Good morning, everybody. Thanks to Laura there for the introduction, and I want to tell the AANS I appreciate them letting me participate. Again, this has always been a very enjoyable conference. So I'm going to have two quick talks. I'm going to first start with benign tumor management, and then we'll quickly move to a second talk on malignant tumor management. And I just want to point out very quickly, at the beginning and end of my talks, there's my cell phone and my email, and you're very welcome to keep that and text me or email me anytime if I can help with questions. I also will apologize because I put a lot of slides and information here for a rather short talk. So I'm just going to go through and I'm going to hit the highlights, and I strongly encourage you guys to just take about 30 minutes later today when you have time or tonight and go through my slides a little slower and shoot me a question by text or email if you have questions after doing that. But do that so you can learn as much as you can about these topics while it's fresh on your mind. At the end of the talks, we'll go over some additional questions that our moderator will help us with. And then I'm going to come back at the 10 o'clock Q&A and help with questions here as well. All right, let's get into this. No disclosures. I'm going to follow this sort of outline for both of my talks. Okay. What are the incidence rates for primary brain tumors like? So let me just emphasize what we mean by primary. So these are tumors that originate inside the head. So these are not the secondary metastatic tumors. I will mention that a little bit later in my malignant talk. But if we just focus on just the primary brain tumors. So in the young age group, very, very common compared to other cancers. But of course, in the older age group where we're mostly treating these patients, it's still a rather rare type of cancer for us. What about mortality rates? So for primary brain tumors, mortality rates in the kids and the older folks is very low. So keep that in mind when we're counseling our patients. What is the distribution of primary tumors by behavior? So if you just look at primary tumors and you look at the pie chart distribution, you quickly realize easily a third of all primary brain tumors are benign meningiomas. And then about 20% are benign pituitary tumors, or we often call these pituitary adenomas. So about two thirds of this pie chart are benign tumors. So that's a good thing for us to keep in mind when we're treating patients with primary tumors. And just to be complete, what about primary tumors in the spinal cord? So similar picture. So over a third are benign meningiomas. And then another third are benign nerve sheet tumors. So these are the tumors like schwannomas and neurofibromas that you hear about. So again, vast majority are benign. What's the incidence rates by sex? So for the benign tumors, meningiomas, pituitary tumors more common in females, all the other tumors a bit more common in males. I'll let you look at some of these other slides on your own when you have a bit more time. All right. Let's focus in on meningiomas, the most common benign primary tumor in the brain. What are some of the characteristics of these types of patients with these tumors? This is a really good study looking at patients who had symptomatic meningiomas. So remember, the vast majority of these tumors that we see are incidental. They're asymptomatic, most likely not going to be treated. But for those that get treated, they're asymptomatic. Average age is about 60, much more common in females, more common in the white race. Neoadjuvant embolization in order to cut off blood supply to the tumors is something that is sometimes considered by some practices, but not all. It's not a way to treat the tumors, but it's a really good way to decrease blood flow to the tumor in order to make surgery much safer. So something to keep in mind, especially if you get a radiology report that says you have a large tumor that might be a bit more hypervascular than typical. We like to think that we do gross total resections on most of these patients. But in reality, it is hard to get a gross total resection on all of these tumors. And we'll discuss that a little bit more later. These other characteristics we're going to dive into in other slides. But the one thing I really want to point out is if your imaging suggests edema, and you have to differentiate that from encephalomalacia. So edema is acute swelling in the nearby brain, much more irritating to the nearby brain, and much more symptomatic. And if you see that, then you might want to be thinking about steroids and even seizure medication for those patients. Very different than encephalomalacia. So try to think about that and figure that out on your imaging. Okay. Symptoms are always based on the location of the tumor. So if the tumor is near the convexity, that is the side of the hemisphere, then you're going to have more