A Discussion with Nels Knutson and Geoff Hugo on Radiotherapy for Ventricular Tachycardia

THE INTERVIEW

 

Tyler Blackwell:
Yeah, well, I want to thank you guys both for coming on. Thank you Dr. Hugo, thank you Dr. Knutson for joining me today on just a little talk about VT. I know Washington University is a world leader in VT or video cardiac radioablation, specifically VT. And so I’m excited to hear your guys’ expertise and your experience with this so far. So really quick, just to get started, I want to briefly introduce the cast of characters here, since we will have people watching. So my guests are Dr. Nels Knutson and Dr. Geoff Hugo. Both medical physicists at Washington University in St. Louis.

 

Tyler Blackwell:
I’m Tyler Blackwell. I’m a medical physicist and I work with Radformation. I worked at a regional cancer clinic for about 10 years before transitioning to industry with Radformation, which is a group that focuses on automation solutions and radiation oncology. But interestingly, I attended undergrad with one of these characters, with Nels. So we both attended the University of Montana and went through the physics circuit their together before going off to study medical physics at some other sites. So Nels, maybe, you can start us off real quick and we can come back to Geoff. But can you backfill some of your history? Where are you? Where’d you come from? What was your path? And what’s your role there at Wash U?

 

Nels Knutson:
Yeah and thanks Tyler. So Tyler and I both graduated from the University of Montana, physics. Tyler was smart and basically went and got into grad school. And I didn’t know what to do, so I ended up getting a math degree, which was pretty weird. And then ended up going to LSU for grad school, and then Wash U for residency, and then was lucky enough to finally end up back here for a job, and took on the chief of clinical physics, just a little while ago, interimly. And yeah, that’s where I ended up.

 

Tyler Blackwell:
Yeah, that’s cool. Yeah. So yeah, for the rest of the world, what Nels didn’t tell you is he’s got a cute little puppy named Louie. And also while we were schooling in Missoula, it was Nels that introduced me to one of his good friends, a girl named Hallie in the math department who is now my wife. So I sort owe Nels on an ongoing basis for the rest of my life. So thanks Nels.

 

Nels Knutson:
No problem.

 

Tyler Blackwell:
Well in the other corner, we’ve got Geoff Hugo, who I know more recently from an interaction at the Winter Institute Of Medical Physics in Breckenridge. That was a pretty fun conference, this one. And one of the last conferences we had, I think, before COVID strike- struck, and we have kind of a moratorium on these types of things. But yeah, Geoff was kind enough to offer me a buddy pass. So we spent a lot of time together on the slopes. So yeah, Geoff, can you give us a little context and background for you?

 

Geoff Hugo:
Yeah. Yeah. Thanks Tyler. Well first we should say I tried to follow you and that didn’t go so well until I got my legs under me a little bit. But it was a good time.

 

Tyler Blackwell:
It was fun.

 

Geoff Hugo:
Great meeting, by the way. I mean that was my first time and it was a blast.

 

Tyler Blackwell:
Yeah. We need to go back.

 

Geoff Hugo:
No doubt. No doubt. Hopefully they’ll have it. Yeah, so my background is in medical physics. I went to Penn State as an undergrad, way before you guys graduated. And did a physics major with a medical physics minor, which was just actually bio-engineering had nothing to do with radiation oncology or imaging, but it got me excited. I went to UCLA and did biomedical physics there through their grad program, and did my PhD. And then moved around a little bit, I was at William Beaumont for a number of years, and then Virginia Commonwealth before I ended up here, at Wash U, about three years ago. And so, like Nels, I’m also in a new role in the interim, division director. And yeah, I love to do research, clinic, and then teaching, so all three aspects.

 

Tyler Blackwell:
That’s great. Yeah, so Geoff is being extremely modest. The last day at Breckenridge, he was streaming down black diamonds, so he’s a pretty excellent snowboarder actually. But yeah, very recently you’ve been doing a lot with VT here at Wash U. And actually, Geoff was moderating a couple talks just last week on cardiac radioablation. You moderated two talks, if I remember correctly. So yeah.

 

Tyler Blackwell:
Yeah, well thanks guys. Well ultimately what I was hoping to accomplish today was just to pull apart this topic of ventricular tachycardia, because to me it was only brought to my attention, I think, less than a year ago. And I suspect I’m not alone with that. So naturally, as a former clinician I want to know more about it. Where it shows promise, what the challenges are, what clinical implementation looks like for those who might be interested, stuff like that. So yeah, I think just starting with the basics, I’ll admit I’m not acutely aware of what VT was, or what it meant aside for just the branches, ventricular tachycardia. So you can put together a little picture, but maybe you guys can explain what VT is.

 

Geoff Hugo:
Tyler, you should know all about this from my talk at WIMP, man. I’m disappointed that you didn’t remember every single word that I said.

 

Tyler Blackwell:
The one great thing about the moderated talks at the AAPM con-virtual meeting, is that you can actually go back. It’s all recorded. You can just go back and listen. You lose focus or attention, you can go back. You can’t do that at WIMP.

 

Geoff Hugo:
Yeah, that’s true. Exactly right. I love that about the meeting, being able to go back and look at all the comments and things. But yes, so VT is, I should say, ventricular tachycardia, it’s a heart arrhythmia. So basically the heart is beating too fast. What happens is it’s beating so fast that the blood can’t get out of the ventricle and get pumped to the body, so it can cause sudden cardiac arrest. So your blood’s basically it’s not being pumped correctly, you get no circulation, and that can lead to death. So it’s a very serious disease. It’s interesting because in the cancer world, we talk about cancer and benign diseases, it’s often classified as a benign disease. For radiation oncologists, it’s not benign. It’s deadly.

 

Tyler Blackwell:
Right.

 

Geoff Hugo:
So it’s super important to treat and to identify. And yeah, so radiation is one option for therapy now or at least it’s an exploratory option.

 

Tyler Blackwell:
Yeah. Yes. So it’s pretty new to the scene. So, but why, I guess, are we just seeing radiotherapy as an option now versus the past?

