Grand Rounds-Principles of Radiosurgery: Methods and Outcomes

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- Hello, ladies and gentlemen, and thank you for joining us. The following presentation will be a discussion regarding minimally invasive treatment of brain and spine using radiosurgical techniques. Dr. Jason Sheehan from the University of Virginia will be our discussion, thank you.

- It's my pleasure to be here, Aaron, and thank you for inviting me. I'm gonna to talk a little bit about minimally invasive approaches to brain and spine disease. In a particular, really focus on radiosurgical applications in modern day neurosurgical practices. If we think about the definition of minimally invasive approaches, really, it boils down to this as depicted on a slide, the notion of avoiding, hopefully some of the pitfalls of an open surgery and using indirect observation to reduce trauma and to minimize hospital stays as well as associated costs and co-morbidities that can arise from open procedures. Certainly, in neurosurgery, we don't think of putting a bandaid over patients and in radiosurgery, we don't use those types of dressings, but the whole concept of using minimally invasive approaches has been one that our discipline has come to embrace. When we think about other fields in minimally invasive approaches, we certainly think about general surgeons who use laparoscopic approaches, orthopedic surgeons who do arthroscopic procedures, percutaneous approaches which we do some of in neurosurgery. Certainly, we do a lot of endovascular approaches for aneurysms and arteriovenous malformations and in some instances we even use robotic surgery and certain radiosurgical devices use robotic approaches as well. Here, depicted here is a typical laparoscopic surgical case for a general surgeon and here's a robotic case of approaches a urologist who might be doing robotic surgery with the Da Vinci. Why do we do minimally invasive approaches? Certainly, we know all too well that opening up the head when it might be helpful to be avoided can convey the patient a better chance of a favorable outcome. A very insightful work entitled, "When the air hits your brain," detailing the tales of neurosurgery by one neurosurgeon. We can think of it though, as being a rather complex approach, almost like building a ship in a bottle. It's not easy to do a minimally invasive approach within the brain in this spot. Over the last three decades, there've been substantial advances that have allowed us to do minimally invasive approaches and to do radiosurgery in centers throughout the world. First, being the application of stereotactic capabilities in 1980s, the idea of using routinely stereotactic datasets and frames to more precisely and safely guide our surgery. And then in the 1990s with the proliferation of CT and MRI, we all of a sudden had a ability to guide radiation beams in a way that utilize those stereotype principles, but with the image guidance in a way to reduce risk and really truly be minimally invasive. But, what does the term stereotactic radiosurgery mean? If we think about it in the context of the underlying words, it stereo is Greek for stereo's, or meaning three-dimensional. Tactic is Latin for tactus or to touch and radio is Latin for radius or beam. And really what we hope to do is to touch a very small area within the brain, an area that's causing problems for the patient, maybe pathologic tissue or, or tissue that's firing too much or, and to cause very little in the way of ripple effects in the surrounding brain tissues. If we think about it in that context of a simple analogy here, you can think about, this child trying to harness the rays of the sun with a magnifying glass and that harnessing of those rays allows him to burn a leaf. Certainly I have a brother who's a neurosurgeon and when he and I would play as children, if we both had magnifying glasses, it was easier to harness the rays of the sun and to converge them on a leaf and to singe it in a way that wouldn't cause damage if we held our hand in between the magnifying glass, but it would cause damage to leaf itself at that focal point of both our magnifying glasses. Leksell embraces principles of stereotactic radiosurgery in the early 1950s. It was really in the 1960s, he developed the early gamma knife, and this is the latest version of the gamma to gamma perfection. Certainly, there are other radiosurgical tools that can be used and we'll touch upon those briefly. There are certain basic requirements for modern stereotactic radiosurgery devices. All of them have to be compatible with sophisticated neuroimaging modalities, certainly MRI and CT. But, also SPECT, PET and functional MRI. They have to be accurate and precise, they have to be user friendly and they have to embrace this concept as we talked about of using minimally invasive tenants. When we're doing radiosurgery, we are thinking about it in a probabilistic fashion, trying to in this case and in the setting of a tumor, trying to be on the high end of the tumor control sigmoidal curve, being on the low end, in terms of the major complications, and typically what drives these are the dose and the volume of the tissue structures that we're treating. There are some basic approaches is listed here at certainly stereotactic radiosurgery and stereotactic body radiotherapy are the most complicated of the radiosurgical approaches that one uses. There are other radiation therapy techniques that we use for our patients. However, we typically refer patients who are getting these techniques. We don't on average perform them ourselves. These include 2D, conformal radiation therapy, 3D conformal radiation therapy, intensity-modulated radiation therapy and ARC therapy. If we think in the last, decade of growth areas within neurosurgery, there's been exponential growth in terms of stereotactic radio surgery. It's this depicted here. But, really, since the early 1990s, when most early radiosurgical centers in the US were started up until the mid 2000s, when there's been a substantial, almost exponential growth in the number of patients that are treated, and also the number of indications. This is a team effort and organized neurosurgery has come to embrace this, concept that as a neurosurgeon plays a vital role in the notion of other team players being radiation oncologists, radiologists nurses and medical physicists. But again, this is a truly a multidisciplinary team approach to do radiosurgery. There are different types of radiosurgical device that we're using for radiosurgery, although most are using for radiation therapy, Cyberknife X-Knife, synergy, and access systems, Tomotherapy, Novalis, TrueBeam and Trilogy, just to name a few. All of these devices can be used for radiosurgery in the brain and the spine. Most devices fall into one of these three categories, either particle beam accelerators using charged particles, protons, helium or carbon ions. Cobalt-60 systems principally, in this case, the Gamma Knife using gamma ray photons or X-ray photons from the linear accelerator. They have certain inherent advantages and disadvantages. Nevertheless, at this point in time, all of these systems are being used for radiosurgery of the brain and the spine. I'm gonna draw upon my experience here at the University of Virginia, and this is our case mix for about 20 years, showing the different indications that we've treated and the relative percentages that they made up of about 9000 patients have been treated here at the University of Virginia for largely intracranial radiosurgery. Can see that the major indications include AVMs, hemangiomas, vestibular schwannomas, pituitary