seizures, more symptoms like seizures, headaches, maybe weakness because it's pushing on your motor cortex. And if the tumors are along the skull base, lots of different symptoms, most common thing will be visual symptoms, either diplopia or maybe even visual field cuts. If the tumors are in the skull base, in the back of the head, you're going to have more cerebellar symptoms like ataxia, dysmetria. So you always want to make sure that your symptoms make sense based on the location of the tumor. Diagnosis. This is probably the one tumor where we all feel very comfortable making the diagnosis by imaging alone. So they have very characteristic findings. This is a typical CT. These are MRI pictures. They're homogeneously enhancing, very avidly enhancing, very well circumscribed. They're dural based, and they almost always have an extension of the tumor along the dura nearby called a dural tail. When we take these tumors out, we always try to resect that as well. So very characteristic features on imaging tell you what you're dealing with. The location is also helpful for making that diagnosis. They can occur everywhere, but we roughly divide them up into these three regions. So about a third of meningiomas are going to be parasagittal. So right up here, right next to that superior sagittal sinus. So for these tumors, you might want to get things like MRAs to look at sinus invasion. About a third off to the side over the convexity of the hemisphere, things like this. This is where they push on your motor cortex or maybe your somatosensory cortex and cause weakness or paresthesias. And then about a third are along the skull base, and they can be anywhere along the skull base. Here's an example of what's called a sphenoid wing meningioma. It's growing off of the dura next to the sphenoid bone and the temporal bone. As these things slowly grow over years and decades, they often will slowly grow around neurovascular structures. And these sphenoid wing tumors are notorious for growing around the MCA branches that are traveling in the sylvian fissure, and they can follow along the back of the orbit and grow around optic nerves. So we always have to think about those neurovascular structures that these tumors are growing next to and growing around. Just a few quick examples. We call this a petro or retroclival meningioma. It's growing off of the dura here next to the clival bone. Here's one that's growing off of the floor of the anterior cranial fossa, right where the olfactory nerve is traveling. So we call that an olfactory groove meningioma. This is a really old case of mine, many years ago, where they presented with this large parasagittal meningioma, and they had this unrelated invasive prolactinoma. So we took this tumor out, gave them cabergoline for this, and both tumors disappeared. Okay, for pretty much all brain tumors, we talk about a grading system from the World Health Organization called WHO-GRADE. That is probably the most critical factor to know about tumors in order to counsel your patients on prognosis and the chances of recurrence. So again, pretty much all meningiomas are grade 1, 85%. So those are the benign ones. If you get it all out with surgery, they're cured. There are higher grade meningiomas, but they're rare. So about 15% are grade 2, about 1% are malignant grade 3. The main thing to be looking at on pathology reports is the mitotic index. So think about that, and especially brain invasion. Grade 1 tumors do not invade the brain. They're totally separate from the brain. So we can take those out and not sacrifice any of the brain. The higher grade ones invade the brain and are a little bit more challenging to take care of. There are some interesting histologies, and I'll let you come back and look at that on your own. Lots of different subtypes of histology. But again, the focus is on the grade. So think about the grade when you're looking at pathology reports. This is what the list of those histologies look like in the WHO classification scheme. So we're always interested in the genomics of brain tumors. And for meningiomas, it is somewhat bland. So for grade 1 tumors, very, very few chromosomal abnormalities, which you would expect for such a slow-growing benign tumor. But when you look at grade 2 and 3, you can really appreciate how genomically unstable these tumors are with all these chromosomal abnormalities. There are a few specific genetic mutations that are well-described for these tumors. The most common is NF2, neurofibromatosis type 2. That is the same gene that we talk about in those neurofibromatosis syndromes as well. There are a few hereditary syndromes that cause meningiomas, but they are so rare we do not worry about them. We don't go searching for them. But if you have a very obvious family history, then you might think about these. But nonhereditary sporadic meningiomas are by far the most common situation. And again, we think NF2 is probably one of the more common genetic mutations