Dr. Sibo Zhao takes us on an exploration of new, novel, treatments and research in pediatric neuro-oncology. She also brings into focus the added complexities in brain tumors in children and how those complexities both challenge and benefit what physicians are learning in order to improve treatment.
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Transcript
00:00:03
Host
Hello and welcome to Cook Children's Doc Talk. Treating brain and spinal tumors can be extremely challenging, especially in children. But there have been many breakthroughs in pediatric neuro oncology with more new advancements on the horizon. Today we're talking with Dr. Sibo Zhao, about what's happening in this field. Dr. Zhao is medical director of Cook Children's pediatric Neuro-Oncology Program. She is actively involved in research here at Cook Children's and has written extensively on this subject. Not only is she dedicated to advancing treatment, she is also passionate about how care is delivered to patients and their families as they go through treatment. Dr. Zhao, welcome. We appreciate your taking the time to talk with us.
00:00:46
Dr. Zhao
Thank you for having me today.
00:00:48
Host
So first off, can you give a little history on yourself? What drew you to the practice of pediatric neuro-oncology?
00:00:57
Dr. Zhao
Well Jan, I think throughout my medical trainings, I feel like I've always been drawn to help the vulnerable patient population. You know, that's kind of how I chose pediatrics in the first place, because I felt like the kids, you know, they can't advocate for themselves, they needed more help. And then during residency, oncology would be something that would feel rewarding, because again, those are the kids that need more, and I was drawn to that. So I went to the hemonc and I kinda was wide open thinking like, okay, I want to do oncology, and really sure what kind of tumors are necessarily even needed to pick one. But during fellowship, and during just kind of my early career, I think the brain tumor patients just always kind of tapped on my heart a little bit. And I wanted to do a little bit more for them. And also, the other main thing is that pediatric neuro oncology has not really advanced as fast or as quickly as some of the other types of pediatric malignancies such as you know, leukemia patient outcomes, I felt like there was a need. And this may be something that if I went into that field, I could change that.
00:02:10
Host
So why did you choose the program at Cook Children's? And how does your research background fit in with your role here?
00:02:16
Dr. Zhao
So I spent several years at Texas Children's Hospital first as a trainee and then became a faculty, I honestly didn't really think I would like any other places or want to go away, but I knew deep down that I was just more than prepared, you know, I was very well trained. And I could go on and take on a different type of role or different programs. So I just thought, Okay, I will look around and see so I went and interviewed at several larger children's hospitals and their programs all felt, you know, pretty similar to Texas Children's and, and then this opportunity came up here at Cook Children's, and I came and was pretty much immediately just blown away. I think the culture here was very refreshing to me. And the philosophy here, I've just really kind of fits with what I wanted. And my beliefs. And I'm very glad I joined, I think is probably one of the best decisions I made. As far as research, I think, I realized that the hemonc program here at Cook Children's had a very heavy focus on clinical research, which is what I want to do. So in that regard, transitioning here from TCH to Cook Children's, and being able to continue to do clinical research just makes sense.
00:03:34
Host
What's the difference between pediatric neuro-oncology and adult neuro-oncology? And how does that impact the treatment of children?
00:03:42
Dr. Zhao
Probably first and foremost, despite that, they have the same names. You know, we may have kids and adults that both have glioblastoma for example, we know that the biology are very different between the pediatric brain tumors and the adult brain tumors. By this I mean that they can have the same name, but they may have different mutations, they behave differently. They have different outcomes. So they're just different. I think we always tell our families and we've been trained that you cannot just apply, you know, what's been done to the adult brain tumors the same way as pediatrics. I think the other thing that's really, really important to know, as far as the difference is that treatment options usually lag behind for kids, sometimes by a decade or more, which is unfortunate. And that's not just for neuro-oncology, that's for all pediatric oncology patients. The adult oncology, they receive more research funding, there's more robust pharmaceutical support in drug development. They get more FDA approvals for new agents, and so I think the treatment for them is far ahead compared to the treatment for pediatric patients.
00:04:58
Host
Brain and spinal cord tumors in children are so complex and very difficult to treat, what factors contribute to this?
