A Novel Vaccine Trial for Children with Rare Brain Cancer, DIPG with Ashley Plant-Fox, MD and Michael DeCuypere, MD, PhD

Diffuse intrinsic pontine glioma, known as DIPG, is a rare and aggressive type of pediatric cancer that forms in the brainstem, resulting in approximately 200 to 300 new cases in the United States each year. Fortunately, investigators at Lurie Children's Hospital are paving the way to breakthrough treatment for children with DIPG. In this episode, Lurie Children’s physicians Dr. Ashley Plant-Fox and Dr. Michael DeCuypere discuss the progress of this first-of-its-kind, phase 1 clinical trial for DIPG that has been open since January of 2022 and offers hope for a disease that currently has no curative options.

“Just having the clinical trials for this rare tumor alone offers a lot of hope to families who might have otherwise heard that there's nothing to be hopeful about. I'm very proud that we have multiple options for DIPG patients who get this diagnosis.”

Ashley Plant-Fox, MD
Attending Physician, Hematology, Oncology, Neuro-Oncology and Stem Cell Transplantation, Ann & Robert H. Lurie Children’s Hospital of Chicago
A.M. Khokhar Research Scholar, Ann & Robert H. Lurie Children’s Hospital of Chicago
Associate Professor of Pediatrics in the Division of Hematology, Oncology, and Stem Cell Transplantation, Northwestern University Feinberg School of Medicine

“We're very accurate with our biopsies. A lot of it comes down to the experience of the surgeon in doing these and being able to pick the safest spot that you can find that will give you the answers you want.”

Michael DeCuypere, MD, PhD
Attending Physician, Neurosurgery; Director of Research; Eleanor Clarke Research Scholar in Developmental Neurobiology Research
Assistant Professor of Neurological Surgery, Northwestern University Feinberg School of Medicine
Director of Translational Research and Clinical Trials in Neurosurgery

Show Notes

  • DIPG is a tumor in the brainstem, specifically in the pons, that occurs in children aged 3 to 8. Given its precarious location and biology, it has a five-year overall survival rate of less than one percent.
  • The onset and progression of DIPG is very fast, often only showing up initially as minor symptoms. Presently, children tend to live less than a year, but are given radiation treatment to prolong their lives as much as possible.
  • Advances in biopsy technology have allowed investigators to gather much more precise molecular information about these tumors, and to do so relatively safely.
  • It’s speculated that DIPG results from a genetic mutation, with the majority of tumors driven by a histone mutation, specifically histone 3.3 or 3.1 with a K27M mutation.
  • Unlike infectious disease vaccines which aim to prevent disease, the novel DIPG vaccine in development and being used in this clinical trial  is designed to retrospectively teach the immune system to recognize the DIPG tumor already present in children.
  • The vaccine combines a heat shock protein with 16 peptides that are unique to DIPG to boost the immune system's recognition of the cancer cells. Children receive the vaccine just like they would any other vaccine.
  • Dr. DeCuypere often meets with families initially to discuss whether or not they want to pursue a biopsy of the tumor for an official diagnosis, and furthermore, if they want their child to take part in the clinical trials.
  • The clinical trial is primarily at Lurie Children’s but satellite cancer centers are offering the trial as well. There are also specialized labs all over the country performing biologic correlates to the vaccine study to expand upon the research.
  • Dr. DeCuypere recommends a biopsy for every DIPG patient. Not only are the health risks quite low, the information gathered from the biopsies are an enormous help to the continued development of possible treatments for DIPG.
  • While government funding has certainly helped DIPG research, the investigators say the financial support from families and foundations has helped get this research off the ground. 


[00:00:00] Erin Spain, MS: This is Precision, Perspectives on Children's Surgery from Ann and Robert H. Lurie Children's Hospital of Chicago. I'm your host, Erin Spain. On this podcast, we introduce you to surgeons at one of the country's most renowned children's hospitals to find out how they're transforming pediatric medicine. Investigators at Lurie Children's Hospital are paving the way to breakthrough treatment to help children with a rare and aggressive type of pediatric brain cancer called diffuse intrinsic pontine glioma, or DIPG. A phase one clinical trial of a novel vaccine that targets DIPG has been open at Lure Children's since January of 2022 for patients newly diagnosed with this disease. Dr. Ashley Plant-Fox and Dr. Michael DeCuypere, join me today to talk about the progress of this first of its kind clinical trial for DIPG. Dr. Plant-Fox is the principal investigator of the trial. She's a neuro oncologist and attending physician at Lurie Children's and hematology, oncology, neuro oncology, and stem cell transplantation. Dr. DeCuypere is a pediatric neurosurgeon at Lurie Children's who specializes in brain tumor surgery and research, and is joining Dr. Plant-Fox's team to perform biopsies of DIPG tumors within this clinical trial. Welcome to both. Welcome to the show.

