>> Helaine: All right. Well, good morning, good afternoon, good evening to everyone. Welcome to the NF2 BioSolutions webinar. I’m surgical management on NF2. My name is Helaine Bader and I’m a volunteer with NF2 BioSolutions. Before we begin please note that we do have live captioning for this webinar, so to see the captions just click the closed caption button at the bottom of your screen and select show subtitles. You can make them as small or large as you like and you may find helpful the full transcript option which will allow you to see the full captioning. Before we get started, the webinar is being recorded and will be available on our website later for viewing. All participants will be muted. You will be able to ask any questions through the Q&A function. Before we get to our panel we’ll hear a few words from our vice president of NF2 BioSolutions, Gilles Atlan.
>> Gilles: Thank you Helaine
I want to thank to all the surgeons who are spending their Sunday to answer the questions. For ones who don’t know me, I’m the father of Karen, Karen is 13 years old, Karen has NF2. That’s why I’m trying very hard at NF2 BioSolutions to change the course of this disease.
And as you all know we need better treatment and more treatment options, we need to stop the tumor to grow, we need to reduce or kill the existing tumor without damaging the nerves.
My daughter has had a few surgeries so far, and the last one was when we removed a vestibular schwannoma preemptively, that was done by Professor Kalamarides who is here with us.
As a parent I know we have a lot of questions to ask, these are very hard decisions to go through a surgery, and having more knowledge will help us decide what to do next.
So Helaine will ask questions that we collected from you in the last two weeks, and we’ll also have time for Q&A.
We’d like to add today is Rare Disease Day and we’d like to continue to receive your support so we can found new therapies that won’t require us to go through these risky surgeries. So please continue to donate and we can advance faster toward a long term safe therapy. So thank you again, and I give you back to Helaine.
>> Thank you Gilles. I’d like to introduce our esteemed panelists.
We have Dr. Rick Friedman, a board certified neurotologist and world renowned expert in the treatment of acoustic neuroma in NF2. In addition to leading the acoustic neuroma program at University of California San Diego health he also treats meningioma, NF2, tumors, hearing impairment, and numerous other conditions, as a professor in the Department of Surgery he trains the future leaders in the field at the UC San Diego school of medicine. He receives funding from the National Institutes of Health for research on genetics of common forms of hearing loss. Welcome, Dr. Friedman.
>> Dr Friedman: Thank you, great to be here.
>> Next is Professor Michel Kalamarides, professor of neurosurgery at Pitie-Salpetriere hospital, Paris, France. Specializes in vestibular schwannoma, meningioma and spinal ependymoma surgery. He is leading the French NF2 reference clinical center located at the Pitie-Salpetriere hospital and the French NF2 network. Dr. Kalamarides is also leading a research group on meningioma using mouse models to dissect the mechanisms of meningioma initiation and progression. Welcome.
>> Dr Kalamarides: Thank you.
>> Dr. Andrew King is also here today. Dr. King —
>> Dr: Kalamarides:
Excuse me, I would add that I’m now leading research on ependymomas thanks to NF2 BioSolutions.
>>Helaine: Oh, wonderful.
>> Dr Kalamarides: Yeah.
Thank you for adding that. Dr. Andrew King is also here today with us. Dr. King is the professor of neurosurgery in Manchester, UK. Along with Professor Gareth Evans, he leads the NF2 program in Manchester and is one of the joint leads of the NHS NF2 service.
Since the inception of the service in 2009, it has demonstrated and published evidence based improvements in survival and quality of life.
Dr. King leads a research group focused on the role of inflammation of vestibular schwannoma, therefore the potential for immune modulation drugs, including antiinflammatory medications as future treatment options. One of four Manchester skull based NF2 neurosurgeons, Dr. King runs an internationally acclaimed subspecialty training fellowship in skull based neurosurgery. Welcome Dr. King.
>> Dr King: Thank you very much.
We also have Dr. Gregory Lekovic with us today, a board certified neurosurgeon and current chief of neurosurgery at the House Institute neurosurgery clinic in Los Angeles, California.
He is also the director of neurosurgery research at the House Institute foundation. Dr. Lekovic is also a voluntary clinical professor in the department of head and neck surgery and neurosurgery at UCLA and an associate in the department of neurosurgery at Cedars Sinai hospital, on the teaching faculty. Welcome.
And next, we have Dr. Marc Schwartz, board certified neurosurgeon who is internationally renowned expert on treatment of patients with acoustic neuromas, skull based tumors and NF2. In addition to leading the acoustic neuroma program at the University of California San Diego Health Dr. Schwartz is also the recognized neurosurgical leader in the fields of auditory brainstem implants.
Dr. Schwartz treats complex cranial problems, meningiomas, brain tumors, pituitary tumors, cranial nerve disorders and intradural spine tumors. Dr. Schwartz conducts research in tumor biology and genetics especially as related to schwannomas and NF2. Welcome, Dr. Schwartz.
Finally we have Dr. William Slattery. Dr. Slattery is a board-certified neurologist at the House Institute Ear Clinic in Los Angeles, California. He’s the head of the Department of Clinical Studies at the House Institute Ear Clinic and a clinical professor at the USC School of Medicine. Dr. Slattery specializes in the medical and surgical treatments of hearing disorders, facial nerve disease, acoustic neuroma, and NF2. He’s maintained a strong presence in the field as respected clinical researcher and is committed to understanding and treatment of acoustic neuroma in NF2 as well as enhancing current methods of drug delivery to the inner ear. Welcome, Dr. Slattery.
>> Dr. Slattery: Thank you very much.
I know it was a long intro, we just wanted to make sure our audience has some good background on our incredible experts before we jump into the questions. We are really thrilled to have this panel with us today, and we want to make sure you use the Q&A and ask as many questions as you can. We do have some early questions that came in, so we will jump right into those. We’re going to start out with questions about the most common tumor in NF2 that’s vestibular schwannomas, we’ll move into ependymomas we’ll move into general questions about surgery, and open it up for some Q&A from the audience. Dr. Friedman, I’d like you to take —
Helaine? Just before we start, could you give another — some tips about the captioning? Explain to people how they can see the whole captioning text.
Absolutely. So you just go to the bottom and click the closed caption button at the bottom of your screen. And you’ll select show subtitle. And then you can adjust those settings. And if you want to click the view full transcript option then you can see the full captioning on the right of your screen, where the chat would be.
>>Giles: Okay. Thank you.
Sure. Okay, so Dr. Friedman we’re going to start with you. Can you tell us when it is advisable to resect vestibular schwannomas? Is it while they’re still small and asymptomatic, or is a watch-and-wait approach a better option.
>> Dr Friedman:
That’s a complicated question. It obviously depends upon size and symptoms. You know, historically, these children have been observed for a long time, long enough that tumors get big enough that we are not able to save hearing. So I would say that at our program Dr. Schwartz, I won’t speak for Dr. Schwartz but I think Dr. Schwartz and I agree, that we like to take a proactive approach, especially when hearing is good in the ear and the tumors are small, because it is the best opportunity to save hearing. So I would say when tumors are small, certainly I understand if it’s a new diagnosis parents may want to sort of take a step back and think. We don’t want to be too aggressive and scare people. On the other hand, establishing a relationship, establishing a rapport with the family, and explaining what can be done, we’ve had some really good success saving hearing small tumors in children. And we do most of that, well we probably do all of that through the middle fossa.
Great. So Dr. Schwartz, what about if you already have some hearing loss at the time of surgery? If you remove the schwannoma is there any chance you get hearing back?
