MR-Guided Radiotherapy for Cancer

Overseen By Nawaid Usmani, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: AHS Cancer Control Alberta

Disqualifiers: Mri contraindications, Pregnancy, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 26 months

112 Participants Needed

Trial Summary

What is the purpose of this trial?

Cancers are often treated with external beam radiotherapy. Current radiotherapy treatments are performed using computed tomography (also known as CT) scans which may not always clearly identify the cancer. In some instances, magnetic resonance imaging (MRI) may be able to better identify cancers. Therefore, efforts are currently underway to use the MRI scans to improve radiotherapy treatments or eventually even use radiotherapy equipment that only uses MRI scans to guide treatments. This new technology that will only use MRI scans to guide treatments is called the Linac-MR (linear accelerator with an MRI). This new Linac-MR is a unique innovation at the Cross Cancer Institute, with theoretical advantages over other Linac-MR machines that are being tested elsewhere in the world. This feasibility study is being done as a first step in clinical development of the Linac-MR, as this new technology has to be tested to see if it is acceptable to both doctors and participants. The purpose of this Phase I/II study is (1) to verify treatment completion as intended and scheduled the oncology team, and (2) to evaluate treatment effects, including any expected or unexpected radiation side effects and cancer response to radiation. This study will allow the researchers at the Cross Cancer Institute to develop this technology further by conducting additional studies to take advantage of MRI scanning on tumor tracking during radiation treatments.

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 the treatment MR-guided radiotherapy for cancer?

Research shows that MR-guided radiotherapy (MRgRT) offers improved soft-tissue visualization, allowing for more precise targeting of tumors and adaptive treatment planning. Early results from studies, such as the MOMENTUM study for prostate cancer, indicate promising outcomes, and initial experiences with MRgRT systems demonstrate successful implementation and feasibility in clinical settings. ^{1 2 3 4 5}

Is MR-guided radiotherapy safe for humans?

MR-guided radiotherapy (MRgRT) has been successfully used in adults for various conditions, and safety systems are in place to ensure its safe operation. Studies have focused on maintaining machine stability and quality assurance, which are important for safe treatment delivery. ^{2 5 6 7 8}

How is MR-guided radiotherapy different from other cancer treatments?

MR-guided radiotherapy (MRgRT) is unique because it uses magnetic resonance imaging (MRI) to provide real-time, high-quality images during treatment, allowing for precise targeting of tumors and minimizing damage to surrounding healthy tissue. This approach enables on-the-spot adjustments to the treatment plan and reduces the need for large safety margins, which can lead to more effective and safer cancer treatment. ^{1 4 5 9 10}

Research Team

Nawaid Usmani, MD

Principal Investigator

Cross Cancer Institute, Alberta Health Services

Eligibility Criteria

This trial is for adults over 18 who can undergo external beam radiation therapy and are available for follow-up. It's not suitable for those unable to lie still during scans, cannot consent, have inferior treatment plans with this method compared to standard CT, are pregnant, or have MRI contraindications.

Inclusion Criteria

I am 18 years old or older.

Accessible for follow-up

My radiation oncologist says I'm fit for external beam radiation therapy.

Exclusion Criteria

I am unable to understand or sign the consent form.

Patients with contraindications for MRI

Pregnancy

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MR-guided radiotherapy using the Alberta linac-MR P3 system in four graduated stages, progressing from palliative to curative treatments.

Approximately 26 months

Weekly visits for radiotherapy sessions

Follow-up

Participants are monitored for adverse events and treatment effectiveness at 1, 3, 6, and 12 months following completion of radiotherapy, with annual assessments for up to 5 years.

Up to 5 years

Annual visits (in-person or via chart review)

Treatment Details

Interventions

• MR guided radiotherapy

Trial Overview The Northern LIGHTs-2 study tests a new MR guided radiotherapy technology called Linac-MR. This Phase I/II trial aims to check if the treatment can be completed as planned and assess its effects on cancer and any potential radiation side effects.

