Case 1: Combining Systemic and Locoregional Therapies in HCC


Centered on the patient case of solitary hepatocellular carcinoma, panelists consider the combination of locoregional and systemic therapies to improve outcomes.


Aparna Kalyan, MD: We’re seeing more of this with the question of how we combine systemic therapy and locoregional therapy. Dr George, as oncologists, we’re always a little late to this game. Historically, this has been managed a lot by radiology and hepatology. How would you approach this in your clinic if somebody came in to see you?

Ben George, MD: This is a gray area, as my colleagues have alluded to and as you brought up. Five or 6 years ago, options for us medical oncologists were so limited, and now we have much more to offer. Particularly in a disease where the entire liver is at risk and where there’s characteristic suggestive aggression, a reasonable case can be made for combining systemic therapy with some locoregional therapy. In what sequence we go after it needs to be discussed medically. If there’s some locoregional therapy being administered, do we go ahead with systemic therapy soon after that? If that’s the case, what do we follow with to see if there’s any efficacy for the systemic therapy? Or should we start with systemic therapy and then bring in locoregional therapy after assessment of disease biology over time? Those are all important questions.

Ultimately, we’re looking at a snapshot in time where we see a tumor that’s over 4 cm with suspicious portal vein invasion. We don’t know how much time it took for the tumor to get there or the inherent biology of that tumor. Ultimately that’s going to dictate how successful we are in whatever approach we take. But certainly, with portal vein innovation, a reasonable case can be made for bringing in systemic therapy. What do you think, Dr Kalyan?

Aparna Kalyan, MD: You’re right. I always say that I felt like Serafina was a cat with 9 lives that never seemed to go away, but things are changing with some of the things we have now. It’s a great point about combining some of the newer therapies we have with the great systemic locoregional options. And, we understand the disease biology and consider things we may not have been able to in the past, including resection and transplantation for some patients.

Dr Kim, I want to see what your thoughts are. If you can, comment on a locoregional therapy in this setting. I know that the portal vein invasion is not ideal in terms of how we would approach it from a locoregional therapy, but perhaps we can talk a little about how this case would play out if we did not have the portal vein invasion?

Edward Kim, MD: Absolutely. Given the size of this tumor, which is within the Milan criteria, the drinking becomes an issue in terms of the transplant. But at our institution [Mount Sinai Hospital], we would try, especially in the setting of a higher AFP [alpha-fetoprotein], to push for a transplant and to assess the tumor biology over a period of time. Because with the T2 priority patients are going to have to wait a minimum 6 months to assess that. And with the higher AFP, they probably want to assess it longer. With the implementation of the acuity circles across the country, we’re seeing much longer transplant wait times. Here in New York, we’re looking at close to 2 years for individuals. Let’s say they’re not a positive blood type. They’re looking at that 2-year mark, so we want a durable locoregional therapy because while the patient may wait for that transplant, the tumor certainly will not. With the size and location, ablation isn’t the best option. Certain institutions don’t prefer ablation for risk of hemorrhage. We’d go with radioembolization in this setting.

Recently, the legacy study was published in Hepatology that supports the use of radioembolization, especially with a solitary HCC [hepatocellular carcinoma]. It’s a technique called radiation segmentectomy in which we try to aim for a less than 2-node segment and deliver a very high dose of radiation. We’ve seen through that study, which is multi-institutional—88 with objective response but 84 with complete response—and then a very sustained duration of response in that patient cohort. That’s the reasoning for us to do a transarterial radioembolization in this type of setting.

Aparna Kalyan, MD: Dr Mantry, I’m curious: from a surgical standpoint, does a patient receiving Y90 affect any decision-making process that you have when you think about surgery down the line?

Parvez Mantry, MD: That’s a great question. Fortunately, it doesn’t. Y90 is fairly favorable to both surgical resection as well as transplant to these patients. This is a very fascinating case, and if I presented this case in tumor board 2 years ago, I would have said first-line therapy Y90. Oftentimes, we even do SBRT [stereotactic body radiotherapy] to the segment of the portal vein and have great results. Then we put them on chemotherapy. There’s no question in my mind that this patient should get chemotherapy because of the vascular invasion, which means there’s already an AFP of more than 400 ng/mL. Oncological advances have been amazing, and I would be torn between starting this patient on Tecentriq [atezolizumab] and Avastin [bevacizumab] and then doing Y90 and continuing the systemic immunotherapy with the Avastin or another I/O [immuno-oncology]–CTLA4 combination. This field has radically changed.

Aparna Kalyan, MD: To close this case out, at our institution [Robert H. Lurie Comprehensive Cancer Center of Northwestern University], we’d probably approach this—having seen the portal vein involvement—by starting with systemic therapy, possibly Y90. It’s a multidisciplinary discussion. We continue the systemic therapy. Based on response, we consider resection or additional options down the line. Would you concur from an academic setting that you would do something along those lines?

Ben George, MD: I think so. There isn’t 1 right way to approach this. He’s not a very old man. He doesn’t have a lot of comorbid conditions. He still drinks, and that could be a problem. But if transplant is going to be an option down the road, then we ought to be careful what systemic therapy we utilize in this setting. This may be 1 situation where you could say, pragmatically, should we give this person liver-directed therapy and see what happens, and see how the biology plays out. If the biology isn’t favorable, not much lost. Why not start with systemic therapy at that point? Alternatively, if we start with systemic therapy, maybe we do a TKI [tyrosine kinase inhibitor] instead of an I/O combination. That way, we leave options open down the road. We bring in liver-directed therapy later depending on biology. But all those sequences need to be carefully discussed with the patient, recognizing the patient’s priorities.

Transcript edited for clarity.

Related Videos
Rohit Gosain, MD; Rahul Gosain, MD; and Pamela L. Kunz, MD, presenting slides
Related Content