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Intrahepatic Radiation in Colorectal Cancer

Panelists: John Marshall, MD, Lombardi Comprehensive Cancer Center; Alan P. Venook, MD, Helen Diller Family Comprehensive Cancer Center; Tanios Bekaii-Saab, MD, The Mayo Clinic; Johanna Bendell, MD, The Sarah Cannon Research Institute
Published: Monday, Mar 06, 2017



Transcript:

John Marshall, MD:
I do want to talk next about the concept that Alan brought forward, which is this radioembolization approach. This field to me has evolved. It went from bland embolization to chemoembolization to DEBIRI, which is sort of chemoembolization. You have intrahepatic pumps. And now we’re at the next version of that, which is intrahepatic delivery of radiation. Johanna, I’m going to pick on you to set the stage around this technology a little bit and the studies that were done to help support it.

Johanna Bendell, MD: So, we’re talking about Y-90 (yttrium-90) treatment. The way I describe it to my patients is they are microbeads that are coated in radiation therapy that are injected directly in the liver and are carried directly to the tumors within the liver preferentially because of the blood flow patterns. And so, we’ve seen in earlier studies, in more refractory patients, that when you inject the yttrium-90 beads, you do get significant shrinkage of the tumors within the liver. Can we use this earlier on? Previously, this was used mostly in a more refractory setting, but the SIRFLOX study, that presented some recent data, looked at it in the first-line setting, using FOLFOX-based first-line chemotherapy and randomizing patients to chemotherapy alone versus chemotherapy plus the use of the yttrium, or Y-90, beads.

John Marshall, MD: And right at the beginning.

Johanna Bendell, MD: Yes. And so, they saw no difference in progression-free survival overall because about 40% of those patients had extrahepatic disease. But, they saw significant improvement in response rates in the liver disease using the Y-90 and then they also saw an improved progression-free survival for the liver-specific disease using the Y-90. And so, we’re hoping to see more data come as more studies start to read out using this type of therapy for these patients.

John Marshall, MD: So, this study has really had an influence on me. I think the liver number is like 20 months of liver disease control. And I think about a frontline patient with liver-dominant or liver-only disease. I’m actually using that number in clinic with patients, but I have to say I’m not following that algorithm. If I’m going to do this, I tend to do it as a premaintenance or part of the maintenance, and I don’t have a lot of evidence to do that, but I just wondered. Tony, let me pick on you on this one. Are you doing any of this? Is there a patient where you might say this is an ideal patient, others that you might not?

Tanios Bekaii-Saab, MD: I agree. I haven’t adopted it as per the study because, again, I’m waiting on the results of the survival data. That was an overall negative study, although it had some positive endpoints. But, in actual practice, when you think about it, I’ve had instances where patients had disease limited to the liver and adamantly refused to continue on chemotherapy after a good response to chemotherapy. And I’ve used it as a maintenance strategy in select patients that refuse to actually go on further chemotherapy, capecitabine plus bevacizumab. As long as the disease has been very well controlled with chemotherapy to a minimal residual component, this actually has been, for a few patients, a good modality. The other place is actually in patients who have failed a couple lines of therapy and do not want to go on any further systemic therapy in disease still limited to the liver. I find that useful. These are the 2 instances where I’ve used it. John Marshall, MD: I’ve been stronger than that. Because, it seems to me to be relatively well tolerated, fairly simple to deliver. If it’s bulky liver disease, I’m trying to fit it in earlier. Don’t get me wrong. I still use a lot in the refractory setting and I use it depending on how they’re doing. Alan, I know you’re very data driven and your practice really is driven by what’s out there. What’s going on?

Alan P. Venook, MD: We’re studying the modality. We’ve typically used it in later lines. I think the SIRFLOX study, which was very well done, leads me to believe it may have a role up front, depending on the results of a few other studies, results of which will be pooled. When we tend to use it early is when there’s a subset of patients who can’t tolerate chemotherapy. You can’t get their platelets or their white blood cells, you just can’t get much in. If it’s clear to me after 1 to 2 cycles that they’re just not going to tolerate aggressive chemotherapy for very long, I might jump in early to try to at least manage the liver involvement right off the bat.

John Marshall, MD: And bulkier disease maybe; not a great initial response.

Alan P. Venook, MD: Correct. That’s where we tend to go with that. Again, it is, in our hands, well tolerated. It’s not a simple procedure. It’s a multi-phase procedure. You need 2 visits to the interventional suite. They need to map the disease, see what the shunt fraction is of the beads going away from the liver. It’s not inexpensive, but, again, I find that you get a lot of bang for your buck in those patients.

John Marshall, MD: And sometimes you’re coming back and doing a second. They’re doing 1 load. This study was, I think, a single injection. And now they’re doing more and more.

Alan P. Venook, MD: Correct. Again, the issue in the study, 40% of the patients had extrahepatic disease and the benefit was much less notable in that population. So, I do believe for patients with any volume of disease outside of the liver, this is not a very great play unless there’s huge volume in the liver where you’re worried about liver progression and failure early on. We’re moving more and more towards this, and, again, I’m waiting for the definitive results from the survival data to see if that is really of benefit, and, in fact, I think it will have a place earlier in many of our algorithms.

John Marshall, MD: I tell my patients there’s fatigue, sometimes lasting a few weeks, but many have very few side effects, sometimes the pain and nausea, but it’s an outpatient procedure. It’s not embolic, right? So, you don’t have that same acute pain and nausea that you see with embolization. Anybody throw in other things?

