BackTable / VI / Podcast / Transcript #379

Podcast Transcript: Management of HCC: Focus on Radiation Segmentectomy Part 2

with Dr. Juan Gimenez and Dr. Tyler Sandow

In this episode, host Dr. Chris Beck continues the discussion on managing hepatocellular carcinoma (HCC) with Dr. Tyler Sandow and Dr. Juan Gimenez, interventional radiologists at Ochsner Health in New Orleans, Louisiana. You can read the full transcript below and listen to this episode here on BackTable.com.

(1) The Sphere Conundrum

(2) Tumor Mapping & Margins in HCC Radiation Segmentectomy

(3) Macroaggregated Albumin (MAA) Delivery

(4) Cone Beam CT for Navigation and Volume Calculations

(5) Using Simplicit90Y as Dosimetry Software

(6) Determining Radiation Dosage

(7) Planning for Radiation Segmentectomy by Tumor Location and Size

(8) Current and Upcoming Research in Radiation Segmentectomy for HCC

(9) Combination Therapy with Other Medical Specialties in HCC Management

(10) Future Directions: Extrahepatic Radiation Segmentectomy and Augmented Reality in Mapping

This podcast is supported by:

Boston Scientific TheraSphere

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Management of HCC: Focus on Radiation Segmentectomy Part 2 with Dr. Juan Gimenez and Dr. Tyler Sandow on the BackTable VI Podcast)

Ep 379 Management of HCC: Focus on Radiation Segmentectomy Part 2 with Dr. Juan Gimenez and Dr. Tyler Sandow

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[Dr. Chris Beck]:
This is part two of a two-part series. We're going to pick this conversation up that we began with Drs. Gimenez and Sandow. We're talking about Y-90 and the HCC program at Ochsner. Enjoy the podcast.

All right, so the patients move through clinic and you guys have settled on intra-arterial therapy. I'll leave it up to you guys how you want to split it. I'd like to talk about radiation segmentectomy, but also what patients end up with lobar treatment and how you choose between those two. Is there a number cutoff, a volume cutoff? It's a big topic, but I'll let you guys chew on it.

[Dr. Tyler Sandow]: I'll take the rad segment. That's the easier one.

[Dr. Chris Beck]: [laughs]

[Dr. Tyler Sandow]: I'm joking.

[Dr. Juan Gimenez]: We were talking about the outline before we got to it. We got to the bullet point that said lobar treatment, and we both look at each other and said, "What is that?" We typically don't do that. We're not saying that there's not a place for it or it's inappropriate. It's just that in our practice we tend to select everything out and go after every little feeder for the tumor. Sometimes, that's four or five different vials. It's a lot of cone beam CT. We not just looked at our data but published data. We know that what's important is not the gray or the amount of radiation but the amount of liver you're putting that radiation under.

[Dr. Tyler Sandow]: That's when it comes to adverse events, I think, you're trying to say?

[Dr. Juan Gimenez]: Yes. We try to keep our volume small. We select everything out. That's our philosophy, and that's what's worked for us the best. Sometimes, in order to be able to achieve that, yes, we have to use a combination of ablation and Y-90 depending on size and location, all these other things. Tyler, what would you add?

[Dr. Tyler Sandow]: I would say we try to make everyone a rad seg candidate even if it's a multifocal disease that has tumors. Say you have four or five tumors, we honestly will try to make you a rad seg candidate. We might not do all the deliveries in one setting. We might split them up, do two one day and maybe three on another day. Even if it's metastatic disease, we try to make everyone a rad seg patient. We don't do a whole lot of lobar. Juan can do tons of fancy multicompartment when it comes to larger volumes of liver that we treat. He's way smarter than me when it comes to basically anything to do with Y-90. I like to keep it as simple as possible. I try to make everyone a unicompartment rad seg and it has worked well for me.

[Dr. Chris Beck]: All right. This is, actually, one of the really core principles that I wanted to get at. I don't want to gloss over it and you just say, "Oh, okay. Everyone, we tried to make into a rad seg." There are a lot of practices out there, advanced practices that are not like that. Can you talk about how you got here? What are the challenges involved in trying to get into all these feeders? How long a mapping stay? Just the nuts and bolts of actually making this a reality.

(1) The Sphere Conundrum

[Dr. Tyler Sandow]: We have something called the sphere conundrum. You told me that you were going to cut me off if I talk about it for too long.

[Dr. Chris Beck]: I tried. I thought I took that out. I have the outline that I send you guys and the outline that I make for myself. I guess I left it in there, but that's irrelevant.

[Dr. Tyler Sandow]: No, so I got the sphere conundrum. I can blast. I can dig deep down into a hole. If you give me three minutes, five minutes maybe, I can probably–

[Dr. Chris Beck]: Let's hear it.

[Dr. Tyler Sandow]: I'll do it-- do you want to do it now? We can.

[Dr. Chris Beck]: Yes, let's do it.

[Dr. Tyler Sandow]: All right.

[Dr. Chris Beck]: Perfect timing. Should we do this now, Juan, or is there a better time?

[Dr. Juan Gimenez]: Do it now. You touch based on that because it'll explain everything as far as our philosophy. I can take it on the back end and answer your question about length of mapping because it's not as long as you would think it is.

[Dr. Chris Beck]: Okay.

