Radioembolization vs Microwave Ablation for Liver Cancer

(REALM Trial)

Overseen By Amy Riehm

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Ochsner Health System

Disqualifiers: Pregnancy, Concurrent malignancy

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 1 cycle

50 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Radioembolization vs Microwave Ablation for Liver Cancer?

Research shows that Yttrium-90 (Y-90) radioembolization, a part of this treatment, can effectively target liver tumors with high doses of radiation while sparing healthy liver tissue, improving outcomes for patients with inoperable liver cancer. ^{1 2 3 4 5}

Is radioembolization with Yttrium-90 safe for liver cancer treatment?

Radioembolization with Yttrium-90 (Y90) microspheres, such as TheraSphere, has been shown to be generally safe for treating liver tumors, with minimal harm to healthy liver tissue. However, there can be liver-related side effects, and factors before treatment can influence the risk of these side effects. ^{1 2 6 7 8}

How is the treatment of radioembolization and microwave ablation for liver cancer different from other treatments?

This treatment is unique because it combines two advanced techniques: Yttrium-90 radioembolization, which delivers targeted internal radiation directly to liver tumors through tiny beads, and microwave ablation, which uses heat to destroy cancer cells. This dual approach aims to maximize tumor destruction while minimizing damage to healthy liver tissue. ^{2 8 9 10 11}

What is the purpose of this trial?

This clinical trial will compare 1-year outcomes in patients with hypoalbuminemia and a new diagnosis of small, early-stage hepatocellular carcinoma (HCC) who are candidates for both 90-Yittrium Therasphere transarterial radioembolization (90Y) and microwave ablation (MWA). The study will determine whether treatment with 90Y lowers the risk of disease progression within the first year after diagnosis. Participants will be randomized to receive either first cycle 90Y or MWA and then proceed with standard of care.

Research Team

Ari Cohen, MD

Principal Investigator

Ochsner Health

Eligibility Criteria

This trial is for adults with a new diagnosis of small, early-stage liver cancer (HCC) who also have low blood protein levels (hypoalbuminemia). They should be in good physical condition and have liver function within certain limits. People can't join if they've had previous treatments for HCC or if their tumor size exceeds 3cm.

Inclusion Criteria

I have not had any treatments aimed at my liver cancer.

I am fully active or can carry out light work.

Albumin level < 3.4 g/dL at HCC diagnosis

Exclusion Criteria

I have another type of cancer besides the one being studied.

Pregnant women

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either 90-Yittrium Therasphere transarterial radioembolization or microwave ablation as a first cycle liver-directed therapy

1 cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment, with data collection on adverse events, response to treatment, time to retreatment, duration of response, and progression of disease staging

1 year

Treatment Details

Interventions

• 90Y Transarterial Radioembolization
• Microwave Ablation

Trial Overview The study compares two treatments: injecting tiny radioactive beads called Therasphere 90Y into the liver's blood vessels versus using Microwave Ablation to heat and destroy the tumor. Patients will be randomly assigned to one treatment and then receive standard care.

Participant Groups

Group I: Microwave Ablation Active Control 1 Intervention

Ablation performed with a high powered, gas cooled multi-antenna system targeting an ablative margin \> 5mm.

Group II: Therasphere Transarterial Radioembolization Active Control 1 Intervention

Two-phase treatment including mapping angiogram with personalized dosimetry followed by complete treatment of the tumor angiosome with 90-Yittrium glass microsphere infusion.

90Y Transarterial Radioembolization is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Therasphere for:

• Hepatocellular carcinoma (HCC)
• Colorectal liver metastases (CRLM)

Approved in United States as Therasphere for:

• Hepatocellular carcinoma (HCC)
• Colorectal liver metastases (CRLM)

Approved in Canada as Therasphere for:

• Hepatocellular carcinoma (HCC)
• Colorectal liver metastases (CRLM)

Who Is Running the Clinical Trial?

