GAMMA KNIFE PROCEDURE PITT COUNTY MEMORIAL HOSPITAL GREENVILLE, NORTH CAROLINA August 15, 2007

Transcription

1 GAMMA KNIFE PROCEDURE PITT COUNTY MEMORIAL HOSPITAL GREENVILLE, NORTH CAROLINA August 15, :00:14 ANNOUNCER: Welcome to Pitt County Memorial Hospital in Greenville, North Carolina. Over the next hour, you'll see a Gamma Knife procedure. The Gamma Knife allows non-invasive brain surgery to be performed in one session while sparing tissues close to the target. Through stereotactic radiosurgery, physicians can ablate or destroy intracranial lesions by focusing multiple gamma rays on a precisely defined target. The technique requires no incision in the scalp or skull and no need for general anesthesia. In most cases, patients experience little pain and are back on their feet within hours. OR-Live makes it easy for you to learn more. Just click on the "request information" button on your webcast screen and open the door to informed medical care. Now, let's join the doctors. 00:01:04 BARBARA E. LAZIO, MD: Good evening. Thank you for joining us this evening for our Gamma Knife webcast. I'm Dr. Barbara Lazio. I'm a neurosurgeon and the director of the Gamma Knife center here at Pitt Memorial Hospital in Greenville, North Carolina. Tonight, we're going to be showing you a Gamma Knife treatment of a patient with a meningioma, which is a benign tumor of the lining tissue of the brain. Joining me here in the studio this evening is Dr. Hyder Arastu. He is one of our esteemed radiation oncologists. He's faculty at the Brody School of Medicine, which is affiliated with Pitt Memorial Hospital. He's my right-hand man and one of the essential members of the Gamma Knife treatment team. He and I or one of the other radiation oncologists and I will often work together to treat the patients with the Gamma Knife. And then the other essential member of the team is our physicist, Dr. Helvecio Mota. His job is very important in the quality assurance of our high-precision instrument. He makes sure that the Gamma Knife is doing what it's supposed to be doing, which is delivering a high dose of radiation very precisely to deep places in the brain. Just a little background information on the hospital and institution. This is Pitt County Memorial Hospital, it's a I'm sorry, a 760-bed facility in eastern North Carolina. This is an academic medical center. It's associated with the Brody School of Medicine and East Carolina University. This is a tertiary medical center. We have every subspecialty that you would need. It's also a level-one trauma center. I came here six years ago out of neurosurgery training, and I was charged with the task of bringing stereotactic radiosurgery with the Gamma Knife here. We investigated several different kinds of radiosurgery to bring here, and we felt that the Gamma Knife was the most precise and the most reliable tool, and since we opened in October of 2005, we're proud to have treated approximately 200 patients. Today's case is a very nice lady who actually is working in one of the hospitals in the neighboring community. She had surgery for a sizable meningioma in She presented to her neurosurgeon in this other community with headaches and some speech disturbances. She was diagnosed with the meningioma and had surgery and recovered quite well. And her headaches resolved, her speech disturbance resolved,

2 and she was living a normal life. Recently, she developed headaches again, and follow-up images showed that she had a recurrence of her tumor. And this recurrence was in the area where she had surgery, but along a very essential structure within the brain, the sagittal sinus. This is an area that's very difficult to get a complete removal of a meningioma, and so her surgeon and I decided that it would be better for her to have a non-invasive procedure rather than open brain surgery like she had initially, and she was sent to me. Now, this patient was referred directly to me. Patients can also be referred directly to the Gamma Knife center through our nursing staff. Our assistant nurse manager Henry Masqueranas will -- will take s and referrals from physicians, from patients, and get them to the Gamma Knife team. Today's patient saw me in the office. I felt that she was a very good candidate and she was interested in pursuing the Gamma Knife treatment to halt the growth of this tumor, and I took her case and discussed it with the rest of our Gamma Knife treatment team at our weekly multidisciplinary conference. Now this is a -- a treatment that involves multiple different specialists, and I've introduced our radiation oncologist and radiation physicist. We -- we generally every week have a meeting which involves our -- our nursing staff, the physicists, social work, administration, neurosurgeons, usually three or four of us. Usually three or four radiation oncologists, and a neuroradiologist. So there's a lot of expertise involved, and every patient who comes through our system gets a few second opinions for free before they get a treatment. And we think this is very important, and this is sort of an internal quality assurance so that we're certain that we're treating the right patients, and certainly every patient who's presented doesn't get treated, but this patient today was a very good candidate. So when we decided to treat her, she was brought in to the Gamma Knife center, and we'll show you sort of the sequence of events that occurred. 00:06:17 After check-in, the patient gets an IV. We give her a little bit of sedation. Now, most people to have this procedure are wide awake with just a little bit of valium or maybe a little bit of IV for sed-- to make them relaxed. But they can talk to us. Usually we have, you know, good conversations and make jokes and try and keep people relaxed during the procedure. I'm just, right here, prepping her scalp with some chlorhexidine because this is a sterile procedure. And we're going to apply a stereotactic frame. This is a Leksell Gamma Knife. Here she's getting the bee sting. This is just a local injection of lidocaine, and here's the Leksell frame. This is ostensibly the most important part of the whole procedure, that the patient's head absolutely has to be fixed in space because we're trying to very precisely deliver this radiation to a small area in the brain and avoid reaching normal parts of the brain. So if you -- if you can fix the patient's head in space and know exactly where it is in relation to the coordinates on this frame and on this fiducial box that's attached to it, then you know where the tumor is and you can treat just the tumor and not the other parts of the brain. These are stereotactic pins. They're a titanium alloy. They are inserted just through the scalp. They make a tiny pierce in the scalp and then lodge on the outer table of the skull. This is probably the worst part of the procedure for the patient. The bad part lasts about a minute, and that's why I do it and Dr. Arastu doesn't do it. He usually makes me do the hard part, so here you see him in the MRI suite, and he can talk to you a little bit about that. 00:08:15 HYDER ARASTU, MD: So after Dr. Lazio has placed the frame, the patient comes to the MRI suite and as you can see, she's getting ready to get the MRI. We use MRI because MRI is a very high-resolution imaging technique, and it helps us to find the target versus the adjacent structures very easily. I mean, in some patients, we -- where we cannot use MRI, we use CT scan. For example, in a patient with

