Why does one child respond well to cancer treatment and another not? The Children’s Mercy Oncology Biorepository hopes to answer that question and more. This research facility includes biobanking technology and the staff to manage patient samples and assist with research. The 200 new pediatric cancer patients at Children’s Mercy each year can contribute to research efforts regardless of diagnosis or age simply by donating their blood, leftover tumor samples, DNA and clinical data.
In this segment, Erin Guest, MD explains that the biorepository is open to research scientists to study cancer and related diseases and hopes to collaborate with other oncology programs on novel research projects.
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Oncology Biorepository: Banking on Finding Answers for Childhood Cancers
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Learn more about Erin Guest, MD
Erin Guest, MD
Erin Guest, MD is an Assistant Professor of Pediatrics at the University of Missouri-Kansas City School of Medicine. She received her degree from the University of Oklahoma College of Medicine and completed her residency in pediatrics at Children’s Mercy Kansas City. She is fellowship trained in pediatric hematology/oncology from Children’s Mercy Kansas City.Learn more about Erin Guest, MD
Transcription:
Oncology Biorepository: Banking on Finding Answers for Childhood Cancers
Dr. Michael Smith (Host): The topic today is “Oncology Biorepository: Banking on Finding Answers for Childhood Cancers”. My guest is Dr. Erin Guest. She's a pediatric hematologist/oncologist at Children's Mercy Kansas City and Assistant Professor of Pediatrics at the University of Missouri Kansas City School of Medicine. Dr. Guest, welcome to the show.
Dr. Erin Guest (Guest): Thank you so much for having me.
Dr. Mike: You know, I guess one of the challenges in oncology, right, whether it's pediatric oncology, adult oncology, is really understanding why one patient responds well to a certain treatment and another patient doesn't. Tell us a little bit, then, about the inspiration for the biorepository.
Dr. Guest: Well, we have over 200 new patients per year here, at Children's Mercy with cancer and, of course, we focus on curing the patients and, you know, giving them the very best and latest clinical treatment but when they're going through their treatment, they sometimes have leftover tumor samples and blood samples and bone marrow and so forth that ends up getting stored in the pathology lab and I think for the best benefit of our patients and for our research community, we wanted to be able to offer to the patient families to be able to donate those samples to research. So, through having a tumor bank, we can store those samples and then they can be made available to researchers at Children's Mercy and at KU and within our community. The big goal being to hopefully improve the cure rates, improve the treatments and even decrease toxicity if we can find better treatment for these types of cancers.
Dr. Mike: So, when there's a sample that is added to the tumor bank, tell us, how exactly is that sample being used and in what research and what, so far, has come out of banking these kind of tissue samples?
Dr. Guest: Well, the tumor bank is actually really new. We just kicked it off in January of 2017. So, we've been enrolling patients for a few months now and then what we do is we ask patients if they'd like to donate their leftover tumors and tissues and if they'd like to give a sample of blood. And, so then, those samples have been stored within a laboratory at Children's Mercy and we actually extract DNA and RNA from them at the time that we store them. We also store, for instance, a part of the blood called “plasma” and we store even live cells. So, those cells could eventually be grown in tissue cultures and new types of drugs can be tested against those tumor cells to see what might work best against them. We freeze all of the samples and store them in this laboratory and then we also store with it data, so we know how old the patient was at the time they were diagnosed and what type of treatment they were given and if they had a good response to treatment or the tumor came back, and then that can be provided to researchers. So, we have several projects that are already underway, even though the tumor bank is so brand-new, but we have a couple of leukemia projects that are planning on using these live cells to take a look at what the genomic . . . how treatments might be designed to treat that very specific leukemia, and that type of mutations that are in it. We have another project where our infectious disease doctors are interested in seeing how cancer patients can metastasize certain antifungal drugs. So, sometimes we have to treat our patients with medicines to try to prevent fungal infections and sometimes that works, sometimes that doesn't. So, we don't know very well yet why that is. It may be there are differences in how the patients handle those drugs. So, that's an example of a project that is actually not using the cancer cells, but it's actually using the patient's blood and their [unintelligible 04:17] which we have stored within the tumor bank as well. And then, there's another project where we're taking samples from patients who have brain tumors that are biopsied and we store those live cells that then can be grown in culture and tested to understand why some patients get them and why some respond differently to different treatment. So, these are all projects that are being done by different researchers at Children's Mercy that are collaborating with folks at KU and around the community and they're able to use this resource and I think it will really honor the patient's donation to the biobank by developing all of these new findings that are hopefully going to improve the cures for these diseases.
