Hepatocellular Carcinoma Update, Issue 1, 2017 (Video Program)Case discussion: A 71-year-old man with chronic hepatitis B infection is diagnosed with Child-Pugh A cirrhosis and BCLC Stage C HCC
6:16 minutes.
TRANSCRIPTION:
DR EL-KHOUEIRY: This patient presented with abdominal pain and weight loss. He was not on surveillance, despite having known hepatitis B, noted to have elevated liver enzymes, AFP of 1,000. And the imaging showed a heterogeneously enhancing infiltrative mass measuring 6 centimeters with extension of the tumor. So this was tumor thrombosis into the right and left portal veins. This patient underwent a biopsy. And this is why I selected this case: This patient, when you look at his imaging studies, he did not meet the established imaging criteria for diagnosis of hepatocellular carcinoma, did not have the typical arterial enhancement with venous or delayed-phase washout. So a biopsy was done and it showed — DR LOVE: Could I just ask you, though, in the face of an AFP over 1,000, what else could he have had? DR EL-KHOUEIRY: He could have had colangiocarcinoma. There are reports of other liver tumors leading to an elevated alpha-fetaprotein, especially in the setting of hepatitis. So hepatocellular carcinoma, even sometimes metastases to the liver. DR LOVE: Really? DR EL-KHOUEIRY: AFP has been removed, actually, from the diagnostic criteria of hepatocellular carcinoma at this point. DR LOVE: Wow! Interesting. So metastatic disease to the liver can cause that? DR EL-KHOUEIRY: Right. I mean, we don’t normally check that. DR LOVE: Right. DR EL-KHOUEIRY: But yes, there are definitely reports of elevated alpha-fetoprotein in that setting. DR LOVE: Fascinating. DR EL-KHOUEIRY: So, biopsy showed poorly differentiated hepatocellular carcinoma. He had Child-Pugh A cirrhosis. Now this patient, we elected to treat him with first-line systemic therapy with sorafenib. The reason for that was that this patient had, really, BCLC Stage C disease — had a large tumor with invasion of both the right and left portal vein, so unlikely to respond to local-regional modalities. This was started in August 2013. And by imaging in October 2013 the patient had significant increase in the size of the mass, from 6 to 10 centimeters. And the alpha-fetoprotein went up to 25,000 along with worsening of the portal vein invasion. So this is a good example of definitive radiologic and clinical progression that led us to discontinue the sorafenib. So he was off therapy for a while. In December of 2013 he had enlarged abdominal lymph nodes. These met criteria as far as size and appearance that they represented extrahepatic disease, so now has extrahepatic documented disease — and then was placed on the clinical trial with nivolumab, and then achieved a partial response by February of 2014. And again, this is another reason I chose this case, to highlight that the objective responses with checkpoint inhibitors tend to occur most commonly within the first 3 months, the large majority of them. So this was a rapid radiologic response and clinical improvement as far as pain reduction, improvement in fatigue, et cetera. And the AFP decreased to below 100. DR LOVE: Wow! DR EL-KHOUEIRY: The patient stayed on this therapy until September of 2014, when there was progression based on a new lymph node measuring 1.4 centimeters. At that point, this was the only site of progression — he’s clinically doing well. So we kept going, again, as indicated with immunotherapy. He continued to be stable until January of 2015, when there was further increase in multiple lymph nodes. And at that point his pain began to recur, and discontinued treatment with nivolumab. DR LOVE: So then he was on treatment for — let me see how long. He started December 2013? DR EL-KHOUEIRY: Yes. So almost 13, 14 months. DR LOVE: And any tolerability issues that he had? DR EL-KHOUEIRY: This patient actually had no tolerability issues whatsoever. As he passed the 8, 9-month mark with nivolumab he began to report a little bit more fatigue for a few days after the infusion. But that was really it. DR LOVE: What happened after that? DR EL-KHOUEIRY: After that he went on another experimental therapy, Phase I clinical trial. DR LOVE: And did he pass away? DR EL-KHOUEIRY: No. This patient is still alive, actually. DR LOVE: Really? DR EL-KHOUEIRY: Yes. DR LOVE: So January 2015. It’s been 2 years since then. DR EL-KHOUEIRY: Right. He went on to 3 different Phase I trials after this. And actually this is a unique tumor because off therapy it does certainly progress. It even causes symptoms. But then it’s treatment-sensitive. It does respond to treatments — either stabilizes or responds — and then progresses again. So it’s certainly an outlier as far as how well this patient has done. DR LOVE: Do you think that, particularly these last couple of years, looking back, do you think it’s just the biology of his particular cancer, or do you think somehow the checkpoint inhibitors changed the biology of it? DR EL-KHOUEIRY: That’s a great question. This is an area that we’re starting to explore. It does seem that checkpoint inhibitors may change the tumor microenvironment and the host environment for these tumors and may alter how these patients respond to subsequent therapies or how their tumors behave even off therapy. I can tell you of some anecdotal experiences of patients who were removed from nivolumab for definitive progressive disease and who were off treatment, and I see them 6, 8 months later with stable disease again and who are doing well. This is something that we need to understand and invest more in understanding, but it’s a great question now. There’re a lot of hypotheses in this area. DR LOVE: I’m really surprised because when I saw the write-up, I figured you just didn’t put in the end. A lot of times that happens when people write up cases. Wow! That is really fascinating. |