3 pacemakers, I mean, we can use as an alternative, but we prefer to use the MRI. MRI also helps us give three-dimensional in three quadrants, you know, three planes of imaging. And also, there is less bony artifact when you're looking at the targets in relationship to the structures, so MRI is -- I mean, we do one millimeter cuts, and even less than that if need be. So it's an excellent imaging modality, and the whole system is designed and integrated with the Gamma Knife treatment unit, so it's easy to transfer the information from this imaging study to the frequency unit. 00:09:24 HELVECIO MOTA, MD: And there you see Dr. Lazio and I, we take measurements of the skull of the patient because MRI cannot inform about the contour of the patient, so we have to do very precise measurement because we have to know the distance that the radiation has to travel to get the tumor. 00:09:40 BARBARA E. LAZIO, MD: It's also important when we're treating the patients that we know how long these -- the posts on this frame are and where the scalp is located so that when we do the treatment, we know that the patient's scalp or the -- the frame itself is not going to collide with the Gamma Knife helmet. And we'll show the helmet a little bit later in the procedure. What you see here is we're drawing the contour of the tumor. It's important to know what volume we're treating, so we outline the tumor margins. Sometimes it's not easy to see what's tumor and what's a vein next to it, so we define that. And oftentimes, we'll use neuroradiology expertise to help us to understand what -- what's the tumor and what are some other structures nearby. And then we're doing 3-D simulation planning on the gamma plan workstation. This is a very sophisticated software. Each time we place a shot of radiation on this screen, it recalculates the dose of radiation that's being delivered and recontours the -- the radiation isodose line so that we know where we're delivering the radiation to the patient's lesion target. You can see the yellow line surrounding the pink line. The pink line's the contour that we drew. The yellow line is where we're placing these shots. So individual small spheres of radiation are put together to try and make a conformal dose plan that fits the pink line. And that's just a 3-D image of the tumor itself that's inside the brain. Now the patient's brought into the Gamma Knife suite. I'm actually injecting her scalp there with just some plain saline, and that's because this particular tumor is close to the scalp. And we measured the scalp dose on our gamma plan to know that it was within a range that she might lose a little bit of hair. So we -- we wanted to move the scalp away from the radiation so that she wouldn't lose her hair there. The frame here is being affixed to the automatic positioning system. This can move the head within a 10 th of a millimeter accuracy so we know exactly where the center of the frame is and position the patient's lesion in the center. 00:12:12 HYDER ARASTU, MD: Once that is done, once the patient is positioned, we come -- all the staff comes out of the -- of the chamber where the treatment is done and into the control area. And from the control room, the entire treatment is conducted at that point. The patient, during this whole treatment, is quite awake. And in fact, most of the patients will bring their own music CDs that they listen to, and some of them even tap their feet while listening to the music while they're getting their radiosurgery done. And there is tremendous amount of safety that is built into this. If for some reason there is a problem that the patient faces or there is an equipment malfunction or something, this treatment can be interrupted and the patient moves out, and so that the safety of the patient is never jeopardized. Now you can see Dr. Lazio. 00:13:08

4 BARBARA E. LAZIO, MD: Right. Here we're just removing the frame. So this is at the completion of the treatment, the frame comes off. Sometimes we threaten the patients that they'll have to wear it home. To date, we've not sent anybody home with a frame on. One of the things that you saw while Dr. Arastu was in the control room was that the -- we all leave the room. So there are fixed sources of radiation within the Gamma Knife itself, and this is a leaded vault. It weighs over 20 tons. And this is all protected by Homeland Security because they're -- they're fixed sources of radiation. When the patient goes into the Gamma Knife, there are lead jaws that open, the patient slides into the -- into the Gamma Knife, and then for each one of the openings in the Gamma Knife helmet, called collimators, there's a single beam of radiation delivered. And I'll talk a little bit about the Gamma Knife procedure, what it involves, and then some of the indications. This is a slide that sort of depicts what you just saw in the video. You see in the center of the slide that the frames -- or that the frame defines the coordinates and the patient's head has to be absolutely fixed still and within this frame so that we can position that frame within 10ths of a millimeter and deliver the radiation in very small beams so that we know we're treating just the tumor. You can see these 201 intersecting pencil beams of radiation on the one point in the center of the -- the helmet. We can move the patient's head within the frame so that those pencil points intersect and create a small sphere of radiation. We -- to make a conformal plan or to treat just the tumor and not the volume outside of the tumor, we combine several shots or several small spheres of radiation so that it fits exactly into the tumor and then not on the outside of the -- where the normal brain is. Some of the things that we treat, I'm going to go through probably the top six indications of -- for Gamma Knife