Ep. 555 Dosimetry University Part III: Optimizing Single-Session Treatments with Dr. Nima Kokabi and Dr. Tyler Sandow

[MUSIC] This week on The Vactable Podcast. >> If they got them to surgical resection and they looked at many different factors, if they had proto-brain thrombosis, if they were above up to seven, if they were all sorts of different things, advance or non-advanced. The bottom line, the conclusion was, the best chance of survival in these advanced HCC patients, similar to what the long-term follow-up, at least the authors of the long-term follow-up of those who have claimed, is that the best chance of survival in these advanced HCCs is to get them to surgical recycling. [MUSIC] >> This is DOS Cemetery University, part three. [MUSIC] >> All right, welcome back everybody. >> Let's continue on. Let's first talk about single session, Y90, which your team has just published on. We talked a little bit about it earlier. Here's now data from UCSD, there's data from Asia as well. >> And Botoskitch's group. >> Yes, I'm sorry. >> Yeah, I forgot mail. >> But talk to me with a single session, Y90, what is the workflow, what is it until? >> As we are getting more and more comfortable with these smaller tumors, on the HCC side of things, but you can definitely be extrapolated to all of them at the Sadiq disease as well. The long-shant fraction for these smaller tumors without any aggressive feature, and what we mean by smaller tumors, you know, T1 and T2, up to 5 centimeter, are very low. And on the other side of kind of the other, the supporting argument for it is that this, because you're generally doing segmental treatments for these, the prescribed activity is also going to be on the lower side, whether you use glass or resin. The bottom line is that the projected long dose will be very low. And there, as you said, there are now four papers out there showing, the Korean paper is mixed glass and resin. There are two specific glass paper and also a specific resin paper that we just published about a week ago now. Showing great safety profile, no reported radiation, no monitis in any of them. Near all of them had 80 to 90 percent complete response rate. So it's very much there for us to kind of start doing, particularly as other liver-directed therapies are gaining more momentum, including SBRT. I can tell you, at our tumor board, it has become a very popular notion that we call it one and done, that you bring the patient in, you treat them in one session and they go home, as opposed to bringing them for mapping, them bringing them for treatment, or bringing them for a judicial placement and they come back for three SBRT sessions. It makes, so for certain group of patients, it makes perfect sense. We looked at the economic value of it and I realized we are in an academic center with a huge backlog, so that makes it more attractive for us to kind of reduce the time. Our average time to treatment for the single session was 21 days, whereas the historical average time to treatment for patients that go through the traditional pathway, from the time of discussion in a tumor board and referral to IR clinic, was 61 days. So it's a significant reduction in the time to treatment and 40 percent reduction in the cost. The mapping component is about $40,000, which actually not $27,000. The treatment was about $40,000, so it's a significant reduction. So I feel that as more data is published, we make it to a point that insurance companies may demand this, actually. I like it. So who do you choose for single session? So HCC is for now, but it can definitely be all of them. I think you're right. I like the HCC. I think you have to pay attention for before advocating it to the masses. I think you have to make sure that your team has a system in place to handle this kind of thing. There are certain tumor locations that are more favorable for single session. That's deliveries, or at least, as you get started. As you get started. So let's say you're just getting out of there. What kind of tumor location are you looking for? Or what would you like if I'm in the community? That's a very case that we talked about in the last session. I would not advocate for that as being your first experience. Because you have no idea how many feeders, those more central to the higher. Because it's central to the right. So more peripheral, I think the segment 6, I think the segment 2 or a segment 3 would be a perfect one as you go. Not like Straving 2, 4, but like on the edge of the lower left side. Well, yeah. You have to do high quality combings. It is essential. That would not even be, it is mandatory. If you're not doing combings, if you're not doing the MA, you really have to rely on your combing CT. And we have certain set of, in fact, I had a patient last week or this week, earlier this week on Monday. We were going to do single session. We reverted back to, this is the first case that we have reverted back to mapping. I saw early enhancement of hepatic range. And I know, yeah. And to your point, we did the MA and the lungesion came back as 0.9 percent of the total job. I told you, I'm winning. I know. I was letting, man, this guy is good because he was predicted. But you can't, you want it, you want to prove it right? It's not. I mean, yeah, if, if I did it, like the hepatic range, they're lighting up. I thought I'm just going to give the MA and the lung shunt would be 20 percent. Yeah. But it was, it turned out even one very hurt. Yeah. It was actually quite surprising to me. But so that, that is the thing. So no macravascular invasion, no tips. Again, all of these are what the original paper that kind of explained the possibility of this other North Western X kind of put it on the map. And the interprocedurally, no early enhancement of the hepatic range or port okay. I agree with you on this. Now you use CERTEX. Yeah. So you're ordering a map, like not a master route, but you're ordering a vibe. A model of, of activity. And your, your team, like let's say you catch two feeders, right? Or your team will draw up two separate doses off that. Yeah. So there are two ways of approaching it. So I learned this to be fair from the Korean group. I was visiting them and I, they were doing, I think they were the first group, at least on the resident side of things doing this. So what they would do is they would do the combing, calculate the volume, call nuclear medicine and ask them to draw to those, which is fine. It takes a little bit longer. It takes about 20, 30 minutes for the nuclear medicine to draw because there's a motorbike and you draw. So I thought about it. I was like, okay, that's, and we did several cases like that. And then to your point, I