00:05:05
Dr. Zhao
Yeah, so the main thing is just there's so many different types. You know, people always talk about CNS tumors or Central Nervous tumors or bring our spinal cord tumors, kind of as a group. But really, there are at least the last time I checked more than 120 different types of brain and spinal cord tumors. And that list of diagnosis are still changing and growing. So I think it says a lot about the complexity, you know, we are now reclassifying tumors, not only by the histology, but also by molecular information are integrated into that. So it's shifting over the last five years or so. And we are constantly being updated on what is this new entity, what this type of tumor is. So it's complex, because there's so many different types, and there's always something new that are being discovered, and that we have to learn about. But I think, in a way, the complexity helps us because it helps us, you know, make better diagnosis, it helps us design better treatment plans, or even give better prognosis for families, as far as you know how I think you will respond to this treatment based on you know, this marker or that. So it's complex. But there's a reason why I think the complexity is very important to really fully understand for us to help you know, these kids.
00:06:30
Host
How does the child's age affect how tumors behave and how they respond to treatment?
00:06:36
Dr. Zhao
I don't think the age in itself really affects how the tumors behave. I think certain types of brain tumors are more common in the age group. You know, some tumors are more common in infants, and some we'll see more in older kids. So any differences in outcomes or behavior is probably still more related to the tumor types than just their age. For me, the most important factor related to age is how the treatment will affect that child's neuro cognitive development in the future. For example, we don't offer radiation therapy to young children, because we know the younger they are, the higher the risk there is for them to have neurocognitive deficits in the future. That's the most important thing that age plays in to the treatment decision for me for the brain tumor patients.
00:07:29
Host
Dr. Zhao, what treatments and care are currently available for children with brain and spinal tumors?
00:07:35
Dr. Zhao
So Jan, that is a pretty broad question. In summary, it's a team effort, most of these kids, usually will need some sort of surgery, whether it's a biopsy, or resection to help us make the diagnosis. And following that, depending on what the diagnoses are, they may need chemotherapy, or they may need radiation or they may just be observed. So there's a wide range of treatment, depending on what we're treating.
00:08:04
Host
Some tumors, for instance high grade gliomas, have very poor outcomes and are nearly impossible to treat, what hope then might be on the horizon for getting ahead of such deadly diseases.
00:08:16
Dr. Zhao
These are very difficult cases. And that includes our DIPG patients as well. The pediatric neuro-oncology world, I mean, all of us who take care of these patients are moving as fast as we can. There are numerous clinical trials out there. Some are targeted therapies, some of them, you know, use the immune system to attack the tumors. Some trials are designed to deliver the drugs closer to tumors, so people are looking at all different ways and what we can try what's innovative, that can maybe bring us new treatment options. You know, we are actively researching and really just desperately hoping that we can find something to improve the outcome for these terrible, terrible diseases.
00:09:02
Host
Neuro-oncology, and especially pediatric neuro-oncology is an ever evolving field. In what areas is medical science currently showing the most success, especially for children?
00:09:14
Dr. Zhao
We certainly are learning more and more about pediatric brain tumors at a very rapid pace. In the last five to 10 years, the amount of molecular information kind of just exploded. I think through genetic and epigenetic studies, we now understand a lot more. For example, we know that not all medulloblastomas are the same. We now know why some children do well and why some children don't with the same diagnosis. So in a sense, I think a lot of our success so far is related to gaining more knowledge about these tumors, but the next step will be translating those knowledge into some successfully improved outcomes in the future.
00:10:03
Host
Are there any promising clinical trials available?
00:10:06
Dr. Zhao
Yes. We have recently opened two new clinical trials here at Cook Children's for patients with low grade gliomas. And these two trials are very similar. The only difference is that one trial is for a patient with neurofibromatosis type one, and the other one are for those without that diagnosis, but both are geared toward low grade glioma patients. The trial are studying this town pound or drug selumetinib. It's a MEK inhibitor. As I mentioned earlier, through research, we have known for a number of years now that all pediatric local gliomas are affected by a similar molecular aberration. And this drug selumetinib is a medicine or compound that targets that pathway. So there's just a lot of excitement within this field, in that maybe one day in the future my new patients with newly diagnosed lower gliomas maybe offer a pill that they can take at home instead of having to come in for their IV chemotherapy infusions, and blood counts and all of that monitoring visits. So these trials specifically are comparing the selumetinib with the commercial IV chemotherapy and hopefully be able to draw some conclusions. You know, we also have opened up two new high grade glioma clinical trials here at Cook Children's. Both of these, again, are molecular driven, targeting certain mutations that are commonly found in high grade gliomas. So I think the field is generally moving in that direction for sure.