[Dr. Tyler Sandow]: All right. Juan will go through our technique, and I think that's important. I think we have to understand at the most granular level why Y-90 works. Y-90 works because beta decay results in a release of high-energy electrons. That essentially becomes microscopic bullets. That's what damages tumor DNA. Now you damage tumor DNA one of two ways. You either create a double-stranded break. If you get that, that's the headshot. That's going to kill them instantaneously. Alternatively, you get a bunch of body hits, single-stranded DNA hits. Some DNA can fix those. You have to accumulate multiple single-stranded hits or multiple body hits to kill a tumor cell. Now, most people would agree that 1 cc of tumor contains about a billion tumor cells. You need either a billion perfect hits or some higher multiple of that to kill a billion cells.

Y-90 is a game of statistics. The goal is to get your activity up. This is why Legacy was so successful if you compare it to everything else. Legacy showed that you had higher rates of CPN with doses greater than 400 gray. That's different than what people used to think of when we were talking about 190 or 200 gray. The difference with Legacy was the activity was doubled. You have more bullets are released, essentially.

Then it becomes a concept, or I guess now, let's say let's look at sphere activity and dose. If we talk about a TheraSphere sphere, like a microsphere, that was delivered at Week 1, Friday at noon, so I guess that's six days after calibration. That sphere is 1175. The mean activity of that sphere is 1175 becquerel. You compare that to a sphere that has much less energy like a 168 sphere, something that would be delivered on the very, very back end of a TheraSphere model. Week 2, Friday, or a 168 sphere is a Flex-3. All right?

An 1175 becquerel sphere will undergo approximately 330 million decays in one week. Now a 168 becquerel sphere will undergo 47 million decays in a week. That's a difference of a quarter of a billion decays. There's a massive difference in the amount of bullets that are released. All right? We know space is limited. If there's already a billion tumor cells in 1 ml of tissue, do I want to pack particles in there until there is no space, or do I want to make sure activity's in there to do what it needs to do? It becomes a concept of the sphere conundrum.

If I had an 1175 becquerel sphere and I need to get 400 gray, and you need about 7,000 spheres. If I had a 168 becquerel sphere, and I need to get 400 gray, and you need about 50,000 spheres. We looked at our results, and we looked at our spec CTs and our post-treatment imaging. We could figure out exactly how many spheres went into these tumors. We rarely got over 20,000 spheres in the tumor, even at the most smallest of volumes and highest of concentrations.

If we use 20,000 spheres as a cutoff for what we would call difficult or undesired saturation, and you wanted to get 400 gray into the tumor, you need a sphere that is about 412 becquerels worth of activity. That's equivalent to about eight and a half days from calibration, so delivering on a Week 1 Monday, or Week 2 Monday, or early Week 2 Tuesday.

If you look at Beau's data, where he actually looked at specific activity, he came to the exact same conclusion that you need to be delivering high-activity spheres to get higher rates of CPN. He said you shouldn't deliver more than eight days after calibration, which would be Week 2 Monday. For that reason, we treat almost all of our patients Week 1 with Week 1 vials, because we know that that activity gets to the tumor the way we want it to.I'll end it with this. I think it sums it up nicely. You look at the studies that actually talk about durable outcomes or CPN, Legacy, Razor, Dosisphere, Target, the Mayo Clinic data, I like to call them Beau 1 and Beau 2. These all used high-activity TheraSphere doses. These guys, the majority of the people that publish these results are Week 1 TheraSphere users. If they're getting durable outcomes doing rad seg like that, I think that's the way that we at Ochsner have found that we can replicate what they do, and our outcomes have ironically replicated everything that they've done. All right. I think that was–

[Dr. Chris Beck]: Not ironically.

[Dr. Tyler Sandow]: Not ironically, I guess.

[Dr. Chris Beck]: Five minutes.

[Dr. Tyler Sandow]: Was it five minutes? Did I do it?

[Dr. Chris Beck]: Yes.

[Dr. Juan Gimenez]: That's good. I actually timed it.

[Dr. Chris Beck]: That was right on.

[Dr. Tyler Sandow]: All right. You could cut me off. I don't need to talk anymore. I did all I needed to do.

[Dr. Juan Gimenez]: I do want to say something, and I hope this makes it on the final version. Tyler said that I was smarter than him. There's no way I can come up with what he said. He was just doing math and talking about millions and billions of numbers. I'm not that smart. I'm just letting you know right now. I'm simple, a simple guy.

(2) Tumor Mapping & Margins in HCC Radiation Segmentectomy

[Dr. Chris Beck]: We'll make sure it gets in there, Juan. All right, Juan, can you digest some of that and talk about how the sphere conundrum ultimately leads to how your guys’ approach – I guess the take home is, how do spheres, Week 1 dosing, and what you've already said is that you select out for individual feeders and you're trying to do rad segs? Just talk – expound on that a little bit.

[Dr. Juan Gimenez]: Tyler said, high-specific activity matters. We do believe that. The only way to do that is to treat as close to day-of calibration, which is on the same day as you can. The problem with that is with increased specific activity, your dose goes up too. Then you have to make sure that you minimize adverse events. The only way that you can minimize adverse events is by treating as small an amount of liver as possible to take care of the tumor. Otherwise, you're going to end up with a lot of specific activity, a high dose in a big volume.

That's what's been shown in all the studies like Target, for example. Beau has some articles too showing that it's about the size, the amount of normal liver that you treat that results in complications not necessarily the dose. When you put all of that together then you're basically left out as we need activity, we need dose, we've got to stay safe. The only way to achieve all those three is by getting as selective as you can. Then you have to go fish all these little vessels out to a point as to you've got to do all these things, your mapping has to take five hours.

