The causes of tumors in children and young adults are different than those in adults. Yet, much of the diagnoses and treatments for pediatric patients have been based on those from adults. But thanks to great strides in research, that's changing. Dr. Anish Ray, Dr. Kelly Vallance. and Dr. Heidi Trinkman take us on a journey through research, oncology, and pharmacology and their impact on pediatric precision medicine.
Anish Ray, MD,
Kelly Valance, MD, MPHD
Heidi Trinkman, PharmD, BOCP
Cook Children’s Precision Medicine Program
Cook Children’s Solid Tumor Program
Cook Children’s Genetic Oncology Clinic
Cook Children’s Oncology Program
Cook Children's Hematology and Oncology
Cook Children’s Hematology and Oncology Research
Cook Children’s Targeted Therapy for Pediatric Cancer podcast
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Music
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Host: Hello and welcome to this edition of Doc Talk. It's a very busy day here in the Child Life Zone at Cook Children's, so you may hear a little background noise.
Today we're talking about precision medicine. So an interesting fact, according to the National Cancer Institute, pediatric cancers are rare, but they are the leading cause of death past infancy in children and teens. We also know the rate of childhood cancer is growing at about 1% per year. One in 285 children will develop cancer before the age of 20.
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The causes of tumors in children and young adults are different than those in adults. Yet, much of these diagnoses and treatments for pediatric patients have been based on those from adults. Chemotherapy and radiation are still the go to drugs. But that's changing because we now know that genes determine how someone's body will react to a drug. That's where pediatric precision medicine comes in. And what we're going to talk about today.
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Our guests are Dr. Kelly Vallance, who led the charge in developing the solid tumor program as well as the genetic oncology clinic here at Cook Children's. Doctor Anish Ray who, together with Dr. Vallance, formed the molecular tumor board here and championed the Precision Medicine Program. We are also joined by clinical pharmacy specialist, Dr. Heidi Trinkman:, who specializes in pharmacogenetics.
Welcome.
00:01:25
Guests: Thank you. Thank you.
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Host: So before we dive into precision medicine, walk us through what it is and how we got here, beginning with the programs that we mentioned in the introduction, where did it all start?
00:01:37
Dr. Anish Ray: It's actually under Dr. Vallance's encouragement that we expanded the solid tumor program several years ago. And she gave me the task of starting molecular tumor board, which by definition is a slightly different taste of a tumor board. Unlike conventionally what was very talked about tumors, and it's attended by oncologists, surgeons and pathologists and radiation oncologists, the molecular tumor board is really looking at the genetic makeup of tumors. And I think very early, she had recognized that we were undergoing to a shift in how we review tumors instead of describing them conventionally and treating them with agents such as chemotherapy and radiation, as you just mentioned. I think we were learning more about what made tumors unique. And the technical term for that could be variation or a mutation. And with those changes, we were looking at the drugs that could help neutralize those changes. And so that's how it all began, I think, wanting to formally look at the molecular makeup of tumors and sort of have a platform to discuss these that then led eventually to a precision medicine program in a broader sense, where we see patients that we have talked about previously and make drug recommendations. Dr. Vallance.
00:02:51
Dr. Kelly Vallance: We certainly, as medicine is expanding with newer technologies, the ability to sequence tumors, newer medications, targeted treatments, we realized that we really needed to specialize and focus, in order to keep Cook Children's at the precipice of cutting-edge therapy. And offer all of our children and their families the best patient care and most up-to-date, cutting-edge treatments here at Cook.
00:03:24
Dr. Heidi Trinkman: I would also tag on to that, just saying that, with more and more targeted therapies coming to the market and these drugs having a lot of traction in adult malignancies, that being able to use them in pediatrics is very important as well, because the targets are the same, even though necessarily the diagnosis may not be. And, so having these drugs, we needed pharmacy to know what to do with them. And how to obtain them and dose them. And, can this pill be crushed for a child that's three years old? That sort of thing. And so that's where pharmacy can bring our expertise to the table of medications to add to the molecular tumor board and the targeting therapy for these children.
00:04:13
Host: So chemotherapy and radiation can both have serious side effects while going through treatment, as well as long term side effects. Because of this, we are more and more moving away from drugs that are one size fits all. And this personalized medicine to better serve the needs of our young patients. What are those treatments? And how does the precision medicine program fit in?