radiosurgery, and some of these are things that can be treated with open brain surgery, and I'll go over why sometimes people choose to have this or need to have this over open surgery. This is a meningioma that's located in the pituitary area, or the cella. This is an example of how we can make a very conformal dose plan so that this shows that the actual shots of radiation, the little spheres that have been combined to deliver this radiation just to the tumor. In blue, the optic chiasm or optic nerve is outlined. You can see the isodose curves are -- are aimed away from that nerve so that we're not delivering toxic radiation to that nerve and we're protecting that patient's vision. This is something that, you know, you're not able to do with fractionated radiation. You can't deliver a dose and you can't deliver as high a radiation dose in one sitting with fractionated radiation. And you're not able to keep the dose to the nerve this far away with fractionated radiation unless you split it up into multiple doses. The meningiomas are benign tumors, again, and so the goal in treating these is not necessarily to make them go away; we'd all be happy if they just disappeared, but what it does is shrink the tumor down or it keeps it from growing. The patient in the slide, it would be beneficial if this tumor didn't grow and start pushing on that optic nerve. So if this tumor stayed exactly the size that it is, that would be considered a success. Somewhere between 30 and 60% of tumors, meningiomas, will actually shrink with the Gamma Knife treatment, depending on which study you look at. This is an example of a malignant tumor. This is a patient with lung cancer, metastatic lung cancer, so cancer that spread from the lung to the brain. The left image shows her Gamma Knife treatment plan. You can see that there are three dots on the side of the image; those are our fiducial markers, so they're defining sort of brain GPS, where the tumor is located, compared to those dots. And each slice on the MRI has a -- those dots located at a different -- a different interval. You can see that after the treatment, the patient's tumor has shrunk. That's the image on the right, six weeks after her treatment. And again, you don't see the tumors immediately go away, and we can't see them during the treatment, but this -- this radiation has -- has slowed down the growth of the tumor and it's also killed some of the tumor cells, and you

5 can see that on subsequent images. This is an example of a patient who -- who might have benefited from surgery, and other neurosurgeons might look at this one particular image and say, "Well, that would be a great patient for surgery." But what you -- what you don't know is that this patient may have other lesions, and in patients who have multiple metastases are not generally candidates for surgery, and we won't usually do an open brain surgery on somebody if they have lesions on the opposite side or multiple small tumors. But those patients are ideal candidates for the Gamma Knife. You can treat all of those tumors that wouldn't necessarily have been treated before without -- I'm sorry, with surgery. This also can help some patients to avoid having whole-brain radiation. Often we'll use whole brain radiation for metastatic tumors in conjunction with the Gamma Knife, but there are certain patients who have tumors that aren't very sensitive to fractionated whole brain radiation like melanoma or kidney cancer, so we'll treat them just with the Gamma Knife unless we really need to use the whole brain. 00:20:01 This is an example of trigeminal neuralgia. For those of you who are not familiar, trigeminal neuralgia is a disease of the trigeminal nerve, or fifth cranial nerve, where there is an artery pulsating against the nerve, and it causes terrific facial pain, just horrible pain that really impacts these patients' lives. Some of these people have to take very high doses of medication that have a lot of side effects or they get to a point where they're almost suicidal from the intensity of this facial pain. One way to treat this is with an -- with a craniotomy, an open brain surgery, where you actually move that artery away from the nerve. But what you can see on this slide is that this nerve is right next to the brain stem. It's very close to the -- the nerves for hearing and the facial nerves, so there's a risk during surgery that -- that the patient's facial nerve function could be impaired or their hearing could be impaired, causing them to have a facial droop or to be deaf on that side. So it's actually not a difficult procedure, and it's usually quite safe, but a lot of people knowing those risks will choose not to have it done. The other thing is that elderly patients who have trigeminal neuralgia have the opportunity to have this treatment done where they wouldn't generally be considered for the open brain procedure. What this procedure does rather than treating a lesion, because there's no lesion on the nerve, is it ablates the nerve fibers that are causing the pain. So there are very few side effects from it. And oftentimes, the patients just have relief of their pain over a four to six week period of time without experiencing numbness or some of the side effects that you would get from other procedures. This is a vestibular schwannoma, and I borrowed this slide from the University of Pittsburgh. The University of Pittsburgh now is a -- they were the first university or the first location in the United States to have a Gamma Knife, and they're -- they're tremendous experts on Gamma Knife radiosurgery. We've only been open a year and a half here, so we don't have twoyear follow-ups, but here is an example of a patient with a benign tumor of the vestibular nerve. This tumor often affects hearing first, but it can also affect patients' balance. The operation to treat this -- this tumor is often very lengthy, and again, it causes the same kinds of side effects as the last surgery I was talking about; it can cause facial nerve paralysis or facial droop, and it can cause hearing loss. The Gamma Knife procedure is an out-patient procedure, so it's certainly much more palatable to patients when they're trying to choose their options. Now, you can see in this patient, the tumor went away. That's not always the case, sometimes the tumor just stays stable or shrinks. Many of the patients we've seen with vestibular schwannomas, you'll see the middle slide on their follow-up images, where you see the center of the tumor is dying. And we hope that they get to the slide on the right. This is an arteriovenous malformation. It's a web of abnormal vessels in the brain. And these can make people prone to having seizures or having hemorrhages in the