Ochsner Health System

Lead Sponsor

Trials

97

Recruited

91,900+

Boston Scientific Corporation

Industry Sponsor

Trials

758

Recruited

867,000+

Michael F. Mahoney

Boston Scientific Corporation

Chief Executive Officer since 2016

MBA from Wake Forest University, BBA in Finance from the University of Iowa

Kenneth Stein

Boston Scientific Corporation

Chief Medical Officer since 2020

MD from Harvard Medical School, MMSc in Clinical Investigation from Harvard-MIT Division of Health Sciences and Technology

Findings from Research

In a study involving 34 patients with unresectable hepatocellular carcinoma (HCC), Yttrium-90 (Y-90) microsphere therapy demonstrated significant efficacy, with 19% achieving complete response and 44% showing partial response after treatment.

The therapy was found to be safe, with no serious side effects reported, and predictors of treatment success included mean tumor dose delivery and the absence of bilobar disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Yttrium-90 (Y-90) resin microsphere therapy for patients with unresectable hepatocellular carcinoma. Identification of successful treatment response predictors and patient selection. Arslan, N., Ince, S., Okuyucu, K., et al.[2022]

In a study involving 28 patients with unresectable hepatocellular carcinoma (HCC), Y-90 microsphere therapy demonstrated safety and efficacy, with no significant complications observed during or shortly after treatment.

The therapy resulted in a complete response in 7% of patients and a partial response in 36%, indicating that it can effectively target liver tumors while minimizing damage to healthy tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Yttrium-90 (Y-90) Resin Microsphere Therapy for Patients with Unresectable Hepatocellular Carcinoma: a Single-Center Experience. İnce, S., Karaman, B., Alagoz, E., et al.[2019]

Selective intraarterial radionuclide therapy (SIRT) using Yttrium-90 microspheres is a safe and effective treatment for unresectable hepatic metastases from neuroendocrine tumors, with a high overall response rate of 90% in a study of 10 patients.

The treatment delivered a significant dose of radiation directly to the tumors (mean 99.73 Gy) while minimizing exposure to healthy liver tissue (mean 26.73 Gy) and lungs (mean 4.45 Gy), indicating its targeted approach reduces potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective intraarterial radionuclide therapy with Yttrium-90 (Y-90) microspheres for hepatic neuroendocrine metastases: initial experience at a single center. Arslan, N., Emi, M., Alagöz, E., et al.[2019]

Selective internal radiotherapy (SIRT) using yttrium-90 microspheres can enhance clinical outcomes for patients with inoperable liver cancer by targeting tumors while protecting healthy tissue.

Effective planning for SIRT is crucial to avoid serious side effects like radiation-induced liver disease, and it is recommended to use multiple planning methods to determine the appropriate microsphere activity for each patient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient selection and activity planning guide for selective internal radiotherapy with yttrium-90 resin microspheres. Lau, WY., Kennedy, AS., Kim, YH., et al.[2022]

Selective internal radiotherapy (SIRT) with yttrium-90 can lead to significant tumor response in patients with hepatic malignancies, allowing for subsequent liver resection in selected cases, as demonstrated by a mean lesion volume reduction of 475 cm³ in 12 patients.

While SIRT is generally safe with no complications noted post-treatment, the study found a 67% morbidity rate and 11% mortality rate within 90 days after surgery, highlighting the need for careful patient selection and further research to optimize outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liver Resection After Selective Internal Radiation Therapy with Yttrium-90: Safety and Outcomes. Mafeld, S., Littler, P., Hayhurst, H., et al.[2020]

Yttrium-90 (Y90) radioembolization therapy using TheraSphere® has been deemed safe and effective for treating hepatocellular carcinoma (HCC), even in patients with portal vein thrombosis, according to the Radioembolization Brachytherapy Oncology Consortium.

Despite promising initial results, there are currently no randomized clinical trials demonstrating a survival benefit for TheraSphere®, indicating the need for further research before it can be fully recommended as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radioembolization for hepatocellular carcinoma using TheraSphere®. Ali, SM.[2021]

In a study of 88 patients with hepatocellular carcinoma treated with yttrium 90 microspheres (TheraSpheres), 42% experienced liver toxicities, with higher risks associated with elevated pretreatment total bilirubin levels and increased liver radiation doses.

