Radiopaque bead treatment at Mount Sinai ‘potential game-changer’ for hepatocellular carcinoma

An estimated 746,000 deaths occur annually from liver cancer worldwide.

Few surgical options are considered beneficial in patients with intermediate- or advanced-stage disease, making it a difficult-to-treat cancer.

Mount Sinai Hospital’s liver cancer program was one of the first to offer patients with liver cancer an innovative, minimally invasive treatment using radiopaque beads that contain the chemotherapy agent doxorubicin.

Edward Kim

Edward Kim

The M1 LUMI beads (BTG plc) were designed with technology that allows for real-time location tracking during embolization. The FDA approved the device in December, and Mount Sinai has been one of the first institutions to participate in a comprehensive clinical evaluation of the beads.

HemOnc Today spoke with Edward Kim, MD, director of interventional oncology and associate professor of radiology and surgery in the division of interventional radiology at Mount Sinai Hospital, about how the treatment works, his experience performing one of the first procedures with the new technology and what benefits he hopes it will provide for patients with liver cancer.

Question: Can you describe how radiopaque bead treatment works?

Answer: The procedure is based upon transarterial therapy. We gain access to the arterial system, either through the left wrist or the femoral artery. We then position the catheter to our target area and, based upon the imaging, we look at what arteries are feeding the tumor. We position the catheter in the tumor-feeding vessels. Then we inject radiopaque beads coated with doxorubicin. These beads are injected into the tumor bed.

Q: What is the history of bead technology ?

A: The first bead technology procedure was transarterial chemoembolization (TACE), in which three drugs — cisplatin, mytomicin and adriamycin — are mixed with the oily substance lipiodol. This was created in an emulsification similar to salad dressing, where one mixes oil and water. Lipiodol is radiopaque, so we can see it under a microscope and know where we are injecting. It was created to show where the drug was going. After injection, we are able to see, with X-ray, exactly where it is going and follow the emulsification with an embolic agent to block blood flow to the tumor. So, one would achieve destruction in two ways: by injecting drugs to destroy the tumor and also by restricting blood supply to the tumor. This was described by researchers from Europe and Asia and showed a significant survival advantage in intermediate-stage hepatocellular carcinoma at the time compared with best supportive care. We treated patients this way for many years.

Several years later, drug-eluting beads called DC/LC Beads were developed. These beads are spheres that can be charged on the outside with the chemotherapy drug doxorubicin, then are injected into the tumor bed. In the phase 2 randomized controlled PRECISION V study, researchers demonstrated that the objective response — or what we see in terms of imaging after therapy — was similar to conventional TACE and its new drug-eluting platform.

Q: What are the differences between these approaches?

A: The significant difference was in systemic toxicity. The amount of drug released was significantly less with this drug-eluting platform, so patients tolerated it better. With conventional TACE, patients usually get some type of pain and fatigue that could last several days after. With drug-eluting beads, this was diminished and the objective response was similar.

A disadvantage of the drug-eluting platform was that one could not directly see the beads under any form of imaging modality. So, in patient follow-up 4 weeks after the procedure, we could ascertain whether we got all of the tumor with adequate coverage and, therefore, received a response. If we did not achieve a complete response, we would perform the procedure again. This is how treatment has been for many years.

Q: What makes radiopaque bead treatment unique?

A: It allows us to make adjustments during the procedure if we are not satisfied with the coverage of treatment to the tumor. We have always attempted this in the past, but we were never sure exactly where the beads were going, so we were making assumptions. In our early experience with larger-sized tumors — tumors around 4 cm or 5 cm — we did make adjustments during the procedure. In one patient, we went as close as possible to the tumor vessel, and we saw that it was going mostly to the lower half of the tumor. We also saw that some of the beads were going to nontarget vessels. We want to minimize this as much as possible because we want to prevent collateral damage. So, we repositioned the catheter to go to a more superior branch and continued the procedure. We achieved two things by doing this: We achieved better coverage of the tumor and we also reduced the amount of nontarget embolization, the amount of material that went to the nontumoral and functioning liver. Our goal is to more precisely target tumors while causing less collateral damage to the liver. The hope is that this will lead to a greater objective response and this, in turn, will hopefully lead to better clinical outcomes.

