Thomas Beaumont, MD, PhD, Neurosurgeon, Professor of Neurological surgery and Deputy Director of Moore’s Cancer Center Biorepository, talks about glioma and how one of his patients is doing after surgery.
Tell me about Sabrina. Tell me what you found in her?
BEAUMONT: Sabrina came to my clinic with a pretty fairly typical picture of a low-grade glioma. She’s a young person who started to have behavioral changes and then subsequently had seizures. And based on the imaging alone when I saw her in clinic, I expected this would be what we call a lower-grade or non-glioblastoma type glioma. These are WHO-grade 2 or 3, the lower-grade tumors.
Can you tell me the difference between glioma and glioblastoma?
BEAUMONT: Gliomas are malignant brain tumors that fall on a spectrum. That spectrum is from low-grade, even grade one – which you generally don’t see in adults, up to grade four, which is glioblastoma, the most aggressive type. And then there’s everything in between so grade two and three are the so called “lower-grade tumors”. They are malignant, as are all gliomas, but they’re much less aggressive and slower growing than the grade four tumor, which, despite 20 years of research and aggressive efforts in many labs, including mine, the survival’s still on average about 18 to 22 months for glioblastoma, where on the flip side, if you do a very aggressive operation on a lower-grade tumor, you don’t hurt the patient in the process and you get essentially all or more than all of it out, patients can survive seven to 12 or15 years on average and, with contemporary technique, even beyond.
Like, the tentacles go through the brain. Do gliomas do that, too, or are there more?
BEAUMONT: They do. These tumors do it to a varying degrees but the difference with primary brain cancer compared to, for example, breast cancer or colon cancer, et cetera, is that when people have metastatic breast, colon, lung cancer taken out of some other part of their body, they sort of visualize it as, you know, a ball of tumor wrapped up in normal tissue and that’s actually correct. It does tend to infiltrate a little bit, but that conception is correct for brain tumors. However, gliomas, on the other hand, are a disease of induced tumor stem cells and those cells are flowing throughout the brain and they’re flowing along all of the wires, if you will, the deep white matter throughout the brain. So, in some places, they take residence, and they grow and they make a large collection. That is the tumor that we see on imaging. There’s a large amount of tumor that we don’t see. Then there’s infiltrating tumor on the edges of the larger enhancing tumor that is visualized on scans.
For breast cancer, there are a lot of these underlying factors. It can be genetic. It could be lifestyle. It can be to much alcohol, way all this stuff. Is there something for glioma that…?
BEAUMONT: It’s a very common question, of course. If you get diagnosed with a brain tumor, the first thing you think is why me? How did I get this? Are my kids going to get it, et cetera? The simple answer is, the overwhelming majority of these tumors occur, as we say, de novo or from within, based on factors in your own genome and the environment that you’ve interacted throughout your life. There are certainly genetic syndromes that predispose you to getting these tumors. Overall, those are few and far in between compared to basically the tumors that just arise spontaneously. What I would say, if I were to put on the scientific hat that I wear often is that it’s really a collection, a collision, if you will, of these two forces; one, the genetics that you received that may predispose you to having cells sort of escape their regulatory control and create tumors and then your interaction with the environment that you live in, diet, et cetera.
So, with Sabrina, where was her tumor located?
BEAUMONT: Her tumor was on the right side of her head, which was good for her. If it’s on the left side, that’s where most of our dominant language and memory function is. Hers was on the right side of her head in the temporal lobe and extending back into the temporal lobe into an area we call the temporal stem, and then back along the hippocampus to the thalamus, a major sensory relay center in the brain.
Removing that, what were the risks for her, in her life? What could happen to her? Like, it wasn’t her speech or her vision?
BEAUMONT: Well, vision for sure. Again, you picked up on an important thing. So left side of the head is a completely different enterprise. You know, I do most of the tumors in the left side of the head here. Those require us to do surgery awake with stimulation mapping for motor areas, neuropsychological testing for language. The good part, if you will, about having this in the right side of the head is we don’t have to do that. The other good part about that is because the right side is less eloquent, less sort of important for these critical executive functions, we can do a more aggressive resection and take out more brain without compromising the patient. What this meant for Sabrina, most importantly, is two things. One is her vision came right over the top of it, we used a bunch of high technology that we have here to map those wires, and respect them while we were doing the surgery. Now, there’s not a good way to do stimulation for visual fibers, we’re working on that but at present, you have to just kind of basically know where those fibers are, map them pre-op, put them into your mind and then take them with you to surgery. Also, what’s nice now is we have augmented reality technology that allows us to really live in that world that we mapped through our microscope when we’re operating. In regard to the surgery that we did for her, vision was probably the biggest risk, the biggest objective risk. It’s also a very risky surgery because we’re basically peeling off her entire temporal lobe and the tumor off all of what we’d say is the medial temporal structures, the brainstem and the blood vessels that pass through there. Counseling a patient about risks for surgery like this, those include stroke, coma, paralysis, death. Nothing unusual for us, because in neurosurgery, as one of my mentors put it, peril is around the corner at every step. While we’re peeling the tumor off, this very thin membrane, called the pia, it sort of gives us a boundary between all those critical little blood vessels that are feeding the brainstem or going elsewhere, large blood vessels. If you punch through that thin membrane and manage to unintentional take one of those blood vessels, Each one’s a little stroke in the brainstem. That’s a problem, the risks for her were significant. Fortunately, though, the discussion is usually pretty intense about what the surgical risks,after surgery, everybody’s like, I feel great, you know? Why’d you scare me so much? But you have to do it because things can go sideways.