 

Geoff Hugo:
It’s been around for a little bit. So there’s some early first-in-man studies done at Strava and Stanford. But then beyond that, there was a good number of animal studies that were done. And the concept was one of the treatments currently is catheter-ablation where they go in with a catheter and map out where the arrhythmia is located. It’s often associated with a scar, like from a heart attack, but not always. But go in and map out where the actual arrhythmia is arising from. And then they can burn it or something like that with this catheter.

 

Geoff Hugo:
And so you’re basically killing off that muscle that’s causing where the arrhythmia is coming through. So the initial idea was, hey, why don’t we try that with radiation. We can necrose tissues, so let’s irradiate to dose and see if we can do that. So there’s a good number of animal studies, and then I think the reason that it’s in vogue now is that there was a trial, or a few case series done here at Wash U first, and then a phase two clinical trial that has good results. And so we have to give the shout out to Cliff Robinson, the radiation oncologist, Phil Cuculich, our electrophysiologist that really took the steps and got that going here, along with a bunch of folks. With that publication of the good results there, I think people get excited about giving it a try. And hence, why we’re seeing people being interested.

 

Tyler Blackwell:
Yeah, so it sounds like you guys got one of the first starts in phase one, phase two trials. Was anyone doing it coincidentally? Or was it just you guys?

 

Geoff Hugo:
Well like I said, there’s a couple of case reports out there of people trying it successfully in humans. But I think here at Wash is where we started doing a trial. And people wanted to look and see what the results were like from that. With good results then I think that gives people some assurance they can go and try it at their own clinic.

 

Tyler Blackwell:
Yeah. Well I think it is a good idea on paper. You look at the just RF, catheter-ablation and it looks like the results can be challenging. I think I saw somewhere between 50 to 70%, oh geez, fail rate, or maybe it’s 50% just curate. So I think the idea is that there’s just limited success. And treating it is invasive and it’s just inherently challenging. So maybe that’s why right now there’s the SBRT advantage for VT, versus the other existing options. So really briefly, can you just describe what we’re starting to see then with radioablation?

 

Geoff Hugo:
Yeah, so I think that’s a really good point. There’s a couple of reasons we’d want to look at other therapies. One, is the success rate of existing therapies, the fact that many are invasive, drugs are pretty toxic that patients go on. But the other thing is the size of the treatment area, some with these catheter approaches, you can’t always get where you need to. With radiation, obviously, we can get really anywhere in the heart that we need to irradiate from a technical standpoint, whether there’s sensitive structures is another story.

 

Geoff Hugo:
And so I think that’s one of the really important aspects of it is that you can get in there, you can do it noninvasively, it’s fast compared to a catheter-ablation. For us in radiation oncology, it’s interesting because we’re used to seeing the patients go in, lie down, get radiation, come out five minutes later. But one of the videos that our physicians often show the cardiologist is this video of the patient going into the room and then walking out. And so, they’re all amazed, because nobody walks out of a catheter-ablation.

 

Nels Knutson:
Right.

 

Geoff Hugo:
So where as all of our patients do. So that’s, I think, a really compelling side of it, looking from the cardiology side and why they might be interested. So yeah, now there’s a lot of people interested. We’re talking to a number of sites, I don’t even know how many worldwide treatments there have been to date, but certainly over a hundred patients treated with cardiac radioablation.

 

Nels Knutson:
Yeah.

 

Geoff Hugo:
We’ve alone, I think, talked to probably close to 40 sites just to help get them started, and share what we’ve learned, and we’re being very open with anybody that really wants to give it a go to really help them get started.

 

Tyler Blackwell:
Yeah, right. And Geoff, I wasn’t completely ignoring your talk at WIMP. I do remember the graph. I remember the graph that showed the rise there in the number of places that are offering it, and I know that you guys have been very open with offering all the expertise, and all your experience, and data, which is really cool.

 

Tyler Blackwell:
Yeah, so are you guys, what’s the treatment fractionation looking like right now? Is it a single fraction or are you guys doing multi?

 

Nels Knutson:
No, we do single fraction 25 Gray x 1. It’s changed a little bit since we first started, as Geoff was saying. When we first started it was you’d treat this really high blade of dose, and cause scarring, and all this stuff. And so originally, we were having these really hot plans, really heating up like an ITV cord type thing. Um, and now we’ve backed away a little bit and are planning it more… It’s still SBRT-like, high doses in the middle, very conformal, rapid falloff. But maybe not pushing higher doses like 35 Gray, to the middle or anything like that, just more natural SBRT-like.

 

Tyler Blackwell:
Okay. More homogenous inside?

 

Nels Knutson:
It’s still heterogenous, for sure. It’s still SBRT.

 

Tyler Blackwell:
It’s still hot?

 

Nels Knutson:
Yeah, still hot. But it’s not necessarily like we’re doing almost an integrated boost-type volume any more. It’s more just let it naturally be hot in the core and go from there.

 

Tyler Blackwell:
Yeah. That sounds good. So curious, before we jump too far into talking about the treatment, but I want to talk about how we know what to treat. We have pretty good experience with SBRT for different sites: liver, lung, spine. And for lung, for example, you can often see the lesion. You’ve got PET to confirm exactly where it is and you can just draw a circle, but how is VT different? Are you able to take a CT scan and see the scar? Or what other imaging data do we need for this?

 

Geoff Hugo:
It’s very different. There’s no specific,…you can’t see the direct target. It’s just not something you can see. So unlike a lung tumor, like you were just mentioning. So there’s really two to maybe three pieces of information that are used. And two of them are pretty critical.

 

Geoff Hugo:
One is anatomical information, like you’re talking about you can often see a scar on CT or MR or other modalities, where if the patient has a scar, and so you can identify that and look at anatomically where the scar is. Then they use electrical information. So we should mention electrophysiologists, this is their bread and butter, is figuring out where these arrhythmias are coming from. And so that’s the person, really working with radiation oncology to really figure out where they want to target. So they’ll use the electrical information 12-lead ECG or some other fancier stuff like ECG imaging, which we can talk about. But they need to use the electro information, because it’s an electrical arrhythmia. So putting those two pieces of information together, they can identify the region that they want to treat.

