Brain Imaging Biomarkers for Brain Metastases

Overseen By Catherine Coolens, Ph. D

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Disqualifiers: Previous radiotherapy, Radiosurgery, MRI inability

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

90 Participants Needed

Trial Summary

What is the purpose of this trial?

A biomarker is a measurable indicator of the severity or presence of some disease state. In this study, brain metastases patients who will be receiving radiation treatment, will undergo CT (Computed Tomography) and MRI (Magnetic Resonance Imaging) scans prior to and after radiation treatment to measure these biomarkers. This is a single-center phase II study to validate the predictive abilities of biomarkers, in terms of determining how patients will respond to radiation treatment.

Do I need to stop my current medications for this trial?

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 using CT and MRI scans for brain metastases?

Research shows that MRI is a key tool for evaluating brain metastases, helping to detect and diagnose these tumors accurately. MRI scans can provide detailed information about the brain, which aids in early detection and treatment planning, potentially improving patient outcomes. ^{1 2 3 4 5}

Is MRI safe for humans?

MRI scans are generally considered safe for humans, even with repeated exposure, but there are some risks if safety guidelines are not followed. Most side effects are minor and reversible, but serious accidents can occur if patients have certain conditions or implants that are not compatible with MRI. ^{1 6 7 8 9}

How does this treatment differ from other treatments for brain metastases?

This treatment is unique because it uses advanced MRI techniques to provide detailed information about the cellular and metabolic features of brain metastases, which can improve early detection, diagnosis, and evaluation of treatment response compared to traditional imaging methods. ^{1 10 11 12 13}

Research Team

Catherine Coolens, Ph. D

Principal Investigator

Princess Margaret Cancer Center - UHN

Eligibility Criteria

This trial is for adults over 18 with confirmed primary cancer and brain metastases visible on scans, who are scheduled for radiation therapy. They must have at least one lesion larger than 1cm without bleeding in the brain and be able to consent. Those with prior whole-brain radiotherapy or radiosurgery to the target lesion, or unable to have contrasted MRI cannot join.

Inclusion Criteria

I have a tumor larger than 1cm without any bleeding inside it.

I am older than 18 years.

My cancer diagnosis was confirmed with a biopsy, and I have brain metastases.

Exclusion Criteria

I have had radiosurgery on the main tumor.

I have had whole brain radiotherapy before.

You cannot have a MRI scan with contrast dye for any reason.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Radiation Treatment

Participants receive radiation treatment for brain metastases

Duration not specified

1 visit (in-person)

Imaging and Biomarker Assessment

CT and MRI scans are conducted prior to and after radiation treatment to measure biomarkers

3 months

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Routine follow-up visits as per standard of care

Treatment Details

Interventions

• CT and MRI Scans

Trial Overview The study tests if CT and MRI scans before and after radiation can act as biomarkers—signs that show how severe a disease is or if it's present—to predict treatment response in patients with brain tumors from metastasized cancer.

Participant Groups

Group I: CT and MRI Scans Experimental Treatment 1 Intervention

Each patient will undergo a 3T MRI scan as well as a dynamic contrast-enhanced CT scan within one week prior to the start of treatment. Patients will also undergo a research 3T MRI scan and research dynamic contrast-enhanced CT scan at the one week post radiotherapy mark. An MRI scan during their 3 month post-treatment follow up visits will take place as per routine standard of care.

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Findings from Research

MRI is essential for evaluating brain masses, but challenges remain in accurately detecting and diagnosing brain metastases, particularly in distinguishing them from primary tumors and infections.

Newer MRI techniques and PET imaging are being investigated to improve the detection and characterization of brain metastases, offering valuable insights into tumor biology that could enhance patient management and treatment response monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain metastases: neuroimaging. Pope, WB.[2018]

Using automated color-coding for assessing brain metastases significantly improved the accuracy of diagnoses, with a correct classification rate of 91.3% compared to 74.0% with conventional methods, based on a study of 121 pairs of follow-up MR examinations.

The use of automated color-coding also enhanced radiologists' diagnostic certainty, as indicated by an increase in the median Likert score from 2 to 4, although it required more time for image processing compared to traditional reading.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Automated Color-Coding of Lesion Changes in Contrast-Enhanced 3D T1-Weighted Sequences for MRI Follow-up of Brain Metastases. Zopfs, D., Laukamp, K., Reimer, R., et al.[2023]

MRI showed a higher tendency for preoperative detection of brain metastases compared to CT, identifying 3.4% of patients versus 0.6% for CT, suggesting MRI may be more effective for early detection in lung cancer patients.

Despite MRI detecting smaller brain metastases (average diameter of 12.8 mm) compared to CT (20.3 mm), there was no significant difference in survival rates between the two imaging methods, indicating that early detection does not necessarily translate to improved survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of brain metastasis in potentially operable non-small cell lung cancer: a comparison of CT and MRI. Yokoi, K., Kamiya, N., Matsuguma, H., et al.[2022]

Multimodal MRI significantly improves the accuracy of tumor delineation in brain metastases compared to single-modality imaging, with a more precise measurement of tumor volume (132 ± 41 μL vs. 85 ± 36 μL from single-modality MRI).

The use of multimodal MRI enhances sensitivity for detecting metastases (0.82 vs. 0.61 for single-modality), which could lead to better treatment planning and potentially reduce relapse rates and improve survival in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving Delineation of True Tumor Volume With Multimodal MRI in a Rat Model of Brain Metastasis. Larkin, JR., Simard, MA., de Bernardi, A., et al.[2021]

Screening MRI scans can help detect brain metastases early in patients with metastatic melanoma, identifying 39% of cases, including 8 asymptomatic patients, which can lead to timely treatment decisions.