6 brain. This patient presented with seizures, and she was actually the first patient we treated at Pitt Memorial Hospital for an arteriovenous malformation. This works in a little bit of a different way: instead of treating tumor cells and stopping them from growing, what this actually does is cause the blood vessels to occlude themselves. They get endothelial perforation, and that causes the vessels to close up and the AVM eventually disappears. This could take up to three years. The folks that we've treated here, we've seen already that they've had some decrease in the size of their AVMs. They still are at risk of having bleeding or seizures during that time that it takes for them to go away, but again, this saves them a potentially dangerous intracranial procedure. This is very close to this patient's motor area. And she could quite possibly suffer right-handed weakness or language problems from having this one removed surgically. And then lastly, these are not all the indications for the -- the Gamma Knife, but these are just sort of the top indications that we treat here at Pitt Memorial Hospital. This is a pituitary adenoma. This is a benign tumor of the pituitary gland. This patient had surgery by another neurosurgeon outside facility. She had a tumor that was twice the size of what we see here, and it was pressing on her optic nerve. She did quite well after the surgery, and she had some visual changes before that improved. But she did have this residual. I spoke with her surgeon, and we decided along with the patient that -- that a second surgery was not what we wanted to do, mostly because the patient didn't really want to go through surgery again. So given her young age and this is a fairly significant residual and the fact that it's quite a bit far away from her nerve now, we decided to treat it with the Gamma Knife. So I think that I've covered a little bit about what the Gamma Knife is and who can be treated. I can defer some of the radiation oncology specifics to Dr. Arastu. A lot of patients ask questions about how -- how the radiation works and what happens to these lesions after we treat them. 00:26:21 HYDER ARASTU, MD: Yeah. And they're -- Dr. Lazio has done an excellent coverage of giving an overview of Gamma Knife radiosurgery. And some of the very common questions that we get from the patients as well as the family members or some of the referring physicians is "how is it different from -- radiosurgery different from the standard or routine radiation therapy that we do," which is what we call fractionated radiation. Both of them utilize external beam radiation sources. I mean, the Gamma Knife radiosurgery uses cobalt 60 sources, which have a half-life of 5.26 years, and they -- and emit lower energy gamma rays as well as some component of beta rays in them. Whereas the fractionated external beam radiation is done with the same x- rays, but they are generally a much higher energy as compared to what we use for Gamma Knife radiosurgery. The major difference between the two modalities is the fact that in standard external beam radiation therapy that we do, routinely the area of radiation is much larger. And by virtue of that, the dose of radiation that we give is relatively smaller and also broken up into several multiple fraction sizes, or small pieces. And the advantage of that is that it allows these normal tissues to tolerate radiation much better. But as you increase the dose, you have to take the normal tissue radiation dose and reduce the normal tissue radiation dose significantly. And Gamma Knife radiosurgery, or this technique, gives us the way of doing it and essentially this is an extremely precise -- to the fraction of a millimeter, essentially -- treatment. We define the target very precisely, and that's the reason why we use the MRI, because it helps us to find that. Once we do that, we -- we have kind of excluded the normal tissues around it, and that way we are able to deliver a very high dose of radiation. So to give an example, I mean, we use doses in the range of 20 gray in a single treatment for doing Gamma Knife radiosurgery, which is equivalent to a dose of approximately 50 gray in fractionated radiation. Or if you -- another example would be a 35 gray Gamma Knife radiation treatment would be

7 equivalent to about 85 gray in 10 fractions, or 10 small treatments broken into. The -- that's the main difference between the radiosurgery and the standard radiation that we do. And the -- the way the tumor or the target responds is also somewhat different. Specifically talking about radiosurgery, typically most of the work was done on animal models and some of the autopsy results. Typically what happens is that when you deliver a high single dose of radiation, there are two primary mechanisms that happen. One is the cytotoxic effects of radiation, radiosurgery. And the second major component is the blood vascular effects of radiosurgery. So cytotoxic effects generally are small as compared to the vascular effect in radiosurgery. Typically, the tumor, when you deliver the radiation, the first thing that happens is increased intratumoral edema, and then there are processes called apoptosis, which is programmed cell death or outright cell necrosis. Those are the several things that happen in an immediate time period after getting radiation. And that is reflected in if you do an MRI or imaging study shortly after the treatment, if you see a regression or a decrease in the tumor size, that's the component of pathophysiology that has happened. The other factor is the vascular effects of radiosurgery, and these are -- typically happen in patients -- in targets which are slow-growing targets or lateresponding tissues, as we call them, which is the normal tissue or the patient -- one of the patients that Dr. Lazio showed was a vascular malformation, an AVM patient. Typically what happens in these patients is after we deliver a dose of radiation, there is an -- the first thing that happens is an acute inflammatory effect of that. This is followed by endothelial cell injury. And this, over the period of months, leads to hylanization of that area and thickening of the blood vessel, and then after that, the blood vessels get occluded. And that ultimately leads to, in the case of AVM, obliteration of the AVM. Now, you may ask -- and people ask, "Okay, that could happen to the normal tissues or normal blood vessels also." The good thing is the normal blood vessels of the brain are extremely, extremely resilient to radiation. They can even tolerate high doses of radiation. It is the