Transcripts - Conversations on Cancer: Beginning the Rare Cancer Journey: Charting the Best Path to an Accurate Diagnosis
Martha Donoghue:
Hello and welcome to another installment of the FDA Oncology Center for Excellence's Conversations on Cancer series. It's a public forum in which we discuss issues relating to cancer that affect our community. Today's session, we'll focus on beginning the rare cancer journey, charting the best path to an accurate diagnosis. Although in the Oncology Center for Excellence, we typically focus on work relating to developing new drugs to treat cancer, we recognize that in order for patients to benefit from these products, they first have to get the correct diagnosis.
And additionally, having the correct diagnosis is vital to timely enrollment and participation in clinical trials, which is a cornerstone of drug development as well as patient care. As we learned through a series of discussions with other stakeholders leading up to today's conversations on cancer session, diagnosing rare cancers can be very challenging, and diagnostic delays can lead to ineffective treatments being given and added stress to patients and their families during an already very difficult time. During this one hour session, we'll hear from an array of perspectives regarding the difficulties that some patients encounter at the very beginning when they learn they have cancer but don't know exactly what type of cancer they have.
We'll also talk a bit about some of the barriers to getting that correct diagnosis as well as the importance of timely access to appropriate diagnostic tests. And we'll also learn a bit about some ways to help overcome some of these challenges. My name is Martha Donoghue. I'm a pediatric oncologist and I also serve as the associate director of pediatric oncology and rare cancers in the Oncology Center for Excellence at the FDA. And today, I'm delighted to be joined by a few of my FDA colleagues as well as an esteemed panel of experts and thought leaders on rare cancers including patients, physicians, and scientists.
I'd like to thank you all and the audience for being here virtually and for your engagement on this important topic. And without further ado, I'm going to introduce somebody who probably does not need introduction, Dr. Rick Pazdur, who is the director of the Oncology Center for Excellence and has kindly offered to help co-moderate this session. Rick, would you like to open with a few words before we introduce the panelists?
Dr. Rick Pazdur:
Thanks a lot, Martha. It's really a pleasure to be here. And I welcome everyone joining us, and particularly those people who will view this both concurrently now being presented, but also when the video is archived also. And a lot of people I know view it in that fashion also. But I really like the term journey because I really believe that many of our experiences are truly journeys that we will experience over many years. The rare cancers really present many challenges to both the diagnosis of the disease as well as treatments, as well as clinical trials, getting sponsors to develop drugs in rare diseases.
But I really think that we're making progress. And progress does not mean that it's always a success, but at least there's an interest in looking at rare cancers. Many of the diseases that we've had in oncology have been sub-segmented into rare diseases, and I think we should be aware of that. Even in lung cancer where we had, when I started in oncology many years ago, two types, small cell and non-small cell. There's various small subtypes based on molecular subtyping of the disease, which poses really challenges to the diagnosis, but also presents unprecedented opportunities for new drug development.
So I'm really interested in hearing from our panel here. I hope that this will be a delightful hour that we'll spend together and we'll make it informal. Let's call everybody by their first names, okay? And just have a pleasant conversation here because I'm really interested in hearing each one of you and your particular role in the rare cancer journey, so to speak. Thanks.
Martha Donoghue:
Thanks so much, Rick. So let's move on to introduction of the panelists, if you wouldn't mind introducing yourselves. And as Rick mentioned, we're all going to go on a first name basis here, but I'm going to go by alphabetical order by last name just so we have some order here. And I'd like to keep just the initial introductions brief if we can, just so we have plenty of time for discussion later. But if you will please let us know who you are and a bit about your background and how your interests intersect with this topic. And so Lisa, if you wouldn't mind starting off, that would be great. You're on mute.
Lisa De Young:
First of all, I'd like to thank the FDA for providing this wonderful platform. My name's Lisa De Young and I'm here representing the sarcoma community and specifically a rare sarcoma that I was diagnosed with in 2011 called epithelioid hemangioendothelioma. But for today's discussion, we'll just call it EHE because it's a mouthful of a disease to pronounce. But I'm happy to be here with everyone.
Martha Donoghue:
Thank you so much, Lisa. We're very happy to have you here today as well. Ashley, I'll move to you next.
Ashley Hill:
Sure. I'm Ashley Hill. I'm a pediatric pathologist and pediatric cancer research, and I'm currently at Washington University School of Medicine in St. Louis. And thanks for having me.
Martha Donoghue:
Thanks, Ashley. Tamron, you're next.
Tamron Little:
Hey everyone. Thanks again, Martha, for having me on. I am Tamron Little, a survivor, thriver and advocate. I am a 16-year and counting peritoneal mesothelioma survivor, and I'm also a contributing writer for The Mesothelioma Center.
Martha Donoghue:
Thank you so much, Tamron. Reena.
Reena Philip:
Hi, Reena Philip, associate director of biomarkers and precision oncology, Oncology Center of Excellence. Thank you, Martha, for inviting me. I have been working in devices for the last 17 or so years, so it's really a great topic. Today's topic is going to be really an exciting.
