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HCC: Role of Radiotherapy and Measuring Response

Insights From: Catherine T. Frenette, MD, Scripps Green Hospital; Darren S. Sigal, MD, Scripps Green Hospital
Published: Tuesday, May 08, 2018



Transcript: 

Darren S. Sigal, MD: Dr Frenette, I’d like to discuss a little bit about the role of radiotherapy in treating hepatocellular carcinoma, whether it’s Y-90, SIR-Spheres, TheraSphere therapy, or external beam radiation. Can you comment on the appropriate setting and how you make a decision in terms of what modality you choose?

Catherine T. Frenette, MD: Absolutely. Radiation therapy, historically, was avoided in liver cancer because the liver was not very tolerable to radiation. But as our radiation treatments have gotten better and more precise, it has actually reemerged as a treatment option. So, Y-90 is a treatment that often we will use. It is not included in the BCLC [Barcelona Clinic Liver Cancer] guideline recommendations for treatment for liver cancer because we don’t have a large randomized controlled trial proving a survival benefit. That’s why it’s not yet in the guidelines for treatment. That being said, I do think there are times that Y-90 is appropriate. We find it to be very helpful for patients who have multiple small lesions, especially if it’s in 1 lobe of the liver. With Y-90, you don’t have to aim as much as you do with TACE [transarterial chemoembolization].

So, with TACE, we really try to get subselective and just treat the lesion itself. With Y-90, they infuse the radiation beads into one lobe of the liver and then the increased blood flow to the tumor draws the beads to the tumor, and that’s how that works. You can actually treat one lobe and then come back a month later and treat another lobe. It’s good for multiple lesions or patients with branch portal vein invasion or thrombosis, where doing a chemoembolization and causing arterial-stasis can actually cause a hepatic infarction.

We also are using more external beam radiation for liver cancer. There are several different ways to do radiation therapy for liver cancer, as long as you try to minimize the liver. As long as you ensure that you have enough liver that is not treated by radiation, that patient should do quite well. In general, that’s considered about 700 cc of liver, although if they have cirrhosis, they may need a little bit more. So, we will often do radiation in combination with chemoembolization. I think of it and explain it to the patients as we do the chemoembolization, we feel like we have a good response but we know there are still cells in there that are alive, and we come back with radiation to sort of mop it up afterwards. We also have combined chemoembolization with other treatments as well, such as ablation or occasionally ethanol. And there are data that combination modalities may actually result in longer disease control and better complete responses on radiology.

The external beam is also very helpful for patients where the tumors are not accessible via arterial therapies. For instance, if you have tumors on the dome of the liver or near the gallbladder, often times you’ll get pericytes vessels, say, from an intercostal artery that will feed the tumor and you can’t get arterial therapies to that tumor. And external beam is a great way to go and deliver some treatment without having to depend on the blood flow.

Darren S. Sigal, MD: Once you treat the patient, how do you measure response? What time interval do you wait to reimage? Are you looking for tumor shrinkage or decreased vascularization?

Catherine T. Frenette, MD: After somebody gets chemoembolization or ablation, we generally do an imaging test, whether it’s a CT [computed tomography] or an MR [magnetic resonance]. We do that about a month after the treatment. And the reason that we do that is because with TACE and ablation, you really should see lack of enhancement within that first month. If you do it sooner than that, you may see some treatment changes that are difficult to interpret, whether it’s cancer or treatment changes, just because they’re still getting over the actual treatment. We’re looking for a zero enhancement. So, there are different ways to measure response in cancer therapy. Oncologists are very used to RECIST [Response Evaluation Criteria in Solid Tumors] where you’re actually looking for shrinkage. Well, liver cancer, we don’t really see shrinkage so much as we do see a decrease in enhancement. We use something called modified RECIST [mRECIST], where we’re actually looking at the arterial enhancement and using that to count as alive. So, somebody who has got a 5 cm tumor that undergoes a chemoembolization and the follow-up scan shows a 5 cm hole with no enhancement, that’s considered a complete response by mRECIST, whereas with by RECIST, that would be considered stable disease because it’s still a 5-cm lesion.

Y-90, or external beam radiation, has responses that are more difficult to interpret. They don’t lose the enhancement the same way, so you generally see with radiation whether it’s internal or external. Rather than seeing lack of enhancement right away, you’ll see either slow lack of enhancement or slow shrinkage. But you really aren’t going to see your maximum effect until the patient is about 6 months out from their radiation treatment. So, you have to be more patient when assessing response in those patients.