[00:01:27] Ashley Plant-Fox, MD: Thanks for having us.

[00:01:28] Michael DeCuypere, MD, PhD: Yeah, it's great to be here. Thank you.

[00:01:30] Erin Spain, MS: Let's talk a little bit about this rare disease, DIPG. What is it, and what makes it such a deadly form of cancer for the pediatric population?

[00:01:38] Ashley Plant-Fox, MD: So DIPG is a tumor in the brainstem, specifically in the pons, that occurs in children around three to eight years of age. Unfortunately, given its location and just the biology of this tumor, It has led to five-year overall survival rates of less than 1%. And we really have no standard of care treatment options for these patients. Some of the issues revolve around the fact that it is not surgically resectable. So as its name says, diffuse intrinsic pontine glioma, it really grows intrinsic to the brainstem. And so it's not able to be separated surgically from the normal tissue. So surgery is just not an option for these patients, which is a really bad place to start in terms of higher grade gliomas. But specifically regarding the biology as well, whether or not this tumor is found on pathology to be grade two or grade four, it doesn't matter in this tumor. Something about the biology, which we can talk more about later, seems to portend worse prognosis than other tumors of its type.

[00:02:37] Erin Spain, MS: And this is a rare disease. Tell me about that, how it compares to other pediatric brain tumors as far as how many kids are diagnosed with this per year?

[00:02:47] Ashley Plant-Fox, MD: Yeah, so only 200 to 300 children per year in the United States are diagnosed with this tumor. Because it's such a poor prognosis in general, a lot of research is still dedicated to this very rare tumor, but it is you know, not even one of our top diagnoses, but we see so many because they need to come for clinical trials because there are no treatment options at, other children's hospitals or hospitals around the country that don't have access to these early phase clinical trials.

[00:03:13] Erin Spain, MS: It seems that the onset of this disease is very fast, and that the progression is really fast. Can you just underscore that a little bit about the timeline that these families have?

[00:03:25] Ashley Plant-Fox, MD: The presentation and time course of this disease is nothing short of terrible. You know, a lot of these families have a 3-to-8-year-old who was doing their normal things, growing and developing, and then two to three weeks before meeting us, a little symptom presents. You know, a change in their eating, the way their eyes are moving, something subtle like that. To go from that and then meeting us and hearing that their child has a fatal diagnosis and less than a year to live, is really devastating. And to see children go from playing and jumping and talking to not being able to eat on their own, not being able to walk on their own you know, really requiring their parent to do everything for them. It's really frustrating for the child too, who otherwise possesses the same neurocognitive function and personality. They're just kind of trapped in their bodies with limited function because of this tumor and how devastating and quickly progressive it's been. So, I have a lot of compassion for families going through this. No one should ever have to go through this. It's really just emotionally hard from day one. So we try to do everything we can to offer hope and support in that direction, but really, it's probably the worst thing any parent could ever face.

[00:04:35] Erin Spain, MS: You all actually see a lot of these cases because people are coming to Lurie Children's. The trial that we're going to get into a little bit, there's opportunities for specialized treatment and care. So walk me through what it's like when you interact with a patient who's been diagnosed with DIPG. Tell me how they end up face-to-face with you and then walk me through the course of this disease.

