DEB-TACE vs Conventional TACE in the Treatment of HCC

[Michael Barraza]
Now Terence, because you have experience with both cTACE and DEB-TACE, could you tell us a bit more about your experience with both? The benefits, advantages, disadvantages and if you have a preference?

[Terence Gade]
Sure. Again, I agree with Justin. I think the side effect profile for DEBs is far better and patients tend to do better afterwards. How much, it's a hard thing to say, I think. From a biological standpoint, I do believe that, and I think Karen Brown's work underscores this, the ultimate therapeutic effect comes from the ischemia we're inducing. So I think that I'm a big believer in the embolization component, and I'm less of a believer in the chemotherapeutic. My concern with DEBs tends to be that that's more focused on drug delivery. It's about getting more doxorubicin or what have you to the tumor.

[Michael Barraza]
Terence, do you think that pressure-directing infusion has the same potential benefits for conventional TACE that it does for DEB-TACE? What's the difference there that you would get?

[Terence Gade]
In my mind, as I was mentioning, I don't think there should be a huge difference because you're only talking about differences in the delivery vehicle. Some of the problems with Lipiodol direct infusion, even if you're using a water and oil emulsion, which is supposed to be focused on drug delivery and not on embolization, is that you will get some early stasis.

Ultimately, when I'm administering conventional TACE, I'm focused on trying to generate that water and oil emulsion so that I can deliver the whole dose. Sometimes, I'll have to thin that out a little bit just so I can ensure that I'm not reaching stasis before I get to my actual embolics. So I think it's going to be hard to tease these two things apart, but potentially, you might get an added benefit from pressure-directed infusion in combination with DEB-TACE only because you're going to be able to ensure you're going to deliver that whole dose more easily and not have the complication associated with potential stasis through the Lipiodol. Like I said, it's going to be a really hard thing to tease those apart, and I'm not sure it would be significant enough where I would favor one over the other in the setting of pressure-directed delivery.

[Terence Gade]
I think that in terms of what data we do have, those chemotherapeutics are probably not the best choices. The ones we're using are probably not the correct drugs. If we're talking about inducing vulnerabilities, if we embolize a tumor and we block off the vasculature and we induce ischemia, those cells are now fundamentally different from the cells that were growing without the embolization. The cells without the embolization tend to be proliferating, as we see on scans. We see tumors grow. But after embolization, they can hang out there without growing, and that tells us a lot about the cell status. In that circumstance, you have cells that aren't cycling anymore or using an agent that's meant to potentiate the ischemia. Using an agent that targets proliferating cells is probably not going to potentiate that ischemia much. Again, I think that JCO article from Karen Brown underscores that concept.

While I do prefer the side effect profile for DEB-TACE over conventional TACE, I think that ultimately, the biology we're targeting is better served through conventional TACE approach than it is through DEB-TACE. I would caveat that by saying that I think we really need to start thinking, and there's a lot of research being done in this area, but start thinking about which drugs we're combining to potentiate the ischemia. There's a lot of progress being made in that area, and I think that we as interventionalists really need to start thinking about that biology and integrating some of those therapeutics into our practice rather than taking what's always been administered and really, when the decision was made to start using those drugs — cisplatin, mitomycin and doxorubicin — there wasn't any real reason. It wasn't that HCCs are susceptible to those drugs because they can be ... HCCs are among the most chemoresistant cells that we know of in cancer. I think we need to do a little better job of thinking rationally about the therapeutics we're using and integrating our science.