Unique Aspects of Pediatric Care Delivery Model: Pediatric Oncofertility 2017

So as we continue for this afternoon, I will be um kind of introducing each section as we go along. And our first topic that we have for today is gonna be about the unique aspects of really the pediatric care delivery model and we've broken that out into several sections thinking that there's an oncology piece that's more specific to the pediatric realm followed then by the uh male and female components. And the options that may be different than what we find in adults and then also some of those ethical concerns so I think that we're gonna start with the first section in the pediatric care delivery model and that first section is going to be delivered by Doctor Karen Burns, who is one of the co-directors, as I mentioned of the program and is our oncology lead so I will let her start her portion great. Thank you very much Leslie and thank you for the chance to to be here this afternoon and to share some perspectives on uh pediatric oncology with you. Um, I will take you through a little bit of the epidemiology behind pediatric oncology as well as um the rhyme and reason behind our therapy and the way we do the things we do and along the way I'll try to point out some of the ways. That we differ in pediatrics from our adult counterparts we'll talk a little bit about survivorship and the role that fertility preservation has in survivorship and then end with the consensus statement, um, that Doctor Woodruff already mentioned and transition into some of the preservation techniques that we have available for our population all in 15 minutes. OK, there we go, so childhood cancer, um. Represents less than 1% of the nearly 1.6 million new diagnoses of cancer in the United States every year. So one of the things I hear most often is, you know, childhood cancer is such a rare disease, but I would argue that it's really not that rare. So less than 1% still amounts to over 15,000 children diagnosed with cancer in the United States. It's 43 children diagnosed every single day. And that amounts to about 40,000 children in treatment in any given year in the United States. Our average age at diagnosis is 6 years old, and so we'll touch on survivorship in a bit, but there is certainly a lifetime in front of our patients that we hope to give them the best quality of life possible. And while achieving cure is our ultimate goal, we like to do it in a way where they grow up to lead a healthy and happy life. Our childhood cancer patients knows no boundaries, um. It has no bias, so it'll affect all ethnic, gender, and socioeconomic groups. Childhood cancer typically results from changes in DNA that allow infinite cell growth and infinite life, and this is not unlike most adult cancers. However, most pediatric cancers, this can be found early in life, so even if the disease itself does not manifest for several more years, those DNA damages can happen very early. Unlike adult cancers, our cancers are usually not linked to any environmental factors and not linked to any lifestyle factors. Most of our patients are treated at a children's oncology group center, and there are hundreds throughout the United States and internationally. And unlike the adults, our children are more likely to be treated on a therapeutic trial than in the adult population. These graphs represent the distribution of diagnoses that we see in pediatric oncology. So you can see on the left are the ages of under 14 years old, the diagnosis that are most common. So leukemia and lymphomas make up the vast majority of our diagnoses, followed closely by CNS or brain tumors. And in our younger patients, the solid tumors are a little bit less likely. As our patients get older and start to get more into the adolescent or young adult realm, you can see that leukemia and lymphomas are still common. However, lymphomas make up a larger proportion of these patients, largely due to our diagnosis of Hodgkin's lymphoma. CNS tumors are still fairly common, but then our sarcomas and solid tumors start to take up, um, a greater percentage of our diagnoses, and you can see that with the carcinomas, um, as well as our germ cell tumors and other solid tumors listed there. Childhood cancers typically grow very quickly and some will also spread very quickly, so we are not exactly known for our patients in the world of pediatric oncology. We like to get things going very quickly, so we have minimal time between the presentation to the diagnostic workup and then the start of therapy. So sometimes this can be within just a couple of days or just a week or two from the time we first meet our patients to the time we get them started on their chemotherapy regimen. Typically our childhood cancer patients respond very well to traditional chemotherapy, and they can tolerate much higher doses and compressed chemotherapy schedules compared to adult counterparts, and this has really allowed us to push the envelope over the years with our therapies to achieve our cure rates. Traditional chemotherapy is specific for the cell cycle but not necessarily specific for the cell type, so it will affect non-cancerous cells just as much as it will affect the cancerous cells, and this can lead to the late effects down the line. It will act um via altering DNA mechanisms or DNA repair mechanisms, and you can see the most common categories of our traditional chemotherapy listed here. We have a tendency to try to minimize radiation in the pediatric population as much as we can. There's certainly a role for it, but if we can get away with chemotherapy, we'll usually opt for that method because of the late effects associated with radiation and the fact that they can accumulate as the years go on. We have learned however that late effects are common and this has played a role in how we do our therapy. So most oncology therapies now, or the vast majority are risk adapted therapy. So you will see our pediatric oncologist stage the disease at diagnosis and come up with a treatment plan that is most appropriate based on that stage or risk group. Then we do. Therapy usually for one or two cycles and go through the staging process again and by doing this we can help to identify who's responding quickly to therapy and who is not. So our rapid early responders will then go down a path of less intense therapy and our slow early responders will continue down a path of more intense therapy to achieve that goal of cure. This is just an example of one of our treatment regimens. This is from a previous study for Hodgkin's lymphoma for our intermediate risk group, and you can see there in the beginning, after staging, they're started on a chemotherapy regimen and will receive two cycles of chemotherapy and then be restaged. The top half then will go on to be. Rapid early responders and receive more chemotherapy and may or may not receive radiation where in somebody who was a slow early responder, so had more disease left at that time of restaging, they get chemotherapy and radiation and may or may not get more chemotherapy so by using an approach like this. We are able to deliver therapy that is appropriate to the patient and still achieve optimal cures and hopefully help to minimize late effects so that those patients who are responding well to therapy do not get extra therapy they don't need and be at a higher risk of late effects. We are also starting to embrace our newer therapies, so we have a new era of immunotherapy coming into the world of oncology, both in the adult world and in the pediatric