Johanna Bendell, MD: The only one thing I would say is I have had some patients present with epigastric pain afterwards, and you have to have a very low threshold to make sure no ulcer occurred. That would be the only thing I wouldn’t want somebody to miss.

Transcript Edited for Clarity

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Transcript:

John Marshall, MD:
I do want to talk next about the concept that Alan brought forward, which is this radioembolization approach. This field to me has evolved. It went from bland embolization to chemoembolization to DEBIRI, which is sort of chemoembolization. You have intrahepatic pumps. And now we’re at the next version of that, which is intrahepatic delivery of radiation. Johanna, I’m going to pick on you to set the stage around this technology a little bit and the studies that were done to help support it.

Johanna Bendell, MD: So, we’re talking about Y-90 (yttrium-90) treatment. The way I describe it to my patients is they are microbeads that are coated in radiation therapy that are injected directly in the liver and are carried directly to the tumors within the liver preferentially because of the blood flow patterns. And so, we’ve seen in earlier studies, in more refractory patients, that when you inject the yttrium-90 beads, you do get significant shrinkage of the tumors within the liver. Can we use this earlier on? Previously, this was used mostly in a more refractory setting, but the SIRFLOX study, that presented some recent data, looked at it in the first-line setting, using FOLFOX-based first-line chemotherapy and randomizing patients to chemotherapy alone versus chemotherapy plus the use of the yttrium, or Y-90, beads.

John Marshall, MD: And right at the beginning.

Johanna Bendell, MD: Yes. And so, they saw no difference in progression-free survival overall because about 40% of those patients had extrahepatic disease. But, they saw significant improvement in response rates in the liver disease using the Y-90 and then they also saw an improved progression-free survival for the liver-specific disease using the Y-90. And so, we’re hoping to see more data come as more studies start to read out using this type of therapy for these patients.

John Marshall, MD: So, this study has really had an influence on me. I think the liver number is like 20 months of liver disease control. And I think about a frontline patient with liver-dominant or liver-only disease. I’m actually using that number in clinic with patients, but I have to say I’m not following that algorithm. If I’m going to do this, I tend to do it as a premaintenance or part of the maintenance, and I don’t have a lot of evidence to do that, but I just wondered. Tony, let me pick on you on this one. Are you doing any of this? Is there a patient where you might say this is an ideal patient, others that you might not?

Tanios Bekaii-Saab, MD: I agree. I haven’t adopted it as per the study because, again, I’m waiting on the results of the survival data. That was an overall negative study, although it had some positive endpoints. But, in actual practice, when you think about it, I’ve had instances where patients had disease limited to the liver and adamantly refused to continue on chemotherapy after a good response to chemotherapy. And I’ve used it as a maintenance strategy in select patients that refuse to actually go on further chemotherapy, capecitabine plus bevacizumab. As long as the disease has been very well controlled with chemotherapy to a minimal residual component, this actually has been, for a few patients, a good modality. The other place is actually in patients who have failed a couple lines of therapy and do not want to go on any further systemic therapy in disease still limited to the liver. I find that useful. These are the 2 instances where I’ve used it. John Marshall, MD: I’ve been stronger than that. Because, it seems to me to be relatively well tolerated, fairly simple to deliver. If it’s bulky liver disease, I’m trying to fit it in earlier. Don’t get me wrong. I still use a lot in the refractory setting and I use it depending on how they’re doing. Alan, I know you’re very data driven and your practice really is driven by what’s out there. What’s going on?

Alan P. Venook, MD: We’re studying the modality. We’ve typically used it in later lines. I think the SIRFLOX study, which was very well done, leads me to believe it may have a role up front, depending on the results of a few other studies, results of which will be pooled. When we tend to use it early is when there’s a subset of patients who can’t tolerate chemotherapy. You can’t get their platelets or their white blood cells, you just can’t get much in. If it’s clear to me after 1 to 2 cycles that they’re just not going to tolerate aggressive chemotherapy for very long, I might jump in early to try to at least manage the liver involvement right off the bat.

John Marshall, MD: And bulkier disease maybe; not a great initial response.

Alan P. Venook, MD: Correct. That’s where we tend to go with that. Again, it is, in our hands, well tolerated. It’s not a simple procedure. It’s a multi-phase procedure. You need 2 visits to the interventional suite. They need to map the disease, see what the shunt fraction is of the beads going away from the liver. It’s not inexpensive, but, again, I find that you get a lot of bang for your buck in those patients.

John Marshall, MD: And sometimes you’re coming back and doing a second. They’re doing 1 load. This study was, I think, a single injection. And now they’re doing more and more.

Alan P. Venook, MD: Correct. Again, the issue in the study, 40% of the patients had extrahepatic disease and the benefit was much less notable in that population. So, I do believe for patients with any volume of disease outside of the liver, this is not a very great play unless there’s huge volume in the liver where you’re worried about liver progression and failure early on. We’re moving more and more towards this, and, again, I’m waiting for the definitive results from the survival data to see if that is really of benefit, and, in fact, I think it will have a place earlier in many of our algorithms.

John Marshall, MD: I tell my patients there’s fatigue, sometimes lasting a few weeks, but many have very few side effects, sometimes the pain and nausea, but it’s an outpatient procedure. It’s not embolic, right? So, you don’t have that same acute pain and nausea that you see with embolization. Anybody throw in other things?

Johanna Bendell, MD: The only one thing I would say is I have had some patients present with epigastric pain afterwards, and you have to have a very low threshold to make sure no ulcer occurred. That would be the only thing I wouldn’t want somebody to miss.

Transcript Edited for Clarity
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