[00:04:57] Ashley Plant-Fox, MD: We usually see these patients two to three weeks after symptoms develop. And unfortunately, from the moment that I see their MRI, I already know what we're dealing with. So, we always talk about the DIPG pace, which basically means we're pacing outside that patient's room trying to think of the most compassionate way to have a conversation, first meeting this family, in which we need to say, unfortunately, your child has DIPG and there are no curative options for this tumor, so we have a few choices here. Do we wanna do a biopsy to find out more information and confirm things so that you can kind of have peace of mind going forward in your decision making? Again, that's optional because it isn't currently required if the imaging is consistent with DIPG. And then, do you wanna take your child home and enjoy the time that you have, or do you wanna pursue clinical trials? When they get this diagnosis at a hospital that doesn't have early phase clinical trials, often they can offer radiation as a way to kinda stabilize symptoms and hopefully give some more quality time at home with the family but there's no chemotherapy that's known to work. We've done many trials in regards to that and it just doesn't change the course of disease and exposes the child to some toxicity as well. So really we are going from radiation straight into clinical trials or nothing. I have a hard time doing my job without access to clinical trials. So I chose to come and work at a place like Lurie Children's where we're a part of multiple early phase clinical trial consortiums for pediatric brain tumors, which is a way that we help centralize our resources in order to run trials on rare tumors, and we can interact with our colleagues across the country and now internationally for some of these consortiums to enroll enough to actually get answers quickly on whether or not a new therapeutic option is actually doing something for these patients or not. But really just having the clinical trials for this rare tumor alone offers a lot of hope to families who might have otherwise heard that there's nothing to be hopeful about. So, I'm very proud that we have multiple options for DIPG patients who get this diagnosis and we do take a lot of referrals in state and out of state and even internationally for some of these.

[00:07:01] Erin Spain, MS: Dr. DeCuypere, can you tell me why it's been so difficult to do biopsies on this tumor, and why you're now able to progress and do more with these biopsies?

[00:07:13] Michael DeCuypere, MD, PhD: As Ashley said, these are rare tumors. And for people not in our field, I think it's an important point to make that not all brainstem tumors are DIPG or DMG, another name, dorsal midline glioma. The vast majority are actually not DIPG. In dark ages of neurosurgery, so this is like pre MRI era, people would see these images on CT and they'd see this expansile, diffusely growing, infiltrating mass in the brainstem, and they immediately made the right call and said, you know, this is not surgically resectable safely. Then we developed different technologies. MRI came along and we got to look a little more closely at the brainstem. So then, as Ashley mentioned people started doing stereotactic biopsies. And what that basically means is taking a small probe that's a little bit bigger than the lead of a pencil. And using coordinates and a frame that allows us to very precisely stick that probe into areas of the brain and take tissue samples. And that actually has proven to be quite safe for pretty much every type of brain tumor, regardless of location with the few exceptions. And that has allowed us to get molecular information. And then we started realizing that, you know, as Ashley said, these histone alterations, these are a different type of tumor. This is not what we thought a bit unexpected and, you know, we're learning things all the time about why these tumors are different and what they're driven by, why they form a disease. But we've still got a long way to go, of course, because we just started biopsying these maybe in the past 15 years. And now it's becoming more commonplace. But technology has also improved and, you know, we're very accurate with our biopsies and a lot of it comes down to the experience of the surgeon in doing these and being able to pick the safest spot that you can find that will give you the answers you want. also picking the right approach to that area. And so, I think nowadays, people are biopsying these lesions more and more. And this has led, again, to more clinical trials. More drugs, more options for these kids. Unfortunately, the survival is still quite poor as Ashley pointed out. But this is the way forward. This is the way we develop these new therapies.

[00:09:29] Erin Spain, MS: So it's speculated that the development of this tumor is due to a genetic mutation. Tell me what else is known so far about the cause of this cancer and why it rarely occurs in adults. It seems to really target these young children, as you mentioned.

[00:09:43] Ashley Plant-Fox, MD: Yes, definitely far more common in children. It was because of a Pediatric Brain Tumor Consortium led trial in which they did the first biopsies of these tumors across the country in specialized centers that we were able to learn the actual molecular drivers of this tumor. So how I explain this to patients is that typically in cancer we find mutations in a single protein and that's if you had an orchestra, maybe there's a problem with the flutes. You just need to fix the problem with the flutes. But unfortunately, this is a problem of the conductor of the orchestra. So really the whole symphony is dysregulated and so the cancer pathways that would normally be turned off are turned on and the cancer suppressive pathways are now not doing their job. So really it's a dysregulation of the whole system and so that makes it particularly difficult to also target from a therapeutic standpoint as well.

