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Associate Director of the Gamma Knife Center at Cleveland Clinic, Samuel Chao, MD, joins the Cancer Advances Podcast to talk about the evolution of gamma knife technology. Listen as Dr. Chao takes us through gamma knife's history, the current advantages and considerations, as well as potential future advances in the field.

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Evolution of Gamma Knife Technology

Podcast Transcript

Dale Shepard, MD, PhD: Cancer Advances, a Cleveland Clinic podcast for medical professionals, exploring the latest innovative research and clinical advances in the field of oncology.

Thank you for joining us for another episode of Cancer Advances. I'm your host, Dr. Dale Shepard, a Medical Oncologist here at Cleveland Clinic, Directing the Taussig Early Cancer Therapeutics Program and Co-Directing the Cleveland Clinic's Sarcoma Program.

Today, I'm very happy to be joined by Dr. Sam Chao, Associate Director of the Gamma Knife Center here at Cleveland Clinic. Dr. Chao was previously a guest on this podcast to discuss distinguishing brain tumor progression from radiation necrosis, and that episode is still available. He's here today to discuss the evolution of gamma knife technology. Welcome back.

Samuel Chao, MD: Well, thank you for having me, Dale.

Dale Shepard, MD, PhD: Remind us a little bit about what you do here at Cleveland Clinic.

Samuel Chao, MD: Well, I'm the Associate Director at the Gamma Knife Center. My main focus is to treat brain tumors, as well as spine tumors, with radiation. I'm also Vice Chair of Quality and Safety in the Department of Radiation Oncology.

Dale Shepard, MD, PhD: Excellent. We're going to talk about gamma knife technology. Give us a little bit of an idea, what exactly is gamma knife technology? What is gamma knife?

Samuel Chao, MD: Gamma knife is a stereotactic radiosurgery platform. It's really designed to treat brain tumors. When it was first conceived back in the '50s and '60s, the thought at that point in time was that the scalpel didn't really have a role in terms of treating anything within the brain. Certainly, we didn't want to cause more damage than any benefit. So the thought is that if you can do anything non-invasively, that's all for the best. Obviously, back then there wasn't enough imaging technologies to really target things like brain tumors.

So really, have to fast-forward to the '80s and '90s, to really develop those imaging technologies to be able to target things like brain tumors and other functional disorders that we do sometimes treat with gamma knife radiosurgery.

Gamma knife uses 192 beams of radiation, at least in its current iteration, all focused on a single point. What we try to do is to dot shots with radiation to the tumor, and cover the entire tumor, and obviously try to kill the tumor.

Dale Shepard, MD, PhD: So, 192 beams, that's a long way from just having a radiation source. It just blasts anything in its path, right?

Samuel Chao, MD: Absolutely, absolutely. There, it spares the surrounding brain as best as we can, and really targets what we need to target with a high-intensity focus of radiation.

Dale Shepard, MD, PhD: Now, you mentioned that this is a platform for stereotactic radiosurgery. How does gamma knife, just from a terminology standpoint, and make everyone understand the differences here, what's the different between gamma knife and SBRT?

Samuel Chao, MD: Gamma knife is a stereotactic radiosurgery system. Just by definition, we usually qualify stereotactic radiosurgery as a treatment for things in the brain or the spine, anything that's CNS related. SBRT is usually thought about in terms of stereotactic radiation. Very similar in concept to what we do in the brain, but to other sites in the body.

So many platforms that we do use, in terms of treating SBRT, could also treat the brain. But the gamma knife is a dedicated system specifically for the brain, which does offer some advantages.

Dale Shepard, MD, PhD: What kinds of advantages would that be? Just the ability to localize a little bit more precisely, or what exactly are we looking at from advantages?

Samuel Chao, MD: Yeah. Some of those advantages include just efficiency in terms of being able to treat. For example, with traditional SBRT systems, linear accelerator based radio surgery, things like the cyber knife, often requires quite a bit of pre-planning. In other words, you have to get a CT scan that's separate, that usually takes a while to do the plan, usually a day or two before you can actually treat the patient.

