New Technologies in Interventional Oncology: An Interview With Erik Cressman, MD, PhD, FSIR

The 2015 Society of Interventional Radiology Annual Scientific Meeting featured 26 sessions in its oncologic interventions educational pathway. Invited faculty included Erik Cressman, MD, PhD, FSIR, a physician scientist at MD Anderson Cancer Center. Dr. Cressman performs multiple roles at SIR, one of which is the chair of the Granson Research Education Division within the SIR Foundation. At the SIR 2015 meeting, he moderated a session on new technologies that are going to affect interventional radiology and interventional oncology in particular. Interventional Oncology 360 asked Dr. Cressman a few questions about what’s on the horizon in interventional oncology. 

Q: Could you describe some new technologies in microwave ablation?

A: There’s a lot going on in terms of how to apply as much energy as quickly as possible and actually asking questions about whether that is actually the right way to do it. If you apply too much energy and heat up the tissue too quickly, that can lead to a different set of problems. As far as how well the device functions, it can also lead to problems with injury or thrombosis of vessels that wasn’t intended. And like every other research project, there are bound to be other questions that come up as the technology continues to be refined. I know there are also methods now for helping the antennae stay in position more reliably and other ways to target it better to make it more easily visualized.

(Related video: Dr. Cressman on microwave ablation.)

Q: What’s new in HIFU?

A: With high-intensity focused ultrasound there are 3 areas that are going to be up and coming. The obvious one everyone thinks of is ablation, but anyone with experience in this area knows that entails figuring out how to track things with motion, understanding the dose that’s actually being delivered, and knowing whether there’s any nontarget heating that needs to be addressed, which leads to MR monitoring. But with that said, there are people working on ultrasound-guided focused ultrasound. There’s a lot of work that’s been going on in China and frankly, China is probably on the order of 10 years ahead of us in many respects. Then again, China also doesn’t have the US Food and Drug Administration to work with in terms of patient safety, reliability, and consistency. 

Another area that’s burgeoning is using ultrasound as a means to help with temperature-sensitive drug delivery. We’ve seen that with the initial wave of thermosensitive liposomes, but there’s also a lot going on with reasons to use HIFU to improve the receptivity, if you will, of the target area to make it more amenable to local drug delivery. Researchers are also working on targeting those temperature-sensitive liposomes, because one of the difficulties there is that you can give a very large dose, but just like nanoparticles, it tends to be only a small fraction that is delivered successfully to the target area, and this is not very satisfying for those of us that are used to a very precision targeting in our specialty. 

Another developing area in HIFU is immune stimulation. There’s a lot of work going on now in cancer research in general with the effect of the immune system, but this is a little like poking a tiger and one needs to be very thoughtful about how to proceed. Turning the immune system on and off can be good and bad at different times under different circumstances, and we need to understand that thoroughly as we move forward with this technology. Nevertheless, one can imagine down the road taking something like a targeted thermosensitive liposome that’s loaded with an immunomodulating agent, doing the stimulation with focused ultrasound all in one procedure, and getting control of systemic disease at the same time. So that would be, to me, the kind of Star Trek medicine of the future.

Q: And how about TACE and new advances in planning and guidance?

A: The idea of doing TACE has progressed from the initial, earliest studies where the entire liver was treated to lobar studies. Now I think the trend is much more toward selective or even subselective embolization. But then the question becomes, how do you know where you are, how quickly can you get there, and are there any alternate feeding arteries that need to be visualized in order to successfully target a lesion? 

On top of that, we are appreciating more and more the difficulties in tumor microvasculature, how far in can we actually get with delivery agents transarterially, and what’s required in terms of complete coverage, or is that even possible? Is that really a windmill we’re tilting at? But in fact we’re still getting a survival benefit and if we can improve that and at the same time, with more targeted coverage, lower the overall exposure and improve the patient tolerability, those are all things that are going to help advance the specialty and improve patient outcomes.  

Q: And new drugs in drug-eluting bead technology?

A: I think we’re getting to the point where we realize that a really nasty drug like doxorubicin should work. We are beginning to appreciate more and more, for example, that one of the targets of doxorubicin, which is topoisomerase II, actually is downregulated in a setting of ischemia, and the drug-resistance mechanism, such as the p-glycoproteins, things that cause the drugs to get pumped out of the cells, are actually upregulated in that setting as well. You look at that and you think, what’s the rationale then for a drug like doxorubicin? But this is where we’re now getting into much smarter technology with much better drugs. For the immune system, why not deliver that via the transarterial method in a more precise way? That would be a perfect example. I know there are people thinking about these things, so that’s just one example, but we’re also looking at the whole question of heterogeneity in the tumors and how to better cover that perhaps with combined agents with antivascular agents along with immune-modulating agents. Those two things in concert may give us even better outcomes with better patient tolerance. 

All that said, we have to keep in mind that when we do an embolization, we’re making it harder for the immune system to get access to that area, not easier, so there may be more further developments with not only the drugs themselves but the duration of the embolization. There’s a lot of work going on with resorbable beads, for example, that will over a period of time disappear and reestablish blood flow to the area, which may ultimately lead to better outcomes. There’s so much that we don’t know about these areas.

Q: And how about nanotechnology? What’s new in nanotechnology for interventional oncology and what’s coming up?

A: Targeted nanoparticles would be the first thing I would think about as well as ways to get nanoparticles into a cell. The classic problem right now has been with the reticuloendothelial system—the lymphatics—that tend to gobble up much of the dose that’s administered systemically, but there are people working on ways to improve the targeting for that, there are people working on ways to use nanoparticles and combine them with something like hyperthermia, there are people who are working on not only targeting but making nanoparticles image-able, and there are people that are combining all of those things together, so overall we’re finding out that the nano world is—I know this is a bad pun—much bigger than we ever thought.

Q: Anything else you’d like IO clinicians to know about new technologies in interventional oncology?

A: There are some areas that are actually even too early to show up on the radar for sessions such as the one we are talking about right now. The first one that comes to my mind is nanoelectronics and resorbable electronics. There are some fascinating things going on in that arena where we could be implanting devices that could report on the condition or on the diagnosis or on the response to treatment. At the same time some of those things may no longer be needed. They may be designed in a way that they are resorbable. 

There’s a lot going on in the 3D printing technology world. It’s not just using molten plastics to build up hard structures; it’s much broader than that. People are printing soft structures, people are building implants, people are working on replacement organs, people are working on ways to encapsulate cells, people are even printing cells. All that is going to be 5 or 10 years down the road, but we’ll be hearing about it.