 

Geoff Hugo:
Sometimes we use metabolic information as well, like a PET or a SPECT to look at regions that are basically deficits in the signal that may be associated with scar or damaged heart muscle.

 

Tyler Blackwell:
So then from the radiation oncology department’s perspective, you guys are just getting a report from electrophysiology, and they provide a map of where it is?

 

Geoff Hugo:
I think it really is like a partnership between radiation oncologist and electrophysiologist. I mean certainly the electrophysiologist is doing that cognitive work, but you still have the core principles. We want to treat the minimum amount of tissue that we need to. We don’t want to over irradiate, because there’s sensitive organs like the stomach, or the esophagus around there.

 

Tyler Blackwell:
Yeah.

 

Geoff Hugo:
The heart itself, right. There’s some concerns, obviously, if you irradiate too much heart, so we want to minimize. So there’s still those same core principles. And then electrophysiologists aren’t typically used to drawing contours on a planning CT. So we still have a lot of partnerships there, where they’re working together with the radiation oncologist, who’s job is to do that exact thing.

 

Tyler Blackwell:
Yeah.

 

Geoff Hugo:
I’d say it’s more of how they work together, they sit together on the computer and then hand it off to us to figure out how to point it out.

 

Tyler Blackwell:
Well, no. I think it’s cool that you guys already have that relationship created. I mean I don’t know that most people have a good relationship yet, maybe, with their electrophysiologist. Or, I mean, sometimes it’s hard even to get pace-maker information from cardiologists. So I think that’s always an ongoing challenge. It’s just creating that pathway for information and collaboration. So good for you guys.

 

Geoff Hugo:
There is a side benefit, I do have a cardiologist… I have his cell phone number now. So if I need to get some info, we can get it kind of easily.

 

Tyler Blackwell:
Yeah, right. You just text him at night and say, “Hey, I mean what’s your restaurant of choice? Where do I need to eat dinner?”

 

Geoff Hugo:
There you go.

 

Tyler Blackwell:
That’s good.

 

Geoff Hugo:
You do learn a lot more. So it’s been helpful from that standpoint. I mean we still have to deal with pace-makers and things like that. But learning a little bit more is always good.

 

Tyler Blackwell:
So, okay. You get the information from them, from a different physician. They work together, the radiation oncologist. And you outline a GTV. What does it look like then from a contouring perspective, because there’s inherent challenges treating a beating heart that’s positioned right in the rib cage with the lungs that move around. So I’m hoping maybe you can talk about… Well this is a big question, guys. So sorry, I shouldn’t unpack this one. But yeah, maybe you can talk about motion management, and contours, ITV if there is one, what margins look like. I’ll just let you guys go.

 

Nels Knutson:
All right.

 

Geoff Hugo:
I’m going to let the master handle that one.

 

Tyler Blackwell:
Nels is pointing at Geoff. Geoff’s pointing at Nels.

 

Nels Knutson:
I think what the key with them working together is identifying the core area where the target in the heart was located, and everybody being in agreement to that. And then it’s taking that information and translating it to the rad-onc world that we’re more used to, with a simulation, et cetera, and how we’re actually going to hit it. I feel like a lot of times, Geoff does his crazy wizardry behind scenes and hands it off to me, and says, “Okay. Now go hit this ugly target.” That he hands to you. They’re pretty complex. I think you can see it in the original some of the more complex shapes. He’s like, “Oh, yeah. This should be no problem, right?” Yeah.

 

Tyler Blackwell:
Nels kicks it back.

 

Nels Knutson:
Exactly. So I think basically like you allude to, there’s all these issues. We’ve come a long way, sort of, in how we deal with it. I feel like… To back up, when I first came back to Wash U, like four years ago, I heard, “We’re going to treat this heart SBRT. And it’s 25 Gray x 1.”I was just like, “What are you doing?”

 

Tyler Blackwell:
Or not.

 

Nels Knutson:
Yeah. And I was like, “Okay. So that’s what we do.” And then I ended up being in charge of the stereotactic program here. And so I got a lot more involved in it.

 

Nels Knutson:
So to walk you through, we treated it very similarly with this philosophy of do not miss when we first started. We leaned on our lung SBRT experience pretty heavily. It’s all the usual suspects, 4D CT, to help assess the motion, and all this. And as you pointed out, the heart beats, and that’s going to be near 4D CT, the respiratory 4D CT. And your lungs move, fill. So we have this motion, so we started there. And got more, and more, I guess, fancy as time went on and we learned lessons.

 

Nels Knutson:
So basically where we would start is the 4D CT respiratory gated, we also get a cardiac gated 4D CT in the treatment position on our scanner. And we use those two. And another key this was going with an untagged recon, the average recon essentially, as our reference image from the respiratory, and then the respiratory 4D CT. And then we get this cardiac gated one, which doesn’t have respiratory motion in it. And we put those two together to try to assess both. So the respiratory 4D CT, obviously, the patient’s heart is still beating, so it has heart motion. It also has respiratory motion. And you have a cardiac gated that has respiratory only, because it’s done under breath-hold.

 

Tyler Blackwell:
Okay. So the cardiac gated CT is a breath hold, and you just want to nail down what the motion is from the heart beat, is that correct?

 

Nels Knutson:
Exactly, yup. And we can look at both of them and the treatment plan system. And we merge those together, along with Geoff’s electrical information. And we can use that to just estimate our motion envelope, or ITV type thing.

 

Tyler Blackwell:
Yeah.

 

Nels Knutson:
And using all that information together, simultaneously, that’s how we would build a traditional ITV type of thing. But assuming it’s cardiac motion and respiratory, and we are getting an estimate of that basically through those two 4D CTs, and then treating it like a PTV.

 

Tyler Blackwell:
Cool.

 

Nels Knutson:
Yeah, man.

 

Tyler Blackwell:
So the way I understand it, you’re saying that you take a respiratory gated CT, so does that mean that you guys are not using immobilization at all or any compression?

 

Geoff Hugo:
We use compression pretty routinely. We aren’t using gating. We’re requiring a respiratory correlated scan to get the ITV, but we haven’t done any gating. I think with the abdominal compression, and the other uncertainties in the process, we haven’t, at least, at our institution a patient where we really felt strongly that gating was needed.