Participant Groups

Group I: MR guided radiotherapy Experimental Treatment 1 Intervention

MR-guided radiotherapy using the Alberta linac-MR P3 system. Contemporary radiotherapy techniques and fractionation schedules will be conducted in the following graduated stages with overlap between stages allowed: Stage 1: Parallel-opposed pair treatments (palliative) Stage 2: 4 field box and breast treatments (curative or palliative) Stage 3: Radical treatments - multi-field 3DCRT (curative) Stage 4: Radical treatments - multi-field IMRT (curative)

MR guided radiotherapy is already approved in Canada, European Union, United States for the following indications:

Approved in Canada as MRgRT for:

• Prostate cancer
• Rectal cancer
• Breast cancer
• Lung cancer
• Stomach cancer

Approved in European Union as MR-Linac for:

• Prostate cancer
• Rectal cancer

Approved in United States as MRgRT for:

• Prostate cancer
• Rectal cancer

Who Is Running the Clinical Trial?

AHS Cancer Control Alberta

Lead Sponsor

Trials

188

Recruited

26,900+

Findings from Research

The implementation of the MR-linac system for magnetic resonance-guided radiation therapy (MRgRT) at a single institution in Turkey has shown feasibility for routine clinical use, successfully treating 72 patients across 84 tumor sites with real-time imaging and adaptive radiation planning.

The system allowed for on-table adaptive radiation therapy (oART) in 93.2% of patients and utilized automated beam gating to manage breathing-related motion, demonstrating its potential to improve treatment precision and patient safety during radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First 500 Fractions Delivered with a Magnetic Resonance-guided Radiotherapy System: Initial Experience. Sahin, B., Zoto Mustafayev, T., Gungor, G., et al.[2020]

A dedicated MR-guided radiotherapy (MRgRT) facility has been developed to enhance the integration of magnetic resonance imaging into the radiotherapy treatment process, improving confidence in dose placement.

This facility combines advanced imaging and treatment technologies, allowing for real-time treatment guidance and adaptive replanning, which can lead to safer and more effective cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A facility for magnetic resonance-guided radiation therapy. Jaffray, DA., Carlone, MC., Milosevic, MF., et al.[2022]

The study successfully demonstrated that high-quality treatment plans for MR-guided radiotherapy (MR-linac) can be created, showing feasibility for clinical use in rectal and prostate cancer patients.

MR-linac plans resulted in slightly higher doses to the target areas compared to conventional plans, but all plans were clinically equivalent to current practices, indicating that MR-linac could be a viable option for improving radiotherapy outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of plan quality in radiotherapy planning with an MR-linac. van de Schoot, AJAJ., van den Wollenberg, W., Carbaat, C., et al.[2022]

The development of a 0.35 T MR-Linac system allows for advanced MR-guided radiation therapy, integrating daily MR imaging for better soft-tissue contrast and enabling precise patient setup and treatment plan adjustments.

This hybrid system enhances treatment precision through features like automated beam gating and structure tracking, potentially leading to reduced margins and increased radiation doses to tumors while minimizing damage to surrounding healthy tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Technical design and concept of a 0.35 T MR-Linac. Klüter, S.[2020]

In a study of 425 localized prostate cancer patients treated with MR-guided ultrahypofractionated radiation therapy, significant declines in prostate-specific antigen levels were observed, indicating effective treatment outcomes over 12 months.

While the therapy was generally safe, with peak toxicity reported at 3 months, patients not receiving androgen deprivation therapy experienced significant worsening of erectile function by 12 months, highlighting the need for patient education on potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic Resonance-Guided Adaptive Radiation Therapy for Prostate Cancer: The First Results from the MOMENTUM study-An International Registry for the Evidence-Based Introduction of Magnetic Resonance-Guided Adaptive Radiation Therapy. Teunissen, FR., Willigenburg, T., Tree, AC., et al.[2023]

The development of an online Magnetic Resonance guided Radiation Therapy (MRgRT) system aims to enhance safety by providing real-time MRI images before radiation treatment, allowing for better image guidance.