Martha Donoghue:
Great. Thanks, Reena. You have a lot to teach us. And last but not least, I'd like to turn to Brigitte Widemann.
Brigitte Widemann:
Thank you so much. I'm excited to be here. I'm also a pediatric oncologist with a specific focus in some very rare pediatric and adolescent and young adult cancers. And I work at the National Cancer Institute and I'm the chief of the pediatric oncology branch. Very happy to be here.
Martha Donoghue:
Thank you again so much to all of you for being here today and your willingness to provide your perspectives and thoughts today. I'd like to hear from our rare cancer patient advocate experts first, if you don't mind. And now, as we said in the beginning, we'd like to keep this informal. And so if any of you have questions that you want to jump in, please do raise your hand and we can go with the flow here. But Tamron, if you could just tell us a little bit about your story. And my understanding is that getting to your diagnosis was a bit of a bumpy road for a bit.
Tamron Little:
Yes, definitely. So originally, I was diagnosed with a fibroid tumor during my pregnancy. I was 21 years old, in college, thought I was living my best life, and I found out that I was pregnant. And during a routine ultrasound, they told me that I had a fibroid tumor. At the time, I didn't know what a fibroid tumor was. I didn't even know what to expect during my pregnancy, but I was reassured by my team of physicians as well as my family because fibroid tumors run in the women of my family. So during the course of my pregnancy, I didn't think not one time that it could be cancer.
So after I had my baby, they were monitoring it and placed me on birth control to shrink the fibroid tumor. But after a repeat ultrasound, the tumor didn't shrink, it actually increased. And at that time, it was the size of a ping pong ball. So still not thinking that it could be cancer. To be honest, I don't really know what I was thinking at the time, but a slight thought of, "Could this be cancer?" did come up in my mind, but it wasn't the cancer that I was diagnosed with. So after my surgery, I was told that I had peritoneal mesothelioma, which is a mouthful, Lisa. So I definitely... And I was in total shock. I hadn't even heard of mesothelioma.
And 16 years ago, this was in 2007, there was not a lot of information about this particular cancer. Mesothelioma is a rare form of cancer, but peritoneal mesothelioma is even rare. Mesothelioma is within the lining of the lungs and it's caused by asbestos exposure. The typical patient is a white male in his late sixties, early seventies. So when they told me I had it and that was the information that I got, I'm like, "No way. I am young. I've never worked in construction or on any naval basis or anything of that nature. So how could I have this?" So that really put me on the path, [inaudible 00:10:29] journey. Take a while to get the diagnosis. It took a while to find the right oncologist specialist that specialize in this rare form of cancer, and really getting them to believe that, "Oh wow, we have this 21 year year old female that has this rare cancer."
So I really jumped into the driver's seat of, okay, I have to advocate for myself and I have to ask those hard questions, I have to get a second opinion. So my second opinion was actually in fact a specialist and he specialized in high PEG. And so I received surgery. And I am here 16 years later, and it is a pleasure of mine to share my story and my journey of how I overcame the medical roadblocks. And even though they gave me 18 months to live, I'm here 16 years later, and I like to share my story and the awareness about mesothelioma in that you can thrive even after giving a rare cancer diagnosis.
Dr. Rick Pazdur:
Okay. Martha, you're on mute.
Tamron Little:
You're on mute.
Martha Donoghue:
I know, I did it. That's really an amazing story, Tamron. And as you were saying you weren't even thinking that you... it didn't even occur to you that you could have cancer, but it obviously didn't occur to your doctors either, right?
Tamron Little:
Right.
Martha Donoghue:
Because your body didn't read the book on who should get peritoneal mesothelioma.
Tamron Little:
Right.
Martha Donoghue:
So it's really an amazing story. Was there something that triggered the surgery, the initial surgery? Because ping pong ball size is not that big initially. Were you having symptoms or were you concerned that it just wasn't going away? How did that happen?
Tamron Little:
Well, actually my doctor was concerned because it was growing out of the lining of my stomach, and it had grew from a stalk, so it was making. And so he was a little like, "To be on the side of caution, let's just take this out and send it for pathology." And so that's pretty much what he did. And because the birth control was not shrinking it at all. It was like, "You can't touch me." So that's why he wanted to do that. Plus during my pregnancy and after, my hemoglobin was low, and it was in six and a half, seven, and that's pretty much what my baseline was. And a lot of my labs were just not coming out to be where they should have been. And iron pills wasn't working, and I was still having stomach pain.
Even though I was having that during my pregnancy, but it was my first time being pregnant. I thought that was normal. I thought the cramping was normal. And the extreme fatigue, I thought that was normal. But found out it wasn't. So that's what prompted him to say, "Let me get a second look at this and really take it out and so we can send it for pathology." And that's what it came out to be. So I'm glad that even when I wasn't even thinking that it could be cancer, that my doctor at the time took the initiative to say, "Hey, I still think [inaudible 00:14:33] tumor bore testing."