 

Tyler Blackwell:
Mm-hmm (affirmative).

 

Geoff Hugo:
We’ve been pretty comfortable with the ITV strategy and the don’t miss strategy.

 

Tyler Blackwell:
Yeah, I mean it-

 

Geoff Hugo:
So there’s a-

 

Tyler Blackwell:
Oh, go ahead.

 

Geoff Hugo:
No, I was going to just say that what Nels was alluding to with the crazy targets that I provide, is I’m not doing the targeting, but we’ve got some prototype software that lets the electrophysiologist input what they’re doing, and it maps it onto a model of the left ventricle that gives them some guidance on where they want to target. And then they’ll clean that up to make the GTV, but it’s just to help them get into the frame of reference of a planning image.

 

Tyler Blackwell:
Mm-hmm (affirmative). Yeah.

 

Geoff Hugo:
But there’s a lot of uncertainty there still, so I think the question is how much benefit is it to do respiratory gating with the heart motion, and all that, and not being able to really see the heart that well on. Maybe fluoroscopy or something like that.

 

Tyler Blackwell:
Yeah, we’ll it’s… No, I think people are doing SBRT lung in a similar way. Some people treat it ITV, some people gate. So I think it just is up to the clinic to do. But you mention, or I think yeah. UCSD, I want to say, is doing a gating program?

 

Geoff Hugo:
Yup.

 

Tyler Blackwell:
So that’s interesting.

 

Geoff Hugo:
Mm-hmm (affirmative).

 

Tyler Blackwell:
Listening to their talk.

 

Geoff Hugo:
Yeah, yeah. Yeah, no they’ve had a couple patients, I think, we’re talking to them, with a lot of motion. And so they looked into gating. They’ve got a nice gating workflow. Todd Atwood there has developed some nice stuff.

 

Tyler Blackwell:
Mm-hmm (affirmative).

 

Geoff Hugo:
Mm-hmm (affirmative).

 

Tyler Blackwell:
Yeah, so you said there’s a bit of uncertainty with the mapping. And I can see that really easily, you may have some physiological information, some imaging data, but then… So there seems to be a bit of uncertainty, so I know you’re drawing an ITV, but what kinds of margins are you putting on for that ITV or are you comfortable just putting on a typical stereotactic, like a five millimeter margin?

 

Nels Knutson:
I think it’s multiple pieces too. So the ITV, it’s not exactly like a lung tumor where you clearly see it move in this envelope. Instead, we’re looking at two different studies that have different motions. And estimating what we think is a reasonable safety envelope of that motion, granted, plus the GTV uncertainties and that as well.

 

Nels Knutson:
And then we handle the PTV margin, we try to handle it separately. It really is the setup uncertainties and all of that. So I think it depends on how you’re doing it. I think when we very first started doing this, or when Cliff did, before I got back here, they were doing it on a TrueBeam no-stick soft couch. This was pre-average the average scan being the reference, all sorts of stuff. And so we slowly fine tuned that process to now we use stick soft couch alignment to the average scan, on a modern TrueBeam Edge stereotactic unit-

 

Tyler Blackwell:
Mm-hmm (affirmative).

 

Nels Knutson:
… and stuff, and so tweaking that down.

 

Tyler Blackwell:
Okay.

 

Nels Knutson:
But largely it’s been very much building a comfort zone and fine tuning.

 

Tyler Blackwell:
Yeah. That sounds like you guys are doing the LINAC-based treatment?

 

Nels Knutson:
Yeah.

 

Tyler Blackwell:
Yeah, great.

 

Nels Knutson:
Yeah.

 

Tyler Blackwell:
I mean if you’re doing it on Edge you’ve got some small leaves there in the center. Using 6FFF?

 

Nels Knutson:
Yup.

 

Tyler Blackwell:
Okay. Yeah. Yeah, what else does treatment look like? How are you guys imaging? How are you guys setting up?

 

Nels Knutson:
Yeah, so we do basically it’s kind of evolved. The basic idea is to use a three arc template with 15 degree couch kicks. So a 15 and 345 couch and then zero. And we’ve adopted those three five arc half templates. So it’s just a one up, one down on each of the 15 degree couch kicks, and a single one at zero.

 

Nels Knutson:
And yeah, six triple F. We have our optimization stuff down to a pretty fine science, because a lot of the time, we try to get these plans turned around as fast as possible. The patients are not doing well with this VT, and stuff, and we really want to get them in and out of here as fast as we can.

 

Tyler Blackwell:
Yeah.

 

Nels Knutson:
Yeah, so that the treatments are fairly straight forward. We do CBCT-guided. I think, or probably the biggest advancement I remember going from a helical reference scan to an average scan.

 

Tyler Blackwell:
Mm-hmm (affirmative).

Nels Knutson:
It was pretty huge, because when you comb them, their heart’s beating, obviously they’re breathing. So your cone beam scan is always this blurring silhouette of the heart. And if you were using a fast helical scan, then you have the snapshot of the heart, versus this blurry heart.

 

Tyler Blackwell:
Right.

 

Nels Knutson:
It’s like well, we’ll probably match all that. So the matching with the average has been really helpful. The six off is helpful, but again, we do a pretty stereotactic, a similar alignment and setup compared to our lung SBRTs. So full SBRT with immobilization with compression and all that stuff.

 

Tyler Blackwell:
Yeah.

 

Nels Knutson:
And that really helps. And basically do that, align to the cardiac silhouette, soft tissue.

 

Tyler Blackwell:
Okay.

 

Nels Knutson:
And yeah, Fluoro to ensure that with motion everything is lining up-

Tyler Blackwell:
Okay.

Nels Knutson:
… as you would expect.

Tyler Blackwell:
Yeah. Just do a quick Fluoro once you’re lined up. So your cone beam shift, do a little Fluoro.

 

Nels Knutson:
Yeah, with the AP non-lateral, sure.

 

Tyler Blackwell:
Hm. That’s cool. Y’all don’t use fiducials. You said you’re aligning just to the heart?

 

Nels Knutson:
Yeah, I mean there are cardiac leads and stuff, but you’ll know that the target doesn’t necessarily correlate with those. They can be pretty distant at times, so we tend not to track off that or anything. I know-

 

Tyler Blackwell:
Yeah, it’s a good thing to note.

