Proton Beam vs X-ray Radiation Therapy for Breast Cancer

Recruiting at 2 trial locations

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Mayo Clinic

Disqualifiers: Severe illnesses, Active lupus, Scleroderma, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 12

146 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase III trial compares the rate of complications of x-ray therapy versus proton beam radiation therapy after breast conserving surgery or mastectomy in treating patients with breast cancer. X-ray therapy is a form of radiation therapy that uses high-energy radiation from x-rays to kill tumor cells and shrink tumors. Proton beam radiation therapy is a type of radiation therapy that uses high-energy beams to treat tumors. It is not yet known what level of complications x-ray therapy or proton beam radiation therapy have in treating patients with breast cancer.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to consult with the principal investigator or your doctor for guidance.

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's principal investigator or your doctor.

What data supports the idea that Proton Beam vs X-ray Radiation Therapy for Breast Cancer is an effective treatment?

The available research shows that Proton Beam Therapy can be more effective than X-ray Radiation Therapy for breast cancer by reducing the amount of radiation that accidentally reaches the heart. This can lead to fewer heart-related health issues after treatment. Additionally, Proton Therapy may better protect other organs and reduce side effects compared to X-ray Therapy. However, more evidence is needed to confirm these benefits, as the number of patients treated with Proton Therapy is still relatively small. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment Proton Beam Radiation Therapy for breast cancer?

Research suggests that proton therapy, a type of radiation treatment, may reduce the risk of heart-related side effects compared to traditional photon therapy by limiting radiation exposure to the heart during breast cancer treatment. ^{1 2 3 4 5}

What safety data exists for proton vs. X-ray radiation therapy in breast cancer?

Proton beam therapy (PBT) for breast cancer shows comparable or improved skin toxicity rates compared to photon therapy, with grade 1 dermatitis at about 25% and grade 2 dermatitis at 71-75%. Esophagitis rates are similar to photon therapy, and PBT may reduce cardiac risks by keeping the mean heart dose at ≤ 1 Gy. Radiation pneumonitis and rib fractures are rare. A randomized trial is underway to provide more robust conclusions. ^{1 6 7 8 9}

Is proton beam therapy safe for treating breast cancer?

Proton beam therapy for breast cancer shows similar or better skin safety compared to traditional X-ray therapy, with rare cases of lung inflammation and rib fractures. It also minimizes heart exposure, potentially reducing heart-related risks. ^{1 6 7 8 9}

Is Proton Beam Radiation Therapy a promising treatment for breast cancer?

Yes, Proton Beam Radiation Therapy is promising for breast cancer because it can target the cancer more precisely, reducing radiation to healthy tissues like the heart and lungs. This may lead to fewer side effects and better outcomes for patients. ^{3 9 10 11 12}

How is proton beam therapy different from X-ray therapy for breast cancer?

Proton beam therapy is unique because it delivers radiation in a more targeted way, reducing exposure to nearby organs like the heart and lungs, which may lower the risk of side effects compared to traditional X-ray therapy. ^{3 9 10 11 12}

Research Team

Carlos E. Vargas, M.D.

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for adults over 18 with breast cancer who've had surgery to remove it. They should be in fair health (ECOG PS 0-2) and able to consent. It's not for those with recurrent cancer, other active metastatic diseases, severe illnesses that could affect the study, or men. Pregnant women and patients needing bilateral radiation are also excluded.

Inclusion Criteria

My cancer is in stages T1-T4c, N0-3, M0.

I can take care of myself and am up and about more than half of my waking hours.

My doctor recommends radiation therapy for my breast cancer.

Exclusion Criteria

My cancer has not spread from another part of my body.

I have active systemic lupus or scleroderma.

My surgery for breast cancer left some cancer cells at the edge of the removed tissue.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Therapy

Patients undergo either x-ray therapy over 25 fractions or proton beam radiation therapy over 5 fractions, with optional boost therapy

5-25 fractions

Multiple visits for each fraction

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Follow-up at 12 weeks, 6, 12, 24, 36 months, and 5 years

Treatment Details

Interventions

• Proton Beam Radiation Therapy
• X-ray Therapy

Trial Overview The trial compares complications from two types of radiation therapy after breast surgery: x-ray therapy or proton beam therapy given over either 5 or more than 15 sessions. The goal is to see which treatment frequency has fewer complications when treating regional lymph nodes.

