Ultra-Hypofractionated vs. Hypofractionated Radiation for Breast Cancer

(SWIFT RT Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Maria Thomas, M.D., Ph.D.

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Washington University School of Medicine

Disqualifiers: Distant metastases, Bilateral breast cancer, others

Stay on Your Current Meds

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

In breast cancer patients with nodal involvement, numerous studies have demonstrated that adjuvant radiation therapy reduces the risk of local recurrence, regional recurrence, and distant metastases, in addition to improving survival. The dose and fractionation for adjuvant breast radiation therapy has evolved over time, as novel schedules have been compared to the current standard of care. Hypofractionated radiation therapy (266 cGy per fraction x 15-16 fractions over 3 weeks) has been shown to result in equivalent oncologic outcomes, as well as equivalent acute and late toxicity, when compared to standard fractionation (200 cGy per fraction x 25 fractions over 5 weeks). Subsequently, hypofractionated breast radiation has become the current standard of care. More recently, ultra-hypofractionated breast radiation (520 cGy per fraction x 5 fractions over 1 week) was shown in a randomized trial to be non-inferior to hypofractionated radiation when treating the breast after lumpectomy. However, the efficacy and toxicity of using ultra-hypofractionated radiation therapy when also treating the regional nodes has not been reported. This is important, as there is greater radiation exposure to several normal tissues, such as the arm/shoulder, brachial plexus, normal lymphatics, heart, and lung, when treating the regional nodes. In this randomized study, the investigators aim to compare the tolerability and efficacy of ultra-hypofractionated breast/chest wall and regional nodal radiation (SWIFT RT) against hypofractionated radiation (RT). The investigators will evaluate acute and late toxicity, oncologic outcomes (including local recurrence, regional recurrence, distant metastasis, and overall survival), cosmesis, and patient-reported quality of life. The investigators will collect blood samples for correlative studies of biomarkers of fibrosis and cardiac toxicity.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it allows concurrent endocrine therapy, anti-HER2 therapy, and immunotherapy during radiation treatment, so you may be able to continue these if applicable.

What data supports the effectiveness of the treatment Ultra-Hypofractionated vs. Hypofractionated Radiation for Breast Cancer?

Research shows that hypofractionated radiation therapy (fewer, larger doses of radiation) for breast cancer has outcomes comparable to traditional methods, with shorter treatment times. Recent studies also indicate that ultra-hypofractionated radiation (even fewer sessions) has shown favorable results, suggesting it could be an effective option for breast cancer treatment. ^{1 2 3 4 5}

Is ultra-hypofractionated radiation therapy safe for breast cancer patients?

Ultra-hypofractionated radiation therapy for breast cancer has been shown to be safe in several studies, with no significant difference in side effects compared to traditional radiation methods. Trials like the UK-FAST and FAST-Forward have demonstrated a safe toxicity profile, making it a valid option for many patients. ^{2 6 7 8 9}

How is ultra-hypofractionated radiation therapy different from other breast cancer treatments?

Ultra-hypofractionated radiation therapy is unique because it uses fewer, larger doses of radiation over a shorter period, which can be more convenient and potentially just as effective as traditional longer treatments. This approach is particularly beneficial during situations like the COVID-19 pandemic, where reducing hospital visits is important. ^{1 2 3 4 5}

Research Team

Maria Thomas, M.D., Ph.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for breast cancer patients with lymph node involvement who have undergone surgery. Participants should be suitable for radiation therapy and willing to undergo different radiation schedules. Those with prior radiation in the treatment area or conditions that could interfere with radiotherapy are excluded.

Inclusion Criteria

My cancer has spread to the lymph nodes in my armpit, confirmed by a biopsy.

I had surgery to remove lymph nodes in my armpit.

My radiation therapy will be done at BJH or its satellite locations.

Exclusion Criteria

Pregnancy, which will be excluded prior to simulation.

I have been diagnosed with cancer in both breasts.

It has been over 8 weeks since my last breast cancer treatment before starting radiation planning.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either ultra-hypofractionated or hypofractionated breast/chest wall and regional nodal radiation

1-4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including evaluation of acute and late toxicity, oncologic outcomes, and quality of life

5 years

Treatment Details

Interventions

• Hypofractionated radiation (Brachytherapy)
• Ultra-hypofractionated breast/chest wall and regional nodal radiation (Brachytherapy)

Trial Overview The study compares two types of post-surgery radiation treatments: standard hypofractionated (shorter, higher-dose sessions over 3 weeks) versus ultra-hypofractionated (even shorter, more intense doses over 1 week), focusing on their effectiveness and safety when treating both the breast/chest wall and regional nodes.