Martha Donoghue:
So thinking outside the box and putting that big picture together was something that was really important for you.
Tamron Little:
Right.
Martha Donoghue:
And you're very lucky about that.
Tamron Little:
Right.
Martha Donoghue:
Thank you, Tamron. Now Lisa,-
Tamron Little:
Thank you.
Martha Donoghue:
... could I turn to you next if you wouldn't mind just sharing a little bit about that initial stage of your journey with rare cancer EHE?
Lisa De Young:
Sure, absolutely. So I live in the San Francisco Bay Area, and I started out at my local private hospital. I had a very tiny bump in my neck that only I could really feel when I would wash my face. There was something about the suds going over my throat where I could feel this little tiny bump. And I went to a series of medical professionals, not only in my primary care office, but also my OB-GYN office, my dermatologist. And no one seemed to be overly concerned. In fact, I felt a little dismissed because I was there saying, "This is not normal for me. This is not going away. This is not resolving." And I really didn't feel heard.
And in fact, at one point, I saw one provider, and they almost alluded to the fact that it could be hormonal related and was somehow connected to maybe hormones of some sort. So finally, I was sent to an ENT. And the ENT suggested that, in addition to imaging, that we do a fine needle aspiration. And at that point, I was just wanting to try and figure out what this was. And I didn't realize that there were CT guided fine needle aspirations, but he just felt around my neck and put a syringe in and the results came back unremarkable.
And so he said, "However with lumps and bumps in the body, it's never a good idea to leave those things in your body. It's better to remove them." So I tried to get on his surgical schedule three different times and had absolutely no luck and got very frustrated. And this was going on over a period of many, many months before I actually found out what I had. And I ended up going to a second ENT out of frustration. And immediately, he was very concerned. He thought I had lymphoma. And he said, "We're not really going to know what we're dealing with here until I get in there and we do a biopsy."
So I had a biopsy done in January of 2012. And I got a phone call from him two weeks later saying, "I'm just so sorry to tell you this, but you have stage four breast cancer." And it was just like something that came right out of left field, and it hit a very sensitive nerve because my mother and my sister and my niece have all had breast cancer. So it immediately put me into panic mode. And we were scrambling. And I had a port installed anticipating that I was going to be starting chemotherapy treatments. And all of a sudden, all my imaging and my labs started coming back within normal range. And things just weren't adding up. Something was not right.
And so I requested that my pathology be sent out from my local private hospital to UCSF and Stanford. And that was actually a lifesaving decision for me. And eventually, it came back as a very rare sarcoma called epithelioid hemangioendothelioma. This is a very rare vascular tumor, a one in a million tumor that likes to grow in the lining of blood vessels. And so by that point, I already had the port put in, it was the first time in my surgeon's career, 40 plus year career, where she installed a port and removed one that had never been used. And so I knew at that point I needed a higher tier of care that my local private hospital was not equipped to deal with something so rare.
And so I headed to Stanford. And I was very, very blessed to be treated by the chief of head and neck surgery. And through his skilled hands, I had a modified radical neck dissection in April of 2012. And they discovered that my tumor had actually started to grow in a branch of my jugular vein on the left side. So they removed that in its entirety along with 27 lymph nodes. And fortunately for me, it had not spread. So I received no other adjunct therapy or treatment after my surgery, just surveillance and scans. But the whole experience turned my world just completely upside down. And I had a child at the time... Not a child, I had a young man at the time away at college who was completely traumatized thinking his mother was going to die. And the whole experience of the waiting and the not knowing.
And one of my first consultations with an oncologist, again, because we were under the assumption that I had breast cancer, I waited in this room for an hour. My husband and I and a very good friend, retired orthopedic nurse, waited for an hour and 40 minutes to be seen. And when she came in, she apologized and she said, "I'm so sorry." She said, "I've been on Google this whole time trying to figure out what you have." And at that point, I hadn't even been told that I didn't have breast cancer. And I said, "Well, what do you mean?" And she said, "Has no one called you, has no one told you, you don't have breast cancer, you have this very rare form of sarcoma?"
And so through all of that pain, I harnessed all of that. And I decided that if I was going to survive this, I had to self-educate, I had to dig and research, and really begin to understand this uninvited guest that had come into my body. And so with all of that, I met four other women through an online patient support group for EHE. And we banded together and started a nonprofit foundation in 2015. And my role was really director of patient services. And so I was the first point of contact for people looking for information on EHE. And really my goal was to get them to an experienced provider as quickly as I possibly could, because it was really a waste of their time and their financial resources to go to anybody who really didn't have a good working understanding of sarcoma or specifically of vascular tumors.
So with that, my journey has grown over the last eight years, and I'm on the steering committee for the Sarcoma Coalition. We are a group of 35 rare sarcoma subtypes that have all come and banded together to really bring a voice to sarcoma, because most people don't even appreciate what sarcoma is. They don't know really a whole lot about it. And in part, it's because it only impacts about 13,000 to 16,000 people a year. But if you happen to be one of those 16,000 people, that changes things dramatically. And so through my advocacy efforts, I've been able to work with an international community of EHE patients all over the globe.
