High Dose-Rate Brachytherapy for Liver Cancer

Overseen By Joshua Kuban

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Infectious disease, Heart failure, Pregnancy, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 6 months

60 Participants Needed

Trial Summary

What is the purpose of this trial?

Over the past three decades, the treatment of both primary and secondary liver malignancies has been improved by the development and optimization of multiple minimally invasive thermal ablative therapies. These advances have resulted in a myriad of benefits for patients including decreased morbidity, mortality, as well as increased longevity and quality of life. However, these therapies can only be performed within certain parameters. Thermal ablative techniques such as radiofrequency ablation (RFA) and microwave ablation (MVA) are recommended for small lesions under 3 cm due to decreased efficacy when attempting to treat larger lesions. Additionally, large vessels in close proximity to a target lesion may result in heat dissipation, termed the "heat sink" effect, and result in incomplete ablation of the lesion. Furthermore, thermal ablative techniques cause off-target damage when utilized near sensitive structures such as the diaphragm, stomach, or bowel, and if performed near thermosensitive bile ducts, can result in cholestasis . Noting these limitations, percutaneous high-dose-rate brachytherapy was brought into clinical practice by Ricke et al. in Europe in 2002 . This therapy utilizes an iridium-192 (192Ir) isotope to administer a cytotoxic dose of radiation to a target lesion. It is not susceptible to heat sink effects and can also deliver radiation with the precision necessary to cause tumor death without destroying the integrity of neighboring structures. Additionally, it can be used to treat larger tumors (\>3cm) as it is not associated the same size limitations as ablative techniques and can also be utilized to treat lesions that are not amenable to intra-arterial therapies (such as trans-arterial chemoembolization and yttrium-90 radioembolization). Since its inception, HDRBT has been evaluated through multiple studies investigating its use to treat lesions throughout the body including both primary and secondary liver malignancies such as hepatocellular carcinoma (HCC), cholangiocarcinoma, metastasis to the liver from colorectal cancer, pancreatic cancer , melanoma , and breast cancer . Its use in treating lymph node metastases has also been investigated . These studies have demonstrated the feasibility, safety, and clinical effectiveness of this method, establishing it as a therapeutic option when use of thermal ablation therapies is restricted. Most studies however, have been retrospective and have been performed outside the United States. Studying this therapy will add a crucial treatment option to our current armamentarium, filling a gap in currently available therapies and additionally allowing for further investigation of the use of HDRBT in a larger and more diverse population.

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 High Dose-Rate Brachytherapy for liver cancer?

Research shows that high-dose-rate brachytherapy, when guided by computed tomography (CT), is effective in treating inoperable liver cancers by delivering targeted radiation. Studies have demonstrated its safety and ability to manage liver tumors, improving outcomes for patients who cannot undergo surgery. ^{1 2 3 4 5}

Is high dose-rate brachytherapy generally safe for humans?

Research on high dose-rate brachytherapy, particularly in prostate cancer, suggests it is generally safe, with studies reporting on its safety and quality in treatment. While these studies focus on prostate cancer, they provide some reassurance about the treatment's safety in humans. ^{1 5 6 7 8}

How is High Dose-Rate Brachytherapy different from other treatments for liver cancer?

High Dose-Rate Brachytherapy (HDR Brachytherapy) is unique because it delivers a high dose of radiation directly to the liver tumor through a minimally invasive procedure, allowing for precise targeting and minimizing damage to surrounding healthy tissue. This approach is particularly beneficial for inoperable liver cancers, offering a treatment option where surgery is not possible. ^{1 2 3 5 9}

Research Team

Joshua Kuban, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults over 18 with liver lesions larger than 3 cm, near large blood vessels or sensitive areas like the bowel. It's also for those with up to five unresectable tumors that are hard to treat due to poor blood vessel access or have a high risk of affecting other organs. People can't join if they're pregnant, have serious illnesses like heart failure, active infections, severe liver disease (Child-Pugh class C), very high bilirubin levels in their blood, low platelets count, or an INR > 1.5.

Inclusion Criteria

I have up to five tumors that cannot be surgically removed.

- At least 3 cm (largest diameter in the axial plane)

My condition involves areas near important internal organs.