abnormal blood vessels, because the AVM is a tumor of the abnormal blood vessels, and also in other tumors like meningioma or from brain metastases or other tumors, there's abnormal vasculature. So that is the vasculature that is relatively much more radiosensitive and gets damage to that. So we use that difference, relative difference in the responsiveness to our advantage to obliterate these tumors or lesions. That's the radiobiological reasons why these patients and these tumors respond. Related to this question is, some people ask, one of the questions was, "How long does it take for the tumor or the lesion to go away after we do that?" And some of these lesions may never go away, but, you know, for in case of AVM, you have to wait for about at least three years or so before we make a judgment whether that treatment was successful or not successful. So it takes a long time. In some of the other tumors which are like the rapid-responding tissue or the tumor tissue like brain metastases, things like those, we can get the results much faster than that. In several months, we can see that. In some of the other areas, for example, trigeminal neuralgia, when we treat that, we are really not looking at the obliteration of the target there because we are looking at the symptomatic relief. The criteria that we use for response is different in that area. 00:32:41 BARBARA E. LAZIO, MD: Right. Now, we're already starting to get some questions, and I would encourage our viewers to click on the icon so that they can e- mail some questions. one question we just received is referring to an AVM, or arteriovenous malformation in the brain: why would someone with an AVM located in a good spot pick the Gamma Knife or brain surgery? And that's a very good question, and this, again, is very patient-driven a lot of the time. You know, patients make a lot of educated decisions in this age, and sometimes patients just choose. And

8 there's -- there's the morbidity of having an open brain surgery. An AVM located in a good location in the brain may be a very straightforward surgery, but it's still an open brain surgery. It still is usually a 2-3 hour procedure or maybe even longer. There's still a risk of stroke or hemorrhage. In good hands, this can be done very -- very precisely and very easily and a patient can have a very good result. But again, the patient still has to go through the open procedure, a day or two in the ICU, or maybe longer, and then several weeks of recovery. Most patients after a cranial procedure have headaches and they also don't feel like going back to work or driving or doing their normal things for -- for at least six weeks after the procedure. With the Gamma Knife, you can return to your normal activities in a day or two. Actually, one of our AVM patients had -- she's a musician, and she played in a musical concert the night after her procedure. She wore a hat to cover the band-aids on her scalp, but -- but she did fine, and she sent us some pictures and she sent us a CD from the performance. Now, the tradeoff, however, is that the AVM may take a while to obliterate, so if you're in for immediate gratification, you probably want to have surgery. The AVM's gone after the surgery's over. If -- if you're willing to wait a while, having the Gamma Knife procedure is a way to do it without interfering with your life too significantly, but just knowing that during that period before it goes away, you're at risk of having it hemorrhage or having it cause seizures. So, you know, we usually let the patient choose, but we'll make educated recommendations. And again, every patient who comes through is presented, even patients who we think, "you know, this isn't a very good idea," we'll show it to the group and let everybody say, "this isn't a good idea," or we'll let everybody say, "this is a great patient." We accept self-referrals, so patients can refer themselves. We accept referrals from physicians from outside the area. People can feel free to us images or send us a CD and we'll review those at our conference even before we see the patient just to let -- let folks know whether they look like a good candidate and whether they should make the trip here. We have actually some testimony from our patient. She's -- she's an excellent patient, and she's seen both sides of the coin. She had surgery in 2004 and she had the Gamma Knife done here, and we have some comments from her about the difference between the open surgery and the Gamma Knife procedure. 00:36:24 PATIENT: Compared to my first surgery, this was a piece of cake. It's a whole lot better, and if it's an option, it's the best one to take. And I would've took it the first time, but it wasn't an option. You don't have O.R. time, I don't have a big incision in my head with staples, and half my head's not shaved, which is a big plus. 00:36:49 HYDER ARASTU, MD: We have some additional questions. One of the questions that was asked is: can I have Gamma Knife radiosurgery if I've had previous surgery or radiation to my brain? And the answer to that is yes, absolutely, you could. And well, one of the examples that a patient of today that we have has had previous surgery and required Gamma Knife for residual recurrent tumor. That's a common indication to do that. In other areas, for example in cancer field, I mean, brain metastases is a common indication where patients have had previous whole brain radiation, and if their tumor or one or two of their tumors that they've had initially, they start acting up again, they can successfully have radiosurgery very safely. In some of the patients who have had radiosurgery alone initially for brain metastases, if they have new lesions, they can be also safely treated or the same lesion can be treated again if it starts acting up. So absolutely the answer to that is yes, we could. 00:37:48 BARBARA E. LAZIO, MD: Right, and some patients also ask, "well, what if it comes back after the Gamma Knife? Can I have surgery then?" And the answer to that is a

