Bradford Wood, MD, Describes the First Use of Radiopaque Embolic Beads

Bradford Wood, MD, director of the Center for Interventional Oncology at the National Institutes of Health, recently participated in the first interventional oncology cases performed using the LC Bead Lumi (BTG), the first radiopaque embolic bead. Additional Lumi microsphere cases were performed at the University of Miami Sylvester Comprehensive Cancer Center within days of these cases. Interventional Oncology 360 asked Dr. Wood to describe the product and the cases at the recent Clinical Interventional Oncology meeting in Fort Lauderdale, Florida.

IO360: Could you describe the radiopaque embolic bead and the first cases you performed? 

Wood: Actually the origin dates back almost a decade to a pub in Bethesda, where we first met Andy Lewis and Sean Willis of Biocompatibles (BTG), and hatched the idea over a stout. The road to clinic is always curvy. Advancing a new technology and having fun while you do it is more important than being “first.” Everything that we learn and do is on the shoulders of others, so no one can really take credit. Were we the first in the world to use imageable microspheres for embolization? Yes, but it’s not me doing it, it’s the whole team here in the NIH Clinical Center. I am proud that we achieved this as a team and brought something forward that might address some clinical challenges. Being able to see the bead and where the bead is going directly has not been available before. 

In parallel, with other industry partners we developed tools to use cone-beam CT with radiopaque bead embolization. It reduces the images to a CT-like picture. Tools that have been developed for the cone-beam CT technology are navigation for catheters to better deliver beads or drug. Drug loading is off-label use in many settings. You’re able to deliver those things better to the vessels that feed a tumor using this sophisticated imaging. Also, the navigation tools and the software components allow you to integrate everything into a treatment plan that’s iterative and in real time. You have feedback loops built in. 

I look at the screen and I try to figure out what’s going on at that moment to really attack a tumor aggressively, when we need that information most, which is when the patient is on the table. There’s no point in waiting 6 months for a tumor to grow back on imaging when we know we’ve undertreated it. That’s one of the exciting things about the imageable microspheres. They let us see where the beads go in three dimensions. We can glue that to an image of the tumor before we’ve treated it and now we have a powerful tool. We have information when we need it most, and information is power. We have a tumor that has been treated in multiple areas and we have areas that haven’t been treated yet, and we know this while the patient is still there. If we can’t get access with a catheter due to no roads in, we go in directly with a needle and we ablate it with microwave, cryoablation, radiofrequency, any of the available ablation technologies. The navigation tools we use have smart computer software to get there with catheter or needle as well. It’s coalescence, or a symphony of technologies that come together to ultimately improve, we hope, how we do this therapy.

IO360: There are different sizes of bead available for the radiopaque embolic bead. Can you describe that?

Wood: There are different sizes of bead available for most embolization procedures. What we’ve done to date is look at an image and try to judge the characteristics and biology of the tumor or of that process that is going on in the body and then randomly pick a bead size, inject it, and hope it’s going in the right place, in the right fashion, and stopping the right size blood vessels. Those days are over now because we have the opportunity to see where the beads go. Information is power. We don’t know yet what this will do for us. Our hope is that, in the name of public health, this will help us standardize embolization. Embolization has been the standard of care for many of the algorithms in treating primary liver cancer for decades, but essentially all physicians do it a little bit differently with different end points. All clinicians stop blood flow differently, inject at a different speed, inject in a different place, stop at different times, or make different choices about how selective they will be. These are all questions that have been done in an incredibly wide variety of ways. It is amazing, considering these treatment differences, that we’ve gotten where we are in understanding what the treatment can do for people. Tools such as guidance software and potentially imageable agents let us level the playing field. We can see outcomes of different techniques. We haven’t been able to do that before to this extent, so that’s what’s really exciting to me scientifically and academically.

IO360: How about the actual technique using the radiopaque bead as opposed to the traditional bead?

Wood: The actual technique doesn’t differ much. It’s the same mixing process, the same equipment, the same table, the same catheters, it just requires a specific commercial contrast, which is important, but again it doesn’t change how we do it. The contrast needs to suspend the beads in an even distribution. Imageable beads can potentially change how we do it, based upon the information we are receiving, and getting that information only helps. Turning on the lights and finding out what you’re doing just makes sense.

IO360: Do you think this could reduce cost in the future?

Wood: The paradigm of cost an how it affects patients’ lives and healthcare systems is very complex. Our goal in general at the Center for Interventional Oncology is to try to promote cost-effective, high-tech, low-cost approaches. Now, we don’t have control over the market or industry. We are a government entity, so we are certainly interested in cost-effective solutions, but many of the solutions that we help develop may rely on just a computer, just a laptop that sits by a procedure, and has some special software on it. 

