Assistant Professor of Pediatrics, Dr. Jennifer McNeer, gives a presentation on how to optimize the care of adolescent oncology patients.
JENNIFER MCNEER: This is a little bit of change in terms of what we're going to talk about. This is not specifically geared towards women's health issues directly. But I am involved in our adolescent and young adult oncology program. And so I'm going to talk a little bit about that today. So what is adolescent and young adult oncology? This is really a discipline within oncology that has evolved over the past 10 to 15 years. And-- sorry, they're looking at me in the back. Am I-- I need to go this way? OK. AYA oncology is a discipline that's evolved over the past 10 to 15 years as it became evident that patients in this age group were not enjoying the benefits of improval of survival that we were seeing in both younger and older patients. And this is probably multifactorial, and I'll get into this a little bit today. It's likely a combination of biological factors of their diseases and also a reflection of the additional psychosocial support and some other gaps in their health care in general that has led to these discrepancies in outcomes. The discipline has become such that there are specific NCCN guidelines for the care of adolescent and young adult oncology patients now. There is a journal dedicated specifically to AYA oncology patients. Meetings throughout the year regarding these patients and also meetings within the larger cooperative group-- meetings specifically towards AYA oncology. So this is a pie chart that demonstrates the types of diseases that we see in these patients. So as you can see, lymphoma is the most commonly encountered neoplasm in this age group. And if we really talk fully about patients aged 15 to 39 years, which is what the NCCN defines as adolescents and young adults, second most common is breast cancer. Then thyroid cancer and melanoma. I will say, however, that the diseases we see in these patient populations shifts a lot when we're talking about the younger end of this spectrum into the older end of this spectrum. So in the adolescent and truly young adults, early 20-something-year-olds, we are seeing mostly lymphomas, leukemias, CNS tumors. We see some sarcomas in the adolescents and young adult population. And then as we get into patients in their late 20s and into their 30s, we start to see an increase in invasive skin cancers like melanoma, breast cancer, thyroid cancer, and things like that. So this graph shows the cancer incidence in the last quarter of the 20th century. And what you can see is that across any age groups, the incidence of cancer was increasing. The adolescent and young adult patients were not spared this increase in cancer incidence. But what we can see is that this incidence is probably leveling off. So if we look at 15- to 19-year-olds, we were seeing an increase in the '80s and into the '90s. This has probably leveled off now. The same can likely be said for patients 20 to 24 years old. And if we look at patients who are 25- to 29-year-olds, we are actually seeing a decline in the incidence of cancer. Some of this may have to do with the incidence of soft tissue sarcoma, like Karposi's sarcoma and non-Hodgkin lymphoma, which were increased during the time of the HIV epidemic. Then if we look at mortality trends during that same time frame, what we see here is a little bit more concerning. So AAPC stands for average annual percent change, and this is in mortality rates. So if we look at our younger patients, the mortality trends are actually decreasing over those 25 years there. Once we get into the 20-year-olds to about 44-year-olds, we're not seeing as much decrease in mortality in those patients compared to their younger counterparts. And if we look here at the relative survival rates, and this statistical analysis takes into account death that will happen in this patient population that's not related to cancer. So it sort of evens out a little bit and is truly looking at just cancer mortality. We see here that the survival rates for young patients with cancer were increasing over that 1975 to 2000 time frame. If we look at our older adult patients, we're also seeing an increase in survival rates. But if you look here at the adolescent and young adults, there's absolutely a drop-off in improvement of survival. And you can see for patients who are 25 to about 35, there's absolutely no change in survival for these patients. And this just breaks it down year by year and also into a little bit more detail based on age group. So for 15- to 19-year-olds, there was a bit of an increase in survival in the early '80s that's really leveled off since then. The 20- to 24-year-old patient group, we really have not seen an increase in survival rates at all. And the 25- to 29-year-olds, again, there was a dip in survival that likely correlated to the HIV era, but overall no improvement in survival. So why is this? It's really multifactorial, but we can break it down into a couple of categories. First is personal and patient issues. We have family and community issues. We have societal issues. And what I'm really going to focus on today are the health professional issues. So as far as the personal and patient issues or concerns, as you can imagine, these patients are really trying to exert their own independence. They're trying to figure out who they are. And they are absolutely unaware that cancer plays into this at all. So these are patients who are trying to get off to college, start careers. They've got evolving relationships. And they're not at all aware that they are at risk of cancer. So one in about 210 adolescent and young adults will be diagnosed with cancer. That's a pretty remarkable number. But because there's no real awareness on the AYA's part that they're at risk, there are a lot of delays in diagnosis. Compliance and adherence, as you can imagine, is really a problem in this age group. So the treatment