that can drive the development of these tumors. As of yet, we have not been able to really target that for chemotherapies, but hopefully in the future. Again, a few more slides I'll let you study on your own. What about risk factors? Everything has been studied from cell phones to radiation therapy to diet. There really are no current risk factors for meningiomas. Decades ago, there were situations where people may have gotten very high doses of radiation to the head that caused a radiation-induced meningioma. But nowadays, we really don't see that. Hormones is interesting. Most meningiomas overexpress receptors for progesterone and estrogen. Those receptors, when they're overexpressed on these tumors, can be triggered to make the tumors grow. So if you are exposed to extra hormones, your tumors will grow. The hormones don't cause tumors. In this case, they don't cause meningiomas. They simply feed them and can make them grow bigger. As an example, this is a recent young patient of mine just from a couple months ago, much too young to have such a giant meningioma. But she was going through fertility treatments, and we suspect because of that, she had a very tiny meningioma that then rapidly grew. So, of course, we had to take that out. She has done very well and now is more judiciously pursuing her fertility treatments. Okay, this might be the most important slide. So here's a good treatment algorithm to think about for meningiomas. So you diagnose it by MRI. If the tumor is asymptomatic, very small, you're probably just going to watch it. My scheme is to do an MRI pretty quickly in three months. I really want to make sure I don't miss something that's rapidly growing. So as an example, breast metastases can look exactly like a meningioma. I don't want to miss that. So I'm going to do an MRI quick in three months to make sure that it is stable. And if it is stable, then I'll do it in six months. If it's stable, then I'll do it in a year. And then I'll follow it for probably about five years. If no growth or changes after five years, many surgeons would stop monitoring it at that point. Okay, if it's a bigger tumor, there's edema, it's causing symptoms, and you need to treat it, surgery is first-line treatment. The goal is to try to get it all out, but that is challenging. If it's a grade 1 tumor and we are left with a little bit of a residual tumor, then we're just going to monitor that with MRI. Very, very low chance that tumor residual will grow. If it's a higher grade tumor, then we need more treatment. If it's grade 2, we strongly encourage radiotherapy. If it's grade 3, they must get radiotherapy. All of those are going to rapidly progress and probably limit their long-term survival if it's not aggressively treated. So for those incidental tumors, the natural history is excellent. So at least a third will not grow. They'll just have a completely flat growth rate for decades. So you can monitor those. All right, what does surgery look like? So we open the scalp. We open the skull. We're looking at dura. And you'll see this vascularity here. All the blood supply to these tumors comes through the dura. This is one reason embolization can be helpful. So the first goal of surgery is to open the dura all the way around this tumor, and that will completely stop all blood flow to the tumor. Once we get the dura cut away from the tumor, then we can start the challenging process of dissecting the tumor away from the brain. To get a complete resection, we have to take away the dura, we have to take away any overlying skull that was involved, and then, of course, take away the tumor. Preoperatively, MRI is going to be the best if you can get it. With contrast, if it's near arteries, think about MRI. CT can be very helpful for looking at bony prominences and calcifications that can make surgery a little bit more challenging. We have strong recommendations from our neurology colleagues that say we really don't need to add antiepileptic seizure medication to any of our brain tumor patients unless there's a clear seizure. However, because of the nature of our practices, we often will put patients on seizure medication. But there's not a strong reason to do it unless they have a seizure. They don't need steroids unless there's obvious edema. Interoperatively, very, very important that we have Manitoul available. That's really going to have the biggest impact on creating space, so allowing the brain to shrink a little bit to create a little extra space to make surgery safer to get those out. What are some of the poor prognostic factors? Probably the most important thing is age and frailty. So think about how frail your patients look when you're discussing their outcomes after craniotomies for these tumors. And there are ways you can assess that. There are scoring systems that you might want to consider. We often talk about KPS status, and I'll show you that in just a second. But that's another good way to kind of assess how well