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Treating Liver or Peritoneal Metastases in CRC

Panelists: Johanna C. Bendell, MD, Sarah Cannon Research Institute; Cathy Eng, MD, FACP, The University of Texas MD Anderson Cancer Center; John L. Marshall, MD, The Ruesch Center for the Cure of GI Cancers ; Michael A. Morse, MD, Duke Cancer Institute; Dale R. Shepard, MD, PhD, FACP, Taussig Cancer Institute, Cleveland Clinic
Published: Thursday, Mar 08, 2018



Transcript: 

John L. Marshall, MD: Alright. We get a scan. The patient’s carcinoembryonic antigen level is 5. The scan shows 2 spots on the liver that, in retrospect, were probably there but now they’re bigger.

Cathy Eng, MD, FACP: How big?

John L. Marshall, MD: One centimeter. How about that? The CEA has gone up a little bit, and there are growing things in the liver, in that first 6-month or year scan. What are we going to do?

Cathy Eng, MD, FACP: Did they complete adjuvant therapy?

John L. Marshall, MD: Yes. They got all of their adjuvant therapy. Stage 3.

Cathy Eng, MD, FACP: Less than 6 months?

John L. Marshall, MD: Yes.

Cathy Eng, MD, FACP: I send them to the liver surgeon. Well, the No. 1 thing that I do is either get a PET scan to make sure there’s no other disease or a dedicated CT with liver protocol to make sure we’re not missing something else in the liver. For 2 lesions that are 1 cm or less, I do send them directly to the liver surgeon. But I send it to the liver surgeon with a discussion.

John L. Marshall, MD: Anybody else? Surgery? You’re a surgeon.

Michael A. Morse, MD: The concern with a relapse that soon is that they probably have a higher risk for having other disease that you might not know about yet. I have to admit, our surgeons are more likely to ask us to treat the person for some time.

Cathy Eng, MD, FACP: Even for 1 cm?

Michael A. Morse, MD: I’m sure that if any of them are watching, they’re going to say, “No, we don’t. Of course, we go right to surgery.” But I think they are very concerned about the outcomes and having somebody pop up with a lung lesion 6 months after they did their liver surgery.

Cathy Eng, MD, FACP: The only thing I would suggest, in that case–and I presume your liver surgeons do this—is to put a fiduciary to mark the lesion. What if the tumor shrinks so much?

John L. Marshall, MD: If they’re going to do a lobe, that’s OK. But if they’re going to wedge resection or radiofrequency ablation, they need to know where it was. This is a really important thing. I think our world has gotten increasingly aggressive in trying to get patients to what we call “stage 4, no evidence of disease” through surgery or other approaches. Most of our centers have all of the bells and whistles. Interventional radiology (IR) is an incredibly important partner for us, now with Yttrium-90 (Y-90). There are interesting new data that weren’t on our program. What do you think about Y-90 and the initial SIRFLOX study?

Johanna C. Bendell, MD: This is where patients got randomized to either chemotherapy followed by Y-90 Yttrium label beads to the liver followed by chemotherapy versus chemotherapy alone. What they saw was a very good response in the liver. So, Y-90 can get a very good response to the liver. But in the end, there was no difference in survival or you had progression outside of the liver. And so, I think it’s great, if you need to control the liver. But you’ve got to worry about the rest.

John L. Marshall, MD: Anybody buy the right/left argument? Maybe you’re thinking about it more for the right side?

Cathy Eng, MD, FACP: I thought those were very, very interesting data. Granted, it was also a post hoc analysis.

Dale R. Shepard, MD, PhD, FACP: My biggest concern is exactly what you said. Particularly with a pretty rapid progression into the liver, we’re pretty likely to have something somewhere else. This is not usually going to be liver confined. What benefit do we get from liver-directed therapy if we’re just going to get more disease outside of the liver? If you really need control of the liver, great. But often we need more therapy.

John L. Marshall, MD: What about intrahepatic FUDR? I’m seeing a resurgence of this. I’ve got more patients with pumps. They’ve gone up to New York and have been seen in the left corridor. So, they get a pump. Is this happening in Texas?

Cathy Eng, MD, FACP: I know that they have a phase I trial utilizing it, but I would say that the majority of us would not use it off of study. But going back to Y-90, I have to say—granted, it’s anecdotal—I have utilized it in a patient predominantly with liver disease while they were on maintenance chemotherapy. Basically, they were on maintenance and have their Y-90 for over a year.

John L. Marshall, MD: I like this approach.