adenomas, and metastatic tumors. The major functional indications trigeminal neuralgia. We also have looked at more rare instances of using radiosurgery for treatment of ocular melanomas and for the purposes of treating temporal lobe epilepsy in the context of an NIH multicenter clinical trial. And then also for treating more rare conditions such as intractable obsessive compulsive disorder. Certainly, there are some inherent advantages to radiosurgery as compared to a microsurgical approach. This indicates one such thing that is the time factor that's involved in the microsurgical approach and the rehabilitation recovery that's often times require as compared to the minimally invasive nature of radiosurgery and a relative recovery period of hours to a day. There's also some cost benefits to radiosurgery as well. This study in 1989, indicating that the disparity in cost between an open craniotomy and microsurgical resection for arteriovenous malformation, acoustic, meningioma versus a radiosurgical treatment. And this really just looks at costs associated with direct care and not that the long-term cost that might be associated with lost work for patients who are recovering from a craniotomy, that may become less than ideally. So perhaps the earliest indication for radiosurgery, one which is dear to my heart in terms of the University of Virginia, because Dr. Lasso Starner published the first successful case of a patient being treated with radiosurgery, using being treated successfully with radiosurgery to treating AVM. We've seen in about 1400 patients, treated with radiosurgery for arteriovenous malformations that the overall iteration rate is about 80%. We have seen patients who have had a substantial decrease in their seizure frequency or severity even with a partial iteration of their AVM. Nevertheless, the goal patients. Here's a typical example of a patient that's been treated here at the University of Virginia, a patient with a posterior circulation AVM, rather difficult to access from a surgical standpoint and approximately two years later, a nice obliteration of the AVM as depicted here on this angiogram. We've also had a great experience with treating patients with pituitary adenomas using stereotactic radiosurgery who treated nearly 800 patients with recurrent or residual pituitary adenomas. Many of these patients have had previous fractionated radiation therapy and have gone on to have growth after fractionated radiation therapy. Can appreciate that the differences in terms of collateral structures, certainly worry about the optic apparatus as depicted here in blue. We can see all too well, the carotid artery and the canvas portion of it and then the pituitary adenoma here depicted in yellow. We've seen excellent rates in terms of growth control for most patients that have non-functioning pituitary adenomas, upwards of 90% endocrine remission rates, though are a little bit less favorable and hovering around 50% for acromegalic and Cushing's disease. Most endocrine remissions occur within one to two years after radiosurgery, which appears to be substantially faster than that with external beam radiotherapy, which in general affords endocrine remission rates on average, about four to five years after radiation therapy. Here's a case of a patient with an invasive procedure, macro-ademona that was treated. She had a case of Cushing's disease and the tumor had been previously resected two additional times. She'd also had external beam radiotherapy. It's a very nice reduction, which is actually the cavernous sinus and in the cell. This is a more typical response. We see here pre radiosurgical treatment of a patient with a non-functioning pituitary adenoma that invades the right cavernous sinus. It's very close to the optic apparatus, but still could be safely treated with radiosurgery. We see a nice contour here depicting that adenoma in the right cavernous sinus region and the bending of the ICD line around the optic nerve to shield the visual pathways from any substantial damage. And here two years after radio surgery, a nice reduction in the size of the adenoma and a increasing gap between. We also see in modern day radiosurgery, a great indication for treating patients with moderate to small acoustic neuromas. We at the University of Virginia, have experience with treating more than 400 patients with vestibular schwannomas and have long-term follow-up on these patients. Overall, we've seen about a 95% tumor control rate, of which 81% will go on to decrease and decrease by more than 15% by volume. We've seen a less than 1% risk of facial weakness and about a 65% chance of preserving useful hearing if a patient has it at the time of radio surgery. Here depicted is the long-term radiologic response after gamma knife radiosurgery for a cohort 400 patients with acoustic neuromas. And we see that there's a long-term durable response well beyond 10 years for patients. This represents a schematic of the challenges of a patient with a moderately sized acoustic neuroma. In this case, stretching the seventh nerve and coming close to the fifth nerve and to a degree, displacing some of the, brainstem and cerebellum. We do know very well that a higher dose affords a greater chance of regression of the acoustic neuroma, but also conveys a greater chance of causing some cranial neuropathies and this slide here depicted from work at the University of Pittsburgh, indicates well that doses above fifteen conveyed a substantially greater risk of neuropathy as compared to doses below fourteen grade two vestibular schwannomas. And typically in the modern era of radiosurgery, we use doses of between 11 to 13 grain to the margin of the tumor. This is a typical dose plan of a patient with a small to moderate size acoustic neuroma with an intra-canular component. You can appreciate the nice conformality in the steep dose follow up on the 50% line here in yellow to the 20% line here in green. This is an example of someone who has a very large acoustic neuroma. We're exploring our experience now with that, institutionally there have been some case series that have shown for patients who have substantial comorbidities that preclude a resection or simply unwilling to undergo resection, that one can use a low dose on average, 11 to 12 grade for these patients and see a nice reduction in the size of the distributed schwannoma over time of a fairly substantial acoustic neuroma that's larger than I would ordinarily treat to something that's moderate in size or something that goes on to be substantially shrunken after radiosurgery. We also have treated an awful lot of patients with skull-based tumors, principally meningiomas. We've on occasion treated patients with convexity meningiomas. Most of these meningiomas are amenable to some degree of resection, but maybe an incomplete resection. We know with radiosurgery that when we're treating small to moderately sized meningiomas at the overall control rate for meningiomas, it's approximately 95%. Here's a typical example of a patient with a parasellar meningioma that was treated with Gamma Knife radiosurgery. Can appreciate that this tumor does, in essence, encapsulate the carotid artery on the left and at the difficult challenge, it would be to access this entire tumor, but a very nice approach. It can be done with Gamma Knife previous surgery, where one can with relative immunity, go into the cavernous sinus and treat this component of the tumor as well as the middle cranial fossa and posterior fossa components to the meningioma with a nice regression of the meningioma over the time span of about three to four years. The major functional indication for