The new technology is what makes something like this even possible, right? Because 15 years ago, it wasn’t possible.
BEAUMONT: Yes, to some extent. I’ll qualify that. What I mean by some extent is some of the best people on the planet who operate on these tumors, frankly, who I try to emulate in any way possible when I’m operating, 15 or 20 years ago, they didn’t have these tools. What they knew is we needed to push the margins of these tumors as far as we possibly could and take out even normal brain very aggressively around the tumor. So, they didn’t have these technologies and what they had were classic studies of neuroanatomy. They had intraoperative mapping and they used it a little bit more permissively then because they really didn’t know. Then they had patients who did well and patients who had complications. This was the frontier, now, fast forward 20 years, we have this ability to use all of these augmented reality technologies and really instead of saying I know from my education where these fiber bundles are. I do know that but yours are different than mine, different than another person’s to some extent andit also all gets shifted by the tumor. Now we can map all those fibers. We can make a model of the tumor. We can have this in three-dimensional space. I can look at it in my office in three-dimensional space and literally walk inside of it with augmented reality goggles on and really live in that world I’m going to operate in before I go there. Then I just know where I’m going. It’s essentially like getting in my car at the end of the operation to drive home, It is quite familiar, that’s what we can do now. We can actually still benefit from the way that, our predecessors who really advanced the field operated because we can take this technology and say we know we need to do a huge operation, a so-called superatotal operation, take more than just the tumor to achieve the best disease-free survival for the patient. Now we have the tools to actually know exactly how to get around a lot of these structures, whether awake or asleep.
Is that done through a special MRI? What’s that called?
BEAUMONT: It is. We have a whole bunch of different sequences of MRI. You could ask my residents about how challenging it is to make sure it’s all right but many things happen behind the scenes. One of those is called diffusion tensor imaging (DTI) and what that is basically saying if I push a water molecule in a restricted space, does it go straight or not? And if those water molecules are inside of tubular wires, they move along anon-random course and we can identify all those wires and map them. So together, that’s called diffusion tensor tractography. We use that, and we map all of these fiber bundles. We also have the ability to segment and map critical brain stem and brain structures that we know we want to avoid or where those fibers should go to help us understand how faithful that mapping is to reality.
if the water molecule doesn’t go straight, does that mean the tumor is there?
BEAUMONT: No. The idea is this. DTI’s used for a whole bunch of things. You’re right to say that because if you take diffusion tensor imaging and you just look at the tumor, you see areas around it where the water molecules don’t diffuse because it’s compact tumor. There’s no free diffusion. It has restricted diffusion. But the advanced thing we can do is say, let’s really talk about restricted diffusion and say, imagine this. If we had a bowl full of water, it’s just all random movement. It’s diffusing all over the place based on temperature, right? But if you have a whole bunch of tubular wires and you want to know where they go right? When you charm those water molecules, push them with MRI, and then ask where they went, you can map them. It’s kind of like when you approach, you know, an interchange on the road in a major city, you can map every one of those wires coming through there because each one of the lanes is restricted.
Is that what you use then for your augmented reality?
BEAUMONT: That’s right. So that’s part of it. So we can map fiber tract, the tumor. And literally anything that you could imagine seeing on a computer screen, in three-dimensional space, I can kind of create within the brain space of the patient, in this case, Sabrina. And so we make a model of the tumor. We make a model of what we think may be infiltrating areas of tumor. We make a model of what we think might be the swelling around the tumor ’cause you can’t know completely, right? We have that. That’s a big volume and we have all the wires mapped. We have, like I said, some anatomic structures mapped. And then what happens is when we’re operating, I’m looking through a microscope and that’s my world. But piped into that world can be whatever I want to see. It can be the brain tissue I’m operating on. It can be the brain tissue with an overlay of all of these structures in three-dimensional space. It can be fluorescent dyes. It can be different imaging studies. It can be a navigation instrument. It can be, for example, during awake surgery, if we’re stimulating, looking for language and motor and we find it or don’t find it, I can save points in space. And when I come back to them, those points will be shown to me again.
And through all of this animation and, you know?
