DR BENDELL: This was a gentleman who I saw in clinic. He was originally diagnosed with hepatitis C in 2000. That was found incidentally when he was hospitalized for cellulitis. He did not have any follow-up with GI but then started to get follow-up again in 2011 when he came into the emergency room with chest pain. And when he came in with that, they did a CT angiogram, which didn’t show a PE but showed some indeterminate liver lesions in his cirrhotic liver.

And so then he started to have more significant follow-up. And they continued to follow these indeterminate lesions. AFP was normal. Nobody could really make a call. He was MRI’d on whether or not this was tumor. And unfortunately, I’ve heard this story all too many times. And then finally, in 2012, he had an MRI, which showed now definitive liver lesions that looked like HCC. And AFP at the time was still normal, but he also had portacaval adenopathy at that point.

DR LOVE: So just one point, Charlie, in terms of this issue of biopsy: If this patient had an elevated AFP, would you still have gone for a biopsy? In what situations will you treat without tissue?

DR FUCHS: Our center, in general, tries to get tissue, because we try to do research on this, but moreover because our clinical trials for the most part insist. And this is a disease where we really do push to get people onto clinical trials. So, whenever possible, we get a biopsy.

There are criteria by which with an elevated AFP and in the appropriate clinical setting and radiographic setting you can make this diagnosis or at least surmise the diagnosis. But this patient had a normal AFP, so a little trickier.

DR BENDELL: Yes.

DR LOVE: So Philip, how would you be thinking through this situation in terms of type of treatment to use?

DR PHILIP: This patient has multiple lesions. My guess is that you felt he’s not a transplant candidate or —

DR BENDELL: Correct.

DR PHILIP: Yes. He not a transplant candidate. So the question is, is he a candidate for liver-directed therapy or not? Your concern about the portacaval nodes, my understanding is that they may well be borderline, which we don’t know if it’s inflammatory or real. He’s a 61-year-old, otherwise good performance status — reasonable performance status and Child-Pugh A?

DR BENDELL: Yes. Sorry. B7.

DR PHILIP: B7. So that’s an early B. And in this patient I would probably consider first the liver-directed therapy. And the point to make here is that we don’t want to confuse the community, because although we have our own preferences in my institution, I agree. I do radioembolization, but the reality is that there’s no head-to-head comparison between these different modalities. We heard Eileen talk about bland embolization, which is probably the cheapest, also, and the easiest to do. And we do radioembolization. But there’s also the TACE and also there’s the drug-eluting beads, which allows you to do it more — also in patients who have some degree of portal vein thrombosis.

And in my practice, this patient, I will consider liver-directed therapy, and I would go for radioembolization, which is probably the one which I’m most comfortable with. And I will keep an eye on the aortic caval nodes.

In terms of the biopsy, background chronic liver disease, we have multiple hypervascular lesions on an MRI. You may need another modality to prove it’s hypervascular. And I can forego the AFP, which is not really mandated as part of the diagnosis. And if I’m not going to put the patient on a clinical trial, I’m not going to do a liver biopsy necessarily. We don’t have an in-house research program, so that I need the tissue for.

DR LOVE: I’m curious, Eileen. We were talking about this issue of liver-directed therapy versus systemic therapy for sorafenib. In that broad context, what would you think about for this patient? What specifically do you think you most likely would do?

DR O’REILLY: Yes. I think it’s a discussion, because both options are on the table. He has reasonable liver performance status, maybe has a little bit of higher risk for liver-directed therapy with B7 but probably would tolerate it. And I think you could make a justifiable argument for systemic therapy here. There’s no head-to-head comparison in this setting. And, actually, we have some data suggesting that actually maybe doing both, not necessarily together, but in the longer — over time, may lead to improved outcome. So I think that’s a very provocative question that needs to be defined more clearly.

And a lot of, I think, our decision-making actually comes from referral patterns into how the patient gets to us. So they see the interventional radiologist first, whether they see medical oncologist or transplant physician, I think that guides a lot of the decision-making.