radiosurgery, currently, is the treatment of patients with trigeminal neuralgia. Typically, when we think about trigeminal neuralgia in young patients, we treat them with a microvascular decompression. But for patients who are older or unwilling to undergo a microvascular decompression because of substantial co-morbidities or patient preference. One can target the root entry zone of the trigeminal nerve and typically afford patients relief within about two to six weeks after radiosurgery. We noted our institutional experience of about 90% of patients had substantial relief within one year. The targeting is of the trigeminal nerve occurs at that transition between central myelin and then peripheral myelin and a small ICER center. Typically a 4 militre ICER center or a three militre ICER center is used right at that root entry zone of the trigeminal nerve that it comes into the brainstem. Example of a patient that I think was reasonable to treat with Gamma Knife radiosurgery for trigeminal neuralgia is this patient. He's a 63 year old who had white B2 and B3 pain. He had trigeminal neuralgia for more than 12 years. At the time he presented, he still had reasonable relief with Tegretol, but was finding it difficult with certain chewing movements and difficult to smile without a lasting pain. He had had a previous glycerol injection, which only gave him short term relief, but did give him some relief of his pain, but that pain had gradually come back after the glycerol injection. He then underwent radiosurgery to treat that affected trigeminal nerve and received a dose of 80 grade to a very small volume of that affected nerve. This is the typical response that we get a patient three, weeks out knowing substantial relief of his pain. Can appreciate me sent this picture, allowing me to use it. But in a very natural smile without any pain. He's been more than a year out now without any pain and awful medications. Certainly there can be a wearing off effect of this approach and we do need to be wary of that and may have to reapply this approach in some patients. That perhaps the biggest indication for expanding indication for radiosurgery has been the treatment of brain metastasis. Most brain metastasis occur by a hematogenous spread, although some can occur through a leptomeningeal spread and appreciate that these are well demarcated and generally spherical and generally a small volume. When we think about the sheer number of patients that have brain metastasis it's staggering, it's compared to any other histopathologic that affects the brain. An annual incidence in the US of new patients with brain metastasis has been reported to be as high as 300,000 to as low as 170,000. But this still represents a substantial increase as compared to patients even with high grade gliomas. We know that about 20% to 30% of patients that have metastatic cancer will go on to develop metastasis to the brain or the spine. And at the average age of onset is about 60 years. Median survival historically had been about six months and the typical histopathologic that lead to brain metastasis or lung, breast melanoma, and gastrointestinal cancers. Historic treatments are surgical resection, which neurosurgeons played a lot, obviously a major role, the use of corticosteroids, whole brain radiation therapy, which we would let our radiation oncology callings perform and systemic therapies. Chemotherapies that would be administered intravenously that occasionally and equally. There have been some studies that have looked at the role of surgery versus whole brain radiation therapy. And radiosurgery is one that was published in Cancer. It was a German study that looked at patients with solitary brain metastasis under three centimeters in size and those patients depicted here on the Kaplan Meier plot had no difference in survival between those patients who were randomized to the surgery alone arm versus the radiosurgery alone arm. Certainly, there are patients that an integrated surgery arm had less dependence upon steroids and a better quality of manifests compared to those patients who underwent resection followed by whole brain radiation therapy. When we think about local tumor control rates after radiosurgery, radiosurgery affords a high rate of local tumor control, Eden radiation resistant tumor histologies tumor control rates locally that is in those areas that we treat with radiosurgery are between 85% to 96%. Some of this depends upon the tumor histologies, but also upon the volume and the location of the tumors that we're treating. We know that improved survival is afforded by additional radiant surgery and occasion, whole brain radiation therapy for some types of patients. When we think about factors that influence tumor reduction, certainly the smaller the tumor, the more likely it is to respond and shrink after radiosurgery cystic tumors respond less well in terms of reduction. And in some instances, we will go ahead and stereotactically aspirate the cyst and then treat the neural nodule and rim of the CIS with radiosurgery, seeing a nice reduction as is depicted here in this set of figures, going from the preoperative MRI here in A, to the aspiration and radiosurgery and B the six month followup showing a nice reduction in the size of the overall mass, and certainly a greater tumor dose appears to afford a greater chance of tumor regression. Whole-brain radiation therapy has traditionally not had a tremendous role in the control of patients with radiation resistant tumor tumors injuries, such as melanoma renal cell carcinoma. In other words, standard fractionation schemes, giving 30 or 35 grade two grade per fraction schemes had very little in the way of reduction and occasionally some diminished role in terms of, tumor control as compared to more radiation sensitive, histologies like breast cancer or non-small cell lung cancer radiosurgery though can overcome these radiation resistant tumor histologies and afford excellent chance of tumor control and regression. Here's a case a young gentleman I treated with with three metastatic deposits from melanoma two that were fairly sizeable, one located in the left frontal region, another one in the right panel region and a smaller one not to pick it on this particular slice. And then the patient had a KPS of 100, despite these three minutes TAC lesions and was treated with radiosurgery and had a very nice regression of all three treated metastatic lesions. These two significant really large ones showing nice regression, seven months after radiosurgery. Other factors that affect survival have been shown to be related to age younger age, a higher Karnofsky performance status, no pre-existing neurological deficits, no active systemic disease. And certainly those patients that had massive effect that they underwent a reception for relief of that mass effect. Again, we note that over a fairly wide volume of metastatic deposits that reassured you offers an excellent chance of controlling the growth and actually causing to regress over time. Here's plotted local tumor control rates as a function of volume small volumes being under 0.5 CCS and more large volumes up to about slightly more than 14 to 15 CCS can be treated generally safely and effectively with radiosurgery controlling the growth within that treated volume. When we look at things that affect tumor volume outcome on followup imaging, we noticed that that most of them will go on and be unchanged or decreased in size about 10% will go on and increase despite a seemingly effective or seemingly a reasonable rate of surgical plan. And some will go on and dramatically disappear like I've shown in some instances up to