00:04:36
Dr. Anish Ray: I think it's a complex world of precision medicine. And while it is widely recognized that chemotherapy agents will cause a lot of side effects because, in general they target cells and tissues that have a high cellular turnover without caring for much else, precision medicine usually targets a particular abnormality that affects the tumor cells only and the idea is thereby sparing the rest of the body and having less side effects. But I also want to point out that targeted agents can have the unique side effects. And we all need to be aware of those side effects as we recommend these drugs. Heidi, do you want to add anything to that?
00:05:14
Dr. Heidi Trinkman: Yeah, a lot of these newer drugs also have a lot of interactions that we have to make sure that we're we're monitoring for. Things that we haven't traditionally had to worry about with our traditional chemotherapy regimens. So the neat thing about the targeted agents is that we can add them to a traditional chemotherapy regimen or sometimes they can be utilized as standalone therapies. So, but knowing how these drugs interact with the other supportive care meds and the other chemotherapy agents is very important as well.
00:05:45
Host: So how do you determine if a patient is a candidate for precision medicine? What are the criteria?
00:05:50
Dr. Anish Ray: Before deciding on who is a candidate for precision medicine, it's important to recognize who is tested for to be a candidate for precision medicine. When I started working here on a fellowship 10 years ago, I think we were sending these extensive gene testing on tumors on a handful of patients who had relapsed second or third time, and it was considered in a more often a desperate need and measure. And part of the reason for such hesitation was also that the newer methods of testing for these tumors were using technologies that we physicians had not learned about in medical school. And so we were overwhelmed by the complexity of these reports, and so on. And that led to the formation of the molecular tumor board where we have multidisciplinary attendance, including a lot of assistance from our molecular geneticists, molecular pathologist, Dr. Jason Wang. And with all of that being available to us, we started testing more extensively. And I think we've come to the stage where we are extending it on all newly diagnosed solid tumor patients, so that would probably about 30 to 40% of our newly diagnosed patients.
00:06:56
Dr. Anish Ray: And also more and more on so called liquid tumor patients or leukemias and lymphomas. So I think we are headed very rapidly to the phase where we would offer this test to all of our patients and then be able to identify more and more patients who would be candidates for precision medicine.
00:07:14
Dr. Kelly Vallance: Absolutely. And along those same lines, we have the ability now and more knowledge and testing is more widely available. And there is a precedent for the benefit that precision medicine, molecular testing, kind of gathering as much information as we can, there is certainly a benefit in treating patients. And we are now not only testing at diagnosis for some patients, but also at recurrence or relapse of disease. And we're finding that sometimes these tumors do have mutations, there may be other treatments that we can use second line and with relapse treatment, whereas they did not possess that mutation the first time around. So it is definitely expanding and important part of care. In a sense, really all patients are candidates for precision medicine. Especially as we are expanding and doing more pharmacogenomics and really tailoring treatment to each individual patient.
00:08:22
Host: So what cancers are you seeing great outcomes in right now?
00:08:28
Dr. Anish Ray: In terms of precision medicine, I think the classic example that everyone cites and will agree upon is something known as infantile fibrosarcoma. This is a disease that typically affects infants, and has been considered a dreaded malignancy with poor outcome in general and a risk of relapse, as well as the treatment modalities come with heavy toxicities from conventional chemotherapy. And until we discovered a track fusion which is basically movement of gene material from one chromosome to another, which in turn forms a protein that is considered to be driving this tumor. And with that discovery, we were then able to find medicines that would block the protein. And this almost seems like a miracle as to how this discovery then led to revolutionising the treatment for these children.
00:09:14
Dr. Anish Ray: And I know one of our partners, Dr. Heym, has recently created one such baby and he has been ,alongside the family, has been mesmerized by how the tumor has basically melted away with the use of this drug. But there are many such examples. Dr. Vallance, you want to talk about the NF one patients who've been treating with considerable ...
00:09:33
Dr. Kelly Vallance: So another group of patients that have had revolutionary changes in their treatments are benign tumors as well that respond to MEK inhibitors and were in the past in children with neurofibromatosis and plexiform neurofibromas. We waited until the tumors were large and causing complications and pain and attempted resection as we didn't have treatments. But now with new targeted agents, they're able to have tremendous responses with their plexiforms and significant improvement in quality of life as well.
00:10:15
Host: What are some of the more challenging pediatric cancers? And what are the biggest challenges in diagnosing and treating them?