Dr. Mike: Right. Right. So, you had mentioned that Children's Mercy takes care of what? 200 new cancer patients a year, right? So, out of that number, how many families are willing to give or donate the tissue samples to the bank? And, when they do, what are some of their concerns?
Dr. Guest: Well, I always say that the overwhelming majority of families are excited and happy to do this. I think they realize that if their child's tumor is no longer needed for clinical purposes, it's best used for research and they want to help other kids. I mean, that's really the benefit there. They know that they're helping other children in the future and helping them to suffer less, hopefully, and with a better chance for a cure with less side effects. And our families, so far, we've had about 40 enrolled and I think we've maybe had one family that declined and I think, sometimes, the families can be just so overwhelmed with the diagnosis of cancer, that it's hard to think about other issues in the future. But, for a lot of families, I think that they really get excited about [unintelligible 06:06] And sometimes, we even have families, who in the past, before we had this biobank, have asked you know, "Can we donate our child's tumor? Is there something to do with it to help other kids in the future?" And, there are some national biobanks also and we participate in that. For example, through the Children's Oncology Group, we do offer that to our patients, as well, but I think it's really neat to see it on a local level because then our families can see really what the outcomes are, the research that they're donating to.
Dr. Mike: Right. Right. And so, this particular tumor bank at Children's Mercy, is it just for researchers from Children's Mercy and in the local area, or is it open to anybody who's doing research that's obviously been vetted by Children's Mercy and accepted? Do you keep it local, or how does that work?
Dr. Guest: Well, it's mostly local, but it could potentially be . . . We'd love for it to become part of national collaborations as well. We're really open to supporting research with lots of different groups. We definitely want to keep a Children's Mercy researcher involved with each project because we want to make sure that we're honoring our patients' wishes and being able to give that feedback to our patients with what is happening with the biobank here on a local level. So, hopefully, it's going to support for many, many years to come, lots of different projects in different cancers and, you know, with current groups.
Dr. Mike: So, you know, the cancer genomic field is growing leaps and bounds, understanding the genetics of a cancer and how that plays out in individual patients and what treatments may or may not work, so that's a huge area of study. How does the tumor bank aid in understanding the genomics of cancer?
Dr. Guest: So, that's a great question. We've thought a lot about that as we've put the biobank together and so, as each patient's blood sample or tumor sample goes to the biobank, we immediately take the DNA and RNA from the samples and store that also. So, we have that ability, then, to do genomic work with these samples in the future. So, essentially, we could study the genomics of patients with the blood cells and that may help us understand why a patient develops cancer or maybe why the responded well, or didn't respond well based on their genetics. And then, when we study the genetic genomics of the tumor, then that can help us understand what other targeted treatments might work better for that patient's tumor. So, it's more of on a research level at the moment but as we develop those resources, [inaudible 08:58] both so that a patient, when they sign up for the tumor bank, can then opt-in and say, "Not only do I want to donate my tumor to this research bank but I would like you to go ahead and do sequencing and then report back that." So, hopefully, that can help guide their treatments and give them even more benefits being part of that tumor bank.
Dr. Mike: Yes. We're learning, too, it's the genomics of a specific cancer, you know, one type of cancer could act very differently in different patients, and I think that's a very interesting aspect of current research in cancer genomics. When you're laying this out and you're taking the DNA and the RNA, are there issues with how stable these molecules are and how you're able to store them and reserve them for research? Is there new technology that you guys are using to ensure the stability of the DNA and RNA?
Dr. Guest: Sure. The RNA is the trickiest, for sure, and it really relies on getting good, quality samples. If the tumor comes from the patient intact and without a lot of necrosis within the tumor, then that's the best for being able to get intact RNA and DNA. DNA stores for a long time and really maintains the quality and RNA can have some breakdown over time. But, there are some tricks that we can do when we first extract those to be able to store them for long-term and that's part of why we're doing the extractions up front. There are some biobanks that may store a tumor, then later on, years down the road, go back and try to extract the DNA and RNA and then, in that case, it usually isn't as good a quality. So, I think that's been a nice part of the biobank as we have set it up to be able to have that--the ability to store it from every tumor right up front and every patient up front, as well.
Dr. Mike: So, Dr. Guest, as somebody who is trained, Fellowship-trained in hematology/oncology and you see something and being a part of creating and developing this oncology biorepository, what's your hope for this? Where do you see this going? What does the future look like for the diagnosis and treatment for pediatric cancers?