00:11:45
Host
Trials like that could be real game changers for these kids, especially the idea of taking a pill at home as opposed to having to go through chemo.
00:11:52
Dr. Zhao
Absolutely. I think the excitement is there, the parents, the patients, and all of us who treat these patients, we're all hoping that's where we're headed. But we're not quite there yet. And these ongoing clinical trials will give us that information or validation of what we think will be the new option for them.
00:12:12
Host
What are the factors that determine whether a child should be involved in a clinical trial or qualifies for a clinical trial?
00:12:19
Dr. Zhao
We are a very clinical trial heavy hospital, meaning that the neuro-oncology program would offer clinical trial to every patient who is eligible. Now there are certain diagnosis or certain factors about their diseases or their diagnosis that make them not a candidate for a clinical trial. But as long as a child is a potential candidate, we offer trial options to all families. And it's a consent process where the family have to understand that the participation is voluntary, that a clinical trial helps us improve our future treatment options. But there's always a risk of not knowing if the clinical trial option is just as good as the center of care. But we feel it's very important to offer those and for families to participate. And we appreciate their participation.
00:13:11
Host
One of your key goals is bringing developmental therapeutics to Cook Children's as well as anti cancer care, can you give us some details on that?
00:13:20
Dr. Zhao
So developmental therapeutics is an effort to help both in facilitating the discovery and the development of any new cancer therapeutic treatment options to patients. So in the past, my focus on developmental therapeutics involved testing novel compounds in mice. And now these are mouse models that developed brain tumors after they were injected with brain tumor tissues from our patient, who graciously donated samples. And these kind of experiments really aimed at finding preclinical evidence that a compound is effective, therefore, we may be able to bring them to human trials. So that's kind of what we call translational research, you know, bringing treatment options from the bench side to the bedside. So now, I obviously don't do those kinds of experiments anymore, but I really value the experiences I had in the past. But researchers like myself can continue to contribute to developmental, therapeutics and other ways. And conducting ongoing clinical research is also part of that spectrum of bringing the best treatments and developing new drugs. And that's what I do here. And I am very passionate about it and I hope to bring more and more options to my patients.
00:14:46
Host
How do you see developmental therapeutics changing treatment of children, teens and young adults with brain and spinal tumors?
00:14:54
Dr. Zhao
I think it will lead to more options. Hopefully, less toxic treatment options, and hopefully improved outcome.
00:15:04
Host
How many children does the neuro-oncology team see on an annual basis?
00:15:08
Dr. Zhao
We see on average about 80 to 100 new diagnoses per year. Now, not all of them require full-on treatment, meaning that not all of these kids need surgery or chemo or radiation. But these are the ones that we diagnose. And we follow.
00:15:28
Host
Can you talk a little bit about some of the most difficult cases you see?
00:15:32
Dr. Zhao
Um, unfortunately, there are so many. And I tend to carry a lot of these cases and memories with me. So I think for me, it's not the treatment decisions that are difficult or helping them go through their therapy that's difficult. It's more just the emotional component. That's really difficult. For example, I remember during my pediatric neuro-oncology training, I took care of a little boy with a pretty aggressive form of medullablastoma, and his tumor came back before he even finished treatment, which is suggestive of how aggressive it is. But this family was going through a lot more than that, because his mom had terminal stage four breast cancer. So they were going through this simultaneously. So his mom was not able to be in the hospital with him when he passed away. And I remember sitting with his dad, just him and I, in ICU, you know, for a couple hours or, you know, during the last few hours of his life, and his dad sang, "You've got a friend in me," from Toy Story Three, which is their favorite movie. And to this day, I can't listen to the song, you know, without thinking of him or, or getting teary eyed.