We boil down our technique, literally – it's not ours. There's three papers that pretty much summarize everything that we do, and it's not my idea. Like I said, I'm not that smart, but I'm a great copycat. No, for real. One of them is Ran Gabas paper. There's an ACR Society of Nuclear Medicine consensus paper, and then there are the consensus guidelines for dosimetry where the most one updated one is from 2022. Basically, those three papers together are what we use.
[Dr. Juan Gimenez]:

Mapping is simple. If you just think of what the purpose of the mapping is then you can understand what it is that you need to do to get it right. Basically, the purpose of a map is to identify all tumor feeders, vessels that are going outside the liver, any potential extrapolate supply. With that being said, literally ours is a protocol. You have to-- always start by reviewing your imaging and try to identify any variant anatomy. Then stick to it. Power runs, heat. No matter how strong you are, you're not going to be able to inject five for thirty. You can't do that. Power runs. Start with the celiac. If needed, do an SMA and then go from big to small, either common or proper hepatic.

Do we do this for absolutely every treatment? No. If you only have left-sided tumors, yes, just into the left. If it's only right, right. If you somebody between segment IV or segment Va you have to interrogate both the left and the right because invariably you will have feeders from both.

Then cone beam. Cone-beam CT is the main state of our practice. Again, it's the same concept. Start big. Do a lower and then get smaller. Start getting selective and more selective until you make sure that you get what you need.

What people are going to say, Y90 don't work or have a residual. Wherever you deposit the radiation, it will kill that tissue. Whether it's liver, stomach, heart, esophagus, it doesn't matter. If it goes in there, you're going to end up with a hole. Whenever you have some leftover or some residual, it's not because the radiation didn't work. It's because you didn't put radiation there. That's why the concept of do a lower spin and then get smaller and make sure you have complete coverage is extremely important.

I will tell you, we use a lot of 2.0 French microcatheter so the liver -- a lot of times, we will not select those arteries you're mapping because they can get spasm or they can get dissected, and then you're not going to be able to treat. You have to be able to identify knowing that that will introduce an unknown at the time of delivery because you may have to spend a little bit of time but then identify everything. You may have bilobar disease, take the time to do it and just follow that big-to-small approach.

If you're on the right lobe, start with the right, come in on the right, anterior division, posterior division, Va, VI, VII, and cone-beam, all of those things, and get smaller. Then, I would say, take your time to look and be very objective about the images. Don't let your ego get in the way. That's how you end up missing things. I would say, take the time to write a mapping even when you have to select and interrogate a lot of vessels. If you do it that way, it will take you at most two hours.

Now, when a mapping takes four to five hours, and when you do the complete opposite, so when you say, "Oh, that solution is segment II. I'm going to go to segment II," and then you don't see anything. Then you start backtracking and backtracking and basically, you end up higher radiation doses, more time, more spins, more of everything. Start big and go small. It saves you time, literally. Everybody that comes through our practice, all of our trainees, that's how we tell them how to do it, and if you, ourselves included, deviate from that, we pay the price for it.

Then just come up with a treatment plan. Do it all at once and then decide. If you know that you have to treat four or five vessels, sometimes, yes, it'll be easy. That can take you about an hour. If you're sub-selecting multiple tiny branches, two of French, very tortuous anatomy, divide it. Just do two at a time. Don't get mentally exhausted and then give up. Just do two, bring them back two weeks later, do the other two, and then just get your imaging. We've learned from our own mistakes to say that our technique has evolved significantly since we first started doing this.

As of today, I can tell you that's what works best for us, and that's what's allowed us to replicate the results of, so like Tyler likes to call them the Y90 giants and I agree with him, all of these guys, but it's just having-- being very methodical and paying a lot of attention to detail.

[Dr. Chris Beck]: There's a lot of questions that I wanted to dig in on that. One of the things that strikes me is complete coverage of tumor. If you're going and sub-selecting each vessel, the way I think about it like on ablation is you want to hit the tumor. You also want to hit the margins around the tumor. Is that a consideration whenever you're treating?

[Dr. Juan Gimenez]: Yes, you'll always have a margin. Unlike, I would say, ablation, which you can get very just a tumor when you ablate that space if you want, if you think of vascular territories there, you're always going to be angiosomes-- that's a term Beau likes to use-- and triangular in shape. You're always going to have a little bit of a margin. We see the biggest issue is you miss part of the tumor and so–

I'm not talking about a centimeter. It's a couple of millimeters. That's where the lobar cone-beam is so important because on that lobar cone-beam it has multiple thing. You can see the entire enhancement, part of that tumor. If you get too selective and you miss something, also, if you do a right lobar and you didn't see complete enhancement, that you may have to go to the left or you have a phrenic or something else going in there that you have to look for, that's where the issue comes.

You're always going to get a margin no matter how selective you are, at least that's been our experience because there's always a little bit of normal tissue. The most important thing is the more selective you get you may just stop isolating other branches and maybe supply that you may miss. I can tell you, it's very easy to do if you just go straight to a vessel and you see a nice, round enhancement area like, "Oh, I got it all," and then you go look back and I'm like, "Oh, yes. I guess, I missed this little edge." That's it.

(3) Macroaggregated Albumin (MAA) Delivery

[Dr. Chris Beck]: You also talked about the MAA delivery.

[Dr. Chris Beck]: Where exactly do you put the MAA if you're not always going to-- I've always thought about putting the MAA exactly to mimic the actual treatment dose.

[Dr. Juan Gimenez]: We used to do that. You hear people tell you that sometimes you need to do selectively. You can occlude that vessel. It's happened to us a couple of times. To me, one or two times is more than enough to want to change my practice because you can't treat that patient. We tend to do the majority of our MAAs lobar. In that way, you just get a good understanding of everything and you avoid any potential occlusion.

