own. So we have to time the medication delivery correctly. 00:11:11 John Honeycutt: There are multiple different ways to disrupt the blood brain barrier. Having a conversation earlier, when I was a resident 30 years ago, we were doing this for brain tumors, but what's different now is that it's less invasive, and also it's more focused, so that we can target really just where the tumor is and leave, hopefully, the rest of the brain alone, or have less side effects from that. Which makes it different from what I was trained with long time ago. 00:11:46 Host: What safety concerns does this technology overcome? 00:11:46 John Honeycutt: The beauty of the focused ultrasound is that this can be directed, hopefully, just to the tumor. And so that the side effects from the chemotherapy of exposing this to the entire brain, hopefully, that is now lessened by using this technique. The side effects from their disruption, in of itself, is usually pretty low. Wouldn't expect much issues there. In the past, we would have to worry about some bleeding and some other things ... damage to the brain. But in this technique, it should be much less than that, so it's less worrisome. 00:12:23 John Honeycutt: One of the biggest downsides is that the patients or the kiddos will have to be sedated, and this takes several hours to do, and so we have to undergo general anesthesia to do this. And so there's some minor side effects there. 00:12:39 Host: What do we know about long term effects and repeated use for recurring tumors. 00:12:44 Dr. Zhao: We don't truly know the long-term effects because it's still a fairly new technology. We know that it can be repeated safely. They've done that in adults. They've done that even in the first center who has this technology for pediatric patients, they've repeated it safely as well. So we know it can be repeated. But long term, long term, I don't think we truly know. I imagine being that the effects are localized. It's precise. Some of the effects are you know, we know exactly how long the effect last. In my opinion, I wouldn't worry too much about long-term effects from the procedures itself, meaning, like the focus, ultrasound, actual procedures to do it. I'm not too worried about long term effect. And whether you know long term effect comes from the chemotherapy itself. Yes. I mean, we know a lot about that. But I think comparing to giving more and more chemotherapy or doing re-radiation, or multiple rounds of radiation for recurrent tumors, comparing to those that we now do as our standard kind of salvage options, focused ultrasound is almost a little bit safer or more attractive, in my opinion, and I think should definitely be something we consider for recurrent tumors. 00:14:08 Host: As the first pediatric system in Texas to offer this clinical trial, this makes Cook Children's uniquely poised for this undertaking, yes? 00:14:17 Dr. Zhao: I mean, that's a great question. There are several large pediatric oncology programs or pediatric brain tumor programs here in Texas. It's not about who is better. I think it's just about the fact that our institution was committed and really believed in this program when I applied. So I think that it says a lot about our drive to have more innovative options and to be a leader in the field. So I'm very proud that we will be the first, and I think more institutions will join in. And this will probably become more widely available in the years to come. 00:15:05 John Honeycutt: Cook does a great job of identifying new technologies and able to pivot and to quickly move in directions that are new and open. I know our neurosciences have done a great job of doing that through the years, such as our intraoperative MRI program, that was one of the first installations in a pediatric hospital in North America. With that, our deep brain stimulation program, our epilepsy program … we've done some things that have been innovative using new technology with. And so our hats off to the departments that have been interested in doing these sort of things. And also hats off to the administration and leadership that allows us to be able to pursue these technologies that sometimes can be expensive, that are new and sometimes unproven, and so the ability for us to do that is one of the great reasons why I love working here. 00:16:07 Dr. Zhao: Absolutely. It's a different kind of experience at different institutions. And I am very grateful that our institution have given me tremendous amount of support to bring this here. And I also want to say that not only we're the first in Texas, we're the fourth in the whole country. So truly leading this field. 00:16:15 Host: And so this is research. So what do we know right now? And what do you guys expect to learn from the Endowed Chair and from the research. 