00:16:59
Host
It has to be really, really challenging to not get emotionally involved.
00:17:06
Dr. Zhao
It's impossible.
00:17:10
Host
So what support programs are available to neuro-oncology patients, and maybe even families at Cook Children's?
00:17:18
Dr. Zhao
Oh, there's many so many awesome support programs here. I think what kids love the most are visits from the therapy dogs. We have a camp, called Camp Now, that we host every September. It's a weekend camp, we invite our patients and families. And so that's a popular program that our kids love. The other things like, you know, Child Life and social workers, and, you know, they're always here to support our kids. For the teenagers. We have the AYA or Adolescent and Young Adult program that we offer the option to participate. Some are not willing to participate. But some teens find that really helpful. You know, we also talk to them about fertility preservation, which is very important for our older patients, there ar a ton, I think the list can go on and on.
00:18:07
Host
It must be extremely difficult to deliver those diagnoses to patients and families, what is your approach to helping them understand the condition, the treatment options, and prognoses?
00:18:19
Dr. Zhao
There's not a set way to do this. And I think every oncologist has his or her own ways, I think it's impossible to prepare a set dialogue, because every family is different. So I think over time, you just kind of develop the skill set or a gut feeling like when you meet a family, how best to approach them. Usually, the first time we meet is pretty overwhelming, and you tell them a lot of things, and you really can't expect them to retain much of that. So I think repetition and just, you know, being patient with them, and we often have to go over things a few times for them to get it. And that's all okay. For me, the other thing that's important is just empowering them with knowledge, you know, tell them why we do things a certain way and why this medicine or why that, and I think once they hear the reason they're not just being told what to do, but they have to understand it. And that helps with them in learning and understanding. And just being honest. I think the patients, their families, they deserve to know everything that I know whether it's good or bad, and we talk about it and I share it with them.
00:19:36
Host
So what are the biggest challenges that you face as a physician and as a mom? How does that inform the way you deliver care and your own empathy in those journeys? And how do you cope?
00:19:47
Dr. Zhao
Being a mom 100% changed who I am as a physician, and as an oncologist because when I meet these families, I think that that could be my own children. So I feel their sense of loss, and I grieve with them. So I think it's important, which I talk about a lot with my team, is to walk this journey with them, because it's really the least we can do you know, their children are going through something that, just imagine that your own child's going through that. So, as a female physician with a little kid, I think we never have enough time. We're always struggling, like, you know, having to be at home and do the kids school stuff, and what's for dinner? And and, you know, balancing that with our commitment to our patients or at work. And I don't think I do it well, but I try. I think a lot of us just get by and and try our best.
00:20:43
Host
In terms of coping skills. I mean, obviously, it can be very emotional. So how do you cope with that?
00:20:50
Dr. Zhao
I don't think I've found the magic answer, or what really helps yet. I try to leave as much as I can here at work. But you know, there are some hard days and you can't just turn it off when you walk out of here. So it's something that even my partners who have a lot more years of experience, are still having a hard time. I think it just comes with what we do, and then something that we all need to learn, but I don't do it well.
00:21:20
Host
So talk a little bit about your neuro-oncology team, and also where the child's pediatrician or family physician fits into the team and the child's care, both in the initial diagnosis and the long term.
00:21:32
Dr. Zhao
I love my team here. That was a huge reason why I chose this program. I think they're phenomenal. It really takes a village to take care of these kids. And then your oncologist is just a small part of it. You know, I can't do it without the colleagues from neurosurgery, neuro radiology, my radiation oncology, pathologist, neuro psychology, palliative care, neurology, rehab, I think the list can go on because everybody on that team are important for the care of kids with brain tumors, you know, as well as my nursing staff, my research team down to all of our therapists, the dietictan, everybody. You know, they're all really important to me. And I don't think that missing any of these pieces will make the team function just as well. As far as pediatricians, we have developed really good relationships with them over time, and we try our best to communicate with them. They're usually the first physician or the first care team to realize that something's wrong, and they order the workups. And that leads to the diagnosis, which is super important that they are able to recognize what are the abnormal signs and symptoms of a potential brain tumor. Many of these pediatricians are family physicians checking on their kids during their cancer treatment, which we always welcome. And we love it. Because eventually, when they're done with their treatment, we do want them to go back to their primary care physicians and continue their care there.