00:10:21
Dr. Kelly Vallance: The harder cancers to treat, and that we've not made a tremendous amount of progress with as far as using traditional cytotoxic chemotherapy and radiation are really, are widely metastatic solid tumors and recurrent tumors. And it's in these patients that a lot of the targeted agents and newer treatments are being focused on. In addition, cancers that are extremely rare, where there's been little information or successful treatments, these patients are certainly very challenging as well, and great candidates for precision medicine and changing their treatments.
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Host: Speaking of challenging, talk a little about babies born with cancer. How does cancer form before they've even taken their first breath of oxygen? Is this inherited or gene anomaly or combination?
00:11:20
Dr. Kelly Vallance: So that is a million dollar question there. I like to talk to families and say that when cancer is starting, it is usually one cell in the body that has all these perfect mutations. And for some reason, the body did not recognize that it was a bad cell and allowed it to grow. So we know in adults who have many, many years of aging, and sometimes abuse on their body and some other vices, or other exposures, those mutations in the cells can increase. And so that's where we believe most adult cancer comes from. Certainly in pediatrics, especially infants, that change has not happened. So we do know that the process is the same, but why they have the mutations is certainly different. And there is, especially with infants, a chance that they have an underlying genetic predisposition, where they already have possible mutations in their cells, and that makes the change to cancer happen.
00:12:26
Host: So how are their cancers diagnosed? And are they also being treated with precision medicine?
00:12:34
Dr. Kelly Vallance: So in the infants, often they can be diagnosed at birth or in the first few months of life as the tumors are growing. And absolutely, and this goes back to the case that Dr. Ray was speaking of with the infantile fibrosarcomas, they used to be extremely difficult to treat and certainly almost impossible to cure. And now that we have these newer medicines, it's revolutionising their treatment and outcomes.
00:13:00
Host: My understanding is that precision medicine is considered a standard of care for adults, but has not yet been recognized as such for kids, as well as adolescents and young adults, AYAs. Why not? And when do you foresee that change?
00:13:16
Dr. Anish Ray: So I think that's a multiple reasons behind that. In general, malignancies or cancers are far less common in children than they are among adults by a very large margin. Having said that, I think in general, some of the newer discoveries have been conducted on adult tumor samples. And once they were discovered, then the pharmaceutical agencies were interested in developing drugs that would target those abnormalities. And so it took some time for the industry to wake up to such needs among children, but also it is well recognized that what we call driver mutations, the mutations that sort of caused the tumor to form in the first place, that whole process is a lot more prevalent among adults than it is in children. The biology is completely different or frequently different among children. And so I think it has taken some time for the field in pediatrics to recognize the needs for children. But also this, I think, highlights the bigger problem, which is that children will likely have unique abnormalities that are not to be found among adult tumors, and hence, the need to search for those mutations is also high.
00:14:26
Dr. Kelly Vallance: Absolutely. And I'd add, you know, children, especially infants are not just little adults, certainly the way their bodies work is different and metabolize drugs, the dosing is difficult to, to nail down and then also, as Dr. Ray said, it is very, very rare, often in a lot of these solid tumors. So it is dependent on clinical trials and kind of translating the adult information down to children. And that goes into FDA approvals and ethics, and clinical trials for children is certainly harder to conduct than informed consent in adults etc.
00:15:07
Dr. Heidi Trinkman: So insurance coverage for some of these therapies for children that don't have the data behind them, like they do in adults, can make obtaining the meds complicated. And so sometimes that's also a challenge.
00:15:22
Host: So as we talk about childhood cancer, where do pharmacogenomics come in at this time?
00:15:29
Dr. Anish Ray: I will start by saying that Dr. Trinkman is one of the smartest persons I've had the privilege of working with. So she was part of our molecular tumor board, and has provided valuable input from the very beginning. And as we conducted molecular tumor boards, and started the precision medicine clinics, Heidi and I had this conversation about yet another emerging field of medicine known as pharmacogenomics, essentially looking at how individuals metabolize drugs and how this metabolism dictates an optimum dose for patients, especially for children. That's so important. And we felt like this was an unmet need for our patients, and not just in the world of cancer, but outside as well. And so that is how the pharmacogenomic component became part of the Precision Medicine Program.
00:16:15
Dr. Heidi Trinkman: The pharmacogenomic program that Dr. Ray and I are creating, building and utilizing for our patients is really there to optimize therapy, it comes along and fits very nicely under precision medicine, where we're looking at tailoring medication regimens towards patients and how they process medications. And so I think that's really where this fits in cancer therapy for children.