We have 25 members. And my goal is to improve outcomes, provide resources, provide support, and I basically help walk them over the bridge into their survivorship and to getting to that other side. Because when you're diagnosed with cancer, at least for myself, I just felt like Alice in Wonderland falling down this dark rabbit hole. And I didn't feel like I had a floor underneath me. And particularly when I was going through all that I did at my local hospital, my local community hospital, it was just life altering and a very traumatic experience, not only for myself, but for my children and my husband and my extended family.
So I'm grateful, beyond grateful to be here. And if sharing my story helps spare one other patient with rare disease or rare sarcoma, that ill-fated experience, I'm happy to share.
Martha Donoghue:
Thank you, Lisa. Oh, thank you so much, Lisa. Go ahead, Tamron. Were you going to say something?
Tamron Little:
Yes. I can relate to your story on so many levels. And I know that current cancer patients that's watching this and that are going to watch this can definitely relate to your story. And it also brings to my point why advocating for yourself is so important, is vital. Because I just think about the many patients who took the initial diagnosis or the misdiagnosis and leaned on that. And they may not be here today to share their story because they may not know that they can advocate for themselves and they may not know that they can have a second opinion.
When I was originally diagnosed, I was referred to an oncologist who didn't know anything about mesothelioma. He was actually honest. So I understand his honesty, but I felt as if he could not help me and he couldn't refer me to anyone that could help me. So I had to find, like you did, I had to go to another resource. And I just think about patients like us and survivors like us that are really speaking about these issues and empowering other patients to let them know that it's okay to change doctors, it's okay to disagree with something, and it's okay to ask those questions. And a lot of patients are hesitant and they are afraid like, "No, I don't want to be a bother, or I want to be respectful to my doctor and not go somewhere else. And I feel like I am betraying them." But you have to think about it. This is your body that you are dealing with.
Dr. Rick Pazdur:
I think, if I could just jump in, I think it's really becoming your own advocate, so to speak. Okay? And that's what's very important here. But I'd like to turn our attention to Dr. Widemann and a ask her how common this is that people have been misdiagnosed, so to speak. There's an old adage in medicine, when you hear hoofs, don't necessarily think of zebras, so to speak. But sometimes you have to think of zebras, so to speak. Right?
Brigitte Widemann:
That is exactly right. And I'm so impressed by Tamron and Lisa's story because it reflects what we see in pediatric oncology. Even though I would say parents tend to be very strong advocates for their kids, and that is wonderful. And I would want to encourage adults with rare cancers or tumors where something isn't right to do just the same. Lisa's story in particular strikes me with some of the aspects that are really important for the diagnosis you need to have adequate material. It sounds like Lisa started with a fine needle aspirate, which infrequently is not adequate material to make a diagnosis. And this is delay number one.
Delay number two is that, indeed for very rare tumors, frequently a second pathology or maybe a third pathology review is required. And typically, that means sending material to a pathologist and this uses up scarce material and maybe there isn't enough for a comprehensive diagnosis. And some of the tumors, at least that we deal with in pediatric oncology, are so rare that many pediatric oncologists don't even see them in their lifetime. And so it's tough to sometimes recognize even clinical features that are associated with a specific rare tumor.
So the most important message from my end, yes, advocate for yourself and ask all the questions and make sure that you get adequate material so that a diagnosis can be made as quickly as possible.
Dr. Rick Pazdur:
Yeah. I guess one of the questions I had for Dr. Hill focusing on Lisa's case, the pathology, breast cancer doesn't mean... I can't understand how somebody could diagnose breast cancer given the fact of what the ultimate diagnosis was. Do you want to comment on that? How frequently? Here again, people want to perhaps give common diseases because that's what we're used to the diagnosis of, but many times, they miss these rarer diseases.
Ashley Hill:
Yeah. I would say... So epithelioid hemangioendothelioma can have multiple appearances and they give that name epithelioid because it looks epithelial. And breast cancer is a very epithelial tumor. And so you can really imagine how that happens. And it might mean that the tissue wasn't adequate and they just had a little bit of it. And the common things being common, the pathologist puts it in a category, and realize that... In private practice, pathology are extremely busy and maybe don't have enough time to go into detail. But I can't speak on that case. But I can tell you that it does happen and it happens with really good pathologists because we think we should know things, but we don't know everything and we can't know everything.
We need to have the humility and to know what we don't know. And that's a really good sign of a good doctor is to be able to say, like some of you did hear, "I have not seen this before. We need to get this to an expert. We need to get you to an expert. I need to help you find an expert." And so I think that's one way a pathologist can help is to really say, "Am I really sure about this diagnosis? Have I done what I need to do to be sure? Have I showed my senior colleagues if that's the case? Or do I need to send it to a major academic center where they will have a number of experienced pathologists who are generally older and have 30 years of experience?" And in pathology experience is really a major part of the game.
