A Study to Assess the Effect of Y-90 Therapy on Non-target/Background Liver

The primary question of interest is quantifying the relationship between Y-90 liver therapy and liver damage. Little is known on this subject. Present assumptions and calculations of Y-90 administration are based on surgical lobar hepatectomies and external radiation beam therapies. The investigators hope that by using a functional model of the liver, the investigators can improve this important knowledge gap.

The investigators will be enrolling patients planning to receive Y-90 therapy for the treatment of liver malignancies. The diagnosis of a primary liver cancer, hepatocellular carcinoma (HCC), is usually made by a combination of specific imaging findings and clinical criteria; only rarely is a confirmatory biopsy performed. This is due to the high accuracy of the present diagnostic model and the significant risk of biopsy and tumor seeding.

Y-90 therapy involves administering radioactive particles to liver tumors by placing a catheter in a hepatic artery supplying the tumor using angiographic techniques and injection of these particles.

Y-90 Positron Emission Tomography-Computed Tomography (PET/CT) imaging has been established as a method to validate and quantitate distribution of Yttrium after Y-90 administration. The post Y-90 therapy PET/CT images provide an imaging distribution of the Y-90, which is essential for validation of administered versus planned dose to the liver lesion and background liver.

If the investigators can compare the Y-90 distribution to estimate background liver radiation distribution and dose (generated by the Y-90 PET/CT scan) combined with the global and regional function map (generated by the hepatobiliary [HIDA] scan performed before and after therapy), then the investigators will be assuming that the difference pre and post therapy in global and regional function can be ascribed to the Y-90 administration. The investigators will also analyze the Magnetic Resonance Imaging (MRI) and CT sets performed before and after therapy and correlate the imaging results collected with clinical findings such as ascites/encephalopathy and routine serological markers (bilirubin, albumin, International normalized ratio [INR], etc.). With this information, the investigators will have the potential to establish whether there is a relationship between Y-90 distribution to non-tumoral (normal) hepatic parenchyma and the incidence and severity of Radioembolization-Induced Liver Disease (REILD). This would have the potential to improve selection criteria and outcomes in populations selected for Y-90 therapy in the future.

Study Overview

• Status: Terminated
• Conditions: HCC; Liver Cancer
• Intervention / Treatment: Radiation: MRI and HIDA scan

Detailed Description

Little is known on the potential relationship between Y-90 liver therapy and liver damage this subject. Present assumptions and calculations of Y-90 administration are based on surgical lobar hepatectomies and external radiation beam therapies.

As most participants that need Y90 based liver therapies have compromised livers, the importance of knowing what potential collateral liver damage could be induced by Y90 is key so as not induce liver failure. Successful treatment of a liver malignancy would not be important if the potential mortality/morbidity risk of the treatment is higher or equal to the existing malignancy.

As apposed to anatomical imaging looking for changes in size/shape which are late changes, the investigators hope that by using a functional model of the liver, which can show early changes of liver damage, the investigators can improve the sensitivity for detection of liver damage and bridge this important knowledge gap. Additionally due to compensatory hypertrophy of the non treated liver, potential liver damage estimated by lab tests may be masked, again this emphasizes the importance of the measurement of the functional approach before and after therapy.

The investigators will be enrolling participants planning to receive Y-90 therapy for the treatment of liver malignancies. The diagnosis of a primary liver cancer, hepatocellular carcinoma (HCC), is usually made by a combination of specific imaging findings and clinical criteria; only rarely is a confirmatory biopsy performed. This is due to the high accuracy of the present diagnostic model and the significant risk of biopsy and tumor seeding.

Y-90 therapy involves administering radioactive particles to liver tumors by placing a catheter in a hepatic artery supplying the tumor using angiographic techniques and injection of these particles.

Y-90 PET/CT imaging has been established as a method to validate and quantitate distribution of Yttrium after Y-90 administration. The post Y-90 therapy PET/CT images provide an imaging distribution of the Y-90, which is essential for validation of administered versus planned dose to the liver lesion and background liver.

The investigators will be performing both specialized nuclear medicine HIDA and MRI scans aimed at constructing a functional map of the liver before and 3 months after therapy.

The investigators will compare the Y-90 distribution to estimate background liver radiation distribution and dose (generated by the Y-90 PET/CT scan) combined with the global and regional function map (generated by the HIDA and MRI scans performed before and after therapy), then the investigators will be assuming that the difference pre and post therapy in global and regional function can be ascribed to the Y-90 administration.

The investigators will also analyze the MRI and NM data sets performed before and after therapy and correlate the imaging results collected with clinical findings such as ascites/encephalopathy and routine serological markers (bilirubin, albumin, INR, etc.).

With this information, the investigators will have the potential to establish whether there is a relationship between Y-90 distribution to non-tumoral (normal) hepatic parenchyma and the incidence and severity of REILD. This would have the potential to improve selection criteria and outcomes in populations selected for Y-90 therapy in the future.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects must have the ability to understand and the willingness to sign a written informed consent document.
2. Subjects must be ≥ 18 years of age at the time of signing informed consent.
3. Subjects must have a diagnosis of hepatocellular carcinoma (HCC) and a treatment plan to undergo radioembolization therapy with Y-90 at Indiana University Health Hospital.
4. Subjects must be willing and able to comply with all procedures and visits required for this protocol (pre-treatment, during treatment, and post-treatment).

Exclusion Criteria:

1. Subjects who have contraindications for receiving Y-90 therapy and any routine procedures and imaging associated with Y-90 therapy, including subjects who are pregnant or are planning to become pregnant, will not be eligible to participate in this study. Female subjects who are of childbearing potential should inform her treating physician should she become pregnant at any time during the course of the study.
2. Subjects with contraindications for receiving hepatobiliary scans (HIDA scans) and Magnetic Resonance Imaging (MRI scans) will not be eligible to participate in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: MRI and HIDA scan	Radiation: MRI and HIDA scan; Pre y90 therapy each subject will undergo a HIDA and MRI scan. 3 months post Y90 - Each subject will undergo a second HIDA scan and MRI scan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary	Difference in regional liver function between pre and 3 months post Yttrium 90 delivery using the HIDA functional imaging scans.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary	Determine the difference in global liver function between pre and 3 months post Yttrium 90 delivery using the HIDA functional imaging scans.	3 months
Secondary	Correlation between the differences in liver function (both regional and global) with the Y 90 dose provided.	6 months

Collaborators and Investigators

• Sponsor: Indiana University
• Collaborators: BTG International Inc.
• Investigators: Principal Investigator: Mark Tann, MD, Indiana University

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 17, 2017
• Primary Completion (ACTUAL): July 15, 2019
• Study Completion (ACTUAL): April 24, 2020

Study Registration Dates

• First Submitted: November 8, 2016
• First Submitted That Met QC Criteria: November 14, 2016
• First Posted (ESTIMATE): November 17, 2016

Study Record Updates

• Last Update Posted (ACTUAL): September 25, 2020
• Last Update Submitted That Met QC Criteria: September 23, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms
• Other Study ID Numbers: RADY-BTG-TANN-HIDA/0603

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plan to share

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No