DR LOVE: Yes. I was thinking about that, Randy, when you were talking about the interdisciplinary approach, because sometimes I think there’s a little bit of a turf issue that comes up, as Eileen was alluding to, who sees the patient first. Is that something that you’ve observed? And how do you determine — this patient has liver-only disease.

DR HECHT: Like Rich, I actually don’t see HCC patients. And so I do go to the multidisciplinary — no. The reason is because we present those also, the patients who have colon cancer and neuroendocrine tumors, who are going to get liver-directed therapy. So I’ve heard a lot, but I actually don’t treat very many of these patients.

But I think your point is actually very well taken, which is that I think that there are turf battles. And hopefully in a multidisciplinary setting, that those, at least, get sorted out from — at least there’s one approach for an institution. I don’t say it’s necessarily the right approach, because there is no absolute right approach. But I think that usually what’ll happen is, within an institution, there’ll be practice patterns that people follow.

On the other hand, you’re right. If someone gets sent just to an interventional radiologist by the oncologist or just to the oncologist, may say, “Gosh, I don’t know much about this, but I do know about sorafenib.” They may never even see someone else. So as I said, I sit back as a fly on the wall and see these patients. And a lot of it also has to do with what the hepatologists tell us about how they feel the liver is going to do after liver-directed therapy. I think that’s another reason why it’s important to have them involved as much as possible. And all these patients are seen even, often they’re referred by hepatologists, but they’re also seen by our hepatologist as well.

DR LOVE: So what actually happened with this patient?

DR BENDELL: So his portacaval adenopathy was just a little bit more pronounced, and I should have given you more of a size measurement on it. So we actually went in and biopsied the portacaval adenopathy, which came back with metastatic HCC. And because of that, like Eileen’s saying, we’re tossing between liver-directed therapy versus systemic therapy. And unfortunately, with the B7, I couldn’t get him onto study, which would be my ultimate preference. So we went ahead and elected to go with sorafenib. So we started him on sorafenib, 400 BID. And within 2 weeks, he came back with a Grade II hand-foot syndrome and Grade II fatigue.

DR LOVE: So maybe you can just bring us up to date.

DR BENDELL: Yes. So we held him, and then we restarted him at 200 BID. And he’s been tolerating that since.

DR LOVE: So Eileen, what about this issue of dosing? Would you have started him off at the full dose? And what do you think about what happened here?

DR O’REILLY: Yes. So it’s a good point, though there’s no clear data to guide us. But with B7, be concerned about his tolerability both from his liver function perspective and, perhaps, heightened other toxicities. So probably we would have punted and started with 200 BID, and then going up if he tolerates this. We have some data from the formerly CALGB cooperative group, which looked at sorafenib in the setting of liver dysfunction, which helped define what the dosing might be, but not particularly a population of patients with hepatocellular cancer and underlying liver dysfunction. So it’s not exactly analogous, but that’s one of the approaches that’s used to guide the dosing.

DR LOVE: So every time we go into a tumor that we haven’t done before, I have to kind of remember again. When you guys said “B7,” I’m like, “What’s B7?” Oh. Now I remember. Child-Pugh. So can you talk a little bit about what we do know about the toxicity and dosing of sorafenib based on the exact Child-Pugh of B7 versus 8, for example?

DR O'REILLY: So the original SHARP study was conducted in Child-Pugh A patients, so the fit of the fittest. And there, the expected toxicities would be skin, primarily, and hand-foot, fatigue, sometimes some diarrhea and sometimes other in terms of bleeding, et cetera, but they’re the main toxicities encountered.

With increasing bilirubin, there is increased toxicity from sorafenib and hence the need to dose adjust, but the criteria are not very clear in terms of what those absolutes should be. But typically we start conservatively for people with B7 level of Child-Pugh function and dose escalate as tolerated. And for many, we probably wouldn’t dose escalate much.

Colorectal cancer

Gastric cancer

Pancreatic cancer

Hepatocellular carcinoma

Gastrointestinal neuroendocrine tumors

Gastrointestinal stromal tumors