Exclusion Criteria

Total serum bilirubin > 2 mg/dl

Platelet count < 50,000/ul

I have cancer that has spread widely, but I need treatment for symptoms caused by a specific tumor.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive high dose rate brachytherapy (HDRBT) for the treatment of unresectable liver malignancies

6 months

Multiple visits as per institutional standard of care

Follow-up

Participants are monitored for local tumor control (LTC) rates and overall survival (OS) at 3-month intervals

12 months

Regular follow-up visits every 3 months

Treatment Details

Interventions

• High Dose-Rate Brachytherapy

Trial Overview The study tests high-dose rate brachytherapy (HDRBT) using an iridium-192 isotope on primary and secondary liver malignancies which are not suitable for thermal ablation therapies. HDRBT aims to precisely target tumor cells without damaging nearby structures and can treat larger tumors effectively.

Participant Groups

Group I: Group B( Retrospective chart review ) Experimental Treatment 1 Intervention

40 patients who meet same eligibility criteria, but did not receive HDRBT between 1/1/2000 and 1/1/2021.

Group II: Group A (Prospective cohort ) Experimental Treatment 1 Intervention

20 patients, will undergo initial diagnostic workup, staging and treatment per institutional standard of care. Intervention: High dose rate brachytherapy (HDRBT)

High Dose-Rate Brachytherapy is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as HDR Brachytherapy for:

• Primary liver malignancies
• Secondary liver malignancies
• Hepatocellular carcinoma (HCC)
• Cholangiocarcinoma
• Liver metastases from colorectal cancer
• Pancreatic cancer
• Melanoma
• Breast cancer
• Lymph node metastases

Approved in United States as HDR Brachytherapy for:

• Primary liver malignancies
• Secondary liver malignancies
• Hepatocellular carcinoma (HCC)
• Cholangiocarcinoma
• Liver metastases from colorectal cancer
• Pancreatic cancer
• Melanoma
• Breast cancer
• Lymph node metastases

Approved in Canada as HDR Brachytherapy for:

• Primary liver malignancies
• Secondary liver malignancies
• Hepatocellular carcinoma (HCC)
• Cholangiocarcinoma
• Liver metastases from colorectal cancer
• Pancreatic cancer
• Melanoma
• Breast cancer
• Lymph node metastases

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

In a study of 95 patients with intermediate- or high-risk prostate cancer, a combined approach of high dose rate (HDR) brachytherapy and external beam radiotherapy (EBRT) was found to be well-tolerated, with manageable levels of toxicity reported by patients.

While urinary and bowel symptoms peaked shortly after treatment, most patients reported a return to baseline quality of life within 6 to 24 months, indicating that this treatment regimen effectively balances dose escalation with patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes and health-related quality of life in prostate cancer treated with a single fraction of high dose rate brachytherapy combined with hypofractionated external beam radiotherapy. Choudhury, A., Arthur, C., Malik, J., et al.[2022]

CT-guided interstitial high-dose-rate brachytherapy (HDR-BRT) is a safe and effective treatment for inoperable liver tumors, with a 66% overall survival rate at one year and a low incidence of severe side effects (4.7%).

The local control rates for metastatic lesions were 79% at one year, while for primary hepatic tumors, the control rate was 88%, indicating that HDR-BRT can significantly manage tumor growth in challenging cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated accelerated computed tomography-guided interstitial high-dose-rate brachytherapy for liver malignancies. Tselis, N., Chatzikonstantinou, G., Kolotas, C., et al.[2018]

High-dose-rate interstitial brachytherapy (HDRIBT) was found to be a safe treatment for liver metastases, with no fatal complications reported among the 10 patients studied, and only minor side effects observed.

The treatment demonstrated a 75% local control rate at 12 months, indicating its efficacy as a non-surgical option for patients who are ineligible for surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose-rate interstitial brachytherapy for liver metastases: first study from India. Sharma, DN., Thulkar, S., Sharma, S., et al.[2022]

CT-guided interstitial high-dose-rate brachytherapy (IRT HDR BRT) shows high local control rates for liver tumors, achieving 89% for metastatic tumors and 90% for primary tumors at 6 months, indicating its efficacy in treating unresectable liver malignancies.

The procedure is considered safe, with only 5% of interventions resulting in severe side effects and no treatment-related deaths reported, highlighting its potential as a viable option for patients with extensive liver tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Computed tomography-guided interstitial high dose rate brachytherapy for centrally located liver tumours: a single institution study. Tselis, N., Chatzikonstantinou, G., Kolotas, C., et al.[2022]

In a clinical trial involving 42 men with intermediate-risk prostate cancer, a treatment combining a single 15 Gy HDR brachytherapy boost with a five-fraction external beam radiation therapy (EBRT) resulted in a high biochemical disease-free survival rate of 95.5% after a median follow-up of 36 months.