you think your patients will do after surgery. What are outcomes after surgical treatments? They're good, but they're not perfect. So if it's an acute presentation and they have symptoms like seizures, headaches, cranial neuropathies, most of those will get better. But you'll notice none of these are 100%. But most will get better. If it's a more chronic neurological deficit, those will also get better. So most of these will get better. But again, there's not 100% for any of those. Again, natural history is excellent for asymptomatic tumors. This is a great study looking at over a couple thousand patients. And the green line follows these patients who had no symptoms, got no treatment, and their long-term prognosis is excellent. So always remember, first do no harm. I just want to mention this because sometimes you'll hear it. So us surgeons, we often talk about the Simpson grade. That is not like the WHO grade. So this refers to how much of the tumor we take out. And this is only for meningiomas. So if we get out all the tumor, all the dura that's involved, all the bone that's involved, then we consider that a true gross total resection. We call that a Simpson grade one. So don't confuse that with WHO grades. A few more slides. I'll let you study on your own. This is a good example of where we took out this benign petrochlebal meningioma. But we had some tumor that was stuck on a cranial nerve. So the best thing is just to leave a little bit of that. Statistically, that will not grow. But we can monitor that with MRI down the road. This is kind of an example of a case I had about a week ago of a patient who had a meningioma down here in this area that we call the CP angle. And so you can appreciate there's a limited ability to retract on the cerebellum. You're near the brain stem. You're near critical arteries. You're near cranial nerves. So this is why it's not always possible to get that gross total resection. We just have to be aware of the anatomy in order to help counsel our patients on what to expect. OK, a few more slides. I'll let you read on your own. Are there good adjuvant therapies for meningiomas? For example, for any residual meningioma or maybe higher grade? Very, very limited. I've already mentioned radiotherapy. So that does have really, really good control rates. So what we mean is it stops the tumors from growing. It will not shrink them and make them disappear. Now, you will occasionally see some tumors shrink. You'll occasionally see some tumors swell in response. But I think the best strategy to counsel patients is the purpose of radiotherapy is to control it so it doesn't grow anymore. So in this example, even after 10 years, 75% had perfect control of their residual tumor. So this is a good option. It's only good for small tumors, tumors with no mass effect, and tumors that are not around critical structures. Those things can be targeted with radiotherapy. But the risks, obviously, are going to be much higher. Radiotherapy, even though we recommend it in many situations, it's still not uniformly used. So we could probably do a better job there. Overall survival for especially the higher grade tumors is slightly better with radiotherapy. We are starting to see clinical trials looking at more targeted chemotherapies. They are targeting specific genomic changes or molecular pathways. None have made it to standard of care. So hopefully, in the next few years, we'll start to see more of this. So as of now, with chemotherapy, we really don't have anything that's kind of effective and considered standard of care. OK, quick take-home points. OK, quick take-home points. Meningiomas, most common brain tumors, 85% are benign. Small asymptomatic ones, you can just observe. If they're symptomatic, then we need to treat them with surgery. And if necessary, consider follow-up radiotherapy. OK. OK, let's quickly hit some highlights for pituitary tumors. So this is about another third of all those primary benign tumors that we see. They have pretty characteristic imaging results on MRI. So classically, they're homogeneously enhancing, just like this one. They symmetrically expand the bony sella turcica floor. So this bony floor gets symmetrically bigger. That's very different from the way other tumors behave. And they characteristically have this sort of snowman shape as it grows superiorly through the opening in the arachnoid around the pituitary infundibular stalk as it grows upward and pushes on the optic chiasm. So in this example, this little gray structure here is the optic chiasm being pushed up. Now, unlike meningiomas, these have a really broad differential. This is a great mnemonic to remember, SACHMO, to remember all these other things that can occur in this part of the brain. The anatomy that we think about. So if we look at this mid-sagittal MRI and we blow up that area. So again, pituitary gland, pituitary stalk, optic chiasm, hypothalamus. This is the sphenoid sinus airspace. So it's normal