Hypoxia Imaging Techniques for Liver Cancer

Overseen By David Schuster, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Emory University

Disqualifiers: Transplant candidates, Second malignancy, others

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

Compensation: Varies

Number of Visits: 3

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to measure how much oxygen liver cancer tumors use to predict the outcomes of Y90 radioembolization treatment. Y90 radioembolization involves placing tiny radioactive beads in the blood vessels feeding the tumor, cutting off its blood supply and delivering targeted radiation. The study employs imaging techniques like PET (Positron Emission Tomography) and MRI to track changes before treatment begins. Individuals with liver cancer that has spread to a few locations and have at least one tumor larger than 3 cm might be suitable for this trial. As an Early Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this innovative approach.

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 prior data suggests that these hypoxia imaging techniques are safe for liver cancer patients?

Research has shown that Y-90 selective internal radiation therapy (SIRT) is usually well-tolerated by patients. In past studies, patients with liver cancer who received Y-90 SIRT did not experience serious side effects. This treatment uses tiny beads filled with radioactive material to target cancer cells and has effectively controlled tumors.

For imaging, techniques like DCE-MRI (Dynamic Contrast-Enhanced Magnetic Resonance Imaging) show promise in assessing tumor response to treatments. This method is non-invasive, meaning it doesn't require surgery or entering the body, and is generally safe.

Positron Emission Tomography (PET) is another imaging method used in this context. Research has shown it to be effective and safe for viewing liver cancer. Like DCE-MRI, PET is non-invasive, enhancing its safety.

Overall, the treatments and imaging methods in this trial have demonstrated good safety records in previous research. Although this trial is in an early stage, these treatments have been used safely in other situations. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about hypoxia imaging techniques for liver cancer because they offer a new way to visualize and understand tumor environments. Unlike traditional imaging methods, this approach uses 18F-fluoromisonidazole, a special tracer that highlights areas of low oxygen within tumors when used with PET and DCE MRI scans. This can help doctors better target treatments like Y90 SIRT, potentially improving outcomes. By providing a more detailed picture of tumor biology, these imaging techniques could lead to more personalized and effective treatment plans for liver cancer patients.

What evidence suggests that these imaging techniques are effective for assessing liver cancer treatment?

In this trial, participants will undergo diagnostic procedures using 18F-fluoromisonidazole, PET, and Dynamic Contrast-Enhanced MRI (DCE MRI) before receiving Y90 selective internal radiation therapy (SIRT). Studies have shown that Y90 SIRT effectively controls liver cancer tumors, managing them without causing serious side effects. Y90 SIRT uses tiny beads filled with radiation to block the tumor's blood supply while delivering radiation directly to it. Research indicates that DCE MRI can effectively monitor how liver cancer responds to treatments like Y90 SIRT. Positron Emission Tomography (PET) effectively visualizes liver cancer and aids in better staging and managing the disease. Together, these methods offer promising ways to evaluate and potentially improve treatment outcomes for liver cancer. ^{1 2 3 4 5}

Who Is on the Research Team?

Nima Kokabi, MD, FRCPC

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

This trial is for adults with liver cancer that has spread but not widely (oligometastatic). They should have at least one tumor larger than 3 cm, be in relatively good health (ECOG <=2), and have a life expectancy over 12 weeks. Women must test negative for pregnancy and all participants agree to use birth control. People with widespread liver cancer, poor liver function, or other serious health issues are excluded.

Inclusion Criteria

My cancer has spread to a few other parts of my body.

I agree to use effective birth control during the study.

I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

I have had treatments specifically aimed at liver tumors.

I have another type of cancer besides the one in my liver.

Patients who are definite transplant candidates

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Diagnostic Imaging

Participants receive 18F-fluoromisonidazole IV and undergo PET and DCE MRI within 30 days before beginning Y90 SIRT

4 weeks

1 visit (in-person)

Treatment

Participants undergo Y90 selective internal radiation therapy per standard of care

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year

1 visit every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 18F-Fluoromisonidazole
• Biopsy
• Dynamic Contrast-Enhanced Magnetic Resonance Imaging
• Positron Emission Tomography

Trial Overview The study tests if measuring low oxygen areas can predict outcomes of Y90 selective internal radiation therapy in oligometastatic liver cancer patients. It involves placing radioactive beads near the tumor to block blood flow and deliver high doses of radiation directly while sparing healthy tissue.