Dr. Guest: Well, the bio-bank's really been a dream of mine for a few years because I have had patients in the past that have said, "I really want you to be able to do something with my tumor, you know? You removed this and it's sitting in a freezer. Let's do something with it and let's make treatments better and let's get better cures." So that, to me, is the most important is being able to offer this as service for our patients where they feel like they can give back and then, as a core resource for our research community within Children's Mercy and then beyond. I think it's critical. We can't do research in pediatric cancer unless we have the tissue to use to be able to do that research. We need the cell's growth so that we can test drugs. We need the DNA so that we can do the genomics and really understand the differences between cancers. And then, the clinical data that goes along with these tumors that is extremely important, too, because, say, if we have two kidney tumors, and just do research without knowing anything about the patients, we're doing a little bit of research in the dark. But, if we know say we had two six-year-olds that both had kidney tumors, but one of them responded to treatment and one of them didn't, then we have that clinical data to sort of back that up, and then we can take that into a lab and really be able to, hopefully, determine why is that? And, the more cases and the more material that we collect, then the more powerful that data becomes to be able to detect the differences between different patients. So, my goal is that this is something that we can continue indefinitely at Children's Mercy and we build a big resource that will support research in the future and we're working to see lots of different projects and lots of publications based within the [inaudible 13:18] for all of our researchers in the area.
Dr. Mike: Yes. This is really exciting and I think the results from this is going to be very amazing and impactful in the clinical practice of oncology. If there's a researcher who's listening to this show, Dr. Guest, and they want to use some of these samples, what's the process for them [inaudible 13:40] the tumor bank?
Dr. Guest: Sure. We have an application form that we ask our researchers just to let us know through this form what types of samples they would like, how many, and how they want them to be prepared and delivered for them and then what clinical information they need, so we don't just automatically give all the information about the treatment necessarily, but they would ask for specific pieces that they need for their project. And, each project that will be formed does need an institutional review board approval. So, if they're simply using tissue, cells, or DNA with no clinical information, then we typically would not consider that human subject research but if a researcher is really wanting to know patient-level data and then the IRB helps them process and making sure that we're protecting the patient rights with confidentiality. So, we have everything, all of our samples are barcoded and de-identified too, even to myself, included, and to all the researchers, so we can protect that confidentiality. So, if a researcher then has an IRB approved project and apply for the samples, they can go through me and our tumor bank staff and we'll provide the sample.
Dr. Mike: Fascinating work, Dr. Guest. I want to thank you for what you're doing with the tumor bank. I really think that you're you know, this is going to really lay out some wonderful results in cancer research so, great job and thanks for coming on the show today. You're listening to Transformational Pediatrics with Children's Mercy Kansas City. For more information, you go to www.childrensmercy.org. That's www.childrensmercy.org. I'm Dr. Mike Smith. Thanks for listening.
Oncology Biorepository: Banking on Finding Answers for Childhood Cancers
Dr. Michael Smith (Host): The topic today is “Oncology Biorepository: Banking on Finding Answers for Childhood Cancers”. My guest is Dr. Erin Guest. She's a pediatric hematologist/oncologist at Children's Mercy Kansas City and Assistant Professor of Pediatrics at the University of Missouri Kansas City School of Medicine. Dr. Guest, welcome to the show.
Dr. Erin Guest (Guest): Thank you so much for having me.
Dr. Mike: You know, I guess one of the challenges in oncology, right, whether it's pediatric oncology, adult oncology, is really understanding why one patient responds well to a certain treatment and another patient doesn't. Tell us a little bit, then, about the inspiration for the biorepository.
Dr. Guest: Well, we have over 200 new patients per year here, at Children's Mercy with cancer and, of course, we focus on curing the patients and, you know, giving them the very best and latest clinical treatment but when they're going through their treatment, they sometimes have leftover tumor samples and blood samples and bone marrow and so forth that ends up getting stored in the pathology lab and I think for the best benefit of our patients and for our research community, we wanted to be able to offer to the patient families to be able to donate those samples to research. So, through having a tumor bank, we can store those samples and then they can be made available to researchers at Children's Mercy and at KU and within our community. The big goal being to hopefully improve the cure rates, improve the treatments and even decrease toxicity if we can find better treatment for these types of cancers.
Dr. Mike: So, when there's a sample that is added to the tumor bank, tell us, how exactly is that sample being used and in what research and what, so far, has come out of banking these kind of tissue samples?
