HCC - Hepatocellular Carcinoma
Conditions
Keywords
MARGIN, HCC, Y90, Liver Cancer
Brief summary
This study is being done to help doctors improve how they treat liver tumors that cannot be removed by surgery or treated with standard ablation techniques. The researchers want to find out the best amount of radiation that needs to be delivered to completely destroy (or ablate) parts of the liver that have cancer.
Detailed description
Currently, doctors use Yttrium-90 (Y90) radiation segmentectomy, a treatment that delivers tiny radioactive beads into the blood vessels feeding the liver tumor. These beads give off radiation that helps kill the cancer cells from the inside, right where the tumor is located. This approach allows doctors to target the tumor very precisely, while keeping the rest of the liver as healthy as possible. However, the exact dose needed to fully ablate a tumor without damaging healthy liver tissue is not well established. To answer this, the study team will use specialized imaging before and after treatment to evaluate how the radiation is distributed in the liver and how the liver responds over time. These imaging procedures include PET/CT or PET/MRI scans, which are standard medical imaging tests that are not considered experimental. During these scans, a small amount of a safe radioactive substance is injected into a participant's vein. This helps show where the Y90 beads are located in the participant's liver. In a PET/CT scan, two types of imaging are performed during the same session. The PET scan detects signals from the radioactive substance and shows how the participant's liver is functioning at a molecular level. The CT scan, which uses x-rays to create detailed cross-sectional images of the body, provides a precise anatomical map that helps localize these functional signals. Together, they give a clear picture of both the structure and activity within the liver. PET/MRI works similarly but uses magnetic fields and radio waves instead of x-rays. It combines the functional information from the PET scan with the highly detailed soft-tissue images from MRI, which can be especially useful in evaluating the liver. Both imaging techniques are done during a single visit, with the PET component typically performed at the same time as the CT or MRI, depending on which machine is used. Participants will also undergo a liver MRI with dual contrast using Eovist and extracellular gadolinium, another standard imaging procedure. MRI uses magnets and radio waves to take detailed pictures of the liver. Eovist is a special dye injected into a participant's vein during the scan that helps highlight liver tissue and shows how well different parts of the liver are functioning. Extracellular gadolinium is a more general contrast agent that enhances blood vessels and tissues, providing complementary information. This imaging helps the doctors confirm whether the tumor area was completely treated. The goal is to determine the safest and most effective dose of radiation to fully treat cancer while preserving healthy liver tissue. This information may help doctors treat future patients more precisely and safely. Yttrium-90 and the imaging methods used in this study, including PET/CT, PET/MRI, and dual contrast MRI, are FDA-approved.
Interventions
OTHERYttrium-90 Radiation Segmentectomy (Y90 RS) using glass microspheres
The objective of this study is to define an optimal "ablative dose" range for Y90 Radiation Segmentectomy that achieves complete sectoral ablation detectable on dual contrast MRI and to determine whether this dose-response relationship differs between cirrhotic and non-cirrhotic patients.
Sponsors
Northwestern University
Radiological Society of North America
Robert H. Lurie Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The investigators hypothesize that an optimal ablative dose exists between 200-500 Gy, with increasing ablation rates as dose increases, and that the threshold dose to achieve ablation differs between cirrhotic and non-cirrhotic livers. This hypothesis will be tested using voxel-based Y90 PET dosimetry and hepatobiliary MRI to assess dose-response relationships in both structural and functional imaging endpoints. Non-cirrhotic patients will begin at a dose of 200 Gy, while cirrhotic patients will begin at 300 Gy. Dose escalation will proceed in 100 Gy increments within each arm, with safety continuously evaluated by the Data Safety Monitoring Committee.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of hepatocellular carcinoma (HCC), cholangiocarcinoma, or liver-dominant metastatic disease not amenable to surgical resection or ablation. * Age ≥18 years. * Child-Pugh class A or B liver function * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. * Adequate organ and bone marrow function as defined below: * Leukocytes (WBC) ≥ 3,000/mcL * Absolute neutrophil count (ANC) ≥ 1,500/mcL * Hemoglobin ≥ 9 g/dL * Platelets ≥ 50,000/mcL * Total bilirubin ≤ 3.0 mg/dL * AST ≤ 100 U/L, ALT ≤ 120 U/L * Creatinine ≤ 2.0 mg/dL or estimated GFR ≥ 40 mL/min/1.73 m² * Ability to undergo imaging and laboratory evaluations required by the study. * Ability to understand and willingness to sign a written informed consent document.
Exclusion criteria
* Extrahepatic metastases. * Pregnant or breastfeeding individuals. * Tumors requiring treatment of more than two Couinaud segments. * Known hypersensitivity to gadolinium-based contrast agents. * Contraindications to MRI (e.g., incompatible pacemakers, claustrophobia unresponsive to sedation). * Coagulopathy or clinical instability precluding angiographic intervention. * Prisoners or individuals under legal custody. * Adults unable to consent. * Individuals under 18 years of age.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ablative Dose Threshold for Y90 Radiation Segmentectomy | From enrollment to the end of post-treatment Y90 12 month follow up visit | To prospectively define the "ablative dose" threshold for Y90 Radiation Segmentectomy (RS) using post-treatment PET dosimetry and hepatobiliary phase MRI |
| Impact of Cirrhosis on Ablative Dose Requirements | From enrollment to enrollment to post-treatment Y-90 12 month follow-up visit | To determine whether cirrhotic patients require a higher threshold dose for ablation compared to non- cirrhotic patients |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation of Y90 Dose with Imaging Biomarkers | Assessed at 1, 4-9, and 12 month follow up visits | To evaluate the correlation between delivered Y90 dose and imaging biomarkers, including signal loss on hepatobiliary phase MRI, ablative margins, extracellular volume fraction, and perfusion changes |
| Tumor Response and Time-to-Progression Assessment | From enrollment to end of post-treatment Y-90 12 month follow up visit | To assess tumor response by mRECIST and determine time to progression (TTP) |
| Safety and Tolerability of Escalating Y90 Doses | From enrollment to end of post-treatment Y90 12 month follow up visit | To assess the safety and tolerability of escalating segmental Y90 doses (200- 500 Gy) using Bayesian optimal interval (BOIN) dose-escalation design under Data and Safety Monitoring Committee (DSMC) oversight |
Countries
United States
Contacts
CONTACTAndrew C Gordon, MD, PhD
CONTACTSaad Abu Zahra, MD
Outcome results
None listed