Raising Awareness for a Rare Cancer with Love4Lucas President Hide Harashima

Episode Transcript

Dr. Correa:
From the American Academy of Neurology, I'm Dr. Daniel Correa.

Dr. Peters:
And I am Dr. Katie Peters. And this is The Brain and Life Podcast. Daniel, we've had many guests that have made the transition from being really a caregiver or a care partner, whether they're a parent, a sibling, a spouse, a child of a loved one with neurologic disorder, to being an advocate. And we practice our service as physicians. We're out there in the service field. But Daniel, do you also advocate for something that impacts you personally or professionally?

Dr. Correa:
In a way, that's just even what brought me here to working with the Brain and Life magazine and then this creation of the podcast with the AAN, was really to improve health awareness about neurologic conditions and brain health. After so many different people in my family and in communities I was in had been impacted by strokes, dementia, migraines, dramatic brain injuries, and epilepsy, all easily, even a short list within my family. It was clear that we had a long way to go in our community to understand these conditions. And so I wanted to have more conversations like this. And I feel, for me, that's one of my areas of advocacy.
I'm also often trying to work in the Bronx and here in New York with community groups and advocacy groups to increase community awareness about these conditions. But also I think part of the fun part of my life, I'm out running and enjoying the city. And when I get the privilege of running those races, I often try to look for an organization to fundraise for to help support both their community work and research. So for several of the races I've done or those big targets to both help motivate me, but increase awareness, I've helped fundraise for several patient organizations, mostly around epilepsy because that's one of the things that has most closely impacted our family.
But I don't want to put any of that in the context of some of the amazing advocates and leaders that we've interviewed. Those are, I feel, like small things where I'm contributing my own work. But I am amazed often by the leadership and efforts to organize and coordinate our communities and develop research programs by so many of the people that we've interviewed but there are, throughout all the different advocacy organizations.

Dr. Peters:
we have had so many amazing guests that have created so many wonderful organizations, advocacy groups, foundations, and platforms. Whether it is Tabatha Coffey who has websites or is doing her coaching, really to support people that were caregivers of all types of neurologic conditions. So I really agree with you. We've interviewed some really amazing people that do some really spectacular things. But kudos to you, Daniel, for being a superb co-host for this podcast. And I mean, you're bringing so much to all of our listeners about brain health and neurologic conditions and what can be done. I think this is a really hopeful part of our job that we get to be part of this community for all of our listeners. Don't you agree?

Dr. Correa:
I agree completely.

Dr. Peters:
Yeah. I love that he agrees with me completely. But today we're going to hear from a really special guest. His name is Hide Harashima. He's actually in business in New York. He does analytics and does some really fascinating things in the business world, but probably his most important job is he's the dad to two young boys, and one of his sons named Lucas developed a devastating brain tumor known as diffuse intrinsic pontine glioma. It's also known as DIPG. He talks about his experience and how it inspired him to be an advocate and start a foundation called Love for Lucas. And I think while this topic is challenging and is sad, I hope our listeners can see that there's hope and meaning when caregiving transforms into advocacy. We'll also hear from a pediatric and neuro-oncology expert, Dr. Paul Fisher about DIPG and other pediatric brain tumors.
Hello, Brain and Life Podcast listeners, I would like to welcome today, Dr. Hide Harashima. He is a doctor. Am I correct on that?

Hide Harashima:
I went to medical school. I do not practice, so I don't call myself a doctor.

Dr. Peters:
Yes, I'm just used to calling people Doctor, but we'll just know him as Hide for today. He's the co-founder for Masa&Boz LLC, a New York based management consulting firm that helps businesses grow and unify analytics and creativity. But he is also a dad, an advocate and founder and president for Love for Lucas Foundation. He created Love for Lucas Foundation in honor of his wonderful son Lucas, who was diagnosed with a very, very serious form of brain cancer, known as diffuse intrinsic pontine glioma. It's also known as DIPG. And as our audience knows, I'm a neuro-oncologist. So we're going to learn a lot more about this today. Love for Lucas raises funds for research to identify causes, treatments, and really, a cure for DIPG. Hide. Welcome to our podcast.

Hide Harashima:
Thank you Dr. Peters. I'm happy to be here.

Dr. Peters:
Absolutely. So I said that you have a New York-based company, but where are you joining us from today?

