High Dose-Rate Brachytherapy for the Treatment of Both Primary and Secondary Unresectable Liver Malignancies

Study Overview
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Brief Summary
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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.

Detailed Description
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Primary Objective -To prospectively evaluate the clinical effectiveness of the use of high dose rate brachytherapy (HDRBT) for the treatment of both primary and secondary unresectable liver malignancies assessed by comparing local tumor control (LTC) rates at 6 months with a historical cohort. Secondary Objectives To compare local tumor control rates at 3-month intervals between cohorts for the duration of the study (3 months, 9 months, 12 months, etc.). To compare overall survival (OS) and progression-free survival (PFS) between cohorts.

Official Title
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High Dose-Rate Brachytherapy for the Treatment of Both Primary and Secondary Unresectable Liver Malignancies

Conditions
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Liver Malignant Tumors, Cholangiocarcinoma Metastatic, Pancreatic Cancer, Melanoma

Intervention / Treatment
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* Device: high dose rate brachytherapy
* Device: high dose rate brachytherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: GROUP A: Patients with liver lesions must be over the age of 18 GROUP A: Any patient with up to five unresectable tumors that are: At least 3 cm (largest diameter in the axial plane) In close proximity to large blood vessels In close proximity to sensitive structures (bowel, stomach, diaphragm, liver capsule, liver hilum, bile ducts) Associated with difficult endovascular access to one or more feeding arterial branches (hypovascular tumors) Associated with a large shunt fraction to other vital organs GROUP B: Historical patients who meet the above criteria for group A but did not receive HDRBT between 01/01/2000 and 1/01/2021 Exclusion criteria: Active infectious disease Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, interstitial lung disease, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Patients with polymetastatic disease with the exception of those patients who may benefit from therapy addressing local complications directly related to the target lesion diminishing quality of life such as pain, vascular/biliary occlusion, and liver disfunction Pregnancy (sexually active patients must be on birth control while participating in this study) Child-Pugh class C Total serum bilirubin > 2 mg/dl Platelet count < 50,000/ul International normalized ratio (INR) > 1.5

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A (Prospective cohort )<br>20 patients, will undergo initial diagnostic workup, staging and treatment per institutional standard of care. Intervention: High dose rate brachytherapy (HDRBT) | Device: high dose rate brachytherapy<br>* diagnostic workup, staging, and treatment per the institution standard of care<br>|
| Experimental: Group B( Retrospective chart review )<br>40 patients who meet same eligibility criteria, but did not receive HDRBT between 1/1/2000 and 1/1/2021. | Device: high dose rate brachytherapy<br>* reviewing historical patients who meet the above criteria for group A but did not receive HDRBT between 01/01/2000 and 1/01/2021<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To prospectively evaluate the clinical effectiveness of the use of high dose rate brachytherapy (HDRBT) for the treatment of both primary liver malignancies. |  | Through study completion, an average of 1 year |