for the gland and the stalk to enhance. So that's a normal-looking gland. A few pictures on some of that important anatomy. So remember the cavernous sinus and the structures inside the cavernous sinus that are lateral to the pituitary. There's carotid arteries, some cranial nerves, important things to think about. The physiology for this area is important to think about. So I encourage you to come back and look at these slides that talk about how the hypothalamus controls anterior and posterior pituitary. These are the pathways and these involved network of capillaries that help control the posterior or neuro hypothesis. When this is irritated, this is what causes diabetes insipidus. Very important that you're familiar with this, especially in apoplexy. So come back and study this little paragraph about diabetes insipidus. And of course, we know about the feedback mechanisms from the target organs onto the hypothalamus that controls the pituitary. This is a little bit of what it looks like. So we go through the nose to take these tumors out. So here we're looking at a ball of tumor. We're separating it from a little pseudocapsule. Optic chiasm is going to be up here. Cavernous sinuses are going to be off to the side. So for the sake of time, I'm going to skip a few of these slides. There are a few hereditary syndromes, but very, very rare. Lots of molecular biology that's being explored, but none of this has made its way to developing any sort of targeted therapies, targeted chemotherapies yet for these tumors. We typically divide these pituitary tumors into two subtypes. The non-functional, that is they do not hypersecrete a hormone, versus the functional, where they are over-secreting a hormone. So we always want to test for this, especially for prolactin-secreting adenomas. Very common. And just remember, prolactin levels, normal is up to 20. 20 to 50 is just from mass effect pushing on the stock. And if the prolactin is in the hundreds and thousands, that's most likely a true prolactinoma. And we want to get those patients to our endocrine doctors, because they can cure this tumor with bromocryptin or cobergelin. So we want to test for these pituitary hormones and make sure we understand what the impact is with respect to caring for these patients. So you want to look at growth hormone secretion. You want to look at ACTH secretion. It might be causing a cushionoid-type picture. Remember, there's Cushing's disease, which is different from the syndrome. So the disease is due to a tumor in the pituitary-secreting ACTH. The syndrome can be due to other things, like excessive steroid exposure. Lots of tests to figure that out. The dexamethasone suppression test is probably the most common test to help figure out that Cushing question. And there are other hormones that can be over-secreted, but very, very rare to see these. In my practice, the vast majority are asymptomatic and incidental, so we just observe them. There's no clinical benefit to taking those out. If they're symptomatic with headaches or optic chiasm compression causing bitemporal hematopoieia, then they need to be surgically resected. If they present acutely with apoplexy, we consider that emergent. In those patients, you have to look for diabetes insipidus and emergently treat that with cortisol supplementation. A little bit more anatomy. There's some interesting histology that I'll let you look at on your own. Outcomes are very good. So for those tumors that do not invade the cavernous sinus off to the side, excellent gross total resection, excellent improvement in visual problems. Excellent remission of hormonal over-secretion in those tumors as well if we take them out with surgery. Excellent improvement in other cranial nerve deficits if we take those out with surgery. And I'll let you look at that on your own. This is a great slide. It shows that visual fields improve for years after taking out these tumors. So up to five years, you'll see the visual field deficits continue to slowly get better and better. OK, a little bit more information I'll let you read on your own. Probably the most important thing to think about when you're looking at imaging is if the tumor grows laterally and invades the cavernous sinuses, we classify that by the NOSP classification scale. Obviously, that means it's harder to get all that out. And the risk to those structures are higher. So we tend not to dissect into the cavernous sinuses. Our main goal is to get the bulk of the tumor out and decompress the optic chiasm. Radiotherapy is also useful for these tumors if you have a little bit of a residual tumor and you want to keep that from growing. Complications from radiotherapies like GammaKnife are very, very low. It's a very safe option if you have to use it. Progression-free survival, so if you have to treat a residual pituitary tumor with radiotherapy like GammaKnife, most likely that residual tumor will never grow. There are a few invasive tumors that grow very