Hide Harashima:
I'm in a small town called Pound Ridge. It's about an hour north of New York City, and our family moved here from Brooklyn in 2015. We love being close to nature, so it's a great place with access to nature as well as to New York City. My wife and I met in New York City and we're the parents of two amazing boys, Kai and Lucas.

Dr. Peters:
Oh, wonderful. And has spring sprung yet where you're at?

Hide Harashima:
It's starting to. I see some bulbs popping out, but it's a little early, but it's coming.

Dr. Peters:
Well, you can probably hear that I'm a little sniffly because all the pollen is out and there's just allergies everywhere here in North Carolina.

Hide Harashima:
It's coming out. Yes.

Dr. Peters:
it's absolutely beautiful. So I gave a short introduction about you. Can you just tell us a little bit more about your professional background?

Hide Harashima:
Sure, sure. So in my day job, I'm a partner at a consulting firm, and we specialize in AI implementation and data strategy. I have a background in developing the enterprise applications and working to understand the importance of data. So that work, it led me to use data for things like predictive analytics, for biostatistics analysis, for example, or machine learning, to categorize data to determine the efficacy of new drugs being developed or even qualifying leads for sales department. And so in short, that means I get to work on technology projects that help companies thrive. But as you mentioned, I do have a bigger goal, life goal, and that's to help find a cure for a pediatric brain tumor called DIPG, which we'll discuss. And so maybe I'll be able to combine my experience with AI to find links that we don't know already know about.

Dr. Peters:
I think that's a great idea because we need those links. And as you mentioned, we're going to talk about DIPG, which is diffuse intrinsic pontine glioma. But can you tell us first about your foundation, Love for Lucas Foundation?

Hide Harashima:
Sure. So we set up Love for Lucas as a not-for-profit foundation to honor my son Lucas in 2018. Our mission, you had mentioned our mission is to find a cure for DIPG. That's our primary mission. We also are trying to bring attention, to raise awareness of DIPG, and also provide grants to help families of children diagnosed with DIPG. And so the foundation's mission is my life's mission. We're a hundred percent volunteer organization, and that means every single dollar that we raise is donated towards the mission. And so to date, we've raised over $500,000 towards DIPG since 2018.

Dr. Peters:
That's amazing. And you mentioned, again, DIPG, that's what we're here to talk about. I'm a neuro-oncologist. I know how serious and scary brain tumors are. Can you tell us what diffuse intrinsic pontine glioma is and also how it affects kids?

Hide Harashima:
Yeah, sure. It's a long name, but DIPG, it is a type of brain tumor found in the pons, which is part of the brainstem. And so it primarily affects children. A lot of diagnosis occur between the ages of five and nine years of age. I know that DIPG, or the studies have shown that DIPG makes up about 10 to 15% of all brain tumors in children. And it is rare. We only see about 150 new diagnosis each year in the US and about 300 each year across North America and Europe. So unlike other cancers, there's been very little progress in improving treatments and cure rates for DIPG. And unfortunately, fewer than 10% of children with DIPG survive more than two years after diagnosis. So if we break down, I think as I said, it's a long name, but if we break down the name, it essentially describes how the tumor grows, where it's found, and what kinds of cells give rise to the tumor.
So for people who haven't heard of it, diffuse, it means the tumor's not well contained. It kind of grows into different tissues in your brain. And so the cancer cells mix in with the healthy cells. And so for that reason, it's really difficult or impossible to surgically remove DIPG tumors without damaging healthy tissue. Intrinsic means in, so it's in. And then pontine is the location. It describes where the tumor is located, in the brainstem, it's called the pons. And so that's responsible for a lot of important body functions like breathing and sleeping and balance and things like that. And because those functions are vital for survival, the pressure from the growing tumor becomes very dangerous in a short span of time. And then the last, glioma is a general term for tumors that originate from the glial cells. And so those are found throughout the brain and they make up the white matter that surround and support the neurons. And so DIPG occurs in the glial cells in the pons.
You also mentioned pediatric, right? So there is a difference between adults and pediatric brain tumors.

Dr. Peters:
Absolutely.