regimens that they need are pretty intense. And they don't want to be taking medication every day. Maybe they have classes at college that are not allowing them to get to their visits to the clinic. Maybe they have a job that's not allowing them to take time off of work. There's a lot of factors that go into compliance with an adherence to their therapy. As you can imagine, health insurance is a big problem. This is by far the most underinsured patient population. I'm sure that this is changing with the Affordable Care Act and more national health insurance policies, so hopefully that will help. But as you can imagine, lack of health insurance also plays into the delays in diagnosis that we see in these patients. And then biology is very important. These patients may have the same type of cancer under the microscope, but biologically they seem to be driven very differently than that which we see in younger and older patients. I'm going to show a couple of slides about that. The toxicity profile also tends to be very, very different. So as patients get into the older adolescent and young adulthood time frame, if they're diagnosed with a quote "pediatric cancer," we want to give them a pediatric treatment regimen. Our pediatric regiments are incredibly intense. We have designed them for younger patients who can tolerate a lot more toxicity. And so we really need to be judicious about the supportive care. And as you heard during the last session, we have lots of antiemetics. We have lots of ways to modify symptomatology. But we really have to be aware that we are going to see a very different toxicity profile in an older adolescent or young adult than we do in our 5-, 6-, or 7-year-old patients who are getting the same treatment regimen. Support for these patients is really important. And what I'm showing here are a number of organizations, many of which have been founded by patients themselves to provide awareness, education, peer to peer support for these patients. You can see some of them have very interesting names. StupidCancer.org is a big one. But it's been very successful and has really raised awareness. And again, has provided support to these patients who felt like they had nobody they could turn to for a long time. So family and community and societal issues are somewhat similar and interlinked with one another. In both cases, there's a lack of awareness. So family and community organizations provide a lot of support for patients. But there's a gap in the support that's provided for the adolescent and young adults. A lot of community organizations are geared towards very pediatric patients or geared towards older adult patients. There are more organizations that have come up in the past decade or so that, again, are trying to provide support to the people who provide support to the patients. Health insurance, again, becomes a societal issue, as you can imagine. And the other societal issues are lack of education of teachers, employers, et cetera. And again, if patients cannot get time off of school, time off of work, there are going to be delays in diagnosis. But we as health professionals are definitely not off the hook here. Again, there's lack of awareness. This is true in the community. Patients may come in with symptoms that a practitioner does not have cancer on their differential. There's also a lack of awareness within the oncology community for what is the best way to treat these patients. There's data coming out that will tell us maybe a pediatric regimen would be better for a patient who is 28 or 29 years old. And if the oncologist who's seeing that patient isn't aware of that, it can certainly compromise a patient's outcome. Delays in diagnosis, of course, again, with a lack of awareness, patients coming in with certain symptoms may not get diagnosed as quickly as we would like them to be. There's a big difference in the pediatric versus the adult pattern of care. So in the pediatric realm, you can see there's a lot of providers that come in and take care of pediatric patients. So you've got your medical team. You've got your attending physician. You've got nurse practitioners. You've got other pediatric subspecialists who are there and consulting on patients, especially because most of the pediatric care occurs at a tertiary center where all of these specialists are right there for the patients. But then there's a lot of psychosocial support. So there are social workers for every patient. We've got child life support for every patient. Psychological support for patients. So there are a lot of other programs there in place to help the younger patients and their families navigate the treatment that those patients need. And you just don't usually see that amount of support in the adult model, whether it's because a lot of the adult care is happening in the community where there are not all of those people right there. And it's also a volume issue. The adult oncologists are taking care of a much higher number of patients. And so setting up all of these other support networks for all of those patients becomes very difficult. Clinical trial participation is vastly different in the pediatric versus the adult world. So probably 3/4 of pediatric patients in this country are enrolled on some type of clinical trial, whereas that number is probably under about 10% for adult oncology patients. And I'm going to focus in on that a little bit later. Tumor specimen banking is very, very important. So without having tumor specimens, we're not going to understand the biology of these patients. And this is where referring to a center where clinical trials are available for these patients is very important, because that's where those tumor specimens are collected, are as part of these clinical trials. I talked a little bit about tolerance to therapy. So again, we just have to be aware that the tolerance for these patients will be different than for younger patients. And then as I alluded to