00:16:39 Dr. Zhao: Given that we're using a research device that has some FDA approval in adults and some approval in pediatric patients, but it's used in pediatric brain tumors, or brain tumors in general, is not approved. So this is, you know, risky research. I think that with anything that we try this early stage, obviously, there are a lot of unknowns. We worry about safety number one, which fortunately has been shown to be pretty safe with the prior patients who have received this kind of treatment. So we feel that we are going to move ahead cautiously, but I think the safety data, the early safety data, is there. The other thing we don't know, obviously, is efficacy, and that is a bigger question in our head, is that, is this going to change the outcome, or how much improvement are we going to see with not only this trial, but other Focused Ultrasound trials that are yet to come? How much help, or how much is this going to change the patient outcome? So we don't know. I think there are a lot to learn to begin with, learning how to use the device, learning how to be safe in operating room, learning the tricks, and, you know, all the technical aspect of this and how patient do after the procedures. And there's so much to be learned. I think this is just a start, and as we expand in the future, we hope to learn how we can use it in epilepsy and movement disorders and other diagnosis and conditions. So the list goes on and on. 00:18:26 John Honeycutt: That's one of the, for me personally, one of the fun things about this is that learning new technology, learning how to implement it, what is available to ... that you can use it for in the future. I think that's just fascinating, and it's one of the reasons why I love getting up and coming to work, is the challenge of learning something new. It's really exciting times. 00:18:49 Host: For me too, just getting to hear all of this and learning it's like it is, makes me get up and come here every day. So what are the qualifications for acceptance to the trial? 00:19:00 Dr. Zhao: So specifically for the trial we're about to open here at Cook Children, which is for patients with DIPG, we're looking for patients between the age of five and 21 who are newly diagnosed with DIPG, and this can be done through radiographic diagnosis without a biopsy. But if they had a biopsy done at their institution, we obviously want to make sure that we have the correct diagnosis and that they fully recover from their surgery. So patients should come to us for trial consideration, at minimum, four weeks post radiation, but no more than 12 weeks from completion of radiation. So that's the window to get on this study. Generally, we say that patients should have a good performance status. Have no deteriorating neurological symptoms, just doing fairly well. There are some very specific eligibility considerations as far as the tumor size, their head size, and on MRI, are there any concerning imaging findings within the tumor? So those are things will be evaluated case-by-case by the study team pretty carefully to make sure that the child is a good candidate to participate. 00:20:23 Host: We focused on brain gliomas, mostly today. But what are other neurological conditions do you see treating in the future? 00:20:32 John Honeycutt: So this is where it gets super exciting for me and our team. Is that, what else can this be used for to do, as you would say, incisionless treatment of neurological problems? Probably the biggest use in the last decade has been for tremors, and so for movement disorders, and it's FDA approved to do that. But can it be used for other movement disorders that we see, such as dystonia, spasticity? Those are things that we currently use deep brain stimulation for. And so, can the focused ultrasound be used to create lesions in the brain to treat those areas instead of doing implants? And so we have been interested in that possibility for the last 10 to 15 years. Is there ways to treat these movement disorders that don't have to leave equipment inside? And so there are side effects from that. You have to have repeat surgery to change batteries out and so forth. And so if you could have one time solution to these problems, that is preferable. There are downsides of doing this, though, this is irreversible when you do that with focused ultrasound. So we'll have to look over time and see if there are specific candidates that could be used for that. We have talked about, can we treat other tumors and use the focused ultrasound for that instead of using other techniques that we currently use, like laser ablation that delivers heat to destroy tumors that we currently do. Can we now do that with the Focused Ultrasound instead of using the laser probe? We also have interest in the can we use it for epilepsy also, and so sometimes in epilepsy, those seizure foci in the brain, we treat, now currently with laser or do an open surgery for resection. And could this be used instead. So we have multiple pathways that we're interested in. This is our initial foray into it, and see how this goes, and if that is promising, and we think the technology is worthwhile, then we can then open that up to other pathways and other treatment possibilities. 00:22:39 Dr. Zhao: Yeah, I'm glad that there are a lot of interest from neurosciences and neurology and neurosurgery, because they're all going to be very important users of focused ultrasound technology. I just want to add these lists of conditions Dr. Honeycutt just mentioned, like movement disorders and epilepsy and things like that, those are currently areas that no one has looked into in children. So it sounds like we have a lot of ideas, but to take this into something that's a real trial in pediatric patients will take some time. But no one else is doing that, so it's very likely we'll be the first hospital to be doing these type of research on other neurological conditions in children. So it's very exciting. 