thought about, okay, these are all segmental treatments. What are my average volume of segment that I would be treating? I thought if you look at the 95% confidence interval, it is something in a 150 to 250 CC. Okay. So I pre-draw three vials with 300 grade targeted to 150 CC, 200 CC and 250 CC. The boxes are ready in the room for me. I don't wait for them to draw or anything like that. We do the combing, we calculate the volume and then go and treat. Yeah. And then if there's more than one feeder, you go to the next one and to the best of your knowledge. You pick which one you have. I want 52 and 52. I like that. And I assume that's how you did it, but I wanted you to say it. So everyone else does. That's how you would go about doing it. So we use rope glass and we do something very similar. We say that our perfused territories are somewhere between 115 and 200. On average, and we say our institutional long-shunt mean is right around 5 or 6%. And so we assume a long-shunt of what our institutional average is. Even though it's negligible for long-dose, really for a radseg, we assume a long-shunt of 6%. We go in 152, 200 ML to whatever perfused territory. Tumors that are 3 centimeters or less in size tend to rarely have more than two feeders. Yeah. So if the tumor's 3 centimeters or less in three species, for HCC. Now HCC is because we're talking about that's where you should really start. If you're going to do that single-greshing, Y90. Tumors less than 3 centimeters or size tend to have less two feeders or less. One feeder perfect, you just burn a dose. Or you can combine, you can deliver both your dose. You can also do that with the split dose the way I say with surtex. You can either double them up or if you catch two feeders and you want to be more selective, you can do that. And so we tend to wind up saying 400 graders per fused or 450 or 500, whatever to the perfused as an assumption, assuming 200 ML volume. And that activity comes out to like 1.2 gigabekerel on a week one Friday. Or somebody's going to challenge me on the math and actually tell me I was wrong. I'm doing this on the fly in my head. So that don't, no one gets to be critical of what I did. So at two doses, 200 CC perfused volume each. Yes. And assuming a long-shunt of 5 to 6% with 400-500 graders per fused. And so the ones that get me like a 4 GB or 5 GB, sure week one Friday. And it'll be a little bit earlier if you do it. But you're still. Come and see co-eats team. Oh, yeah. Getting that volume is, what the dose are actually going to be. Just like you would have done a mapping. Right, it's a power injection. Power injection. Power injection. injection and then you're in a curing inventory. - Make your way. - Yeah, curing a inventory too. - I just know, yeah. - And then if you just happen to be there ready to deliver, that's what you did. - So let me ask you our honest opinion. - I really do think this can become the standard of care. - Good. I think it is good. I think you have to be careful in the appropriate selected patient. - Yes. - The counter argument is what if I didn't account for a fourth vessel or a third vessel and I'm just playing devil. - I'd advocate here because I've already discussed. - So do you even come back? - I'm not gonna say yes. Well, you were gonna come back anyway, right? - Because it was a man. - I don't know, it is like five to 10% of the tumor. - Could also just-- - Some bland them going this way. - You could bland them. - I think I'd be going into Y90. So there are some cute techniques to try to to try to alter flow to tumor, which I think you brought up. We might have to talk about some point. - If you were gonna do a map, you know how many sessions, or if you were gonna do a map and treat, you know how would you be session to? - Two. - So if you brought them in and you treated part of it and you just realized there's another food and you know how many they're gonna get. - Two. - Actually, there was a case that I did the treatment. It was a single session. I realized after that, I totally missed half of it. I brought her back two weeks and I retreated. - Yeah, nothing wrong with that. - Not retreated. - No, they didn't put a point in them. - It was basically doing a mapping and a treat. Yeah, same time. - Yeah, they're financial incentives. You know, a lot of people in private practice, there are RVs that can be captured by doing a mapping. I don't think that can be, I'm not saying that's the right thing to do or the wrong thing to do. I don't have any factor, but I think there's something that weighs into that. - Yeah. - But I do like single session treatments. We have people that come from out of the country. We have people that just like you and everyone else, we agree that come from several hours away. It's not always feasible for them to come back and forth and back and forth. And I would rather them get a good treatment than be lost to follow up or decide that they, it was just too hard to get in. - And then the other group that was one of our first group of patients that we did, where the patients that were incarcerated. - Prison people. - Okay, 'cause there's a lot of logistics. I don't know if you treat any of those people. There's a lot of logistics involved. It takes months to bring them, even if you approve a procedure and you want to do something. So bringing them once makes it so much easier than bringing them. - It's a great point. Two things I wanna come in on. One is soul 5% thing. Let's say you have a little bit of an edge of a tumor. What to do with that? I totally agree for me, it is what is the perfused volume that is around that edge of the tumor, right? If I have to get that 5% of tumor, I have to take 200cc's normal liver with it. Then I'm probably not gonna do that. I mean, they're gonna balloon the outflow and then give a proximal dose with a cypher or something like that, or I'll do blend. I know you don't like blend, but it's number one is killing tumor. Number one A for me is sparing your liver, right? - So, re-eye. We learned that technique from re-eye. I'm not advocating this for someone to just try this on the fly. I think you need to understand what you're dealing with. But you can get, as opposed to doing a particle embolization, you can get right up on the tumor and you coil it prior to treating it. It altered the vascular inflow of the tumor. So, if you coil as close as you can to the tumor, I'm talking like right up on it. Sure. If you can get right up on it and coil it or get close to it and coil it, all of a sudden the inflow associated with the tumor can get redirected. And so- - This fellow can I? - This is for the tiny segment. - For that tiny little 5% if eater. If