Hide Harashima:
So one of the labs that we support brought this up to us recently, and it's important to make this distinction because we don't really think about it enough. So there's three main takeaways. One is the location. Pediatric brain tumors. They're not just smaller versions of the adult tumors, they're biologically distinct and require different treatment approaches. So for example, in kids tumors often form in the brainstem or the cerebellum, affecting movement and balance and essential functions. Whereas in adults, tumors are more likely to be in the cerebral cortex impacting cognition and behavior. So that's the first difference.
The second difference is the biology. The molecular properties of pediatric brain tumor cells are really different from the adult cells or tumors. So that means the treatments that may work in adults, may not work in children. And then the third big difference between adults and pediatric tumors, brain tumors, is that there's limited treatment options. So because pediatric brain tumors are so rare or considered rare, research and funding really lags behind adults oncology. And so we need to learn a lot more about these tumors before we can treat them in the clinic, which is why the options have been so limited.

Dr. Peters:
You have so many important talking points there. I think one of the key ones as a neuro-oncologist that I want to mention and just repeat is that these are not adult brain tumors in children. These are very different entities, species. They behave differently. Another point is the pons is so critically important. All of the information that we have that tells us about how to move our body goes through the pons, goes through the brainstem, out to our spinal cord, to our muscles, so all that motor function. And then all the way, all the information from the outside world about sensation comes up through our spinal cord from the outside, through our spinal cord up into our brainstem and also the pons. So it's so, so critically important.
And the next thing is I remember when I first became a neuro-oncologist, there was really a trend to not biopsy patients. One of the concerns, of course, is because this is such a delicate area, the pons, but because of that, research really suffered and got somewhat stagnant because we didn't have things to study. So I think it's really with foundations like yours that are really, I guess, uplifting the community to say we need to have answers. We need answers, not yesterday. We need answers now. We needed answers yesterday. We don't need answers in the future. We need answers now. But this is all about Lucas, Love for Lucas. Tell us more about Lucas.

Hide Harashima:
Yeah, I'd love to. Before we go there though, one thing I wanted to mention is that while I mentioned the meaning behind DIPG and the biology, the location and the limited options. In real terms, can I talk about DIPG in real terms?

Dr. Peters:
Absolutely.

Hide Harashima:
It's a horrible cancer. It has no known causes and it robs children of their lives. And so in the span of 18 months, Lucas, he suffered through multiple serious brain surgeries, radiation sessions, port surgeries, MRIs, CAT scans, PET scans, intraarterial and intrathecal surgeries for chemotherapy. He went through immunotherapy sessions, GI surgeries, hundreds of needle injections, and sticks. And so in real terms, this is what families go through. And this is not just for DIPG, but for many types of cancers, especially when there's difficulty in finding the cause.
And so through all those procedures, Lucas, he rarely complained. He was just a smile and a joy that we'll always remember. But because as you mentioned, because it's in the pons, week-by-week, he started losing functions, one-by-one. First he lost his balance, so he couldn't walk. He lost his speech, he lost the ability to swallow. His sight was going. Facial and body muscle control, because it's in the pons started to lose control. And then towards the end, the autonomic nervous system starts to fail because the pons is a place where the heart beats. And so what happened is his heartbeat started to beat uncontrollably. And so ultimately that failed and he had went into cardiac arrest.
And so we take for granted these normal everyday things that happen, like a heartbeat or the ability to walk. And so going to this experience really makes me feel or realize how fortunate we all are to not have to worry or think about those things. So that's a little bit about DIPG and what we experienced. And so I could now get into your question about Lucas. So he was in kindergarten. He was a really active, silly, curious, energetic kid. And so, he and his older brother, Kai, we really enjoyed camping and swimming, karate, things like that. Things like little boys always love to do. He was a happy and engaged person and managed to make everyone smile.
As I said, over all those operations and procedures, his personality did not change. So he continued to be the most positive and happy kid who never complained despite all his doctor's visits every morning. So like most six-year-olds, he just wanted to be with his friends at school. That's a little bit about Lucas. And so he was diagnosed in May of 2011, and he was given six to nine months to live. He went 18 months. But again, it's just, it's one of those things that you just hate to see over a short period of time because the cancer is so aggressive.

Dr. Peters:
Thank you so much for sharing all of that about Lucas, and especially about his personality and how nothing changed. And I mention this over and over again to my patients and their care partners and their parents and their loved ones, is that even though they're going through some neurological challenges and even a horrific battle with something like DIPG or a brainstem cancer or any kind of brain cancer, they're still in there and they can benefit from a smile and a handshake or a hug or just love. And that's why I love the name of your organization, Love for Lucas, because it's all coming back to him.

