NYU Conference 10-27-12: Section 1: Neurosurgery

Next Topic: Section 2: Neurootology

Topic Speaker

Dr. John Golfinos
New York University, NYU
Chairman of the Neurosurgical Department
Professor in Otolaryngology
Board Member of the Children's Tumor Foundation

Topics

1. Management of NF2
2. Radiation
3. NF Clinics

Neurosurgery

Carole Mitchell: I'm going to open our NF2 session with our keynote speaker, I like to say. Dr. John Golfinos, NYU. He's the Chairman of the Neurosurgical Department here at NYU. He is a Professor in Otolaryngology. He works very closely with Dr. Tom Roland. I apologize, Tom. He's not here. He's in Germany. Otherwise he would have been here with us today too. Without further ado, let me introduce Dr. Dr. John Golfinos, NYU. (Applause).

Dr. John Golfinos, NYU: Let's just check a few things first. I'm a native New Yorker, born and raised, which means I'm going to speak really quickly probably. You let me know at any point if I'm going too fast.

Dr. John Golfinos, NYU: Let's check the lighting. Can everyone see? The CART is coming up okay? Great. And then if there's any problem with the sound also, let me know. I will try and speak as close to these microphones as I can.

I've done this before. The first time I did this, I came out here as a young neurosurgeon at the time. I don't think of myself as young at all anymore. I came out and I gave a talk that I thought was really sophisticated. What I clearly didn't appreciate is that I was talking to a room full of people who are experts in the field of Neurofibromatosis Type 2. That was a little embarrassing. I've learned since then that I think my job here is hopefully to give you some new things. Today we're going to do something like this. This grew out of a talk I delivered in Germany last year. It's about the real problems with surgery for NF2. That's a real problem for surgeons to talk about. Most of the time we talk about how great surgery is. But today we're going to talk about; the limitations in surgery why this is such a complicated decision in NF2, more than any other topic that we deal with - why it's such a difficult decision when you're going to do surgery and what type of surgery.

Dr. John Golfinos, NYU: Okay. Here we are on the East River, it's going to be under water in another two days. I also put up my disclosure slide. I receive a honorarium/pittance from Medtronic. I'm an investor in a company called ViewRay. They're trying to provide a new type of radiation. I am a surgeon. I guess that's a conflict since I'll be discussing surgery. But I'll be talking about all treatments by modalities (factors and circumstances that cause symptoms). I forgot to put on here, I'm also a board member of the Children's Tumor Foundation which is a nice thing. I don't view it as a conflict, we're all in the same boat together. Everything I've done in the 17 years I've been at NYU has been made possible by all these people. Tom Roland, the Chairman of the ENT Department here at NYU. Jessica Schafrick, a Nurse Practitioner for 12 years now. At the end of the schedule, you'll meet all of them today. Carol has been instrumental in that in getting coordination for our patients. And Ashwatha Naryana and Bernadine Donahue are our Radiation Oncologists.

1. Management of NF2

Learning to manage NF2. Confucius said,
"By three methods we may learn wisdom. First by reflection, which is noblest, second by imitation which is easiest, and third by experience which is bitterest."
If we can just sit there and think about it, it would have been easy. But we have to do it. The experience that we've earned in NF2, some of it has been bittersweet. Fine words butter no parsnips.

First thing, make sure we're talking about the right thing. I put this up for my residents and I put this up for other doctors. Probably everyone in this room has learned, as you go through your medical care you'll find early on a lot of doctors have no idea what the difference is between the two. NF1 is in the room next door, the disease of optic gliomas, malignant peripheral nerve sheath tumors. NF1 is really a pediatric disease. These are children.

But we're here to talk about NF2 which is a disease of bilateral, both sides, vestibular schwannoma, tumors on the balance nerves that come out of the brain cells. It's also a disease of the meningioma which we're going to talk about. People can have cafe au lait spots. They're not as common in NF1 but they do happen in NF2 as well. Frequently end up doing surgery and it's a disease of hearing problems.

These are the diagnostic criteria for it. Manchester Criteria. I bet everybody in this room is familiar with these. Hallmark is a first line bilateral vestibular schwannoma. But any first degree relative that has NF2, unilateral vestibular schwannoma, that makes the diagnosis. You can see on the bottom line, anyone with multiple meningiomas, and any type of schwannoma and unilateral vestibular schwannoma, is diagnosed as having NF2.

