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Chemoembolization in Hepatocellular Carcinoma

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 16, 2016


Transcript:

Ghassan K. Abou-Alfa, MD:
Riccardo, it might be that sometimes patients might be still cured but don’t need surgery. Tell us a little bit more about RFA (radiofrequency ablation).

Riccardo Lencioni, MD: I would say this is probably even more common than with surgery itself because of the reasons that we described at the beginning: many patients either have compromised liver function or they have comorbidities. So, they are truly not very good candidates for major hepatectomies. So, in these patients, with image-guided ablation, the chance to get a complete cure—in terms of complete pathologic eradication of the tumor approach—is 90%. Of course, there are some limitations, like the size and location of the tumor, but we also have a variety of tools now, from radiofrequency to microwave to cryoablation to non-thermal technologies such as irreversible electroporation. This is really the kind of cancer where cure exists beyond surgery. I think this is extremely important because truly—for many patients—when surgery is risky, the best chance for a cure is an interventional procedure.

Ghassan K. Abou-Alfa, MD: Well, definitely we see that perspective, and we might argue in regard to surgery versus RFA. This probably would require some specialized discussion and obviously a visit with an expert like Riccardo Lencioni as an interventional radiologist, plus, of course, a surgeon. And sometimes surgeons might apply both therapies or practice both therapies, and it’s very important to look into those options. But this is a great sprint into the second layer of how to treat liver cancer—which we’re going to address right now—which is the local approaches, the specialty of Dr. Lencioni here with us, in regard to what can interventional radiology offer.

Riccardo, I’ll say what I understand as an oncologist about embolization, so correct me when I’m wrong. And then I’m going to challenge you on some questions. The liver has a dual blood supply, and it appears to be that cancer cells are always finicky. They love to live on arterial blood supply. You try to suffocate them somewhere, throw some chemotherapy on them. You depend on the fact that the portal system is still feeding the liver and, as such, it can’t kill tumor. Is this fair?

Riccardo Lencioni, MD: That’s very good.

Ghassan K. Abou-Alfa, MD: I’m glad you say that. However, now, my biggest challenge—and Richard, please help me here—is that the data that was reported back by Lovay and Lowe in regard to embolization really looked at rather small tumors. And now you see those things being embolized no matter how big size they are. Tell me a little bit more.

Riccardo Lencioni, MD: Well, first of all, the trials that you mentioned established chemoembolization as the standard-of-care for liver only or liver-dominant disease. And I would say this is truly one of the therapies that is more of a global therapy because it’s the most popular treatment for HCC anywhere in the world. Those trials were performed 15 years ago. So, the same way the surgeons improved the technology, we also did a little bit of homework. So, we have new catheters, and tools, and microspheres, and a variety of solutions that can truly address different kinds of disease. That being said, I think the key here, again, is to really understand the whole benefits. Definitely, chemoembolization is a very good option for patients who have disease limited to their liver. It can be explored in patients with more advanced disease in the setting of combination regimens, and this is an area for clinical research. But, currently, I would say the best indication is for those patients that the Barcelona classification will call intermediate-stage.

Ghassan K. Abou-Alfa, MD: Fair enough. As you know, we published some data from Memorial Sloan Kettering Cancer Center not that long ago in JCO (Journal of Clinical Oncology) on February 1, 2016, arguing that bland embolization and chemoembolization probably would relay the same outcome. Your thoughts on that.

Riccardo Lencioni, MD: As I say, the technology has improved significantly. So, currently, it is possible to truly achieve the very precise calibrated vascular obstruction.

Ghassan K. Abou-Alfa, MD: Locate, in other words, you mean?

Riccardo Lencioni, MD: Yes. So, the new generation of beads are radiopaque. So, you can truly do a kind of manicured devascularization of the tumor. We still have data that suggest that having a drug administered along with the embolics improves the efficacy. But it is also true that we may not be using, currently, the most powerful drugs. I mean, the drugs that are used in chemoembolization are cytotoxic chemotherapy drugs, mostly doxorubicin, cisplatin, mitomycin-C. There are several different new forms of therapies, new agents that are worth exploring. Potentially, changing the drug can increase the delta between what you can achieve with, let’s say, a bland embolization versus chemoembolization.