Hide Harashima:
Yeah. Oh yeah. So we did start the foundation in his name, obviously. And it's essentially to continue our efforts to find a cure for DIPG, for not just for Lucas, but for any child, any family who's going through this. And like I said earlier, it's our life's mission.

Dr. Peters:
So what are your hopes and aspirations for patients, for children with DIPG? What is going to be the big discovery? Of course we all want to cure, but can you give us any insights about what you find exciting that could be the next step towards treatment and a better quality of life?

Hide Harashima:
There is hope for sure. There is will and there's hope. And so as his name suggests, Lucas he gave us the light for life. His name means bringer of light. So he was always thinking about others. And I have a short story to demonstrate that. And so we took him to the toy store one day. He wasn't able to walk and he couldn't talk at this point. So we had him in a stroller going through the toy store, and we wanted to see what he wanted. And after walking around for 40 minutes, which is a long time, he managed to tell us something or we tried to decipher what he was trying to tell us, couldn't understand, but we finally understood what he said. And he said he didn't want anything for himself. He wanted to pick a few gifts for all of his friends. So in that spirit of giving, we do want to let families know that there is, as I said, there's a will to find that cure.
We speak to PIs and physicians and oncologists around the world to better understand where they are and how we're supporting research for DIPG. And I see the passion that's running through them. And I think that there will be, I believe talking to them, there will be a cure at some point in our lifetime. And so that hope was keeping our mission alive to find that cure for DIPG.

Dr. Peters:
I agree. And I think about sharing, this is a very rare condition, and I think when you have foundations like Love for Lucas, it is a collective space where those physicians and advocates and care partners and parents and patients can come together and say, this is the collective goal. This is rare, this is not ... We can run very large big studies in patients with very common diseases like Alzheimer's, Parkinson's, in the neurologic space, in the oncology space, leukemia or lung cancer or breast cancer. But when something is very rare, this is where foundations can really have a place and can be that collective environment that allows people to come together. So I just want to say thank you for doing that.
I mean, and I love that your own company is all about unifying and analyzing and then creativity, all of those elements, that's what we need to find cures. And I would say to find cures that are also not going to devastate our patients because radiation and all those injections are really tough and really tough on a developing nervous system that should be developing instead of being ravaged by not just the cancer, but also the treatments.

Hide Harashima:
Absolutely. I think if I could take, you mentioned my work, what I try to do is with my consulting work, I surround myself with experts and people who are driven by that similar purpose. And so similarly with these family foundations, as we band together, we can leverage our collective expertise and connections and funding or fundraising efforts towards that goal. And so while we were going through Lucas's challenges, his school, our geographic community, my wife and my works colleagues in the DIPG community, they all really helped us get through each day. And so we were really lucky to have everyone pitch in to make our lives as memorable as possible with Lucas.
And so our thought was to give back to these communities by continuing our search for the cure as our life's mission. And so what we did was ask our biggest supporters to help us in our mission and continue that even though Lucas has passed. And so that keeps us connected to the communities that supported us. And so we continue to speak with families, with our doctors, our PIs and researchers who are dedicated to finding a cure and anyone who, even just from a parent's perspective, what to expect or what we went through, just to provide a different viewpoint as well.

Dr. Peters:
Well, I appreciate that you've shared with us. I mean, now you've shared with our entire Brain and Life podcast community, all of our wonderful listeners. And so I just want to thank you, Hide, for sharing your experiences, your advocacy, and for everything that you do for DIPG. And don't forget to check out Love for Lucas Foundation, and it's www.love4lucas.org.

Hide Harashima:
Thank you so much Dr. Peters for having me

Dr. Correa:
Want to learn more about the conditions discussed in this episode and other factors that could impact your brain health? For the latest on causes, symptoms, diagnosis, treatment, and management of more than 250 of some of the most common and rare neurologic conditions, please visit brainandlife.org/disorders.

