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Jacqueline Palfy (Host):   Hi. I'm Jacqueline Palfy with Sanford Health News. We are here today with Dr. Sam Milanovich to talk a little bit about pediatric cancer and research and personalized medicine. Welcome.

Sam Milanovich M.D. (Guest):  Thanks Jacqueline.

Host:   Thanks for coming here today. First of all, tell me a little bit about where you're from and how you got into…Who decides they want to be a cancer doctor?

Dr. Milanovich:   Well, so I'm a pediatric cancer doctor and cancer researcher here at Sanford Health. So my interest is in both taking care of children and young people with cancer, but also studying the cause of cancer and how can we learn more about what causes cancer and why it responds to treatments.

Host:   Did you start out wanting to work with children or wanting to work with cancer? Which came first?

Dr. Milanovich:   I had a little bit of both. I think like so many of us cancer touches our lives in different ways. So as a science major and a young medical student, I was curious about the biology and the cause of cancer. What makes it happen and behave the way it does. That kind of coupled with, as I started getting into clinical medicine, just I enjoyed the challenges and rewards of working with children because you're also working with families in that case. So that sort of spoke to me and was kind of my calling was to help kids.

Host:   I've heard you say before that working with kids is so different because they just kind of roll with things differently than adults.

Dr. Milanovich:   Kids are amazing. We can learn a lot from kids. They will…Maybe sometimes they just accept things a little more at face value.

Host:   Less jaded than the rest of s.

Dr. Milanovich:   Sometimes perhaps. Kids also understand things a lot more than I think we often give them credit too. Sometimes just listening to what a young person is trying to tell you you can learn a lot.

Host:   Well, I think that knowing that you have to explain all of your work to very young folks will be helpful for me today. So I’ll be able to hopefully understand as much as they do.

Dr. Milanovich:   Well and you know Jackie children have—Their minds are more geared towards learning. So sometimes that might be easier.

Host:   I better put my mind in a different gear today. Tell me a little bit…We’ve done a lot of these podcasts where we talk about personalized medicine, which is that seems to be what everyone is calling it now. We’ve kind of given it a different name over the years trying to find the right fit. What exactly…How do you define that in your work?

Dr. Milanovich:   So when I hear about personalized medicine—and this kind of became more of a hot topic or topic of discussion over the last several years—it kind of hit me as that’s what we’ve been doing for even longer in pediatric oncology at least. So, to me, that means learning as much as we can about the biology of a patient’s tumor or their cancer and understanding how that’s driving that tumor. Then how can we use that information to better tailor the treatment for the child? So we use a combination of a child’s DNA and how they respond to treatment to really dial in what we think is the best treatment possible rather than sort of a one size fits all approach to treatment.

Host:   What does that look like? I mean does that mean that you figure out the right thing faster or does it reduce your trial and error? What does that really look like on the ground?

Dr. Milanovich:   Yeah. So I mean we really do it through clinical trials. So we’ve ran generations of clinical trials over decades. An important part of what we've learned is that when we do these clinical trials, we collect as much information as we can from a patient’s cancer. So the DNA of their cancer, which is different than their own DNA, right? So a tumor cancer, by definition, is going to have mutations. We can find patterns of mutations in different tumors. So what we do now is when someone’s diagnosed with cancer, say leukemia which is the most common. It’s blood cancer. It’s the most common cancer that we deal with in children. We run a series of tasks to find any combination of mutations. We combine that with how the patient responds to the initial couple weeks of treatment. Then based on that we assign specific treatment regimens based on that, including sometimes adding specific drugs that directly align to or match up with a specific DNA mutation that we found in the tumor. We hope to, through future studies, find more and more of those kind of direct matches.

Host:   That seems kind of crazy, right, that you can find the specific thing that might work, and different even maybe then from when you started, right.

Dr. Milanovich:   Oh yeah. It’s continually evolving. One of the challenges as genomic technology and science is advancing and we can understand and using computational biology understand the complex interactions. It is a challenge to take all that complex science and convert it into meaningful information for patient treatment.

Host:   So you do a fair amount of…How is your time split between research and practice? Is that the right word for it?

Dr. Milanovich:   So I mean yeah. Clinical or patient care and research. As a physician who also does research it kind of intertwines a lot. My breakdown’s about 50/50. It never really feels—I don’t know where one stops and the next starts, right? Which is part of the joy. Part of my job is we’re learning about research. We’re conducting clinical trials which is research. Through that research we’re also doing patient care, finding the best clinical trial for the right patient. So it’s hard for me to say that there's a hard line there but.

Host:   How many clinical trials do we have—do you know right now—that involve some of your patients or the work that you're doing?

Dr. Milanovich:   We have several clinical trials. I did not pull the list for--

Host:   That’s okay. I know we have over 300 in general. We have a ton.

Dr. Milanovich:   Yeah. I can tell you that per percentage of patients—So pediatric cancer’s much more rare than adult cancers. We have a very high relative percentage of clinical trials. So we, in pediatric oncology, are able to enroll our patients on clinical trials. We have even just some sort of simple registries where we can collect tumor samples and collect information. So we might not have a trial where we’re testing a new drug or combination of drugs. We have those kinds of trials where you can at least learn more about the DNA of your tumor and how you responded to standard treatments. We have that open and available for every single patient that we take care of.

