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[ Music ]Lisa Garvin: Welcome to Cancer Newsline, a podcast series from the University of Texas and the Anderson Cancer Center. Cancer Newsline helps you stay current with the news on cancer research, diagnosis, treatment and prevention providing the latest information on reducing your family's cancer risk. I'm your host Lisa Garvin and today my guest is Dr. John Slopis, he is a professor of pediatrics and neuro oncology here at MD Anderson and he is also a nationally known neurofibromatosis expert which is what our subject is today. Dr. Slopis, what exactly is neurofibromatosis?Dr. Slopis: Well neurofibromatosis is actually a collection of three different disorders that all carry the same name and it has to do with a genetic condition that produces tumors that are fibrous and they are around nerves. So it is neurofibromatosis.Lisa Garvin: And it is, these tumors, this generally strikes young children, does it not?Dr. Slopis: Well it's a genetic disorder, about half of the cases are the first, within a family or spontaneous mutations and after that, it's what we refer to as autosomal dominant so, that person that has neurofibromatosis has a 50% chance with each pregnancy of passing it down to his or her children.Lisa Garvin: And when is the typical onset?Dr. Slopis: Well it's present, the gene mutation is present when you're born. You may not actually signs or symptoms, or features of this disorder, or these disorders until you get towards mid childhood or even later in adolescence.Lisa Garvin: What sort of symptoms are we seeing, I mean, I've seen pictures of people that have many visible tumors all over their body.Dr. Slopis: Well the most obvious form is neurofibromatosis type I and that one is also the most common. 1 out of 3,000 people have a gene mutation on chromosome 17 that creates this neurofibromatosis type I. But it's extremely variable, some people will have it and only have small spots called café au lait spots on the skin, coffee with cream or coffee with milk, like big freckles. Later on in life, they may have bumps on the skin that are benign tumors of the skin. If you look in their eyes, they have, very interesting colored pigment in their eyes, which are called Lisch nodules. Some folks with neurofibromatosis type I will also have a significant impact on the formation of their bones, so they may have curved bones in their legs or arms, or unusual type of spinal curvature we call dystrophic scoliosis. Meaning the spine is formed in a very unusual way and those usually are obvious at birth or shortly after birth.Lisa Garvin: And there's a different, there's also neurofibromatosis that's called NF for short,Dr. Slopis: Okay.Lisa Garvin: Because that's typically how it's abbreviated, there's and NF type II as well.Dr. Slopis: That's correct and that's from a different chromosome mutation, on chromosome 22. That's much less common, 1 out of 50,000 people will have it. It's also autosomal dominant so once you have it you can pass it on with the same risk. But it produces a different type of neurofibroma that's called a schwannoma, that's a very specific type of tumor around the nerve. They also produce other types of tumors that are called meningiomas that are in the skull, around the brain and up and along the spine. They also produce another type of tumor that's a benign tumor that is, called an ependymoma that can occur in the spinal cord. Now, neurofibromatosis type II is particularly known because tumors form on the nerves to the ears, the acoustic nerves and so, these folks very often if they're not aware they carry the disease, or disorder is probably a better term. Then what will happen is one day they begin to lose hearing and suddenly they realize there's a problem with either ringing in the ears or loss of hearing and then they have that checked out, an MRI or a CAT scan will reveal that they have these tumors of the acoustic nerves.Lisa Garvin: How is this different from acoustic neuroma, which I think is also called vestibular schwannoma.Dr. Slopis: They are all the same thing.Lisa Garvin: They are, okay.Dr. Slopis: Mmm hmm. Different terms for the same thing.Lisa Garvin: How is it that, and most of, most NF tumors are benign?Dr. Slopis: Most are benign. Now an NF type II, they are benign, meaning they don't turn into, rapid growing cancers that can spread to the rest of the body. But they cause their problem by growing in small spaces and compressing nerves or other vital structures like the brain stem or the spinal cord, or the nerves to the eyes. Neurofibromatosis type II actually is associated with the production of true cancer. So many of the tumors called neurofibromas are benign, but there's about a 10% risk in those individuals that at some point in their life, one of those neurofibromas or more will being to transform into a very serious type of tumor called a malignant peripheral nerve sheath tumor, and it's a form of what we call a sarcoma.Lisa Garvin: How is it that MD Anderson has become a nationally known center for treating neurofibromatosis and when it's not purely cancer?Dr. Slopis: That's a really good question and people ask us that all the time. Neurofibromatosis has gained the interest for many, many years of scientists studying cancer. We talked about the fact just a minute ago that these benign neurofibromas can transform into malignant tumors, and so there are a great number of clues there that help us unlock the question as to why cancer develops in general, especially