9 guarded yes. If they were a candidate for surgery before the Gamma Knife, then they would be a candidate after the Gamma Knife, and it doesn't really increase their risk of problems afterwards. We have another question from a viewer: I had a benign perasagittal meningioma removed via open craniotomy several years ago -- this is the same thing as the patient we're treating today, by the way -- thus far, no tumor has reappeared. I am curious if there was a regrowth, would I then be a candidate for the Gamma Knife procedure or would another craniotomy be necessary? And I would say, yeah, most certainly this is a very good indication for the Gamma Knife. And you know, in the past, there weren't as many options for people with these meningiomas on the -- on the sagittal sinus, this large vein. It puts them at a higher risk of having a stroke, a hemorrhagic stroke after the procedure if you have to remove that tumor that's on the sagittal sinus. So oftentimes when we're removing these tumors, if we know we just can't get that last piece off, we'll just plan to do the Gamma Knife afterwards. Our -- our patient from today had some comments about the benefits of the Gamma Knife and her advice to other patients, and we can show you her experience. 00:39:24 MARY: It's probably the best thing to have because it's a non-invasive, really, procedure. They don't have to cut -- you know, put -- drill a hole in your head. To me, that's like a, you know, a no-brainer. It's the best option. 00:39:39 BARBARA E. LAZIO, MD: She was a really great patient. We were really lucky to have her participate with us today. 00:39:46 HYDER ARASTU, MD: One more question that we have is from a patient asking how many treatments that are done during a Gamma Knife procedure. The answer to that, as was obvious in Dr. Lazio's presentation initially was usually we do a single treatment at one time. And we could treat more than one area, and that was also another question, how many areas that we can treat. We can treat multiple areas in one sitting, but all the radiation dose to that particular target is delivered in one treatment, and this is, as I said earlier, the major difference between Gamma Knife radiosurgery versus the fractionated radiation therapy that patients get for days or weeks together. So the answer to that is single treatment. 00:40:27 BARBARA E. LAZIO, MD: We have another viewer question: I have trigeminal neuralgia, and I've heard that the placement of the head frame can be extremely painful. Can this be done without conscious awareness? We -- we have done this under conscious sedation. Actually, most patients we give just a little bit of versed, which is an anti-anxiety medication, and it makes them a little sleepy, and oftentimes they forget that they even had it done or they say, "wow, that was a breeze." Other patients who are extremely nervous and need more sedation, we can sedate more heavily. It can actually be done under general anesthesia. And most children who have to have the procedure will be done under general anesthesia. We were lucky that our 10-year-old, who's the youngest patient we've treated here so far, was able to be done with -- with sedation, conscious sedation. 00:41:25 HYDER ARASTU, MD: One -- one related question about the number of sites we can treat, I answered that we can treat quite a number of sites at one time. In fact, the question -- the question also included how many sites did we treat here? One of the patients, we treated almost 11 sites, right, Dr. Lazio? And more recently, we treated another patient nine sites at one sitting. So do we do that routinely, that many sites? Ordinarily, we don't routinely do that. I mean, these other patients have had whole brain radiation because the benefit of doing radiosurgery is somewhat lost if you

10 start doing too many sites. But in patients who have been previously treated with whole brain radiation, it is perfectly okay to do multiple sites of treatments. 00:42:09 HELVECIO MOTA, MD: In a single day. 00:42:11 BARBARA E LAZIO, MD: Right, and I think that a lot of patients are surprised at how -- how easy the treatment is. And you know, sometimes it can be long, but really at the end of the day, when the frame comes off and they say, "is that it, are we done?" And I know we have -- have some comments from our patient, Mary, who's in the webcast today about -- 00:42:35 MARY: This experience has been a surprise because I thought it was really going to hurt when they screwed that thing on me. I was really scared about that. And the whole thing was just -- I don't know, smooth. It just -- everything went smoothly, and it was a great team in there. 00:42:50 HELVECIO MOTA, MD: Kind of a surprise for her. 00:42:52 BARBARA E. LAZIO, MD: We have some other questions from our -- our viewers: what is the largest tumor you can treat with the Gamma Knife? The largest tumor we will generally treat with the Gamma Knife is approximately three centimeters. Beyond that, there's a much higher risk of radiation necrosis or radiation damage to the brain tissue and also radiation breakdown of the tumor that can be toxic to the brain. And Dr. Arastu, you might be able to comment a little bit more about radiation necrosis and you may have a little more experience with that. 00:43:31 HYDER ARASTU, MD: Yes. That's true. As Dr. Lazio mentioned, I mean, the larger the tumor -- if you just go beyond usually three centimeters we take as a cutoff point -- the amount of radiation or the distribution of radiation, because the way the radiation's prescribed for Gamma Knife radiosurgery is we prescribe the dose to the 50% line. The 50% of the dose line that is there around the tumor, that's the way we describe the dose. So there are parts of the tumor that, if you suppose we give 20 gray to the 50% line, there are parts of the tumor that will get a much higher dose inside there. Plus, the larger the tumor, the larger the dose that has to come from the surrounding -- passing the surrounding brain into that area. We call it the integral dose. So that increases. So the complication rate increases with that. Brain necrosis essentially is actual breakdown of the brain tissue. I mean, there is such a high dose of radiation that you have done more of the cytotoxic damage or effective radiation as compared to the vascular effect as I mentioned earlier. So those patients are at a higher risk of having the cytotoxic -- actually, liquefaction of the tumor there. So that's the reason why we have to limit the size of the tumor to a certain degree. And if we have tumors larger than three centimeters, it's not that we do not have an option; they do have an option. In those patients they are better off getting treated with either fractionated external beam radiation therapy where we have much better control in terms of late, long-term, or late effects of radiation, or some patients actually may be better off getting surgery, so... 00:45:09 BARBARA E. LAZIO, MD: Right. Dr. Mota, we have a viewer asking how often do we check the Gamma Knife to ensure its accuracy. 00:45:20 HELVECIO MOTA, MD: That's part of the procedure, we check the Gamma Knife. We do what we call QA, daily QA, and we do monthly QA to check the dose to the -- to the isos center of the machine. Because as you know, the radiation stays always on.

