Proton vs. Photon Therapy for Breast Cancer

Not currently recruiting at 47 trial locations

Overseen By Justin Bekelman, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Abramson Cancer Center at Penn Medicine

Disqualifiers: Metastatic disease, Prior radiotherapy, Dermatomyositis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 5-7 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two types of radiation therapy—proton (also known as Proton Beam Therapy or Proton Radiation Therapy) and photon—to determine which is more effective in controlling locally advanced breast cancer and improving quality of life. The researchers aim to track how each treatment affects heart health, overall well-being, and cancer control over time. Individuals who have undergone surgery for non-metastatic breast cancer and are scheduled to receive radiation therapy may be suitable candidates. As an unphased trial, this study provides a unique opportunity to contribute to research that could enhance future treatment options.

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.

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

Research has shown that both proton and photon therapies are generally safe for treating breast cancer, but they differ in side effects. Studies have found that patients receiving proton therapy experienced fewer side effects than those undergoing photon therapy. Proton therapy is less likely to harm nearby healthy tissues, reducing issues with the lungs and heart.

In a large study, patients treated with either proton or photon therapy achieved excellent results, but proton therapy was preferred due to fewer side effects. Specifically, proton therapy is linked to a lower risk of side effects such as lung inflammation from radiation and heart problems.

Overall, both treatments are well-tolerated, but proton therapy may be slightly safer in reducing certain side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about comparing proton and photon therapies for breast cancer because these approaches might offer unique benefits over traditional radiation treatments. Photon therapy is the standard radiation treatment that uses X-rays to target cancer cells, while proton therapy uses positively charged particles. The key advantage of proton therapy is its precision; it can deliver radiation more accurately to the tumor with minimal exposure to the surrounding healthy tissue. This precision could potentially reduce side effects and improve patients' quality of life. By comparing these two therapies, researchers hope to identify which method is more effective and safer for breast cancer patients.

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

This trial will compare the effectiveness of proton therapy and photon therapy for breast cancer. Studies have shown that both therapies effectively treat breast cancer. Proton therapy, a treatment in this trial, precisely targets tumors due to the "Bragg peak." This precision can potentially reduce radiation exposure to nearby healthy tissues, such as the lungs. Research suggests this might lower the risk of certain long-term side effects. Both treatments have been reported to provide excellent cancer control. Some patients prefer proton therapy because of these benefits. ^{2 6 7 8 9}

Who Is on the Research Team?

Bonnie Ky, MD, MSCE

Principal Investigator

Abramson Cancer Center at Penn Medicine

Alexander Lin, MD

Principal Investigator

Abramson Cancer Center at Penn Medicine

Shannon MacDonald, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for adults (21+) with non-metastatic breast cancer, regardless of surgery type or breast size. Participants must be planning radiation therapy and have insurance coverage for the treatments tested. People with HIV can join if treated and meet certain health criteria. Excluded are those with prior chest radiation, current metastases, or specific autoimmune conditions.

Inclusion Criteria

I am scheduled for radiation therapy on my breast/chest and lymph nodes, including the internal mammary nodes.

I have been diagnosed with breast cancer and have had surgery to remove it.

I have non-metastatic breast cancer at stage I, II, III, or loco-regionally recurrent.

Exclusion Criteria

There is clear proof from the doctor or scans that the cancer has spread to other parts of the body.

I have had radiation therapy on the same side as my current breast or chest cancer.

I have not received radiation for my current breast cancer before joining this study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either proton or photon therapy once a day, 5 days a week, for 5 to 7 weeks

5-7 weeks

Follow-up

Participants are monitored for cardiovascular morbidity and mortality, health-related quality of life, and cancer control outcomes

10 years

Long-term Survival Assessment

Assessment of longer-term rates of breast cancer specific and overall survival and development of second malignancies

15 years

What Are the Treatments Tested in This Trial?

Interventions

• Photon
• Proton

Trial Overview

The study compares proton therapy to photon therapy in treating locally advanced breast cancer, focusing on long-term heart health, quality of life, and effectiveness in controlling cancer.

How Is the Trial Designed?

Group I: Photon Active Control 1 Intervention

Photon therapy: once a day, 5 days a week, for 5 to 7 weeks

Group II: Proton Active Control 1 Intervention

Proton therapy: once a day, 5 days a week, for 5 to 7 weeks

Who Is Running the Clinical Trial?

Abramson Cancer Center at Penn Medicine

Lead Sponsor

Trials

425

Recruited

464,000+

Abramson Cancer Center of the University of Pennsylvania

Lead Sponsor

Trials

360

Recruited

108,000+

Patient-Centered Outcomes Research Institute

Collaborator

Trials

592

Recruited

27,110,000+

Published Research Related to This Trial

In a phase II trial involving 38 women with early-stage breast cancer, proton therapy for partial breast irradiation achieved 100% cancer control over a median follow-up of 35 months, indicating its efficacy.