Ghassan K. Abou-Alfa, MD: Fair enough. I will switch to Richard because one of the things many of us were involved in is kind of the marriage between local therapy and systemic therapy. Your thoughts on combining a chemoembolization plus sorafenib.

Richard Finn, MD: So, when sorafenib initially was approved, there was a lot of excitement about moving it into earlier stage disease, given that it improved survival in advanced disease. The first studies that were launched were a postsurgical study, which we spoke about a few minutes ago, and then studies after local regional therapy. As Riccardo mentioned, the majority of patients globally are getting chemoembolization as their backbone of treatment when they’re diagnosed. And we know it has limitations. Can we improve on that? There were several global studies launched looking at chemoembolization with sorafenib. And while there were hints of signals in various pockets, the majority of these studies showed that there was really no improvement in overall survival with the addition of sorafenib in earlier stage disease. There was the great hypothesis that by inducing embolization—or cutting off the blood supply to the tumor—we know that that ischemia that normally occurs with embolization increases the secretion of VEGF, vascular endothelial growth factor, a potent mitogen. And, as we know, the target of sorafenib is the vascular EGFR. So, there is a lot of scientific rationale for that, but, unfortunately, the clinical data at the end of the day did not, and does not support, its use right now.

Ghassan K. Abou-Alfa, MD: Fair enough. Obviously, this is an important reminder that this kind of, and sometimes we see it, back-and-forth approach—chemoembolization here, sorafenib there, chemoembolization here, sorafenib there—it’s not necessarily what would be medically appropriate here. And the reason is, as in oncology, always our aim—as actually Dr. Finn brought up a little bit earlier—is toward survival. Improvement in outcome, this is really the criticality of it, and not necessarily seeing only tumor change, or shrinking, or changing in texture, or what have we, even though these could be kind of surrogates to the outcome. But the outcome at the end of the day is survival, and that’s really what we need to focus on in that regard.

Transcript Edited for Clarity
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Transcript:

Ghassan K. Abou-Alfa, MD:
Riccardo, it might be that sometimes patients might be still cured but don’t need surgery. Tell us a little bit more about RFA (radiofrequency ablation).

Riccardo Lencioni, MD: I would say this is probably even more common than with surgery itself because of the reasons that we described at the beginning: many patients either have compromised liver function or they have comorbidities. So, they are truly not very good candidates for major hepatectomies. So, in these patients, with image-guided ablation, the chance to get a complete cure—in terms of complete pathologic eradication of the tumor approach—is 90%. Of course, there are some limitations, like the size and location of the tumor, but we also have a variety of tools now, from radiofrequency to microwave to cryoablation to non-thermal technologies such as irreversible electroporation. This is really the kind of cancer where cure exists beyond surgery. I think this is extremely important because truly—for many patients—when surgery is risky, the best chance for a cure is an interventional procedure.

Ghassan K. Abou-Alfa, MD: Well, definitely we see that perspective, and we might argue in regard to surgery versus RFA. This probably would require some specialized discussion and obviously a visit with an expert like Riccardo Lencioni as an interventional radiologist, plus, of course, a surgeon. And sometimes surgeons might apply both therapies or practice both therapies, and it’s very important to look into those options. But this is a great sprint into the second layer of how to treat liver cancer—which we’re going to address right now—which is the local approaches, the specialty of Dr. Lencioni here with us, in regard to what can interventional radiology offer.

Riccardo, I’ll say what I understand as an oncologist about embolization, so correct me when I’m wrong. And then I’m going to challenge you on some questions. The liver has a dual blood supply, and it appears to be that cancer cells are always finicky. They love to live on arterial blood supply. You try to suffocate them somewhere, throw some chemotherapy on them. You depend on the fact that the portal system is still feeding the liver and, as such, it can’t kill tumor. Is this fair?

Riccardo Lencioni, MD: That’s very good.