>> Dr Schwartz:
I don’t think we’ve ever told somebody to expect hearing to get better. That’s not really a realistic thing. It’s a difficult decision to operate correctively in a situation of a small tumor. Even that’s not an ideal response because there is a significant risk of not being successful in saving hearing. Our results are quite good for saving hearing in that situation, but certainly not perfect. I’d also add that with NF2 especially, that’s — we wouldn’t consider that to be a cure even if we got the whole tumor out because we do see there is a recurrent risk or regrowth risk. The indication for thinking about (indiscernible) is we see so many patients who have not (indiscernible) and to have missed the opportunity is also not a good situation to be in.
>> So building off that a little bit, there were some questions about total resection versus subtotal resection or debulking in order to possibly preserve hearing or facial nerves. Should patients consider this, is this something that is a good option in terms of trying to preserve? Dr. Slattery, do you want to address that?
>> Dr Slattery:
The likelihood of preserving nerve function with partial resection is actually very poor. One of the things that was demonstrated early on with NF2 is that the cochlear nerve fibers tend to be more invaded with a vestibular schwannoma in NF2 than say sporadic tumors. For that reason to do a subtotal debulking of the tumor rarely results in hearing preservation. In many, many patients that I’ve seen where this has been tried I’ve only seen one patient, and this is not — not at our institution, our institution we typically do not believe debulking is a good option, but in patients that I’ve seen who have had attempts at debulking, I’ve only seen one out of probably 75 NF2 patients who have undergone that that’s ever had hearing preservation. So there’s a good histological reason for that, and I think the outcomes from at least my experience from seeing patients that have been tried in other institutions, has been very, very poor. So I would not recommend that.
Thank you for that answer. Dr. Lekovic kind of on that same line, what about facial nerve, is it possible to preserve facial nerve through debulking and is it possible for an already weakened facial nerve to regain any kind of function after surgery if the tumor affecting the nerve is removed and the nerve remains intact? Sorry, you’re muted. Dr. Lekovic. There you go. We still can’t hear you.
>> Dr Friedman:
While we’re waiting on Gregory maybe I can make a comment. I completely agree with Dr. Slattery said. There’s also some evidence these days that the presence of the tumor for some reason is causing a protein accumulation in the cochlea, and so subjecting an individual to surgery in an attempt to save hearing by debulking in my opinion is it’s a wasted attempt, it’s putting somebody through a surgery that’s not going to have the long term benefit of hearing preservation. So I would agree with Dr. Slattery.
>> Dr Lekovic: Am I live now?
>> Helaine: You are, yes.
>> Dr Lekovic:
Great. I started to say that’s a great question sort of nested within a question about regarding the facial nerve. I would say that as in sporadic tumors, in neurofibromatosis generally speaking the goal of debulking in the first place is to preserve facial nerve function. We talk about debulking primarily because of its — our ability by retaining some discretion in the aggressiveness of tumor removal, to spare the facial nerve when it can be identified and traced, and that is usually the case. No matter really the size of the tumor so even some very large tumors can be removed safely without injury to the facial nerve through the employment of this strategy.
That’s probably — it depends, as everything, for vestibular schwannomas, the size of the tumor. For smaller tumors where a cure is possible, aggressiveness is warranted. But particularly in neurofibromatosis we have patients who as already been referenced in this discussion with potentially polyclonal tumors; on the same nerve three or four tumors like beads on a string. So even with complete removal of a tumor in a child, as Dr. Schwartz mentioned earlier, that doesn’t equate a cure. We’ve seen this in patients we’ve followed in the clinic here 30, 40 years and tumors do come back, on nerves that have been clinically clean after surgery. So I think discretion is warranted above all in removal of tumors with regard to facial nerve, and that is the paramount goal.
The second question you nested, can facial nerve improve after surgery, facial nerve weakness — let’s take sporadic tumors for a motion, facial nerve weakness is a very rare — relatively rare or uncommon presenting sign for sporadic tumors. It happens, it’s rare, and in those cases I think you do see improvement in facial nerve function with removal of the tumor after some amount of time.
In NF2, I worry that a patient who has a facial paralysis prior to surgery that they would have — my concern would be they have a polyclonal or multi tumor sometimes called a collision tumor where you have two tumors nested together that are abutting together, and even on a MRI, even with a sophisticated MRI you can’t necessarily disambiguate the relationship of two masses that are sort of kissing like that. So we counsel patients not to expect facial nerve improvement. Rather if we have a patient presenting with a tumor we suspect might be a mixed tumor, that we would in fact leave the part of the tumor on the facial nerve if the facial paralysis isn’t complete. If the facial paralysis were complete rather than saying we’re going to remove the tumor and the facial nerve function would improve, we would generally recommend removing the tumor and the facial nerve and do anastomosis, where you take the two cut ends of the nerve and put them together. And that actually gets a pretty good result given sufficient time.
We have two questions from the audience to follow up on what you’ve suggested. One is what is small. When you say a small tumor, what do you consider as a small vestibular schwannoma.
>> Dr Lekovic: Is that to me?
>> Gilles: That’s to you or anyone.
>> Dr Lekovic:
I think that’s a question there are several classification schemes that compete for definitions and I’m not sure there’s an absolute consensus. I would certainly say under 15 millimeters would be considered small. Sometimes when we talk about hearing preservation numbers like 15 millimeters or, 1.5 centimeters or 2 centimeters can be important demarcations. In my opinion I would say under two centimeters I would consider a small tumor. Although as I say, for hearing preservation you might say that even you make a further distinction about very small tumors that are confined to the canal or under 15 millimeters in size. I think we all agree big tumors are 3 centimeters plus, but in the literature you’ll see differences between two and a half centimeters whether you measure them in the brain cavity space or you take the total measurement. So I think it is still, in spite of all that’s written about it, somewhat of a judgment call.
>> Dr Friedman:
I think I find, Gilles, I find often that when parents come to us with a child with a very tiny intracanalicular tumor it has been historically the idea that they’re reticent to move forward because the tumor is so small. But I think that’s the best time really to be able to save hearing. And I totally agree with both Dr. Lekovic and Dr. Schwartz that tumors do come back to fill the canal, they’re typically tumors on a different nerve, and even though these tumors do come back, it’s disappointing, but the fact is that even with recurrence these kids can have very long term hearing preservation. I’ve had patients that I took care of as children who have gone on as adults to have careers and retain their hearing. There often is a gradual decline but they certainly can get decade or more hearing preservation.
That’s really helpful. Thank you. So in terms of any of these types of surgeries I know there are different approaches for surgical removal. Dr. King, do you want to talk a little bit about those different approaches that are used and the pros and cons of each of these approaches for removing vestibular schwannomas?
>> Dr. King:
Yeah, sure. So I think — well, there are three. There are the middle fossa approach described by Dr. Friedman which is I think much more popular in the U.S. than in the UK. So it’s almost not done in the UK. But it is one of the two routes that you can employ to preserve hearing. The other being the retrosigmoid approach. The translabyrinthine approach is a approach through the petrous bone and by definition renders the patient deaf at the end of the operation. So clearly the translab is not one that is a hearing preservation attempt. I think that it would be fair to say that notwithstanding that criteria about whether you’re wishing to preserve hearing or not, the panel here will have traveled around the world as I have listening to great debates about routes and so on. I think the answer is probably that you do the route that you like and you’re familiar with. And it’s as simple as that. So you make a decision about whether you wish to preserve hearing or not. If you’re not going for that, you may prefer the translab, there are plenty of people who don’t ever use the translab even if they’re not trying to preserve hearing. But that’s the basic bipolar decision-making between hearing preservation and not.
Does anyone else want to add on to that or — all right, good. Well, we are going to switch gears to ependymomas — oh Dr. Slattery, yes.