[Dr. Tyler Sandow]: Also, the caveat I would add to that where we talk about MAA is-- and Juan does this much better than anyone – but whenever it comes to multicompartment, when we do a multicompartment or partition dosimetry, I think if we're going to treat a larger volume, that's where we care that MAA is actually delivered close. Sometimes, not all the time, sometimes MAA will behave like you would expect the particle to behave. If it does, you have a great way to anticipate how your dose will be delivered. When we're planning to do multi compartment, which again is a rare part of our practice, or at least mine, if we plan to do multi compartment, we care where the MAA gets delivered. We might deliver it in a division or in a large portion of a segment. Otherwise, if it's just going to be a unicompartmental segmentectomy, it's going to be a lobar MAA.

(4) Cone Beam CT for Navigation and Volume Calculations

[Dr. Chris Beck]: Do you guys use any of the software, the software like OncoSuite that helps you select the feeders or–

[Dr. Tyler Sandow]: To select feeders? No. We have navigation software with Siemens, like EmboGuide. We don't use it routinely. I will say to plug one on this cone beam CT thing-- he's a big advocate for lobar cone beam. What he does, and I think we all should do, he goes back after his mappings and will confirm that he completely covered the tumor in the same way with all of his segmental or sub-segmental cone beams. He will confirm that he had complete coverage of the tumor. He actually overlays them to make sure that he had everything laid out well. I think that's the only way to make sure that you covered it and you aren't going to be surprised about any bad responses or suboptimal responses. We do use dosimetry software though.

[Dr. Chris Beck]: Before we get to the dosimetry software, which I do want to talk about, I wanted to talk about how you guys calculate your volumes or the volumes of tumor treated are based off. Do you use it off the old cross-sectional or can you just calculate it off the cone beam?

[Dr. Tyler Sandow]: We love to use cone beam.

[Dr. Juan Gimenez]: Yes, cone beam.

[Dr. Chris Beck]: Cone beam?

[Dr. Juan Gimenez]: Everything straight from cone beam.

(5) Using Simplicit90Y as Dosimetry Software

[Dr. Chris Beck]: All right. Now I do want to talk about dosimetry. Do you guys have some software that you like that's been helpful or been an unlock to how you treat these guys?

[Dr. Tyler Sandow]: We do.

[Dr. Juan Gimenez]: Yes. We're biased.

[Dr. Tyler Sandow]: A little. It was forced on me. I should say that dosimetry software was forced. I wasn't always this way, but I have come to be a believer. Before we used to use the TWI Excel spreadsheet that a lot of people use for TheraSphere. It worked well for us. We had no issues. I absolutely hated the way we had to draw volumes. We had a-- gosh, what was the name of the-- it was a vital product that we had to use.

[Dr. Juan Gimenez]: Vitria.

[Dr. Tyler Sandow]: Vitria. Yes. We had to use Vitria to map out our cone beam volumes, and it took forever. It was probably one of the most challenging products to use. Then we switched over to MIM. MIM is okay. I don't love it. I don't hate it, but it's just okay. Murata had – I think Juan has been working with them for quite some time. We had a lot of case volume and Juan had a lot of interest in dosimetry, and so he's been working to refine Simplicity for quite some time. He actually pushed me to start using it.

I will say that I didn't really like switching from what I'm used to with the Excel spreadsheet, which is working fine, but I do believe in the Simplicit90Y. It has allowed us to up our game when it comes to multicompartment, when it comes to looking at post-treatment spec and making sure you can do voxel-based dosimetry so we know what our D70 looks like, the dose to 70% of the tumor or D99. A lot of the stuff that we've been able to do with Simplicit90Y has been great. It's made ordering smoother. I think I should also plug Juan too. Juan is actually setting up a course. He's got a Simplicit90Y course coming up.

[Dr. Juan Gimenez]: I saw it on the SIR forum.

[Dr. Tyler Sandow]: Did you see it? Yes.

[Dr. Juan Gimenez]: You're making me blush, Tyler.

[Dr. Tyler Sandow]: I know. Juan is going places. I don't know if you realize this, but you better get on board now. Juan is there, man.

[Dr. Chris Beck]: I feel like a rocket ship.

[Dr. Tyler Sandow]: Exactly.

[Dr. Juan Gimenez]: Because of Tyler.

[Dr. Chris Beck]: All right. Simplicit90Y, that's the Boston side product?

[Dr. Juan Gimenez]: Yes.

[Dr. Chris Beck]: The software? When did you guys start using it? What do you like about it, Juan?

[Dr. Juan Gimenez]: We started using it around COVID. To Tyler’'s point, we had been working with Boston, and they had this new product. I think Boston understood that the whole ordering process was, and the dosimetry process was cumbersome. Nobody was really doing it. Even MIM didn't have a dedicated software for Y-90 at that point. We had a lot of headaches. We were switching packs. With the switch of the packs, our volume software went away. We needed to do it. We brought it in.

Like its name implies, it's simple to use. At the same time, it allows you to get as granular as you want. You can, to Tyler's point, draw all your tumors, look at how much radiation went to each of them and get as granular as you want. It's something that, we have-- some of the guys in our group have difficulty using computers, and some are very advanced. This catered to pretty much everybody. I could just show and they can just do it themselves. It was very easy.

It allowed everybody to keep their ordering on time because otherwise, people would just procrastinate. It helps us keep a huge database of all our patients. They're all saved. We can go and literally open any of them. It's been key to look at our outcomes, and research, and a lot of the things that we've been doing – with what Tyler's been doing, I should say. I just ride his coattails when it comes to all of the research stuff. Yes, it's simple.