00:16:43
Host: Heidi, what is your role in the work that Dr. Ray and Dr. Vallance are doing with the Precision Medicine Program.
00:16:49
Dr. Heidi Trinkman: As a pharmacist, I have a unique perspective. And when I approach these things, I'm looking at it from a medication perspective. And so it's a beautiful partnership, as far as working with these molecular tumor boards, and precision medicine, because medications play a huge role in it. And so I can bring my expertise of how drugs are metabolized, how they interact with each other, how we can alter dosage forms, and fit it nicely into how it's going to help the patient and treat their malignancy. And so in working together with both doctors Ray and Vallance that we can try and optimize the therapy regimen for these patients.
00:17:36
Host: Can you talk about pharmacogenomics? What is it? And when does it come into play? Like how does it differ from genetic sequencing and next gen sequencing.
00:17:47
Dr. Heidi Trinkman: Pharmacogenomics is basically the study of variations of your genes, and how that variation affects how medications work in your body. And it really comes into play in the patients that are going to be receiving a lot of these medications. If we can have that information ahead of time, it helps us be able to better dose those medications, for better safety for better efficacy of medications for these patients. And some of these medications have some pretty severe toxicities. And if we can avoid the potential for some of those, and we have that information ahead of time, then we can avoid a lot of grief, avoid a lot of medical costs to that patient or family and better quality of life, better outcomes. There's a lot of things that that can improve. And so some of them are chemotherapy agents that we have information for how to dose based off of genetic variations, and a lot of it is the supportive care, medications that these patients are going to be meeting as part of their therapy as well. And so all of this information put together gives us a little piece of the puzzle of how this patient will deal with these medications. As far as how it varies from next gen sequencing. The difference is in pharmacogenomics, we're looking at those inherited variations in genes that are associated with either how you metabolize a drug or how you create a protein that is going to bind to a drug. And so those variations are part of your DNA set that don't change. And so the information we get in the beginning is going to be lifelong for that patient as well. Whereas next gen sequencing is looking at those variations in a tumor that are driving the malignancy or that we could potentially target for that malignancy. So those are acquired variations.
00:19:48
Host: So how long have we been able to use a pediatric patient's genetic makeup to determine the right medication and dosage? And is it fair to say that it's not yet been adopted into frontline therapy, it's still in its infancy? And what is the biggest challenge to moving it forward?
00:20:07
Dr. Heidi Trinkman: We've been able, since like 1980, I think is when we first identified in pediatric malignancies that variations in TPMT, or associated with toxicities for patients receiving 6-mercaptopurine for pediatric leukemia. So we've had this information that one particular gene could then impact toxicity for children receiving this drug. And so since then, it's taken a long time, but we've built on that information. And we've utilized it. And it wasn't initially an upfront thing that we checked, it was based reactionary on a patient having significant toxicity, and then more of an explanation as to why looking at that particular gene. And so now, fast forward to today, it's considered standard of care to check that particular molecular genetic variation to determine how best to dose that patient's medication throughout their therapy. So, we're making small strides in those directions of being able to move this pharmacogenomic testing and using it to impact therapies proactively, as opposed to reactionary, where technology has caught up and surpassed us. We have the technology to do these panels, looking at all sorts of different variations and having the knowledge base to then know how best to utilize and adjust therapies based off that information is still proving itself in worth. And so we're moving much more towards these panels of looking at large amounts of genetic data to give us information. But some of that knowledge of what to do with it has lagged a little bit behind. And so we're still building upon that knowledge to be able to use it proactively versus being reactionary. As far as the biggest challenge, moving it forward, I would have to say one, reimbursement is a big part because insurance, they will pay for some of these smaller one-gene testings as opposed to a panel. But now technology has gotten so much further and cheaper in doing these tests that the gap of cost between a single gene test and a panel has gotten significantly smaller. And again, in pushing this forward, it's going to make a lot more sense, 'well, if I can get all this information for just a few bucks more look at all you get,' right? So trying to convince insurance companies that the value is there for looking at all that information is going to be the challenge going forward. Because I think that's what's holding people back from being able to send this and using the information that they get to guide their therapies. I also think research is a big thing. We really, really, really need a lot more research in just exactly how to use this information to impact toxicities and to impact therapies.
