DR BENDELL: This was a very interesting case that sent all of us reeling a little bit. So this gentleman originally presented 5 years ago to the emergency room with a bleeding gastric ulcer. He had it locally treated. He went on a PPI. And then he came back to the emergency room last year with just significant left flank pain. So he got his mandatory CT scan in the ER. And interestingly enough, there was nothing going on with the left flank pain, but he had a liver full of tumors. And he also had some thickening in the gastric area, got an EGD, which showed a gastric mass. He ended up having a CT-guided core biopsy, because when he was originally presented to me, everybody thought this was going to be a metastatic gastric cancer.

Has a core biopsy of his liver lesion, and it shows a metastatic, well-differentiated neuroendocrine tumor. Ki-67, less than 5%.

DR LOVE: So I’m curious how you all would be thinking through this situation. Randy, what would you be thinking?

DR HECHT: This is probably a Type 3 gastric carcinoid that’s unfortunately metastasized, as these usually have by the time that you — this is not the small, incidental one that you find or even related with ZE. And so your person has an excellent performance status. The problem is, is that we talk about all the new drugs. But all the new drugs so far that have been approved, of course, have been for pancreatic neuroendocrine tumors rather than for carcinoids, which is the vast majority of the NETs that we see.

There are — I mean, octreotide LAR is a reasonable thing, though that’s based on the PROMID trial — and this is a gastric, but we tend to do it. He doesn’t sound like he has any hormonal symptoms. Is that correct? I think it’s — someone brought up, I can’t remember — earlier, I mean, you have a CT scan that looks like salami and that, at the same time, has preserved liver function, which is sort of common, and that’s always a teaching point for this. And right now I think that the question comes up about — first thing, with the very low Ki-67, I probably would put the patient on octreotide LAR and then try to get a sense to see how he’s doing, because he still has the primary in place. This is not liver only, even though it seems like his burden of disease is liver dominant. And I’d put that I don’t have to worry about hormonal symptoms or getting rid of them. And I kind of put that in my back pocket to see which way he’s going, because he’s someone who may have had it for years and years. We all have patients like that, who show up, have the CT scan for some other reason and there is that subgroup of patients who do extremely well just on octreotide alone.

DR LOVE: What would it take as you would follow him to get you to start thinking about liver-directed therapy?

DR HECHT: Basically that things are getting worse on the scans. I mean even though he has multiple lesions, you would probably see, particularly if he does not blossom outside the liver, as often these people will just be in the liver. It sounds like his primary tumor is doing okay. I mean, this was an incidental. It’s not causing obstruction or anything like that. So I would leave that alone. So I think that if, probably on the basis of a kind of weaker, but we can get it, if someone progressed at this point, I would consider — if it were slow progression, I’d consider something like everolimus, even though the RADIANT — I think it was RADIANT-2, if I remember correctly, was the one that was negative, was barely negative — but usually we can get everolimus.

The other thing — I think it was brought up a little bit earlier, about difficulty getting things approved. The problem is, all the liver-directed therapies are devices. And the burden of proof is much different than it is for a device, than for a drug. A drug, you have to show that patients live longer, that it’s reasonably tolerable, all these other things. Or just basically you have to show that you can do it. And once the makers can do this, it’s really led to very few studies. And they’re not funded in order to do those trials.

So then what I would do, if I thought he was progressing, would be to actually send him to our multidisciplinary group.

How old is the patient?

DR BENDELL: Sixty.

DR HECHT: You could — he purely has liver only?

DR BENDELL: Yes. Purely liver only.

DR HECHT: You could even make a case, though — I’m going to probably cause lots of discussion — that transplant, if you could take out the primary, would be something to think about. But a 60-year-old — I mean, I’m just —

DR BENDELL: And a lot of liver only.

DR HECHT: — just saying. And a lot — that’s the ultimate liver-directed therapy. And I hate to have — he still has his primary in. So that’s something that also comes up.

DR LOVE: Has that been done?

DR HECHT: Transplant? Yes. That is one of the — so UNOS allows — basically, HCC, some cholangios and neuroendocrine tumors. And that’s the only other — so if you have colon cancer, sorry. But — even though there was a Norwegian trial with that. But neuroendocrine tumors, the problem is, is that you probably select out the ones who are going to do really well by the time they get a liver. And those patients tend to do fairly well, but they usually recur. So transplant is an option. That’s sort of the ultimate liver-directed therapy.

DR LOVE: So what happened with this patient?