We have four or five vial cases routinely. I would say if we get one patient with one vial, that's unheard of. When you're ordering multiple vials to be able to understand how much you're going to send to the lungs, how much you're putting into the liver, the percentage of the liver that you're treating, that makes it very simple. To Tyler's point, MIM works. It's just that, I don't know, there's this thing about MIM that they like to make it a little bit of complex and it's unintuitive in my opinion. I was not able to figure it out. I know all the nuclear medicine guys love MIM, so more power to them.

[Dr. Chris Beck]: What do you guys use Simplicit90Y for as far as Tyler, you mentioned you guys do specs on the back end after treatments to look at dose and where it's going?

[Dr. Tyler Sandow]: Yes. We so specs after map, SPECT/CT after mapping, and after delivery. That's the one protocol. He has made sure that where we do Y-90, we do SPECT/CT. I think that's a good thing to do. Not everybody has access to SPECT/CT, but we do. We're going to make sure that we do it that way. if we're going to do multicompartment, we'll use the mapping SPECT/CT if it can help give us an idea about dose to tumor, dose to normal and we can tailor our dose that way.

Then we'll also use Simplicit90Y, the actual dosimetry aspect of Simplicit90Y to track what the dose to tumor was and actually look at-- you can take even more granular, do voxel-based dosimetry. They call it D70, or D50, or D99. You can see what the dose to 70% of the tumor, or 90% of the tumor, or what your dose to normal was. We'll use that. That detailed information has allowed us to figure out how spheres were deposited in tumors. Because if we know what the dose was in those areas based on the SPECT/CT, we know how many spheres went there if we know when we delivered the spheres. We've been able to figure out sphere concentrations in normal tissue and tumor tissue and optimize how we choose what day to deliver particles.

(6) Determining Radiation Dosage

[Dr. Chris Beck]: We've talked about it in a roundabout way as far as you guys try and get selective as possible, high dose matters like as far as hitting 400 gray. Can you get a little bit more specific about when you're ordering your dose? You already know the volume that you're going to be treating, you want to minimize or keep the volumes as low as possible. When you're dosing these patients, you care necessarily if it's 500 gray, 600 gray, or you just try and pick a vial that is going to be above 400?

[Dr. Tyler Sandow]: Dead is dead.

[Dr. Juan Gimenez]: I would say our baseline is 400s. There's a little bit of caveats to that, but we've gone as high as over 1,000 gray to perfuse volumes and tumors. Granted, small volumes, putting 1,000 gray in a 300 to 400cc volume, that's dangerous. Small volumes, yes. The biggest caveat that we noticed that we try to be careful is close to a porta hepatis and that common bile duct because you may get some issues with the bile duct and then you end up with strictures and they need biliary drain. I would say close to the hilum, be a little bit careful. If you're peripheral, right there next to the gallbladder doesn't matter.

[Dr. Tyler Sandow] has a case, like you showed, so 1200 gray, segment V, right there next gallbladder, and nothing happened to it. We've done it next to the colon, next to the stomach. We have not seen any complications from the procedure itself. It's not an issue for transplant according to our transplant surgeon. We have been told sometimes if you're going to go to resection, not necessarily transplant, there may be some adhesions that may make the operation a bit more complex. We'll just say 400.

We do follow the dosing recommendations from the consensus guidelines. If you look through all of those, and most of this comes from a dosing sphere, they'll tell you that you need to put at least 205 to tumor, preferably 250 to 300. We try to follow that as our lower end of radiation. We cannot get that much into tumor, then we might have to switch to a different modality. Using 200, even close to that porta hepatis region has been safe for us.

[Dr. Chris Beck]: Does this mean everyone is Week 1, Wednesday, Thursday, Friday treatment, or virtually–

[Dr. Tyler Sandow]: Just about. Now, we will occasionally – if you're treating really small volumes like, let's say, if you're only treating 25 mLs worth of volume and you put in the smallest file size you can get as a 350q, and you're going to put that in 25 mLs worth of tissue, that's going to be close to – I'm trying to spitball. I think it's 1,200 gray. Now, talking to people, and you never know who you're talking to about this, 1,200 gray can make people nervous because they just associate gray with, "Oh, that's too hot. I'm going to cook my hands on it," or something. Granted, dead is dead. If it was going to be dead at 400, it's going to be dead at 1,200. Really, dead is dead.

I like to come back to that whenever we're talking about radiation delivery. Occasionally, rarely, we'll deviate into a Week 2 Monday, especially if it's a small volume and we want to keep our radiation in the porta hepatis region. We want to keep our actual gray low in the 250, 200 range. We'll deviate a little bit. I would say, again, 90% to 95% of our deliveries are in that Week one, Wednesday to Friday range.

(7) Planning for Radiation Segmentectomy by Tumor Location and Size

[Dr. Chris Beck]: There's another scenario that I wanted to get at. Some of what we talked about is the tumors that you can just dunk all over like the ones where you can achieve a 25 ml volume. What about if you have a centrally located, maybe away from the porta hepatis, but big tumor, centrally located, multiple feeders, how do you tackle it?

[Dr. Tyler Sandow]: We are cone beam crazy. Our team expects us to do cone beams. We go in there with the anticipation to get-- we will cover every possible feeder. I think there's multiple ways to do this. I don't disagree with the philosophies. Our practice, we want to make it subsegmentectomy because we know that if we can maximize dose to tumor and limit dose to normal, we have a better opportunity to come back on the backend. If we don't perfuse the whole liver with dose, even though the majority of it might get sucked up into tumor, we have an opportunity. In an 8, 9-centimeter tumor, we might be coming back to retreat them.