[00:10:32] Erin Spain, MS: Dr. Plant-Fox, I want you to talk to me a little bit more about this trial that you've been working on that you were the principal investigator for. You've been developing a new vaccine for DIPG. Tell me more about that. How does it work and how is it being used in this clinical trial?

[00:10:48] Ashley Plant-Fox, MD: So unlike an infectious disease vaccine where we're actually trying to preemptively get an immune response, here, we know that they already have the cancer cells and the markers of those cancer cells in their body. And we're trying to retrospectively have the immune system learn to recognize the tumor. So, what we've seen in the data, specifically for DIPG and a lot of the other pediatric brain tumors is that they generally don't have a lot of immune response. Although they're definitely foreign and abnormal cells. So there are multiple mechanisms at which the tumor can evade the immune system. Some is to not actually send up signals to turn off the immune system if the immune system is recognizing the tumor cells initially as foreign. They can also kind of act normal, act like a normal cell and not have a lot of these markers out on the cell surface. So what we're trying to do is take advantage of the radiation that they're initially getting, which exposes a lot of the markers of these cancers being foreign to the immune system to really rev up an immune response. So the vaccine itself contains 16 peptides that are unique to DIPG. What we were very happy about in finding out this data from the DIPG biopsies is that there's very few very conserved, genetic alterations in these tumors. So an off-the-shelf vaccine that targets most of what we see out there could be used for every patient, as opposed to having to delay and make a new vaccine for each patient.The vaccine backbone, you might have heard in infectious disease, there's mRNA backbones, peptide vaccines, et cetera. So, we're using actually a heat shock protein backbone. Heat shock proteins in general, we always think of them in biology as being involved in the folding of proteins to make sure they're folded correctly, but they actually interact with the immune system, both the innate and adaptive immune system through some cell surface receptors, including CD 40 and CD 91. So we are exposing the immune cells to these peptides, complex with the heat shock protein to tell them, hey, this is something that we want you to recognize and go and fight. So the vaccine is one component of the trial. We are also combining it in subsequent arms which checkpoint blockade molecules, specifically anti-PD-1, anti-program cell death, and anti-CTLA-4. And the reason we're doing that is because we don't wanna give DIPG a chance to learn what we're doing. So the whole idea is to take advantage of the fact that radiation is killing these cells and kind of releasing these intracellular markers into that space to tell the immune system, hey, go seek this out and fight this. And then also kind of have the backup of these checkpoint blockchain molecules to kind of fend off any resistant mechanisms that develop. So that's really the theory behind this vaccine and whether or not that's gonna do what we want it to do is to be determined.

[00:13:35] Erin Spain, MS: That's right. You're in phase one of this clinical trial. It started in January of 2022 at Lurie children's, but you also have a few other centers around the country that are able to offer this clinical trial. Tell me about the role that each of you play in this trial.

[00:13:50] Ashley Plant-Fox, MD: It's definitely a team approach. Specifically for these tumors and in pediatric neuro-oncology in general, but a lot of the time Dr. DeCuypere meets these patients first and really the first question is do you want a biopsy or not? And then having us come in and kind of have the conversation of like what we globally expect, the risks of biopsy are discussed by our surgery team and we kind of discuss Hey, how might those results Be helpful or not. And a lot of the time what we're saying is, you know, if you wanna pursue clinical trials, having that information so we can kind of guide decisions around which trial might make the most sense for your particular child is helpful, but there are some risks involved and no guaranteed benefit from getting this information. So that's a hard to discussion upfront. in itself. At least I can come back and say, hey, we have one of the neurosurgeons with the most experience. This is a specialized hospital. I don't think that we are taking on unnecessary risk by offering this biopsy. So, I think having that context is helpful. The other thing is that we can meet ahead of time and think about what clinical trial options we wanna preserve for them going forward. So, some clinical trials require a lot of tissue and that's a very sensitive area of the brain, getting a lot of tissue. We rely on Dr. DeCuypere to tell us how much is okay. Then we decide how to strategically send the tissue cores in different directions depending on what clinical trial the family wants to pursue. So, we wanna know what the diagnosis is confirming that histologically, sending molecular tests to find out what particular genetic alterations they have. Often it's a histone mutation, but there are other secondary mutations that might point us in a direction of one treatment or trial over another. So we want that information. For this particular trial for the DIPG vax, we actually wanna see what the immune system is already doing in the tumor. So we have specialized labs actually all over the country and even one in Canada that do a lot of biologic correlates to the vaccine study in order to help us learn as much as possible. When it's a rare tumor, not only do we wanna learn everything about patients who are currently enrolled, but if we ever wanna improve upon the treatments that we're offering, this information is, you know, pivotal to making some of those decisions. So, we collect not only the tissue upfront from the biopsy, but also blood samples along the way, too, to kind of monitor the immune response to that.