Radiopaque beads are a bit of a different story, because you have industry and market factors mixed into the equation, so it’s a difficult question to answer. The important point is that in general, minimally invasive, image-guided therapies have much less cost, much quicker recovery, less time away from family, less time away from work, and are better tolerated with less risk and complications than many of their more invasive and surgical counterparts. Some might say that’s a big generalization, but I think it’s very true and it’s at the very core of what we do. 

I think that at times, high technology is hypnotizing to the point that we are compelled to use it, just for technology’s sake; our inner video-gaming child gets us excited about it. It is cool. But you always have to ask yourself, “Does this make sense? Where is it going to improve things? Is it going to be cost effective if applied across a broad population?” Some of those questions I’m not going to be able to answer today. It will take many years, but that is the fun part.

IO360: If you were able to see the beads that you injected and have a more effective embolization, that could enable fewer repeat procedures or more effective treatment.

Wood: I don’t want to blur the line between speculation and high-quality randomized controlled trials data. It’s very hard to say how this is going to impact things. Yes, it makes sense to me, but I’m biased. I think in general as a society we have trouble evaluating the cost of a saved life or the cost of an extra year of life with family, or to see a child get married. How do we put a price tag on that? We can’t. As a society we want to do better, we want to improve things. So how does that translate into the cost of the technology that is potentially going to help? These are all difficult questions.

IO360: What are a few of the questions that are still unanswered about the radiopaque embolic bead? What are the things that need to be optimized?

Wood: Many questions remain, and each new question could prompt a separate study. For example, if you inject the beads very slowly, you would probably get a much better distribution of the beads or whatever the therapeutic from the beads is, whether it’s better ischemia or better (off-label) drug delivery. That’s probably true, in general terms. But in practical terms, we don’t know the true meaning of “slow” and “fast” in this context. We’ve gone with a 3-heart-beat stasis definition or a 5-beat stasis (slowing down in the blood vessels). So, our standards change over time too. What we have now is a way to study the difference between fast and slow injection, or other techniques, in order to know which is best and then standardize it. 

It’s my particular opinion, without tons of science, that slow injection is the better way to go, even though we may become impatient when we do long procedures. Two of my colleagues who helped develop some of the early technology injected differently very early on when the imageable bead was just a research tool, in a pre-clinical model. We saw that small beads penetrate and get further in blood vessels than larger beads in general. So the small beads penetrate more and work farther distally into a tumor compared to big beads. I could tell apart these two IR physicians’ injections based just on the image. I could tell you with certainty which physician injected that particular procedure because one went fast and the images were splotchy. One went slow, was patient, and the images showed uniform distribution. It’s speculation, but I know we can improve how we do this as a global specialty by having this information available to us. Now we can know what we’re doing when we’re there, and we will be able to answer many more questions. 

Another exciting thing about the beads, and specifics of this will be coming out soon in the literature, is that we can identify tissue at risk for under-treatment. To date, when we treat, we get to a certain point, we slow down the blood flow, we walk away, and we see what we’ve done. If we’re lucky, we’ve killed a lot of tumor. If we’re not lucky, we haven’t killed enough tumor, and many times this therapy is not curative. 

What we can do now is inject, and instead of walking away, we get a cone-beam CT to see what’s left and we fuse pretreatment tumor vessels (that are open) to where the beads are, and now you have vessels and tissue that you can identify in real time as still being alive, and still needing treatment. Then we try to go back to that area while the patient is still on the table with some of these other navigation tools, such as a needle or catheter. It’s another way to do combination therapy maybe in a smarter fashion, and our clinical trial will examine approaching this combination therapy (that we’ve done for many years) but now that makes more sense with more information available to us. 

IO360: Anything else you want to add about imageable microspheres for embolization?

Wood: Having the imageable microsphere available while we are doing procedures is somewhat akin to driving at night to an important appointment, without headlights, hoping you’re not going to hit anything, and suddenly your headlights turn on and you can see where you’re going. Is it going to improve your chances of getting there? It stands to reason that it might, but we don’t know that for sure yet. I feel like having done these cases that suddenly I have the lights turned on. I have more information. 

How is that going to pan out? What’s that going to do for us? What’s it going to do for my patients? I don’t know yet but we are certainly excited. It’s one of the reasons I love what I do. I love my discipline. I love being an interventional radiologist and an interventional oncologist. It’s a great way to keep up with technology, gadgets, video game software, and new devices and help people at the same time who might otherwise not have other options. And we do this together as a team; from Vickey Anderson, NP, to interventional radiologist Elliot Levy, MD, to preclinical expert modelers John Karanian and Bill Pritchard, to drug-delivery expert Andrew Mikhail, to chemist Ayele Negussie, to partners at Yale – Jeff Geschwind, MD – or Miami – Raj Narayanan, MD – to Biocompatibles BTG industry partners Sean Willis, Andy Lewis, and Chelsea Macfarlane. It takes a village.