00:23:19
Dr. Anish Ray: I agree with what Heidi just said that the technology has surpassed the ability of the medical system to the data and digest and then come up with a meaningful interpretation for our patients. So I think the patients and families have been there, especially with regard to the known toxicities of chemotherapy. But we are seeing a lot of patients who are coming from the non-oncology world also seeking this exact same service. Parents are concerned with the degree of side effects seen in their children from non-chemo drugs. And they are wanting answers. And I think Heidi and her team is fulfilling that great unmet need by trying to provide some light in this sort of gray zone of medicine. And hopefully, as the community wakes up and the medical fraternity warms up to the idea for multivariate testing, this will become more mainstream over time.
00:24:09
Host: So what do you do in the case where let's say you see that a child has a fast metabolizing gene for that medication? Do you start small and work up to see how they do or do you just go a different direction altogether?
00:24:22
Dr. Heidi Trinkman: I'll give you the best answer which is depends. It depends on the medication. And let me give you an example. Say a patient has a CYP2D6 ultra rapid metabolizing phenotype. Then that means say if I want to prescribe codeine, well codeine has to be converted to morphine to be active in the body to get that pain relieving effect, which means that this patient with the ultra rapid metabolizing status would actually convert way more of the codeine to morphine, putting that patient at risk of significant toxicity should they be given a normal dose of codeine. Where, on the flipside, say a medication like Zofran, ondansetron, is prescribed for this patient to prevent nausea and vomiting associated with chemotherapy. Well, in this instance, the ultra rapid metabolizing status of this patient means that they would basically metabolize the drug so quickly that they're not going to get the effect of the drug, and then that drug's ineffective for that patient and won't be there to protect them against the nausea and vomiting associated with their chemotherapy. So it really depends on the medication and how it's metabolized and the background of it to know how we can use that information to best prescribe those drugs.
00:25:46
Dr. Kelly Vallance: And I think Heidi pointed out in explaining that it really does take a team of people and a team of experts to be able to analyze the results from the pharmacogenomics and really to apply that to each individual unique situation.
00:26:04
Host: So how does next gen sequencing work and where in the patient's journey does it fit?
00:26:09
Dr. Kelly Vallance: Next generation sequencing is a sequencing or array panels of the tumor. So those are acquired mutations, or somatic mutations. And in the journey, it really fits in for solid tumors. I believe it fits in throughout the entire course for the patient, and that is diagnosis to help us best know how to treat the patient. But also if it does recur, it gives us additional information if the tumor has changed.
00:26:43
Dr. Heidi Trinkman: Do you want to mention anything about following them for relapse like with the liquid?
00:26:47
Dr. Anish Ray: That's a good question. Also, just measuring or doing this type of test at one time point, I think we are starting to do this over multiple time points. And the understanding is for patients who have undergone relapse and or been exposed to medications like chemotherapy, radiation, etc., it is possible that profile of those tumors may change over time. And so if it is possible for newer mutations to manifest, and that can then create a path for medications to be tested or tried for these patients and that would not have been possible based on the original report. So things can evolve over time, it's just not one time testing only.
00:27:26
Dr. Kelly Vallance: And that brings up also, and certainly not mainstream yet, especially for pediatric cancers, but increasing ability to detect fragments of tumor in, in a patient's blood for solid tumors. So considered either a liquid biopsy or circulating tumor DNA, there's a movement to be able to identify amounts in patients' blood so that relapses may be detected even prior to being able to see recurrent tumors on imaging studies. And in theory that would give more information as far as catching something very early, initiating relapse treatment very early and hopefully translates into improving survival and cures.
00:28:15
Host: So Dr. Vallance, some of the work you are doing in your genetics clinic is looking for ways to catch those genetic disorders that have a high prevalence of malignancies. Can you tell us more about it?
00:28:26
Dr. Kelly Vallance: Absolutely. So when I was in medical school, which at this point is a very long time ago, and we won't mention that I just had my 20 year reunion. But my kind of new patient diagnosis talk was always we don't know what causes cancer, it's just that the cell changed and just the perfect storm of mutations. But now we know especially as we are sequencing more tumors and have so much more knowledge about genetics, we now believe that up to 10% of children and young adolescents, and infants that have cancer actually have an underlying genetic predisposition syndrome, or mutations that are present in their germline. So meaning, in some of the cells in their body that already predispose them to getting certain types of cancer. So through the awareness or the ability to know that someone possesses one of those germline predisposition syndromes, it helps us be able to monitor and do closer surveillance for other types of cancers that may be specific to those syndromes. So it truly opens knowledge is power, but it truly opens the door for knowing that these patients may be at risk for secondary cancers. It may change the way we treat upfront cancers, and it certainly can change the frequency, or how we do surveillance and scans, in order to catch anything early.