[00:15:59] Erin Spain, MS: Dr. DeCuypere, you're the one that is initially meeting with these families. Tell me about those interactions and how you're able to communicate with them during this really difficult time about their options and explain things to them. Tell me about your approach.

[00:16:14] Michael DeCuypere, MD, PhD: Yeah, it's difficult, like Ashley said, right? We can look at an MRI and know that it doesn't look good. I think you have to be very honest and just upfront and say, look, doesn't look good. This is what we think it is. I personally recommend a biopsy on every single one. And that's a little controversial probably because some surgeons who trained a while ago and who don't see many of these tumors. They may see one a year or maybe not even one a year, were trained to, oh, you can't biopsy them, you can't take them out, it's too dangerous, don't touch them, sorry, I can't do anything. But if you actually, if you look at our literature about biopsying these tumors, the risk of causing a new neurological deficit, or making a neurological deficit that they already have worse is about 10%. And that's not bad, right? So 90 percent chance that we do the biopsy and the patient wakes up the same as they did when they went to sleep. The risk of death or a catastrophic hemorrhage, for example, in a biopsy is virtually zero. Like if you look at the literature, over a thousand biopsies that have been reported, there's almost zero deaths that have been reported attributable to the biopsy itself. That's the way I approach it. And, and I say, look, you know, is safe. If it were not safe, I wouldn't even offer it to you. But I think it's safe and we can actually get a lot of valuable information about your tumor. We can, A, confirm the diagnosis, which like Ashley said is not absolutely necessary, but it sure helps. And then I think in the future, moving forward, it's going to be even more important. Because as Ashley said, these tumors are very smart. They have lots of ways to evade the immune system. Not just one or two. And the only way we learn about these tumors is looking at the tissue and getting ideas about, Hey, what are some strategies that we can employ here that will make the vaccine work better or that we can partner with the vaccine, as Ashley mentioned? Because, as an examplePD 1 is an immune checkpoint. molecule. And what that means is it's a way that some tumors can use to hide from the immune system by sort of expressing these molecules and activating them. A lot of that comes from adult research, right? This is from adult tumors.. We assume that, well, if being expressed in these adult tumors, maybe it's being expressed in pediatric tumors. We're learning it's not necessarily the case, and in a lot of tumors, it's not the case at all. So just because it's found in adults or different types of tumors does not mean that this tumor is going to use it. And so I think, moving forward in the future, in the next, you 5, 10, even beyond, we might even be tailoring each individual patient's treatment. We don't even know if all DIPGs are the same, right? Like, we assume it's, oh, we have a DIPG and it's exactly the same as the last DIPG we saw. I'm not sure that's the case. And so, the more we learn and the more advanced therapeutics we develop and the more options we have, the better it is for everyone moving forward.

[00:19:07] Erin Spain, MS: And not only are you working on this clinical trial, you're doing additional research with specimens and information that you're able to gather from these biopsies. Can you tell me a little bit more about the research that you're pursuing?

[00:19:18] Michael DeCuypere, MD, PhD: Sure. So, I'm very interested in immune therapies and sort of like what, what Ashley was mentioning and what Ashley does. I'm very interested in looking at each type of tumor in pediatrics and learning more about what we call the tumor microenvironment. And basically what that means is, what type of immune cells are present in the brain tumor itself and next to the brain tumor. What types are there? How many of them are there? And then what types of strategies is the tumor using to hide from the immune system or shut it down? And as I mentioned, every tumor is a bit different. But other tumors that we routinely resect we use the tissue on, and we use a lot of different microbiological and molecular biological methods to really study these. And, we can kind of screen them and say, Hey, look, there's a target that we noticed on this tumor that's very much present . And if there's a drug on the market or there's a drug that a company is developing that targets that specific molecule, hey, maybe we can partner with them and start our clinical trial for this tumor, because the drug companies are always looking for applications of their drug or new reasons to use it, and we just don't know, a lot of times we don't know if it's going to work or not. This way is a little more of a strategic method to take a look inside first and say, Hey, wait a minute. I don't think a PD1 inhibitor is going to work here because it's not really being expressed very much, the tumor microenvironment, but this other one is. Maybe we should use that one instead.