A thorough failure modes and effects analysis identified potential risks during the design and operation of the MRgRT system, leading to design improvements and safety measures before installation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Poster - Thur Eve - 05: Safety systems and failure modes and effects analysis for a magnetic resonance image guided radiation therapy system. Lamey, M., Carlone, M., Alasti, H., et al.[2019]

A 7-month longitudinal study of an MR-guided radiotherapy system showed that daily quality assurance procedures effectively monitored the system's accuracy, with isocenter accuracy averaging 1.6 mm across cardinal angles.

The system demonstrated stable performance in safety interlocks, output, and MLC positioning, indicating reliable dosimetric and mechanical stability, despite some drift in dose rate over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization and longitudinal assessment of daily quality assurance for an MR-guided radiotherapy (MRgRT) linac. Mittauer, KE., Dunkerley, DAP., Yadav, P., et al.[2023]

A survey of 12 pediatric radiotherapy institutions indicated that while the expected benefit of magnetic resonance guided radiotherapy (MRgRT) for reducing toxicity and improving outcomes is modest, there is a significant potential for benefit in 55% of primary tumor scenarios and 62% of metastatic tumor scenarios.

The study highlights the need for further investigation into MRgRT's role in pediatric oncology, particularly through prospective studies or registration trials, to better understand its impact on treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential role of MR-guided adaptive radiotherapy in pediatric oncology: Results from a SIOPE-COG survey. Seravalli, E., Kroon, PS., Buatti, JM., et al.[2022]

Magnetic resonance-guided radiation therapy (MRgRT) provides superior soft tissue contrast compared to conventional CT-based methods, enhancing the visualization of tumors and surrounding healthy tissues in abdominal and thoracic cancers.

The use of MRgRT allows for high-precision localization of tumors through real-time tracking and adaptive capabilities, improving treatment accuracy for difficult-to-visualize targets like those in the lung, kidney, liver, and stomach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A New Era of Image Guidance with Magnetic Resonance-guided Radiation Therapy for Abdominal and Thoracic Malignancies. Mittauer, K., Paliwal, B., Hill, P., et al.[2022]

Magnetic resonance-guided radiation therapy (MRgRT) has been successfully implemented in treating localized prostate cancer for 140 patients, allowing for daily plan re-optimization and improved targeting during treatment delivery.

Patient feedback indicated that MRgRT was generally well tolerated, although the treatment sessions were longer (averaging 45 minutes) and some patients reported discomfort from noise during the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical implementation of magnetic resonance imaging guided adaptive radiotherapy for localized prostate cancer. Tetar, SU., Bruynzeel, AME., Lagerwaard, FJ., et al.[2022]

References

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

First 500 Fractions Delivered with a Magnetic Resonance-guided Radiotherapy System: Initial Experience. [2020]

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

A facility for magnetic resonance-guided radiation therapy. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Evaluation of plan quality in radiotherapy planning with an MR-linac. [2022]

4. Ireland pubmed.ncbi.nlm.nih.gov

Technical design and concept of a 0.35 T MR-Linac. [2020]

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

Magnetic Resonance-Guided Adaptive Radiation Therapy for Prostate Cancer: The First Results from the MOMENTUM study-An International Registry for the Evidence-Based Introduction of Magnetic Resonance-Guided Adaptive Radiation Therapy. [2023]

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

Poster - Thur Eve - 05: Safety systems and failure modes and effects analysis for a magnetic resonance image guided radiation therapy system. [2019]

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

Characterization and longitudinal assessment of daily quality assurance for an MR-guided radiotherapy (MRgRT) linac. [2023]

8. Ireland pubmed.ncbi.nlm.nih.gov

The potential role of MR-guided adaptive radiotherapy in pediatric oncology: Results from a SIOPE-COG survey. [2022]

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

A New Era of Image Guidance with Magnetic Resonance-guided Radiation Therapy for Abdominal and Thoracic Malignancies. [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Clinical implementation of magnetic resonance imaging guided adaptive radiotherapy for localized prostate cancer. [2022]