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Radioembolization in HCC

Panelists:Ghassan K. Abou-Alfa, MD, Memorial Sloan Kettering Cancer Center; Richard S. Finn, MD, Geffen School of Medicine; Riccardo Lencioni, MD, Sylvester Comprehensive Cancer Center; Amit Singal, MD, UT Southwestern Medical Center
Published: Monday, May 23, 2016


Transcript:

Ghassan K. Abou-Alfa, MD:
I have to say that, that question of adding therapy to the local treatments—that is, adding sorafenib or any other modality—is not over yet. I mean, this is really way too open of a field. But let’s talk about two other modalities of local therapy and then try to bring up that question one more time. And the question back to you, Riccardo, tell us a little bit more about radioembolization. What’s that?

Riccardo Lencioni, MD: Well, radioembolization is a form of liver-directed therapy that uses yttrium-90 (Y90). The basis for this is that because of the cirrhosis and the underlying disease, external radiation may have limitation. Radiation-induced liver disease is an issue, probably currently slightly underestimated, but it is an issue that then shows up even with time. So, with this approach in radioembolization, we actually load microspheres with Y90 and then we can selectively administer the beads into the tumor. The same procedure that we follow for a chemoembolization, we can do for a radioembolization, although the indications are not the same. As we discussed, chemoembolization is truly supported by a robust amount of data, while the trials for radioembolization with Y90 are now ongoing.

Probably this year, in 2016, we’ll have results available with a trial comparing Y90 with sorafenib in the advanced setting. Technically, the most important difference is that although the name suggests that there is a vasculature blockage, this is truly minimal. So, the procedure can be performed even in patients with portal vein occlusion, according to the anatomical description that you kindly provided at the beginning. Even if the portal vein is occluded, there will be a microembolic effect, so there would be no infarction in a Y90 radioembolization. This is why this can be offered with patients with vascular invasion.

Ghassan K. Abou-Alfa, MD: So, that’s very critical. I have to admit, as an oncologist, you might be very well be confused by, or I might be very well confused by, the different therapies that could be available for local treatment. One of them is the chemoembolization, as we heard, which is commonly used pretty much all over the world. Some data on bland embolization, as we mentioned, come from Sloan Kettering Cancer Center, and the procedure is practiced by other colleagues as well, where it showed there’s no difference between the two, even though I like very much what Riccardo mentioned, which is the technology has evolved to an extent where probably we can claim that kind of equivalence per se. But then we brought up the radioembolization.

Riccardo, correct me if I’m wrong. Based on the data available (some of it from a randomized trial for the chemoembolization, some of it from, literally, data available from collective work on the radioembolization), if there is no vascular involvement in the portal system, probably an embolization (i.e., bland or chemoembolization) would be appropriate. While for the radioembolization, because infarction is less likely, we can probably apply that in the setting of a portal vein thrombus. And here it seems is where the debate is: these patients might have sorafenib as applicable therapy for them, as well. And that’s why there is this clinical trial that’s ongoing for radioembolization versus sorafenib. With this said, Amit, back to you. That’s a lot going on, how concerned should we be about liver function when we are doing all of this stuff?

Amit G. Singal, MD: I think it’s something that’s definitely worth monitoring as we’re going through therapy. I think it’s something that you take a look at when you first start to see where somebody starts. Are they starting with a Child-Pugh A or a Child-Pugh B going into therapy? Obviously, if you start with some degree of liver dysfunction, it’s something you have to monitor even more closely. But, as you’re going through therapy, even though we try to be as targeted as possible and as selective as possible, there is some non-target effect that happens. And so there will be some potential for decline in liver function as you’re going through these therapies.

Our standard procedure is to monitor liver function after every therapy and continue to reassess, and say if somebody’s liver function is declining, should we continue therapy? And if we decide to continue therapy—meaning the liver is still functioning—either Child-Pugh A or B, what therapy should we choose? But somebody who is going through local regional therapy and starting to have liver decline, we may say this is somebody that we want to switch over to another therapy.

Ghassan K. Abou-Alfa, MD: So, that’s very important to stress. And what we started discussing is a multidisciplinary approach for therapy. The multidisciplinary approach is not about sitting at a meeting and saying, “Okay, we’re going to do the therapy.” It’s really continued engagement at all times, because if a patient is to get a certain form of treatment, the input of the medical oncologist in regard to what the impact is, or the input of the hepatologist in regard to what the concerns are, about the liver function, I think that is going to be very critical.

I would like to add here that one more approach that’s being still investigated quite well—and a lot of work actually has been done by Laura Dawson and colleagues from Princess Margaret Cancer Centre in Toronto, Canada—is about SBRT, or stereotactic body radiation therapy. That’s really very highly targeted in regards to protecting the liver. As we heard from Riccardo, which is very true, the liver is a very radiosensitive organ, and as such, SBRT probably might make up for that. There is a beautiful study that actually includes SBRT plus sorafenib that’s underway and definitely can be checked out on clinicaltrials.gov, as well.