00:30:06
Host: So your team also does genetic testing on the families, what is the advantage of this testing and what determines when genetic sequencing is done for them?
00:30:16
Dr. Kelly Vallance: So there are several different ways that we recommend testing, or this comes about in our genetic onc clinic. If a patient has a tumor that is sequenced that has a mutation that we often see in cancer predisposition syndromes, then at that time, family is counseled that there could be a genetic predisposition syndrome and meet with genetic counselors and then move on to have testing done of their actual germline tissue. So either blood cells or sometimes skin biopsies to determine if there is that syndrome and that risk. If we do find a cancer predisposition gene, then we do recommend and help families pursue testing for parents and then any affected siblings, any extended family members that would benefit from having that knowledge that there is a slight increased risk for cancers, and they can do appropriate screenings as well. So that is one way that we find patients. Another is certain types of tumors are more common, and people that do have hereditary syndromes. So that is one, there's multiple, usually solid tumors that trigger a genetic workup as well. And often we can find that genetic syndrome that way,
00:31:40
Host: A trend in medicine, particularly pediatric medicine, is coordinated care. This is care that literally brings the team to the patient and the family. Both the genetics clinic and the precision medicine program are designed to do just that. What are the short- and long-term advantages to these patients and families and to you as providers in improving outcomes.
00:32:00
Dr. Anish Ray: So I think you raise a great point. A lot of what we are learning about precision medicine is new emerging, and it is rare. So it is so important that we get together and coordinate care for these patients and families. And we have kept that in mind as we have built our program, which consists of a team of specialists, including Heidi who represents pharmacy, and also Dr. Wang from molecular pathology. We also have significant participation from our medical students who come and rotate with us and can bring a new knowledge to the table, as well as Dr. Vallance and her genetic oncology team to get together to form a plan for these patients, to interpret the results adequately and make drug recommendations. But, also, a lot of times at the end of the meeting, and having discussed a patient, we would then send a referral to the genetic oncology program, because we have identified abnormalities that signal towards a genetic basis for the patients, but also other siblings possibly. So it is a coordinated approach and we open feel that our patients will benefit both in the long- and short-term from this approach.
00:33:05
Dr. Heidi Trinkman: Also, research is very heavy at the table because they also, you know, from investigational drugs that are potentially options for these patients, as well as they have a good idea of maybe a study that these patients might be eligible for. And so they play a big part in what kind of options we can also offer.
00:33:26
Host: So as part of coordinated care, how can the Precision Medicine Program assist other pediatric oncologists who are seeking this for their patients,
00:33:34
Dr. Anish Ray: Again, going back to the fact that these tumors are rare, and we really rely upon coordination of care, but also collaborating with other oncologists in both other leading academic institutions, as well as non-academic institutions, so that we can all share our experiences and learn from each other. And so we are as an institution part of some of these larger consortia. But also we have invited several hospitals in Texas and the doctors from those hospitals would participate in our malignant tumor board so that we can all learn from each other.
00:34:07
Host: So how many patients in your program have been treated with precision medicine? And what's been the response thus far?
00:34:14
Dr. Anish Ray: It's kind of hard for us to give an exact figure because it's such a moving target in general, but we have formed a database where we are exactly tracking this particular question. We're also looking at outcome for patients who are being treated with precision medicine, and how that outcome compares with those who have been treated with conventional chemotherapy agents. This is a project that's currently underway. We have seen probably over a dozen patients in precision medicine consults, and we're starting to get somewhat overwhelmed with the pharmacogenomic consults.
00:34:45
Dr. Heidi Trinkman: It's been very well adopted.
00:34:49
Dr. Kelly Vallance: Because it's so valuable. We appreciate you.
00:34:53
Dr. Heidi Trinkman: It's definitely a need that we didn't know was as strong as it was.
00:34:58
Host: So what clinical trials is Cook Children's involved in when it comes to precision medicine therapies?