earlier, the ability to relate to other patients in care facilities. So one of the biggest concerns that patients have when they are adolescents and young adults diagnosed with cancer is that if they're seen in a pediatric clinic, they're there with a whole bunch of little bald 5-, 6-, 7-year-old kids running around. And they can't relate to these little kids, who are more interested in what cartoon is on Disney Junior. If they're treated in an adult facility, they're there with much older and elderly patients that they also don't have anything in common with, because those people are not dealing with how do I get to my college classes, how do I start this job? I'm just embarking on a career, and I just don't have time off. Things like that. So I want to focus in on the clinical trial piece of this and why that is so important. So the focus for pediatric versus adult oncology trials is pretty different. So in adult oncology, the focus has really been on discovering new approaches and new therapies to treat diseases that have very poor outcomes. So there are a lot more early phase trials, phase one, phase two trials. And those trials have been very successful. That's why we have imatinib or Gleevec now and why the treatment of chronic myeloid leukemia is so different than it was a couple of decades ago. But there are limitations in the way that we can enroll young patients or minors on trials. And so we're really limited in terms of the phase one, phase two trials that we can do in pediatrics. That is really reserved for a relapsed or refractory patient population. In pediatric oncology, we are much more focused on randomized phase three trials or trials that do a lot of risk stratification. We have diseases that have good outcomes. Now we're trying to figure out which patients we can actually spare them some of the therapy because we are thinking about a lifetime ahead of them. And so we have to minimize long-term effects. And so risk stratifying and understanding who needs that intense treatment versus who doesn't need such intense treatment is really important. And probably the optimal approach to the adolescents and young adults is going to be a combination of these approaches. There are going to be some diseases that are much more aggressive and require early phase adult type trials, but also diseases that we can have very good outcomes. And what we really need is risk stratifying these patients better, getting the tumor specimens or the bone marrow or blood specimens. So that way we can understand the biology better. So a good example of this is the cytogenetics or the chromosome abnormalities that we see in acute lymphoblastic leukemia. So if you look here at our young patients-- we're not going to talk about the infants here. I think I'm probably the only person in the room who would take care of an infant. So if we look at our pediatric patients, most of these patients have what we consider to be favorable cytogenetics. So that's what these orange and these yellow bars are. You can see an absolute drop-off as we get into the adolescent years of what we would consider to be favorable cytogenetics. And then as patients get older, we see an increase in this purple bar. And that's the Philadelphia chromosome. So many older patients with ALL have Philadelphia chromosome-positive ALL. But what I want to point out is the adolescent and young adult group here, most of whom fall in this light blue category, which is other, meaning we don't have characteristic cytogenetic abnormalities that we can identify in these patients that drive their tumors. So this is where the biology component of clinical trials becomes very important. So what Children's Oncology Group and M.D. Anderson and St. Jude did is through their studies, they collected samples from several thousand pediatric adolescent and young adult patients who had ALL. And using gene expression analysis, they identified a group of patients who had no characteristic cytogenetics but on gene expression analysis looked very much like patients who have Philadelphia chromosome-positive ALL. Then they dug deeper into these samples and using gene sequencing identified kinases that are activated and mutated in these patients that seemed to be driving these leukemias. So now we understand this is about a quarter of these patients who previously we had no idea what was driving their leukemia. Now we understand it a lot better for about 25% of those patients. And besides just understanding what is driving their leukemia, what's most exciting is that many of these mutations are targetable by kinase inhibitors. So this is a really nice example of how collecting the biological samples on a clinical trial has led to a finding that now can be parlayed into clinical practice. And this is very exciting and is going to be applied to patients in the very near future on Children's Oncology Group and NCAL GBR alliance trials. So do the clinical trials themselves actually matter? And I'm going to argue that the answer is absolutely yes. So we have seen incredible increases in survival rates for pediatric cancer. So in the '70s, only about 28% of children diagnosed with cancer had any type of five-year survival. Now 80% of children who are diagnosed with cancer are going to survive. But what you can see here is that there's a big drop-off in the absolute number of patients who are enrolled on clinical trials as they get older. We see an increase in the absolute number of enrollments as we get into older patients. But to be honest with you, the percent doesn't change that much. So 60% of children are enrolled on clinical trials. Only about 2% of adolescent and young adults with cancer are enrolled on clinical trials. And of older adults, it's about 3% to 5% that are enrolled on clinical trials. So clearly, the improvements in survival that we're seeing in these older adult patients is not purely due to enrollment on clinical trials. In these patients, screening