Case 3: 68-Year-Old Man With Borderline Resectable HCC

EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Riad Salem, MD:This case is a 68-year-old man who presented with vague intermittent right-upper-quadrant pain with some weight loss, anorexia, and fatigue over a long period of time. The patient has a significant past medical history of high blood pressure and diabetes, elevated cholesterol, and treated hepatitis C. In terms of social history, there’s a remote history of IV [intravenous] drug abuse and moderate alcohol and tobacco use. On physical examination, there’s abdominal discomfort and tenderness, ascites, and lower extremity edema.

The ultrasound demonstrates multiple focal liver nodules and enlarged liver. As is appropriate, the patient had a CT [computed tomography] scan that revealed multiple hepatic lesions, ranging from 3.2 cm to 4.5 cm, and metastatic work-up is negative, so there’s nothing outside the liver. The liver function in terms of bilirubin is maintained. Albumin is slightly low at 3.0 g/dL, and the platelet count is also low at 102,000 m³. INR [International normalized ratio] is 1.0. When tested for chronic liver disease, this was a Child-Pugh A patient, but by staging is BCLC [Barcelona Clinic Liver Cancer] stage B. This person has a diagnosis of hepatocellular carcinoma with an inoperable condition at this point, based on tumor burden. And the patient underwent 3 cycles of chemoembolization with ultimately a complete response. However, unfortunately, he ultimately suffered worsening ascites and decreasing liver function, again deeming the patient as a noncandidate for future treatment with chemoembolization.

Ghassan Abou-Alfa, MD, MBA:Not good. I give you credit for bringing your case for discussion among all of us. It’s not necessarily something that we sometimes see. We don’t like to see this. But where do you think really things went wrong? How did we get this patient to get to that level of poor liver function?

Riad Salem, MD:I think everything in terms of the work-up, the evaluation, the diagnosis, and the staging was fine. I think the patient was discussed at multidisciplinary tumor board. But I think, as I mentioned before, the reality is that no patient should be managed with locoregional therapy or any of these therapies in isolation of 1 subspecialty. In reality, we do 1 chemoembolization, we assess response, we look at the liver function, and we repeat. And if we’re doing well and the patient is tolerating it, we continue to do so. I think, not having images to really look at this, hopefully they treated everything and they did it with a complete response. And presumably after the second chemoembolization liver functions were maintained, which supported the third chemoembolization, which I believe is why they did it.

But one has to remember that these patients have 2 conditions. They have the tumors, they have cancer, but they also have cirrhosis. When that decomposition will occur is unfortunately unpredictable. This is what happened with this patient. Again, I think the recurring theme here is patients are managed in a team, and that includes managing and monitoring the liver functions. It’s not in isolation, and it’s not 1 subspecialty that manages the patient.

Ghassan Abou-Alfa, MD, MBA:No, I totally agree. Amit, teach us a little here from the liver function perspective. If you can put on your hepatology hat, is there anything that could have been done better or differently to preserve liver function?

Amit Singal, MD:Yes. I think there are a couple of things. The good news is that he was actually treated for his hepatitis C before. Actually, you take away that as another insult to the underlying liver function. As we had mentioned, unfortunately, we don’t have images to take a look at, but it says multiple hepatic lesions ranging from 3.5 to 4.5 cm. I think it matters where those liver lesions are and exactly how many we’re talking about. But I think the thing we do realize is that if you have extensive multifocal disease, even if it’s liver localized, some of those patients may be better treated with systemic therapy up front rather than locoregional therapy. I think as a team, we have to be more cognizant that this is a real risk sometimes when we’re “overly aggressive” with locoregional therapy. So I think it’s considering systemic therapy sometimes in these patients with multifocal disease earlier.

Then as Riad mentioned, I think it’s really following that patient through the course. And so the question is, was this a slowed window where basically after each chemoembolization, we saw the liver function get worse but the patient was still re-treated? Or did they actually have stable disease for the first 2 and then have a big hit after the third one where we saw a sharp decline in the liver function?

The other thing that we do is talk routinely with our interventional radiologists. When they’re doing the chemoembolization, if they then say, “Look, I can treat the liver lesions but you’re going to have a high risk of liver dysfunction because there’s going to be a lot of off-target effects,” we then will actually say it’s probably better not to treat them with the chemoembolization even though they’re already in there. We say it’s better to stop and to transition to systemic therapy at that time. I think Riad hit on the important points of constant communication between the full team, not just with the tumor board as you’re going through the treatments.

Riad Salem, MD:Can I just add 1 other thing, as Amit mentioned? Again, while technically this person is BCLC stage B, and the textbook tumor recommendation is chemoembolization, there’s a wide spectrum of what BCLC stage B looks like. It’s amazing that you can have actually very limited disease and be just outside transplant criteria and be BCLC stage B—where you can do a couple of selective chemoembolizations—all the way to multifocal bilobar disease, which is also multinodular BCLC stage B. There’s a spectrum there that people don’t recognize. Based on the data I’m seeing, in combination with all the systemic agents that are available, early stage B patients are still in the wheelhouse of locoregional therapies. But later stage B situations are clearly things that we need to be careful of, because as Amit mentioned, for me to treat the entire liver, I need much more than 2 chemoembolizations; hence you can go on to systemic therapy.

Amit Singal, MD:When you look at the data for locoregional therapy, they really are more so on the early stage B patients than the midstage B patients.

Riad Salem, MD:That’s correct.

Amit Singal, MD:So really, there are very limited data for locoregional therapy on the stage B patients who are more like a stage C patient. It’s just like the Child-Pugh class, when you said it’s a spectrum. And we’re finding the same thing is true for the BCLC staging.

Transcript edited for clarity.