I think another school of thought is to do a larger volume. Knowing that the tumor is going to soak up the majority of the tumor, you can either do a partition or multicompartment dosimetry for it or you just do a lobar dose maybe at 200, 150 gray knowing the tumor is going to take a dramatic more amount of those spheres. You're probably going to be coming back.

I think both ways hold merit, but our practice is we will select every feeder. If it's seven feeders, we'll do it. That's the detail that I think we like to push for because we're competing with surg onc for cases. I shouldn't say we compete. We share cases, and we do what's best for patients. In the real world, surg onc they're going to take the time to dissect out and make sure that they carve a margin on a tumor. Those cases might take some time. I feel like if we're trying to produce the same results as our colleagues in other specialties, we owe it to the patients to spend that much time trying to select this stuff out.

[Dr. Chris Beck]: How about tough locations? We talked about centrally-located tumors, but what about tumors that are wherever they are, they end up having some extrahepatic feeders. How do you guys deal with that?

[Dr. Juan Gimenez]: We map them out and then it goes back to the same. You got to understand what you're dealing with. Have we done extrahepatic? Yes. We've done a couple of phrenics, adrenals, even gastric branches, GDA branches, Tyler has done] splenic branches. The key thing there is just to make sure that you can control where the radiation is going to go, so the liver is low. That might be one of the instances, if we're doing an extrahepatic, that we may put the MAA there just to be 100% sure that we don't have any distribution that we may not be able to account for. Then we infuse a little bit slower and we dose a little bit lower.

I would just tell you with anything that may be going to bowel, the number one thing is just to make sure that you're not going to get anything in the bowel. You can still go pretty high. With some of the other things that may be going to skin and diaphragm, particularly skin, you have to be careful because you may cause radiation burns, and they may end up getting wounds and things like that.

I think the spin case reports of people inadvertently putting Y90 into a falciform artery and they end up with skin burns. Tone it down, making sure that you understand where everything is going to go, and try to get selective. You'll see even with some of these phrenic branches that sometimes it'll be one dominant one that'll just go to tumor. Get into that.

I would say treat everything that it's fed by the liver first just because that's going to be safe. Sometimes you'll get a little bit of an expected result from that extrahepatic. Fortunately, you'll see that some of that will respond to treatment. Can't really explain why, but I've had that happen. Always treat the liver first and then just take the time to analyze. If you're going to hurt skin, taste, maybe you can ablate that component. Be open to other things. You can do it. It's just you have to pay attention. I would say don't go trying to do that on your first case or your first 10, 20 cases. Maybe give yourself a little bit of time to get comfortable with everything.

[Dr. Chris Beck]: Get your chutzpah. Is coiling a part of your practice for the mapping part of the procedure if you're trying to redistribute flow or just exclude branches that you're not sure if you're going to get reflux into?

[Dr. Juan Gimenez]: I would say for reflux purposes, no. If we have to, we'll just get more split doses. Now redistribution is a concept that I understand. I think it works great for some people. I have not been successful at making it work the way I want it where it is reproducible every time, so I don't use it. I don't do it for that.

[Dr. Chris Beck]: Tyler?

[Dr. Tyler Sandow]: I have a technique called the Sandow spasm. Sometimes it happens in the tumor vessel, sometimes it happens in the normal vessel. What I try to do is I always try to – if I want to redistribute flow, I try to spasm the normal vessel. It works sometimes, it doesn't work other times, and sometimes what'll happen is I'll spend a couple minutes trying to spasm a normal vessel and gently select the tumor vessel and the tumor vessel shuts down on me and the normal vessel looks beautiful. We'll play with that. Same kind of concept as Juan. I'll occasionally coil. If it's a falciform artery or something and it's huge, I'll coil. I really love putting ice packs around people's belly button. That's my thing.

[Dr. Chris Beck]: Fair enough. Let's see. Is there anything that I didn't cover in terms of y'all's mapping, treatment, dosimetry? We talked a little bit about unicompartment and multicompartment. I feel like y'all reference multicompartment a couple of times, but I think you said earlier that 95% of the time you're doing unicompartment.

[Dr. Juan Gimenez]: Yes, it's just because we're doing multiple segmentectomies. It's easiest to a point. The biggest thing with multicompartment dosimetry is that you need very good distribution of your MAA. For whatever reason it clumped or something happened and it's clutchy and it doesn't correlate with tumors, you can't use it.

We just say if we have somebody that has those multiple tumors everywhere, and then you're looking at doing a lobar or a pretty large liver and you know you may have to come back, then yes, definitely doing multicompartment. Rather than dosing to tumor, dosing to normal parenchyma to stay safe, then that's when we would use it. The majority of our cases truly tend to be either advanced or bigger tumors. We get segmentectomy. Everything is just teasing out as much as we can and delivering into a smaller volume.

[Dr. Chris Beck]: Speaking of tough scenarios, as far as underlying liver disease, do you guys have a cutoff for how much volume you want to preserve depending on their Child-Pugh A, B, and C, or each patient is individual and you just have to case-by-case basis?

[Dr. Tyler Sandow]: I think we look at it on a case-by-case basis in a situational basis. I think if we know that we always have transplant as a background option for the patient, we feel more comfortable being aggressive because we know that should we run into problems, we do have an option for liver failure should we progress. Juan, I should say, he pushes this on everybody. We look at bilirubin and a trend in bilirubin more so than we look at a number and we use direct bilirubin too. If someone comes in and it's not just about their Child-Pugh class, but we pay more attention to albumin and bilirubin independently, one as an anticipation for outcomes and one as an anticipation for adverse events.