 

Nels Knutson:
Yeah.

 

Tyler Blackwell:
I’ve seen or have heard that leads, you think, well that looks like a fiducial, it’s metal. We can easily match to that better than soft tissue perhaps. But yeah, I’ve heard that maybe it’s not a good surrogate, or maybe a good rough surrogate for motion, but maybe not for localization. I don’t know if you have a comment on that, Geoff?

Geoff Hugo:
Yeah, I think you got to… The short answer is it depends. So it depends where it is, and Nels said. We’ve got a study, one of our residents, Mike [Prusader 00:29:06] has done a study. He’s going to present at ASTRO on this. And you have to keep in time that the lead that goes down into the ventricle is often in the right ventricle and it’s in healthy heart muscle, because it needs to be electrically active as you’re pacing through that, or they’re sending a signal through it. So it can’t be in the scar in the dead tissue where we’re treating it.

 

So depending on the size of the scar and the location, it may or may not be in a good spot to use. Some of the CyberKnife folks have actually put an inert lead in and mounted it near the target to use as a surrogate.

Tyler Blackwell:
Mm-hmm (affirmative).

Geoff Hugo:
So that’s a strategy that’s been used before. Yeah.

Tyler Blackwell:
Okay. Well those-

Nels Knutson:
I was-

Tyler Blackwell:
Go ahead, Nels.

Nels Knutson:
I was going to say, like Geoff’s saying, it totally depends. If you just watch some Fluoro of some patients, you can see how complex the lead motion can be sometimes, versus just a nice swoop end motion that we’re used to, sort of gating a liver case with fiducials, where it’s like oh yeah, they’re breathing up down, up down, nice and easy. These can just be crazy trajectories and stuff.

Tyler Blackwell:
All right, gotcha.

Nels Knutson:
It’s just like, “Oh, I’ll just gate on the lead, it’ll be no problem.” It really is a patient selection type thing, and I think we really want to get the full process down pat before we investigate any gating and stuff like that.

Tyler Blackwell:
Yeah. Have you guys had patients that you rejected because there was too much motion? Have you gone there yet?

Nels Knutson:
I don’t… No. No. But again, we’re not trying to gate.

Tyler Blackwell:
Mm-hmm (affirmative).

Nels Knutson:
And I would say… Yeah, I don’t think we’ve had any that we’ve just turned away.

Tyler Blackwell:
All right. Yeah. That’s cool. So yeah, one quick treatment and then they’re out. Waving on their way out, right?

Nels Knutson:
Mm-hmm (affirmative).

Tyler Blackwell:
That’s pretty cool. That’s got to feel really good.

Geoff Hugo:
Most of them. Some of the sick ones have to be wheeled out.

Tyler Blackwell:
Yeah. Yeah. Well I think it’s great-

Geoff Hugo:
Yeah, wheeled in and wheeled out.

Tyler Blackwell:
Yeah, because I mean the data I’ve seen, I think, Geoff with your talk with Dr. Robinson’s papers, shows really, really, dramatic reduction comparing the previous six months tachycardia rates versus the following six months. And I think you guys even have a little bit more longitudinal data that’s showing that even over the next couple years, you see a really big reduction. More than just 50 to 70%, or whatever.

Geoff Hugo:
Right. Yeah. Cliff’s reported at ASTRO some longer term, and the results are pretty durable. The patients seem to, it seems to hold at least as far out as we’ve looked so far. The nice thing is all these patients have an ICD implanted, a defibrillator, so that’s measuring basically if they’ve given a tachycardia or not.

Tyler Blackwell:
Right.

Geoff Hugo:
So you have that nice outcome data you can measure beforehand, you can measure after. And there’s some subtleties to it, but in terms of getting you some immediate feedback, how well the treatment did, it’s really nice to have that.

Tyler Blackwell:
I’m glad you brought up the pace-maker, because I wanted to ask about that. I mean you’re treating the heart, for goodness sake. Have you guys run into any issues keeping dose down? Or what have you encountered with respect to the pacer?

Nels Knutson:
I can only think of one case out of all of them that we altered our planning template. And we removed one of the swooped in arcs, or that part of the template, and basically it was just a pretty strange placement of the ICD. It was a lot closer than normal.

Tyler Blackwell:
Mm-hmm (affirmative).

Nels Knutson:
But most of the time in that standard placement, we haven’t had any issue. It’s usually really easy. I mean with the five arcs with couch kicks that fall off is really fast.

Tyler Blackwell:
Yeah.

Nels Knutson:
And typically we can avoid dosing a pacemaker pretty well. And we use the [crosstalk 00:33:04], just to minimize risks or anything.

 

Geoff Hugo:
Yeah, if you think about where the can, where the electronics are that you’re worried about.

Tyler Blackwell:
Yeah, right.

Geoff Hugo:
It’s usually up here, right?

Tyler Blackwell:
Mm-hmm (affirmative).

Geoff Hugo:
And so it’s more like a breast treatment where you’d be concerned about giving dose to that being-

Tyler Blackwell:
Right.

Geoff Hugo:
… where we’re treating with the heart. But there’s some questions, it’s interesting, some people have asked us about treating the lead tips, because that scenario where, like I said, the lead to function correctly needs to be in healthy heart muscle. So if you irradiated that, would you do some damage? We haven’t seen anything like that. But it’s an interesting question. Should we put some constraints on that or not? So I don’t know. I think it’s to be seen.

Tyler Blackwell:
Yeah, I’m not aware… I mean when I was in the clinic, I don’t think we really paid that close of attention to those. And even when we were treating a really adjacent lung, and you’re treating to 70 grade, or something like that. It’s the same with SBRT. Sometimes you get… SBRT lung rather, where you can potentially be really close to those leads.

Geoff Hugo:
Right.

 

Tyler Blackwell:
So you guys have done quite a bit. How many patients have you treated so far? Do you know?

Geoff Hugo:
I think it’s, let’s see, maybe 41 now, Nels?

Nels Knutson:
Something like that.