Why is that important? Here is a patient that we saw early on referred from elsewhere in New York City. This was sent to us as a patient with NF2. The patient had had surgery on the left side before. This is actually the bone of the skull is this black area. You can see it's missing here. The surgery was done on the left side. And there's this large tumor sitting next to the brain stem. So she was referred to us as she was going to lose her hearing. What can you do for it? If you look closely it's not a Schwannoma. It doesn't go out into the canal that the nerves travel into. This is a meningioma. This is a patient with multiple meningioma. Entirely different disease. This tumor was removed. We could preserve the hearing because it didn't involve the nerves coming out of the brain stem.

What we should -- I put this slide up just to say it once. Age and diagnosis is the strongest predictor of diagnosis of NF2. But there are additional predictors. The presence of meningiomas in the skull. Type of treatment center you go to is an independent predictor, and the type of mutation that occurs.

I put up this list, and we talk about some of these things today. Why is surgery so difficult in this disease? We already covered number one. If you think you're covering NF2 and you're not, it's making a wrong diagnosis. Number two, and it's a really important one, underestimating vestibular nerve tumors, and overestimating your ability to save the hearing. That's something that's changed in the last ten years in neurosurgery for NF2.

Underestimating facial weakness or what happens. Underestimating the degree of involvement of the facial nerve. Facial neuromas are common with this disease. I think we realize now far more common than we thought. You see patients with bilateral facial palsy, and we try to avoid that. Not to be aware of other tumors that are part of the cell, especially the tumors on the lower cranial nerves, responsible for swallowing, keeping the air way open, for voice.

Other problems: Not planning for the next operation. There's usually going to be a next operation in NF2. Not using MRI compatible things. Not leaving behind things that prevent the patient from having an MRI. That's a problem. We worry about the veins. When people think about blood in the brain, we think about blood getting into the brain. Everybody knows what a stroke is. Blood doesn't get into the brain. But we're more concerned in NF2 with the blood getting out of the brain. These meningiomas will affect the veins and sinuses. When I say sinuses, most people think about the air sinuses around your nose. I'm talking about big pools of blood as they come out of the brain and how they get out. The problem is that patients with NF2 will have multiple operations. When you do that if you're not careful you can reduce the size of the skull. When you reach adulthood you have a certain volume in the skull. After multiple operations it's possible to reduce that and that causes problems too.

The lure of radiation. We'll speak about that. I think the last problem is one hopefully we're addressing today in this meeting which is a lack of comprehensive care. Not being able to get to an NF2 Center, having careful follow up, being able to connect with a clinical coordinator and communicate with your physician.

So how do these vestibular schwannomas differ? We do about 60 vestibular schwannomas a year at NYU. The vast majority of those are in patients who do not have NF2. Those are relatively straightforward cases, tend to be smaller tumors, and tend to come out relatively nicely. NF2 is a different story. You can see on the slide, NF2, vestibular schwannoma presents at an earlier age. Remember these are tumors on the balance nerves. They tend to be larger in size. Usually patients with NF2 have worse hearing function before the surgery. And these tumors I can tell you in our experience are more adherent to nerves and we have a lower rate of getting the whole tumor out, especially when we're worried about that patient and we're trying to preserve their hearing.

Therefore in NF2 we have worse hearing outcomes and greater rates of facial nerve injury. And because we're often leaving some tumor behind so we don't injure the facial nerve, that means the risk of tumor coming back is higher.

There have been some studies, Gareth Evans did this paper looking at how else are these tumors particularly different than NF2, and what they found is the growth rates in NF2 can be highly variable. Meaning the tumors may not grow for some years and then suddenly take off. One of the good things that has come out of that is growth rates tend to decrease with increase in age. As patients get older, the growth rates tend to slow down.

What we do in terms of hearing preservation, I can tell you now compared to when I started 17 years ago, our confidence in being able to save hearing with surgery alone with NF2 has gone down. We compensate for that by being better at picking patients. The ones we're really trying to save the hearing nowadays tend to be early on with very small tumors and we'll go for it on one side and attempt to get the tumor out and save the hearing. That's the first line you see there. But it's really a conversation with the patient and their family. Do you really want to take this risk? Do you want to go for it because you may lose your hearing on that side on the day of surgery. You may wake up and be unable to hear in that ear.

Some of the other strategies that we tried is just doing a subtotal resection. We've had mixed results with that. I can tell you more and more now, especially in patients that have lost hearing on one side and only have (inaudible) hearing on the other, tend to go for conservative management, you'll hear about drug management until the hearing is lost on that side.

