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HCC: Candidates for Liver-Directed Therapies

Insights From: Richard S. Finn, MD, Geffen School of Medicine;Arndt Vogel, MD, Hannover Medical School
Published: Thursday, Nov 17, 2016


Transcript:

Arndt Vogel, MD:
If you think about liver-directed therapies, you can roughly distinguish two approaches. One is for patients that have smaller tumors. In general, tumors shouldn’t be larger or bigger than 3 cm. In those patients, we can use radiofrequency ablation or microwave ablation. We also used ethanol injection, specifically in patients with liver cirrhosis. This was quite effective, but the problem is if you have small micrometastases around these tumors, these patients are at risk to local recurrence. Therefore, and specifically if the tumors are larger, patients are treated with TACE. TACE is trans-arterial chemoembolization. So, the basic principle of this treatment option is to do an embolization of the tumor to cut the vessels and, with that, to induce a tumor necrosis. And this works really well in patients who have tumors that are bigger than 3 cm. It’s not really clear-cut at which point you shouldn’t do it anymore, but probably tumors that are bigger than 7, 8 cm will not respond, in most cases, very well to TACE. There are some patients that still might benefit from it, but, in general, tumors shouldn’t be too big and the liver function should be appropriate to use TACE in patients with HCC.

Richard Finn, MD: Chemoembolization plays a major role in the management of patients with liver cancer, especially those with liver-confined disease. There have been randomized studies that have confirmed the role for this approach, really in patients who have well-preserved liver function, who have a good performance status and tumor confined to the liver without significant liver cancer-related symptoms, and, importantly, patients who do not have significant involvement of the vasculature of the liver, specifically portal vein invasion or portal vein thrombus. That is an area of controversy, I think, in the setting of managing patients with chemoembolization. There are systemic therapies that have shown to improve survival in that group of patients. Certainly, patients often receive several chemoembolization procedures during their course of management, but once we see that the tumor is growing despite chemoembolization or that it’s transitioned from not invading the vasculature to invading the vasculature, those are all cues that a patient should probably be transitioned to systemic therapy. It’s where the data with chemoembolization are lacking. And what is critical for, I think, the optimal management of all these patients is that they get stage appropriate management. If someone develops characteristics of advanced stage disease, it’s important that they get an opportunity to receive systemic treatment.

Arndt Vogel, MD: Y-90 is increasingly used for the treatment of HCC. One problem we have here is that we do not really have prospective trials that have shown that we can achieve a survival benefit for our patients and that could really indicate in which patient population we should use Y-90 therapy. We do have a lot of retrospective single-center studies that give us an indication that it’s feasible, and we probably will not see too much toxicity, so we can use it in patients with HCC, even if they have underlying liver disease, more advanced liver fibrosis, or liver cirrhosis. But, as I said, we do not have prospective trials. And this is, probably, at the moment, the main problem we have here because we have seen a lot of promising phase II trials for systemic therapy and they never really translated in a survival benefit in larger phase III trials. So, this is something we clearly need. What we also know is with TACE, for example, we might induce a deterioration of liver function. The same could happen with Y-90. Therefore, the prospective trials are really important.

At the moment, most physicians most likely will use Y-90 in patients who have vascular invasion of the portal vein, for example, because, in contrast to TACE, we do not do an embolization here. It’s most likely safer than TACE in patients with portal vein infiltration and in patients who failed TACE, that are maybe not good candidates for systemic therapy. So, after TACE failure, a lot of physicians use Y-90 as a next therapeutic option.

Transcript Edited for Clarity
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Transcript:

Arndt Vogel, MD:
If you think about liver-directed therapies, you can roughly distinguish two approaches. One is for patients that have smaller tumors. In general, tumors shouldn’t be larger or bigger than 3 cm. In those patients, we can use radiofrequency ablation or microwave ablation. We also used ethanol injection, specifically in patients with liver cirrhosis. This was quite effective, but the problem is if you have small micrometastases around these tumors, these patients are at risk to local recurrence. Therefore, and specifically if the tumors are larger, patients are treated with TACE. TACE is trans-arterial chemoembolization. So, the basic principle of this treatment option is to do an embolization of the tumor to cut the vessels and, with that, to induce a tumor necrosis. And this works really well in patients who have tumors that are bigger than 3 cm. It’s not really clear-cut at which point you shouldn’t do it anymore, but probably tumors that are bigger than 7, 8 cm will not respond, in most cases, very well to TACE. There are some patients that still might benefit from it, but, in general, tumors shouldn’t be too big and the liver function should be appropriate to use TACE in patients with HCC.

Richard Finn, MD: Chemoembolization plays a major role in the management of patients with liver cancer, especially those with liver-confined disease. There have been randomized studies that have confirmed the role for this approach, really in patients who have well-preserved liver function, who have a good performance status and tumor confined to the liver without significant liver cancer-related symptoms, and, importantly, patients who do not have significant involvement of the vasculature of the liver, specifically portal vein invasion or portal vein thrombus. That is an area of controversy, I think, in the setting of managing patients with chemoembolization. There are systemic therapies that have shown to improve survival in that group of patients. Certainly, patients often receive several chemoembolization procedures during their course of management, but once we see that the tumor is growing despite chemoembolization or that it’s transitioned from not invading the vasculature to invading the vasculature, those are all cues that a patient should probably be transitioned to systemic therapy. It’s where the data with chemoembolization are lacking. And what is critical for, I think, the optimal management of all these patients is that they get stage appropriate management. If someone develops characteristics of advanced stage disease, it’s important that they get an opportunity to receive systemic treatment.

Arndt Vogel, MD: Y-90 is increasingly used for the treatment of HCC. One problem we have here is that we do not really have prospective trials that have shown that we can achieve a survival benefit for our patients and that could really indicate in which patient population we should use Y-90 therapy. We do have a lot of retrospective single-center studies that give us an indication that it’s feasible, and we probably will not see too much toxicity, so we can use it in patients with HCC, even if they have underlying liver disease, more advanced liver fibrosis, or liver cirrhosis. But, as I said, we do not have prospective trials. And this is, probably, at the moment, the main problem we have here because we have seen a lot of promising phase II trials for systemic therapy and they never really translated in a survival benefit in larger phase III trials. So, this is something we clearly need. What we also know is with TACE, for example, we might induce a deterioration of liver function. The same could happen with Y-90. Therefore, the prospective trials are really important.

At the moment, most physicians most likely will use Y-90 in patients who have vascular invasion of the portal vein, for example, because, in contrast to TACE, we do not do an embolization here. It’s most likely safer than TACE in patients with portal vein infiltration and in patients who failed TACE, that are maybe not good candidates for systemic therapy. So, after TACE failure, a lot of physicians use Y-90 as a next therapeutic option.

Transcript Edited for Clarity
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