The treatment demonstrated low toxicity, with only one case of acute Grade 3 gastrointestinal and genitourinary toxicity, and no significant differences in health-related quality of life across urinary, bowel, or sexual domains, suggesting it is a safe and effective option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase IB clinical trial of 15 Gy HDR brachytherapy followed by hypofractionated/SBRT in the management of intermediate-risk prostate cancer. Den, RB., Greenspan, J., Doyle, LA., et al.[2023]

The Single Fraction HDR brachytherapy protocol (15 Gy in one session) demonstrated a high biochemical disease-free survival rate of 95.1%, comparable to the Standard Fractionation protocol (97.9%) over a median follow-up of 45 months, indicating its efficacy in treating intermediate risk prostate cancer.

Both treatment protocols showed similar rates of late urinary and rectal toxicity, as well as health-related quality of life, suggesting that the Single Fraction approach is not only effective but also safe, potentially offering a more resource-efficient option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is single fraction 15 Gy the preferred high dose-rate brachytherapy boost dose for prostate cancer? Morton, G., Loblaw, A., Cheung, P., et al.[2022]

In a study of 164 men treated with high-dose-rate (HDR) brachytherapy for prostate cancer, the procedure showed a low incidence of genitourinary (GU) and gastrointestinal (GI) complications, indicating it is a safe treatment option.

With a median follow-up of 18.6 months, HDR brachytherapy resulted in a high overall survival rate of 98.7% and a disease-free survival rate of 96.2%, demonstrating its efficacy in treating localized prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Building a High-Dose-Rate Prostate Brachytherapy Program With Real-Time Ultrasound-Based Planning: Initial Safety, Quality, and Outcome Results. Zhang, H., Kang, S., Ali, N., et al.[2022]

High-dose-rate (HDR) brachytherapy provides better coverage of clinical target volumes (CTVs) for complex and curved skin lesions compared to electron external beam radiation therapy (EBRT), especially when the lesions are large or have complicated shapes.

The study found that while both HDR-BT and EBRT can effectively treat superficial lesions, HDR-BT showed superior dose distribution, particularly in cases where the curvature of the treatment area increased, leading to a significant loss of coverage with EBRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selection criteria for high-dose-rate surface brachytherapy and electron beam therapy in cutaneous oncology. Buzurovic, IM., O'Farrell, DA., Harris, TC., et al.[2022]

The study developed a new treatment planning system (TPS) for low-dose-rate (LDR) permanent seed brachytherapy targeting liver tumors, which integrates advanced deep learning for multi-organ segmentation and improves planning efficiency.

Testing showed that the TPS outperformed commercial systems in terms of dose-volume-histogram criteria and execution time, indicating its potential for optimizing treatment while minimizing complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Embedding expertise knowledge into inverse treatment planning for low-dose-rate brachytherapy of hepatic malignancies. Zhu, J., Wang, C., Teng, S., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes and health-related quality of life in prostate cancer treated with a single fraction of high dose rate brachytherapy combined with hypofractionated external beam radiotherapy. [2022]

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

Hypofractionated accelerated computed tomography-guided interstitial high-dose-rate brachytherapy for liver malignancies. [2018]

3. Poland pubmed.ncbi.nlm.nih.gov

High-dose-rate interstitial brachytherapy for liver metastases: first study from India. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Computed tomography-guided interstitial high dose rate brachytherapy for centrally located liver tumours: a single institution study. [2022]

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

A phase IB clinical trial of 15 Gy HDR brachytherapy followed by hypofractionated/SBRT in the management of intermediate-risk prostate cancer. [2023]

6. Ireland pubmed.ncbi.nlm.nih.gov

Is single fraction 15 Gy the preferred high dose-rate brachytherapy boost dose for prostate cancer? [2022]

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

Building a High-Dose-Rate Prostate Brachytherapy Program With Real-Time Ultrasound-Based Planning: Initial Safety, Quality, and Outcome Results. [2022]

8. Poland pubmed.ncbi.nlm.nih.gov

Selection criteria for high-dose-rate surface brachytherapy and electron beam therapy in cutaneous oncology. [2022]

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

Embedding expertise knowledge into inverse treatment planning for low-dose-rate brachytherapy of hepatic malignancies. [2023]