Ghassan K. Abou-Alfa, MD: I’m glad you say that. However, now, my biggest challenge—and Richard, please help me here—is that the data that was reported back by Lovay and Lowe in regard to embolization really looked at rather small tumors. And now you see those things being embolized no matter how big size they are. Tell me a little bit more.

Riccardo Lencioni, MD: Well, first of all, the trials that you mentioned established chemoembolization as the standard-of-care for liver only or liver-dominant disease. And I would say this is truly one of the therapies that is more of a global therapy because it’s the most popular treatment for HCC anywhere in the world. Those trials were performed 15 years ago. So, the same way the surgeons improved the technology, we also did a little bit of homework. So, we have new catheters, and tools, and microspheres, and a variety of solutions that can truly address different kinds of disease. That being said, I think the key here, again, is to really understand the whole benefits. Definitely, chemoembolization is a very good option for patients who have disease limited to their liver. It can be explored in patients with more advanced disease in the setting of combination regimens, and this is an area for clinical research. But, currently, I would say the best indication is for those patients that the Barcelona classification will call intermediate-stage.

Ghassan K. Abou-Alfa, MD: Fair enough. As you know, we published some data from Memorial Sloan Kettering Cancer Center not that long ago in JCO (Journal of Clinical Oncology) on February 1, 2016, arguing that bland embolization and chemoembolization probably would relay the same outcome. Your thoughts on that.

Riccardo Lencioni, MD: As I say, the technology has improved significantly. So, currently, it is possible to truly achieve the very precise calibrated vascular obstruction.

Ghassan K. Abou-Alfa, MD: Locate, in other words, you mean?

Riccardo Lencioni, MD: Yes. So, the new generation of beads are radiopaque. So, you can truly do a kind of manicured devascularization of the tumor. We still have data that suggest that having a drug administered along with the embolics improves the efficacy. But it is also true that we may not be using, currently, the most powerful drugs. I mean, the drugs that are used in chemoembolization are cytotoxic chemotherapy drugs, mostly doxorubicin, cisplatin, mitomycin-C. There are several different new forms of therapies, new agents that are worth exploring. Potentially, changing the drug can increase the delta between what you can achieve with, let’s say, a bland embolization versus chemoembolization.

Ghassan K. Abou-Alfa, MD: Fair enough. I will switch to Richard because one of the things many of us were involved in is kind of the marriage between local therapy and systemic therapy. Your thoughts on combining a chemoembolization plus sorafenib.

Richard Finn, MD: So, when sorafenib initially was approved, there was a lot of excitement about moving it into earlier stage disease, given that it improved survival in advanced disease. The first studies that were launched were a postsurgical study, which we spoke about a few minutes ago, and then studies after local regional therapy. As Riccardo mentioned, the majority of patients globally are getting chemoembolization as their backbone of treatment when they’re diagnosed. And we know it has limitations. Can we improve on that? There were several global studies launched looking at chemoembolization with sorafenib. And while there were hints of signals in various pockets, the majority of these studies showed that there was really no improvement in overall survival with the addition of sorafenib in earlier stage disease. There was the great hypothesis that by inducing embolization—or cutting off the blood supply to the tumor—we know that that ischemia that normally occurs with embolization increases the secretion of VEGF, vascular endothelial growth factor, a potent mitogen. And, as we know, the target of sorafenib is the vascular EGFR. So, there is a lot of scientific rationale for that, but, unfortunately, the clinical data at the end of the day did not, and does not support, its use right now.

Ghassan K. Abou-Alfa, MD: Fair enough. Obviously, this is an important reminder that this kind of, and sometimes we see it, back-and-forth approach—chemoembolization here, sorafenib there, chemoembolization here, sorafenib there—it’s not necessarily what would be medically appropriate here. And the reason is, as in oncology, always our aim—as actually Dr. Finn brought up a little bit earlier—is toward survival. Improvement in outcome, this is really the criticality of it, and not necessarily seeing only tumor change, or shrinking, or changing in texture, or what have we, even though these could be kind of surrogates to the outcome. But the outcome at the end of the day is survival, and that’s really what we need to focus on in that regard.

Transcript Edited for Clarity
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