Geoff Hugo:
41, 42, something like that. I mean I know we treated 40 and then we’ve had one or two since then.

Tyler Blackwell:
That’s really cool.

Geoff Hugo:
Yeah.

Tyler Blackwell:
Yeah. What kind of studies are you doing now, for future Wash U, or for future patients? So I know you guys have made it this far, and you guys have been working on this, investigating it for a number of years, and you’ve already seen some really good, initial success. So where do you see this going for you guys then, in the next 12 months, 24 months?

 

Geoff Hugo:
Yeah, that’s a great question. I mean besides the physics studies, we’re talking about looking with motions and things like that, that we’re interested in, I mean the main thing is to move this into a multi-institutional trial. I think that’s the big push. So we’ve been looking at different means to do that, and exploring how we’re going to do it, and designing what the trials would look like. But the smaller study that has shown that it has potential, but now we have to show that it’s robust and it can go into the community, and we can get it out to other institutions, and all do it similarly, and get the same results. So that’s the crucial next step in my mind, would be looking at just cardiac radioablation and then how we might, since that’s multi-institutional.

Geoff Hugo:
Beyond that, I mean, there’s all kinds of things that could be done. You could look at questions like is the dose right? Should we lower? It probably doesn’t need to be higher, but perhaps in certain cases it might need to be. Could it be lowered? I think looking at comparison with other treatment modalities. People are always interested in those kinds of, maybe phase three studies, or something. A head to head against something else, and then are there other populations of patients? Because we’re treating quite sick patients right now.

Tyler Blackwell:
Mm-hmm (affirmative).

Geoff Hugo:
They’ve really run out of options. They’ve maybe failed catheter-ablation, or they’re not eligible for it for some reason. And so they’ve been referred to us for that. So the question is that the right population or are there other populations-

Tyler Blackwell:
Sure.

Geoff Hugo:
… that can benefit?

Tyler Blackwell:
Oh, sure.

Geoff Hugo:
So lots of interesting questions. Yeah.

Tyler Blackwell:
Yeah. So yeah. You mentioned a good point. So you’re currently treating people, patients that have failed RF-ablation, catheter-ablation. I mean do you envision this could be an alternative to that in the future?

Geoff Hugo:
Oh gosh, I don’t know. I mean that’s a good question probably for the electrophysiologist.

Tyler Blackwell:
And a crystal ball, Geoff.

Geoff Hugo:
Yeah, I mean it’s hard to say. But I think it’s certainly… In the way we’ve looked at it and the patients we’re treating, my impression is that it’s used more right now as, like you said, a salvage therapy for patients that have failed or they just, for whatever reason, they’re contraindicated to getting another therapy. So that’s what the focus is now and who knows what the future may hold.

Tyler Blackwell:
Yeah.

Geoff Hugo:
But possibly? I mean I don’t know.

 

Tyler Blackwell:
Kind of an oddball question for you guys. I’m going to give you a challenge. Was there anything and the past few years that you tried, just any part of the process that just didn’t work out, that just failed, and that you had to reassess and readdress? Anything that pops to mind?

Geoff Hugo:
I mean I’ve tried some image registration. I think that was the main thing that drove us to this prototype software. I was like, “Oh, the easy thing is we’ve got a cardiac MRI scan and a cardiac CT scan, and then the 4D cardiac gated scan, and the 4D respiratory. Let’s merge all this, because I’m an image registration guy.” So it’s like, “Let’s register everything. Let’s register this ECGI imaging. And we’ll get a really nice thing that cardiologists can flip back-and-forth, and draw the target directly in the treatment planning system.”

Tyler Blackwell:
Right.

Geoff Hugo:
But it’s really challenging to do that. The imaging quality is hard. The patient’s either in breath-hold in one scan and they’re free-breathing in another, and there’s artifact, and all that. And so we abandoned that strategy.

Tyler Blackwell:
Yup.

Geoff Hugo:
Pretty quickly. That’s my failure right there. But maybe Nels has something else?

 

Tyler Blackwell:
Well Nels, he was an all star undergrad. I know he didn’t fail anything quite like I did.

Nels Knutson:
I have so many failures, man.

Tyler Blackwell:
But maybe he’s got something new. What do you got, Nels?

Nels Knutson:
Yeah, so thinking that the cardiac 4D and the respiratory 4D would give us the traditional, oh, I’ll just follow this thing around, and draw an ITV, that was a pretty epic failure. I mean it’s not a failure, but it’s difficult.

Tyler Blackwell:
Right. We’re learning, right? We don’t fail, we just learn what not to do.

Nels Knutson:
Right. I think it’s more of an educational tool, and really helps estimate, I would say, a little bit of the uncertainty in the motion envelope. And it’s more of a guide. It’s never going to be a perfect registration between those two 4Ds, to allow you to just do the traditional, I’ll just trace the motion envelope.

 

Tyler Blackwell:
Yeah.

Nels Knutson:
Because that’s really impossible. So like I said, the cardiac 4D is done under breath-hold, so how do you have the patient hold their breath? Do you do it on exhale, inhale?

Tyler Blackwell:
Sure.

Nels Knutson:
What’s the plan, right? So I think the first one we did was DIBH, and we’re like, “Holy, that didn’t work at all.” Because most people don’t spend their average time on inhale, it turns out. So then we tried exhale, and it’s similar issues. And we settled on this mid-exhale. “Blow half your breath out and hold it.”

Tyler Blackwell:
Yeah. Oh, that’s what you’re currently doing now?

Nels Knutson:
Yeah, we went through these iterations, yeah. And it’s still not ever going to be perfect, so it’s more of just an informational tool. And it’s super helpful, I think. And you can see these cases where for a given patient, maybe the respiratory and cardiac component combined versus the cardiac component alone are really not that much different. So it would be hard to argue gating would be good in that case. Right?

Tyler Blackwell:
Mm-hmm (affirmative).

Nels Knutson:
For instance. Or maybe the cardiac motion is just very complex.

Tyler Blackwell:
Yeah. Good.

Nels Knutson:
I think the other big, huge thing that I learned was OARs… We spend so much of the beginning time focusing on targeting and don’t miss, and realizing that the OARs move too, especially the stomach, is super key. For some of the targets. Some of the targets can be very stomach adjacent.

