MRI-Guided Radiation Therapy for Breast Cancer

(PPI Trial)

Overseen By Lhaden Tshering, B.S.

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Weill Medical College of Cornell University

Disqualifiers: Previous radiation, Metastatic, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1-2 weeks

17 Participants Needed

Trial Summary

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

The trial protocol does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more information.

Do I need to stop my current medications for the 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 idea that MRI-Guided Radiation Therapy for Breast Cancer is an effective treatment?

The available research shows that MRI-Guided Radiation Therapy for Breast Cancer can be effective because it helps to reduce the amount of healthy tissue exposed to radiation. This is important because it can lower the risk of side effects. For example, one study found that using MRI guidance in a prone position (lying face down) can reduce the radiation dose to the heart and lungs, which is beneficial for patients with left-sided breast cancer. Another study highlights that MRI guidance can improve the visibility of the tumor, allowing for more precise targeting and potentially better outcomes. Compared to traditional methods, MRI guidance can also reduce the number of treatment sessions needed, which can be more convenient for patients. ^{1 2 3 4 5}

What data supports the effectiveness of MRI-guided radiation therapy for breast cancer?

Research shows that MRI-guided radiation therapy can improve the precision of targeting tumors, reducing the amount of healthy tissue exposed to radiation. This approach, especially in the prone position, can lower the risk of damage to the heart and lungs, which is particularly beneficial for left-sided breast cancer. ^{1 2 3 4 5}

What safety data is available for MRI-guided radiation therapy for breast cancer?

The safety data for MRI-guided radiation therapy for breast cancer includes studies on the risk of radiation-induced secondary malignancies with partial breast irradiation using a 1.5 T MR-linac, which highlights potential long-term toxicities. Additionally, prone positioning for whole breast irradiation has been shown to result in lower toxicity and reduced lung and heart doses compared to supine positioning. MRI-guided stereotactic accelerated partial breast irradiation (MRgS-APBI) offers reduced irradiated volumes and radiation exposure while maintaining clinical outcomes, suggesting a favorable safety profile. ^{1 5 6 7 8}

Is MRI-guided radiation therapy for breast cancer safe?

MRI-guided radiation therapy for breast cancer, such as prone whole breast irradiation, has been shown to result in lower rates of toxicity and reduced radiation exposure to the heart and lungs compared to other methods. Additionally, MRI-guided approaches can reduce the amount of healthy tissue exposed to radiation, potentially lowering the risk of long-term side effects. ^{1 5 6 7 8}

Is MRI-guided Precision Prone Irradiation a promising treatment for breast cancer?

Yes, MRI-guided Precision Prone Irradiation is promising because it can focus radiation more precisely on the tumor, reducing the amount of healthy breast tissue exposed to radiation. This precision helps lower the risk of side effects and improves the effectiveness of the treatment. ^{1 2 9 10 11}

What makes MRI-guided radiation therapy for breast cancer unique compared to other treatments?

MRI-guided radiation therapy for breast cancer is unique because it uses MRI technology to precisely target the tumor, reducing the amount of healthy breast tissue exposed to radiation. This approach can potentially lower the risk of side effects and improve treatment accuracy by allowing better visualization of the tumor before and during each treatment session. ^{1 2 9 10 11}

What is the purpose of this trial?

The Investigators are investigating the potential role of MRI-guided Radiation Therapy for patients receiving breast radiotherapy in the prone position with a MRI-Linac radiotherapy system, the Precision Prone Irradiation (PPI) technique. Hypothesis: The investigators would like to hypothesize that breast radiation therapy using MRI-guided system including the MRI-Linac (Arm 2) is comparable to the current standard of treatment using conventional CT-based system (Arm 1), in terms of local control of the disease at 2 year time point.

Research Team

John Ng, M.D.

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

This trial is for women over 50 with early-stage breast cancer (DCIS or Stage I) who've had a lumpectomy with clear margins. It's not for those who've had radiation on the same breast before, can't have an MRI, are more than 90 days post-surgery without chemo, or more than 60 days post-chemo.

Inclusion Criteria

I am over 50, had surgery for early breast cancer or DCIS, with a small tumor removed cleanly.

My breast cancer was removed with clear margins.

My cancer has not spread to nearby lymph nodes.

Exclusion Criteria

It has been over 60 days since my last chemotherapy session.

I cannot undergo MRI or am not suitable for MRI-based treatments.