With the gamma knife system, all of that can be integrated within the day. The patient would come in early in the morning, we can do the MRI scan, the CT scans, the immobilization, whether that's going to be with the frame or the mask. And then, literally plan out the treatment. The treatment is very, very straightforward in terms of its planning, and go ahead and deliver that treatment all in the same day. That's a little bit more difficult to do with other systems.

Dale Shepard, MD, PhD: All right. Again, just trying to help people understand this whole process. You mentioned immobilization with a frame and a mask. Tell us a little bit about that, why you might use one over the other?

Samuel Chao, MD: Excellent question. Historically speaking, frame was the de facto standard for treating brain tumors using stereotactic radiosurgery. You put on this frame, using two screws in the front, two screws in the back, it holds the head rigidly. And then, you get a CT scan for localization, then you deliver the treatment.

That being said, there are other improvements in terms of gamma knife technology. For example, with the Icon, which we obtained several years ago, that allows us to do a cone beam CT before treatment, which does allow for flexibility in terms of a mask based treatment. And now you can, going from a frame based treatment now to a mask based treatment, with exact same precision and accuracy with the frame. The advantage of that is that now you don't have to put on the frame, which can be sometimes concerning for some patients. It's completely non-invasive now.

And it also allows us to be able to do fractionated radiosurgery. Rather than just having to do just single session radiosurgery for some of the larger tumors, they may have some benefit in terms of fractionating. Now, we're able to do these treatments over five days, to be able to better be safe about the brain.

Dale Shepard, MD, PhD: That safety comes from less energy per fraction?

Samuel Chao, MD: Exactly. Less energy per fraction allows for some normal tissue healing in the surrounding structures. And for things that are bigger that you really need to get the dose in, sometimes fractioning and delivering the radiation over multiple days can be safer.

Dale Shepard, MD, PhD: And we talk about size. When we think about doing this as a procedure, what are the limitations practically in terms of size of lesions, number of lesions? What are some of the restraints from that standpoint?

Samuel Chao, MD: That changes ongoing. Historically speaking, we used to say, well anything four centimeters or less is something we can target with stereotactic radiosurgery. That was back in the days when we were doing frame based, and doing single session or single fraction radiosurgery. Nowadays, with the ability to both either fractionate or even do what we call staged stereotactic radiosurgery, we're allowed to treat not only bigger lesions, but also many more lesions.

In terms of the practical limitations, we could treat 10, 20 spots within the brain for metastatic disease. Historically speaking, that was actually fairly cumbersome. But with improvements in terms of technology, and the efficiency in terms of treatment delivery. And not only that, being able to sometimes even spatially space these apart. Rather than having to force the patient to be treated for 20 lesions in a given day, which could probably even take many, many, many hours, giving them a break and coming back another week to get another handful treated, so that we could even treat upwards of 20 plus lesions if need be.

Dale Shepard, MD, PhD: From a practical standpoint, it's hard to count the number of times you go in a hospital service, and someone comes in with a brain met. And of course, radiation oncology gets consulted, neurosurgery gets consulted. What are situations where radiation's clearly better, situations where surgery clearly would be better?

Samuel Chao, MD: Often times, we try to think about radiosurgery as our number one modality for treating brain metastases because it's non-invasive and it's really easy to do. It gets patients back on their feet quicker, they can go on to systemic therapies much quicker than if we do something invasive like a craniotomy.

That being said, craniotomies to take out tumor still has its role, in terms of the management of brain metastases. Patients who are very symptomatic, tumors that are extremely large, impinging heavily on the brain, causing a lot of swelling or edema in the surrounding brain tissue, may benefit from doing surgery. With us going up and seeing the patient up on the hospital floor, as well as neurosurgery, it allows us to chat about the patient, decide on what's the best option.

One of the things that we have started to do over the last several years is to even consider doing the radiosurgery before we do the surgery, what we can an neoadjuvant radiosurgery. Therefore, it can make things a lot more straightforward, a lot quicker in terms of their treatment. They don't have to wait afterwards for us to do radiation, to clean up the resection cavity. It makes the radiation much tighter. It prevents the development of leptomeningeal disease, and also reduces the risk of radiation necrosis. Many of these patients even that come in the hospital and we decide that we want to do surgery, sometimes we can strategize by doing some radiosurgery in advance, to essential "sterilize" the tumor.