Tyler Blackwell:
Mm-hmm (affirmative).

Nels Knutson:
And adopted that kind of reverse strategy of PRVs, and really thinking about the robustness of your plan. What’s the worst case scenario if the stomach changes, or if stuff like that. So converting isotopes lines the day of, and really having that do not cross threshold-

 

Tyler Blackwell:
Yeah.

 

Nels Knutson:
… line has been super helpful.

 

Tyler Blackwell:
Okay.

 

Nels Knutson:
Actually, some of the feedback we got from other groups that started doing this. We were like, “Oh, man. What you’re doing is really scary. We’re going to definitely do this.” And I was like, “Oh, that’s a great idea.” And yeah, so using tools like that and just really learning each case, has been really eye-opening and great.

 

Tyler Blackwell:
Yeah, well it’s good to know that these trajectories or straight lines, that they curve around and back-and-forth a little bit. Yeah. Yeah, I know we didn’t really touch on OARs, but it’s cool. So thanks for touching on it. But it sounds like the stomach, especially, being so sensitive and being so close to the… Yeah, that aims for your portion of the heart, that would be a big one. And if you’re delivering 25 Gray, that could be a pretty hotspot for the stomach.

Nels Knutson:
Right.

Tyler Blackwell:
So yeah.

Geoff Hugo:
Yeah, I think stomach, esophagus, and the heart itself, the substructures like coronary arteries, or aspects of it that we’re-

 

Tyler Blackwell:
Okay.

 

Geoff Hugo:
… concerned about. I mean these very sick patients, they may end up getting a heart transplant, or we may just be palliating, and they may not last, end up living very long. And then I guess the question is, for them, the trade off the physicians have to make is their quality of life, and reducing this arrhythmia, which is really just debilitating.

Tyler Blackwell:
Yeah.

Geoff Hugo:
Versus heart dose. Whereas, maybe, if we’re looking at healthier, younger patients, there may be different considerations there. But certainly things like stomach are always a concern if the target’s nearby.

Tyler Blackwell:
So you mention substructures, are you contouring all the substructures for the heart for this?

Nels Knutson:
Not for optimization. We have done a pretty good series of retrospective contouring and looking at all of this.

Tyler Blackwell:
Mm-hmm (affirmative).

 

Nels Knutson:
But not for optimization.

Tyler Blackwell:
Gotcha.

Nels Knutson:
We contour the heart and we have a heart minus ITV type structure that we use all the time. It’s really important when we first started. A lot of people say, “You can just make an SBRT fast falloff plan. And the NTO will handle it.” And all this.

Tyler Blackwell:
Mm-hmm (affirmative).

 

Nels Knutson:
We found that it was really advantageous to hammer that, and really get the dose to the uninvolved heart as low as possible. And some targets are much easier than others, some are more peripheral, so obviously you can spare the heart minus ITV easier than if it’s central. But yeah, we always tried to minimize that.

Tyler Blackwell:
Yeah.

Nels Knutson:
And I really feel like our drivers are basically conformity, the falloff making us as fast as possible, and then sparing as much normal heart, and then the OARs of course, would always win out.

Tyler Blackwell:
Yeah.

Nels Knutson:
PRVs type thing.

Tyler Blackwell:
Cool. Well I mean is there some… I feel like we got a pretty good impression of what you guys are doing at the Wash U. I’ve asked a lot of questions to poke holes, or rather just really figure out what you guys are doing start to finish, and so I appreciate the explanation on everything VT. I think it’s really cool. I think it’s sort of a hot topic right now, where people have been introduced to it just at the last few meetings and conferences. And people are looking for more information. So thanks for sitting with me to do this. But if you are okay with it, I feel like I want to hear a little bit about St. Louis too. I want to get a St. Louis flavor, if you guys want to answer a couple questions for me that are not related at all to VT?

 

Geoff Hugo:
Yeah. Go shoot.

 

Tyler Blackwell:
So you were mentioning that you’ve got physician’s phone numbers, well I’ve got your guys’ phone numbers too. So let’s say I’m going to go to St. Louis, and I want the best grub, and I want the best food ever. So I want you to think about what’s your go to? What’s your favorite meal in St. Louis?

Geoff Hugo:
This is a good way to start a fist fight in St. Louis, is like what’s your favorite barbecue? Or what’s the best barbecue joint in St. Louis, right?

Tyler Blackwell:
Yeah.

 

Geoff Hugo:
Be careful what you ask.

Tyler Blackwell:
Oh. So-

Geoff Hugo:
No, if you live here long enough-

Tyler Blackwell:
… Geoff, you’re a barbecue guy?

Geoff Hugo:
I do love my barbecue. I got to say I’m a big fan. There’s some good ones around here. But I got to think of my favorite… You know what? There’s also, it’s best versus proximity.

Tyler Blackwell:
Right. Yeah.

Geoff Hugo:
And there’s a pretty, pretty good one called Salt + Smoke that they just put a second one in right up the road, and we can walk there from the hospital. So that’s always a good one.

Tyler Blackwell:
Are you a brisket guy, Geoff?

Geoff Hugo:
I grew up in Arkansas and Mississippi, so I’m kind of that, I don’t know, pulled pork. But I do like a good brisket as well.

Tyler Blackwell:
Yeah.

 

Geoff Hugo:
Just none of that North Carolina stuff. That’s not my style.

Tyler Blackwell:
Yeah, I wish I could be there. If I go I will be getting barbecue, because there’s a bit of a dearth of places up here in the Pacific Northwest. Barbecue is not the forte here.

Geoff Hugo:
You can find your fair share of barbecue-

Tyler Blackwell:
Yeah.

Geoff Hugo:
… in the St. Louis area.

Tyler Blackwell:
What about you, Nels?

Nels Knutson:
Yeah, there’s so many in St. Louis. It’s great. St. Louis is a really awesome city. It’s a little weird in this pandemic, but I definitely love Happy’s. It’s right next to a brewery that is hockey themed.

Tyler Blackwell:
Mm-hmm (affirmative).