about 21%. These that go on to disappear are typically reading and should sensitive histology such as breast cancer and on non-small cell lung cancer. Here's a case of a timber disappearance, a patient who has a solitary metastatic deposit that measured 3.4 CCS at the time of Brega surgery, six months afterwards, no demonstrable disease on the fault post contrast MRI, there's a substantial regression of a team that was up to 24 CCS had planned on operating on this patient, but the anesthesiologists had indicated that his comorbidities precluded him having a safe craniotomy resection. And you can see a very small residual metastatic deposit here nine months after radiosurgery with a volume of only about 0.2 CCS. Here's another case. And I think is if you excuse the pun, be a no brainer in terms of treating patients with radiosurgery. We see that patients with metastatic deposits in the brainstem really have tremendous response with radiosurgery in terms of growth control on the ventral shrinkage, neurological improvement when the shrinkage occurs and very little in the way of side effects, despite this being a very eloquent part of the brain, this is depicted here, a mid-brain lesion that was treated with gamma creative surgery and 12 months out after radiosurgery a volume that is almost half the size with even a slight regression in metastatic deposits to the brains. And we've seen dramatic improvements in patients from a clinical standpoint. One of the arguments in favor of radiosurgery has been that radiosurgery appears to give a chance to avoid neurocognitive neuropsychological problems that are oftentimes associated with the addition of hope and radiation therapy to patients with stage four cancer and brain metastasis. This was a pivotal study that looked at at VF randomization of patients to either radiosurgery and whole brain radiation therapy or patients with Rick randomized to really surgery. These were predominantly RPA class one and class two patients with one, two or three brain metastasis. The study that that Dr. Chang report in Lancet oncology was stopped early because there was a noticeable difference in neuropsychological testing. And there were cognitive testing in particular executive functions between those patients who underwent radiosurgery versus those who had radiosurgery and whole brain radiation therapy, the combined group doing substantial worse than the group that just got released surgery. In other words, whole brain radiation therapy, giving it to normal tissues isn't is inherently causing a risk of some degree of neurological decline in patients. Certainly one can argue that disease progression is perhaps the greatest risk. Whoever I demonstrated to a degree that radiosurgery alone can offer excellent local tumor control rates. This is a rather busy treatment paradigm showing the current practice at our institution for patients with brain metastasis. The patients that have five or fewer brain metastases will typically use radiosurgery. If there's local progression, we'll do salvage radius surgery. If there's diffused progression, we'll use whole brain radiation therapy, but those that have greater than five metastasis, we'll oftentimes do whole brain radiation therapy. But those that have massive fat or have a undiagnosed histology, we will go ahead and do either biopsy or an open craniotomy, again looking at cost effectiveness of what we do when we think about microsurgery versus radiosurgery for treatment of patients with different histologies such as, meningiomas in this case, we see a tremendous cost benefit for patients who are undergoing the surgical case. And I do think that in modern healthcare era, we're gonna have to be cognizant of the, cost-effective medicine that we're providing our patients. And if all things be equal or a patient is equally indicated for microsurgery or radiosurgery, that we have to think about the cost that we're charging to the healthcare system. If we perform one versus the other. This is a case looking at cost of radiosurgery versus whole brain radiation therapy in that cohort of patients that had multiple brain metastasis and the quality adjusted life year for radiosurgery, as compared to whole brain radiation therapy, it was substantially more cost-effective to deliver radiosurgery alone as compared to whole brain radiation therapy, even at one factor, then the need for salvage radiosurgery for patients that had distant brain metastasis formation. And when I started the presentation off, I had talked about the, basic principles of radius surgery being applied, not just to the brain, but also to the spine like cells work and his principles so successful that you see stereotactic body radiotherapy principles being applied to the long, had a biliary prostate and other head neck sites and different organ systems as neurosurgeons, we've gone on to use a slightly less precise, a slightly more image, intensive approach for treating spinal disorders, principally paraspinal and spinal metastasis. These devices can deliver radiosurgery to other parts of the body, the true beam, the X nigh, the Novalis, the CyberKnife Tomotherapy, synergy, Asur access system. All these systems are linear accelerators that require some degree of onboard imaging to track subtle patient movements if they occur and to compensate for those, but to deliberate, highly focused image, guided radiation in high doses, the areas in and around the spine that may be pathologic. This is one of the early systems that we use at the university of Virginia, a TomoTherapy system. It involves real-time CT scanning and preoperative, CT and MRIs are used to do the dose planning. It shows a patient with a pair of spinal metastasis, and you can appreciate that the tumor involves the vertebral body as well. Some of the posterior spinal elements to pick the here in the reddish purplish hues and the green area here is contour out. That's where the spinal cord is. And what we've done is to be able to render a dose that would basically avoid spinal cord toxicity in this patient. This is a typical patient that is treated with radiosurgery in the sense that she's older as metastatic cancer. In this case she'd had a previous corpectomy and she had undergone radiosurgery after prior external beam, radiation therapy. She had focal recurrence at C6/7, and her pain was principally in her neck and arm with a little bit of right arm weakness within a month after treatment of this patient, she had dramatic relief of her pain and ended up having tumor control, really graphically demonstrated up until the last point of fall prior to her dying. And she did not die of disease progression at this site, but of disease progression outside of the CNS. So I'll conclude by saying that I think radiosurgery is an important part of the neurosurgical practice. It's been demonstrated over the last two to three decades as being very safe and effective for many benign and malignant brain tumors psychologies. It offers low morbidity a high chance of affording a patient, a reasonable quality of life, minimizing neurological deficits, and a rear chance of causing any kind of radiation induced complications certainly has an excellent chance of reporting tumor control, enhancing quality of life and giving substantial pain relief for patients, either a functional disorder, such as struggling, lounger or pain associated with a pair of spinal or spinal metastasis, certainly dose escalation and careful fall to these patients are required. But I think that neurosurgeons play an incredibly important part in and frequently lead this treatment team when it's delivering lady's surgery to patients with CNS disease.