sarcoma type cancers. When we first really opened the formalized program in neurofibromatosis, it was many years ago, our objectives were to take care of those folks that had cancer. Many of them were already in our system, in the sarcoma clinic, but it was recognized that they had many other special needs, problems as we've mentioned with bones, problems with other types of tumors. And in fact, even learning disabilities, are a huge problem in children with neurofibromatosis type I and so we bit my bit began to construct a program that was a comprehensive program to study these issues. To learn the best way to treat these issues, and in our comprehensive program at MD Anderson, we work with, specialists in many different fields, all of whom have a great deal of experience with neurofibromatosis because we've all worked together for so long in this area.Lisa Garvin: Is the program at MD Anderson unique, or are there similar programs across the nation?Dr. Slopis: There are similar programs at other places, but not very many. It would be difficult for me to give you a list of them but I would guess there are problem a half a dozen or so true comprehensive programs in large institutions that either study cancer or they're a medical university based programs.Lisa Garvin: How do the patients typically enter MD Anderson? Are they diagnosed elsewhere and referred here or, what's their journey to come here to be treated for NF?Dr. Slopis: Many different ways. As we mentioned it runs in families, so very often a family member will recognize that their child has neurofibromatosis or one of their other relatives has neurofibromatosis. They come here first for a confirmation of the diagnosis. Frequently, within the institution that a patient will be sent here for treatment of a large tumor or a sarcoma or a brain tumor, and of these malignant peripheral nerve sheath tumors I mentioned or a brain tumor, and then once they begin treatment folks will recognize that that person has neurofibromatosis and then we, begin to take over their care. Orthopaedic surgeons, who are treating children with scoliosis or problems with bones, will refer the children to us. And sometimes geneticists from the outside will diagnose neurofibromatosis and then ask us, to see the children and begin the process of comprehensive care and surveillance and maintenance of care for the children.Lisa Garvin: So typically most of our NF patients here tend to be pediatrics, children?Dr. Slopis: Well at this point, it's about half and half. About, oh I don't know exactly 12, 15 years ago we really opened the adult neurofibromatosis program because we had so many of our pediatric patients that were growing to the point of age of 18, they had the transition and there was nowhere to transition them to. For that reason we opened the adult comprehensive program, it's many of the same people but not all the same people, physicians, specialists that I work with. And once the adult program was opened, then all those channels that we just discussed were opened for people to refer adult patients in for neurofibromatosis.Lisa Garvin: It seems like NF is a chronic disease that probably requires lifetime surveillance, is that correct?Dr. Slopis: That's correct. That's absolutely correct.Lisa Garvin: What's the risk over time, why is that surveillance needed?Dr. Slopis: Well, it's different depending on the different types of neurofibromatosis and, this is one of the reasons to actually need someone that's really well versed in these different conditions. Because there's a huge amount of variability, even in people with neurofibromatosis type I. Some with NF type I will have only minor problems, some with NF type I will have very severe problems, disfigurement, disability related to spinal disorders from the tumors or abnormalities of the bones. Different types of brain tumors, different types of malignant sarcomas that we talked about. And so, in a sense each patient has to be assessed, their family history has to be assessed and then after they're completely evaluated then we begin to develop, sort of a long term plan for the most appropriate way to maintain surveillance for health maintenance in that individual. It's very much a form of personalized care.Lisa Garvin : And of course, obviously you said, you know the symptoms and how patients manifest is quite variable but, what are some of the treatment options they would find?Dr. Slopis: Well, that's a vergining [phonetic spelling] area right now, and with neurofibromatosis type I, depends on what we're talking about treating. So there are some special issues with the learning disabilities, in children, the first and most important is to define those. We have neuro psychologists here who help define learning disabilities and we manage those, in a sense much the way you would in any child but, with learning disabilities but the important thing is the recognition that this is not just a kid whose uncooperative or unwilling, this is a kid that has a very specific, medical condition that causes his learning disabilities. With respect to the tumors that form in the, peripheral nerves, these neurofibromas or malignant peripheral nerve sheath tumors, in the past many of them have been treated with chemotherapy, with some limited success. One of our goals, very early on was to determine a method or methods for early detection so they could be removed, the tumors can be removed from the nerves, so that those nerves continue to function. So that a person still has the