Nels Knutson:
It’s great, called Center Ice. They’re connected. There’s also a chicken joint in there called Southern. And it’s spicy chicken, barbecue and beer.

 

Tyler Blackwell:
Is this like a co-op kind of thing?

Nels Knutson:
No, I don’t know. It’s, I guess, an old building that got taken over piece-by-piece. And those were the three awesome businesses that ended up there. Yeah, I love the breweries here. There’s so many awesome breweries.

Tyler Blackwell:
Mm-hmm (affirmative).

 

Nels Knutson:
4 Hands, Civil Life, 2nd Shift. They’re all great.

Tyler Blackwell:
Geoff is nodding. He’s like, yes.

 

Geoff Hugo:
Yeah.

Nels Knutson:
Yeah, Narrow Gauge, all of them. Just awesome, you know?

Geoff Hugo:
Can’t leave out Narrow Gauge. That’s-

Nels Knutson:
Yeah. Basically I have our satellite clinics mapped out by brewery.

 

Tyler Blackwell:
If I’ve got to go to this place-

Nels Knutson:
Right.

Tyler Blackwell:
… if I’ve got to go to this satellite for a clinical duty, I’ve got to visit X.

 

Nels Knutson:
Well, yeah, exactly. Where can I go and make sure I can bring home a six pack from wherever, and always super fun.

Tyler Blackwell:
Yeah, right.

Geoff Hugo:
Yeah, when I’m heading up to Alton, I’m like, “All right, take orders at Narrow Gauge.” Because it’s pretty far up there, but it’s well worth the trip.

Tyler Blackwell:
Fill up the growler.

Geoff Hugo:
Yeah, exactly.

Nels Knutson:
It’s about a 45 minute drive for most of us.

Tyler Blackwell:
All right. Yeah, so I’ll pivot to a landmark question. So we all know about The Arch, so let’s exclude The Arch from this conversation. But what do you think is the coolest other landmark in St. Louis?

Geoff Hugo:
Oh that’s easy.

Tyler Blackwell:
What’s a place that you want to go to? Okay.

Geoff Hugo:
That’s an easy one. It’s got to be Forest Park. I mean we’ve got this beautiful, huge park just right next to the hospital. And I remember when I was interviewing here, and you just hop out of the hotel, and you can go for a run around there, and it’s gorgeous. There’s all kinds of stuff. There’s a free zoo there. There’s an art museum that’s free. It’s all free to enter, so it’s a really cool park.

Nels Knutson:
Tower Grove Park is also really awesome. I live two blocks from it. It’s another, just huge… St. Louis is a great city of parks. And there’s just tons of them that are big. And yeah, I definitely love that. And actually, the Missouri Botanical Garden here is pretty incredible too.

Tyler Blackwell:
Okay.

Nels Knutson:
Yeah.

Tyler Blackwell:
You guys must work a lot of hours, because you’re in the department so much, what you guys really appreciate are the parks. You get outside and it’s like a big thing.

Nels Knutson:
Sure.

Tyler Blackwell:
I think I visited the zoo. I went to Purdue for undergrad, which is in West Lafayette, Indiana. And I can’t remember, maybe it was four hours away? So we visited St. Louis really briefly. And I think we, and I remember going to a free zoo, so that’s probably what you were referencing, Geoff.

Geoff Hugo:
Yeah. That would be it.

Tyler Blackwell:
Cool.

Geoff Hugo:
Cool.

Tyler Blackwell:
Wait, what else? What else is there, Nels?

Nels Knutson:
One more thing.

Tyler Blackwell:
You’ve got more to say?

Nels Knutson:
Yeah, the Blues arena is pretty awesome. You can see where the Stanley Cup was won. That was pretty great. Downtown-

Geoff Hugo:
When was that, that St. Louis won the Stanley Cup, Nels? Do you remember?

Nels Knutson:
We’re the Champions.

Geoff Hugo:
Yeah that’s right. Okay. Okay.

Nels Knutson:
They haven’t lost it, so they’re still the champs. And City Park downtown is really cool. It connects all the way from The Arch down most of Market Street. And it’s just a bunch of green space right in the middle of downtown. So you’ll be around tall buildings and then this really nice green space in the middle.

Tyler Blackwell:
Mm-hmm (affirmative).

Nels Knutson:
It goes past the Blues arena, and the Cardinals arena, and all that.

Tyler Blackwell:
You guys are making me want to go there.

Nels Knutson:
You can come visit, Tyler.

Tyler Blackwell:
Yeah, can we advocate to AAPM that we need to set up an annual meeting there?

Geoff Hugo:
There we go. Well we got our SNORAD meeting, which is the Symposium of Non-invasive Radioablation cardiac, basically our… So we’re doing that once a year, although I think we were planning to maybe move it out of St. Louis, just to get a little bit of a different place. But we’ve done some meetings.

Tyler Blackwell:
Yeah. So that’s a new meeting that you guys have created?

Geoff Hugo:
We’ve done it two years now.

Tyler Blackwell:
Okay.

Geoff Hugo:
In St. Louis. And it was just probably 200 people or so from around the globe interested in cardiac radioablation came and just shared ideas, talked about what they’re doing, patients they’re treating, and studies they’re doing. And then, yeah, we were going to plan to have it in the fall, here, in Europe, but it’s going to be postponed as everything is.

Tyler Blackwell:
Yeah. Yeah. Yeah, we’ll come out of it sometime. Conferences in the future we’ll all warmly embrace. It’ll be good to share a cold one with everyone. And yeah, just reconnect. For sure. Well I want to respect your guys’ time, but I want to thank you guys both again for taking the time to share with me. I’m scratching my own itch. I’m really curious about VT. And just really interested and really happy that I know both of you and can reach out to you guys. I know that if I had a clinic that was interested, you are the two that I would reach out to and get all the details. So yeah, thank you so much for your time here today.

Geoff Hugo:
Yeah, thanks, Tyler. It was a lot of fun. Appreciate the opportunity to chat with you.

Tyler Blackwell:
Yeah, cool.

 

Nels Knutson:
That was a blast, Tyler.

 

Tyler Blackwell:
All right, we’ll do it again another time. All right, see you guys.

 

Geoff Hugo:
Sounds good. All right, take care.