Bilirubin is our key metric for adverse events. If they come in with the bilirubin that is 1.5, most people would say if it's a small segmentectomy, we're going to do fine, but if the bilirubin was 0.5 three weeks ago, we might pay a little bit more close attention to that or closer attention to that because they're in a trend of liver decompensation. We don't want to be the kick into a full-on liver failure so we look at trends. I should say we follow the data.

Beau has published a great paper talking about patients with compensated liver function. You don't really have to pay attention to volume. In patients with some underlying liver dysfunction, ALBI2s, Child-Pugh Bs, you need to be treating less than 15% of the total liver. That's where we are. We try to keep the total volume of liver that we treat with segmentectomies in just about anyone, normal, normal abnormal, less than 20% for anyone if it's going to be a segmentectomy dose. We'll split. If it's going to be more than 20%, we'll split doses, we'll bring them back, and maybe treat another, maybe get 15%, 20%, and then bring them back and treat a little bit more. Make sure that the liver is holding steady.

[Dr. Chris Beck]: How far do you wait between treatments?

[Dr. Tyler Sandow]: Three to four weeks. 2, 3, 4 weeks. We'll get a bilirubin at whatever that midpoint is because that's another metric in time, and then we get a bilirubin on the day of treatment. As long as those are holding steady, then we know we're pretty good. Obviously, in patients with liver dysfunction, we don't want to treat more than 15% and we'll try to treat even less than that. Again, why subsegmentectomies have really worked for us because our treatment volumes are so small compared to the total liver volume that we can get away with a lot.

(8) Current and Upcoming Research in Radiation Segmentectomy for HCC

[Dr. Chris Beck]: Switching gears like left turn a little bit, research you guys are doing. Are you all publishing any of this?

[Dr. Juan Gimenez]: That's on Tyler.

[Dr. Chris Beck]: Is this Ochsner secrets?

[Dr. Tyler Sandow]: We like to keep it. We hold our cards close. No, I have zero academic time. Basically, if anyone from Ochsner administration hears this maybe they'll give me some. No. We work with some of the most brilliant research. We have a research team that works with transplant and has agreed to partner with us. Paul Theibinaeux, Kelly Nunes they have built-in protocols and algorithms for tracking these patients. That has gained the interest of a lot of companies even outside of the local regional spectrum but just in the HCC spectrum as a whole.

One of the coolest things is that – and we're in the process of publishing a lot of this stuff. In the last several years we put out about three, or four, or five papers a year with our group. The coolest stuff that we have coming down the pipeline is we're looking at tumor markers, and tumor markers that aren't readily available in the US. They are available in China. they've been used for a while but they're not really pushed in the US.

What we've identified is there's three tumor markers, one of them being AFP but the other two are not routinely ordered. What we found is that if you have multiple biomarkers that are positive, your tumor tends to behave incredibly aggressive. If you have biomarkers that are negative you basically could flick the tumor and it's going to die. If you have three that are positive you got to throw the kitchen sink at it.

Even if you throw the kitchen sink at it, you rarely get on top of it and get control. We have Kaplan-Meier curves showing how that lays out., and I have never seen Kaplan-Meier curves look as beautiful as this. It literally follows how you–

[Dr. Chris Beck]: It's a nice Kaplan-Meier curve.

[Dr. Tyler Sandow]: Yes, I was shocked. Tumor markers is a big thing. Another thing that we're looking at and that we mentioned earlier how we deviate off the BCLC spectrum is albumin. We use albumin as a marker for tumor response. We can get on the nitty-gritty but albumin is a marker of nutrition, nutrition is a marker of immune function. All those key concepts tie into tumor response. If you have good immune function the body can help compensate and take some of that tumor down.

We've looked at maybe 500 patients and ideal patients if you stack apples to apples or even apples to oranges. What we found is that there was an unusual situation with our ablation patients. Our ablation patients when they had low albumin, so an albumin 3.4 or less, they tended to have higher rates of recurrence at one year and at two years compared to any other modality, intra-arterial, taste, or Y-90.

We did a deep dive on it. We're like, "Oh, so the first question you would ask is maybe Veejay left and you guys just became bad ablationists?" That would be the first thing you would say. He gets involved in this data too. Ironically if you have an albumin greater than 3.4 you almost have no progression after for ablation. With our Y-90 population, we have almost no progression at two years or any intra-arterial therapy, no progression. We're going to study that a little closer now. For patients that would otherwise be candidates for ablation, if you have an albumin less than 3.4, we're actually choosing to treat those patients with Y-90 because of the results that we've seen over the last several years with the ablation patients.

(9) Combination Therapy with Other Medical Specialties in HCC Management

[Dr. Chris Beck]: Very nice. Is there anything I didn't bring up, that I glossed over as far as the Ochsner way for treating HCC that was kind of agast. Is there anything that we need to go back and cover?

[Dr. Tyler Sandow]: I think there's-- we could talk about combination.

[Dr. Chris Beck]: Combination therapies?

[Dr. Tyler Sandow]: Or oncologists in combination with systemic too, I think.

[Dr. Chris Beck]: Oh, okay.

[Dr. Tyler Sandow]: If we can partner up, two heads are better than one. We try to, especially for those infiltrative tumors or those huge 8-centimeter, 9-centimeter tumors, tumors that might not make it to transplant or certainly going to sit on the waitlist for a long time. We try to get oncology involved readily. We actually refer patients to oncology just as they would refer patients to us. It's a shared partnership in outcomes. I find that if we combine our treatments, we tend to have incredible results.