you can coil it, you're gonna change the flow dynamics of the tumor and you can wind up treating. Re-eye has talked about the hour or more times one, one has had great experience with this. I don't love it. Just because I feel like it's a factor that you can't always guarantee that you're gonna get the best response. So, also if there's a 5% residual or a 5% area that you can't go, you can always change your modality of treatment. You can- - Yes. - You can apply it, you can put it 100%. - The other thing to consider, I always think about it at least, is radiation travels as well. So, we have a range that if you have 5% in the rim of the tumor, but you have a hot dose of radiation right next to it. There is a half a centimeter to centimeter that this radiation travels. - But it's only 10% of the time. A 10% of every decay. And so, I should be not to rely on you. - I think it's a fair consideration, but I don't wanna- I would like to rely on factors that I feel I can give you the most lethal kill possible and I feel more confident doing either an ablation or Y9. - Yeah, I just don't like bland info for the intent that you're going in there to try to use it for. - So, there's a plan that I'm gonna for re-perfusion and there's a plan for treatment. In a case like this, I would use a smaller particle. I would use one to 300 and was fierce for the treatment. If I was doing re-perfusion, I would use larger particles because I would want the Y9 to go, that this is not a case that we're talking about, but- - But anyways, I actually think it has, it will have a bigger role in the future, notwithstanding the financial implications in private practices of biodeficient academic centers, where there is generally a backlog of patients that have large re-perfusion. - A subset can definitely be treated. - Oh, I love it. I think it's a great, it's a great opportunity. Single session of Y9 is great, I'm really on for patients. - And streamlining the process for the patient, right? I mean, that's what this is about and getting them treated faster. I will say though, from a flow-reader at the standpoint, I'm sure we're aligned on this, but I don't agree with calling the left hepatic to then just treat the right hepatic for a large lesion. - Oh, no, no, no, no, no. - I mean, it never, like, fly a percent of a very small gray area, like a sub-segmental vessel, that you just didn't want to treat 200 ml through that territory. And the predator technique is good, right? You talked about using a balloon of cleftin, you know, Botoshkitch, and this is, you got to do this very, very well, but it's called predating a vessel, so predator, like it's actually like, you know, pruning off the vessel. And if he listens to this podcast, he's gonna destroy me, but the gel film has to be mixed perfectly in a way that he talks about it is you get all the air out. It's a very, very thin solution and you can actually see the gel film particles sit in suspension in the syringe if you were to hold it up to the light. So it's not a thick gel film, yeah. And it's, it winds up, and it's all intended to go do a very distal embellization. And Sirtex is coming out with a rapidly dissolving particle. - They have it in Europe already called embossup. - Yeah. - And so it should be-- - But it's small, it's 50 micro, right? - 50 micro, 50 micro. - But they are, the company at least has the capability of making a larger particle, it was with different resorption rate. So what is your go-to technique for reperfusion? - So reperfusion? - Yeah, so if you want to protect the certain-- - So I will do-- - Or not the-- - Re-direction. - Re-direction. - Re-direction. - Very rarely. Will I use gel film to kind of screw it out the distal? I would say I've tried to use the balloon thing. The balloon thing I've had, people don't understand how hard it is to put two catheters through a sheet, through a single sheet. And so our six-frint sheet, if I situated in the accommodate paddock artery, and I try to put a sniper or a scepter through it, and then try to put even a true select through it. - Oh, these are-- - It's not the easiest thing in the world, and the things just get steeped. - You have to go through the hub of the sheet. - Yeah, there's a lot of complexity. So say what that, the tens, give me a second. Give me a second, I know what you're gonna say. 'Cause I do it all the time, and I like-- - Yeah, so you and I think it sucks. I'm not saying we can disagree on a few things. - I tried to do it a couple of times, and I was like, "Covvy's full of shit." I was like, "He tells me it doesn't, and it works fine." I was like, "No, it doesn't." I was like, "I'm sitting here, I'm getting frustrated." Now, Covvy will say you can access both vessels, and you can do it two different catheters. - You can, I don't do that. - I know you have techniques that make all this work. I have not had many goods. And I might not be as good as you guys at Y90. I, for flow, for redirection, I like distal gel film. I use it very rarely. At the end of the day, I am pretty good with a micro catheter. And I love the shape, steerable micro catheter, the direction micro catheter. Everybody hates it. - I actually love it. - I'm going to be the only one that keeps them in business. - Which one? - There I should. - Daughter, daughter, daughter, daughter, daughter, daughter. - Oh, shit, that, that, that, that, that, that, that. - Oh, so I, or your shape actually-- - I did it actually torques. - Yes, the rest of them-- - They don't even true select. - Yeah. - Which is made by Boston. The shaped one. - But if you don't like it-- - You don't treat that direction nicely. It, it'll go out. - It'll, yeah. - Oh, you can break it because of the way that, so you gotta be very delicate with it. But it is very steerable, very shapeable. I, I find that I can catheterize most of the branches the way that I want to. So I rarely run into an issue where I need to alter flow. But that said, I like gel film. I use it rarely. The coil thing, bear, and crit. I might have used done it once. And that balloon thing, I tried it several times 'cause Covey swore by it. - I've done this thing. It does it. - I can't even get rid of it. - I've done it with the radio. So I put a R2P sheet. It's a little bit easier than the groin. I don't like gel film. I had something-- - You gotta add a gel. - I know, I'm not-- - And you gotta mix it very meticulously. - Yes. - And that was rich. - That was what I did. - I was a large particle. I get more consistent. I do three to five hundred fears. - There are calibrated gel film particles in Asia. Hopefully they will come to the US at some point. That would be ideal. - But it intercepts. It's gonna be, I