Participant Groups

Group I: Arm II (proton beam radiation therapy) Experimental Treatment 2 Interventions

Within 12 weeks of the last breast cancer surgery or last dose of adjuvant chemotherapy and no sooner than 14 days since the last chemotherapy, patients undergo proton beam radiation therapy over 5 fractions in the absence of disease progression or unacceptable toxicity. Optionally, patients may receive a concurrent 5-fraction boost of proton beam radiation therapy.

Group II: Arm I (x-ray therapy) Experimental Treatment 2 Interventions

Within 12 weeks of the last breast cancer surgery or last dose of adjuvant chemotherapy and no sooner than 14 days since the last chemotherapy, patients undergo x-ray therapy over 25 fractions in the absence of disease progression or unacceptable toxicity. Optionally, patients may then receive a 4-fraction boost of x-ray therapy.

Proton Beam Radiation Therapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Proton Therapy for:

• Esophageal adenocarcinoma
• Esophageal squamous cell carcinoma
• Gastroesophageal junction tumors

Approved in United States as Proton Therapy for:

• Esophageal adenocarcinoma
• Esophageal squamous cell carcinoma
• Gastroesophageal junction tumors

Approved in Canada as Proton Therapy for:

• Esophageal adenocarcinoma
• Esophageal squamous cell carcinoma
• Gastroesophageal junction tumors

Approved in Japan as Proton Therapy for:

• Esophageal adenocarcinoma
• Esophageal squamous cell carcinoma
• Gastroesophageal junction tumors

Approved in China as Proton Therapy for:

• Esophageal adenocarcinoma
• Esophageal squamous cell carcinoma
• Gastroesophageal junction tumors

Approved in Switzerland as Proton Therapy for:

• Esophageal adenocarcinoma
• Esophageal squamous cell carcinoma
• Gastroesophageal junction tumors

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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]

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]

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 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]

Proton beam therapy for lung cancer significantly reduces the average dose of radiation to the lungs (Dmean) and the volume of lung receiving higher doses (V20, V10, V5) compared to both three-dimensional conformal photon radiotherapy (3D-CRT) and intensity-modulated photon radiotherapy (IMRT), based on an analysis of six clinical trials.

While proton therapy does not lower the average dose to the esophagus, it does reduce the dose to the heart, suggesting a safer profile for patients undergoing lung cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Dosimetric comparing between protons beam and photons beam for lung cancer radiotherapy: a meta-analysis]. Tian, G., Li, N., Li, G.[2021]

In a study involving five breast cancer patients with complex breast tissue, proton beam therapy significantly reduced lung irradiation compared to conventional photon techniques, with mean lung doses of only 3.5 Gy versus 12.9 Gy from conventional methods.

Both three-field non-IMRT and proton techniques provided comparable coverage of the target breast tissue while minimizing lung and cardiac exposure, suggesting that proton therapy may be the best option for patients with challenging anatomical considerations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Critical appraisal of treatment techniques based on conventional photon beams, intensity modulated photon beams and proton beams for therapy of intact breast. Fogliata, A., Bolsi, A., Cozzi, L.[2019]

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 beam therapy (PBT) can deliver lower radiation doses to surrounding healthy organs compared to traditional photon (X-ray) radiotherapy, potentially reducing side effects for lung cancer patients.

Early clinical results indicate that PBT, when combined with chemotherapy, shows lower toxicity rates and may improve survival outcomes, although further randomized studies are needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton beam therapy for locally advanced lung cancer: A review. Schild, SE., Rule, WG., Ashman, JB., et al.[2021]

Postoperative radiation therapy for breast cancer significantly reduces local relapse and moderately lowers mortality, but it can lead to increased late mortality from heart issues and secondary cancers.

Using advanced techniques like proton therapy can improve treatment by minimizing radiation exposure to the heart and lungs, thanks to its precise dose distribution, which could enhance the safety and efficacy of breast cancer radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation therapy planning with photons and protons for early and advanced breast cancer: an overview. Weber, DC., Ares, C., Lomax, AJ., 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]

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. 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]

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

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

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

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

5. 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]

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

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

7. China pubmed.ncbi.nlm.nih.gov

[Dosimetric comparing between protons beam and photons beam for lung cancer radiotherapy: a meta-analysis]. [2021]

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

Critical appraisal of treatment techniques based on conventional photon beams, intensity modulated photon beams and proton beams for therapy of intact breast. [2019]

9. China pubmed.ncbi.nlm.nih.gov

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

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

Proton beam therapy for locally advanced lung cancer: A review. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Radiation therapy planning with photons and protons for early and advanced breast cancer: an overview. [2018]

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

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