I’d like to make a couple of comments. Because I think it’s important, all of the experts that you have on your panel here are very familiar with what I’m about to say, but I think it’s important that the patients that are listening to this also make sure that they follow this. And that is before we even talk about acoustic neuromas or vestibular schwannoma treatment it’s important that patients are fully evaluated for their NF2. And unfortunately, I think we’ve all seen this where patients have been evaluated for NF2 and they’ve never truly been fully evaluated. And that is if the patient needs a full head MRI scan with a dedicated series to look at the auditory canal, but they need to make sure they have a full spine series, someone needs to talk to them about family members, genetics, ophthalmology, there are all these other parts of NF2 that we need to make sure that a patient is truly getting a full evaluation for. And I know that all the clinics represented here do that, but unfortunately there are a lot of patients that get their first experience somewhere else and, we find that for several years they’ve been seeing people, told they have NF2, and they’ve never necessarily been evaluated fully. And it’s just important they have a comprehensive evaluation. So I’d just like to put that out there.
>> Helaine: Yes.
>> Dr Kalamarides:
I just want to add some remarks. First of all, in France we are not in favor of corrective treatment of very small tumors. I prefer to follow the patient and do surgery on a tumor that’s really growing, with good hearing. And as Andrew King said we are not doing any middle fossa approach anymore on a very small tumor. It’s different than U.S. where middle fossa approach has been brought. I think the first vestibular schwannoma surgery is very important. Because if you get facial paralysis because the first vestibular schwannoma surgery, then the situation would be very difficult to manage in the future. So you have to — I don’t like debulking, but if you have to leave a small piece on the facial nerve it’s okay for me. It’s better than facial paralysis. And you can monitor the facial nerve during surgery using facial nerve monitoring, it helps to understand the risk of facial paralysis. Even if you see a normal facial nerve during surgery, you can say the monitoring will indicate that maybe there will be facial paralysis, so you can stop. So I think it’s crucial first to avoid surgery. So as Bill Slattery said, I think the surgery must be performed by a trained surgeon. Very useful to do vestibular schwannoma for sporadic (tumors). For example I’m sure that in the panel all surgeons are doing a lot of vestibular schwannoma surgery, but I’m doing maybe 100 vestibular schwannoma surgeries a year. You need to have a very well trained surgeon to do this. So it’s very important to say to the patient. Because we are discussing, but after that if they go to see a surgeon with very few NF patients it will not be the same results, so keep this in mind.
>> Dr Friedman:
I would like to echo what Michel is saying. In good hands, I would want the parents out there to know in good hands the risk of facial paralysis should be pretty low. I know that that’s a frightening potentiality when you’re thinking about your child having surgery, we’re all parents, I believe. But in the hands of somebody that — in the hands of a team that does it a lot, that incident should be fairly low.
>> Dr Lekovic:
I’d like to add something as well. Just to comment on a prior comment that Michel made, Professor Kalamarides, this goes back to the approaches as well. I think there is a difference in sort of European practice and American practice with regard to the middle fossa, and I think — I don’t want to speak for Drs. Schwartz and Friedman, but I would say that the experience in the United States, from — as Professor Kalamarides said, from Dr. Brackman’s experience or even before that, House, the advantage of the middle fossa is that superior hearing preservation outcomes have been achieved by multiple centers, not just House, but repeatedly through different surgical series in the United States and elsewhere.
So we generally consider, all things being equal, so for an appropriately sized tumor, the middle fossa is most likely to provide a superior opportunity to preserve hearing. And that kind of dovetails with Professor Friedman’s point, which he’s made a couple times, which is for small tumors you have this sort of opportunity to remove the tumor and save hearing. So there’s almost an opportunity kind of cost calculation that needs to be made on the point of the patient or in the case of child in the patient’s parents, which is that for a small tumor you have the opportunity that could be lost to remove the tumor and provide many years of meaningful hearing preservation. But also, that will be a safer surgery for the facial nerve. Because facial nerve preservation will track with tumor size, and also for the third benefit so will extent of resection. So extent of resection has been the other variable that we haven’t really discussed explicitly.
You mentioned debulking earlier, I don’t think anyone here really is a fan of debulking as it is used in medical parlance. Really, what we try and do, I’ll speak for myself and I think Dr. Slattery will echo that, and I’m sure the others feel similarly, but I don’t want to presume to speak for them, we attempt to remove as much of the tumor as is practicable. And oftentimes when we are talking about leaving tumor to save the facial nerve as Professor Kalamarides said, we’re talk about leaving a scrap or a rind of tumor that follows the facial nerve. Not debulking and leaving a third of the tumor or half the tumor there. Which is a strategy employed by some in the NF2 community, NF2 world. But it’s not one that we would do.
So and as was made — the comment was made earlier that that first surgery is so important, that again is — not that I’m advocating that everyone would get a small tumor in the future to have surgery, quite the opposite, but certainly there are circumstances in which it makes sense to be proactive. And then the last thing I would say about approaches, there are two sort of variants on the approaches that come up only in NF2, and those are bony decompressions. Bony decompression for hearing preservation, and for facial nerve function. So if we are confronted, and you mentioned this in your question Helaine, patients that present with facial weakness, and I said sometimes there’s a facial nerve tumor and we leave those alone. When we talk about the different approaches and really about the merits of intervention we also need to recognize sometimes we’re surprised let’s say and we are doing a middle fossa for hearing preservation and we find out that’s a facial nerve tumor, not an acoustic neuroma, or maybe it’s both and there’s a big vestibular tumor. We’re still doing the patient a service by removing the bone around that canal. In other words sort of giving that tumor a little room to grow, to delay the point at which the tumor puts pressure on the facial nerve, and causes facial nerve weakness. The same can be said for hearing preservation. We have some experience with that at House, doing middle fossa decompressions for hearing preservation. It fits somewhere in the algorithm with Avastin and all the other things we use to preserve hearing, can’t be discussed in isolation but it’s certainly worth mentioning that it comes up under appropriate circumstances when we’re talking about the overall management of the patient’s hearing, left or right ear, et cetera. Rather than the narrow thing, which is proactive tumor removal, which we’ve been talking about so far.
This is interesting, thank you. I think what’s hard with parents you’re highly regarded NF2 institutions, some of us are not close to those types of institutions, and so how are best practices shared? How do you learn from one another? And is it something you see collaboration happening on an international level? Because I think that’s one of the things that parents are concerned about, if they don’t go to one of you, and they end up with someone in a smaller area, how do they figure out what’s — where are they getting their lessons from, and is there a place that they’re learning from all of you?
>> Dr Schwartz: Can I address that a little bit?
>> Helaine: Yes please.
>> Dr Schwartz:
So it may not be an issue — certainly not an issue in the UK or in England, France probably not to the same degree, but we face narrow networks and people in different areas. And really, the people in this group, at least as the state of the art today are the ones we don’t have to worry about, it’s the people that haven’t connected to something like this. But I always talk about this not only for NF2 but also for sporadic tumors, the question of the debulking and preservation of facial nerve. It is to me a red flag when a surgeon says oh, we’re just going to debulk the tumor and not engage the facial nerve, because that will be a lot easier than it was before. You have to respect the facial nerve, but you also have to respect the tumor. There’s a real art and experience in taking out as much tumor out as you can which is beneficial for the facial nerve. We’re talking about here having high regard for the facial nerve and high stakes, and also doing the best for the patient. The idea of debulking and preserving the facial nerve, with subtotal resection, we’re really putting the facial nerve first, actually makes the resection more difficult than easier. So I think that when you talk to a surgeon who has that balanced view with respecting both the tumor and the facial nerve, and is very straightforward about the fact that this is not going to be easy, this is going to be hard, that’s the important thing to have that recognition. The surgeon who says oh it’s going to be easy, we’re just going to debulk the tumor, that’s actually a red flag and a sign that the surgeon doesn’t really understand the principle.
