What are the principal treatment options for this patient with recurrent uHCC?

So this is a fairly typical patient we would see in the office. This is a gentleman who&rsquo;s had chronic hepatitis B probably his whole life. We can see that from the family history, as well, that they&rsquo;ve had a history of hepatitis B and liver cancer related to that. Unfortunately, this patient has not been in a screening program even though they have a family history of hepatitis B. This lesion is being found quite late. From the case, we see he is presenting with a fairly large lesion, a 12 cm lesion in the liver which is symptomatic. He&rsquo;s having some pain. His performance status is 1. The diagnosis of this cancer can be made radiographically given the underlying history of hepatitis B, and if imaging were to suggest a hypervascular lesion, a biopsy would not be required.

The other data we have in this case is that he is well compensated. Again, not so uncommon with hepatitis B is we do see liver cancer before the development of overt cirrhosis and decompensated liver disease. It&rsquo;s a little different than patients with hepatitis C. I think, for many of us, when we see a patient with a newly diagnosed liver cancer that&rsquo;s confined to the liver, from the data we have, there&rsquo;s no evidence of disease outside of the liver, there&rsquo;s no mention of vascular invasion, that this patient would be reviewed at a multidisciplinary tumor board with the possibility of a surgical resection. Resection offers the only chance of cure for this disease or transplant, for that matter, but he is well beyond any transplant criteria. And while the lesion is large and the chance of recurrence after a resection is higher with a larger lesion, I think still many surgeons, if the patient was an operable candidate, would consider them for a resection even though the chance of cure in this specific case might be considerably low.

But, as we learn from the case, he has a disease burden that is not resectable or he has some other physiologic reason he can&rsquo;t be resected, always keeping in mind liver cancer is two diseases. It&rsquo;s a malignancy and complications of liver disease.

Richard Finn, MD: Principal Treatment Options for a Patient with Recurrent uHCC 

How does interventional radiology (IR) figure into the local/regional therapy of this patient with uHCC?

So he has a liver confined tumor, and it&rsquo;s very reasonable to consider local regional therapy. Strictly speaking by the Barcelona Criteria, this patient might be considered Barcelona C, given that they have performance status of 1 and symptomatic disease. But, again, it is confined only to the liver and local regional therapy, I think, would be considered by many physicians and multidisciplinary tumor boards as something to consider.

So, as we learn, the patient undergoes a chemoembolization procedure. The majority I think of the patients we see in managing this disease do present with disease that is treated with local regional therapy. In that regard, interventional radiology is a key component of any multidisciplinary tumor board. As we learn in this case, the patient had a chemoembolization. Chemoembolization has been shown to improve survival in patients with organ confined disease, though typically a patient with this size tumor would have been excluded from the randomized prospective studies that showed a survival benefit with TACE. But, needless to say, they undergo local regional therapy and we learn on follow up imaging that there&rsquo;s residual disease and perhaps some residual satellite lesions or even new lesions.

The question is what do we do next for this patient. I think seeing a 12 cm lesion on a scan and in sending that patient for local regional therapy, most of us would not expect them to have a complete response to one round of TACE. A lesion this size likely would require more treatment. The question here is should we do another TACE or move on to another treatment option. Keep in mind in the United States largely TACE is not done with a predetermined number of TACE. Again, that is different from the prospective randomized studies that evaluated TACE, typically had a pre-described sequence of chemoembolization regardless of response to the first TACE. But, often, in the United States, we&rsquo;ll do a TACE, get some imaging a few weeks later and if there&rsquo;s residual disease, proceed with a second, or third, or fourth TACE, etcetera.

I think given the findings on this patient, assuming they&rsquo;re still good performance status and medically amenable to a TACE, then it would be reasonable to consider a second TACE. The one red herring here in this case is the fact that it&rsquo;s possible they have progression with new nodules. It sounds like they&rsquo;re small and maybe indeterminate, then in that regard we could give them the benefit of the doubt and consider another chemoembolization and repeat imaging after.

Richard Finn, MD: Interventional Radiology and Local/Regional Therapy 

Would you consider using Selective Internal Radiation Therapy (SIRT) in this patient (i.e., Yttrium-90 spheres)?

The new local regional therapy on the block is radioembolization. Yttrium-90 is being used more and more. In reality, the data supporting the use of Y-90 is somewhat limited. There is a lot of single arm phase II type of data, and there are numerous phase III randomized studies that are ongoing. These will be very important studies to read out, and some of them are in combination with sorafenib as well which would probably include a patient like the one we&rsquo;re talking about. Y-90 has not been shown to be superior to chemoembolization.

