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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method of delivering radiation therapy to individuals with breast cancer. Researchers aim to determine if an MRI-guided system, which provides clearer tumor visualization, is as effective as the standard CT-guided method in controlling cancer over two years. The trial includes two groups: one receiving standard CT-guided Breast Irradiation (also known as External Beam Radiation Therapy or Whole Breast Irradiation) and the other receiving MRI-guided Precision Prone Irradiation (PPI). It seeks participants who have undergone surgery for early-stage breast cancer and meet specific criteria, such as having a tumor smaller than 2 cm with clear margins (no cancer cells at the edge of the removed tissue). As an unphased trial, this study presents a unique opportunity to explore innovative treatment options that could enhance precision in radiation therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both CT-guided and MRI-guided breast radiation treatments are generally safe, though they carry some risks.

CT-guided radiation effectively lowers the chance of cancer returning. However, it may also affect healthy tissue, leading to side effects such as skin irritation or fatigue.

MRI-guided radiation is a newer method. Early research suggests it can accurately target cancer areas, potentially protecting healthy tissue. However, due to its novelty, less information exists about its long-term safety compared to CT-guided treatment.

In summary, both treatments are considered safe. MRI-guided treatment might offer greater precision and fewer side effects, but more research is needed to fully understand its long-term safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how MRI-guided precision prone irradiation (PPI) might offer a more precise method of targeting breast cancer compared to traditional CT-guided radiation therapy. Unlike standard treatments that use CT scans, MRI-guided therapy provides better soft tissue contrast, potentially allowing doctors to target tumors more accurately and sparing surrounding healthy tissue. This precision might lead to fewer side effects and improved outcomes for patients. By comparing these two approaches, the trial aims to find out if MRI-guided radiation can enhance the effectiveness of breast cancer treatment while reducing the risk of damage to healthy tissue.

What evidence suggests that this trial's treatments could be effective for breast cancer?

Research has shown that using CT scans to guide breast cancer treatment effectively reduces the risk of recurrence by half in early-stage cases, helping patients remain cancer-free longer. In this trial, participants will receive either CT-based breast radiation treatment or MRI-guided Precision Prone Irradiation (PPI). Researchers are studying the newer MRI-based technique for its potential to improve treatment outcomes. Early results suggest that MRI-guided PPI can target cancer more accurately, possibly leading to better results. Both treatments in this trial aim to control the disease effectively while minimizing side effects. ^{2 6 7 8 9}

Who Is on the Research Team?

John Ng, M.D.

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

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 surgery showed all cancer was removed.

My breast cancer was removed with clear margins.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

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]

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]

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]

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]

Citations

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A meta-analysis of the efficacy and safety of accelerated ... This meta-analysis evaluated the efficacy and safety of accelerated partial breast irradiation versus whole-breast irradiation for early-stage breast cancer

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A systematic review on the techniques, long-term outcomes ... Adjuvant radiotherapy after breast-conserving surgery not only halves the risk of local recurrence, but also prolong the disease-free survival, ...

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The role of the radiation therapy breast boost in the 2020s - PMC This article reviews the evolution of the radiotherapy boost in breast cancer, discussing who to boost and how to boost in the 2020s, and arguing that, in both ...

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Adaptive radiotherapy for breast cancer For breast cancers, ART might allow margin reduction and might consequently reduce the volume of lung, heart and chest wall musculature being irradiated. In ...

5. advancesradonc.org advancesradonc.org/article/S2452-1094(24)00039-3/fulltext

Master Breast Radiation Planning: Simple Guide for ... This article focuses on various aspects of breast radiation treatment planning, from simulation to field design.

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Benefits, risks, and safety of external beam radiation ... Although radiation provides significant benefit to many women with breast cancer, it is also associated with risks of toxicity.

7. mayoclinic.org mayoclinic.org/tests-procedures/radiation-therapy-for-breast-cancer/about/pac-20384940

Radiation therapy for breast cancer Radiation therapy for breast cancer uses high-energy X-rays, protons or other particles to kill cancer cells.

8. sciencedirect.com sciencedirect.com/science/article/pii/S1879850025000980

Partial Breast Radiation Therapy in Low-Risk ... This study investigates the feasibility of stereotactic magnetic resonance imaging-guided adaptive radiation therapy (SMART) for PBI, with emphasis on toxicity ...

9. redjournal.org redjournal.org/article/S0360-3016(22)03386-7/fulltext

A Meta-Analysis of Trials of Partial Breast Irradiation A meta-analysis of aggregate data from published randomized trials was performed to examine the effectiveness of PBI compared with WBI in patients with ...