Q: Is this used to treat patients with any other types of cancer ?

A : This procedure is only indicated for patients with liver cancer. Mount Sinai is one of the largest hepatocellular carcinoma centers in the United States. So, by nature, we have a very large liver cancer population to treat with this technology. There remains the possibility of evaluating this technology for treatment of other cancers through clinical trials.

Q: Are other institutions begin ning to perform this procedure ?

A: We are one of first to have the opportunity to use this new technology. The NIH, which helped to develop the procedure, is also among the first to use it, as well as University of Miami. The procedure just gained approval for wide use and now is available at other institutions. It is very early in clinical use, but we will gather more information as the technology becomes widely used in the United States and Europe.

Q: W hat is your ultimate hope for this procedure?

A: My hope is that, through prospective clinical studies, we can generate meaningful data that can inform us if improved visualization and technique will translate into increased objective response and, ultimately, improved OS. Historically, OS is approximately 16 months for patients with untreated intermediate-stage liver cancer. The initial studies with conventional chemoembolization extended that survival to 20 months. Now, we are getting data with the new platforms going out as far as 45 months. Whether we extend this even further with precision targeting of these tumors with less collateral damage remains to be seen. The thought is, however, why not? The technology continues to improve and we are seeing better OS in this patient population. Hopefully this new technology will translate into better patient outcomes and safety.

Q: Is there anything else you would like to mention ?

A: It is early in clinical use and clinical trials are still being developed, so it is hard to make definitive conclusions about the technology, but it is promising. I do not want to make any false assumptions that this is going to radically change what we do and radically change OS, but it is a potential game-changer that will really allow us to be more precise and advance our technology so that we can improve patient outcomes. – by Jennifer Southall

For more information:

Edward Kim, MD, can be reached at Mount Sinai Hospital, 1460 Madison Ave., New York, NY 10029; email: edward.kim@mountsinai.org.

Disclosure: Kim reports consultant and speakers bureau roles with BTG plc.

An estimated 746,000 deaths occur annually from liver cancer worldwide.

Few surgical options are considered beneficial in patients with intermediate- or advanced-stage disease, making it a difficult-to-treat cancer.

Mount Sinai Hospital’s liver cancer program was one of the first to offer patients with liver cancer an innovative, minimally invasive treatment using radiopaque beads that contain the chemotherapy agent doxorubicin.

Edward Kim

Edward Kim

The M1 LUMI beads (BTG plc) were designed with technology that allows for real-time location tracking during embolization. The FDA approved the device in December, and Mount Sinai has been one of the first institutions to participate in a comprehensive clinical evaluation of the beads.

HemOnc Today spoke with Edward Kim, MD, director of interventional oncology and associate professor of radiology and surgery in the division of interventional radiology at Mount Sinai Hospital, about how the treatment works, his experience performing one of the first procedures with the new technology and what benefits he hopes it will provide for patients with liver cancer.

Question: Can you describe how radiopaque bead treatment works?

Answer: The procedure is based upon transarterial therapy. We gain access to the arterial system, either through the left wrist or the femoral artery. We then position the catheter to our target area and, based upon the imaging, we look at what arteries are feeding the tumor. We position the catheter in the tumor-feeding vessels. Then we inject radiopaque beads coated with doxorubicin. These beads are injected into the tumor bed.

Q: What is the history of bead technology ?

A: The first bead technology procedure was transarterial chemoembolization (TACE), in which three drugs — cisplatin, mytomicin and adriamycin — are mixed with the oily substance lipiodol. This was created in an emulsification similar to salad dressing, where one mixes oil and water. Lipiodol is radiopaque, so we can see it under a microscope and know where we are injecting. It was created to show where the drug was going. After injection, we are able to see, with X-ray, exactly where it is going and follow the emulsification with an embolic agent to block blood flow to the tumor. So, one would achieve destruction in two ways: by injecting drugs to destroy the tumor and also by restricting blood supply to the tumor. This was described by researchers from Europe and Asia and showed a significant survival advantage in intermediate-stage hepatocellular carcinoma at the time compared with best supportive care. We treated patients this way for many years.