Yeah. Thank you, that’s really interesting and I think that’s something we all need to hear, as parents and as patients. I think we could definitely keep talking about all of this but I know we need to switch gears to ependymomas because we have a lot of questions to cover. In the interest of time — Dr. Friedman I see you asking, go ahead.
>> Dr Friedman:
One quick comment before we transition, I think we need to defer the ependymoma questions to our neurosurgical colleagues, but I can’t emphasize enough the whole concept that Malcolm Gladwell brought to us and that’s 10,000 hours. These cases should be done at centers, centers of excellence across the countries. There’s no question. It’s absolutely worth travel, it’s absolutely worth getting on an airplane. So I really would want to emphasize that.
>> Yeah, thank you.
>> Dr King:
Can — can I just say one thing, that I just want to emphasize Dr. Kalamarides point. I think there are sort of two approaches to the small tumors in the kids, both of them are entirely reasonable. There’s the get it out while it’s small and preserving hearing. And there’s the one in the UK — I’d like to thank Dr. Heinrich describing Britain as serving Europe, I wish it was. But we in the UK would almost never almost never operate on a small tumor. Maybe the whole point about NF2 is there are not right and is wrongs, there are when you do something you must do it well. And the alternative to a really high class bit of surgery in a small tumor in a young person, is to leave it alone on the basis that you allow the natural history, which will not be of a facial palsy, and very low hearing preservation over a period of time. It’s a tough call, and one we all hear great debate about.
Yeah definitely sounds like it’s something that as you said speaking to the experts, really getting different opinions, and then depending whether you’re in the U.S. or Europe, kind of following at least someone who like you said 10,000 times really is an expert in what they’re doing, and doing it well. So I’m going to move on. Like I said I think we could definitely talk about this for awhile, but I want to make sure we cover ependymomas. So Dr. Kalamarides can you talk about the surgical management of solid spinal ependymomas?
>> Dr. Kalamarides:
Yeah, it’s a tumor type in NF2 and it’s like vestibular schwannoma, I’m not in favor of corrective treatment of ependymoma except if they are very large, and if sometimes you have patients presenting in NF2 with ependymoma, with pain, with deficit, so you have to go. But I like to observe the tumor, and if the tumor are growing you have to decide surgery. Because it’s not compression of the spinal cord like for meningioma or schwannoma. So the goal of surgery is to resect the tumor, not to improve the patient. So if you are waiting a lot to have a deficit to say okay, there would be few risks. If the patient has a deficit, it’s too late. So I think that for ependymoma you have to decide surgery where the tumor is growing and large. And maybe Andrew King can say, we’ve done a very interesting study between Paris and Manchester, because when I decide to analyze all the results of the ependymoma surgery, I was about to compare all the surgical cases. And sometimes you have some worsening after surgery, because you have to open the spinal cord, so it’s a risky surgery. And when I compare my results of the surgery versus the observed patient, I say okay, after surgery sometimes I add some worsening. So maybe surgery is not good. And then we compare our results to the Manchester results. In Manchester, although you can say somewhere else, you were observing the patient, and what is —
>> Dr King:
So this is again just like the discussion about acoustics, about schwannomas, there isn’t a set answer. But we have always had — and you can get the theme that’s coming out of Manchester — but that if you’re going to operate, operate well, but don’t operate unless you have to. And we had adopted a much more conservative policy. And based on my friendship with Michel over the years we compared the two series. And I was particularly keen on it for many years, I was actually convinced there was no case for surgery. And in the space of two or three — within a year, two or three cases suddenly got worse. So I went 15, 16, 17 years never, ever regretted the decision not to operate. And then there was a sudden deterioration in two or three in very short order, which led to Michel and I writing the paper. Which Michel will remember much better than I what we said in the paper. So I’ll return back to him.
>> Dr Kalamarides:
So it’s a tough decision, but you have to take the decision not too late. When the patient is still okay.
>> Helaine: Yeah, sounds like. Dr. Lekovic do you want to comment as well I was going to direct the next question to you as well, is it common to see malignant spinal ependymomas in NF2. So if you could cover both.
>> Dr Lekovic:
Thank you I’m glad you asked that because I was going to make that comment proactively. So it’s really important to recognize that ependymoma in NF2 appears to be a different entity than sporadic ependymoma in a much more important qualitative way than the difference between sporadic vestibular schwannoma and vestibular schwannoma in NF2. By which I mean to say a vestibular schwannoma in NF2 is very similar to a sporadic vestibular schwannoma as far as we know, other than these exceptions that we’ve given about polyclonal tumors, maybe some vision and cochlear, but fundamentally the tumor behaves the same way. Benign tumor, what have you.
Whereas in ependymoma, it’s a completely different situation. And particularly with regard to malignancy, ependymoma is a tumor that classically has a heterogeneous classification of histologies, meaning that under the microscope there’s different sort of subcategories of ependymoma. We now know that some genetic modifications are associated with different of these categories. And that can predict behavior but that all again is referring to the sporadic ependymoma which can be a very bad tumor. The closest thing in my experience, the closest thing or analogous thing would be something called a tanycytic variant of ependymoma which is generally considered a sort of benign lump that grows very slowly and benignly. To my knowledge, Professor Kalamarides, Dr. King or Dr. Schwartz if you have a more current information, chime in. But in general, we will see really no malignant potential for spinal cord tumors in NF2. We do not see metastases, we do not see malignant generation of ependymomas, we do not see ependymomas, intracranial ependymomas or ventricular ependymomas that have malignant potential. Although we call them ependymomas, they still are ependymomas histologically they’re a very different animal.
I would add there’s an important lesson to be learned in the common theme of not waiting until the shoe has dropped to intervene, and so Professor Kalamarides is saying we don’t want to wait with a spinal cord tumor until the patient is weak in all four limbs. If it’s a cervical tumor it’s kind of too late at that point. So there’s a judgment call that needs to be made. It’s sort of similar to the discussions that are made with vestibular schwannoma. I think it’s very important to recognize that the ependymomas in NF2 generally speaking are well demarcated from the spinal cord irrespective of their size. In my practice, generally speaking at House we had also like the UK have a very conservative approach to ependymomas. And actually very similarly last couple years we’ve had some that have changed dramatically. And I think part of this has to do with — or part of the decision-making has to do with recognizing that that’s a clear indication, when the tumor is enlarging or there’s sometimes what we call a cyst or fluid space or cap, that can form on either end of the tumor within the spinal cord, and we need to sort of parse the imaging and parse the history and identify these tumors individually with the intention of recommending surgery when surgery is favorable. And sometimes that will be even let’s say the tumor the solid component hasn’t gotten bigger, but that cyst is getting bigger and that cyst kind of does a lot of the surgical work for us, it makes a fluid space around the tumor, so when we open the spinal cord it opens like a book from behind we can see the tumor is more amenable to safe removal. So all that goes in.
But in addition there’s a lot of decision-making, diagnostically, because unlike vestibular schwannoma, in ependymoma this is sort of the paramount example of what we sometimes called tandem lesions and the diagnostic difficulties associated with tandem lesion. What I mean by tandem lesion patient has hand weakness, is that hand weakness caused by tumor on the radial nerve in the arm? Is it caused by one of the nerve roots in the shoulder, the brachial plexus where the nerves come off the spinal cord? Is it ependymoma in the spinal cord itself or is it from a brain tumor? Again the point has already I think already emphasized maybe beaten to death, that’s a benefit of going to a comprehensive sort of center where we’re not looking at things individually but holistically. One thing I think we underrecognize or undertreat potentially are tumors in the spinal court, cervical ependymomas in particular, that are presenting insidiously. And we really need to do a very diligent job of managing and examining patients and following subtle changes in the upper extremity physical exam. Because even very large tumors in the cervical spine or cervical medullary junction can be removed safely, but it’s better to do — again, common theme — when they’re smaller rather than when they’ve taken over the whole cord.