Dr. Peters:
Hello, Brain and Life podcast audience, and of course, thank you for joining us again today. I'm Dr. Katie Peters, your co-host, and I am just so delighted to introduce our medical expert, Dr. Paul Fisher. He is the Professor of Neurology and Pediatrics and the Beirne Family Professor of Pediatric Neuro-Oncology, and the Dunlevie Family University Fellow in Undergraduate Education. He completed his residencies in pediatrics and neurology at Johns Hopkins Hospital, and then a fellowship in neuro-oncology at the Children's Hospital of Philadelphia and Johns Hopkins. I remember stories of him riding on the train, I think, back and forth from Philly to Baltimore.
He also obtained a master's in epidemiology at Johns Hopkins University. He is at Stanford, and he started the Pediatric Neuro-Oncology program where he's now a professor. His clinical work and research focuses on epidemiology therapy and late effects of childhood brain tumors and other childhood cancers. He's authored over 300 scholarly publications on these and other neurology and pediatric topics. And he is going to talk with us today about diffuse intrinsic pontine glioma. Dr. Fisher, welcome to the Brain and Life Podcast.

Dr. Fisher:
Thank you for having me, Katie. It's like hanging out with an old friend, so it'll be fun.

Dr. Peters:
Oh, absolutely. Full disclosure, everyone, I was a spry med student at Stanford University and I learned everything about neuro-oncology from Dr. Fisher. So again, it is just really wonderful to have him here today. So Dr. Fisher, I gave a short introduction. Can you tell us a little more about yourself?

Dr. Fisher:
Yeah, so pediatric neuro-oncologist do a lot of academic things in terms of research, but I think probably my favorite thing, particularly on a Friday, is hanging out in our clinic and seeing kids with brain tumors. That's something I enjoy. I always say it's like hanging out in the field, hanging out with a familiar group of friends and family.

Dr. Peters:
Absolutely. I couldn't agree more because a lot of people will say, in the world of neuro-oncology, I'm a neuro-oncologist, I see adult patients. They ask me, how could you do that? Does it have to be sad? But I think there's a lot of hopeful things about our patients and they can do well and thrive. Don't you agree?

Dr. Fisher:
I think you're right. There's a lot of hope. And I think also, I tell fellows and students, you get to see parts of families and their lives that many other people don't get to see. So I've been very blessed to be part of some very deep, intimate conversations in families and kids, and I think it's really rewarding, and I think there is a lot of hope. There's way more excitement now than when I started about 30 years ago, riding the train up to Children's of Philadelphia.

Dr. Peters:
I agree. There is a great deal more of hope. And can you just give us sort of the basics, since you're also wear that epidemiology hat, where do pediatric brain tumors sit in childhood cancers?

Dr. Fisher:
That's a great question. So pediatric brain tumors are about a quarter of childhood cancer. So leukemia is about a little bit more than a quarter, but then brain tumors are the second most common. So it's a little bit different than in adults where things like prostate, lung, and breast cancer are far more common than glioblastoma and other adult brain tumors.

Dr. Peters:
So why do children develop brain tumors?

Dr. Fisher:
Great question too. Yeah, I think the best we understand, people always talk about the environment, but what we've really understood more and more is there's probably, it's not to dismiss the environment, but there's probably more of a genetic component and not genetic in terms of a mom or dad has brown hair and then the child has brown hair. But there's probably differences in how the developmental genes work. We know that brain tumors really occur in set periods, particularly before age 10. We'll talk about it with, I can even say it now, we're going to talk about DIPG, diffused, intrinsic pontine glioma, and with a very predictable pattern, which comes from epidemiology.
These tumors almost always occur between ages five and 10, which sort of yells out that there's probably something developmentally going on with the genetic machinery. But again, people shouldn't take it as, oh, I gave my child cancer. It's not that. It's more of, there's just a difference in how the genes that regulate growth of the brain and the brainstem probably misfunction and lead to tumor.

Dr. Peters:
So you mentioned DIPG diffused intrinsic pontine glioma. Can you tell us about that and what is that diagnosis?

Dr. Fisher:
So I always tell patients the brain is like an upside down pumpkin. There's a big orange thing, and then there's the stem. That's the brainstem coming out. It connects to the spinal cord. DIPG is the tumor that basically envelops that whole middle part of the stem. It typically comes more from the front or the face side of the body in terms of where it comes out of the brainstem. The problem is it's in the brainstem, and it's basically like the master cable of all the electrical wires and things going in and out of the body. And so it's in a really rough location where things like a person's movement, their breathing, their heart, even their vocalizations, all sorts of things are affected. And so it's in an area that's really rather tricky with a lot of nerve cells.

Dr. Peters:
So what are common symptoms if a child develops this, what triggers you to sort of say, "Uh-oh, I think this could be the diagnosis."