- Thank you, Jason. That was really a spectacular presentation, very thorough and comprehensive review of the principles of radiosurgery for diseases of spine and the brain. I would like to ask you some of the issues that are personal controversial in surgeon, my point of view, and I would like you to add some expert opinion to that. Number one is for a patient who has a small acoustic neuroma and has still some serviceable hearing, what are your thoughts there? Is it the way to go radiosurgery? Is there a chance their hearing can be better or is it best to watch and see how the tumor acts or hopefully the tumor would stay quiet and for awhile?

- Well, you're absolutely right. And you've touched upon a very controversial subject one, which is frequently debated at pet regional national meetings. It very much depends upon patient preference and patient age and their functional status of their hearing. In general, we've seen about 5% of patients who will have some degree of improvement in hearing after successful radiosurgical treatment of their acoustic aroma. In other words the tumor goes on and shrinks, and their hearing does functionally improve as well as improve on formal audiogram testing. But it's rare. And I tell patients that in general, that their hearing will, never be better than it is at the time of presentation of when they're discussing the option of radiosurgery. In other words, I don't think that radiosurgery typically affords improvement in hearing, and as I've indicated, that despite a greater than 90% control rate for acoustic neuromas after a single session radius surgery, hearing preservation rates at most centers are between 50% to 70%. So despite controlling the tumor, either as a result of longstanding compression of the tumor against the cochlear nerve or against, or because of eye Ultragenyx effects of radiation to the cochlea or to the nerve itself, hearing's declining in about 30% of patients that undergo radiosurgery. And so in general if it's an older patient, I would be more inclined to watch a patient with a small acoustic drama and follow them with closer Balal scans and audiograms as a younger patient. Unfortunately, my experience has been that watchful waiting doesn't last long, but I'm not opposed to watching and follow them closely. But in general, if a patient has more than 10 years in terms of a life expectancy, watchful waiting will only work for a short period of time.