think. - It's gonna wait to try. - I think what's happening is gonna be-- - I think it's gonna be awesome. - That's actually a perfect-- - Oh, I don't like that. - And application form. - And so, yeah. - Covey, how do you do this? - The double loon bullshit. - This will talk about. - So, six French sheets, or double access, or six French sheets. The goal is six French sheets, right? Interestingly, the R2P's, I find them a little stiff. So I don't like doing this from radio personally. - Uh-huh. - But definitely done it through radio. - Definitely can be done. But six French sheets, you gotta take the cheque flow off. And then it's the double to-e neuro technique. That's the way that it works, right? - Well, it's called me. - Two two-e is connected to each other. Two micro catheters go inside by side, and I like it. Now, I will say, on the topic of gel foam, and Bo talks about this a lot, especially with ACC, you'll get intrapatic paribillary collaterals that can collateralize around the blue. I've also seen it many times. So you can then, with the balloon up, inject your gel foam safely, because it's not gonna reflux, right? - Yeah. So they both talk about that a lot as well. I think that's a great little technique, but I do I have more partial to this. So again, sparing normally looking. - You have to say. - Yeah. What about other flow diverting or flow modifying micro catheters? It is a great question. This is controversial. To say, we have to better bring it because I get asked all the time and I don't actually. I get asked this a lot. I get told that people say that I use this often and we actually don't. So our practice, again, is built around a lot of radsets. I would say 90% even in the metastatic game, we try to radset and we talked about this because it allows you to spare normal tissue. I think there is a role for flow, I guess we're going to talk about the trinav catheter. - I was at one and I looted or sniper. - I think that it is a. Tri-Nav is a very good anti-reflex catheter and it allows you to protect approximately what you're trying to. Assuming the valve gets situated, opposes the vessel from which it's treating. I have not had 100% reproducible experience of altering the TDN ratio using either a sniper or a trinav. So I mean comparing MAA to. Or seeing an altered. Even when I have the trinav in. Let's say I'm dealing with the diffuse hypovascular set of tumors or even or multifocal hypervascular tumors. I don't see the vascular changes that I would want to see with the trinav catheter to trust it all the time. - And you're radically. - Angiographically. Because there's no way to really do it with MAA and then say it on the back end. To have confidence that it's going to do behavior the way I'd want it to do to do favorable flow to tumor. That said, if there's no other option, if I have a patient with. And we'll probably talk about this in a little while. With bi-lobar, hypovascular metastatic disease, or even uni-lobar, multifocal, hypovascular metastatic disease. I will pull that catheter out in the hopes that it alters the pre-usion and use it in that setting. But the majority of our practices, Rad-Seg, I would rather get the catheter closer to the tumor and do a more distal rad-seg to a smaller territory. We'll have more confidence that the dose gets delivered into the tumor the way I want to. So I tend to not use them. I actually resisted. I'm sorry, you had sniper at Emory and I used it quite a few times. Not for distal protection. We were injecting with the blue now. Yeah, right. So, yeah. I've been approached to use the trinab and until very recently I didn't use it because to me that basket size that they had was too small for anything low bar. To your point, I think the biggest potential benefit of any of these potential flow-modifying catheters are for in a low bar setting, not in a segmental setting. I have started using it since they came up with the larger basket size that goes up to 5mm because then you can actually do it in a low bar setting. I've. again, I haven't looked at the data apples to apples to see truly whether it has increased the T-2N or not. But in terms of the trackability and terms of the ease of use, I've been quite impressed with it. But definitely it requires more data to claim what it could do. That's what it is. I know. I think we're lacking clinical data, right? It's a hard one to do though to generate the data as well. That's the problem. Yeah, that is exactly. Because, yeah, how do you prove? Because evocation is different. Every catheter position is different. There's a lot of nuances to it. That's not to say it's not a good tool. And I think it has its role and I think you just got to understand where you're going to apply it in your practice. I don't think it should be applied in a rat's egg. No. Application. I think it's more in a large volume low bar type approach. When you have a lot of background liver in the territory, right? So low bar I'll use trying to have. If I'm more selective and I still have a lot of background liver that I can't protect, then I'll treat with the blue nut. But you're right. I mean, I think the clinical data is lacking and that's. Yeah, and I especially when the catheters are expensive. For any of them, I don't consider them an anti-reflock. Yeah. I don't care about that as much. I truly I care about if they. Sure. Or they claim is if you put the balloon up or the basket is opposing the wall, there will be vasoconstriction in the normal liver pranking more than the tumor. And that is the hypothesis of that. Yes. That's the hot pot. Yeah, but we need to generate that data to prove that. Exactly. I agree with you 100%. And worth noting on an economic standpoint, both catheters are expensive but hopefully reimbursed on the back end with proper coding. Yeah. But those aren't RV use that go to you there. That's very. People need to understand that you're not getting more RV use because you use catheter. But you're getting C codes would get reimbursed to your. Your posture. And the straiters like you. Yes. So you should not be losing money on the catheter. That's what I'm trying to. Right. You join the pilot practice, your partners. These catheters allow you to be more symbolic. Yeah. So you can put more particles like we use trinaffer our chemo-imblizations for the most part. When we treat, you know, multifocal neuroendocrants, you can be more symbolic. But I don't know that that's necessarily the game with why night. Well, there's also some concern that you can push if you're really getting the stasis, you can push particles through shunts. Actually, a colleague of mine had. And that's why since I've started using it, I do mapping and