programs are probably what is helping survival a lot. So screening mammograms, screening colonoscopies, pap smears, things like that. Whereas in the pediatric world, when they've attempted screening programs, they really have not been beneficial. So what we have found is that when we do any type of screening, we have found tumors that were not going to become malignant after all. And so it's not the screening programs that are helpful in the pediatric world. It's the clinical trials and treating patients in a very cohesive fashion that has really improved our outcomes. Likely for the AYA patients, it's going to be a combination of these approaches. Many of the cancers that happen in the younger end of this age spectrum are not ones that screening programs are going to be helpful for. They've never been proven for lymphomas, leukemias, CNS tumors. It would be important for adolescents and young adults as we get into the older end of that age range to increase awareness about melanoma is one where screening and education could certainly be helpful. But that's not the case for most of the cancers that we see there. So we really feel like increasing clinical trial enrollment will drive the improved survival for this patient population similar to the pediatric patients. So I have a couple of disease-specific examples. So this is data from CTEP, the Clinical Trials Evaluation Program, and SEAR, Surveillance Epidemiology and End Results, which is epidemiologic data on cancer in the US. And what this is showing, these hatched bars are patients with sarcomas who are accrued to clinical trials. And the dark bars are the average annual percent change in survival. And you can see there's a falloff of clinical trial participation when we get to about the 20-year-old age group. And the improvements in survivals that we have seen are in the age groups where we are seeing more patients enrolled on clinical trials. If you look at rhabdomyosarcoma, this is a sarcoma that makes up more than half of the sarcomas that we see in pediatrics but only about 1% to 2% of the sarcomas that are seen in patients over 18 years of age. A group in Italy looked at their outcomes for patients who were adults. They were 18 or over. And they categorized patients as having been treated with a pediatric model versus an adult model. And that had to do with the types of chemotherapy used, the intensity of the chemotherapy used, the intensity and timing of radiation relative to surgery. And those patients who were treated with a more pediatric approach had a five-year event-free survival of just over 60%. The patients who were treated with a more adult approach or less intense approach only had about a 30% five-year event-free survival. The same has clearly been shown in ALL. So this is a study out of France. This is a study out of the US here that was actually spearheaded by Wendy Stock and Jim Nachman at the University of Chicago. And this is a Dutch study. And all of these studies looked at patients who are enrolled on either a pediatric trial or an adult trial. But they were in the same age group. So we're talking about our late adolescence here. And those that were treated on pediatric studies had somewhere between a 60% to 70% five-year overall survival. And those treated on the adult studies had a much lower event-free survival. It's not always the case. The pediatric way is not always better. That's not what I'm coming up here to say. There are certainly cancers that we see in adolescence. We occasionally will see an adolescent with colon cancer or lung cancer or melanoma. And absolutely the medical oncologists know much better how to treat those patients. What we tend to do is we work with our adult colleagues. In fact, I've had a couple of patients with ovarian tumors that I've come to the gyn-onc tumor board. And we get the treatment protocol from the medical oncologists. But we apply it in the pediatric setting, where we have that nice, supportive environment that these adolescent and young adult patients really, really need and do much better in. So what sort of barriers to clinical trial enrollment are there? Age limitation is certainly one. And this is a very interesting example. So germ cell tumors. If a patient is between the ages of 16 to 19, a young man with a testicular germ cell tumor in that age group is most likely going to be treated by a pediatric oncologist. That tends to be the referral pattern. They're still seeing a pediatrician. They tend to get referred to a pediatric oncologist. The pediatric trials, however, will only enroll patients up to age 14, because starting at age 15, the biology of those tumors is much more similar to that which is seen in the adult world. The adult trials will enroll down to age 16. But the adult oncologists tend not to see these patients who are in the 16- to 19-year-old age group. So one of the barriers is figuring out how we can get the patients who have these diseases to the oncologists who have access to the trials that they're eligible for. And this is important in terms of community practices versus tertiary care centers. Community practices, if they have access to the clinical trials, they tend to be the adult trials rather than the pediatric ones. And so referral to a tertiary center, where that patient would have access to enrollment on a clinical trial, would be beneficial for those patients. Insurance is also a problem. If the insurance company will not cover a patient being seen at a center that offers a clinical study, then that, of course, prevents the patient from being treated there, unless we can come up with an exception. So what have the larger cooperative groups done? So the Children's Oncology Group, or COG, in 2000 developed an adolescent and young adult committee. They enacted a couple of measures where they increased the age limits for enrollment onto trials. So specifically, the leukemia and lymphoma trials now enroll up to about age 30. Sarcoma trials