>> Dr Kalamarides:
I would add one technical point. I think, a neurosurgeon it’s not risky to remove thoracic spinal cord ependymoma. Because the lower level of the spine, spinal cord, it’s very small. The spinal cord is very small, so it’s very dangerous because there are very few fibers. So it’s technically more difficult to remove ependymoma at the lower part of the spinal cord compared to the cervical part or the brainstem. So it’s strange, because it’s more risky to do upon the brainstem but in fact it’s easier. From a technical point of view.
>> Helaine: So you mentioned, just in terms of talking about the different tumors, you mentioned tumors in the brachial plexus, Dr. Lekovic. I’m just curious, whoever wants to answer this, but is that the same approach, is it something that you would watch and wait or is it something you don’t wait and you go right in? Or are there varying opinions on that as well?
>> Dr Lekovic:
Well, I think that it’s always a similar approach. You’re always — we don’t ever remove tumors just because they’re there, I think. Even the tumors that we are proactively, because of the incipient threat they pose to the patient because of sort of triple loss of function. In the brachial plexus I generally speaking watch those tumors until they’re growing, and I think it’s the same principle. They can be safely removed when they’re smaller we had a recently published study looking at about 30 peripheral nerve tumors on major nerves in NF2, and we found around 10% of them had a mixed histology which we thought was interesting. In other words, some nerve fibroma elements which we don’t really think of in terms of usually with NF2, and that may indicate some of these tumors may be a little more invasive. Really in our experience we’re able to remove the whole tumor in almost every case without injure to the apparent nerve. But again, this is probably going to be easier to achieve when the tumor is smaller. Again with the brachial plexus if you wait until you have a wrist drop or grip weakness or some sort of neurological deficit, it’s going to be very hard to remove that tumor and expect that to improve.
>> Helaine: So that leads me to the next question that worries everyone but needs to be asked. Maybe Dr. Schwartz you can take this. But are there tumors that are considered inoperable? Tumors that you can’t operate on?
>> Dr Schwartz:
Hi. Yeah, depends — it depends on what your definition of inoperable is. Because we can operate on anything. The question is always what’s the risk versus the potential benefit. And there are certainly very difficult tumors, and there are different reasons for that. I don’t think there is for instance acoustic neuroma or tumor of a facial nerve that we can ever say is inoperable. We’re always very concerned about schwannomas on the — nerve for swallowing or vocal cord function. The spinal cord might not be that complicated, but it might be inoperable because of the function of the nerves is so critical. There can be meningiomas and other tumors that are just in difficult locations that make it not feasible or safe to operate. And there can be situations in severe cases where there are just so many tumors that there’s no way to think that there’s much benefit to be made. Or that it’s possible to debulk to remove tumor mass but not think it’s going to be anything that’s definitive, or just buying time. We luckily do have other treatment options which are sometimes –especially schwannomas like Avastin, in those cases that’s more difficult. Meningiomas where Avastin is much less effective. And thinking about other drugs, and also frankly in some cases roles for radiation when it gets to that point. So radiation for very benign things, there’s always a down side to that also, but looking holistically what the best option is in a certain situation.
>> Helaine: Thank you. I’m glad you actually — sorry, was someone going to say something?
>> Dr King:
I was just going to say I think with regard to the ependymomas I think perhaps at least as much as for the VS, they need to be managed in an experienced NF2 center. That having had this experience of absolutely recognizing after an appropriate study of when you should — there are ependymomas that you should remove. But the decision is an entirely different one to the decision of a sporadic ependymoma. That absolutely as Dr. Lekovic said, you want to go in before the neurological harm is done. So you want to select a certain number of those that are growing. But of course, some ependymomas are multifocal in the cord. And so you’re not going to achieve a cure, but even that we learned in our paper or I learned from Dr. Kalamarides there are some way if you can identify a growing symptomatic lesion that it is reasonable to resect that. But it’s serious surgery, and the criteria are not those of a sporadic ependymoma, which is essentially if it’s there you take it out.
So you both brought up using other techniques as well, and I know there are a lot of questions we had about radiation and gamma knife, so I was thinking we could move into that. We had a lot of questions about hearing that radiation wasn’t recommended for NF2 tumors in the past, and that some surgeons have been recommending it now when you can’t fully resect without compromising nerve function. So I was wondering maybe Dr. Slattery if you can take this and tell us maybe about the long term sequelae about using low dose radiation or gamma knife on brain tumors, any of the NF2 related brain tumors?
>> Dr Slattery:
I think one of the things we know, and this has been demonstrated in multiple centers, is that when you’re comparing — well, let me back up. With any of these treatments, unfortunately with NF2, it’s — there’s never a good option. Surgery is not a great option, radiation is not a great option, chemotherapy is not a great option. But unfortunately we have to choose between these different things. And it is a matter then of kind of looking at what are the risk-benefit ratios of each of these for each of the different tumors. And what I would say is that in general, the effects of radiotherapy, whether it’s gamma knife or cyberknife, compared to — in NF2 — compared to sporadic tumors, for all the different tumors, the results are not as good for NF2 as compared to sporadic tumors. And that’s consistent across institutions and pretty much across different tumors.
That said, there is a role for these therapies, depending on the situation. For instance we know for vestibular schwannomas the chance of saving hearing is much less with NF2 than it is with sporadic tumors. The incidence of vestibular problems are slightly higher. There is a very small risk of cancer formation, it’s a little bit higher in NF2 than it is in sporadic tumors. Still very small, but it is still something that has to be at least addressed. So for vestibular schwannomas it is something that could be done. I think it’s — you know, for small tumors, that still have good hearing. It’s not something that I would not recommend. It’s a situation that some patients will choose to do that. And do it when the tumor, for instance, gets to be, say, two centimeters, they still have good hearing. One of the things we did talk about is staging of tumors from the perspective of other testing that can help predict hearing preservation from a surgical perspective.
If, for instance, you have someone who has a tumor on the cochlear nerve you take that tumor out you’re going to lose hearing 100% of the time. So that may be a case where radiotherapy would be indicated.
>>Helaine: So just to follow up on that, so then the radiation would not necessarily compromise the cochlea if it was done in that way as opposed to the surgery? For the cochlea?
>> Dr Slattery:
No, it could still cause loss of hearing. My point is if the tumor is coming on the cochlear nerve, so there’s typically — we call these vestibular schwannomas, but in NF2, the reality is you can have — there’s three nerves that run through the internal auditory canal. You have the facial nerve, the balance nerve and the hearing nerve. Most of the time they come on the balance nerve but with NF2 you can get tumors on the hearing nerve, you can get tumors on the facial nerve. So if this is a tumor on say the facial nerve or the tumor is on the hearing nerve, and you do surgery, you’re going to either lose hearing, if it’s on the hearing nerve, 100% of the time. If it’s on the facial nerve you’re going to have to take it out and do a nerve graft, as Dr. Lekovic described earlier. So that may be a situation where we consider doing radiotherapy. Now, does it still hurt the hearing nerve? Yes, they’ll still probably lose hearing, but then at least the hearing nerve is intact and that’s where a cochlear implant, for instance, could potentially be something. And I think one of the things we have to, kind of the take away of this seminar, which is also always very difficult, is that unfortunately every NF2 patient is a little bit different. Whether it’s the tumor burden that they have, whether it’s the nerves that are involved that are different, their hearing status and nerve function status is different, and that’s why it really is important to have someone with expertise that can actually look at this and put all those different pieces together. Because NF2 is not just a straightforward simple — you have a vestibular schwannoma, here’s what we’re going to do.
