Hypoxia Imaging Techniques for Liver Cancer

Overseen by Nima Kokabi, MD, FRCPC

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Waitlist Available

Sponsor: Emory University

Disqualifiers: Transplant candidates, Second malignancy, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial evaluates using tiny radioactive beads to treat liver cancer that has spread to a few sites. The treatment involves placing these beads into the blood vessels feeding the tumor, blocking its blood supply and delivering targeted radiation. This approach aims to kill cancer cells while protecting healthy tissue.

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 this treatment for liver cancer?

Research shows that using 18F-Fluoromisonidazole PET/CT imaging can help identify areas of low oxygen (hypoxia) in tumors, which can improve the targeting of radiation therapy in lung and head and neck cancers. This suggests that similar imaging techniques might help optimize radiation treatment for liver cancer by better targeting the tumor. ^{1 2 3 4 5}

Is Yttrium-90 Selective Internal Radiation Therapy (SIRT) safe for humans?

Yttrium-90 Selective Internal Radiation Therapy (SIRT) has been used safely in clinical settings for over two decades, with its safety and effectiveness confirmed for treating liver cancers. It is approved by international guidelines, and while it involves radiation, it is designed to target liver tumors specifically, minimizing exposure to healthy liver tissue. ^{6 7 8 9 10}

How does hypoxia imaging differ from other treatments for liver cancer?

Hypoxia imaging for liver cancer is unique because it uses advanced imaging techniques like PET/CT to detect low oxygen areas in tumors, which can help tailor treatments more effectively. Unlike traditional treatments, this approach focuses on identifying and targeting hypoxic (low oxygen) regions that are often resistant to standard therapies. ^{5 11 12 13 14}

Research Team

Nima Kokabi, MD, FRCPC

Principal Investigator

Emory University

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• 18F-Fluoromisonidazole (Radiopharmaceutical)
• Biopsy (Procedure)
• Dynamic Contrast-Enhanced Magnetic Resonance Imaging (Procedure)
• Positron Emission Tomography (Procedure)

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.

Participant Groups

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+

Dr. R. Donald Harvey

Emory University

Chief Medical Officer

MD from Emory University School of Medicine

Dr. George Painter

Emory University

Chief Executive Officer since 2013

PhD in Synthetic Organic Chemistry from Emory University

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

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 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]

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]

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]

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]

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]

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 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]

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 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]

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]

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]

References

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

Multimodal hypoxia imaging and intensity modulated radiation therapy for unresectable non-small-cell lung cancer: the HIL trial. [2021]

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

The influence of changes in tumor hypoxia on dose-painting treatment plans based on 18F-FMISO positron emission tomography. [2021]

3. China pubmed.ncbi.nlm.nih.gov

[Value of 18F-FETNIM PET-CT for detection of tumor hypoxia in non-small-cell lung cancer]. [2019]

4. Ireland 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. [2016]

5. United States 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. [2018]

6. China pubmed.ncbi.nlm.nih.gov

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

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

Yttrium-90 (Y-90) Resin Microsphere Therapy for Patients with Unresectable Hepatocellular Carcinoma: a Single-Center Experience. [2019]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Outcomes and Predictors of Toxicity after Selective Internal Radiation Therapy Using Yttrium-90 Resin Microspheres for Unresectable Hepatocellular Carcinoma. [2020]

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

90Yttrium PET/MR-based dosimetry after liver radioembolization (SIRT). [2018]

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

Liver Resection After Selective Internal Radiation Therapy with Yttrium-90: Safety and Outcomes. [2020]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Advances in PET and MRI imaging of tumor hypoxia. [2023]

12. Italy pubmed.ncbi.nlm.nih.gov

Hypoxia PET/CT imaging: implications for radiation oncology. [2016]

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

Imaging tumoral hypoxia: oxygen concentrations and beyond. [2016]

14. Germany pubmed.ncbi.nlm.nih.gov

Longitudinal PET imaging of tumor hypoxia during the course of radiotherapy. [2019]