treatment with it because I'm the assurrent that things would change significantly. During the mapping, we got to end hold versus a. A trinaffer, the treatment. A colleague had a radiation pneumonitis from a radiation segment, tech to me, using trinaffer. Yep. With a very negligible lung shunt fraction on the end hole catheter with MAA. I think it's a great point. You got to replicate what you're doing in the. And I'm guilty of this. I don't always think about it at the time of the mapping, but replicating mapping to. Well, I agree. The other issue was that financial aspect. Up until April 1st of a month ago now, they didn't have a code that would get reimbursed for mapping. Now they. For trying to have antsnaper or just trying to. I think the code would apply to both. To both. I'm actually not sure. I don't know. I mean. I suspect. I suspect so as well. But. Okay. All right. Time for a case. Sure, let's do it. Let's do a case. All right. So, large tumor case from Tyler Sandow. Yes. So, Nima shows easy cases. I just want you to. I'm going to show hard cases. I brought this case only because I think there's some important things to consider during the mapping. And we had some great discussion on that red set. And I don't necessarily need to dive too too heavy on this. But the mapping is going to play a critical role in this case. And there's some things to consider because they come relevant on the back end. 49-year-old patient with Hepatitis, Massive tumor, right? It's a fun one because you see how it's well encapsulated. You can imagine that you're probably going to get a good response because it tends to. That encapsulation tends to suggest that it's more of a well-diff-moderate-diff-biology as opposed to the infiltrative component 12. I worry about those when I see a size of infiltrative? Yeah, you know you're probably on the back end. But this is AFP's low, large tumor. I bring this up only to highlight some of the important parts of the mapping. So, we always do power injections proximally and then we try to catheterize from the area that we treat. Now, I was a big proponent. The first time I gave one of my talks, I was presenting in front of Rheod, and I talked about how when we treat large tumors, we try to do multi-vessel rad-sex. We treat each individual vessel as a rad-seg. And Rheod told me at one point he was like, "You may get tired of doing that." And you may just give a proximal, like 20 GBK dose or a proximal dose, recognizing that you're going to come back regardless of what you're doing. And this gives you the opportunity to clean it up. Now, I did this maybe four years ago. I, this case, was four or five years old. I learned my lesson here because I almost got burned. But there's two big components feeding this tumor. There's a segment for branch, which you can see. And there's also a right hepatic artery that's basically profusing the entirety of the tumor. I thought, "Hey, this is covering the majority of the tumor on that right hepatic artery branch." I didn't recognize how much that volume of profused territory was going to impact my dose decision down the road. And Neement, we would talk about this just a second ago. So I did the mapping. And this was basically as far as I took my catharsis. I didn't actually go any further. I did that segment for branch. I'm going to do a radseg right there. And I'm going to do a low bar dose from the right hepatic artery right here. And I was saying, "Hey, dosis fears showed 200 gray target to the profused territory. I'm just going to try to shoot for 200 gray target to the profused territory." All right. And so here we, and Neema's laughing because he knows exactly what's about to happen. And so the good thing, what worked in my favor, and only because of this, it worked in my favor, the long shun is three. And so because the next thing is if your profused volume is 1500 and you're trying to get 200 gray to 1500 mls worth of tissue, your long dose, if it's 5% is you're really teetering on 30 gray to the total to the long. We haven't really hit on this yet. Optimal particle count in these types of tumors. How does that 200 gray and particle count, how does particle count weigh into determination for what vial to choose or what dose to give? I don't necessarily know that 200 gray is the right target, right? So dosis fear targeted 200 gray to the profused or to the tumor. That was where that concept of personalized dosimetry with partition, yes, they're symmetry that we talked about earlier came into play. The dosis fear targeted 200 gray to the tumor. The tumor dosis were actually closer to 330 gray. So that's very important. They say 200 and 5 or higher. But the dosing was the tumors actually got closer to 330 gray. But they were dealing with tumors 10 centimeters or greater similar to this. And the ones that were targeted 120 with standard dose symmetry actually got tumor all doses closer to 200. So again, the concept of higher doses to tumor implies a better kill because again more hits, more lethality. But this is 200 gray to profused volume. So you do expect your you're going to be able to act to be a tumor is occupying your entire profile. And the whole volume, exactly. You can't really improve on 200 gray. And so that's that's an important piece to consider. go in here with the thought of, I know I'm coming back, right? There's going to be clean up work that needs to be done for a big tumor like this. I don't think regardless of whether you used a high particle count with low sphere activity, I don't think you're ever going to be done. I always prepared it for at least two sessions. Yeah, for a big tumor like this, you're going to be playing. And so now this is four years ago and you use a week one Wednesday. Because if I was using glass for here, I would go as late second week as possible. Would you consider that now or so? Would you still use the same? I recognize for a tumor like this, I recognize that there's going to be heterogeneous for your deposition in the chair. And there's going to be areas that are going to die right away and then the areas that are going to be viable. I still like because I would rather each particle be Chuck Norse like, you know, says I would rather throw a bunch of Chuck Norse's and then throw a bunch of other more Chuck Norse's. I don't know that I would do week one Wednesday, but I might do week two Monday or I might do getting there week two. He's low. But just you need to check more said down, right? So I in a large tumor because it's huge. It's huge, right? The perfused tumors like 2000, you know, it's 2000 and else. But again, I don't necessarily like 190 great, but I got stuck, right? So four years ago, this is