Dr. Guest: Well, the tumor bank is actually really new. We just kicked it off in January of 2017. So, we've been enrolling patients for a few months now and then what we do is we ask patients if they'd like to donate their leftover tumors and tissues and if they'd like to give a sample of blood. And, so then, those samples have been stored within a laboratory at Children's Mercy and we actually extract DNA and RNA from them at the time that we store them. We also store, for instance, a part of the blood called “plasma” and we store even live cells. So, those cells could eventually be grown in tissue cultures and new types of drugs can be tested against those tumor cells to see what might work best against them. We freeze all of the samples and store them in this laboratory and then we also store with it data, so we know how old the patient was at the time they were diagnosed and what type of treatment they were given and if they had a good response to treatment or the tumor came back, and then that can be provided to researchers. So, we have several projects that are already underway, even though the tumor bank is so brand-new, but we have a couple of leukemia projects that are planning on using these live cells to take a look at what the genomic . . . how treatments might be designed to treat that very specific leukemia, and that type of mutations that are in it. We have another project where our infectious disease doctors are interested in seeing how cancer patients can metastasize certain antifungal drugs. So, sometimes we have to treat our patients with medicines to try to prevent fungal infections and sometimes that works, sometimes that doesn't. So, we don't know very well yet why that is. It may be there are differences in how the patients handle those drugs. So, that's an example of a project that is actually not using the cancer cells, but it's actually using the patient's blood and their [unintelligible 04:17] which we have stored within the tumor bank as well. And then, there's another project where we're taking samples from patients who have brain tumors that are biopsied and we store those live cells that then can be grown in culture and tested to understand why some patients get them and why some respond differently to different treatment. So, these are all projects that are being done by different researchers at Children's Mercy that are collaborating with folks at KU and around the community and they're able to use this resource and I think it will really honor the patient's donation to the biobank by developing all of these new findings that are hopefully going to improve the cures for these diseases.
Dr. Mike: Right. Right. So, you had mentioned that Children's Mercy takes care of what? 200 new cancer patients a year, right? So, out of that number, how many families are willing to give or donate the tissue samples to the bank? And, when they do, what are some of their concerns?
Dr. Guest: Well, I always say that the overwhelming majority of families are excited and happy to do this. I think they realize that if their child's tumor is no longer needed for clinical purposes, it's best used for research and they want to help other kids. I mean, that's really the benefit there. They know that they're helping other children in the future and helping them to suffer less, hopefully, and with a better chance for a cure with less side effects. And our families, so far, we've had about 40 enrolled and I think we've maybe had one family that declined and I think, sometimes, the families can be just so overwhelmed with the diagnosis of cancer, that it's hard to think about other issues in the future. But, for a lot of families, I think that they really get excited about [unintelligible 06:06] And sometimes, we even have families, who in the past, before we had this biobank, have asked you know, "Can we donate our child's tumor? Is there something to do with it to help other kids in the future?" And, there are some national biobanks also and we participate in that. For example, through the Children's Oncology Group, we do offer that to our patients, as well, but I think it's really neat to see it on a local level because then our families can see really what the outcomes are, the research that they're donating to.
Dr. Mike: Right. Right. And so, this particular tumor bank at Children's Mercy, is it just for researchers from Children's Mercy and in the local area, or is it open to anybody who's doing research that's obviously been vetted by Children's Mercy and accepted? Do you keep it local, or how does that work?
Dr. Guest: Well, it's mostly local, but it could potentially be . . . We'd love for it to become part of national collaborations as well. We're really open to supporting research with lots of different groups. We definitely want to keep a Children's Mercy researcher involved with each project because we want to make sure that we're honoring our patients' wishes and being able to give that feedback to our patients with what is happening with the biobank here on a local level. So, hopefully, it's going to support for many, many years to come, lots of different projects in different cancers and, you know, with current groups.
Dr. Mike: So, you know, the cancer genomic field is growing leaps and bounds, understanding the genetics of a cancer and how that plays out in individual patients and what treatments may or may not work, so that's a huge area of study. How does the tumor bank aid in understanding the genomics of cancer?
Dr. Guest: So, that's a great question. We've thought a lot about that as we've put the biobank together and so, as each patient's blood sample or tumor sample goes to the biobank, we immediately take the DNA and RNA from the samples and store that also. So, we have that ability, then, to do genomic work with these samples in the future. So, essentially, we could study the genomics of patients with the blood cells and that may help us understand why a patient develops cancer or maybe why the responded well, or didn't respond well based on their genetics. And then, when we study the genetic genomics of the tumor, then that can help us understand what other targeted treatments might work better for that patient's tumor. So, it's more of on a research level at the moment but as we develop those resources, [inaudible 08:58] both so that a patient, when they sign up for the tumor bank, can then opt-in and say, "Not only do I want to donate my tumor to this research bank but I would like you to go ahead and do sequencing and then report back that." So, hopefully, that can help guide their treatments and give them even more benefits being part of that tumor bank.