Transcript Edited for Clarity 
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Transcript: 

Darren S. Sigal, MD: Dr Frenette, I’d like to discuss a little bit about the role of radiotherapy in treating hepatocellular carcinoma, whether it’s Y-90, SIR-Spheres, TheraSphere therapy, or external beam radiation. Can you comment on the appropriate setting and how you make a decision in terms of what modality you choose?

Catherine T. Frenette, MD: Absolutely. Radiation therapy, historically, was avoided in liver cancer because the liver was not very tolerable to radiation. But as our radiation treatments have gotten better and more precise, it has actually reemerged as a treatment option. So, Y-90 is a treatment that often we will use. It is not included in the BCLC [Barcelona Clinic Liver Cancer] guideline recommendations for treatment for liver cancer because we don’t have a large randomized controlled trial proving a survival benefit. That’s why it’s not yet in the guidelines for treatment. That being said, I do think there are times that Y-90 is appropriate. We find it to be very helpful for patients who have multiple small lesions, especially if it’s in 1 lobe of the liver. With Y-90, you don’t have to aim as much as you do with TACE [transarterial chemoembolization].

So, with TACE, we really try to get subselective and just treat the lesion itself. With Y-90, they infuse the radiation beads into one lobe of the liver and then the increased blood flow to the tumor draws the beads to the tumor, and that’s how that works. You can actually treat one lobe and then come back a month later and treat another lobe. It’s good for multiple lesions or patients with branch portal vein invasion or thrombosis, where doing a chemoembolization and causing arterial-stasis can actually cause a hepatic infarction.

We also are using more external beam radiation for liver cancer. There are several different ways to do radiation therapy for liver cancer, as long as you try to minimize the liver. As long as you ensure that you have enough liver that is not treated by radiation, that patient should do quite well. In general, that’s considered about 700 cc of liver, although if they have cirrhosis, they may need a little bit more. So, we will often do radiation in combination with chemoembolization. I think of it and explain it to the patients as we do the chemoembolization, we feel like we have a good response but we know there are still cells in there that are alive, and we come back with radiation to sort of mop it up afterwards. We also have combined chemoembolization with other treatments as well, such as ablation or occasionally ethanol. And there are data that combination modalities may actually result in longer disease control and better complete responses on radiology.

The external beam is also very helpful for patients where the tumors are not accessible via arterial therapies. For instance, if you have tumors on the dome of the liver or near the gallbladder, often times you’ll get pericytes vessels, say, from an intercostal artery that will feed the tumor and you can’t get arterial therapies to that tumor. And external beam is a great way to go and deliver some treatment without having to depend on the blood flow.

Darren S. Sigal, MD: Once you treat the patient, how do you measure response? What time interval do you wait to reimage? Are you looking for tumor shrinkage or decreased vascularization?

Catherine T. Frenette, MD: After somebody gets chemoembolization or ablation, we generally do an imaging test, whether it’s a CT [computed tomography] or an MR [magnetic resonance]. We do that about a month after the treatment. And the reason that we do that is because with TACE and ablation, you really should see lack of enhancement within that first month. If you do it sooner than that, you may see some treatment changes that are difficult to interpret, whether it’s cancer or treatment changes, just because they’re still getting over the actual treatment. We’re looking for a zero enhancement. So, there are different ways to measure response in cancer therapy. Oncologists are very used to RECIST [Response Evaluation Criteria in Solid Tumors] where you’re actually looking for shrinkage. Well, liver cancer, we don’t really see shrinkage so much as we do see a decrease in enhancement. We use something called modified RECIST [mRECIST], where we’re actually looking at the arterial enhancement and using that to count as alive. So, somebody who has got a 5 cm tumor that undergoes a chemoembolization and the follow-up scan shows a 5 cm hole with no enhancement, that’s considered a complete response by mRECIST, whereas with by RECIST, that would be considered stable disease because it’s still a 5-cm lesion.

Y-90, or external beam radiation, has responses that are more difficult to interpret. They don’t lose the enhancement the same way, so you generally see with radiation whether it’s internal or external. Rather than seeing lack of enhancement right away, you’ll see either slow lack of enhancement or slow shrinkage. But you really aren’t going to see your maximum effect until the patient is about 6 months out from their radiation treatment. So, you have to be more patient when assessing response in those patients.

Transcript Edited for Clarity 
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