what I would have done. Today, I would have actually catheterized each individual branch. And that's where the mapping plays a critical role. Had I catheterized all of those feeding, because my perfused vans might have been 500 and 400 and 600. And then we were talking about doses of 200 would be talking about individual dose in a staged fashion multiple sessions at maybe 400 or five. So I would have been a little bit more lethal. I don't know that I was still done week one Wednesday. I might have done week one Friday or week two Monday. That's where I would probably state. But and a point is, if you're not paying the teaching to this and you do a mapping, approximately without going out and feeding or getting into these branches, that long shot was three. The long shot is six. The long dose is going to be 30 degrees. You've experienced even with a very minimal long shot fraction. Yes. That's why long shot fraction should not be used projected dose. Agreed. Yes. Agreed. Agreed. Agreed. Agreed. Two comments. One, based on the available true or false for both you, basically available literature we have, you cannot overcome completely overcome heterogeneous fear of density by just increasing particles. I agree. It's about true. You're about to grow. Yeah. Yeah. Agreed. In a case like this, I don't particularly pay attention to the number of microspheres. Yes. Because I only care about number of microspheres at least at this point. Yeah. For cases that I want to get complete response. Sure. Yeah. Because we say, okay, this is the goal here is curative. That is the bar. Anything below that is suboptimal. So let's maximize our chances of because I think paying attention to the number of microspheres here could lead you down very dangerous paths. Especially when you're just starting out. Yeah. Get the dose in there. Right? Like you're going to there's going to be cleanup. Well, I'm just making the point that you're never going to get homogenous deposition of particles. You can go to 200 million particles. 200 million particles. Exactly. You're still not going to get homogenous deposition. If I was doing this with resin, I would say that's why I asked Tyler what he would do now. And I think he would use at least a calibration that has higher number of particles. Not to the extent that all we want 40,000 or 30,000 microspheres per se. There's no way you can get that. It's still I was still a if I were using resin, I was still going to use a pre-cal 7. Just because I I wouldn't. So well, that's fine. Yeah. But I still like the individual sphere activity component. Yeah. And so yeah. So that I would use a two-day pre-cal or a one day pre-cal here because I kind of again, a lot of this was more of an art of it as opposed to the size of it. Very and hopefully you don't know the radio. I don't know what the run under it. I still like I still like for I like high activities. And so I think we're all going to say at some point getting the activity in those voxels is going to be what's going to drive your best your best component. So yeah, so he did great. But we do one month follow-ups for everybody. Now there's this is another I do the same touch or point right. Yeah. So we have a patient that has a one month follow-up and the tumor looks like it was hardly touched. Now we put 200 gray in there not 500 gray. You don't necessarily see big responses. Yeah, we have with sub-ablative dosing. Yes. One. Very good point. But it's also not something you want to see here where it's like well, the tumor looks like it might have gotten a slightly bigger. Or can I play devil's ad go say that you had very hot islands of hot shrill. And that's why I ask you I think eventually we will get to a point that say regardless of what device you use this is for a certain size tumor. This is the optimal intersect between specific activity and how much particles you need to achieve a certain. But I still think if we're going to go to the let's play it at the one ml level or at the 1% level. I still think that whatever drives your activity whether it be hot spheres or mini spheres like I I know that there is going to be voids here. But on the same token there may be activity voids with very with mini cold spheres right. Or sub less less than hot. That is true that the issue with large perfused volume like this is your limited for your projected long dose. Exactly. It's always about the long. Yeah. And then you have to just kind of high trade based on now. My goal here would be to do whatever the long dose would allow me to do. And from a convenience standpoint I didn't want to put like if I would have had to do 400 grade of this perfused territory I would have had to do several connected boxes and I hate connecting my boxes. So an 18 GBQ vial week one win stage is kind of fit within what I felt like the parameters were and I know we're cleaning this up. Yeah. So then we cleaned it up. Right. So we should have now and you at one month I guess reasonably you could say hey there's no progression should we be there in control. Yes. Disease control. It's good to be RT data right here for you. Yeah. Exactly. I will make the point we're not disparaging any other vocal rival therapies. We're optimizing one. That's a big. Tyler is. I'm not. Bye. None of us. None of us. We're on two afternoons that are rads on. They're we're good. The um no I love our guys and they're I work with some of the most special rad on. I just like to joke everybody knows me. The um I think you could wait. I think you could wait and say maybe I'm not seeing the very early oven follow-up. Yeah. I don't like doing that. So we brought them back and we remapped. I would totally agree with you. So we brought them back. We did more of a selective mapping. We were sought out the individual feeders but this time the lump shot went up on us. That's interesting in itself. Redder it actually went up or was it just how it really was? Yeah. Yeah. Yeah. You just didn't capture it. Well, let's go even if it was six the first time the lung does would have been 30 gray but we were okay. And but this time we're on a pretend like it's six. So my my intention now is to do multiple rads sec. And that's how I like to treat large tumors. I like to do multi-catheter unique compartment rad seg. That's also what I like to do. So I want to point out this is two months after initial therapy. So this is probably I mean in terms of scheduling this this is probably like three three month four. Okay. Fuck down. So if you had any long issues from the first therapy you would have seen it by this point now yes you have seen it. So in reality this is probably about four months from the time of the patient. Okay. Okay. And so I