What about the facial nerve? As I mentioned earlier on, bilateral facial palsy is difficult with our patients. We try in any way to repair that or improve it. That can mean at the time of surgery we know the nerve is lost, we'll do this on the upper and bottom. Remember when you're taking nerve grafts in NF2 you don't know if the nerve is completely (inaudible) not always so involved. You have to be careful with that. The best way to fix a facial nerve is to actually take the nerve that goes to the tongue, the 12th cranial nerve and to hook it into the nerves that go to the face. The brain reprograms itself. Patients think about moving their tongue and it moves their face and they generally learn to do that well. You get a good nerve supply into the face. But the difficulty again is this is NF2 and that 12th nerve may have a tumor on it as well. We have to be very careful of that.

Dr. Samii was one of the surgeons with a large experience in Germany, similar to our own. A large number of patients. He was one of the people that pointed out that patient education is probably the most important determinant in this disease of outcome and patient satisfaction, which is what we're really aiming for as surgeons. We've sort of come to accept that we've gone against the idea of the surgeon causing hearing loss. It's not really acceptable to us anymore. We talk about facial nerves. For all these reasons we hope patients get to the NF2 Center early on. So we can have these talks and conversations.

These are some typical problems that we see. Here is a patient who lost hearing on the left side and lost facial movement on the right. We're looking at an MRI scan. This is front, this is back. Radiologist did this to us so we're stuck with this being right, this being left so you're looking at it from the bottom. It's not the way a normal person would have done that but the radiologist did it that way because they're not so normal. What you see are the two big tumors of NF2. But there are other tumors around it. These little white spots are other tumors on other cranial nerves. This is after surgery on the left side. Large tumors taken out. Still the patient had hearing on the right. So we did the left side where the hearing was (inaudible). Then on the right side where there was facial nerve weakness we did that 12th nerve to 11th nerve, tongue nerve to the face graft. Because there was only hearing on this side we didn't operate again. You can see the tumor got larger and it got larger rapidly despite drug treatment. That left us only with the option of taking it out. This is the fat graft we took behind. You can see the tumor is gone off the brain stem. We removed that tumor. It was really two tumors, a tumor on the balance nerve and one on the facial nerve as well.

This was an 18-year-old cheer leader referred up to us from Florida. Same idea we see with bilateral tumors. This is what's so difficult about NF2. The brain stem is caught between them. You can see tumors on the other cranial nerves around it. Again that's the same patient looking from the front now. These are all little tumors on the other nerves there.

What is the right followup for patients? Currently we're recommending every six months getting an MRI scan of the brain, and and MRI scan of the spine. But I tell you those recommendations are still controversial. Depends on what health care system you're in. How many resources is the country going to devote to things like this? The reason we say every six months is we've seen tumors take off on a moment's notice. So we've had patients who have gone a year without an MRI scan and have come back with a large tumor. So we think that at least every six months is a reasonable thing to do.The United Kingdom, they do CAT scans only every two years. Involves a radiation dose. MRI scan of course involves no radiation.

With this particular disease, vestibular schwannoma is most often first presenting the tumors. Our surgeries have gotten better. Our patients are living longer. The downside is it's given time for tumors on the other nerves to grow. So we deal more with problems with swallowing, voice, things like that. Let me say a few words about meningiomas, the other big tumor in this disease, and probably one of the more frustrating ones for us. As we said the defining tumor for this diagnosis. It comes to dominate the late phases of the disease. Meningiomas for this are very different than others. It's a very common brain tumor. You find it five times more in women than men. But with NF2 these are different meningiomas, just like the vestibular schwannomas are different.

Presence of intracranial meningiomas is a predictor of how a person with NF2 will do. (Inaudible) This is a paper that was done by Harry Parry. I put it up here just to show that only 40 percent of these are called regular run of the mill meningiomas. 49 percent are atypical. 11 percent of the time they're taken out are anaplastic, which used to be called malignant. (Inaudible). These are the strategies we use. We're always thinking about the next surgery. We have to deal with the surgery we did before and the need for an MRI scan afterwords.

Our strategies in terms of meningiomas were generally treating only the symptomatic ones. To me that means also radiologically symptomatic, if it looks like it's causing a lot of swelling on the MRI scan, that counts for the swelling and compression on the rest of the brain. We're always as I mentioned before always looking at the veins around this, are we going to damage the brain's ability to drain itself by taking this tumor out? That's a problem.

We're always worried about making the skull too small afterwords. We're always trying to keep the skull in its original shape after the surgery. And of course, the first principle is don't do any harm if at all possible. What we have to consider, the skin incisions that we use, the flaps that we make. We're sure that we can do another surgery if we need to. We worry about spinal fluid getting trapped. We call that hydrocephalus. I mentioned the venous problem, the problem with the veins. So we're always particularly concerned about that.