[00:20:50] Ashley Plant-Fox, MD: Yeah, that's so true, Mike. I think the other thing that we're learning as there have been a flood of clinical trials for DIPG since we found out these molecular findings is that there are definitely variations in response, even for the tumors with the same molecular phenotypes. That's why it's so important to do everything we can with these initial biopsy samples to figure out, maybe one day, even if the vaccine isn't necessarily successful, the data that we got from this trial could tell us, hey, there's actually particular DIPG patients who should get immunotherapy and there's some that shouldn't. And that we can kind of piece that out a little more based on their immune response to this treatment. So we really wanna, you know, maximize the amount of data that we have on every single patient so that we can continue to progress in this field. I mean, it's been devastating to have so many clinical trials without results or moving on to later phase clinical trials for this particular tumor type.. I think we have to, you know, treat every patient as precious, valuable information for the next group as well as we're trying our best to treat the patient in front of us. So I think that that's all super important.

[00:21:51] Michael DeCuypere, MD, PhD: Great point. I think the highlight is the altruism of these familiesThe idea is even if this doesn't work, you could help other kids and other families in the future in the same boat. And it takes a lot of bravery, I think. You just got the worst news you could possibly imagine about your child. And you know what, even if this looks grim, if we can do anything to help other kids and other families that might be situation and as horrible as this feels, I think that's super brave. And I'm constantly inspired by families who undergo trials and just pure research based things to help other kids and other families.

[00:22:26] Ashley Plant-Fox, MD: The amazing thing too is actually the trial itself is actually funded by families who either have a, a child that was treated for a brain tumor or have lost their child because of a brain tumor, and a hundred percent of the funding is actually from families. So they're pretty amazing.

[00:22:42] Erin Spain, MS: Wow. Tell me about this particular trial and some of the families that you've brought in. How many folks have you enrolled? How many children have you enrolled? And are you on target to move on to the next phase?

[00:22:53] Ashley Plant-Fox, MD: We have enrolled a total of nine patients already and that is across our center and our other centers as well. A lot of these families have been out of state. We have travel funds to be able to help support that because on top of a devastating diagnosis having your family potentially separated, issues with work, et cetera, can make pursuing a clinical trial really challenging. So we opened up the other sites in order to make that easier. We're very happy to be able to do that. Now we are able to enroll most of the kids that come across Lurie Children's. Again, these are rare tumors and they actually have to be in pretty good shape to get onto a clinical trial after radiation. So, some of these patients actually progress before they even get the opportunity to try. So we're really trying to, you know, really be accessible, find out about these kids early, I'm part of a DMG-DIPG National Tumor Board, in which actually families can submit all their information at diagnosis upfront and get a panel of 12 neuro oncologists across the country that have trials to be able to review their case and say, hey, you might be eligible for one in Seattle, one in California, one in Chicago. You know, so they have the whole list and they can decide and kind of make moves as early as possible before their child has a recurrence. So, definitely we're moving forward now and we've been able to see some good immune responses in the blood samples that we're seeing so far, but the true efficacy of this treatment is kind of yet to be determined. We need a little bit more time and more patients before we can fully say that, but we have been happy to see that there are antibody responses, specifically to ACVR1, one of the peptides in the vaccine, as well as sometimes 20 fold increase in the immune cells after receiving a few vaccines. So, the blood is telling us that something is happening with the immune system and, of course, we'll follow very closely to see what kind of responses these kids might have.

[00:24:42] Erin Spain, MS: And you mentioned after a few doses, just explain to me when they're coming to the hospital, how long are they staying and what are they receiving?

[00:24:51] Ashley Plant-Fox, MD: So when they come, we see them in clinic, they get labs, we make sure everything's going well with them, they're not having any side effects of the treatment, and then they'll get a vaccine, which is actually very typical of how you would get a vaccine, either in one shoulder or the other Most patients so far have actually tolerated it very well in the subsequent arms of the study where we're adding the checkpoint blockade. Those will be IV drugs administered over 60 to 90 minutes in our infusion center, But all of this is outpatient. Patients are able to go home after they get their treatment and come back kind of every two weeks to get their treatment until you know, they're either showing progression or they're responding to the treatment. Up to a year, they can receive this treatment. 