Dale Shepard, MD, PhD: When we think about the technology, we're 192 beams, its ability to do masks now with localization and with CTs. What are some of the things that are still limitations? Are there things that are being developed to make this an even more effective therapy?

Samuel Chao, MD: Absolutely. I think, one, we think about how successful we are with gamma knife radiosurgery in the management of let's say brain metastases, and for the most part, I think 80, 90 percent of time, we get good control. But there are some issues that do develop. One, there is local recurrence. Perhaps, we could strategize more with systemic therapies to decrease the chance or recurrence for brain metastases. Some of that has been shown, particularly with immunotherapies and other targeted therapies that can be done in addition to radiosurgery to act synergistically for tumor control.

The other thing that we struggle with is also radiation necrosis. If you give enough radiation to the tumor, and we talked about this in the past, you can cause quite a bit of inflammation that could develop, months out, or years out. Sometimes, that could also be frustrating to manage and take care of so we also want to reduce those risks.

Trying to treat more brain metastases. When we talk about the management of brain metastases, we try to do radiosurgery as much as we can. But as you get to the higher numbers, in the 15 and 20 range, certainly that makes it much more cumbersome to deliver. Hopefully, with improvements in terms of efficiency with planning that may come out in the future, especially with the new Esprit system, that make it more straightforward to treat many more lesions.

Dale Shepard, MD, PhD: Are there any particular areas in the brain, the spinal cord, are there areas that are still difficult to treat based on location?

Samuel Chao, MD: The brain stem is always a little bit risky in terms of treating, though we've done it multiple times and determined to be it safe. It's always something that sits in the back of our minds and we have to always give fair consideration about the potential toxicities of brain stem necrosis.

The optic nerve and chiasm is usually a no-fly zone for radiosurgery. Those structures are very, very sensitive to radiation. But if we could figure out a way or a strategy to treat them, radiosurgery wise, either fractionating in some way, shape or form, those things could be considered. But still, yet to be discovered. That's yet to be thought of.

Dale Shepard, MD, PhD: I guess if we're talking about radiation, we're talking about different types of radiation. We talked about SBRT versus gamma knife. Something that would inevitably come up is protons. What are situations where people might advocate for protons instead of gamma knife? Just so people get a sense of what the practical application of that would be.

Samuel Chao, MD: Protons has an interesting physical feature. It delivers a very modest dose of radiation, until it gets to its target, delivers a lot of radiation, and beyond that it doesn't deliver any radiation. For tumors that are really close to very critical structures, it certainly offers some advantage. Radiosurgery does it a bit of a different way. What we're trying to do is really try and minimize dose to the surrounding structures and focus the radiation directly on the tumor.

There are things that we still need to treat with protons. For example, things that are a little bit largely infiltrative in the brain, we're going to be fractionating it and delivering radiation over six, seven weeks, for instance. We still have to utilize proton therapy, we can't use radiosurgery to achieve that effect, in terms of keeping dose away from critical structures.

There's always going to be a role for proton therapy in terms of management of things like craniospinal radiation, which obviously requires a larger field of radiation. But yet, you're trying to spare normal tissues and structures.

People are trying to figure out whether or not they can do proton therapy in a radio surgical format. Using protons as a means to deliver radiosurgery. There's a lot of things that we still don't necessarily understand about protons in terms of its biological effects and radiobiological equivalents. In that case, it's still things that we need to work on in terms of understanding the physics of proton therapy and the radio biology of physics better before it becomes prime time. But stereotactic radiosurgery in the form of gamma knife or linear accelerated based radiosurgery already has a long, safe track record.

Dale Shepard, MD, PhD: We talked about using gamma knife for things like metastases. What's the role for benign lesions?

Samuel Chao, MD: It definitely has a very important role in terms of managing benign lesions. We treat things like meningeomas, pituitary adenomas, vestibular schwannomas with radiosurgery, all with 90% plus success rates in terms of tumor control. Certainly, in some of those cases it's very difficult to do anything from a surgical standpoint. Often times, they're in the base of the skull. They're next to or adhering to critical structures. That's where the advantage of radiosurgery comes into play.