This is an example of a gentleman with NF2. You can see this large tumor in front. This is front, back, right, left. You can see it on this image. You can see there's other meningiomas in the brain. There's a large one here, another one back here. This is the same image. This is from looking further up, and from the side. This was that tumor that we were looking at before. Typical for NF2 we have to get past this tumor to get to this one. As you can see, this tumor is actually causing a deformity of the skull. This is a tumor that has percolated through the bone. Meningioma will do that, and it's caused swelling of the bone up here. This is a lump you could feel on the skull. This is what the veins look like.

I know you're not familiar with regular angiograms. This is a picture of all the veins of the brain. If you look, it looks like varicose veins in the leg. That's exactly what happens in this disease. The reason is normally you have veins draining all the way over the top and going out the bottom of the skull. But because of the meningiomas along the top, the blood can't get out. So it has to find other ways out of the skull. And this one is coming down the skin.

This is a before and after picture. Get in there and get that out. But more importantly, this is from the side. Again, getting past these tumors to get it out. When we recreate the skull, we restore the curvature to make sure the skull stays the same size. Just another example of getting there the right way. This is before and after. And again, look at the other tumors that are here. Again, this is another example of getting that big bone out but saving the curvature of the skull.

2. Radiation

If surgery is so difficult, why don't we just radiate everybody? There's a really good reason why you shouldn't in NF2. There's still some controversy about this but I don't think there should be, to be honest. There's probably at least a 14-fold increased risk of malignancy for radiated vs. Non-irradiated NF2 patients.

Here is a study from Gareth Evans. These are other studies. This study from Rowe, a gamma knife study. Gamma knife is a type of radiation surgery that is giving radiation one big dose. They reported this because they thought their results were really good. They thought only half the patients had growth in their tumors at 8 years follow up. Yeah, but that means the other half did. Those are the people that we have to operate on after surgery. For us this is not good enough. Radiation doesn't do what you want it to do. They saw it as the glass is half full. We see it as half empty with radiation. There are several reports of rapid growth of radiated tumors. Here is one of them. Malignancy in a vestibular schwannoma. 8 reported cases in the literature, four had radiation, four did not in this review.

Here is another review. Patients from the University of Toronto. In regular patients with vestibular schwannoma, regular sporadic everyday acoustic neuroma. It's very rare to see radiation caused malignancy. But the patients with malignancy were patients with NF2. 12 time higher rate than expected. And that includes not just a malignant acoustic neuromas, but malignancy (inaudible). Here is another review. 26 cases in the literature. 13 of those were in NF2 patients.

This is why we think that radiation can have unpredictable results also even within the same patient. This is a patient who had gamma knife. Hopefully you're getting used to looking at these MRI's by now. This is right, left, front, back. You can see a big tumor on the left. A tiny one on the right that got radiated in 1988 when the patient was 19 years old. Lost hearing three months after the radiation on that side. (Inaudible) on the left side. And 5 years later was radiated on the left side. And two years after radiation lost the hearing on the left side. Didn't go for an MRI scan for nine years and then came back to us with a big tumor sitting on the brain here. This is the size of the tumor. Believe it or not this is a post operative scan. The thing was cemented to the brain stem. We didn't get the whole thing out. This is years later, the tumor is growing, two years later. Then you can see even after that it continued to grow, and the patient passed away from this tumor. This is a pathology report, it was called an atypical schwannoma. It's no longer a run of the mill vestibular schwannoma after radiation.

We think that radiation causes poor hearing preservation rates, poor control rates. You heard earlier on that people who had a defect in the NF2 have difficulties stopping the bad effects of radiation. Then there are questions about patients, do you still put in the auditory brain stem implant, the cochlear implant? And in our cases at least, it's been harder to save the facial nerves in patients who have had radiation before when it comes time for surgery.

What about patients with meningiomas? Not that useful. They tend to be thin things that cover the entire surface of the brain. This is looking from the front. Top, bottom, right, the ear lobe here, and left, the ear lobe here. This thin white thing is a meningioma covering the entire surface of the brain. Using radiosurgery doesn't seem to work.

3. NF Clinics

Just to finish up, I think obviously people have said this enough today. I want to say it one more time. Having a dedicated center enables clinical trials. It's probably the most important thing. There are as we heard before maybe 8,000 people with NF2 in the entire United States, in a population of 300 million. There are only 2,500 neurosurgeons in the United States. Hopefully people can get to places where they can share their knowledge and participate in clinical trials. That's our center here.

