Transcript:Ghassan K. Abou-Alfa, MD: Let me go back to a rather very critical question. We do all the therapies. Remember, when we do surgery, we do a transplant—i.e., we explant and transplant, we have tissue. But when it comes to local treatments, we sometimes base our decision on radiologic evaluation of HCC. It is a big question that’s definitely evolving from different perspectives. Richard, your thoughts?
Richard Finn, MD: Well, how do we follow these patients once they go into a treatment paradigm? And that becomes a challenge. I think in the context of local regional therapy—and Riccardo can comment more—when we do a chemoembolization procedure, we see this classic enhancement pattern of liver cancer lost. To us, we assume that means there was a success. Even though the total tumor might not shrink, it loses its vasculature. On subsequent imaging, if we see that vasculature come back, we’d say the tumor is coming back. And, at that point, is that a failure of the therapy? Is that progression on therapy? I think most of us will look at that in the context of a tumor board and say there’s new enhancement, we’ll try local regional therapy again.
In the context of something like radiofrequency ablation, I think it’s a similar discussion. You might treat one tumor and you see the loss of enhancement, sometimes those tumors might shrink, but then you might see a tumor pop up that was not treated. Is that progression? Is that a new tumor? How do you approach that? And, again, I think the approach, as long as it’s still confined in the liver and they’re healthy and doing well, we would probably go ahead and treat those patients locally as well. Riccardo, you can probably comment a little bit on the significance of the loss of enhancement after chemoembolization.
Riccardo Lencioni, MD: This was an issue that has been around particularly in HCC because most of the therapies that we are used to administering—even before the advent of sorafenib—were truly kind of mechanical type therapies, either producing direct necrosis with ablation or embolization. So, the usual criteria that are adopted in oncology, like RECIST criteria based on tumor size changes and shrinkage as a measure of a response and effectiveness, clearly are completely useless. This has been shown in several studies. Currently, the criteria that are more commonly used are modifications of RECIST, or un-RECIST, in which it is the viable portion of the tumor that really needs to be measured. That being said, clearly, there is no dogma—and there should be no dogma when following a patient—that presents after local regional therapy. And then, not all the progressions and progression patterns have the same implications. This has been shown particularly with regard to localized progression in the liver versus progression with extrahepatic disease. In general, I would say that for patients who are primarily treated with local regional therapy, we may want to give a second attempt after an incomplete success—for instance, after the first TACE—because there is at least a 50% chance to achieve a response with a repeat treatment. This is also something that has to do with the ability of the tumor to be now reached by collaterals, and we can again go back and fix this with a repeat TACE. After two TACE or in front of progression with extrahepatic manifestation of the disease—or liver decompensation, or general deterioration—I think that’s the time where you may want to discontinue the TACE.
Ghassan K. Abou-Alfa, MD: My colleagues here, Richard and Riccardo, are taking me where I don’t want to go, but let me go back one step. My intent was to talk about biopsy and the value of treatment. I’ll put this in the parking lot for a second because they took us on a very fascinating discussion about response, which kind of added another layer of complexity. Now, we kind of discussed with you what you can apply as local therapy. We spoke about chemoembolization and bland embolization; we spoke about if there’s vascular involvement, maybe Yttrium 90. And now wait a minute, we apply the therapy, and then how do you know that we’re doing well or not? And that’s really what’s being discussed over here, which is a fascinating subject by itself because, really, we don’t have a clear understanding yet. If anything, it appears to be that the criteria that we are used to—which started with the two-dimensional WHO (World Health Organization) criteria, evolved to RECIST, and evolved to RECIST 1.1, which is more of a linear collective of all the measurement of disease, plus what we call the non-measurable disease—now is evolving into the field or the camp of modified RECIST. This adds the necrosis component, which, I have to admit, we might have differing opinions on.
If anything, this has not been validated yet in a prospective fashion, which is a collective improvement in outcome prior to survival when it comes to, for example, metastatic disease. Nonetheless, the camps differ in that regard. When you have your patient coming back to you from an embolization or from a radioembolization, have a discussion with the interventional radiologist, and have a discussion with the radiologist, as well. Because looking at those pictures, trying to interpret them might very well reveal to you certain patterns that are going to be very specific for your patients, and you need to put all that in perspective. But, most importantly—probably I would agree with Riccardo—is not to give up on a therapy until you have a good understanding with regard to and dissecting that material that you are talking about.
Transcript Edited for Clarity