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Neoadjuvant and Local Therapy in HCC

Panelists: Ghassan K. Abou-Alfa, MD, Memorial Sloan Kettering Cancer Center; Richard S. Finn, MD, Geffen School of Medicine at UCLA; Masatoshi Kudo, MD, PhD, Kindai University Faculty of Medicine; Arndt Vogel, MD, Hannover Medical School
Published: Thursday, Aug 16, 2018



Transcript: 

Ghassan K. Abou-Alfa, MD: That really brings me to another point to ask, which is not necessarily something that we commonly use, but it’s nice to hear all the perspectives from all over the world. And I’ll start with our friend from Japan, Dr. Kudo. Masatoshi, so a patient comes with a tumor that might ultimately be resectable, but the surgeon would like to see it a little bit smaller; ie, they would like to see some neoadjuvant or some conversion therapy to make it smaller per se. I might be totally wrong, but does this approach at all exist in Japan?

Masatoshi Kudo, MD, PhD: Not at the present. We do not perform.

Ghassan K. Abou-Alfa, MD: Fair enough, fair enough. And I think the same thing, Arndt, for Germany or Europe, like an approach of trying to reduce tumors so that they can become resectable, because this is a practice we use in other cancers, in different malignancies.

Arndt Vogel, MD: I think it really depends. Sometimes the question is—and we had this discussion before—who decides whether a tumor is resectable or not? So, it depends on the liver surgeons. Some surgeons might say no; the others might say yes. This is the first thing you need to ask somebody who really has experience. On the other hand, if you have a large tumor, which is really not a good candidate for resection, if you do a local or whatever kind of treatment and you shrink the tumor, it’s not neoadjuvant, it’s downstaging here. And so, I think we can downstage some patients, and we also discuss it in our tumor board sometimes. So, if we have here a tumor that gets a little bit smaller, then we would do the resection—and not only downstaging; it’s also to learn a little bit about the biology of the tumor. So, if it’s a large tumor or if you have 2 or 3 metastases around the tumor, is it a tumor that is likely to have very early recurrence after local therapy? So, we do some kind of selection with the downstaging and selection of appropriate candidates. It’s rare, but it’s something that we are doing in our treatment algorithm, yes.

Ghassan K. Abou-Alfa, MD: No, absolutely. If anything, really, the only example that comes to my mind is that this is like really relatively old now. We had the regimens of platinum, interferon, Adriamycin, FOLFIRI. And if anything, it was tried here and there, despite that it did not show necessarily any survival advantage compared with doxorubicin at that time. But, nonetheless, it definitely did show that there was a potential for resectability after giving that therapy. I would not necessarily say that we are recommending in any way, shape, or form, because it was rather toxic. But at least there was an attempt here and there to divert or convert a certain disease from being nonresectable to become resectable either by systemic therapy or, as we heard from Dr. Vogel, by the use of local approaches of therapy. This will bring us actually to the second point to discuss in the program, which is the locally advanced disease. What should we do about that? I’ll start again with Masatoshi. A patient with locally advanced disease in Japan comes in, heard about some local therapy; what would you recommend? What will be the standard of care?

Masatoshi Kudo, MD, PhD: So, locally advanced means an intermediate-stage disease.

Ghassan K. Abou-Alfa, MD: Fair enough.

Masatoshi Kudo, MD, PhD: In that stage, of course, standard of care is TACE. And sometimes in Japan—sometimes in the largely focal disease—in the past, very frequently, we performed hepatitis artery infusion chemotherapy using a low-dose 5-FU and cisplatin. But recently, because of systemic therapy, a very good systemic agent came in. So, in the largely focal disease, artery infusion chemotherapy is not frequently performed. In Japan, Y-90 is not approved, so we do not perform it.

Ghassan K. Abou-Alfa, MD: So, if anything, we hear that you use probably a chemoembolization and also, there’s a Japan-specific approach to give infusional chemotherapy into the liver with a platinum and the like. If anything, Richard, for TACE—your thoughts.

Richard S. Finn, MD: Well, I think when we’re talking about intermediate disease or Barcelona B; this is a heterogeneous group of patients. But needless to say, they have a well-compensated liver function, and they have a tumor burden that is multifocal or not resectable with curative intent. And the backbone for that has been chemoembolization. The liver vasculature lends itself to that approach, but the studies that defined the role for TACE were pretty stringent in their inclusion criteria. And what has happened is that has expanded over time. Part of it has been expanded because there’s a vacuum for other treatments. There was nothing else to offer patients, but there’s no doubt that for a true intermediate patient, TACE is the backbone and the standard of care.

There have been interesting data developing with radioembolization showing that. There haven’t been head-to-head comparisons with TACE, but single institution series show that it’s very active in controlling intratumoral disease. Maybe it’s better tolerated because it’s not embolic. It doesn’t block the blood supply, so you don’t get a post-TACE flulike illness, transaminitis. But needless to say, both of those techniques have their limits, and it’s important to use these approaches appropriately. No one would say that these treatments are going away in the management of liver cancer; they shouldn’t. They’ve been shown to help people, but they also have their limitations.