You heard -- these are the people who get involved with our patients. Neurosurgery, both the head -- I don't even do the spine. We have spinal surgeons cover that, Neurotology, ear doctors like Dr. Roland, Rehab, medicine doctors, Orthopedics for some peripheral nerve tumors, Ophthalmologist, Neuropsychologist, Geneticist. A lot of different specialties.

What's changed in the last five years? Surgery is less common but an intent to hearing preservation. Because we also recognize that when we do that, these patients recur. We think we take out tiny tumors, we still see them come back later. The risk of return is higher. And then our recognition that trying to save the hearing and take the tumor out at the same time is very difficult. We continue to use the Auditory Brain stem Implant and there has been some increased use of Cochlear Implant. The tumor is sitting there, just as a way to retain hearing for some time until the tumor finally has to come out. More attention to preserve the facial nerves. Probably the last and most controversial thing is drug management prior to surgery? It's a lot trickier than it sounds, believe it or not. Those chemotherapies, the drugs that we use, tend to shut down tumors. They also tend to shut down the cells that repair the skin. So you get wound infections. You can't operate on someone that has had a drug for six weeks. Timing it becomes tricky. We can see patients progress when they stop the drug and they have to wait six weeks, so the tumor can progress.

The other problem is patients want to hold onto hearing. We understand that. But tumors can get really large and you're balancing saving the hearing against saving the facial nerve. For low amounts of hearing, you really have to have the discussion about what's our number one priority now? Follow up is everything in NF2. Multi-specialty management and surgery I think remains the optimal treatment but only done when necessary.

I want to say one last thing. I'm looking out across this room and there are a lot of my patients in this room. That's about the most humbling thing you can expect as a surgeon. Thank you very much. (Applause). I'm on call for Bellevue Hospital, believe it or not, today. So.

Carole Mitchell: We'll give you five minutes to ask Dr. Golfinos some questions.

FROM THE AUDIENCE: If I have facial nerve reconstruction through the tongue, can you operate again?

Dr. John Golfinos, NYU: Yes.

FROM THE AUDIENCE: I have two questions. First, are there enough data on the effectiveness of Proton Radiation Therapy and its rate of malignant transformation? And second question, what more can you tell us about the use of Cochlear Implants without removing the vestibular schwannoma? Just piggybacking over the tumor?

Dr. John Golfinos, NYU: I'll leave the Cochlear Implants for later on. Let me say something about Proton Beam. You understand all the forces involved here. To build a Proton Beam Center it costs over 100 million dollars in some cases. Proton Beam is another type of radiation. Normally when we radiate people we use photons, same thing in these lights, only really high energy photons. That's what we call radiation. Gamma radiation for the Gamma Knife. Creating photons that have really high energy. Plain old radiation. Protons are a little different. They're a slightly larger particle but there's still radiation. All radiation is radiation. It all works the same way, by damaging the genetics of the cell. By damaging the DNA. So it's hard to understand how there would be a different risk for causing malignancy. Probably the only difference is in patients who get either Radiosurgery, which is one dose one time, versus Fractionated Radiation, people are trying to do that as five doses. Down at Thomas Jefferson they do 33 doses. And the more doses you have of radiation, the higher risk of malignancy later on. But in patients with NF2, all radiation is radiation. Same type of damage.

One last thing about that, the younger you are, the higher risk of radiation induced malignancy. For everybody in America, but especially patients with NF2.

FROM THE AUDIENCE: Have there been studies on the drugs?

Dr. John Golfinos, NYU: We're going to talk about that today.

FROM THE AUDIENCE: Is a normal life expectancy if you're keeping up with everything not reduced?

Dr. John Golfinos, NYU: Ask me in 20 years. Hopefully that's what we're all here working on. That's what we're trying to do. We're trying to take care of the tumors in any way possible. I can tell you this, the good news is we're doing far better than even when I started 17 years ago. Hopefully that progress continues.

Carole Mitchell: Thank you, Dr. Golfinos. (Applause).

FROM THE AUDIENCE: One more question. In Winthrop Hospital they are using a Carbon Dioxide Radiation treatment, what are your thoughts on that for treatments for people with NF2?

Dr. John Golfinos, NYU: Probably not. All radiation is radiation. Doesn't matter which particle you use. Carbon nuclei are another type of radiation particle. Radiation all has its effect the same way by damaging the genes inside the cell. In NF2 there's an inability to repair that damage.

Carole Mitchell: Thank you again.

Next Topic: Section 2: Neurootology