There is perhaps some toxicity benefit to Y-90, specifically in cases of portal vein thrombosis. But, at this time, I think most places would pursue with chemoembolization, given the large amount of data. Second to that would be consideration of systemic therapy, and Y-90 is, I think, an institutional preference if it is used.

Richard Finn, MD: Use of Selective Internal Radiation Therapy in a uHCC Patient 

Would you consider systemic therapy in this patient?

I think my sense in the way this case is going, this patient is going to require systemic treatment. In regards to that, the only agent that&rsquo;s been proven to extend survival is sorafenib. And this paint would be a candidate for sorafenib from the beginning, from the presentation given they had symptomatic disease. It&rsquo;s confined to the liver which is a group of patients that seem to get a greater benefit from sorafenib versus those who had more advanced disease.

This is in retrospective subgroup analysis of the SHARP study or they should be referred for a clinical study that would also be an acceptable option for systemic treatment in this patient. When to start systemic treatment is not written in stone. Again, that could have done at the presentation. It could be considered after the first TACE, but, again, whether it&rsquo;s done after the first TACE or second TACE, my sense, given the large nature of this tumor, the fact that it sounds like they have progression outside of the larger lesion, this patient will soon require systemic therapy.

It&rsquo;s also important to keep in mind, for most patients who get chemoembolization, if they don&rsquo;t die of their underlying liver disease or something else, they will eventually progress beyond disease that can be controlled with chemoembolization. They&rsquo;ll develop portal vein thrombosis, clear progression outside of the liver, or even recurrence in a prior chemoembolization site.

Richard Finn, MD: Systemic Therapy in a uHCC Patient 

What are the principle treatment options for this patient with recurrent uHCC?

The treatment choices for patients who have recurrent, unresectable HCC once again largely depend on the degree of tumor burden when they have recurrence. If you have a small degree of tumor burden, you're actually within transplant criteria and that would actually be the ideal solution. It not only treats the underlying HCC but also the liver disease, and thus offers a cure rate of 60% to 70% at 5 years. This is the best long-term solution for HCC.

Amit Singal, MD: Principal Treatment Options for a Patient with Recurrent uHCC

Amit Singal, MD: Interventional Radiology and Local/Regional Therapy 

This is actually a big debate in the field in terms of when you should use chemoembolization and when you should use radioembolization. Unfortunately, there are very few studies that can really guide the choice between chemoembolization and radioembolization. The only studies that we have comparing the two are non-randomized, so there is inherent selection bias in terms of who receives chemoembolization versus who receives radioembolization. Overall, when you look at the data, I think the data suggests they're both pretty equivalent in terms of effectiveness, but chemoembolization has a much stronger evidence base behind it.

The other thing that we notice is that patients may tolerate radioembolization better than chemoembolization with lower rates of post-embolization syndrome. Without high-quality data to guide us in terms of the choice between chemoembolization and radioembolization, you see a large variation in terms of practices across the country. It's very interesting, because some people who have localized disease that is small in nature will be treated routinely with chemoembolization, whereas if that patient was seen down the street, they would be routinely treated with radioembolization for that very same cancer in that very same patient. Really, it's just a matter of which center you're seen in and the local expertise.

At our center, we tend to use radioembolization for patients who have a larger tumor burden where you're afraid that either they're going to have significant post-embolization syndrome, or that you're not going to get a very good effect from chemoembolization. Radioembolization can definitely be considered in this person, it's just that we don't have great data comparing it to the effect of chemoembolization.

Amit Singal, MD: Use of Selective Internal Radiation Therapy in a uHCC Patient

The only systemic therapy that is currently approved is sorafenib. Sorafenib's indication is really for patients that have unresectable HCC. So within the FDA approval, this patient could be treated with systemic therapy. However, when you look at the data comparing systemic therapy to locoregional therapy, the survival benefit you appear to get from locoregional therapy appears to be better than with sorafenib. That being said, there is no randomized data comparing sorafenib to locoregional therapy in these patients, so there is an inherent selection bias of who's undergoing locoregional therapy and which patients are undergoing systemic therapy.

Unresectable Hepatocellular carcinoma with Amit Singal, MD and Richard Finn, MD: Case 1