My cancer has spread to other parts of my body.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 3000 cGy in 5 fractions partial breast radiotherapy with either CT-based or MRI-based system

1-2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with annual follow-ups up to 10 years

10 years

Treatment Details

Interventions

• CT-guided Breast Irradiation
• MRI-guided Precision Prone Irradiation (PPI)

Trial Overview The study compares two types of radiation therapy after breast-conserving surgery: standard CT-guided treatment and a new MRI-guided method called Precision Prone Irradiation (PPI), to see if they're equally effective at controlling cancer after two years.

Participant Groups

Group I: ARM 1 - CT-based breast radiation treatment Active Control 1 Intervention

Patients randomized to ARM 1 will receive 3000 cGy in 5 fractions partial breast radiotherapy with CT-based breast radiation treatment.

Group II: ARM 2 - MRI-based breast radiation treatment Active Control 1 Intervention

Patients randomized to ARM 2 will receive 3000 cGy in 5 fractions partial breast radiotherapy with MRI-based breast radiation treatment.

CT-guided Breast Irradiation is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as CT-guided Breast Irradiation for:

• Breast cancer
• Early-stage breast cancer
• Locally advanced breast cancer

Approved in United States as CT-guided Breast Irradiation for:

• Breast cancer
• Early-stage breast cancer
• Locally advanced breast cancer
• Ductal carcinoma in situ (DCIS)

Approved in Canada as CT-guided Breast Irradiation for:

• Breast cancer
• Early-stage breast cancer
• Locally advanced breast cancer

Approved in Japan as CT-guided Breast Irradiation for:

• Breast cancer
• Early-stage breast cancer

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

Findings from Research

In a study involving 18 breast cancer patients, the use of preoperative MRI images to define target volumes for postoperative radiation therapy showed poor spatial overlap with the actual tumor bed identified on postoperative CT scans, indicating a potential mismatch in treatment planning.

The findings suggest that relying on preoperative MRI for guiding postoperative target delineation in external-beam partial breast irradiation may not be effective, highlighting the need for accurate imaging techniques in radiation therapy planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative study based on deformable image registration of the target volumes for external-beam partial breast irradiation defined using preoperative prone magnetic resonance imaging and postoperative prone computed tomography imaging. Yu, T., Li, JB., Wang, W., et al.[2020]

Neoadjuvant partial breast irradiation (PBI) is being researched to minimize the amount of breast tissue exposed to radiation, which could lower the risk of long-term side effects from treatment.

Magnetic resonance (MR)-guided radiotherapy, particularly using MR-linac systems, may enhance tumor visibility during treatment, potentially allowing for even more precise targeting and reduced radiation exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing MR-Guided Radiotherapy for Breast Cancer Patients. Groot Koerkamp, ML., Vasmel, JE., Russell, NS., et al.[2021]

The study compares the effectiveness of prone versus supine positions in radiotherapy planning for breast cancer, highlighting that the standard supine position may lead to uneven radiation exposure and potential harm to surrounding healthy tissues.

MRI's application in treatment planning is limited due to image distortion and lack of electron density information, which could impact the accuracy of radiotherapy delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MRI in breast cancer radiotherapy in prone and supine positions. Shang, L., Liu, Z., Rong, Y., et al.[2022]

In a feasibility trial involving five left-sided breast cancer patients, the prone crawl position for whole breast and lymph node irradiation (WB+LNI) showed effective target coverage similar to the supine position.

The prone position significantly reduced radiation doses to critical organs such as the ipsilateral lung, contralateral lung, thyroid, and oesophagus, while maintaining similar heart and humeral head doses, suggesting a safer option for patients undergoing radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Whole breast and regional nodal irradiation in prone versus supine position in left sided breast cancer. Deseyne, P., Speleers, B., De Neve, W., et al.[2018]

The MR-guided stereotactic accelerated partial breast irradiation (MRgS-APBI) approach demonstrated high feasibility, achieving 88.5% of dosimetric objectives in a study involving 48 single-fraction and 19 three-fraction patients, indicating effective treatment planning and delivery.

No technical issues related to MRgS-APBI led to treatment discontinuation, suggesting a safe implementation of this advanced radiotherapy technique that can potentially spare healthy tissue while maintaining effective cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implementing stereotactic accelerated partial breast irradiation using magnetic resonance guided radiation therapy. Price, AT., Kennedy, WR., Henke, LE., et al.[2021]

In a study of 242 patients undergoing whole breast irradiation, setup accuracy was found to be significantly worse in the prone position compared to the supine position, particularly in the lateral and longitudinal directions.