Transcript Edited for Clarity 

Brought to you in part by Eisai

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Transcript: 

Ghassan K. Abou-Alfa, MD: That really brings me to another point to ask, which is not necessarily something that we commonly use, but it’s nice to hear all the perspectives from all over the world. And I’ll start with our friend from Japan, Dr. Kudo. Masatoshi, so a patient comes with a tumor that might ultimately be resectable, but the surgeon would like to see it a little bit smaller; ie, they would like to see some neoadjuvant or some conversion therapy to make it smaller per se. I might be totally wrong, but does this approach at all exist in Japan?

Masatoshi Kudo, MD, PhD: Not at the present. We do not perform.

Ghassan K. Abou-Alfa, MD: Fair enough, fair enough. And I think the same thing, Arndt, for Germany or Europe, like an approach of trying to reduce tumors so that they can become resectable, because this is a practice we use in other cancers, in different malignancies.

Arndt Vogel, MD: I think it really depends. Sometimes the question is—and we had this discussion before—who decides whether a tumor is resectable or not? So, it depends on the liver surgeons. Some surgeons might say no; the others might say yes. This is the first thing you need to ask somebody who really has experience. On the other hand, if you have a large tumor, which is really not a good candidate for resection, if you do a local or whatever kind of treatment and you shrink the tumor, it’s not neoadjuvant, it’s downstaging here. And so, I think we can downstage some patients, and we also discuss it in our tumor board sometimes. So, if we have here a tumor that gets a little bit smaller, then we would do the resection—and not only downstaging; it’s also to learn a little bit about the biology of the tumor. So, if it’s a large tumor or if you have 2 or 3 metastases around the tumor, is it a tumor that is likely to have very early recurrence after local therapy? So, we do some kind of selection with the downstaging and selection of appropriate candidates. It’s rare, but it’s something that we are doing in our treatment algorithm, yes.

Ghassan K. Abou-Alfa, MD: No, absolutely. If anything, really, the only example that comes to my mind is that this is like really relatively old now. We had the regimens of platinum, interferon, Adriamycin, FOLFIRI. And if anything, it was tried here and there, despite that it did not show necessarily any survival advantage compared with doxorubicin at that time. But, nonetheless, it definitely did show that there was a potential for resectability after giving that therapy. I would not necessarily say that we are recommending in any way, shape, or form, because it was rather toxic. But at least there was an attempt here and there to divert or convert a certain disease from being nonresectable to become resectable either by systemic therapy or, as we heard from Dr. Vogel, by the use of local approaches of therapy. This will bring us actually to the second point to discuss in the program, which is the locally advanced disease. What should we do about that? I’ll start again with Masatoshi. A patient with locally advanced disease in Japan comes in, heard about some local therapy; what would you recommend? What will be the standard of care?

Masatoshi Kudo, MD, PhD: So, locally advanced means an intermediate-stage disease.

Ghassan K. Abou-Alfa, MD: Fair enough.

Masatoshi Kudo, MD, PhD: In that stage, of course, standard of care is TACE. And sometimes in Japan—sometimes in the largely focal disease—in the past, very frequently, we performed hepatitis artery infusion chemotherapy using a low-dose 5-FU and cisplatin. But recently, because of systemic therapy, a very good systemic agent came in. So, in the largely focal disease, artery infusion chemotherapy is not frequently performed. In Japan, Y-90 is not approved, so we do not perform it.

Ghassan K. Abou-Alfa, MD: So, if anything, we hear that you use probably a chemoembolization and also, there’s a Japan-specific approach to give infusional chemotherapy into the liver with a platinum and the like. If anything, Richard, for TACE—your thoughts.

Richard S. Finn, MD: Well, I think when we’re talking about intermediate disease or Barcelona B; this is a heterogeneous group of patients. But needless to say, they have a well-compensated liver function, and they have a tumor burden that is multifocal or not resectable with curative intent. And the backbone for that has been chemoembolization. The liver vasculature lends itself to that approach, but the studies that defined the role for TACE were pretty stringent in their inclusion criteria. And what has happened is that has expanded over time. Part of it has been expanded because there’s a vacuum for other treatments. There was nothing else to offer patients, but there’s no doubt that for a true intermediate patient, TACE is the backbone and the standard of care.

There have been interesting data developing with radioembolization showing that. There haven’t been head-to-head comparisons with TACE, but single institution series show that it’s very active in controlling intratumoral disease. Maybe it’s better tolerated because it’s not embolic. It doesn’t block the blood supply, so you don’t get a post-TACE flulike illness, transaminitis. But needless to say, both of those techniques have their limits, and it’s important to use these approaches appropriately. No one would say that these treatments are going away in the management of liver cancer; they shouldn’t. They’ve been shown to help people, but they also have their limitations.

Transcript Edited for Clarity 

Brought to you in part by Eisai
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