How Is the Trial Designed?

Group I: Diagnostic (18F-fluoromisonidazole, PET, DCE MRI) Experimental Treatment 4 Interventions

Patients receive 18F-fluoromisonidazole IV and undergo PET and DCE MRI within 30 days before beginning Y90 SIRT. Patients undergo Y90 SIRT per standard of care.

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study involving 7 patients with head and neck cancers, changes in tumor hypoxia detected by serial FMISO PET imaging affected the effectiveness of intensity-modulated radiotherapy (IMRT) dose painting, leading to reduced coverage of hypoxic tumor volumes.

Despite the challenges posed by changing hypoxic volumes, dose painting with IMRT consistently increased the equivalent uniform dose (EUD) to these hypoxic areas, suggesting that it remains a beneficial strategy for targeting difficult-to-treat tumor regions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The influence of changes in tumor hypoxia on dose-painting treatment plans based on 18F-FMISO positron emission tomography. Lin, Z., Mechalakos, J., Nehmeh, S., et al.[2021]

The study involving 42 patients with newly diagnosed non-small-cell lung cancer (NSCLC) demonstrated that (18)F-FETNIM PET-CT imaging can effectively detect hypoxia in tumors, with significantly higher uptake in cancerous tissue compared to normal lung tissue.

(18)F-FETNIM PET-CT may help identify tumor cells that are resistant to standard treatments, suggesting its potential as a valuable tool for tailoring therapy in NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Value of 18F-FETNIM PET-CT for detection of tumor hypoxia in non-small-cell lung cancer]. Hu, M., Kong, L., Zhao, SQ., et al.[2019]

In a study involving eight head and neck cancer patients, (18)F-FMISO PET/CT-guided intensity-modulated radiotherapy (IMRT) allowed for a safe dose escalation to 78Gy for hypoxic tumor volumes without increasing radiation exposure to normal tissues.

The feasibility of this approach was confirmed in six out of the eight patients, suggesting that targeted radiation therapy can be effectively tailored based on tumor hypoxia, potentially improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Planning study for available dose of hypoxic tumor volume using fluorine-18-labeled fluoromisonidazole positron emission tomography for treatment of the head and neck cancer. Choi, W., Lee, SW., Park, SH., et al.[2016]

Tumor hypoxia, which occurs when there is not enough oxygen in tumor tissues, negatively affects how well tumors respond to radiation therapy, making it a critical factor in cancer treatment.

The review highlights the use of positron emission tomography (PET) tracers as a method to measure tumor hypoxia, which can help predict treatment responses and improve radiation therapy strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypoxia PET/CT imaging: implications for radiation oncology. Arabi, M., Piert, M.[2016]

The HIL trial is investigating the use of multimodal hypoxia imaging techniques, specifically (18)F-FMISO dPET-CT and functional MRI, in combination with intensity modulated radiation therapy (IMRT) for treating 15 patients with inoperable stage III non-small cell lung cancer (NSCLC).

The study aims to determine how well these imaging methods correlate in visualizing tumor hypoxia and to assess their potential impact on treatment outcomes, such as locoregional control and overall survival, which could inform future larger clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multimodal hypoxia imaging and intensity modulated radiation therapy for unresectable non-small-cell lung cancer: the HIL trial. Askoxylakis, V., Dinkel, J., Eichinger, M., et al.[2021]

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 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]

In a study involving 42 patients with inoperable stages III-IV lung cancer, 18F-fluoromisonidazole (18F-FMISO) demonstrated significantly higher uptake in tumors compared to 18F-fluoroerythronitroimidazole (18F-FETNIM), suggesting it may be a more effective tracer for assessing hypoxia in lung cancer.

Both imaging techniques showed higher uptake in stage IV lung cancer compared to stage III, indicating that hypoxia levels may correlate with cancer progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Comparative Study of Noninvasive Hypoxia Imaging with 18F-Fluoroerythronitroimidazole and 18F-Fluoromisonidazole PET/CT in Patients with Lung Cancer. Wei, Y., Zhao, W., Huang, Y., et al.[2018]

The study highlights the feasibility of using PET/MR imaging for assessing biodistribution and dosimetry in liver selective internal radiotherapy (SIRT), which is important for effective radionuclide therapies.