00:35:03
Dr. Kelly Vallance: There are numerous ones were doing. Really anything that we foresee any benefit for our patients we certainly have available and open. One that is used more often is the NCI Children's Oncology Group Pediatric MATCH trial. We also have several industry trials open with Tapestry and other early expansion, early access trials for patients. We also have an amazing research pharmacy department and staff that are really able to help us get drugs for compassionate use. So compassionate use, or an expanded access protocol or individual plan is really beneficial if we know of a drug that is FDA approved for possibly other diagnoses are in adults, but has not been FDA approved in, for use in children yet, often a lot of the pharmaceutical companies do have programs where we are able to access that medication for families and for patients.
00:36:12
Host: So how do you determine if a patient is eligible for match drug therapy?
00:36:17
Dr. Anish Ray: So that's an interesting question. And when we look at these complex reports, there are several tiers of recommendations based on the evidence available. So tier one would be let's say patient has condition A, and it is recommended that patient receive drug B. And there is a clinical trial that has already been conducted with plenty of information available that proves the efficacy of drug B for condition A, perfect match. And next tier would be patient has condition A or drug B is borrowed from a different tumor type. But it's found to be efficacious. So we are overcoming the pathological diagnosis. And we're looking at mutation specific conditions to address the individual patient needs. So all of these types of information need to be considered before a patient is considered eligible for matched drug therapy. So it's not as straightforward as it may seem, but it is rather complex, given the multiple layers of evidence and evidence can be strong or weak, as the case may be.
00:37:25
Host: We've talked a lot about diagnoses, treatments, and even relapse. But what about the patients and their families? What does their journey look like?
00:37:35
Dr. Anish Ray: So this is a great question. And I just want to highlight how the field is warming up to addressing patients and families needs. Forever we have had clinical trials that would cater to certain conditions. So you have condition A, drug B can be available through clinical trial. And this combination of condition A and drug B may be available at Cook, may be available elsewhere in Texas, may be available in anywhere else in the world. And so if not available, let's say at Cook, then patients and families would have to travel and become eligible to get access to these medications. But only in very recent past, are we looking at setups where we can actually have a trial available, but not necessarily open at institution. But that trial can become available to the patient and families if a mutation is identified on the patient's tumor testing. So basically, it is a bunch of mutations and drugs associated similar to the ones that Dr. Vallance mentioned earlier, the match. And the Tapestry trials. But they're not specifically open at physical locations. They are open and available, let's say for example in the cloud, and they become available to a particular institution, as the patient shows up at that institution. So their patients and families will not have to travel and give up their lives and jobs and everything else. And so that in my mind is the future of clinical trials. And at Cook, we are already partnering with industry to be able to offer these for our patients.
00:39:02
Dr. Heidi Trinkman: Also, I can piggyback for pharmacogenomics. Much of the progress we have made has been driven by patients and families. The need for it, the request for it. Our very first patient was the instigator for us going ahead and starting to do this where the parent reached out and just said, "I need someone to listen to me, my kid's not reacting to medications the way that you would expect. And is there anybody that can help us?" And so you hear that cry, and that just hits your heart. So, much of the requests that we have gotten has been from families. So I think their journey, looking for answers sometimes to why their child is experiencing some of these toxicities. Pharmacogenomics doesn't give the entire answer. It's a little piece of the puzzle. And so it's, sometimes it's hard to get that message across because they put all their hopes and dreams there. But it is some of that information that can go into answering some of those questions.
00:40:08
Host: So if a physician has a pediatric or young adult patient with a history of childhood cancer, what would be the process for referring? Would they start with a consult?
00:40:19
Dr. Kelly Vallance: So yes, through our hematology oncology program and clinic, there's a new patient coordinator. And they would be able to point in the right direction as far as contacting or consulting with solid tumor coordinator, genetic oncology or precision medicine, the information or self referral as well. And then information we set up in consultations would be scheduled and arranged.
00:40:45
Host: Well, this has been fantastic. Is there anything else I haven't asked you that you would like to share?
00:40:49
Dr. Kelly Vallance: It takes a village. And I feel that we are very fortunate here, to have a lot of resources to work together and to really improve the care for kids in in Texas and around here and hopefully really make a difference in long term survival and the field of precision medicine.
00:41:10
Host: Fantastic. Well, again, thank you all so much for being here.
00:41:13
Dr. Kelly Vallance: Thank you. Thanks for having us.
00:41:14
Host: If you'd like to learn more about precision medicine or any programs here at Cook Children's, visit our website at Cook Children's dot org.