Not only do we use radiosurgery to treat benign brain tumors, we also use it to treat functional disorders. Tremors can be treated with stereotactic radiosurgery, as well as trigeminal neuralgia can be treated with stereotactic radiosurgery. Some vascular disorders like arterial venous malformations, or AVMs, are treated with stereotactic radiosurgery.

One of the programs that we're starting to develop here is to use gamma knife radiosurgery to treat pain syndrome. Patients with cancer pain syndromes that are very refractory to medications, by treating the pituitary, you can actually exert some pain relief. There's been some studies to show that so we're going to be starting our program fairly soon.

Dale Shepard, MD, PhD: That's great. When we think about these therapies, we talked about gamma knives and some possible improvements on that. Do you think the future in terms of better treatment for patients is primarily improvements in gamma knife? Or is there some other technology that you find particularly exciting that might be more effective?

Samuel Chao, MD: That's a great question. We certainly feel that gamma knife is going to constantly continue to improve on itself. We're looking forward to what those improvements are going to be that's going to be developed by the company. But there's a lot of other things that are coming that are exciting, that I think work together with gamma knife radiosurgery.

For example, laser interstitial thermal therapy, which was developed her in part at the Cleveland Clinic, certainly has a role in terms of being able to take care of recurrent disease that recurs despite gamma knife radiosurgery. In which case, then, we can do a laser interstitial thermal therapy, biopsy the tumor so we know exactly what we're dealing with. And then, sometimes following that up with fractionated radiosurgery. Or, if the patient develops radiation necrosis and we can use that to treat that.

Something in terms of technology that almost looks similar in concept to gamma knife radiosurgery is HIFU, or high-frequency ultrasound. That's used to, actually, can cause lesions within the brain. And they are using that, for example here at the Cleveland Clinic, to treat tremor disorders as well.

Dale Shepard, MD, PhD: I guess given the range of different ways things can be treated, the expertise you have within these therapies. One thing I always like to think about is what type of patient, what type of condition would someone benefit from coming to a high volume center like Cleveland Clinic, compared to being out in the community setting and getting radiation therapy? Are there particular types of patients that really need to have that discussion about different modalities and expertise?

Samuel Chao, MD: No, absolutely. We treat about 900 plus cases per year at the Cleveland Clinic, between our two machines. We have an Icon machine, as well an Esprit machine. I think there are things that we can do that may not be easily offered over in the community.

For example in the community, they may be able to treat one, two or three brain metastases fairly easily. But as the number of brain metastases goes up, it can be much more trickier to treat. Also, it can be much more difficult to follow because you have to follow these multiple lesions. These are things that we do as experts in terms of what we do here at the Cleveland Clinic.

Managing toxicity. Even though we talk about gamma knife radiosurgery as being an excellent modality to treat brain metastases for instance, there's still a five to 10 percent risk of radiation necrosis anytime we do a treatment. We need to follow for that and we need to be able to manage that. Places that done really have a lot of expertise may not easily manage those indications. They may even not have the modalities to be able to accurately diagnose radiation necrosis for instance. Certainly, we have a huge team to be able to do that.

Dale Shepard, MD, PhD: Well, Sam, you guys are doing great work, have a lot of exciting technologies available to help patients. Appreciate your insight.

Samuel Chao, MD: Well, thank you very much.

Dale Shepard, MD, PhD: To make a direct online referral to our Taussig Cancer Institute, complete our online cancer patient referral form by visiting clevelandclinic.org/cancerpatientreferrals. You'll receive a confirmation once the appointment is scheduled.

This concludes this episode of Cancer Advances. For more podcast episodes, visit our website, clevelandclinic.org/canceradvancespodcast. Subscribe on Apple Podcasts, Spotify, or wherever you listen to podcasts. Don't forget, you can access real time updates from Cleveland Clinic's Cancer Center experts on our Consult QD website at consultqd.clevelandclinic.org/cancer.

Thank you for listening. Please join us again soon.

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