use of their arms, hands or their legs. And then, if possible, completely remove the tumor that may be curative. That's a very specialized type of neurosurgical procedure, and if that's not possible then we move forward into perhaps chemotherapy and in some cases radiation therapy. We have a group here, actually several groups that do investigation looking at new types of treatment for the tumors in neurofibromatosis type I and type II, and so experimental therapies are being developed here now as well as other places across the country.Lisa Garvin: So I'm guessing, you know, I don't know if targeted therapies might be an option but immunotherapy would be off the table I would think because this is a genetic mutation.Dr. Slopis: Well immunotherapy is very much under consideration right now. And, but you're right it's a particularly touchy situation because this gene may be in all the cells of the body, it may be in only some cells of the body. So if we try to find an immune based therapy that only goes after the tumors, it may be difficult to make it specific enough to not go after other things that are normal structures. But targeted therapy related to changing the way cells behave, not necessarily killing them with chemotherapy but, causing them to reduce their growth rate or to shrink, that's very much the, the primary direction of research right now for neurofibromatosis.Lisa Garvin: Are there any promising targeted therapies out there that are in clinical trials currently?Dr. Slopis: Well with neurofibromatosis type I there are a few very, promising approaches and these, many of these are a so called phase I. So they're still in the safety assessment, but one is called minor gene kinase inhibitors, MEK inhibitors. Another class of medications, referred to as PARP inhibitors and there are several others that are, I think, have shown great promise in animal models and many of them were in phase I trials in various places in and around the country including here.Lisa Garvin: How many people know that they carry either one of these mutations?Dr. Slopis: Oh it's, it's really surprising how many people do not know they carry these mutations. First of all I think about, a NF type I, that's 1 in 3,000 people have one of these mutations. Now,Lisa Garvin: That's a lot.Dr. Slopis: That's a lot of people. And so, you may very well find that, many of these folks have only a few skin markings or they may have problems in school but they don't really recognize any particular health related problem, nothing that stops them from living their lives. So a lot of people carry the mutation, the big problem is if they have a child who is born with this gene, the child may be much more severely affected. So a lot of people and frequently families will come to us for a diagnosis of NF type I in their child and as we began to meet the parents, talk with them we recognize that one of the parents may actually carry the gene, and they may have features that are minor but there are clues that that person also carries the gene. Neurofibromatosis type II, or NF II reveals itself in a different way. If you don't know you've got it usually you don't have symptoms until, late teen years, early adult years. And one very common scenario is a young woman with her first pregnancy, unaware she's got the gene, during the pregnancy a number of factors related to the pregnancy to bring about the growth of the fetus will also induce growth of the acoustic neuromas you were asking about. They grow quickly during the pregnancy and suddenly, sometimes even before the baby is born the mother will be in significant trouble because these tumors grow and compress the brain stem, right around the time when mom needs to be healthiest in order to deliver the baby. So we have seen a number of times young woman that have a pregnancy, a normal life and then towards the end of the pregnancy suddenly they discover that they have neurofibromatosis type II. Not only that, but they discover that their baby has the gene. So, the last category of neurofibromatosis is actually called multiple schwannomatosis. These do not affect anything, these cases do not affect anything within the brain but they cause painful schwannomas all throughout the body. So these folks will usually get to adulthood without complaint begin to experience pain that's unexplainable and it's because schwannomas have developed around nerve fibers and they are nerve fibers that specifically generate the message for pain. So they come to attention in that way.Lisa Garvin: It sounds like the chances for misdiagnosis or a missed diagnosis are pretty high.Dr. Slopis: Absolutely.Lisa Garvin: So I, it sounds like the best advice for people who might suspect this or know that they have the gene to actually get to a comprehensive treatment center.Dr. Slopis: Well absolutely, and, if you can't make it directly to a program like ours then you should ask your pediatrician or your family doctor to at least have you evaluated by a geneticist to begin as the next step and from there move forward toward a larger program such as MD Anderson School of Derm.Lisa Garvin: Great, thank you very much.Dr. Slopis: Your welcome, thank you for having me.Lisa Garvin: If you have questions about anything you've heard today on Cancer Newsline contact ask MD Anderson at 1-877-MDA-6789 or online at ask. Thank you for listening to this episode of Cancer Newsline. Tune in for the next podcast in our series. [Music] ................
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