Dr. Mike: Yes. We're learning, too, it's the genomics of a specific cancer, you know, one type of cancer could act very differently in different patients, and I think that's a very interesting aspect of current research in cancer genomics. When you're laying this out and you're taking the DNA and the RNA, are there issues with how stable these molecules are and how you're able to store them and reserve them for research? Is there new technology that you guys are using to ensure the stability of the DNA and RNA?
Dr. Guest: Sure. The RNA is the trickiest, for sure, and it really relies on getting good, quality samples. If the tumor comes from the patient intact and without a lot of necrosis within the tumor, then that's the best for being able to get intact RNA and DNA. DNA stores for a long time and really maintains the quality and RNA can have some breakdown over time. But, there are some tricks that we can do when we first extract those to be able to store them for long-term and that's part of why we're doing the extractions up front. There are some biobanks that may store a tumor, then later on, years down the road, go back and try to extract the DNA and RNA and then, in that case, it usually isn't as good a quality. So, I think that's been a nice part of the biobank as we have set it up to be able to have that--the ability to store it from every tumor right up front and every patient up front, as well.
Dr. Mike: So, Dr. Guest, as somebody who is trained, Fellowship-trained in hematology/oncology and you see something and being a part of creating and developing this oncology biorepository, what's your hope for this? Where do you see this going? What does the future look like for the diagnosis and treatment for pediatric cancers?
Dr. Guest: Well, the bio-bank's really been a dream of mine for a few years because I have had patients in the past that have said, "I really want you to be able to do something with my tumor, you know? You removed this and it's sitting in a freezer. Let's do something with it and let's make treatments better and let's get better cures." So that, to me, is the most important is being able to offer this as service for our patients where they feel like they can give back and then, as a core resource for our research community within Children's Mercy and then beyond. I think it's critical. We can't do research in pediatric cancer unless we have the tissue to use to be able to do that research. We need the cell's growth so that we can test drugs. We need the DNA so that we can do the genomics and really understand the differences between cancers. And then, the clinical data that goes along with these tumors that is extremely important, too, because, say, if we have two kidney tumors, and just do research without knowing anything about the patients, we're doing a little bit of research in the dark. But, if we know say we had two six-year-olds that both had kidney tumors, but one of them responded to treatment and one of them didn't, then we have that clinical data to sort of back that up, and then we can take that into a lab and really be able to, hopefully, determine why is that? And, the more cases and the more material that we collect, then the more powerful that data becomes to be able to detect the differences between different patients. So, my goal is that this is something that we can continue indefinitely at Children's Mercy and we build a big resource that will support research in the future and we're working to see lots of different projects and lots of publications based within the [inaudible 13:18] for all of our researchers in the area.
Dr. Mike: Yes. This is really exciting and I think the results from this is going to be very amazing and impactful in the clinical practice of oncology. If there's a researcher who's listening to this show, Dr. Guest, and they want to use some of these samples, what's the process for them [inaudible 13:40] the tumor bank?
Dr. Guest: Sure. We have an application form that we ask our researchers just to let us know through this form what types of samples they would like, how many, and how they want them to be prepared and delivered for them and then what clinical information they need, so we don't just automatically give all the information about the treatment necessarily, but they would ask for specific pieces that they need for their project. And, each project that will be formed does need an institutional review board approval. So, if they're simply using tissue, cells, or DNA with no clinical information, then we typically would not consider that human subject research but if a researcher is really wanting to know patient-level data and then the IRB helps them process and making sure that we're protecting the patient rights with confidentiality. So, we have everything, all of our samples are barcoded and de-identified too, even to myself, included, and to all the researchers, so we can protect that confidentiality. So, if a researcher then has an IRB approved project and apply for the samples, they can go through me and our tumor bank staff and we'll provide the sample.
Dr. Mike: Fascinating work, Dr. Guest. I want to thank you for what you're doing with the tumor bank. I really think that you're you know, this is going to really lay out some wonderful results in cancer research so, great job and thanks for coming on the show today. You're listening to Transformational Pediatrics with Children's Mercy Kansas City. For more information, you go to www.childrensmercy.org. That's www.childrensmercy.org. I'm Dr. Mike Smith. Thanks for listening.