The treatment resulted in minimal adverse effects, with no severe toxicities reported, and patient-reported quality of life remained stable, supporting proton therapy as a safe option for breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes and toxicities after proton partial breast radiotherapy for early stage, hormone receptor positive breast cancer: 3-Year results of a phase II multi-center trial. Choi, JI., Prabhu, K., Hartsell, WF., et al.[2022]

A large-scale randomized clinical trial is underway to compare the effects of proton therapy and photon therapy in 1278 patients with non-metastatic breast cancer, focusing on cardiovascular health and cancer control outcomes.

The primary goal is to determine if proton therapy, which reduces radiation exposure to the heart, leads to fewer major cardiovascular events compared to traditional photon therapy, potentially improving patient safety and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pragmatic randomised clinical trial of proton versus photon therapy for patients with non-metastatic breast cancer: the Radiotherapy Comparative Effectiveness (RadComp) Consortium trial protocol. Bekelman, JE., Lu, H., Pugh, S., et al.[2023]

Proton beam radiation therapy for early-stage breast cancer may improve cosmetic outcomes by delivering a lower dose to non-target breast tissue during partial breast irradiation, although more research is needed to confirm these benefits.

In patients with locally advanced breast cancer, proton therapy shows a better dosimetric profile compared to traditional photon and electron techniques, with early clinical results indicating acceptable levels of toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel applications of proton therapy in breast carcinoma. Cuaron, JJ., MacDonald, SM., Cahlon, O.[2018]

In a study of 30 breast cancer patients treated with postoperative proton therapy, the treatment was well tolerated, with a median dose of 50.4 Gy delivered over 5 weeks and no patients requiring a treatment break.

While 71.4% of patients experienced grade 2 dermatitis and 28.6% had grade 2 esophagitis, the therapy effectively spared normal tissues, showing a median heart dose of only 0.88 Gy, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early toxicity in patients treated with postoperative proton therapy for locally advanced breast cancer. Cuaron, JJ., Chon, B., Tsai, H., et al.[2018]

Proton beam radiotherapy (PBT) for breast cancer shows promising results, with skin toxicity rates (grade 1 dermatitis at ~25% and grade 2 dermatitis at 71-75%) comparable or better than traditional photon therapy.

PBT has the potential to significantly reduce cardiac risks by keeping the mean heart dose at ≤ 1 Gy, although more definitive clinical data is needed, and ongoing randomized trials will help clarify its efficacy compared to photon therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Outcomes and Toxicity of Proton Radiotherapy for Breast Cancer. Verma, V., Shah, C., Mehta, MP.[2022]

Adjuvant proton beam therapy (PBT) for early breast cancer has been studied in 32 trials involving 1452 patients, showing that it may lead to fewer severe adverse events compared to traditional photon radiation therapy, particularly with scanning PBT.

The most common severe adverse effect reported after scanning PBT was dermatitis, affecting 5.7% of patients, while other severe outcomes like infection and pain were less frequent, indicating a generally favorable safety profile for PBT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton Beam Therapy for Early Breast Cancer: A Systematic Review and Meta-analysis of Clinical Outcomes. Holt, F., Probert, J., Darby, SC., et al.[2023]

Proton radiation therapy has better dose distribution characteristics than photon radiation therapy, which could lead to improved treatment outcomes in certain clinical applications.

However, there is still a lack of substantial clinical evidence demonstrating clear advantages of proton therapy over more affordable photon treatments, partly due to the smaller number of patients receiving proton therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton versus photon radiation therapy: A clinical review. Chen, Z., Dominello, MM., Joiner, MC., et al.[2023]

Proton breast radiotherapy can effectively deliver the prescribed dose to the target area while minimizing exposure to surrounding organs, with a low normal tissue complication probability (NTCP) for the lungs (<1%) across all patients studied.

While the variable relative biological effectiveness (RBE) of protons may slightly affect treatment outcomes, its impact is generally minor in cases with low organ at risk (OAR) doses, suggesting that RBE considerations are important for identifying outlier cases but may not be critical in most scenarios.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The influence of breathing motion and a variable relative biological effectiveness in proton therapy of left-sided breast cancer. Ödén, J., Toma-Dasu, I., Eriksson, K., et al.[2018]

Proton therapy is being explored as a treatment option for breast cancer due to its ability to reduce radiation exposure to the heart and lungs while improving coverage of the tumor target.

This report provides a technical guide and patient selection algorithm to optimize the safe and effective use of passive-scattering proton therapy for breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Technical Guide for Passive Scattering Proton Radiation Therapy for Breast Cancer. Bradley, JA., Ho, MW., Li, Z., et al.[2020]

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