[Dr. Chris Beck]: Are the oncologists asking for biopsies or they'll still treat four or five?

[Dr. Tyler Sandow]: No our oncologist if it meets imaging criteria for HCC and the AFP's elevated or even if the AFP's elevated or not, but if it meets imaging criteria for HCC they are comfortable going for systemic immunotherapy too. I shouldn't just say systemic, it's immunotherapy.

[Dr. Chris Beck]: Actually, that was my next question. Are they actually getting sorafenib or is it mostly they're getting immunotherapy?

[Dr. Tyler Sandow]: It's immunotherapy. We will either do the STRIDE regimen or Atezo/Bev. If we're going to treat with Y-90 we're going to hold the Bev, the Avastin, or if it's STRIDE, we'll try to go. We tend to do we'll map and treat while they're on immuno. Anecdotally, I think we tend to see immunotherapy responses after the second cycle, so within one month of starting immunotherapy because they're biweekly.

By two cycles you probably will see what immunotherapy is going to do. Y-90 has either been used to clean up what residual we see with immuno, or we'll hit it first and let immuno be there to sit and hold it so get a great response and no progression.

[Dr. Chris Beck]: Very cool. Juan, anything else that I didn't talk about?

[Dr. Juan Gimenez]: No I think you did a pretty good job, covered pretty much everything. I'm glad Tyller brought up that systemic combo aspect of our practice because it's grown a lot over the last couple of years. The one thing I want to let people know is typically you think of your multidisciplinary conferences. We don't think about than this. You may think that the more players you have the less chance of getting referrals and things like that.

Ultimately, what we've realized is the more people that you have on all your multidisciplinary conferences you capture and they're capturing more patients. Otherwise, you're going to get patients that you may not have the best option for, but because you didn't have maybe an oncologist, or a surgical oncologist, or a transplant surgeon as far as your team you may not be able to refer to them. It has allowed us, literally, to all work together. Sometimes they'll get resection, and we come back and do lobectomies, or we'll do an embolization, same thing to Tyler's point.

Working with oncology at the same time or coming after them or them coming after us as patients progress sometimes, it's been extremely helpful. Our results as a team have gotten better.

(10) Future Directions: Extrahepatic Radiation Segmentectomy and Augmented Reality in Mapping

[Dr. Chris Beck]: That's good. Anything you guys are excited about as far as things that are coming down the pipeline or things that are y'all are doing with your practice, whether it's HCC or something else that you want to talk about? Final thoughts.

[Dr. Juan Gimenez]: You didn't put that one on the outline. Now I got to think about it. [laughs]

[Dr. Chris Beck]: No, I didn't, man. There's got to be some kind of spontaneity.

[Dr. Tyler Sandow]: I think we're starting to see segmentectomy play a role as an ablative modality for metastatic disease. I think we always used to think of Y-90 as a lobar-only treatment for metastatic disease, whether it be trying to control multifocal or microscopic diseases that you couldn't see. At least what I'm seeing is that the paradigm seems to be shifting. There seems to be more of a push for us, surgeons, anyone to be more aggressive in controlling tumor burden, especially inside the liver.

We're using the segmentectomy game to our advantage. We'll do multiple subsegmentectomies for multiple metastatic tumors applying the same concept among the sphere conundrum thing to our practice. I think we're going to start to see Y-90 re-emerge as a treatment for metastatic disease but it's going to be Y-90 as a ablative modality similar to what you see with microwave ablation or RFA when it comes to treating metastatic tumors.

[Dr. Juan Gimenez]: I'm a little bit more of a geek so I'm more into technology and things like that. What I would like to see or I'm excited about is how augmented reality AR are going to play a role not after the fact or before fact, but as you're mapping this patient. All the opportunities and I just look at Apple's new headset that Vision Pro, I think of all of the things you can do with that while you are in the suite and all the processing power and analyzing all these images.

It can help not just us out but it can also help level out the field amongst people that may not necessarily do as many of us. If you have something guiding you as you go through helping you understand the images as you acquire them I think that could be huge. I would just say that's what I would like to see. That's what I'm getting excited about.

[Dr. Chris Beck]: Have you guys been seeing anything or talking to anyone who's doing Y-90 for organs outside of the liver? Is that the horizon for you guys by any chance?

[Dr. Juan Gimenez]: Yes. Not necessarily for Tyler or I, but as you know they have a trial going on for GBM or one of our partners Paul Glada who does mainly neuro IR is getting involved with that. I think some of the preliminary results for that have been very promising. I think that would be great. I know there's another trial looking at up prostate I'm not very familiar with that and there could be other applications. I think this is what we should borrow.

A lot of times people see what we're doing and they try to apply that techniques to what we do. This is what we should mainly radiation oncology we should do the same. Everything that they radiate we should be able to go after. I think if you look at it that way soft tissue sarcomas, a bunch of other things. Lung, I think there's an interesting-- lung that I think we should be applying it the same way.

Podcast Contributors

Dr. Juan Gimenez

Dr. Juan Gimenez is an interventional and diagnostic radiologist with Ochsner Health in New Orleans, Louisiana.

Dr. Tyler Sandow

Dr. Tyler Sandow is an interventional radiologist with Ochsner Health in New Orleans, Louisiana.

Dr. Christopher Beck

Dr. Chris Beck is a practicing interventional radiologist with Regional Radiology Group in New Orleans.

Cite This Podcast

BackTable, LLC (Producer). (2023, October 27). Ep. 379 – Management of HCC: Focus on Radiation Segmentectomy Part 2 [Audio podcast]. Retrieved from https://www.backtable.com

Disclaimer: The Materials available on BackTable.com are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.