The analysis revealed that patients with a higher body mass index (BMI) required larger uncertainty margins, indicating that individual patient characteristics can impact the precision of radiation delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Setup accuracy for prone and supine whole breast irradiation. Mulliez, T., Gulyban, A., Vercauteren, T., et al.[2018]

In a phase 2 trial involving 100 patients, prone positioning during whole breast irradiation significantly reduced late toxicity rates, particularly for pigmentation changes, compared to supine positioning.

At the 5-year mark, 92% of patients in the prone group reported good or excellent cosmetic outcomes, compared to 75% in the supine group, while overall survival rates were similar at 96% for both positions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

5-Year Outcomes of a Randomized Trial Comparing Prone and Supine Whole Breast Irradiation in Large-Breasted Women. Vakaet, V., Van Hulle, H., Vergotte, M., et al.[2021]

Patients treated with partial breast irradiation (PBI) using the 1.5 T magnetic resonance guided linear accelerator (MRL) showed a lower projected risk of radiation-induced secondary malignancies (RISM) in the contralateral breast compared to those treated with conventional linear accelerator (CTL) PBI.

The study indicated that while the ipsilateral lung had the highest projected risk for RISM across all groups, the MRL-PBI treatment did not present additional risks compared to CTL-PBI, making it a promising option for breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estimation of secondary cancer projected risk after partial breast irradiation at the 1.5 T MR-linac. De-Colle, C., Dohm, O., Mönnich, D., et al.[2022]

In a study involving 20 patients with early-stage low-risk breast cancer, MRI-linac based single dose accelerated partial breast irradiation (APBI) was found to be dosimetrically feasible, meeting all predefined coverage and organ at risk (OAR) constraints.

The prone position for treatment showed better dosimetric outcomes for the chest wall and ipsilateral lung compared to the supine position, suggesting it may be the preferred approach for minimizing radiation exposure to these areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single dose partial breast irradiation using an MRI linear accelerator in the supine and prone treatment position. Charaghvandi, KR., Van't Westeinde, T., Yoo, S., et al.[2022]

Magnetic resonance imaging (MRI) guided radiotherapy allows for high precision in targeting tumors while sparing surrounding healthy tissue, which is crucial for effective treatment delivery.

The innovative approach of 'dose painting' enables tailored irradiation based on the biological behavior of tumors, potentially improving local control and reducing the risk of recurrence by addressing areas that are more resistant to standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment planning with functional MRI]. Georg, P., Andrzejewski, P., Pinker, K., et al.[2018]

In a study involving 30 women with early-stage breast cancer, the use of MR-guided radiation therapy for accelerated partial-breast irradiation showed minimal intrafractional motion of the surgical cavity, with an average displacement of only 0.6 mm.

The difference between the planned and delivered radiation dose was very small, at just 0.6%, indicating that this method effectively delivers the intended treatment with high precision.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic Resonance Image Guided Radiation Therapy for External Beam Accelerated Partial-Breast Irradiation: Evaluation of Delivered Dose and Intrafractional Cavity Motion. Acharya, S., Fischer-Valuck, BW., Mazur, TR., et al.[2022]

References

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

A comparative study based on deformable image registration of the target volumes for external-beam partial breast irradiation defined using preoperative prone magnetic resonance imaging and postoperative prone computed tomography imaging. [2020]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Optimizing MR-Guided Radiotherapy for Breast Cancer Patients. [2021]

3. Singapore pubmed.ncbi.nlm.nih.gov

MRI in breast cancer radiotherapy in prone and supine positions. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Whole breast and regional nodal irradiation in prone versus supine position in left sided breast cancer. [2018]

5. Ireland pubmed.ncbi.nlm.nih.gov

Implementing stereotactic accelerated partial breast irradiation using magnetic resonance guided radiation therapy. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

Setup accuracy for prone and supine whole breast irradiation. [2018]

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

5-Year Outcomes of a Randomized Trial Comparing Prone and Supine Whole Breast Irradiation in Large-Breasted Women. [2021]

8. Germany pubmed.ncbi.nlm.nih.gov

Estimation of secondary cancer projected risk after partial breast irradiation at the 1.5 T MR-linac. [2022]

9. Ireland pubmed.ncbi.nlm.nih.gov

Single dose partial breast irradiation using an MRI linear accelerator in the supine and prone treatment position. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

[Treatment planning with functional MRI]. [2018]

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

Magnetic Resonance Image Guided Radiation Therapy for External Beam Accelerated Partial-Breast Irradiation: Evaluation of Delivered Dose and Intrafractional Cavity Motion. [2022]