Johanna C. Bendell, MD: Well, here’s the concern I have with Y-90. Maybe I just had a slew of patients who got this? But, especially when you use it early, we see the issues of scarring, fibrosis, and then cirrhosis. I’ve seen a number of folks who end up getting this.

John L. Marshall, MD: I do warn patients on this subject. “We don’t really know what you’ll be like in a couple of years and if you will be eligible for phase I trials, and all of those things. Your platelets are 80 and your bilirubin is up.” At Duke, what have they been doing?

Michael A. Morse, MD: Well, we have very aggressive IR physicians. However, I think that they still take their cues from what we think the disease is doing. For a very motivated patient, I agree with you. For the maintenance phase, if there’s an area that you think you can control, I’d go ahead and do it. I think they’re very selective in how they deliver it. The “treat the whole liver widely” thing may not apply for certain patients.

John L. Marshall, MD: What’s the craziest thing you have ever recommended taking out?

Cathy Eng, MD, FACP: Taking out?

John L. Marshall, MD: Bone lesion?

Michael A. Morse, MD: Bone.

John L. Marshall, MD: Yes?

Michael A. Morse, MD: Occasionally, the surgeons will try to do something to a vertebral body, if they think they can get it.

John L. Marshall, MD: Paraaortic lymph nodes?

Cathy Eng, MD, FACP: I have done that. Yes.

John L. Marshall, MD: That’s crazy.

Cathy Eng, MD, FACP: But only once in a blue moon, for very select cases.

John L. Marshall, MD: That’s not crazy. I do it every now and then. Yes, you have to pick your spot, right? Mediastinal adenopathy, how about that one? Isolated mediastinal adenopathy, have you ever done that?

Michael A. Morse, MD: No.

John L. Marshall, MD: The question that I’m really asking is, is this kind of a debulking? Surgery has gotten better. The original theory was curative. “I’m going to get the last cell” versus “Surgery is better. They recover well. Maybe getting that out of there, if it’s easy, may be worth it.” Are you going there?

Cathy Eng, MD, FACP: Then why aren’t we taking the primary out in all of our metastatic colorectal patients?

John L. Marshall, MD: I like taking primaries out. I think it’s actually the right thing to do, if you can find the window. Are you taking anything crazy out?

Dale R. Shepard, MD, PhD, FACP: I don’t take anything crazy out. When you start doing things like taking out mediastinal nodes, and all of these things, you just worry that you’re getting to a point like a Whac-a-Mole game. You take one thing then you take something else. And, well, if you took those out, “Why not this?”

Cathy Eng, MD, FACP: Yes. I’m not a big fan.

Dale R. Shepard, MD, PhD, FACP: It’s bad for the patients because they tend to think it’s a curative rather than a debulking procedure.

John L. Marshall, MD: But we all have these long-surviving patients. Once a year or so, they develop a new crop of tumor (whether it’s liver metastases or lung metastases), and we feel that’s more rational.

Cathy Eng, MD, FACP: But that’s good biology. That’s a different story.

John L. Marshall, MD: Well, that’s the kind of patient I’m thinking about.

Cathy Eng, MD, FACP: That might be more appropriate. But the way that he’s describing it, I think is what we see quite a bit. There’s a little bit of cherry picking.

John L. Marshall, MD: Yes. The last extension of this, for me, is HIPEC (hyperthermic intraperitoneal chemotherapy) peritoneal surgery. I live in a city where we do lots of it. What is sane and rational in a colorectal patient? Appendix, we’re all cool with this, right? So, is there a patient in whom you might do this?

Johanna C. Bendell, MD: A low-grade, mucinous appendix–type of patient. Somebody who has had isolated peritoneal disease for a year. Somebody who has really proven that there’s no other metastases and it’s something slow growing.

John L. Marshall, MD: Peritoneal disease about to obstruct?

Michael A. Morse, MD: That sounds like very bad biology, to be attempting that.

John L. Marshall, MD: OK. We ask the surgeons to come see them, right?

Michael A. Morse, MD: And they usually politely leave.

John L. Marshall, MD: They decline?

Michael A. Morse, MD: Yes.

John L. Marshall, MD: I think there’s pressure here, because there are more and more of these surgeons that are trained in this. Hospitals and hospital systems are investing in these teams.

Michael A. Morse, MD: But there are tumors that seem to behave peritoneally—the ones that metastasize to the ovaries, for example. I think you can make a case. But too often, somebody will also have a small liver lesion. Then, I think trying to address both of them doesn’t make sense.