Which sporadic tumors tend to all be much more similar than NF2. It’s just so many more things to think about. You have both sides, all those factors have to be considered.
>> Helaine: Absolutely. Very good point.
>> Dr. Kalamarides:
I have a question for Bill or Rick. Does gamma knife — what is the function of cochlear implant after gamma knife on the cochlea they have? You say it works, but I’m not really sure. What is your experience as a neurotologist? What do you recommend to a patient?
>> Dr. Friedman:
I have a few of those cases. And I have not been impressed with the outcomes. Typically, the auditory nerve is desynchronized from the tumor, and I do believe radiosurgery impacts the cochlear nerve. I’ve just not been overwhelmed by the positivities of cochlear implant. I think in many cases it may function better than an auditory brain stem implant, but it’s rarely if ever — maybe occasionally but rarely if ever functions at the level of a non-NF2 cochlear implant patient. Bill?
>> Dr. Slattery:
I would agree. When you’re comparing the cochlear implant patient with say a normal cochlear nerve that lost it from nerve hair cell loss, those patients definitely do better. But the cochlear implant is an option for patients who have had radiotherapy and lose their hearing. And so I agree, they don’t do as well. But again, as Rick said, it is better than an ABI if the tumor is in place, it’s definitely something worth trying first.
That’s a good question, you actually asked one of the questions on our list, so thank you for addressing that. One of the other questions that I wanted to ask is about the impacts of radiation before surgery. So is surgery more challenging on a previously radiated tumor? Dr. Friedman, do you want to respond to that?
>> Dr Friedman:
Yeah, I think four of us here published a paper together looking at microsurgery after radiosurgery. It’s a very, very rare case where hearing can be preserved. Mostly because hearing declines after radiosurgery, sort of the way it would having done nothing for the tumor. But the bigger issue is facial nerve adherence. And it’s not necessarily so much that the tumors are more adherent to the facial nerve after radiosurgery, although that can be the case. More importantly, I think it’s the blood supply, the microvasculature to the facial nerve. Radiation does a lot of damage to small blood vessels. That’s part of the reason we think it can stunt the growth of these tumors. And so historically, we’ve had cases where we feel very good about the facial nerve dissection. Patients may wake up with normal facial function, and then it would decline more rapidly in somebody who hadn’t had radiation. So the answer to your question is yes, I do believe very strongly that surgery after radiation is more difficult.
>> Dr Lekovic:
Can I just add one little tweak to that. I think we need to distinguish between radiosurgery for vestibular schwannoma or schwannoma in general. And the growing body of evidence that suggests radiosurgery for meningioma may be a little more effective than radiation for schwannoma. And the role of radiation I think in the management of meningioma in NF2 is in my mind anyway somewhat still ill-defined. I would recommend generally speaking that NF2 is a surgical disease. Patients have a tumor disposition syndrome and therefore radiation ought to be avoided, particularly in children, and that would certainly for a child remain my recommendation. But I think as Dr. Slattery mentioned earlier, there are times we do recommend radiation. Usually not for vestibular schwannoma, even residual. Because ultimately, the path of removal of that tumor and facial nerve anastomosis is always going to be an option. But sometimes patients will present with surgically intractable or, quote unquote, inoperable meningiomas. Again, back to Dr. Schwartz’s point, meaning the risk of removing a tumor might not be worth the benefit, or they may be contiguous lesions that cover a large portion of the brain.
In our experience, and we just recently cooperated with a consortium of radiosurgery centers who published two papers, one in January of this year, looking at meningiomas for skull based tumors, and there is reason to think that this is sort of not definitive evidence but there is definitely promise that radiation does play a better role. That may have something to do with the genetics of meningioma. The genetics of meningioma are fascinating and, and Professor Kalamarides, I’d love for you to comment on this. We know meningioma genetics vary by origin of the tumors. The meningioma that occurs above the nose has a different genetic profile — this is for sporadic tumors, all tumors — than the genetics of a meningioma in the cerebellopontine angle, which is the region where these auditory and facial nerves occur.
So there may be something a little bit different about the meningioma in NF2 given that it has a very specific genetic lineage that makes it more amenable to radiation. Professor Kalamarides, can I hijack the conference call just to get your thought on NF2 meningioma genetics and implications for treatment?
>> Helaine: You’re muted, Dr. Kalamarides.
>> Dr. Kalamarides:
You’re right, Greg but I’m always surprised by the paper on gamma knife on meningiomas. Because you see patients with 10 or 12 gamma knife surgery for meningioma in NF2, and I don’t think that proactive treatment of meningioma is a good option in NF2. Because you know, there are multiple meningioma and I’m afraid to see, you know, multiple gamma knife. So yes, for growing meningioma, okay, maybe. In old NF2 patient. But I’m not that convinced by the results of gamma knife for meningioma in NF2. In terms of okay, it works because then the patient has no surgery after gamma knife. It’s not convincing.
>> Dr. Lekovic:
No, I totally agree, and I’m not advocating — I think the role is ill defined, particularly in the same consortium we published a paper last year on convexity meningiomas, which is I think one of the situations where other centers in our consortium were doing 10 or 12 gamma knife procedures on small meningiomas of the convexity. I think all of us would disagree with that strategy. Nevertheless, It was done, and so the data is there. And the data does say that after the radiation treatments to these tumors there is a satisfactory response rate. That doesn’t mean that that’s what I would recommend, and I totally agree with you on that.
But for some skull based tumors, I think radiation has a role, not only in the very elderly or medically infirm patient. But certainly not in a child, I think we would all agree on that.
So just what you’re saying too, one of the questions we had is about some of the smaller centers, the more formal NF2 clinics may be for adults only. And so how do we figure out if we have children to get them treated, do the neurosurgeons from the adult ever operate on pediatrics, do people who work on only adults understand pediatrics? Because it sounds like there may be a difference how you may approach treating a child versus an adult. I’d be curious, I don’t know who wants to answer that, but it is a question that came up and I know a lot of us have run into that.
>> Dr. King:
I think if it’s an American audience, which of course it is, then it’s an American answer. In the UK just for interest sake, there are all of NF2 has got a single national coordination, I think France is the same, with Michel. So there are four centers that are all coordinated. So you’re not allowed to have your surgery outside of one of the four centers or at least supervised by it. And I think we would all agree whatever our differences in our philosophy. It’s a lifetime disease, you want to control the number of operations, you want to control the number of treatments, and when do you them you want to do them definitively and properly. But the American system is different, it’s a bigger country.
>> Dr . Friedman:
Yeah I think it’s a downfall in some ways, because we see patients who are unfortunately managed by people who don’t do this very often, or maybe not managed, but given advice from practitioners that don’t do this very often, and it’s sometimes very difficult to overcome the misinformation. We do not have any mandatory direction. And maybe who knows, maybe that’s the way American health care is heading, and I think in some ways it wouldn’t be such a bad thing. At UCSD we have a very, very well regarded Children’s Hospital in San Diego, but we also have a very, very skilled neuroanesthesia staff and a pediatric neuroanesthesia staff at our main hospital where we’re able to keep kids who are 14 years and older. But for kids who are younger, we operate on them, we let them recover, when they’re stable they go to the Children’s Hospital for recovery so they can be followed by pediatric neurointensivists and pediatric neurosurgeons and otolaryngologists.
>> Dr. Kalamarides: I have a question for Rick. What is your youngest NF2 patient you have done surgery? The youngest?