you know you can always shade or window how this thing looks. This is what the rad seg looks like. We put 268 gray. This is week two Monday now. So we're using 570 back rail persevere type activity. And so we're at 260 gray to 268 gray and then 400 gray off that segment five. So now the lung dose again is 18 for this session. Cumulative lung dose is 33. Still heterogeneous distribution. Some of those those voids but this is one month follow up again. Again we're still at this point. What do you do? Bring it back remapped. Did another long time keep scoring up. I know if you notice. Yeah. I know. I don't know what to tell you about. I'm reporting it the way it is. And we do another one. So now we have done basically we have done a fractionated type approach to this where we've hit 200 gray 200 gray 200 gray but we we played on the heterogeneity associated with the areas of viability. You can see there are areas that are are viable now that weren't as viable before. Then we get another follow up. And this is what it looks like again at one month. And so you can see it's dying. Now what I know now I've probably sit on this for another three six months. Oh really? It's probably going bad. It's probably dying tumor. You see that spider like look to it from the subblated dosing. Yeah. We painted subblated dosing right at this point would probably accumulate it like 200 plus 200 to the same territories is probably closer to 400. Yeah. And so the that wispy spider like approach or spider like appearance of the tumor now is dying tissue. And your hypertrophy in the left lobe as well. I know. Right. It's great. Yeah. Yeah. And so it's not growing. That's the thing. The tumor is not growing. Yeah. The tumor is so yeah. This so still didn't like the way it looks at that point in time. This is again three years ago or four years ago. So I wanted to clean up make it look pretty. So I so I you can particle the hell out of something and then make it not enhance anymore. And that's what I did. And so I mean to pace. I know. Well, it's you know, I think he has its role into the tumor appropriately so right. So but here we go. And this looks great. You can see that little wispy tissue that it will not fit. Yeah. Well, you would hope. Well, I originally thought it was nothing, but this is what it looks like six month post. Oh, well, that's something. And so that was I you're like, all right. Well, and so we actually brought this guy back for Y90 again. And we had two different feeders to it. And that was that was where we are. And we had a, you know, incredibly lethal dose to the tumor. So now we're at 500 great because again, we're looking at perfused volumes of 30 and 40 or 30 and 24. - Yeah. - Yeah. - And you're actually-- - What were you doing, long shot fraction? - Oh gosh, 12%. - Yeah, but okay, I was not. I wanna say it was probably close to eight, or yeah, I'm, but. - So here's what, let's say you're already at 50, 51, 50, which is like 50, great, from the previous treatments. - I think I would still try to, would you? - Okay. - So this is a guy that's been treated over the course of year, - Yeah. - year to two years worth of Y90. And he's had good responses. He tolerated the long dose as well. He's a male, he's taller. So his lung volumes are probably, archer, probably larger. So the lung doses are probably overestimated in him. So he could probably tolerate a little bit more. - And you're using smaller particle counts, right? - Yeah, but if he were a petite female, I might consider that I've probably touched my limit, but he's a larger male. - Okay, right. - I would taste it. - You would taste it. - Okay. - And I like sea taste. I done, yeah. - You can also oblate this. - You know, I think it's reasonable to do a percolablation. Having ablated Y90 cavities before, it feels very, very funky when you're putting the needle in. It feels like you're pushing through rubber tire when, because it's-- - Just scarlet issues, yeah. - I brought a issue, right? Gotta be careful with that. But yeah, I think all those approaches are reasonable. - SPRT here? - Really, SPRT here. - I don't think any radon could agree to SPRT just given how much radiation is already given. - Maybe I've, it's not my area of expertise about it, don't. - I don't know, either. I think Michigan just published a pilot trial on combination Y90 plus SPRT. I think if you're focal and localized and there's not a lot of normal tissue dose from the Y90, like you didn't give a lot of low bar dose, right? These were all selected, except for the first treatment. Maybe that's a reasonable thought. We're not radiation oncologists, I don't know. But it's an interesting thing. - It's an offset. - Yeah, it's a really, really, really, yeah, this thing. - On the combo Y90 and SPRT. So anyway, just a dissident aside. - So, you know, when you calculate the volume of liver treated to, I think this is an important point when you're drilling the large tumors and you talk about, you know, percent total liver treated. You need to exclude the volume of the tumor. - Right, and so actually we're not treating a lot of normal liver in any of these. - So let me ask you this. This is an important kind of thing that I've recently recognized. And we don't do this as much here in the United States. Well, is this patient so surviving? - Oh brother, he's alive and thriving. - He's alive, that's great. - That's me. - That's great. So a very kind of eye opening data that I was published was the long-term follow-up of doses fear trial. - Yeah. - That they showed significant sustained benefit of survival for those patients that were all large tumors. But only if they got to surgical resection. - Yeah. - Actually, there was no difference in survival for the personalized those symmetry versus no personalized those symmetry if they did not undergo surgical resection. I'm ready for me to hit this one. I would love to, because this is the perfect - Yeah. - It's patient of that sort, try us. - And so he actually, they tried to do surgical resection. They went in and kind of barked at it when they opened them. They thought that there was more tumor burden than they previously assumed. And so we wound up having him back to us to do one, nine, exactly that little focal area. That was what they thought. - So initially they took him to, they were going to. - Yeah, they barked at it. - So why don't you think about that? - That's not the thing we do. - I think it's important to understand doses fear. People don't know this, but doses fear, because it was a randomized control trial, all the patients received one treatment. The majority of the responses in doses fear were partial responses. Now they had great response