So what you've experienced is unfortunately not uncommon. And how do you know that your diagnosis was correct? It's difficult. I think that asking for second opinions should be pretty common practice. And like Tamron said, do not be afraid to ask for a second opinion. Do not be afraid to ask how confident are you about this diagnosis. Because those are the questions that may, in a busy pathologist or a busy oncologist day, make them stop and think, "Do I need to do more? Do I need to think about this differently?" And that unfortunately falls a lot on the patient's responsibility, but it is, you should take that power and direct those questions and make sure you're getting the diagnosis you need. That'll be the first thing so that you get the right treatment.
Dr. Rick Pazdur:
And also looking at more sophisticated pathology examinations other than just like microscopy, obviously, to give you a hint of what's going on. Would you comment on that?
Ashley Hill:
That's right. That's exactly right. And it is getting very sophisticated both with stains that you can look at under the microscope that you have available to you at big places, or genetics. Genetics is now really telling the difference between things that look very similar under the microscope but would have two different prognosis and two different treatment plans. So this is what we call personalized medicine, that your tumor, it gets a look, but then understanding the personal genetics of it too can help.
Brigitte Widemann:
Yeah. I think that's a great point, Ashley, that you're making, and Rick too. Personalized and precision medicine ideally we want to, at least for the rare tumors, study them comprehensively, and that includes molecular characterization and potentially methylation, looking for fusions, and that ultimately might refine the diagnosis and allow patients to participate in clinical trials.
Dr. Rick Pazdur:
I think that's a natural lead into bring Reena into this conversation. As I mentioned before, when I started in medicine and oncology, we had two types of lung cancer bringing it to adult medicine, non-small cell and small cell. And over the past decade or so, or less than a decade, that has been transformed into multiple subtypes based on some molecular testing and a greater understanding, which also gives us better therapeutics. And Reena, the floor is here, as I'll turn it over to you.
Reena Philip:
Yeah. Excellent. As some requesting, in lung cancer, this molecular testing has transformed lung cancer. Now there are so many different biomarkers that could be used to target the different treatments in lung cancer. But for the rare diseases, it depends. Sometimes you can also call these NTRK fusions. You can call them as a molecular subset of a disease that... It's actually a rare tumor, right? It's a NTRK defined tumor. I was thinking of the sarcoma example that was brought up by Lisa earlier.
I mean, sarcoma also makes an example of how personalized these molecular profiling is so important because they are actually... There's a diagnostic challenge because sarcomas, it's almost like what, 80 different subtypes. So what is the right testing that will be used for sarcoma? Because right now, the current mainstay could be, a lab may choose to just do IHC, which could miss some of these fusions. So what is the type of testing that's used in the lab actually could determine the diagnosis. And we heard these tests are critical. These are, we call them in vitro diagnostic tests. And depending on the accuracy of the testing, that can change the diagnosis and can change the entire life, the treatment decisions, how you decide what to do next. So yes, this is now a critical step in the diagnosis of the cancer.
Martha Donoghue:
Reena, can you talk a little bit about how FDA is involved or not involved in this testing part of things?
Reena Philip:
Yeah. Sure, Martha. So similar to how FDA regulates drugs, FDA also regulates devices. As I mentioned, in vitro diagnostic tests, these are considered as device. These are actually clinical tests. The testing is done on samples, like blood biopsy samples. And so when a manufacturer is developing a test, and if they would like to market a test for a specific clinical use, they have to submit studies to FDA in a pre-market application and before they're bringing these tests to market. There is also a program called Humanitarian Device Program that was specifically designed for getting rare disease devices to market.
Even with this program, the number of FDA cleared approved in vitro diagnostics tests in rare diseases is not so many. But you may have heard of this lab developed tests because some labs choose to develop their own tests. They are sometimes called LDTs or home brews. And these are in vitro diagnostic tests that are supposed to be designed, manufactured and used within a single lab. And traditionally, these LDTs were used only for ultra rare diseases and they were simple tests. But recently, we know these have become really complex.
The reason I brought up about the LDTs is because, since labs can choose to develop these own tests, so they may actually develop a single analyte test. The example we were talking earlier for sarcomas, a lab can just do an IHC and they can actually miss the big picture of the disease, and they may not get the right diagnosis. But recently, I think the molecular testing is increasingly recommended. And I guess this is where we should talk about how to educate the healthcare providers and coming up with guidelines so that they could actually get the appropriate test for each specific diagnosis.
Lisa De Young:
Martha, I just wanted to add that I think we really have to redefine what sick looks like. And I think that Tamron and I probably both experienced that. When I went to the doctor, I didn't look sick. She was 21. I can't imagine they thought there was anything very sinister going on with a 21 year old. And so I think we really need to take a step back and say, what does sick look like? Because in many instances with sarcoma, you can look perfectly healthy on the outside and literally be dying on the inside. So it really takes that position to really stretch and go beyond maybe their schooling or what they've experienced in their career to entertain the idea that possibly something that is not even on their radar could be at play, and to take those extra steps.