BEAUMONT: Yeah, I spent three decades getting here, studying and being excited. I rarely go home even after a 12 or 14-hour case not still excited because it’s just a tremendous place to be able to be. I can tell you that my OR staff always says, how do you do it? Because I just get in there, and the time constant stops. And then all of a sudden, we’re done.
How long was Sabrina’s surgery? Do you remember?
BEAUMONT: The actual operating part in her case was probably about eight-plus, maybe eight to 10 hours. In the family eye, it’s usually, you know, oh, gosh, this was all day, 16 hours, because they come in at 7 o’clock in the morning and we finish at 10 or 11 at night. There’s set-up time, interoperative MRI, preparation, all these things, but I’d say it was a good 10 hours, about eight to 10 hours of operating.
So, what is Sabrina’s outcome?
BEAUMONT: She’s doing fantastically. Our goal with her surgery was first and foremost to not hurt her, and secondly, to take out all of the tumor. If we could achieve what we call superatotal resection or take out the tumor and take out any brain around it in a very aggressive way, that basically, for lack of saying a better way, she wouldn’t miss, we achieved that essentially on all of the margins around the tumor, with the exception of one. That temporal lobe structure that I told you about even if it’s your dominant or nondominant, it doesn’t matter. They’re both the same. They’re wired similarly, grossly at least, and they connect very similarly. There’s a lot of connections that come out of the temporal lobe because it’s your sort of basic emotions, your instincts, your memory, etc. There’s a lot of wires that come out of there and where those wires come around and go into the brainstem, basically, as we call it, the hippocampal tail where it comes into the back part of the brainstem. She had a little bit of tumor on there that kind of wrapped around the corner that from that approach, we were not, able to get. We achieved about 98% resection by volume, I believe is the number that I have on her and there’s around 5 cubic centimeters of tumor left in that area, and we watch it. If it’s stable, we do nothing. If it starts to expand, we ask what’s the velocity of expansion? Two things push our hand to take her back to surgery, regardless of whether she’s symptomatic or not, the velocity changes or the volume crosses about 6 to 8 cubic centimeters. Then I just take her back.
Well, what’s key for Sabrina is you were so successful that she didn’t have to have chemo and radiation, and all those things?
BEAUMONT: That’s right. You have to qualify that a little bit, though. I told you there’s four grades to gliomas, and grade four is the worst. Grade one’s the best. We rarely see those [grade 1]in adults. Grade two and three can have very good prognosis. The grade three’s really the threshold point. When you take out a grade two, you ask yourself – are there any areas on imaging that have heightened blood flow or so-called hyper perfusion that we look for? Were there any little areas that had enhancement? Because if they do, that little area might be grade three, even though the entire sea of tumor is grade two, you’ve got to treat it like a grade three because there’s parts of it that already transformed. And that means there are tumor stem cells circulating through that brain that have already transformed. In her case, the entire thing was grade two. There was no area of it that appeared to be grade three. And because we essentially had around every margin with the exception of that very small one, posteriorly going on to the brainstem, a superatotal resection, we’re just watching it with surveillance imaging. Now, she gets MRI scans every two to three months. And we’ve also talked about some clinical trials that can be done for low-grade tumors, you know, sort of prophylactic treatments upfront before there’s progression. And right now, she’s just undergoing surveillance imaging and living her life, fortunately, anxiety-free and seizure-free.
How many more years do you think you gave her worry-free?
BEAUMONT: Well, so what I told her when I met her is that on average, if you take people with lower-grade tumors, the classic numbers we talk about are the median or approximately average survival is about seven to 12 years for a young, healthy patient with a low-grade tumor. What we do know actually from some data and ongoing studies, if you achieve a super total resection, I say that number’s at least 15 years and probably more like 20. But we don’t really know because those few people in the world who have a study going where they do superatotal resection, we don’t know what the median survival is because they haven’t achieved it, which is a good thing. I would say in her case, 15 to 20 years is what I hope we gave her. My goal, as I told her as well, is we convert this thing into a chronic disease for her now that within 15 to 20 years, the landscape could change entirely. And, hopefully, we could cure it.
Now you just got to keep her safe, and the car is going 150?
BEAUMONT: Yeah. She tolerates thrill and risk quite well, much like she shows when she’s accelerating super rapidly in some hyper car with her business partner and life partner. She was nervous preoperatively but basically said, great, great. So when can we do it? I can’t wait till you can get this out of there. I’m going to feel so much better. Then she said, oh, and what happens if I die? Will you, like, use my brain for research or could I donate my organs? She’s very objective about these things and I think part of that was motivated out of anxiety in retrospect. Now she’s, you know, super grateful. We talk about it all the time. I’ve already told her in her lifetime, I do expect, unfortunately, to operate on her again. I’m going to do everything I can do to convert this into a chronic disease for her, hopefully one that we can cure in her, and in my lifetime.
Interview conducted by Ivanhoe Broadcast News.
END OF INTERVIEW
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