- Let's touch another controversial topic. You described a case of a 63 year old male, very typical to a general neuralgia, or let's make it 58, let's put it that way, and they undergo medical treatment or refractory let's discuss microvascular, decompression nurses, ready to surgery. What do you coat as your recurrence rate of pain for patients undergo radiosurgery for trigeminal neuralgia?

- Well, first and foremost, for patients who are under the age of 60, who have a present with trigeminal neuralgia or refractory to medication, I tell them that we really need to come up with a lifetime strategy for dealing with their trigeminal neuralgia. And that is they will need at least one surgical intervention to maybe perhaps multiple interventions over a projected life expectancy in the US of more than two decades. And so I usually encourage patients to consider strongly a microvascular decompression first and foremost, if they don't have comorbidities that preclude them from that, I typically think of age as a general barometer of co-morbidities. Although obviously it's not necessarily the case. And there were some healthy 70 year olds who could easily undergo a microvascular decompression. And there are some rather sickly 50 year olds who shouldn't undergo microvascular decompression. So I think you've got to look at age as being one indication, and then obviously do a more thorough assessment on the patient's comorbidities in general, I think of microvascular decompression as being a longer and more about, radiosurgery is being a shorter term, although lower risk transit of giving patients pain relief we've seen in our institutional experience, that pain relief usually wears off in about 20% of patients that had initial pain relief at one year, we've seen about a 20% reduction, so that at three years, only about 70% of patients have dramatic relief of their pain after initial treatment with radiosurgery. So there's a wearing off effect with radiosurgery. That seems to me in my experience to be greater than that with microvascular decompression. And I think inherently, I'm a bit more comfortable with doing microvascular decompression for patients that have trigeminal neuralgia, because it's not an ablative procedure. In other words, typically with patients that undergo radiosurgery, if they're gonna have a beneficial effect, they can't have some slight degree of numbness that arises. And that's what we thought to be the ablative aspect of the underlying mechanism of radiosurgery. Whereas if everything goes well in experienced hands, microvascular, decompression shouldn't convey numbness in the trigeminal nerve distribution after effect of painful.