11 So that's good for one part. You cannot ever shut down the machine, so the machine's always on. You have to check that and make sure it's confined in the chamber. So the -- the machine is all automated, so we have to check all the system is working all the time, so that's -- that's what I can say. 00:46:06 BARBARA E. LAZIO, MD: Yeah, Dr. Mota does some pretty sophisticated testing of the machine every day, not only checking the mechanics of how the machine is working, but also checking to make sure, again, that the radiation's going to the center where we -- we want it to be delivered. He also is excellent at troubleshooting when things aren't -- you know, this is a sophisticated computer program, so you know that in an automobile, the more computer systems you add to it, the less it works. So he's been extremely helpful and we never like him to go on vacation because he's the guy. 00:46:46 HELVECIO MOTA, MD: When the equipment goes, moves, we used to say... so because otherwise we -- whenever you go in the computer, you cannot deliver. So sometimes you are in trouble, you have to go back to the planning equipment. We don't like that, but sometimes that happens. We -- the computer, everything goes easy, but when you go to deliver, sometimes things gets complicated, so that's why you guys like to have me around. 00:47:11 BARBARA E. LAZIO, MD: Right, that's why it's essential to have a team. You know, I wouldn't like to be in there by myself using a sophisticated piece of machinery like this, and it's -- it's really important to have these three brains or sometimes five brains together in the room to make sure that the patient's getting the best treatment. 00:47:35 HELVECIO MOTA, MD: Yeah, that's -- make sure after you do all the -- the calculation, everyone has to agree and we all sign the paper, the description. That's how we document the procedure. 00:47:49 HYDER ARASTU, MD: There's one more question that has come: is this an outpatient procedure? And the answer to that is most of the time it is, and Dr. Lazio sometimes keeps the patient overnight. Dr. Lazio, you might want to answer that, but... 00:48:02 BARBARA E. LAZIO, MD: Right. Most of the -- most of the patients can be discharged the same day, pretty much anybody with a benign lesion like a trigeminal neuralgia or a -- a -- the benign tumor like a meningioma or an acoustic schwannoma can leave the same day. You know, some patients, if they have comorbidities like they're elderly or they have heart disease or they have a seizure disorder, we'll certainly keep those folks overnight. I personally like to keep anybody with an intraparenchymal lesion or a tumor inside the brain or an ateriovenous malformation inside the brain, I like to keep those patients overnight. There's about a 2% risk of having a seizure immediately after the procedure. In the 200 patients we've treated, we've seen one, and that was our first patient, unfortunately, but she's doing terrific, and as is the patient who was filmed today. 00:49:02 HELVECIO MOTA, MD: One more question coming in. 00:49:04 BARBARA E. LAZIO, MD: Right, another question. I appreciate everybody ing their questions. There are really a lot of questions. I don't think we're going to be able to answer them all. This one is: what is the risk of the healthcare professionals

12 for exposure to radiation and what are the benefits of using both surgery and Gamma Knife in brain tumor therapy? So Dr. Mota or Dr. Arastu can probably address the healthcare professional risk. 00:49:31 HELVECIO MOTA, MD: That's one part, Hyder, you can address. We all use what we call a dosimeter badge. Actually, it's not a film, it's a dosimeter. And then we are regulated by -- by rules, state rules, so we -- we have limits of dose we can receive during the year because worker's regulation, there is an assumed risk that we can get some damage in the future by working with radiation, so in the early days of radiation, some people, they had damage. Now -- nowadays, it's very low-risk probability to have any damage, but we keep controlling. There is a radiation safety officer, a research committee, that oversee all we do in here in the hospital with using radiation. 00:50:28 BARBARA E. LAZIO, MD: And they -- the Gamma Knife is very highly shielded. The sources of radiation in the Gamma Knife are deep within this core. 00:50:39 HELVECIO MOTA, MD: That's right. There's no shooting off -- we still have radiation outside. Low-level radiation, we still have. That's why inside the Gamma Knife vault is not a place to go dance, stay talking, go there and study and something like that. There's radiation inside there, so that I keep the door always closed so people go there only if it's needed. 00:51:01 BARBARA E. LAZIO, MD: Dr. Mota actually has studied with little radiation sensors, TLDs, various sites on the patient's -- their thyroid, their mediastinum, the gonads, to detect what -- what negligible amounts of radiation those patients are receiving to those other areas of their body as they're passing in and out of the -- the Gamma Knife. This newer technology, the automatic positioning system, has decreased those -- those gonad doses, those thyroid doses quite a bit because the patient doesn't have to go in and out as many times. It decreases the transit time so that they're getting a lesser radiation exposure. Even that said, they really get very little radiation to the rest of the body. It's almost undetectable. 