Because in my situation, my local oncologist went back to the pathologist that worked on my biopsy in January of 2012 and said, "Why did you give this woman a diagnosis of stage four breast cancer?" And he said, "Well, I wasn't really sure what I was looking at." Well, if you weren't really sure what you were looking at, why didn't you involve your senior scientists in your lab or your lab director to say, "I'm not sure what this is." And I think part of the reason they went to the breast cancer diagnosis in my case is because he might have peaked at my history, my family history on the forms that were included with my biopsy.
And also, my biopsy tested slightly patchy for mammaglobin, which I think might have also influenced his decision or his findings. So I think that it's really important with rare disease, and particularly rare cancers, that you do advocate for a second opinion. And in sarcoma, one of the leading labs here in the US is Dr. Brian Rubins at the Cleveland Clinic. He has a dedicated team for sarcoma. And I've read in literature that there's more than 150 rare sarcoma subtypes. And even within EHE, we have different drivers that are driving these tumors.
In 90% of the tumors, it's CAMTA1. In the other 10%, it's YAP, is their gene fusions. So it gets really complicated. And sometimes, like you said, you need a second opinion, a third opinion, maybe even a fourth opinion. And I think that we as patients need to feel comfortable initiating those tough conversations, because I was definitely chastised for wanting to send my samples out to UCSF in Stanford. I was told, "It's not going to make any difference. You have to get on treatment right away." And fortunately for myself, I listened to my gut and I knew something wasn't right. So for the patients that are listening to this event, I would encourage you, you know your body the best, you know what's normal, you know what's not right, what's not going away, and to follow and trust your gut.
Martha Donoghue:
Thanks, Lisa. You touched upon a lot right there. You talked about the importance of education, the importance of really, as Ashley said, humility and the part of the healthcare providers who are helping to reach that diagnosis to understand and be willing that they may not know everything, and if you don't know everything, it's okay, and you should seek help and assistance from others who might know that. So I think that seems to be a continuing theme here. Ashley, do you have other recommendations for patients based on your experience? And I know you've done some work on some really rare cancers.
Ashley Hill:
I think the recommendations for patients from Lisa and Tamron are really right on. And that is to make sure that you ask your questions and ask hard questions, and see what you think about those answers and how confident are the answers, and ask for a second opinion for things that are rare. It really shouldn't be a big deal to do and should be pretty common practice. Because I think what most people will find who really get into the healthcare system, and this is true for me as a patient or if my parents are patients, you realize how much people don't actually know. We know a lot, all right? We've studied, we've gone to school, we know a lot. But there are just things that aren't known. And there's a lot of them still. And every day, we're learning more and molecular is teaching us more.
But patients need to understand that it's not like the old days where you think that your doctors just know things. It's just not like that. It's too complicated. You should be free to ask for a second opinion and encouraged, and how your doctor response to that would be an important insight into should you stay where you are or should you go somewhere else. I was thinking about my experience in how do we improve on diagnostics in general for rare diseases. And I can tell you that I didn't write this story, but I became a passenger in this story, and it has worked for a few other tumors since. So you realize that it's difficult to master diagnosis for things that you just don't see very often. You can read about them, but it's very different having the confidence to make a diagnosis with things you don't see.
And I was really lucky to train in a large academic center with a very experienced pediatric and adult pathologist Pepper Dehner, who now has over 50 years of experience. And in the late seventies and eighties, he saw a few examples of this rare lung cancer that was in children and it appeared to run in families. And he called this tumor pleuropulmonary blastoma or we call it PPB for short. And he started telling his other pediatric pathologist friends about it and presented it at meetings and people would raise their hand. I've seen one of those. But I didn't know what it was.
And so those cases start to be sent to Dr. Dehner. He and a pediatric oncologist at the time, Jack Priest, decided to form what they called a tumor registry, and had an infrastructure where people could send their cases. And they developed a website. Now, families can find them by searching PPB and the website, and can go to the website, learn information, learn about what research programs they can participate in and so forth. And so cases started to come in. And this is probably, at the time, maybe 30 or 40 cases in the US each year. It's actually worldwide now. Maybe 150 cases a year.
But by having a place where people can go, it is very much like Lisa developing her group of epithelioid hemangioendothelioma experts, providing a place where people can start collecting information and providing advice. Ultimately, in 2005 where I entered the story, it was clear that these PPBs ran in families. And some of these 150 patients that had participated in research had more than one case. And so we did a family study and we were ultimately able to find that they shared mutations in a single gene that's called DICER1. And that then started diagnostics, new ideas for treatment, identification.
And now, people are a lot better at diagnosing this rare cancer because they know about it now. So this is one example. But I think, like Lisa presented, getting a group who's committed to improve the understanding of these tumors and do what it takes. And for patients, please be willing to participate in research if you can. Those are the sorts of things that can maybe get it better known in front of the frontline pathologist who may be reviewing it out in the community.