Several years later, drug-eluting beads called DC/LC Beads were developed. These beads are spheres that can be charged on the outside with the chemotherapy drug doxorubicin, then are injected into the tumor bed. In the phase 2 randomized controlled PRECISION V study, researchers demonstrated that the objective response — or what we see in terms of imaging after therapy — was similar to conventional TACE and its new drug-eluting platform.

Q: What are the differences between these approaches?

A: The significant difference was in systemic toxicity. The amount of drug released was significantly less with this drug-eluting platform, so patients tolerated it better. With conventional TACE, patients usually get some type of pain and fatigue that could last several days after. With drug-eluting beads, this was diminished and the objective response was similar.

A disadvantage of the drug-eluting platform was that one could not directly see the beads under any form of imaging modality. So, in patient follow-up 4 weeks after the procedure, we could ascertain whether we got all of the tumor with adequate coverage and, therefore, received a response. If we did not achieve a complete response, we would perform the procedure again. This is how treatment has been for many years.

Q: What makes radiopaque bead treatment unique?

A: It allows us to make adjustments during the procedure if we are not satisfied with the coverage of treatment to the tumor. We have always attempted this in the past, but we were never sure exactly where the beads were going, so we were making assumptions. In our early experience with larger-sized tumors — tumors around 4 cm or 5 cm — we did make adjustments during the procedure. In one patient, we went as close as possible to the tumor vessel, and we saw that it was going mostly to the lower half of the tumor. We also saw that some of the beads were going to nontarget vessels. We want to minimize this as much as possible because we want to prevent collateral damage. So, we repositioned the catheter to go to a more superior branch and continued the procedure. We achieved two things by doing this: We achieved better coverage of the tumor and we also reduced the amount of nontarget embolization, the amount of material that went to the nontumoral and functioning liver. Our goal is to more precisely target tumors while causing less collateral damage to the liver. The hope is that this will lead to a greater objective response and this, in turn, will hopefully lead to better clinical outcomes.

Q: Is this used to treat patients with any other types of cancer ?

A : This procedure is only indicated for patients with liver cancer. Mount Sinai is one of the largest hepatocellular carcinoma centers in the United States. So, by nature, we have a very large liver cancer population to treat with this technology. There remains the possibility of evaluating this technology for treatment of other cancers through clinical trials.

Q: Are other institutions begin ning to perform this procedure ?

A: We are one of first to have the opportunity to use this new technology. The NIH, which helped to develop the procedure, is also among the first to use it, as well as University of Miami. The procedure just gained approval for wide use and now is available at other institutions. It is very early in clinical use, but we will gather more information as the technology becomes widely used in the United States and Europe.

Q: W hat is your ultimate hope for this procedure?

A: My hope is that, through prospective clinical studies, we can generate meaningful data that can inform us if improved visualization and technique will translate into increased objective response and, ultimately, improved OS. Historically, OS is approximately 16 months for patients with untreated intermediate-stage liver cancer. The initial studies with conventional chemoembolization extended that survival to 20 months. Now, we are getting data with the new platforms going out as far as 45 months. Whether we extend this even further with precision targeting of these tumors with less collateral damage remains to be seen. The thought is, however, why not? The technology continues to improve and we are seeing better OS in this patient population. Hopefully this new technology will translate into better patient outcomes and safety.

Q: Is there anything else you would like to mention ?

A: It is early in clinical use and clinical trials are still being developed, so it is hard to make definitive conclusions about the technology, but it is promising. I do not want to make any false assumptions that this is going to radically change what we do and radically change OS, but it is a potential game-changer that will really allow us to be more precise and advance our technology so that we can improve patient outcomes. – by Jennifer Southall

For more information:

Edward Kim, MD, can be reached at Mount Sinai Hospital, 1460 Madison Ave., New York, NY 10029; email: edward.kim@mountsinai.org.

Disclosure: Kim reports consultant and speakers bureau roles with BTG plc.