00:23:32 Host: What about oncological as well? 00:23:34 Dr. Zhao: Yeah, absolutely. So within central nervous system, other kind of recurrent tumors that we talked about, right? So not just DIPG, but we have other malignant brain tumors that once they recur, we don't have great treatment options for. So can we think about using this to treat recurrent medulloblastoma, recurrent pendaloma, or these kind of other diagnosis? Dr. Honeycutt and I are brainstorming options to treat benign brain tumors kind of similarly to laser ablation, but using focused ultrasound. So these are things that I'm thinking about as a neuro-oncologist, but absolutely I have had conversations with my partners in oncology or general oncologists. Focused ultrasound, has a different device that's specifically meant to use on the body. So not a neural device, but a body device that can be moved around the treatment table to different parts, like extremities and body abdomen, anywhere. So recurrent solid tumors and different things. So in fact, desmoid tumor is an area that has a lot of interest overseas and has been approved in Europe to use focused ultrasound to treat desmoid tumors. So I think that there are potentials to expand in oncology in general. 00:25:01 Host: I can certainly see why you guys are excited. For families and patients Focused Ultrasound is proving to be a beacon of hope, providing neuro-oncologists, neurosurgeons and neurologists, the possibility of less invasive and even, dare I say it, curative treatment, for referring physicians or even families where can they learn about this trial. 00:25:21 Dr. Zhao: So for this specific trial, I encourage those who are interested to check it out on our website, at Cook Children's, dot org, and especially if you look at the neuro-oncology program here at Cook Children's, or my Endowed Chair program, you should be able to find a link to this particular trial. But for more general information about focused ultrasound, whether it's used in research in kids or adults, one of the website that I love is Focused Ultrasound Foundation. On that website, there are buttons to click for clinicians, and a different button click that says for patients, and it lists everything by diagnosis, so you can look and see what's being done for a specific disease, what trials are open, what trials are closed, what has been published. There are lots of information. So that's a great resource. 00:26:19 Host: This is just really super exciting. And of course, we're still kind of at the beginning of this, so hopefully we can come back in ... how long do you think it'll take before you have some information that we can update? 00:26:32 Dr. Zhao: I think in a couple years, we should have more patient treatment experiences and hopefully more data on this trial outcome, because it will be a trial with a small number of patients, so hoping that the study will finish its enrollment and have some preliminary data to share, but I think that the hope is that we come back and report with more activities and other studies and other trials and different research that we're getting into. 00:27:04 Host: Fantastic. So we look forward to rescheduling or scheduling in the future. Is there anything you'd like to add that we haven't touched on today? 00:27:14 John Honeycutt: One of the beauties of working here is the collaboration between the departments and how easy it is to just pick up the phone or find someone in the hallway and then expound on ideas. And being here for 20 years, I've seen that play out time and time again, and it's been a real joy in working with Dr. Zhao and the oncology department and Dr. Murray that used to be here before, and coming up with ideas and acting on them and moving forward. And it's always a pleasure, and it's always fun. It does mean extra work sometimes, and worry and this and that, but in the long run, it's fruitful and productive, and I believe it gives better care to our patients. And so just one of those reasons that, once again, it's just a great place to work, to be able to have that collaboration. 00:28:12 Dr. Zhao: Yeah, thank you. Thank you for that comment, because they're very busy neurosurgeons, and for them to carve out time for this research, or for any research, it's extra time out of their busy schedule. And I think that through the last few years of working here, I have convinced myself that I can bother them and ask them and and come up with crazy things, and sometimes it's a little more hesitation, but most of the time, they have been very supportive of our program, and I think we all have the same interests. It's just to do best for our kiddos. 00:28:53 Host: Thank you both for being here and for sharing the details of this program. Really looking forward to seeing where it goes and what you guys can accomplish. 00:29:02 Dr. Zhao: Thank you. 00:29:02 John Honeycutt: Thank you. Appreciate it. 00:29:04 Dr. Zhao: Thank you for having us. 00:29:05 Host: For our listeners, if you'd like to learn more about this program, visit our website at Cook children.org. You can also access clinical pathways on the health professionals section of the website, and while you're there, sign up for our Doc Talk newsletter. Want more Doc Talk? Get our latest episodes delivered directly to your inbox when you subscribe to our Cook Children's dot talk podcast from your favorite podcast provider, and thank you for listening. 00:29:29 (music out)