Martha Donoghue:
Thank you, Ashley. I think you brought up a really important point that you need to reach this critical amount of information, this critical mass of aggregated information where people can start looking for patterns and digging into the science a bit more to help enable that breakthrough that you were able to be part of with DICER1. And the point about clinical trials I think is an excellent one. Moving on to Brigitte, I was wondering if you could talk a little bit about what NCI does to help improve this path to diagnosis for rare cancers and navigation after that, which I think we've touched upon a little bit. Even once you get the diagnosis, the navigation to getting the right people to help take care of you is also can be difficult.
Brigitte Widemann:
Yeah. I think this has been such a great discussion. I have to say I'm really fascinated. The NCI, and I think many, begin to realize how rare cancers while rare are common in that they are about a quarter of all of the cancer diagnosis, and there's a lot more effort on understanding rare cancers. Within the NCI, there's several areas. One is, at the NCI pathology here, you can get a free second opinion at any time of the cancer. So if it is a question about resources, this is one tool that is available to any patient.
We have, in the pediatric oncology field, the Childhood Cancer Data Initiative. And with a collaboration with the large cooperative group, the Children's Oncology Group, now an initiative called the Molecular Characterization Initiative, that every newly diagnosed pediatric cancer patient can get a state of the art molecular characterization of their tumor. And we're focusing in the future to get this to other patients that are outside of the Children's Oncology Group, like adolescents, young adults that may see community hospitals, and also to patients with relapse cancers.
Another initiative that we have is called My Pediatric and Adult Rare Tumor Network for any patient, pediatric or adult with a rare solid tumor, where we offer a second pathology opinion, molecular characterization. And it's actually said, actually the patients participate in research by providing their experiences, their quality of life information longitudinally over time so that we hopefully not only come up with the right diagnosis, but also learning more about the cancers. And then our NCI director, Dr. Monica Bertagnolli, is very interested in helping with patient navigation, which I think we heard today how critical it is and how much Lisa and Tamron were on their own essentially when they started.
So if there were navigators that would help navigate the path through a diagnosis or to treatment. The other aspect that she's very interested in, Dr. Bertagnolli, is an portable informed consent, that then allows you to take your information in the clinical medical records to any place, and that would be a big advantage as well. So those are some of the initiatives that we have ongoing at the NCI. I agree with Ashley, and that's been my experience, patients with rare cancers typically want to give back and want to help others. So by participating in clinical research or by engaging in advocacy organizations to then help other patients with this diagnosis is a very effective way to accelerate the knowledge and help others at the same time.
Tamron Little:
I definitely agree. And coming from a patient to a caregiver, and helping my own husband because he was diagnosed with the rare cancer as well a decade later after me, helping him navigate, and tapping into those resources that were given to us. He's not the type of person, and I know it is a lot of patients out there, that they're not the type of person that want to ruffle the feathers or ask or seen bothersome, or even talk about their diagnosis with other people. But I know people like Lisa and I are really forming that pathway.
But in the sense of clinical trials and different testing and things like that, it's important to make sure that patients are knowledgeable that these things exist, that the clinical trials do exist, or that they can ask for a certain test. Because my husband, he was misdiagnosed for years. We thought he had gastritis. We thought he had IBS. And he's a veteran as well. But it turned out to be mucosal lymphoma, and that he could have requested for a certain test or things like that, then we would've known more sooner that he had mucosal lymphoma. So just a lot of patients, and giving them that knowledge of what is available to them.
Even if it is a community hospital or the VA clinic, letting them know that they have the right to go outside, like Lisa did, and go somewhere else, and that everything is just not within their community and that they are primarily stuck at where they live. So just allowing them to know that, hey, this is an option for you, this is an option for you. I believe that if they know that they have that option, then they will definitely take it. Just in my case, I spoke about this on another panel discussion that preserving my fertility was not offered to me. I was just told that the one child that I did have, that was the only child that I was going to have pretty much. But it wasn't giving me as an option to say, "Hey, you have the right to preserve your fertility." That wasn't given to me.
If it was presented, I was just thinking about, "Okay, I just want to get treated, have this surgery that involved the radiation and the heated chemotherapy, and then..." I wasn't thinking about that. But as a woman, you will think about that later on down the road. But in my case, I was blessed to have three more children. So I didn't need that. But it's just going to show that if the options are laid out there for the patient, then that's putting the ball back in their court saying, "Well, hey, here are the options that we have." But if they don't know, then how are they going to ask?
Dr. Rick Pazdur:
You're on mute, Martha.
Martha Donoghue:
Again. Yeah. No, thanks Tamron. I think your point is well taken that, just as we're taking the time to have a conversation today about this topic, realizing that you as a patient have the right to step back a bit and have a conversation with your healthcare provider. I can imagine that when you're receiving a difficult diagnosis, things seem to be going by super fast and you just want to get through it. But having that ability to know you have the right to take your time to process things, maybe go back later if you have additional questions and bring that up, talk to other people and other resources. This is where advocacy, it sounds like, comes into play.