Dr. Fisher:
These go back, these symptoms go back, for those of us who were around when MRIs started, before we had brain MRI, we had just head CTs, but we always knew these kids would come in with basically two out of three things. It was usually some sort of weakness of one of the nerves called cranial nerves, most commonly either weakness of the face or most commonly a crossed eye. So a pattern of where one of the eyes is unable to go to the side toward the ear. So a problem in vision. The second thing would be always be weakness, usually right sided or left sided weakness. And then a clumsiness, or the term that the doctors use for coordination impairment is ataxia. The kids might come in walking a little bit like they look like the old term, a drunken sailor or something coming into port. So they would typically come in with two of those three things that we knew right away, between some weakness, one side or the other, the uncoordination and a cross eye or a weak face that it almost always was now what we call DIPG.

Dr. Peters:
So you mentioned MRIs. I assume that's what we do to detect the condition, but it has to be challenging to do MRIs in the pediatric populations. Can you tell us the nuances of that?

Dr. Fisher:
Right. So when these kids come in, sometimes they'll be seen in an emergency department, big or small hospital they might get a CAT scan, a head CT. But that doesn't give you the resolution at that level of the brain. It's kind of at the bottom of the brain. So they have to get brain MRI. So typically what we do is we go ahead and they'll need some sort of sedation. Many times because they're ill or under the weather, they'll wind up getting general anesthesia and families should accept that. If there's suspicion that there is a tumor or something in the brainstem, really the risks of getting sedation or anesthesia for the MRI are extremely low. So we typically do an MRI and frequently we put something in the IV called contrast or gadolinium so that we can actually see the tumor even a little bit better.

Dr. Peters:
Now, you and I have discussed this before, diagnosing this condition, really the next thing you need is tissue, which is a biopsy. And I remember when I first started in the world of neuro-oncology, we were very gun shy about wanting to biopsy the pons or the brainstem, but there's now been a revolution to get this tissue and get this tissue safely. What do you think about that for making, really, the definitive diagnosis?

Dr. Fisher:
I think it's a colossal advance. It's kind of gone full circle. When I started in the late eighties, early nineties, we were doing biopsies, but we stopped. And part of it was our therapies were not very novel. We were doing radiation only pretty much. And there was sort of a lazy, what's the point? And then I think really in the last 10 years, there's been a renaissance, a rebirth of thinking about this tumor and a lot of excitement about the treatments and the biology.
So doing a biopsy has become routine now. One, to confirm that it truly is DIPG and not some other tumor, not something inflammatory. And then secondly, we try to characterize the subtypes or different molecular markers or machinery because we're starting to get to a point where some of these markers or signals may pair up with certain types of therapies, immune therapies, or other targeted drugs. So we're at the birth of that, but that's where we're going. The last thing to say about surgery is it's just safer. The pediatric neurosurgeons, there's a lot more of them than 30, 40 years ago, and they're very good and the risk is very low. So it's become, for them, it's easy to say for someone who's not doing it, but it's become rather routine for most pediatric neurosurgeons.

Dr. Peters:
Yeah, like when I graduated from medical school, it was really, no, we don't do this. And then really by the time I got into my fellowship, it was like, we need to get that tissue because it's only going to benefit if we can understand those drivers and underpinnings for those patients. Now you mentioned radiation as a treatment. Can you just give us the basics of how you would treat a child with DIPG?

Dr. Fisher:
Yeah, so a typical scenario, as we mentioned, they come in with a little bit of weakness, disc coordination, eyes crossed, and usually it's been only going on about a month or so. We'll do a biopsy and then start on the first standard therapy is to do radiation. We know radiation just focused at the brainstem, we don't radiate the whole brain. We know that will improve their quality of life and improve their survival. So we do that. There are some side effects because the brainstem can swell. So sometimes we have to put them on a steroid called dexamethasone or a Decadron is the old brand name. When we do that, I think it's always important for families to know there's a balance. Too much dexamethasone causes a lot of weight gain, some muscle weakness, changes in mood, insomnia, and the kids eat like a trucker, we always say.
So you have to balance that. So use it a little bit. But we go through radiotherapy. The radiation's typically about six weeks. It's done typically on a Monday through Friday. Some of the kids, depending on their age, may or may not need to be sedated if they can't stay still. But it is really something that improves their quality of life and does extend the time that they will survive with this tumor, such that we can try to then bring them to other newer and exciting therapies.