[00:25:09] Erin Spain, MS: You mentioned that the research is funded by families, and this really is a group effort. It's a team science effort, but it's a family effort too. Tell me about some of these foundations and organizations that are supporting the work.

[00:25:43] Ashley Plant-Fox, MD: We are very thankful that we have some foundations out there that are specifically looking at pediatric cancer and have identified pediatric brain tumors is a big area of need. So I don't think we've mentioned it yet, but brain tumors are the number one cause of cancer related mortality in every age group in children. So it really is a significant problem. So, there's two big groups that fund the majority of my particular clinical trials. So, the Team Jack Foundation is one of them, and that's a Midwest based foundation, and they've been very generous supporting this trial. And also, the Pediatric Cancer Research Foundation, PCRF, which is based out in California. There's a particular fund within that called the Irwin Fund, the Will Irwin Fund, and that's actually a patient that I treated and a lovely family that has been more than generous to, in their words, you know, make sure that this doesn't happen to any other children in the future. So, really, spending so much of their time and effort and using their network and resources to be able to move this forward has just been amazing because most people have never heard of DIPG, so it's really, you know, getting the word out and, and telling their story from these families experiences and going through various treatments to, you know, motivate other people to, you know, donate. So it's really been pretty fantastic. Yeah, you mentioned this is a decade in the making and Dr. DeCuypere, you mentioned just in the past 15 years, so much has changed with your ability to understand these tumors better. Let's talk about the future and the big picture. Where do you see this research going and evolving

[00:27:10] Michael DeCuypere, MD, PhD: As Ashley mentioned, I don't think anyone therapy is going to move the needle per se for DIPG. I think it's going to be a combination of things. I think the only way we get to know what's going to work and what's not going to work, rather than just simple trial and error, is really profiling each individual patient, maybe. And so I think sort of like a precision medicine or personalized medicine where we actually look at each patient's tumor individually, in the future will be very important. And I think even to utilize each patient's own immune system and some of the features of their tumor, I think is sort of in the future. I think immunotherapies are the future of brain tumor treatments. And I think Ashley's study is a great you know, example of that, of where it's going, especially with DIPG. And again, I'm excited about it. It's the work that I do. I think it's very interesting. As Ashley said, I appreciate all the support we get from families and foundations because funding from the NIH and the federal government is great, but it's hard to get off the ground without these families and foundations giving us the seed money to get started to generate the data to prove our concepts.

[00:28:22] Erin Spain, MS: And Dr. Plant-Fox, as we wrap up today, is there anything else that you want share about this trial and the work that you're doing and the hope that you're trying to offer these families?

[00:28:33] Ashley Plant-Fox, MD: Yeah. I mean, it definitely takes a whole community to do the work that we're doing between the hospital, the physicians, the scientists, the families that work with us on this. And really the fact that there have been over 70 clinical trials in the past couple decades that have enrolled DIPG patients for something that occurs in only two to 300 patients per year in the US is truly a feat in itself. And I believe strongly that the prognosis and the course of DIPG is gonna change in my lifetime in my career. I'm gonna see a difference. And you know, I look patients in the eyes and, state that to them every day that,  I promise that we are doing everything we can in this disease space and really proud to be part of the pediatric neuro-oncology and neurosurgery communities in which people have devoted their careers towards this, not wanting to have to tell a family that there are no options ever again. So, I think Lurie Children's is really at the forefront of that and, you know, I'm proud to be a part of that and to work with Dr. DeCuypere and his team as well. So, I think that there's a bright future ahead.

[00:29:34] Erin Spain, MS: Well, the work that you are both doing is incredible and thank you for sharing the story. And there's a lot of hope here for the future. So I appreciate both of you coming on and sharing this with me today. Thank you so much for your time.

[00:29:47] Ashley Plant-Fox, MD: Thank you, Erin.

[00:29:48] Michael DeCuypere, MD, PhD: Yeah, thanks. Appreciate it.

[00:29:49] Erin Spain, MS: For more information, including how to make a referral or an appointment, visit LurieChildrens.org.

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