Ultrahypofractionation Radiation Therapy for Breast Cancer

Overseen By Rachel Jimenez, MD

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Disqualifiers: Pregnancy, Breastfeeding, Chronic kidney disease, others

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

Compensation: Varies

Number of Visits: 8

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This research is being done to see if proton beam radiation therapy (PBT) results in fewer changes to a participant's heart measured with MRI-imaging than conventional or "photon" radiation therapy (XRT) for participants with non-metastatic left sided breast cancer. The names of the two study groups in this research study are: * Proton Radiation Therapy (PBT) * Conventional or "Photon" Radiation Therapy (XRT)

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but it mentions that no cytotoxic therapy or radiotherapy can be used during the study's radiation therapy.

What data supports the effectiveness of the treatment Ultrahypofractionation Radiation Therapy for Breast Cancer?

Proton beam therapy (PBT), a component of the treatment, is known for achieving better dose distributions than standard photon radiation therapy, which may reduce risks in breast cancer treatment. However, clinical evidence specifically supporting its effectiveness in breast cancer is still lacking. ^{1 2 3 4 5}

Is ultrahypofractionation radiation therapy generally safe for humans?

Proton beam therapy (PBT), a type of radiation treatment, has been studied for various cancers and is generally considered safe, with some studies showing minimal toxicity and reduced side effects compared to other radiation methods. However, more research is needed to fully understand its safety across different conditions. ^{1 4 6 7 8}

How is ultrahypofractionation radiation therapy for breast cancer different from other treatments?

Ultrahypofractionation radiation therapy for breast cancer is unique because it uses proton beam therapy (PBT), which can provide better dose distribution and potentially reduce risks compared to standard photon radiation therapy. This approach is particularly beneficial for tumors with complex anatomy or those near sensitive tissues. ^{1 2 3 4 9}

Research Team

Rachel Jimenez, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

This trial is for adults over 18 with non-metastatic left-sided breast cancer needing radiation, including internal mammary lymph nodes treatment. It's also open to right-sided or unfavorable cardiac anatomy cases as determined by the study lead. Pregnant/breastfeeding individuals, those with conditions like scleroderma or chronic kidney disease, and patients on other investigational studies evaluating cardiac toxicity are excluded.

Inclusion Criteria

I have had chemotherapy before.

I have right-sided breast cancer or left-sided with specific heart concerns as determined by the study lead.

I have breast cancer that has not spread and will receive radiation therapy to the left side or both sides, including the internal mammary lymph nodes.

Exclusion Criteria

I cannot have gadolinium contrast due to a health condition like kidney disease.

I cannot receive radiotherapy due to certain health conditions.

Person who is pregnant or breastfeeding

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Radiation Therapy

Participants receive either proton beam radiation therapy or conventional photon radiation therapy 1x daily for 5 days over 1 week

1 week

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including cardiac MRI, blood tests, and questionnaires

12 months

2 visits (in-person) at 6 and 12 months

Treatment Details

Interventions

• Accelerated Photon Radiation Therapy (XRT)
• Accelerated Proton Beam Radiation Therapy (PBT)

Trial Overview The study compares two types of radiation therapy for breast cancer: Proton Beam Radiation Therapy (PBT) and Conventional Photon Radiation Therapy (XRT). The goal is to see if PBT causes fewer heart changes than XRT in patients with left-sided breast cancer, using MRI imaging for assessment.

Participant Groups

Group I: Accelerated Proton Beam Radiation Therapy (PBT) Group Experimental Treatment 1 Intervention

Participants will be randomized 1:1 to XRT group and stratified by receipt of chemotherapy and cardiac risk factors and will complete: * Cardiac MRI and blood tests within 1 month prior to start of radiation therapy. * Radiation therapy 1x daily for 5 days over 1 week. * End of radiation therapy visit with blood tests. * 6 month follow up visit with cardiac MRI, blood tests, questionnaires, and photographic imaging. * 12 month follow up visit with questionnaires and photographic imaging.

Group II: Accelerated Photon Radiation Therapy (XRT) Group Experimental Treatment 1 Intervention

Participants will be randomized 1:1 to XRT group and stratified by receipt of chemotherapy and cardiac risk factors and will complete: * Cardiac MRI and blood tests within 1 month prior to start of radiation therapy. * Radiation therapy 1x daily for 5 days over 1 week. * End of radiation therapy visit with blood tests. * 6 month follow up visit with cardiac MRI, blood tests, questionnaires, and photographic imaging. * 12 month follow up visit with questionnaires and photographic imaging.

Accelerated Photon Radiation Therapy (XRT) is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Conventional Radiation Therapy for:

• Breast cancer
• Non-metastatic left sided breast cancer

Approved in European Union as Photon Radiation Therapy for:

• Breast cancer
• Non-metastatic breast cancer

Approved in Canada as X-Ray Radiation Therapy for:

• Breast cancer
• Locally advanced breast cancer

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

American Society of Clinical Oncology

Collaborator

Trials

40

Recruited

148,000+

Findings from Research

Proton beam therapy (PBT) usage in the US increased from 0.4% in 2004 to 1.2% in 2018, particularly among patients with cancers recommended for PBT by the American Society of Radiation Oncology, indicating growing acceptance and application of this treatment.