Dr. Peters:
And what are some of those new exciting areas?

Dr. Fisher:
Yeah, there were a series of clinical trials done through something called Children's Oncology Group, COG, basically in the nineties and into the 2000s where we've tried things like temozolomide or Temodar, which is used in adult glioblastoma. The downside is it doesn't seem to work quite as well in DIPG. So we've started now really moving on to newer therapies, particularly things that are either targeted drugs or where there's been really a lot of excitement, where the research is, where things are going is things like CAR-T therapy, something chimeric antigen receptor T-cell therapy, where you try to basically take someone's own immune cells and have them trigger or target and attack the DIPG.
There's also been some other immune therapies too, things that are called ... Drugs called checkpoint inhibitors where they basically try to have the immune system attack at the tumor. So we're getting a little bit more clever there in terms of those things, trying to mobilize the body's own immune system to attack the tumor. We're also doing things too that, similar to immunotherapy. We've done some things there at select centers, and these are all under the heading of clinical trials that are basically under either the National Cancer Institute or different children's hospitals and regulated.
But people have done things like viral therapies, oncolytic viruses, viruses that are basically controlled so they're not going to make the child sick, but viruses that might allow the tumor to be broken down by again, the immune system attacking when the virus is put there. There's also been some excitement of trying to do things where delivering drugs better to the tumor. One of the questions has been, would some of these tumors respond? Would DIPG respond maybe a little bit better to chemotherapy, some of the older chemotherapies I mentioned, temozolomide, Temodar, are, if we could get the drug there.
So there's an idea of something called convection enhanced delivery where you use basically, I guess, probably the easiest way to think about, it's sort of a warming technique, just like a convection oven, but a way to get something there mobilized, getting the drug closer to the tumor in the brainstem. Because the brainstem itself is not the most easily accessed area. As we said before, back to the biopsy, it's usually done often through a stereotactic or a needle biopsy, not opening up the whole child's brain or cell to get at it.

Dr. Peters:
I think immunotherapy is very exciting, but I can imagine that you don't want to really disturb the brainstem too much. How can these children, how do they handle those side effects from those immunotherapies?

Dr. Fisher:
So there's a lot of excitement and I think parents, people who listen to this, are going to hear a lot about immune therapies that's done in a number of institutions, my own included. And I think they're all doing a good job. Right now, the immune therapies, it's important to say these are really early. These are therapies where they're in what's called phase one clinical trials, where we're looking at the feasibility and the safety and the side effects as you mentioned. Also, we're starting to see some shrinkage in the tumors, but we're not at the point where what we call phase two trials, where we're actually looking how effective can we be in curing children, or things like that. So we can't make any promises at this point and shouldn't that a CAR-T therapy or other immune therapy is going to cure the child, but we do think it's going to improve quality of life and extend life.
But your point is there are side effects when you put immune therapies in the brainstem, there can be a lot of inflammation. Inflammation is basically swelling. It's like falling down in your knee and your knee gets swollen. Well, that's okay for your knee. But the problem in the brainstem is it's surrounded in an area of the skull where there's not a lot of space. So when there's swelling there, the kids can get into some difficulties with side effects, like the same type of swelling that's seen with radiation, but even a little bit more severe. So sometimes we do have to use basically the dexamethasone. Sometimes we use other drugs, other drugs that are called cytokine or interleukin inhibitors, fancy doctor names, but drugs to basically decrease the whole inflammatory process. So your knee or your brainstem doesn't swell quite as much yet we preserve the anti-tumor effect of the immune therapy.

Dr. Peters:
Yeah, often tell my patients when they go on immunotherapies for brain tumors is that a lot of times it's almost like we don't know what the right setting is yet. We either have the setting of it's off or boil, and sometimes we need to find the right simmer so that we don't cause things to over boil and to hurt the patient. I think I use cooking analogies a lot.