Follow-up MRI scans significantly influenced treatment strategies in 45% of cases for patients with melanoma brain metastases, although fewer changes were noted in patients who had been on immune checkpoint inhibitors for a longer duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Value of screening and follow-up brain MRI scans in patients with metastatic melanoma. Eggen, AC., Wind, TT., Bosma, I., et al.[2022]

MRI is generally safe for humans, even with repeated exposure, but certain components can cause temporary inconveniences or severe accidents if safety protocols are not followed.

The article reviews reported MRI accidents, explaining their mechanisms and emphasizing the importance of strict safety measures to prevent serious adverse effects, including potential fatalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Risks associated with MRI: safety rules, incidents, and accidents]. de Kerviler, E., de Bazelaire, C., Mathieu, O., et al.[2019]

In a study involving 148,489 patients over 10 years, gadoteric acid (Dotarem®) was found to be a safe MRI contrast agent, with only 0.3% of patients experiencing adverse events, primarily mild symptoms like nausea and vomiting.

The diagnostic effectiveness was high, with 99.8% of examinations yielding useful results and excellent or good image quality in 97.7% of cases, indicating that gadoteric acid is effective for routine MRI procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baseline characteristics, diagnostic efficacy, and peri-examinational safety of IV gadoteric acid MRI in 148,489 patients. Braun, J., Busse, R., Darmon-Kern, E., et al.[2020]

The study successfully established a VX2 rabbit model for brain metastases, demonstrating its feasibility and safety, as no rabbits died during the procedures and they regained lost weight within 14 days.

Dynamic contrast-enhanced MRI (DCE-MRI) significantly improved the detection of brain metastases, achieving a 100% detection rate compared to only 12% and 32% for T1-weighted and T2-weighted images, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional dynamic contrast-enhanced magnetic resonance imaging in an animal model of brain metastases: a pilot study. Zheng, L., Sun, P., Zheng, S., et al.[2021]

Magnetic resonance imaging (MRI) is generally considered both safe and effective for diagnostic purposes, with ongoing improvements in technology and clinical practices enhancing its safety profile.

The article reviews various safety considerations related to MRI operations, highlighting the importance of understanding both bioeffects and operational safety issues based on extensive clinical experience and reported incidents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Operational safety issues in MRI. Gangarosa, RE., Minnis, JE., Nobbe, J., et al.[2019]

Advanced magnetic resonance imaging (MRI) techniques can provide quantitative parameters that help in diagnosing and managing cerebral metastases, improving the accuracy of distinguishing these from primary brain tumors and other mimics.

These imaging biomarkers may also assist in predicting the origin of the primary tumor, which is crucial for effective treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advanced magnetic resonance imaging biomarkers of cerebral metastases. Mills, SJ., Thompson, G., Jackson, A.[2021]

Brain metastases are the most common type of intracranial tumors, affecting 20-40% of cancer patients, with lung cancer, breast cancer, and melanoma being the primary sources.

Advanced MRI techniques, such as magnetic resonance spectroscopy and diffusion-based imaging, can enhance the detection and management of brain metastases by providing detailed insights into tumor characteristics and treatment responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advanced Magnetic Resonance Imaging Techniques in Management of Brain Metastases. Mehrabian, H., Detsky, J., Soliman, H., et al.[2020]

Functional neuroimaging techniques like MRI and PET are becoming crucial for diagnosing brain metastases, monitoring treatment responses, and predicting patient prognosis.

As cancer therapies improve and patients live longer, these advanced imaging methods help in better detecting brain tumors and assessing the effectiveness of new targeted and immunomodulatory treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The emerging role of advanced neuroimaging techniques for brain metastases. Nowosielski, M., Radbruch, A.[2015]

Neuroimaging, particularly computed tomography and magnetic resonance imaging, is essential for diagnosing and differentiating brain metastases in patients with known or unknown cancers, helping to identify solitary brain lesions effectively.

Advanced imaging techniques and the integration of artificial intelligence enhance the accuracy of diagnosis and treatment assessment, allowing for better differentiation between tumor recurrence and treatment-related complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Morphological and Functional Neuroradiology of Brain Metastases. Grazzini, I., Venezia, D., Del Roscio, D., et al.[2023]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Brain metastases: neuroimaging. [2018]

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

Automated Color-Coding of Lesion Changes in Contrast-Enhanced 3D T1-Weighted Sequences for MRI Follow-up of Brain Metastases. [2023]

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

Detection of brain metastasis in potentially operable non-small cell lung cancer: a comparison of CT and MRI. [2022]

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

Improving Delineation of True Tumor Volume With Multimodal MRI in a Rat Model of Brain Metastasis. [2021]

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

Value of screening and follow-up brain MRI scans in patients with metastatic melanoma. [2022]

6. France pubmed.ncbi.nlm.nih.gov

[Risks associated with MRI: safety rules, incidents, and accidents]. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Baseline characteristics, diagnostic efficacy, and peri-examinational safety of IV gadoteric acid MRI in 148,489 patients. [2020]

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

Functional dynamic contrast-enhanced magnetic resonance imaging in an animal model of brain metastases: a pilot study. [2021]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Operational safety issues in MRI. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Advanced magnetic resonance imaging biomarkers of cerebral metastases. [2021]

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

Advanced Magnetic Resonance Imaging Techniques in Management of Brain Metastases. [2020]

12. China pubmed.ncbi.nlm.nih.gov

The emerging role of advanced neuroimaging techniques for brain metastases. [2015]

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

Morphological and Functional Neuroradiology of Brain Metastases. [2023]