Transcript Edited for Clarity
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Transcript:

Ghassan K. Abou-Alfa, MD:
I have to say that, that question of adding therapy to the local treatments—that is, adding sorafenib or any other modality—is not over yet. I mean, this is really way too open of a field. But let’s talk about two other modalities of local therapy and then try to bring up that question one more time. And the question back to you, Riccardo, tell us a little bit more about radioembolization. What’s that?

Riccardo Lencioni, MD: Well, radioembolization is a form of liver-directed therapy that uses yttrium-90 (Y90). The basis for this is that because of the cirrhosis and the underlying disease, external radiation may have limitation. Radiation-induced liver disease is an issue, probably currently slightly underestimated, but it is an issue that then shows up even with time. So, with this approach in radioembolization, we actually load microspheres with Y90 and then we can selectively administer the beads into the tumor. The same procedure that we follow for a chemoembolization, we can do for a radioembolization, although the indications are not the same. As we discussed, chemoembolization is truly supported by a robust amount of data, while the trials for radioembolization with Y90 are now ongoing.

Probably this year, in 2016, we’ll have results available with a trial comparing Y90 with sorafenib in the advanced setting. Technically, the most important difference is that although the name suggests that there is a vasculature blockage, this is truly minimal. So, the procedure can be performed even in patients with portal vein occlusion, according to the anatomical description that you kindly provided at the beginning. Even if the portal vein is occluded, there will be a microembolic effect, so there would be no infarction in a Y90 radioembolization. This is why this can be offered with patients with vascular invasion.

Ghassan K. Abou-Alfa, MD: So, that’s very critical. I have to admit, as an oncologist, you might be very well be confused by, or I might be very well confused by, the different therapies that could be available for local treatment. One of them is the chemoembolization, as we heard, which is commonly used pretty much all over the world. Some data on bland embolization, as we mentioned, come from Sloan Kettering Cancer Center, and the procedure is practiced by other colleagues as well, where it showed there’s no difference between the two, even though I like very much what Riccardo mentioned, which is the technology has evolved to an extent where probably we can claim that kind of equivalence per se. But then we brought up the radioembolization.

Riccardo, correct me if I’m wrong. Based on the data available (some of it from a randomized trial for the chemoembolization, some of it from, literally, data available from collective work on the radioembolization), if there is no vascular involvement in the portal system, probably an embolization (i.e., bland or chemoembolization) would be appropriate. While for the radioembolization, because infarction is less likely, we can probably apply that in the setting of a portal vein thrombus. And here it seems is where the debate is: these patients might have sorafenib as applicable therapy for them, as well. And that’s why there is this clinical trial that’s ongoing for radioembolization versus sorafenib. With this said, Amit, back to you. That’s a lot going on, how concerned should we be about liver function when we are doing all of this stuff?

Amit G. Singal, MD: I think it’s something that’s definitely worth monitoring as we’re going through therapy. I think it’s something that you take a look at when you first start to see where somebody starts. Are they starting with a Child-Pugh A or a Child-Pugh B going into therapy? Obviously, if you start with some degree of liver dysfunction, it’s something you have to monitor even more closely. But, as you’re going through therapy, even though we try to be as targeted as possible and as selective as possible, there is some non-target effect that happens. And so there will be some potential for decline in liver function as you’re going through these therapies.

Our standard procedure is to monitor liver function after every therapy and continue to reassess, and say if somebody’s liver function is declining, should we continue therapy? And if we decide to continue therapy—meaning the liver is still functioning—either Child-Pugh A or B, what therapy should we choose? But somebody who is going through local regional therapy and starting to have liver decline, we may say this is somebody that we want to switch over to another therapy.

Ghassan K. Abou-Alfa, MD: So, that’s very important to stress. And what we started discussing is a multidisciplinary approach for therapy. The multidisciplinary approach is not about sitting at a meeting and saying, “Okay, we’re going to do the therapy.” It’s really continued engagement at all times, because if a patient is to get a certain form of treatment, the input of the medical oncologist in regard to what the impact is, or the input of the hepatologist in regard to what the concerns are, about the liver function, I think that is going to be very critical.

I would like to add here that one more approach that’s being still investigated quite well—and a lot of work actually has been done by Laura Dawson and colleagues from Princess Margaret Cancer Centre in Toronto, Canada—is about SBRT, or stereotactic body radiation therapy. That’s really very highly targeted in regards to protecting the liver. As we heard from Riccardo, which is very true, the liver is a very radiosensitive organ, and as such, SBRT probably might make up for that. There is a beautiful study that actually includes SBRT plus sorafenib that’s underway and definitely can be checked out on clinicaltrials.gov, as well.

Transcript Edited for Clarity
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