DR BENDELL: So we discussed him at the multidisciplinary tumor board, because I was on the same question — do you watch and wait, or do you not? And my sphincter factor was a little bit high just because of the amount of liver disease that he had, even though his Ki-67 was low and, also, due to the fact that it was a gastric carcinoid, which tend to be poorer actors than your small bowel. So I went ahead and put him on octreotide LAR. But we went ahead and gave him radioembolization to the liver.

DR HECHT: Which is reasonable.

DR BENDELL: Yes. And he had 2 courses of it and actually has had significant amount of shrinkage of his liver disease. So now we just follow him and he’s on every 4-week —

DR HECHT: The nonrandomized data, we were just having this discussion with our interventional radiologists, because once again, the interventional radiologists are — generally, the data is, “We did this,” as opposed to randomized trials. But the thought is, is that even though we use radioembolization or Y-90 for a number of different tumors, the thought is, is that neuroendocrine tumors may have the best responses of — though, once again, that’s kind of their gestalt.

DR LOVE: And I’m curious, Philip, how you would have thought this through, particularly in view of the lack of symptoms or flushing or diarrhea and getting into the issue of whether octreotide slows the disease down. And we saw some data now, maybe a survival benefit in the PROMID study. What’s your general approach to this kind of situation?

DR PHILIP: In a patient like this, I will give him the options. I will briefly tell you that the octreotide LAR is a reasonable option. But if you look at the results of the study, the people with the light burden in the liver were the ones who benefited more than the ones with heavy burden. So that’s something to keep in mind, which means that octreotide may not be the best treatment for this patient. Certainly I would have approached the issue of liver-directed therapy with this patient, given the large tumor burden in the liver. But I also keep in mind the fact that if he goes down to Switzerland for the other treatment, then one has to be careful how much radiation you want to pump into the liver, because there’s some concern that we don’t have enough experience with adding 2 modalities. One is the radioembolization with radiation to the liver. And if he chooses to go to have the other treatment in Europe — although, the vast majority of the patients will not end up there.

DR LOVE: Just out of curiosity, did this man have any questions about the peptide receptor radionuclide therapy? Was that on his radar at all?

DR BENDELL: He actually didn’t. When I first met him, he was more just expecting to be told he was going to have metastatic gastric cancer. And so once he found out that this was a very rare tumor, he just went with the flow and didn’t have —

DR LOVE: What’s his current situation?

DR BENDELL: He’s actually getting his octreotide every 4 weeks and doing well and back at work. And we see him every few months for scans.

DR LOVE: How long has it been since you first saw him?

DR BENDELL: About a little over a year ago.

DR LOVE: And I don't know if he’s asked you this, but if he did, how would you respond, which is, what do you see in his future?

DR BENDELL: So what I usually tell people is we have to watch to see how his disease behaves, much like what Randy was talking about. I mean, for him we’ve stacked the decks for him by treating his liver disease. But most of it’s going to be watching with time to see if anything starts to grow again. It’s been quite a few months since he’s been treated. So I’m hopeful. But at the same time, the radioembolization can tend to have effects for months down the road. So I think that with each scan he gets further away from radioembolization without progression of his disease, I think portends better for him.

DR LOVE: Rich?

DR GOLDBERG: So it would be lovely to have a randomized trial of bland versus radioembolization versus chemoembolization in this setting, because we really don’t know how to compare them. My sense is that each time you embolize the liver, you do some collateral damage to the hepatic parenchyma and eventually end up with liver fibrosis and abnormal liver function. And so my instinct for this is to use bland embolization, at least initially, and to try and minimize the collateral damage. And obviously, this guy had bulky enough disease that you were uncomfortable watching him.

In these really slow-growing tumors with the Ki-67s of under five — 5%, the kind of debulking that you get from embolization, I think, can be dramatic often and can really extend life in these folks. And so I likely would have managed him with bland embolization and then somatostatin and then continue to watch. And I suspect he’ll be with you for at least 5 years and maybe a decade.

DR BENDELL: Knock wood. I hope so.

DR O’REILLY: And speaking to that, there is some data in hepatocellular cancer, a randomized Phase II study looking at bland embolization versus doxorubicin-eluting beads and no difference in outcome. And this is not the same disease, but at least in the disease where those modalities are frequently used, suggesting equivalency.

And that would be our thoughts as well, but maybe holding radioembolization for a frailer patient, just concerned about the longer-term toxicity of this and especially in somebody who you anticipate is going to do hopefully fairly well.

Colorectal cancer

Gastric cancer

Pancreatic cancer

Hepatocellular carcinoma

Gastrointestinal neuroendocrine tumors

Gastrointestinal stromal tumors