>> Dr. Friedman:
Six years old. We did — when I was at USC we did a middle fossa on a six-year-old, saved his hearing. As I always say to the parents, when we do cases like this and are able to save hearing it makes all of the hours of study and all of the hours of time in the hospital worth it. It’s a case of a lifetime.
>> Dr. Slattery:
If I may address, one of the issues that comes up is that the NF clinics typically tend to be the clinics that NF2 patients get referred to, and the NF clinics for the most part are 99.9 percent NF1 as opposed to NF2. So I think in that regards it’s important that the parents then have to take the responsibility of actually getting these children to an NF2 experienced individual. And unfortunately, even some of the best children’s hospitals around the country, those centers still do not see many NF2 children. So I think it is really important that they do get to an NF2 center even, you know, I think in the United States several of us review films for free and help coordinate that, you know. And then actually many times have to help fight for the insurance company to actually allow that child to come to an NF2 center. We also operate on small children as well. And I think if it is a small child you have to — small kids are not adults, but you then have the rest of the team that has experience with the post op care, the post op nurses and things like that, so that’s the important part that you have to make sure that piece is in place. But I think it’s more important from the parent perspective to actually get that child to an NF2 center that has experience seeing these children.
I think that’s one of the roles of NF2 BioSolutions, because I know, even personally, you have to be able to realize that your center isn’t the right center for you, that you don’t have the right health care providers. You have to know the questions to ask. And not everybody everyone realizes that. So they’re going to their provider and trusting in that, and not realizing that there are experts like you that they could access and get, you know, the experience that you have, and they’re trusting what they have in their local area. Or they don’t have the resources to be able to go somewhere else. So it’s a challenging thing to not have experts in all of the areas that we need.
>> Dr. Lekovic:
I would like to add one comment sort of on the tails of what’s been said already. So in general in neurosurgery in this country, I would say, for subspecialty neurosurgical problems, so not just acoustic neuroma, but brain aneurysms and other subspecialty neurosurgical problems, sort of the Venn diagram of the rarity of these lesions and that of pediatric population results in a very, very small number of patients. And given our geographic dispersion over the country, it’s really not practical, I don’t think, for most pediatric neurosurgeons to frankly be the primary surgeon on a vestibular schwannoma surgery or aneurism, there are exceptions of course, but I think patients looking for good care with a child, not necessarily for every tumor in NF2, but certainly for skull based tumors and spinal cord tumors, really are probably best served by looking for adult surgeons with that — neurosurgeons with that subspecialty interest developed as a big part of their practice. Because you’re just not going to see very many pediatric neurosurgeons in the country — no fault of their own, but that have sufficient volume of these rare tumors to maintain their skills at a level the adult would have. And what we generally speaking do here is we collaborate. So we will do a case with a pediatric neurosurgeon for pediatric neurosurgical issues that may arise, but the primary operative responsibilities are maintained by our team.
>> Helaine: Well, in the interest of time I am going to move —
>> Dr. Schwartz: — also
>> Helaine: Oh sure, go ahead Dr. Schwartz.
>> Dr. Schwartz:
Yeah, operating on a baby or very, very young kid is a very different experience than operating on an adult as a surgeon. But operating on a teenager or 12-year-old or even a 10-year-old is really much more similar to operating on an adult than it is on operating on a baby. So all of us who do these kinds of tumors not only in the United States but other countries as well we’re all totally able to handle adolescents, teenagers, preteens, just I’ll be very, very frank with you, than on a little baby. Which is not an issue with NF2.
So thank you all for all those great answers. I do want to make sure we get to some of the audience questions. So I’m going to turn it over to Gilles to ask those. But I do want one other question we had from one of our volunteers, it was a specific question for their case. They’re in South Africa. And they said their daughter has von Willebrand disease, and how will this affect her options for surgery. Because surgeons in South Africa have already canceled surgery as they don’t have the von Willebrand platelet. So I don’t know if that’s something any of you could answer or respond to, but I think we are going to get some more specific questions, so if you have any thoughts on that, that would be great.
>> Dr. Friedman:
We have done cases on patients with von Willebrand’s disease, and obviously we include our hematology colleagues.. There are a number of medications including something called DDAVP that can be given to these patients to help them with their coagulopathy. So it’s certainly doable.
>> Helaine: Wonderful. Gilles, do you want to ask some of the audience questions.
>> Gilles :
Yes, there are a lot of questions there, and also by the way, you as the panelists you can also go in there in the Q&A and type in the answer. That’s a possibility, while someone else is talking. But I noticed there are a few important ones, I think — I mean they’re all important, but I had to pick up a few here. So one about the technology that is used, maybe the imaging technologies. What are the newest technologies that really help you to do better your job, especially in imaging techniques. Are there things we as patients would have to look for or be prepared for with type of imaging
>> Dr. Kalamarides:
Yes, I’d say if you can see the facial and cochlear nerve on pre-op it would be fantastic. To imagine the difficulty of the surgery and say okay, it will be easy or difficult. Then to decide to do surgery. I think that tracking of the cranial nerve would be fantastic. But there are some studies, but it’s not really working. You can be confident enough to go to the surgery based on this image, but I think it will improve the results of surgery.
>> Dr. Friedman:
In our program here at UC San Diego, one of our colleagues has proprietary data on labeling nerves. So it’s beautiful, they’re done preoperatively, they’re in clinical trials right now for tumors of the head and neck. But nerves can be mapped out fluorescently and seen under the operating microscope, the very microscopes that we use. And as soon as that clinical trial completes, we anticipate it will be FDA approved and then we’re going to start using it in the cerebellopontine angle. So if you can imagine the facial nerve lighting up fluorescent green during surgery, which I think certainly will help.
>> Dr. Slattery:
This reminds me of a question, or actually a little bit of history, and I was thinking about this with the ependymomas. So in the late 1990s the U.S. Department of Defense authorized a natural history trial which I was the principal investigator, and of course Manchester group, Paris group and centers around the United States and around the world we all kind of came together, and it kind of got back to your first, Helaine, your earlier question, how do we communicate between centers. That was one of the first attempts with NF2 where we brought all the different centers and started communicating together. When we first started looking at MRI scans of the neck, we’d say there’s a faint imaging we’re not quite sure what it is in the cervical spinal cord. That turned out to be ependymomas that we were looking. But the imaging study at that time was not really good enough to really define the ependymomas very well.
So the good part is there’s been this kind of progression of improvement of studies that have happened over the years, so that now as an example, as Dr. Kalamarides was mentioning, we actually can do studies to look at the hearing cochlear and vestibular nerve. But that means specifically in small tumors, and that gets back to the staging concept. So I think from just a bottom line study what should be done, as I mentioned earlier, you need a full head, internal auditory canal, full spine. Past that, depending on what tumors, the tumor burden that the person has, is when we start looking at specific studies such as brachial cleft studies, peripheral nerve studies, and then also studies within the head depending on what that individual person needs, and those are subsequent studies that need to be addressed. But that’s again where it gets into that expertise of an NF2 center looking and saying aha, you really need these special studies to be done. So it’s not like we can make this broad statement and say hey everybody needs this. I think there is a minimum that everybody needs, but then it’s also tailored on the individual person.
Thank you. And another question about the growth pattern of the tumor. From your experience, or your research, did you really identify some growth pattern for the different types of tumors in NF2? So based on the age, or on what’s happened, what is happening with the patient, since last time?
>> Dr. Kalamarides:
From a meningioma we have seen that each meningioma is growing differently. It’s not based on the mutation. So the type of mutation, we give you a number of tumors. But after that, the growth of every tumor is independent. So it’s a difficulty, NF2 is giving some tumor — but yes, it’s not linked to the NF2 mutation. The growth of the tumor. It’s — meningioma, certainly.