PET/MR offers advantages over traditional PET/CT, including better lesion detection and reduced radiation exposure, making it a promising tool for repeated imaging in SIRT dosimetry.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

90Yttrium PET/MR-based dosimetry after liver radioembolization (SIRT). Wissmeyer, M., Delattre, BM., Zaidi, H., et al.[2018]

Selective internal yttrium-90 radioembolization therapy ((90)Y-SIRT) is an effective and safe minimally invasive treatment for liver malignant tumors, supported by clinical applications over the past two decades and recognized by major cancer treatment guidelines.

A consensus was formed by experts from various medical fields to standardize the management and treatment procedures for (90)Y-SIRT, addressing critical aspects such as indications, contraindications, postoperative follow-up, and radiation safety, to enhance treatment safety and success rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chinese expert consensus on selective internal radiation therapy with yttrium-90 for primary and metastatic hepatocellular carcinoma]. [2021]

Hypoxia, or low oxygen levels in tumors, significantly affects cancer outcomes, prompting the development of noninvasive imaging techniques to detect and localize these hypoxic regions.

Emerging molecular imaging methods using radiolabeled markers and hypoxia-related genes show promise for directly targeting hypoxic areas in tumors, which could enhance cancer treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging tumoral hypoxia: oxygen concentrations and beyond. Graves, EE., Giaccia, AJ.[2016]

In a study of 27 patients with unresectable hepatocellular carcinoma (HCC) treated with yttrium-90 selective internal radiation therapy (90Y-SIRT), the treatment was well-tolerated with no Grade 3-4 clinical toxicities reported, although 38% experienced significant laboratory toxicities within 3 months.

Patients with higher pretreatment bilirubin or transaminase levels were found to be at increased risk for worsening liver function after treatment, indicating the need for careful monitoring in these individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes and Predictors of Toxicity after Selective Internal Radiation Therapy Using Yttrium-90 Resin Microspheres for Unresectable Hepatocellular Carcinoma. Gabrielson, A., Miller, A., Banovac, F., et al.[2020]

Tumor hypoxia is a critical factor that affects tumor aggressiveness, spread, and resistance to treatments, making accurate imaging tools essential for effective cancer management.

This review discusses various imaging techniques, including PET and MRI, highlighting their strengths and limitations in detecting hypoxic tumor regions, which is crucial for understanding tumor behavior and guiding treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in PET and MRI imaging of tumor hypoxia. Gouel, P., Decazes, P., Vera, P., et al.[2023]

Tumor hypoxia, which is common in head and neck cancers, makes cancer cells more resistant to treatment and is associated with a poorer prognosis, highlighting the importance of measuring tissue oxygenation.

Among various techniques to assess hypoxia, hypoxia positron emission tomography (PET) is the most validated for clinical use, particularly using tracers like 18F-fluoromisonidazole (FMISO), which can help identify stable hypoxic regions during radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longitudinal PET imaging of tumor hypoxia during the course of radiotherapy. Stieb, S., Eleftheriou, A., Warnock, G., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5674259/

Selective internal radiation therapy using yttrium-90 resin ... Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: a European evaluation.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2542568421000441

Clinical outcome of Yttrium-90 selective internal radiation ... Y-90 SIRT is an effective treatment for the local tumor control of HCC without serious adverse events. Single lesion, AFP level and ECOG status were predictors ...

3. bmcgastroenterol.biomedcentral.com bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-021-01805-6

Efficacy and safety of selective internal radiation therapy with ... SIRT was an effective treatment for unresectable HCC. Unilobar disease before SIRT and tumor response (CR/PR) were positive prognostic factors.

4. accscience.com accscience.com/journal/ARNM/1/1/10.36922/arnm.0385

Safety and effectiveness of selective internal radiation ... The study aimed to evaluate the safety and effectiveness of selective internal radiation therapy (SIRT) in patients with unresectable hepatocellular carcinoma ...

5. jgo.amegroups.org jgo.amegroups.org/article/view/10538/html

Selective internal radiation therapy with SIR-Spheres in ... This article outlines mechanisms involved in SIRT administration and reviews key efficacy and safety data that are currently available in the literature.