Despite the occurrence of liver toxicities, most resolved over time, and no patients developed confirmed radiation-induced liver disease, indicating that doses up to 150 Gy for a single treatment and 268 Gy for repeated treatments were well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of unresectable hepatocellular carcinoma with intrahepatic yttrium 90 microspheres: factors associated with liver toxicities. Goin, JE., Salem, R., Carr, BI., et al.[2019]

Yttrium-90 radioembolization therapy (90Y) effectively delivers high doses of radiation directly to liver tumors while minimizing damage to surrounding healthy tissues, making it a promising treatment option for liver malignancies.

The review highlights the safety and efficacy of using TheraSphere, a specific type of 90Y microsphere, in the management of liver tumors, supporting its role in locoregional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Yttrium-90 radioembolization using TheraSphere in the management of primary and secondary liver tumors. Riaz, A., Lewandowski, RJ., Kulik, L., et al.[2009]

Microwave thermosphere ablation (MTA) demonstrated improved local tumor control in patients with colorectal liver metastasis (CRLM), showing a lower local recurrence rate of 10% compared to 20% for radiofrequency ablation (RFA).

MTA also significantly reduced total ablation and operative times (19 minutes for MTA vs. 37 minutes for RFA), while maintaining similar hospital stays and morbidity rates, indicating it may be a more efficient treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of microwave thermosphere versus radiofrequency thermal ablation in the treatment of colorectal liver metastases. Takahashi, H., Kahramangil, B., Kose, E., et al.[2019]

Yttrium-90 (90Y) radioembolization is an effective catheter-based therapy that delivers targeted internal radiation directly to liver tumors using microspheres, either glass (TheraSphere®) or resin-based (SIR-Spheres®).

Clinical evidence supports the use of 90Y radioembolization for treating unresectable liver cancers, demonstrating its potential as a viable option for patients with these malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Yttrium-90 radioembolization of hepatocellular carcinoma and metastatic disease to the liver. Lewandowski, RJ., Salem, R.[2021]

CT angiography allows for more precise targeting of Yttrium 90 (90Y) radioembolization in patients with unresectable hepatocellular carcinoma (HCC), significantly increasing the effective radiation dose to tumors from a mean of 100 Gy to 348 Gy (P < .001).

This method does not adversely affect liver function, as evidenced by minimal changes in serum bilirubin levels and no significant alterations in Child-Pugh classification in 13 out of 14 patients, indicating its safety for use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of catheter-directed CT angiography on yttrium-90 radioembolization treatment of hepatocellular carcinoma. Rhee, TK., Omary, RA., Gates, V., et al.[2005]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Yttrium-90 (Y-90) resin microsphere therapy for patients with unresectable hepatocellular carcinoma. Identification of successful treatment response predictors and patient selection. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Yttrium-90 (Y-90) Resin Microsphere Therapy for Patients with Unresectable Hepatocellular Carcinoma: a Single-Center Experience. [2019]

3. Serbia pubmed.ncbi.nlm.nih.gov

Selective intraarterial radionuclide therapy with Yttrium-90 (Y-90) microspheres for hepatic neuroendocrine metastases: initial experience at a single center. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Patient selection and activity planning guide for selective internal radiotherapy with yttrium-90 resin microspheres. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Liver Resection After Selective Internal Radiation Therapy with Yttrium-90: Safety and Outcomes. [2020]

6. India pubmed.ncbi.nlm.nih.gov

Radioembolization for hepatocellular carcinoma using TheraSphere®. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Treatment of unresectable hepatocellular carcinoma with intrahepatic yttrium 90 microspheres: factors associated with liver toxicities. [2019]

8. Italy pubmed.ncbi.nlm.nih.gov

Yttrium-90 radioembolization using TheraSphere in the management of primary and secondary liver tumors. [2009]

9. England pubmed.ncbi.nlm.nih.gov

A comparison of microwave thermosphere versus radiofrequency thermal ablation in the treatment of colorectal liver metastases. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Yttrium-90 radioembolization of hepatocellular carcinoma and metastatic disease to the liver. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

The effect of catheter-directed CT angiography on yttrium-90 radioembolization treatment of hepatocellular carcinoma. [2005]