rates. - As you would expect with large tumors, - Yes, you would see the antiltrious rate. - So yeah, yeah, yeah, yeah. - Here it is. - Partial response. So take dose fear within the context of the way it was done. You did one treatment, you were allowed one, one, 90 treatment, you were not allowed to. So a lot of them are partial responses. In our world, I treat that patient, and I know that they get a partial response, whether or not it's a partial response at a year or whatever, you're coming back to clean that up, right? That's what you would do, that's what I would do, that's what anyone would do. They weren't allowed to do that in dose fear. So if you have to sit there and watch a tumor for a progress short of getting it resected, obviously the ones that got more, a better long-term treatment with resection are going to do better than the ones that got Y90 only. So dose fear, the limitation of understanding the data talking about resection and the long-term survivability in resection and dose fear, has we taken in the context of those patients were only allowed one treatment? We don't know what would have happened if, if you would have gotten the opportunity to go back and clean it up over and over and over again. So I thought about that exactly, and all of us have been involved in clinical trials, we know the limitations. But then a similar data came out of Singapore under Resinside, 413 patients treated with Resins with HCC, 70 of them were down, these were all large tumor-ish. They were not as advanced, all of them were not as advanced as the dose fear study. If they got to surgical resection, the median overall survival of 72 months. Which is similar to what doses fear showed under six year follow-up or five year follow-up. Again, downstaging them to surgical resection. That was not part of a trial, so I have to go back and look and see if they were re-treated all times or not. Multiple times, but the bottom line was, if they got them to surgical resection and they looked at many different factors, if they had proto-ventrum doses, if they were above up to seven, if they were all sorts of different things, advanced or not advanced. The bottom line, the conclusion was, the best chance of survival in these advanced HCC patients, similar to what the long-term follow-up, at least the authors of the long-term follow-up of those fear claim is that the best chance of survival in these advanced HCCs is to get them to surgical resection. We don't practice that in the US, and it's kind of, it's been a bit of an eye-opening, I think it allows you great collaboration with surgical oncologists, right? But again, I think why 90 can kill, right? And if you know why 90 the right way, a blade of you have to blade it. - A blade of you have to blade it. - Yeah, you just wind up. - But not everybody is as persistent as you are. You have to realize that, right? - Yeah, but you would have done this. - I know, but I mean, that's not, again, that's not something that happens in a real world. - But I think that's the evolution in the space, right? Like we are not just giving a low bar dose and running away, we are hammering these, especially larger tumors with repeated doses with repeated treatments. And then you brought up the concept of multimodal therapy, right? I mean, like we get stuck in this box where we're 90, we're just gonna winety everything. And it can only be winety. And in reality, you can mix and mash therapies in these patients for better efficacy, right? We know that. - Yeah. - The loyal paper that came out, right? I mean, like you get good outcomes. - Yeah, so I do think this is the way of the future. Yes, maybe there's a little bit of a disparity in practice around across the country and in the world. But to me, this is the direction. - But I wouldn't stop anybody if they wanna go resect it. - Yeah, I think there. - I'm Michael so I was to bring this up was, I mean, I obviously believe in my 90, but should we push more or should we bring these data to the attention of our surgical oncologists at look? - Oh, see, I, I see. - This is something that we haven't done before here much because when we talk about, oh, this is not a surgical candidate. - So he came from a surgical oncology. - Yeah. - And we were treating him every time. And I was like, hey man, do you wanna, looks like this is some viable tumor. Do you wanna go take, do you wanna resect now? We're kind of at the top end of what our lung dose would be anyway, you wanna go resect it. - But this was after multiple treatments. - That's right. - Multiple lineators. - Yeah. - And so he tried and their issues associated with trying to resect the liver and I worked with some incredible surgical oncologists. They're doing an ex plant, a liver, a whole liver ex plant as opposed to a partial liver resection. Their intricacies are doing that after getting a wineniny. And so there's a lot of it, he's, there's scarring, there's, there's, all that anchors to it. So it's not like it's an easy resection for them anyway. But I think, so if they can get resected, I'm on both. - 'Cause you had adequate future liver or FFR, and short by doing all of that. - But you're not saying stop trying to treat. - No. - And go to resect, you're saying treat until you can't treat. - But it is, yes, about treat. - And then you did that for a while. - It seems like at least based on both, again, doses fear was more partial response, but even the Singaporean data. It seems like despite what you get, if you wanna follow these patients for five, six plus years, their best chance of survival is to get that better than a tumor is viable or not, get it out of there. - Yeah, I can't disagree with that statement. I think if you can't resect it, then you look at doing something else. But I think it's, yeah, often. - And this goes back to what we talked about earlier. You effectively gave that patient a test of time. They didn't recur on the left side. So then, you go to search, I mean, it takes a complete sense. (upbeat music) - Thank you guys so much for tuning in. If you haven't already, please be sure to subscribe, follow, and rate the show. Let us know how we're doing and what we can do to improve it. We work really hard at making this a valuable resource for you and we wanna continue to do that. So give us your feedback. Lastly, tell a colleague about the show. We think they'll like it. If you have any questions or comments, direct messages at underscore backtable on Instagram, LinkedIn, X, TikTok, and Blue Sky. Backtable is hosted and produced by myself, Chris Beck, and co-hosts. - Ali Beheadie. - Michael Boraza, Sabine Don, and Aaron Fritz. 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