>> Dr. Slattery:
I think there are some times where we do know that tumors grow. So sporadic tumors definitely grow during pregnancy many of them grow during pregnancy, hopefully NF2 this has been discussed with them about the genetics and whether or not to have children. But puberty tends to be a time where we’ll also see growth of these tumors.
Okay, thank you. It was mentioned by you, Dr. Slattery, about second opinion, is it something common for all of your clinics to review the CD of patients that are not your patient yet, maybe? But can they submit their CD and get the second opinion from you?
>> Dr. Slattery:
I think UC San Diego does this, House has done this for years, we started doing that in about the mid-1990s. I can’t comment about what’s being done with UK or Paris, but they have centralized centers, which is helpful to make sure the patient actually gets to a center that has expertise. But in the United States, I would encourage people to actually send the studies to, you know, one of these centers. To have another opinion, where you actually have people who can actually talk with you about kind of pros and cons of the different things. We have an NF2 conference once a month where we actually review different studies, to help manage, because there are so many different factors that play a role, and make sure that people are getting comprehensive care.
Thank you. And another question about the recovery after surgery, so there have been a few questions about sometimes hard recovery after vestibular schwannoma surgeries. What is your input regarding that, what are the different kinds of problems that we might face after a surgery?
>> Dr Friedman:
Children are — I’ve found children to be incredibly resilient. So after vestibular schwannoma surgery obviously there’s pain, like from any surgery. There’s disequilibrium, because you’re removing a balance nerve tumor. But the child brain is far more plastic than the adult brain, and these kids — these kids recover I think dramatically well. I have a picture that I’ve saved of a young girl that when Dr. Hitzelberger was alive he and I did, we saved hearing on both sides, so obviously removed vestibular function from both sides. She sent me a picture of herself balancing on a tightrope at camp. So kids are remarkable in their — I won’t say regenerative capacity, but in their ability to — the ability of the brain to redirect information to other centers when there’s a deficit.
>> Giles: Thank you. Any other input about —
>> Dr King:
I think that — age as we’d so much like is a key thing, but in an operation that goes straightforwardly one would be hoping to be back at work at six weeks, but it does depend — obviously some people with NF2 have already gotten neurological problems that may take a greater time. But six weeks would be the normal thing. The balance thing is a very interesting one. If you operate on someone and you lose — you will lose their vestibular nerve obviously, because the tumor is growing on that. So that can make them terribly unwell, terribly seasick afterwards. We started doing a thing — I don’t know whether any of my other colleagues on the panel are doing this, are giving Gentamicin beforehand. And as a simple neurosurgeon I found it wipes out vestibular function over the course of three injections, and just looking at something that like most ENT I don’t really understand, it’s absolutely remarkable about how rapidly they mobilize. I hate to give credit to ENT surgeons, but it is a miraculous thing that they do.
>>Gilles: Good. Thank you. And anyone want to close down the webinar?
Well, I would love to have all of you, before we wrap up, tell us one piece of advise you’d give to patients or parents making a decision to have surgery and choosing a surgeon. Because we know for all of us it’s a complex and emotional process. So Dr. King, would you start, and just give a piece of advice, then we’ll just go around and have everybody give a final word.
>> Dr King:
Yeah. See someone who knows what they’re talking about. Recognize that even amongst that there will be debate. So you won’t necessarily, if you see the right person, you won’t necessarily get a black and white answer, you’ll get a balanced view. The consultation is long, probably multiple, to discuss the pros and cons. But see someone who knows what they’re talking about, and who knows the disease.
>> Helaine: Thank you. Dr. Kalamarides.
>> Dr Kalamarides:
I think except some cases you have time to discuss, to see maybe many doctors, so take time to think about surgery and decision. Important decision.
>> Helaine: Dr. Schwartz.
>> Dr. Schwartz:
Yeah, a lot of times these decisions are very difficult. And different people say different things, and frankly, what I would say to a patient on one day versus another it’s such a close call it may be different based upon what my feel — you know, how things seem that day. But as I’ve previously said before it’s a 10,000 hour principal, which is you need to see somebody who is thinking about NF2 specifically. Not every surgeon every neurosurgeon every neurotologist has 10,000 hours in their specialties, but they’ll think they’re an expert, but you don’t want somebody who has 10,000 hours just on everything, and frankly even 10,000 hours in acoustic neuromas isn’t enough. You need somebody who has got 10,000 hours in NF2.
>> Helaine: Thank you. Dr. Friedman.
>> Dr. Friedman:
I concur with Marc. Also I think one way to know — I think patients need to feel empowered to ask questions. How many of these have you done, how many do you do a year, do you have a comprehensive program. Is my child or am I as an adult going to be treated holistically. Those are the kind of questions that you can ask, and the answers are — they can be subtle, and I think one can determine pretty well how experienced a center is. Because somebody asked on here how do we know which centers, and are we planning — you know, is there a plan to have centers of excellence in the United States. It’s such a difficult question, because it’s tough for anybody to swallow the possibility that they may not be a center of excellence. You know, across the country. That’s partly why we started the program we have, where we have an ease of patient access, because these questions should be answered and they should be answered fully and they should be answered early on in the care of this very, very delicate disease.
>> Thank you. Dr. Lekovic.
>> Dr. Lekovic:
Sorry, I had to unmute myself. I would agree with all the sentiments that have been echoed. And I would say that, you know, particularly — as I understand this conversation we’ve had an emphasis on pediatric patients and I understand why that is. But I think there are very, very few NF2 programs that bridge pediatric to adult, they tend to be sequestered and we haven’t really addressed that in great deal except in passing. It’s really advantageous to seek out advice that is comprehensive all over the length of the age of the patient. But also, comprehensive in doing the spinal tumors, peripheral nerve tumors, meningiomas, the whole panoply of pathology that occurs. And because these can interact in ways again which we just touched on tangentially with tandem lesions, et cetera.
>> Helaine: Thank you. And Dr. Slattery.
>> Dr. Slattery: So I think maybe three things. Number one, is make sure that you — again I said this earlier, but I see that it’s not always done — is make sure that the entire body has been evaluated for NF2. So that needs to be done at the early stages of first diagnosis. Number two as has been said is there’s not a rush. Take your time, understand the disease, get some second opinions. And then along that line is number three is reach out to some NF2 centers, such as represented here, to actually have — you know, a discussion. You know, it’s kind of our mission that, you know, we talk to patients from all over the world that send in their studies and, you know, we don’t charge them for it but it’s also a passion because unfortunately we see too many patients who have rushed into things and have had unfortunately poor outcomes or bad decisions that have been made. So take the time, get some expertise, visit a center, communicate with a center. I mean, obviously with — you know, mechanisms we have now you can transfer your MRI scans easily over the internet, you can have video calls over the internet. The world is getting smaller in some respects, which this pandemic there are maybe some good things that have come out of it which is hopefully going to be helpful for patients feeling more comfortable at reaching out in these type of venues.
>> Helaine: Wonderful. Well, thank you so much, so much for joining us. We really appreciate all of your expertise and taking time out of your busy schedule to speak with us today. I feel like we could have kept going and asked so many questions. I thank all the participants for our questions, we’re sorry we couldn’t get to everything, but I think we covered a lot of ground today so we really appreciate it. And we hope everyone learned something valuable. So please visit us at http://www.NF2BioSolutions.org for more information. And thank you again, and be well.
>> Dr. Friedman: Thank you so much.
>> Giles: Thank you very much.
>> Bye bye. Thank you for hosting.
>> Thank you.
>> This was great, you did a great job, Helaine.
>> Thank you.