Dr. Fisher:
Yeah, well, cooking is always good, but I agree it is, and that's why it's phase one trust. We're really trying to find the right dose. Just like phase one, people are familiar with when new drugs, where doctors are trying to find the right amount of the right dosage of a drug. While in phase one trials with immune therapies, CAR-T and others, people are trying to say how much of a mobilization of the immune system is right? How many cells do we inject when we make these CAR-T cells? Do we put them in once, several times? Do we put it in monthly? People are looking at all sorts of different things there.
So that's why it's exciting. I mean, along the way, and again, it's case-by-case. We are seeing some tumor shrinkers. There's no doubt about that. What we're unclear is how long that shrinkage will last before the tumor starts to grow again. But the exciting part here is that for those of us who were doing this back in the eighties and the nineties and taking the train to Philadelphia, when we gave therapies before we saw a little bit of shrinkage with radiation. But all the other therapies we've done over the decades haven't shown shrinkage of tumor. So for the very first time in these immune therapies, particularly CAR-T, we're seeing shrinkage of tumors, whether it's basically enduring for months or years, we don't know. But we are seeing, and again, this is a case-by-case thing, some kids who are often living longer than we had seen in the past with these tumors, which is very exciting.

Dr. Peters:
And thank you for giving us so much hope. And it's really also organizations like Love for Lucas that Hide Harashima started in honor of his son. What do you think advocacy can do for both patients with DIPG, but also caregivers?

Dr. Fisher:
Yeah, so I think first for the caregiver, I always say, you mentioned analogies of cooking. I always talk about sports, their time when your team goes out in the field and you're kind of feeling overmatched or overwhelmed. But there are winners here, and I have to always say that we're going to assume you're a winner until we don't have information or we have information that says you're not winning. So I think we have to go in there. We know that there are children who survived multiple years or the rare one in a hundred who's a long-term survivor. And I always say to the caregivers, let's assume that's you until we get information otherwise. I think that's important.
And then I think for the caregivers and then either the larger community in terms of advocacy, I think first and foremost, working together as a community. This is something where it is going to take a village. There's a great scientific community, but what I think I've marveled at the years, over the years is all the different family foundations to support each other and to support research. So I think those elements of groups that are either family support groups or foundations that sometimes either raise money to support families or to support research, I think that's great.
I think the other part of advocacy is to consider for families and caregivers, families often develop teams where they have a whole team of family members and friends trying to figure out what to do. I think they should look at experimental therapies, but when they do that, they need to think about what are the benefits and risks? They need to individualize it to themselves and say, "Hey, we live in Indiana. Do we really want to go to California, New York, Texas, for a therapy, or do we want to be somewhere close to home in Chicago?"
I think they need to think about that and they need to say, "Is this clinical trial right for us?" I would encourage people, this is something where you can certainly look on the internet, probably the most trusted place to look is clinicaltrials.gov, just like the word is spelled out. Clinicaltrials.gov has both information for the doctors or researchers, but also information for the families and patients about where different trials are. So if they type in words like DIPG, diffuse intrinsic pontine glioma, brainstem glioma, those trials will come up and they can find them and try to consider what's best.
I think the last thing to say about advocacy, and it goes back to the analogy of a game, we don't have as many winners as we want. We're getting more, I hope, more winners down the road. But as we do that, I think families need to be very intent that they've put up a good battle wherever they go. Because there is a lot of hope. So that's where they should say, "What makes us feel best for our child, for our family? What do we think is going to be really, given our values, our family customs, and our culture, what really works best for us?"

Dr. Peters:
I couldn't agree more. And Dr. Fisher, thank you so much for this hopeful and enlightening conversation and really also for sharing your journey from the beginnings of really your career as a pediatric neuro-oncologist to sort of now seeing real change for these patients.

Dr. Fisher:
It's just like the old days hanging out in clinic with you on a Friday, Katie.

Dr. Peters:
I'm ready.

Dr. Fisher:
Just got some patience to see.

Dr. Correa:
Thank you again for joining us today on the Brain and Life Podcast. Follow and subscribe to this podcast so you don't miss our weekly episodes. You can also sign up to receive the Brain and Life magazine for free at brainandlife.org.

Dr. Peters:
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Dr. Correa:
You can also find that information in our show notes and you can follow Katie and me and the Brain and Life Magazine on many of your preferred social media channels. We are your hosts, Dr. Daniel Correa, connecting with you from New York City and online at neurodrcorrea.

Dr. Peters:
And Dr. Katie Peters joining you from Durham, North Carolina and online at katiepetersmdphd.

Dr. Correa:
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Dr. Peters:
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Raising Awareness for a Rare Cancer with Love4Lucas President Hide Harashima

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