00:23:13
Host
Sounds like it takes a huge village. And a lot that goes into the care of these kids. You mentioned earlier, your team follows patients through the Life After Cancer program. What is the significance?
00:23:27
Dr. Zhao
So we follow most of our patients for five years after they're diagnosed. Sometimes we follow them up to 10 years, if they have certain tumor types that we worry more about late recurrences, so we'll follow them extra long. But most of the patients once they are five years out of their treatment, or they're five years have stable disease. And you know, we send them to their survivorship clinic, which is a big milestone for them. The Life After Cancer program here is really designed to address the late effects that our patients experience after their treatment. I think it's super important. Because as these kids grow up, they may not remember exactly everything that's happened to them. So this program is designed to teach them what they have been through and why it's important for them to continue to receive ongoing medical care and surveillance. And so that's a part of our kind of transition, right? So we take care of them for a number of years, but their follow up doesn't end there. They continue to be followed in the Life After Cancer program, which is part of the program within hemonc.
00:24:37
Host
You mentioned late effects are they pretty common?
00:24:40
Dr. Zhao
Unfortunately, more common than most other types of pediatric cancers, because we're dealing with the brain, whether it's brain surgery, radiation, or sometimes even chemotherapy. Delayed effects that we see can be devastating. Um, we have kids that may have various degrees of learning difficulties. They may not be independent fully as an adult. Some kids have deficits in their strength, their balance, they may not be able to eat, see, hear well, they may have hormone issues. So all of these are complications as a result of their diagnosis in the first place, and then the treatment they receive.
00:25:28
Host
So when you diagnose a patient and talk about treatment with the family, do you talk about the late effects? Does that go into their decision making?
00:25:36
Dr. Zhao
We do, because we know how common that happens. And that is part of the conversation from the beginning. Because it's not a surprise, or this may not happen, it's more than likely your child will be experiencing these late effects. So we absolutely educate them early on. Now, sometimes we predict the worst and the kids do really, really well. And that's great. But it's always better to tell them what could potentially happen, than having them see their children not be the same.
00:26:12
Host
So cook children's is one of the largest freestanding pediatric health care systems in the nation. Even though it's not part of the university system it does have a close partnership with the TCU and UNT Health Science Center based in Fort Worth. How is the relationship with the medical school broadening the advancements in pediatric neurological medicine and research at Cook Children's today? And what do you foresee in the future?
00:26:36
Dr. Zhao
I think that's a really interesting question. And I know before I came to Cook Children's, this has always been a topic of discussion. I can see potential for future collaborations on research. This partnership between Cook Children's and the university system is also important for medical education. The Hematology Oncology program here, has always worked closely with medical student research projects. Earlier this year, I helped develop a curriculum for pediatric neuro-oncology elective, and we had our first medical student came and spent a month with us. It was a great experience, because now she's actually finishing up a publication as a result of her time spent here with us. So I think that relationship definitely needs to continue.
00:27:30
Host
That said, what are you working on?
00:27:33
Dr. Zhao
I'm working on a lot of things. There's always a lot on my plate that I can't cross off my list. But I do want to take this opportunity to bring a little bit more focus on our retinoblastoma program. So retinoblastoma falls within the Neuro-Oncology program, which is something that I also take care of. We have a multidisciplinary team here. And we are actively working on bringing intra arterial chemotherapy to our retinoblastoma patients here at Cook Children's. This is something that's only offered at a number of hospitals in the country. And we will be the first center in North Texas to offer this therapy to the patients. So I'm very excited. Stay tuned for updates.
00:28:20
Host
That is exciting news and super cool. Look forward to meeting again and talking about it. Yeah. I love that. Dr. Zhao, thank you so much for talking with us today. We're so glad you could join us today. If you'd like to learn more about this program or any program at Cook Children's, please visit us at Cook Children's dot org
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