00:51:57 HYDER ARASTU, MD: I think related to that, radiation safety, I mean one of the questions that came in was asking if the patient's pregnant, can we do Gamma Knife radiosurgery, and as a matter of policy, we do not do that. I mean, because of the same risks. 00:52:10 HELVECIO MOTA, MD: But we could. 00:52:11 HYDER ARASTU, MD: Even though it's possible to do that, the amount of radiation that is delivered to the fetus would be very low, but -- but still, as a matter of policy, we do not treat patients who are pregnant. In fact, even if one of our employees are pregnant, you know, they cannot be in the area. And in fact, the younger patients in the child-bearing age have a pregnancy test before they go into the Gamma Knife, so it's -- we take a tremendous amount of precaution in that area. And the second part of that question -- this question was: what is the benefit of using both surgery and Gamma Knife in brain tumor therapy? I think that's -- the answer there -- you have to understand that both surgery and Gamma Knife radiosurgery or traditional surgery, open surgery, or Gamma Knife, they both have the same objective, is to, you know, address the target. The target could be a nerve that you're trying to do, as trigeminal neuralgia, or a tumor. So both are -- can be used in lieu of each other, depending on situations. It is sometimes a patient factor where the patient may

13 choose one modality or the other. Sometimes it's the medical necessity because the patient may not be a surgical -- candidate to undergo anesthesia or surgery. Or the tumor location may be in such a place. So we use those two modalities as a, you know, to -- sometimes you use a combination, like in a patient who has had recurrence or a patient who has had surgery and some of the tumor was left over because that tumor was sitting next to a critical area. Then we combine the -- add Gamma Knife radiosurgery to that. And the important thing is I think radio-- Gamma Knife radiosurgery is an extremely, extremely safe modality if it is done correctly and if it is done by people who know what they are doing. And you have to be very familiar with the doses that the different parts of the brain can tolerate. And you may be giving a very high dose to an area as your target, but next to the target may be sitting a very sensitive area where we cannot cross. I mean, a good example is when you're doing trigeminal neuralgia patients, I mean, the brain stem is sitting right there. So I mean, we -- a restrictive dose, even though we may be giving 80 gray to the trigeminal neuralgia, to the nerve, but we restrict the dose to the brain stem to less than 8 gray. So it's very, very important. So those are the important differences between -- you can use them, both of them in combination or in lieu of each other to your own advantage. 00:54:43 BARBARA E. LAZIO, MD: Right. Some other questions that -- that folks have submitted: would it be beneficial for me to get this surgery if my lesion is minor but causes me much pain with migraines? And you know, a lot of these questions are going to be very specific, and as I've said earlier, we're happy to review things and we will accept CDs and films and show them to the -- to the committee to decide if patients are candidates. What I will say, addressing small lesions but with migraines, is that we do have a collection of patients and we are planning to study the effects of treating small lesions like meningiomas or smaller meningiomas with the Gamma Knife and the patient's experience in terms of quality and headaches post-treatment. I have found that several of my patients just anecdotally have said that their headaches are better after we treat the tumor with the Gamma Knife. In the patient that we filmed earlier and showed today, she's already had relief of the headaches that she was having with her recurrence. So, you know, I'm optimistic, but I can't say that there's any data to support that the headaches are going to go away with the Gamma Knife treatment, but it is something that we're looking into. Let's see, here we have another question: I was diagnosed at the Mayo Clinic in Rochester about three years ago with a schwannoma; is the Gamma Knife procedure an option, and if so, what are the side effects that could be expected? If this is a vestibular schwannoma or a -- a cranial nerve schwannoma, essentially any schwannoma that's -- that's intracranial. This is a procedure for lesions inside the skull. Anything below the neck, you have to use other kinds of radiosurgery procedures because this relies on the head being completely fixed. Other parts of the body we cannot fix in space like we can the skull. But yeah, any intracranial schwannoma theoretically can be treated with the Gamma Knife within the limits of the size. Large schwannomas we won't treat, three centimeters or above or with, you know, serious brain stem compression. 00:57:12 HYDER ARASTU, MD: There is another question that came in: can an AVM mask other conditions, as in tumor? The answer to that is, can it, answer is, yes, it can, but generally does not. And with the imaging techniques available to us, it's very easy to detect if there is anything else -- any other component within the AVM, including the MRI and when you do the arteriograms, it's easy to find that, so the answer to that is yes, it can, but generally it's easy to detect that. The one other question that came in was: what is the contraindication to Gamma Knife therapy? I