- Thank you. May I please ask, what are your thoughts on radio surgery for recurrent glioblastomas of high-grade tumors? And if you do surgery and a small residual tumor is left, what are the indications there versus recurrence later? And what are the risks and how would you consider consulting your patients and other physicians about that?

- Well, you're touching upon all the controversial subjects, which I've tried to avoid and a general overview. And in fact, this was, I had just come from the society for neuro-oncology meeting last week. And this was part of our educational days, a discussion about glioblastoma and the indications for radiosurgery. And I would say that thus far in the best level of evidence that we have so far radiosurgery has not shown a consistent effect in patients with high grade gliomas, in terms of prolonging life, at the life expectancy. We have seen anecdotal reports, mainly single center, retrospective studies that will come out of my institution and others where we inherently have a selection bias. But by and large, what I've seen is that some patients do benefit from radiosurgery that have high-grade gliomas, but we usually use it in the setting of patients that have small volume recurrent disease, not as an upfront boost to conventional external beam, radiation therapy, and Temodar. Again, as a neurosurgeon, I feel very strongly that maximal safe resection of a patient with a hybrid glioma is what we can deliver best for the patient met in some select patients, radiosurgery may have a benefit. I would say though, that there's increasing momentum to think about the use of radiosurgery in the context of patients that have recurrent glioblastoma and get radiosurgery while they're getting Avastin. And let me go back and say that the very notion of recurrent disease, most of these patients never have disease that's gone away. They always have some evidence of active glioblastoma, but patients that have recurrent a nodule of enhancing tissue, that's consistent with a concentration of glioblastoma and who are getting advanced and may very well benefit from the addition of radiosurgery. There've been two studies that have come out in the last year that have been looking at the addition of radiosurgery to Avastin and patients with recurrent disease that do suggest some degree of survival benefit. And remarkably, she suggests a little in the way of toxicity when radiosurgery is given with Avastin may allow us to give higher doses of radiosurgery to a GBM, and we could do without, the use of Avastin concurrently.

- Yeah, that's a very thoughtful answer. And I wholeheartedly agree with you on that. I think the verdict is still out there regarding GBMs and radiosurgery especially the high risk of radiation necrosis in that disorder. Let's touch on another topic may not be as controversial, but comes to mind if you have a young woman or a man with a small cavernous sinus meningioma, it is absolutely a symptomatic. Would you consider radiosurgery? Would you watch the lesion cuts reminding yourself of these reports that often come about once in a while of meningiomas that could potentially become malignant from radiosurgery? In other words, watching them could be a better option than doing radiation or with an increased chance of malignant transformation years down the line, especially among the young patients.