John L. Marshall, MD: It was fascinating. At ASCO’s 2018 Gastrointestinal Cancers Symposium, a presentation in gastric cancer revealed that HIPEC showed that the chemotherapy part of that was important. I’ve actually doubted that for many years. It was just the surgery. But this suggested that chemotherapy is important. So, we’ll see how that goes from there.

Transcript Edited for Clarity 

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Transcript: 

John L. Marshall, MD: Alright. We get a scan. The patient’s carcinoembryonic antigen level is 5. The scan shows 2 spots on the liver that, in retrospect, were probably there but now they’re bigger.

Cathy Eng, MD, FACP: How big?

John L. Marshall, MD: One centimeter. How about that? The CEA has gone up a little bit, and there are growing things in the liver, in that first 6-month or year scan. What are we going to do?

Cathy Eng, MD, FACP: Did they complete adjuvant therapy?

John L. Marshall, MD: Yes. They got all of their adjuvant therapy. Stage 3.

Cathy Eng, MD, FACP: Less than 6 months?

John L. Marshall, MD: Yes.

Cathy Eng, MD, FACP: I send them to the liver surgeon. Well, the No. 1 thing that I do is either get a PET scan to make sure there’s no other disease or a dedicated CT with liver protocol to make sure we’re not missing something else in the liver. For 2 lesions that are 1 cm or less, I do send them directly to the liver surgeon. But I send it to the liver surgeon with a discussion.

John L. Marshall, MD: Anybody else? Surgery? You’re a surgeon.

Michael A. Morse, MD: The concern with a relapse that soon is that they probably have a higher risk for having other disease that you might not know about yet. I have to admit, our surgeons are more likely to ask us to treat the person for some time.

Cathy Eng, MD, FACP: Even for 1 cm?

Michael A. Morse, MD: I’m sure that if any of them are watching, they’re going to say, “No, we don’t. Of course, we go right to surgery.” But I think they are very concerned about the outcomes and having somebody pop up with a lung lesion 6 months after they did their liver surgery.

Cathy Eng, MD, FACP: The only thing I would suggest, in that case–and I presume your liver surgeons do this—is to put a fiduciary to mark the lesion. What if the tumor shrinks so much?

John L. Marshall, MD: If they’re going to do a lobe, that’s OK. But if they’re going to wedge resection or radiofrequency ablation, they need to know where it was. This is a really important thing. I think our world has gotten increasingly aggressive in trying to get patients to what we call “stage 4, no evidence of disease” through surgery or other approaches. Most of our centers have all of the bells and whistles. Interventional radiology (IR) is an incredibly important partner for us, now with Yttrium-90 (Y-90). There are interesting new data that weren’t on our program. What do you think about Y-90 and the initial SIRFLOX study?

Johanna C. Bendell, MD: This is where patients got randomized to either chemotherapy followed by Y-90 Yttrium label beads to the liver followed by chemotherapy versus chemotherapy alone. What they saw was a very good response in the liver. So, Y-90 can get a very good response to the liver. But in the end, there was no difference in survival or you had progression outside of the liver. And so, I think it’s great, if you need to control the liver. But you’ve got to worry about the rest.

John L. Marshall, MD: Anybody buy the right/left argument? Maybe you’re thinking about it more for the right side?

Cathy Eng, MD, FACP: I thought those were very, very interesting data. Granted, it was also a post hoc analysis.

Dale R. Shepard, MD, PhD, FACP: My biggest concern is exactly what you said. Particularly with a pretty rapid progression into the liver, we’re pretty likely to have something somewhere else. This is not usually going to be liver confined. What benefit do we get from liver-directed therapy if we’re just going to get more disease outside of the liver? If you really need control of the liver, great. But often we need more therapy.

John L. Marshall, MD: What about intrahepatic FUDR? I’m seeing a resurgence of this. I’ve got more patients with pumps. They’ve gone up to New York and have been seen in the left corridor. So, they get a pump. Is this happening in Texas?

Cathy Eng, MD, FACP: I know that they have a phase I trial utilizing it, but I would say that the majority of us would not use it off of study. But going back to Y-90, I have to say—granted, it’s anecdotal—I have utilized it in a patient predominantly with liver disease while they were on maintenance chemotherapy. Basically, they were on maintenance and have their Y-90 for over a year.

John L. Marshall, MD: I like this approach.

Johanna C. Bendell, MD: Well, here’s the concern I have with Y-90. Maybe I just had a slew of patients who got this? But, especially when you use it early, we see the issues of scarring, fibrosis, and then cirrhosis. I’ve seen a number of folks who end up getting this.