Host:   I always like to remind folks when we do these that you're under no obligation to be on a clinical trial and that you still get the same standard of care if you’re involved in one. It’s not that you get less care. You just get that care plus some. You can choose to not be involved in it at any point, right.

Dr. Milanovich:   Correct.

Host:   There's sort of a patient bill of rights about it.

Dr. Milanovich:   Yeah, absolutely. It’s always up to the patient, or in this case the patient and their families whether or not they want to conduct clinical trials. As pediatric oncologists we do lots of clinical trials. First and foremost we always are about giving our patients what's the best option. So there are often times where I’ll say, “We have a clinical trial that while technically you may be eligible for it, in our judgement based on everything we know, we don’t think that that’s the best treatment option for you.”

Host:   Sure.

Dr. Milanovich:   So sometimes that comes from us as providers saying, “Yeah, there are clinical trials, but we think there's a standard of care that’s very good and you should do that.” The flipside is also true.

Host:   It’s not a hard sale on clinical trials.

Dr. Milanovich:   Right. So many people are interested in clinical trials. Some people are not. They're not comfortable with the concept or that particular trial. That does not at all impact the quality of care that we deliver.

Host:   Talk to me a little bit about some of the research that you're working on. What's exciting about it in a level that I can understand.

Dr. Milanovich:   So I think—We work on research on different levels. I think some of the exciting things that we do is one, we’re part of a couple groups of children’s hospitals. So we’re part of a couple groups of children’s hospitals. So we have an international collaboration called the Children’s Oncology Group. That’s really exciting because through that we’re able to open trials across the country and part of north Europe. We can really design some pretty innovative detailed clinical trials to really start to get down to some of these—To start to answer questions about treatment for different kinds of tumors.

Host:   What are the questions you're asking?

Dr. Milanovich:   So for some of our tumors we have pretty high success rates. Meaning we treat your cancers—for instance, childhood leukemia. Some of the common subtypes we have more than 90% long term survival. 95% and one of our last clinical trials was we had a subset that had a 99% survival. In those cases, we’re left with a lot of toxicity. This circles back to personalized medicine. We can treat the leukemia and make it, so it never comes back. So many of our patients go on to live pretty happy healthy lives, but not as healthy as they could be. So our chemotherapy right now causes lots of complications. Heart disease, lung disease, problems with the ability to have children later in life, some cognitive effects. So it’s one thing to at least treat the cancer, but then we’re left with a lot of sort of collateral damage from the treatment. So we are designing trials to help be more precise in our treatment, and hopefully limit some of those long term or life effects.

Host:   What does that mean to be more precise?

Dr. Milanovich:   So that is learning as much from our previous clinical trials and then about the individuals we’re taking care of. So what is your exact tumor DNA and how does that tell us which therapies it’s gonna respond to or not.

Host:   So you may remove some of the things that you would—If you were doing a blanket treatment, maybe you’d take some of it out.

Dr. Milanovich:   Exactly. So if you show us signs of being a very high responder, we can take away some of the more toxic chemotherapies. Sometimes we incorporate pharmacogenomics. We do some genetic testing to see how we metabolize drugs. Then that can help us start at a different dose and thereby reduce some of the side effects we may cause.

Host:   We talk about that a lot on these podcasts. Just about how time saving that is for people to sort of feel better faster with—not specifically in cancer, but in different areas.

Dr. Milanovich:   It’s a little different in cancer, but the same thing. If we have a treatment that if you metabolize it slowly causes side effects. It then needs you to take—One, feel sick from those side effects and two, pause your treatment. That’s not optimal for your treatment. If we can predict how you're gonna metabolize that drug and get you the right dose to get in that spot where we’re maximizing treatment while minimizing side effects, that’s beneficial to patients.

Host:   How does it feel seeing that now compared to when you started to know that—which maybe wasn’t that long ago. It was a little while ago. We’ll have this conversation again in 10 years, right?

Dr. Milanovich:   Okay yeah.

Host:   But to know that you're able to maybe not cause some of that collateral damage as a provider.

Dr. Milanovich:   Yeah. As I look back and that all comes from clinical research and the trials we’ve been able to do and how we combine clinical trials with the biology that correlates with it to help understand. Our trials are a lot more sophisticated. We use a lot more of the genetics of a patient’s tumor to be more specific with the treatment. Our treatment arms are a little bit more complicated than they used to be, but I think that is to the benefit of our patients.

Host:   Then it probably feels good. Like maybe someone’s not going to have some of the issues, as many of the issues, or to such an extent later because of treating their cancer.

Dr. Milanovich:   Yeah exactly. I mean to see some of the strides we made, and we are continuing to improve our rates of long-term remission essentially cures and do that with a little bit less side effects is very rewarding. You also appreciate that it’s incremental. It’s step by step to get there and that’s kind of how clinical research works.

Host:   Well, I think that I have a little bit of a better understanding. So thank you so much for coming on today and we’ll talk again soon.

Dr. Milanovich:   Alright thanks Jacqueline. My pleasure.