- Well we were certainly worried about surgical remedies neoplasia, and we know that in the setting of delivery of fraction of radiation therapy to the power cell region that risk of radiation DC aplasia is probably about 1% at about 10 years and maybe as high as 2% at 20 years, we have rare anecdotal case reports of radiosurgical induce transformation, or re surgical induced neoplasia after radius. Although we don't really know, I would say that risk of a radiosurgical induced the aplasia is probably lower than the risk of death with general anesthetic, and some have likened it to getting struck by lightning in terms of that risk. I mean, it's out there and it is a concern certainly is a greater concern for patients who are younger than patients who are older, that particular tumor psychology. If someone has a small trigeminal neuralgia more inclined to follow them and to get radiologic imaging, that helps us to map out the growth of that tumor and then to treat it when there's evidence of some degree of growth and or when there might be any concern about a neurological sign or symptom that could be to microsurgical resection. As I've said, numerous times, obviously in the hands of someone who's competent at traversing, the parachute region, I would say that there appears to be growing momentum to look at at maximum safe resection, via sculpins to approach placing priority upon neurological preservation and using radiosurgery judiciously to treat something that may and would potentially put the patient's neurological function, nerve function in particular at risk with a more complete resection. So I think we wanna use our tools. Why is it as neurosurgeons use a scalpel and microsurgical instruments when appropriate, usually the surgical approaches when appropriate and at times use the combination to maximize the benefits for our patients.

- I'm gonna ask one last controversial questions, but before I do that, do you have any other major areas of controversy that you think our viewers would like to hear an expert opinion such as yours? Well I would say that there are a lot of dogmas within radiosurgery. I would in general say that, some of the things such as a great tolerance to the optic apparatus to the three centimeter rule that is oftentimes used, these are just rules of thumb and dogmatic approaches that oftentimes really are based upon very little in the way of true hard scientific data. And that is someone who's reviewing this session might question that data at times, and to look back in the literature and recognize it much like other aspects of neurosurgery that although we have general guiding tenants or principles, even Don was that we at tangent here too, that we oftentimes have to look beyond those. And to think about the complexities of the care that we have to give patients.

- I really appreciate. I think that maybe you should tolerance of optic nerve versus that three centimeter rule or rule for the mass diameter that can be ready to surgically treated is definitely not always accurate. But something very close to that. As a closing question, I love treating acoustic neuromas, micro surgically, but I do agree there is significant risk associated with microsurgery for such lesions, for lesions that are above three centimeters. Going back to that three centimeters, do you strongly believe that if there's no evidence of brainstem compression, the surgery will play a major role on acoustics that are larger than three centimeters?

- Not here at my institution, not in my practice. I think that in general, patients who have larger case to go on less than I showed you, that one provocative case are better served by a safe and perhaps complete, although perhaps incomplete resection, followed by radiosurgery requiring that I think that there's nothing more gratifying and decompressing that the male cerebral peduncle on the brainstem and with interoperative monitoring, one can generally do that safely and effectively in patients who are even into their seventies. I do think that complete resection at the expense of the facial nerve is not to be done in the modern era of neurosurgery, at least not knowingly. But in general, I think for those patients that have large acoustic dilemmas and really wanna think about volume, not linear dimension, as you touched upon, and I've alluded to as well that drives should decision-making, but that by reducing the volume can make this a more appropriate target with radiosurgery. And so there's a complimentary roles of microsurgery followed by radiosurgery, but I see that there's not a great role for patients with large acoustic neuromas and the use of radiosurgery. I will say though, that there does appear to be an increasing, incidents of early diagnosis within the US so those patients that used to come in with large and moderately sized six is crucial moments are coming in now, after they've been involved in a motor vehicle accident, and they've gotten a CT scan that suggests something widening of the poor acoustic gifts, and they have a small acoustic neuroma that's been diagnosed, or they'd simply had a small episode of tinnitus and their primary care physicians ordered an MRI and diagnosed a very small acoustic arauma. And I follow a number, those patients, and we don't know what is the absolute like course. And I think it very much depends upon the patient too.

- I totally agree with you, Jason. I think the role of microsurgical essential for acoustics is important, but saving the face is the most important factor. We have completely turned over our acoustic practice for large tumor, too much to maximizing section with leaving a small piece of tumor. And here, of course, with a high rate of anatomical preservation, I think that's just makes sense in the era where utility and efficiency and safety of radiosurgery has been established when moving a small piece of tumor, a benign tumor from the facial nerve at the expense of a major facial nerve injury is not warranted. So I wanna thank you again, Jason. Obviously we love listening to you always, from your expert opinions, a very rational decision-making tree to radiosurgery. You make sense it's safe and it doesn't obviously... it's not biased. So I wanna thank you again and thank you for all the academic great work that you do.

- My pleasure and thank you very much. And I look forward to working with you on additional projects.

- Thank you.

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