differently than your typical pituitary. Fortunately, those are also very, very rare. This is a case of mine where we went in and we just debulked it. But there's a lot of tumor that left behind. But we got all the pressure off of his chiasm, so his primary problem of visual field deficit's improved. So we're just going to monitor that because there's no great benefit to take this out if it doesn't grow. So know about apoplexy, so very acute presentation, worst headache of life. They have ophthalmoplegia, causing diplopia. This is different from the simple visual field cut. This is due to the tumor suddenly infarcting and swelling or hemorrhaging. So there's a very rapid increase in the size of the tumor and compression on the structures. These patients have diabetes insipidus. Most of them will have DI. You have to recognize that and urgently treat it. And then we often urgently take them to surgery to decompress those structures. OK, there's some quick take home points about pituitary tumors. Again, very common, 100% are benign. Small asymptomatic ones can be observed. If they're symptomatic, then we need to treat it. And the primary treatment is surgery. If we feel like we need to follow up with other therapy, radiotherapy is a good option. And like meningiomas, we don't have any effective chemotherapies at the moment. Remember to look out for prolactinomas because that's a great tumor that you can quickly cure it with a medication. OK, I added a few pictures of a few other benign lesions that you might think about. And you can look at these at your leisure. OK, so again, there's my email and text. So please go back when you have time and just spend a little bit more time on those slides and let me know how I can help you with questions. Let's ask our moderator if there's any quick questions before we move on to our malignant brain tumor talk. Thank you so much, Dr. Adamson, for this very thorough overview of tumors. And I look forward to the next section. A couple of questions from the audience here. We talked about, you mentioned the lady with fertility treatment. And one of the questions is, do you recommend avoiding OCPs, hormones, in these patients? No. And the reason is because that's such an important part of their life. And meningiomas are rare. So the chances of having a patient like I showed you are very, very low. So I would not avoid those treatments. But it's something to be aware of. So if you're treating a patient like that and they have some complaint that localizes to the brain, then, of course, scan them and look. But the chances of that happening are very, very low. So don't worry about it. Move ahead with their treatments. Very good. And then one of the sessions yesterday, we talked about artificial intelligence. And tell us about, do you use stereotactic guidance in some of your tumor surgery? And how do you think AI might help you with resection? Great question. So at the moment, we don't really use AI anywhere. Now, it is standard of care for most brain tumor resections to use some type of neuro-navigation. So you probably have heard of things like the Stealth System Brain Lab. And there are a couple of others out on the market where we use preoperative imaging to help us guide our way around the brain and the structure. So we are using neuro-navigation during many of our brain tumor surgeries. So that's very, very helpful. We're also using a lot of intraoperative neurophysiological monitoring to monitor the activity of the brain and cranial nerves basically in real time. So for example, I mentioned that case of the CP angle tumor and the tight space of working down next to the brain stem and the cranial nerves. So that's an example where we monitor, for example, facial nerve activity throughout surgery to try to keep that safe. I think the first place we're going to see AI is probably going to be on analyzing imaging. There are a lot of other situations where imaging could be used more to help us clarify the diagnosis. And we're doing some of that. And I kind of think that we'll probably see AI make its way into analyzing imaging to help us tell us what we're looking at. In my next talk, I'll emphasize some of the challenges with imaging. And that's a place where I think AI could be very, very helpful. There's also lots of studies going on of trying to use imaging to predict molecular changes and genomic mutations. And believe it or not, that's a good feasible question. So AI might help us predict, especially in malignant tumors, what is going on genomically. And that might help us think about more targeted chemotherapies in the future. Wonderful. Thank you so much, Dr. Adamson. That's a good lead-in to your next talk. There's been some good comments in the chat. Sorry we couldn't get to everybody. But we're trying to stay on time. So on to the next lecture. Thank you so much.

benign brain tumors

meningiomas

pituitary adenomas

radiotherapy

neuro-navigation

AI in imaging

tumor management