Proton vs. Photon Therapy for Breast Cancer

Recruiting at 45 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

1238 Participants Needed

Trial Summary

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 Proton vs. Photon Therapy for Breast Cancer?

Proton therapy for breast cancer may reduce radiation exposure to the heart compared to photon therapy, potentially lowering the risk of heart-related issues after treatment. It also shows promise in reducing radiation to non-target breast tissue, which might improve cosmetic outcomes, though more research is needed to confirm these benefits. ^{1 2 3 4 5}

Is proton therapy safe for breast cancer treatment?

Proton therapy for breast cancer appears to have similar or better safety compared to photon therapy, with skin reactions and esophagitis rates being comparable or improved. It also shows potential to reduce heart-related risks, but more research is needed to confirm these findings. ^{1 2 3 6 7}

How does proton therapy differ from other treatments for breast cancer?

Proton therapy for breast cancer is unique because it delivers radiation more precisely to the tumor, reducing exposure to surrounding healthy tissues like the heart and lungs. This precision may lead to fewer side effects and a lower risk of heart problems compared to traditional photon radiation therapy. ^{3 5 6 8 9}

What is the purpose of this trial?

A pragmatic randomized clinical trial of patients with locally advanced breast cancer randomized to either proton or photon therapy and followed longitudinally for cardiovascular morbidity and mortality, health-related quality of life, and cancer control outcomes. Quality of life is the outcome measure for the estimated primary completion date of December, 2024, www.radcomp.org.

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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]

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 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]

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]

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]

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]

References

1. England 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. [2023]

2. England pubmed.ncbi.nlm.nih.gov

The influence of breathing motion and a variable relative biological effectiveness in proton therapy of left-sided breast cancer. [2018]

3. China pubmed.ncbi.nlm.nih.gov

Novel applications of proton therapy in breast carcinoma. [2018]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Proton versus photon radiation therapy: A clinical review. [2023]

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

Proton Beam Therapy for Early Breast Cancer: A Systematic Review and Meta-analysis of Clinical Outcomes. [2023]

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

Clinical Outcomes and Toxicity of Proton Radiotherapy for Breast Cancer. [2022]

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

Early toxicity in patients treated with postoperative proton therapy for locally advanced breast cancer. [2018]

8. Ireland 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. [2022]

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

A Technical Guide for Passive Scattering Proton Radiation Therapy for Breast Cancer. [2020]