John L. Marshall, MD: I do warn patients on this subject. “We don’t really know what you’ll be like in a couple of years and if you will be eligible for phase I trials, and all of those things. Your platelets are 80 and your bilirubin is up.” At Duke, what have they been doing?

Michael A. Morse, MD: Well, we have very aggressive IR physicians. However, I think that they still take their cues from what we think the disease is doing. For a very motivated patient, I agree with you. For the maintenance phase, if there’s an area that you think you can control, I’d go ahead and do it. I think they’re very selective in how they deliver it. The “treat the whole liver widely” thing may not apply for certain patients.

John L. Marshall, MD: What’s the craziest thing you have ever recommended taking out?

Cathy Eng, MD, FACP: Taking out?

John L. Marshall, MD: Bone lesion?

Michael A. Morse, MD: Bone.

John L. Marshall, MD: Yes?

Michael A. Morse, MD: Occasionally, the surgeons will try to do something to a vertebral body, if they think they can get it.

John L. Marshall, MD: Paraaortic lymph nodes?

Cathy Eng, MD, FACP: I have done that. Yes.

John L. Marshall, MD: That’s crazy.

Cathy Eng, MD, FACP: But only once in a blue moon, for very select cases.

John L. Marshall, MD: That’s not crazy. I do it every now and then. Yes, you have to pick your spot, right? Mediastinal adenopathy, how about that one? Isolated mediastinal adenopathy, have you ever done that?

Michael A. Morse, MD: No.

John L. Marshall, MD: The question that I’m really asking is, is this kind of a debulking? Surgery has gotten better. The original theory was curative. “I’m going to get the last cell” versus “Surgery is better. They recover well. Maybe getting that out of there, if it’s easy, may be worth it.” Are you going there?

Cathy Eng, MD, FACP: Then why aren’t we taking the primary out in all of our metastatic colorectal patients?

John L. Marshall, MD: I like taking primaries out. I think it’s actually the right thing to do, if you can find the window. Are you taking anything crazy out?

Dale R. Shepard, MD, PhD, FACP: I don’t take anything crazy out. When you start doing things like taking out mediastinal nodes, and all of these things, you just worry that you’re getting to a point like a Whac-a-Mole game. You take one thing then you take something else. And, well, if you took those out, “Why not this?”

Cathy Eng, MD, FACP: Yes. I’m not a big fan.

Dale R. Shepard, MD, PhD, FACP: It’s bad for the patients because they tend to think it’s a curative rather than a debulking procedure.

John L. Marshall, MD: But we all have these long-surviving patients. Once a year or so, they develop a new crop of tumor (whether it’s liver metastases or lung metastases), and we feel that’s more rational.

Cathy Eng, MD, FACP: But that’s good biology. That’s a different story.

John L. Marshall, MD: Well, that’s the kind of patient I’m thinking about.

Cathy Eng, MD, FACP: That might be more appropriate. But the way that he’s describing it, I think is what we see quite a bit. There’s a little bit of cherry picking.

John L. Marshall, MD: Yes. The last extension of this, for me, is HIPEC (hyperthermic intraperitoneal chemotherapy) peritoneal surgery. I live in a city where we do lots of it. What is sane and rational in a colorectal patient? Appendix, we’re all cool with this, right? So, is there a patient in whom you might do this?

Johanna C. Bendell, MD: A low-grade, mucinous appendix–type of patient. Somebody who has had isolated peritoneal disease for a year. Somebody who has really proven that there’s no other metastases and it’s something slow growing.

John L. Marshall, MD: Peritoneal disease about to obstruct?

Michael A. Morse, MD: That sounds like very bad biology, to be attempting that.

John L. Marshall, MD: OK. We ask the surgeons to come see them, right?

Michael A. Morse, MD: And they usually politely leave.

John L. Marshall, MD: They decline?

Michael A. Morse, MD: Yes.

John L. Marshall, MD: I think there’s pressure here, because there are more and more of these surgeons that are trained in this. Hospitals and hospital systems are investing in these teams.

Michael A. Morse, MD: But there are tumors that seem to behave peritoneally—the ones that metastasize to the ovaries, for example. I think you can make a case. But too often, somebody will also have a small liver lesion. Then, I think trying to address both of them doesn’t make sense.

John L. Marshall, MD: It was fascinating. At ASCO’s 2018 Gastrointestinal Cancers Symposium, a presentation in gastric cancer revealed that HIPEC showed that the chemotherapy part of that was important. I’ve actually doubted that for many years. It was just the surgery. But this suggested that chemotherapy is important. So, we’ll see how that goes from there.

Transcript Edited for Clarity 
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