Really spreading the word about resources that are out there. Are there toolkits available to help you order your thoughts so that you can be sure you're asking the right questions? And all of those things. I really appreciate everybody taking the time to be here to talk. And we just have a couple of minutes left. I'd like, for each of you, if you have some final take home messages and points that you'd like to share, if you could do so now, that would be great. And I want to lead the last words to Lisa and Tamron because I think those are probably the most important. So I'll start off with you, Rick. Do you have any final thoughts?
Dr. Rick Pazdur:
No. I think we didn't talk about, and this is maybe part two of this discussion on another session is treatment and clinical trials, which is a whole different conversation. And we have to approach these tumors differently and patients differently than we would for diseases that are much more common because clinical trials can't be done in the same way. We just simply don't have the patient number. So we have to look at different endpoints and be realistic as far as how we can accurately get safe and effective drugs developed, how and where patients are treated.
I think this is an important area for further discussion, but we've had, the FDA have had a lot of discussions on what types of endpoints, what kind of clinical trials do we use for rare diseases. It's just a different disease orientation, a different paradigm of drug development. And I think that deserve some further discussion. But here again, that's an entire discussion onto its own.
Martha Donoghue:
We have our marching orders for the next time then.
Dr. Rick Pazdur:
Yeah.
Martha Donoghue:
Thanks, Rick.
Dr. Rick Pazdur:
I got the title also.
Martha Donoghue:
Oh, you do? Okay, great. I look forward to hearing it. Reena?
Reena Philip:
Yeah. Just one quick thought, which also we didn't get to is, we've talked about there are not many FDA cleared approved devices for rare diseases. That's also because of the lack of sample. There are really few tissue banks for these rare cancers. So just something to think about for patients and healthcare providers listening to this. These samples are hard to source. So saving samples from these patients is very important for developing quality diagnostics for future.
Martha Donoghue:
And I think patients have the right to ask where their samples are going as well, right, to have some custodianship of that. Brigitte, your last thoughts?
Brigitte Widemann:
Yeah. I think Rick spoke for what I was thinking about. The diagnosis is so important, but it would be wonderful next discussion to think about how we develop treatments for these very rare cancer. I'd be thrilled to participate in. This was wonderful discussion today. Thank you.
Martha Donoghue:
Thanks, Brigitte. You're on my list. And Ashley?
Ashley Hill:
The main thing I can advise is, if offered to participate in research, please participate in research. It usually involves sharing your time and maybe sharing pieces of your tissue. You'll get informed consent. But it really will make a difference for a lot of families in the future, for a lot of patients in the future.
Martha Donoghue:
Thank you so much, Ashley. Lisa? And then Tamron, I'll let you have a last word. Go ahead, Lisa.
Lisa De Young:
I would just like to drive the point home about getting a second opinion on your pathology, and if needed, even a third opinion. The other suggestion I have for patients who might be listening in or their caregiver would be to create a binder with plastic sleeves and go back to the beginning of your diagnosis and start to collect reports, whether it's labs, imaging. Get them burned onto CD and start to create your own medical library on your disease. Because over time, we lose track and we don't recall, did I have that test two years ago or last year? So it's a great reference.
And I actually travel with my binder to my appointments because many times, they're supposed to share images and I get there and they haven't been sent. And so instead of a wasted appointment, you can pull out your CD and say, "Here are my images." And it really saves the day. And then finally, the last point I would make is get connected with an experienced provider. It may require you to go outside of your hometown or your local private hospital, but with rare disease, it's really important to get to an academic center that sees a large volume of these patients.
Martha Donoghue:
Thank you, Lisa. Really good practical tips. And last but not least, Tamron, I'll give you the last word.
Tamron Little:
Yeah, that was definitely some great tips, Lisa, especially about the binder. But my last takeaways is that you are your best advocate. You know your body better than anyone. Don't be afraid to ask questions, and don't be afraid to get the second opinion. And also, be present within your plan of care. And the next time that you have a doctor's appointment, make a list and check it twice, and make sure that you have your list of questions to ask. Because sometimes when you get in there, you get that anxiety and you're hesitant. And then when the physician says, "Do you have any questions?" You're like, "No, I don't have any questions." But you do.
So never leave out of your appointment not knowing your next steps and what to expect. So by knowing that, you will know which road you need to take and where you need to go next. But always remember, just take it one step at a time and be present within your plan of care. And just baby steps, baby steps, you're going to get through it.
Martha Donoghue:
Thank you so much, Tamron. And I think that's a wonderful message to leave with. I would like to thank you all for taking the time to participate. And to those of you who are listening, thank you for taking the time to be part of this. And please stay in touch with us at FDA. We're @FDAOncology through social media. You can find us through Project Community and also the OCE Rare Cancer Program. So we'll be back with a second installation of this on treating rare cancers. Thanks everyone.
Dr. Rick Pazdur:
Bye.
Martha Donoghue:
Take care. Have a great day.