While PBT use for prostate cancer temporarily decreased from 2011 to 2014, it rebounded by 2018, suggesting fluctuations in treatment preferences or insurance coverage that may influence patient access to this advanced therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of Proton Beam Therapy Use Among Patients With Newly Diagnosed Cancer in the US, 2004-2018. Nogueira, LM., Jemal, A., Yabroff, KR., 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 beam therapy (PBT) has seen a significant increase in usage in Korea, with 5,398 out of 54,035 patients receiving it between 2007 and 2019, indicating its growing acceptance in clinical practice.

Liver cancer has become the most common type of cancer treated with PBT, rising from 20% of cases in 2008-2009 to 32% in 2018-2019, while its use for prostate cancer has declined significantly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patterns of Proton Beam Therapy Use in Clinical Practice between 2007 and 2019 in Korea. Lee, SU., Yang, K., Moon, SH., et al.[2022]

Proton beam therapy (PBT) shows potential benefits for treating certain cancers, such as pediatric CNS tumors and large ocular melanomas, but current evidence does not support its superiority over traditional photon-based therapies for most other cancer types.

The American Society of Radiation Oncology (ASTRO) recommends further robust clinical trials to better define the appropriate use of PBT, as existing data is insufficient to endorse its routine application in many malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evidence based review of proton beam therapy: the report of ASTRO's emerging technology committee. Allen, AM., Pawlicki, T., Dong, L., et al.[2018]

Proton beam therapy (PBT) combined with concurrent chemotherapy (CChT) shows promising results in treating esophageal cancer, with a pathologic complete response rate of 28% in surgical patients and a near complete response rate of 50%.

While the treatment is associated with some acute toxicities, such as esophagitis and fatigue, the overall clinical outcomes are encouraging, suggesting that PBT/CChT may be a viable option for managing thoracic malignancies, warranting further comparison with traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton beam therapy and concurrent chemotherapy for esophageal cancer. Lin, SH., Komaki, R., Liao, Z., et al.[2022]

Hypofractionated proton beam therapy (hPBT) demonstrated a more favorable toxicity profile compared to normofractionated proton beam therapy (nPBT), particularly in patients treated for abdominal and pelvic cancers, with fewer severe toxicity events and better recovery rates.

Quality of life outcomes were similar between hPBT and nPBT, with some specific improvements noted in role functioning and pain management for hPBT, suggesting that hPBT is a safe and effective alternative that merits further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Normofractionated and moderately hypofractionated proton therapy: comparison of acute toxicity and early quality of life outcomes. Pelak, MJ., Flechl, B., Hug, E., et al.[2022]

Proton beam therapy (PBT) for prostate cancer patients receiving pelvic radiation significantly reduces acute gastrointestinal (GI) toxicity compared to intensity modulated radiation therapy (IMXT), with rates of grade 1, 2, and 3 GI toxicity at 16.4%, 2.4%, and 0%, respectively.

The study involved 85 patients with a median follow-up of 14.5 months, and while GU toxicity was higher, the results suggest that PBT may spare the small bowel, leading to less GI side effects, warranting further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minimal toxicity after proton beam therapy for prostate and pelvic nodal irradiation: results from the proton collaborative group REG001-09 trial. Chuong, MD., Hartsell, W., Larson, G., et al.[2018]

In a study of 64 patients with unresectable stage III non-small cell lung cancer (NSCLC), concurrent chemotherapy and proton beam radiotherapy (PBT) resulted in a median overall survival of 26.5 months and a 5-year overall survival rate of 29%, indicating promising efficacy for this treatment approach.

The treatment was associated with relatively low rates of severe toxic effects, with no grade 5 toxicities reported, suggesting that PBT may reduce the harmful side effects compared to traditional photon therapy, although further optimization of the technique is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton Beam Radiotherapy and Concurrent Chemotherapy for Unresectable Stage III Non-Small Cell Lung Cancer: Final Results of a Phase 2 Study. Chang, JY., Verma, V., Li, M., et al.[2022]

In a study involving 36 patients with unresectable pancreatic cancer, proton beam therapy (PBT) using a concomitant boost technique delivered a total dose of 67.5 gray equivalent (GyE) while minimizing exposure to the gastrointestinal (GI) tract, indicating a safer treatment approach.

The results showed that the dose distribution was significantly affected by the distance from the GI tract, suggesting that this technique could enhance local tumor control compared to conventional PBT methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simulation study of dosimetric effect in proton beam therapy using concomitant boost technique for unresectable pancreatic cancers. Fukumitsu, N., Okumura, T., Hiroshima, Y., et al.[2018]

References

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

Assessment of Proton Beam Therapy Use Among Patients With Newly Diagnosed Cancer in the US, 2004-2018. [2022]

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

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

3. Korea (South) pubmed.ncbi.nlm.nih.gov

Patterns of Proton Beam Therapy Use in Clinical Practice between 2007 and 2019 in Korea. [2022]

4. Ireland pubmed.ncbi.nlm.nih.gov

An evidence based review of proton beam therapy: the report of ASTRO's emerging technology committee. [2018]

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

Proton beam therapy and concurrent chemotherapy for esophageal cancer. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Normofractionated and moderately hypofractionated proton therapy: comparison of acute toxicity and early quality of life outcomes. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Minimal toxicity after proton beam therapy for prostate and pelvic nodal irradiation: results from the proton collaborative group REG001-09 trial. [2018]

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

Proton Beam Radiotherapy and Concurrent Chemotherapy for Unresectable Stage III Non-Small Cell Lung Cancer: Final Results of a Phase 2 Study. [2022]

9. Japan pubmed.ncbi.nlm.nih.gov

Simulation study of dosimetric effect in proton beam therapy using concomitant boost technique for unresectable pancreatic cancers. [2018]