enroll up to about age 30 through the Children's Oncology Group. And in fact, the rhabdomyosarcoma studies enroll up to age 50, believe it or not. SWOG, or the Southwest Oncology Group has also developed an AYA committee. And SWOG and COG have actually partnered for a couple of sarcoma trials where they've run the same trial through both consortia in order to truly enroll the patients across the age range that they're trying to target. CALGB, now part of the alliance. Dr. Stock at University of Chicago is the PI for the ALL study where they took the pediatric standard ALL therapy and gave it to young adult patients. The outcomes were remarkably better compared to what they had been seeing in the past. And that's really now the standard way to treat a young adult patient who has ALL is with a pediatric-type regimen. There are more trials that will likely be open between the groups that have to do with melanoma, sarcoma, and different lymphomas. And really, there's a lot of interest in trying to lift some of these artificial age restrictions. So I think as we learn more about the biology of these tumors, we'll understand that it's better to stratify these patients based on their biology rather than their age, which is a fairly artificial way to divide up patients. So the enrollment onto national cancer therapeutic trials really has improved since the early 2000. So if you look just before 2000, only about 4.2% of AYA patients were enrolled onto trials. In the early 2000s, it was up to 6.5%, which was a significant difference. A lot of this was driven by the Children's Oncology Group studies, which allowed older patients to be enrolled onto the leukemia and lymphoma trials. But we're also seeing improved accrual for sarcomas as well. So you can see here for sarcoma patients who are under the age of 40, there's absolutely been an increasing trend of increased accrual onto clinical trials since this awareness was really put in place that these adolescent and young adult patients need to be focused on as a group in and of themselves. So what are approaches at individual institutions? So individual institutions can really work to facilitate enrollment of patients from the adult side onto the pediatric trials, and vice versa. So having joint conferences, having conversations between the pediatric oncologists and the adult oncologists, so that way there's an awareness of what is available for patients, is very important. And enacting support services for the AYA patients. So addressing education, addressing finances, addressing sexuality and fertility, which a lot of people may be reluctant to talk about with a 16- or 17-year-old. But you've got to do it. If they have a sarcoma and they are going to get a lot of alkylator chemotherapy, you have to talk to a young man about sperm banking. You have to talk to a young woman about at least speaking with our fertility team about what options might be available to her. So having those conversations, even in these young women and young men who are not ready for a family yet. But you need to prepare for the future. Peer support is important. So whether there's peer support on site or being aware of some of these organizations that are available. A lot of these will do computer chat room conversations with patients. So it provides a way for these patients to get peer to peer support even if they're not meeting with somebody in person. And the psychosocial support. So having a psychologist or a psychiatrist who really understands adolescents and young adults and understands oncology care is very helpful for these patients. And so this is a nice example out of the University of Pittsburgh and the Children's Hospital of Pittsburgh. So they started by doing a retrospective look at adolescent and young adult patients who had been cared for at either institution. So Children's Hospital of Pittsburgh had seen 91 patients in the AYA. I think they use 15 to 22 years as their bookends for this. And the University of Pittsburgh Cancer Institute had seen 121 patients in the 15- to 22-year-old age range over the course of four years. In the children's hospital, 26% of those patients were enrolled on some type of a clinical trial. In the cancer institute, only 4% of those patients were enrolled onto a trial. None of the ones who had a pediatric cancer were enrolled onto a trial, even though there were trials open for at least some of those patients during those years. What they did then is they implemented an AYA program at the University of Pittsburgh. Much of it was more of a consultative program. A patient who was in the appropriate age range would come in for a consult with a pediatric oncologist or a medical oncologist who is aware of the issues for this population. And what you can see here is that 4% that we had seen for the University of Pittsburgh Cancer Institute went up to 33% enrollment onto a clinical trial once they raised the awareness. So what have we done at the University of Chicago? We started with a relatively small group of people. This was a picture taken about two years ago. There were three of us from the pediatric oncology side and two from the medical oncology side who really wanted to focus in on adolescent and young adult patients. And this is a photo we took on Tuesday at clinic. And you can see it's grown exponentially. So we now have four attending physicians. We have a fellow from each side. We have physician assistants from the adult side who come to see patients. We have a research nurse in clinic almost every week. And we have social work support, both from the adult oncology side and the pediatric oncology side. And most recently we've added physical therapy support. And a pharmacist now comes to clinic periodically to make sure patients are able to access their medications, make sure they understand what they're supposed to be taking. So I don't know if we're doing questions now or later. I put this in. But it seems like there's group Q&As.