world. So some examples of this would be the immunotherapy with our CAR T cell therapy, where the patient's own T cells are harvested and then genetically engineered to attack a specific target on the cancer cells. They're given back to the patient then. And then they go to work to kill the cancer cells. We also have more targeted therapy that is specific to the cancer cells and specific targets on those cells. So our monoclonal antibodies like the rituximab and ofatumumab are bite therapy, which is bioelic T cell engineered therapy, um, like bleatumumab, kinase inhibitors. You may have heard of Gleevec or dasatinib. Our PDL1 inhibitors, so the um pembrolizumab, which is in the news, Keytruda, small molecules and anti-angiogenesis, so these are more specific for cell type and so fewer non-cancerous cells are damaged by using this therapy with the hope that they will ultimately have late effects while still achieving some of these great cure rates that you can see here displayed on this graph. We have had increasing childhood cancer survival rates over the last several years and currently our 5 year cancer free survival rate in pediatrics is at over 83%. So this is something that we are very proud of. In 2013 it was estimated that we had about 420,000 childhood cancer survivors living in the United States. So again, not as rare as one might initially think, and the estimation is that this will be 500,000 or half a million cancer survivors by the year 2020. So with our increasing numbers of cancer survivors, we have increasing awareness of the effects of our therapy, and the one we're gonna focus on today is the gonado toxicity associated with some of our therapies with delayed puberty, early menopause, azospermia, and the loss of fertility, and the research has shown over the years that this is extremely important to our patients and to their quality of life post therapy, regardless of their age and diagnosis and whether or not they've already had children. So it's important to remember that premature menopause may allow us a window of opportunity to do fertility preservation in our female survivor patients. So there was some recent data presented at ASCO back in 2016 by Doctor Levine from the CCSS data. That showed that patients who were female patients who were childhood cancer survivors between the ages of 20 and 29, did not have any statistically significant difference in pregnancy rate compared to their sibling controls. However, if you looked at them a decade later, between the ages of 30 and 39, there was a significantly decreased rate of pregnancy in these childhood cancer survivors. So there is a window of opportunity, but it's very important to act quickly. And to remember that these survivors are at risk of early menopause. Male patients have also been shown to be very interested in knowing their risk status and being offered a review of their risk as well as a semen analysis to know where they stand post therapy, and all patients benefit from counseling and from reviewing their risks. As Doctor Woodruff mentioned, this is very important to the medical community as well, and many of the large organizations, including the American Society of Clinical Oncology, the American Society of Reproductive Medicine, and the Association of Pediatric Hematology and Oncology Nurses have all come out with consensus statements regarding fertility and fertility preservation, and I just summarized the ASCO consensus statement here. So it really um says. That as part of education informed consent should happen before cancer therapy and as early as possible to allow the greatest number of fertility preservation options be available to that patient. If they are not available in your area, they should be offered through a referring center who can provide that service for the patients, and it's important to talk to the parents of children and minors as well as patients of um consenting age, and this treatment should continue through survivorship as well. So with that statement I'm going to turn it over to my colleagues um to talk more about the fertility preservation options in the males and females. I, I realized, Todd, when we got started that we really didn't have really a good feel for our participants if they're really focused in the pediatric population or if they're more focused in the adolescent or young adult population, and I wondered if we could perhaps query those that are participating if there's more of. Focus or do they really treat the spectrum of ages young adults as well? I think we're focusing a bit more on the pediatric population, but we also serve young adults and obviously some of those conditions affect those who are also through puberty and into young adulthood. I know that we have a session set aside as we move forward in regards to a panel discussion and some questions. I, I wondered in summary from Doctor Burn's presentation. My assessment always as being one of the gynecologic providers is that the oncologists are like right out of the gate and ready to go forward with their treatment. I wondered if she could comment on maybe some of the ways she's interacted with her colleagues and sort of slowing down the pace to get a chance to sort of have these discussions. Yeah, it's, it's definitely been a work in progress. Um, it is true that we have a tendency to meet the patient and try to get started as soon as possible, but. Um, as we'll hear some of our fertility preservation techniques really don't require a lot of time to complete, and they really don't, um, interfere very much with the timing of therapy, so they can be done quickly, um, they can be done efficiently, and they can really provide a great service to the families. So sometimes just going to, uh, my oncology colleagues over and over and sometimes over again to ask them to remember, um, to think about fertility, um. And to talk to families about it and to get us involved to talk to the families, um, is really important and over time, um, I think it's really caught on and seeing the patients really embrace that and really be extremely appreciative of the the knowledge of the chance to even just think about having children in the future, giving them that hope for the future, um, that we think they're gonna get through this and they're gonna grow up and they're gonna have families of their own has really been good too and and having my colleagues. Hear that from their patients and see how much it's helped them has helped them to remember it again with the next patients coming in. So awesome, right? I think that you've really taught me in our time working together. I think you've been very actively engaged in the um support group community with patients and families and really you hear their voice about how important this is to them and I think that's one of the ways that we can really kind of knock down those barriers that might be there for providing the service even before therapy starts so awesome presentation. And we'll continue to be watching for other questions or comments, and it looks like there are some responses about different centers kind of doing a little bit of pediatric and young adult patients. I don't know if you saw that, Dr. Ponsky, but we're, we're gonna put the polls up now, so if people could answer, it'll take about 30 seconds to get those, OK? And as we get that, that'll help guide us in our conversation as we kind of tailor it to who's listening and what sort of options we discuss. I think we had to cover all the topics that our participants are interested in.