Participant Groups

Group I: Ultra-hypofractionated breast/chest wall and regional nodal radiation (SWIFT RT) Experimental Treatment 1 Intervention

Breast/chest wall and regional nodal radiation (2600 cGy in 5 fractions over 1-2 weeks).

Group II: Hypofractionated radiation (RT) Active Control 1 Intervention

Breast/chest wall and regional nodal radiation (4256 cGy in 16 fractions over 3-4 weeks).

Hypofractionated radiation is already approved in Canada for the following indications:

Approved in Canada as Hypofractionation for:

• Breast cancer
• Node-positive breast cancer

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

David H. Perlmutter

Washington University School of Medicine

Chief Executive Officer since 2015

MD from Washington University School of Medicine

Paul Scheel

Washington University School of Medicine

Chief Medical Officer since 2022

MD from Washington University School of Medicine

Findings from Research

Hypofractionated radiation therapy (HypoRT) was found to be effective in treating inoperable advanced non-small cell lung cancer (NSCLC), with an overall response rate of 83% among 30 patients, and a median follow-up of 13 months.

The treatment was well-tolerated, with manageable acute toxicities; however, 37% of patients experienced locoregional recurrence, and 57% developed distant metastasis, indicating the need for further studies to compare HypoRT with conventional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Image guided hypofractionated 3-dimensional radiation therapy in patients with inoperable advanced stage non-small cell lung cancer. Osti, MF., Agolli, L., Valeriani, M., et al.[2018]

Hypofractionated radiation therapy (HypoRT) for breast cancer, which delivers higher doses per fraction (2.5-3.0 Gy), has shown favorable outcomes in clinical trials, suggesting it can be an effective alternative to conventional radiation therapy.

The review highlights that despite some concerns among radiation oncologists, the evidence from high-quality randomized trials supports the safety and efficacy of HypoRT, making it a timely option for treatment, especially during the COVID-19 pandemic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Journey to hypofractionation in radiotherapy for breast cancer: critical reviews for recent updates. Kim, N., Kim, YB.[2023]

In a study involving 396 patients treated with ultra-hypofractionated breast radiotherapy, the five-year local-relapse free survival (LRFS) rate was an impressive 98.8%, indicating high efficacy in controlling breast cancer.

While ultra-hypofractionated radiotherapy showed excellent tumor control, certain regimens, particularly the 5.7 Gy weekly fraction and tumor bed boost, were linked to a higher risk of acute and late skin toxicities, highlighting the need for careful treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Large scale experience of two ultrahypofractionated 5 fractions regimes after breast conserving surgery from a single centre. Sauvage, LM., Loap, P., Vu-Bezin, J., et al.[2023]

The UK-FAST trial showed that a once weekly hypofractionated radiotherapy regimen (5 fractions of 5.7 Gy) for whole breast irradiation had similar toxicity levels compared to the conventional regimen (50 Gy in 25 fractions) over a 10-year follow-up, indicating it is a safe alternative.

The FAST-Forward trial demonstrated that a 5-fraction regimen (5.2 Gy per fraction) over one week is non-inferior in local control compared to the standard 40 Gy in 15 fractions over three weeks, supporting the efficacy of extreme hypofractionation in breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Extreme hypofractionation: New indications for breast cancer radiotherapy]. Bockel, S., Louvel, G., Brion, T., et al.[2021]

In a study of 393 breast cancer patients treated with moderately hypofractionated radiotherapy (HYPO-RT) over a median follow-up of 5.7 years, the overall survival rates were high at 96.0% at 5 years and 79.3% at 10 years, indicating the efficacy of this treatment.

HYPO-RT demonstrated excellent local control with only 4.3% local recurrences and low toxicity rates, with severe acute dermatitis occurring in just 0.9% of patients, highlighting its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated radiotherapy in breast cancer: a 10-year single institution experience. Najas, GF., Stuart, SR., Marta, GN., et al.[2022]

Hypofractionated radiotherapy is gaining popularity for breast cancer treatment in the UK and Canada, but there are concerns about potential increased toxicity associated with this approach.

The article emphasizes the importance of careful planning and dosimetry in hypofractionated radiotherapy to ensure effective treatment while minimizing risks, and it provides recommendations for both planning and monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What are the minimal standards of radiotherapy planning and dosimetry for "hypofractionated" radiotherapy in breast cancer? MacLeod, N., McIntyre, A., Canney, PA.[2018]

References

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

Image guided hypofractionated 3-dimensional radiation therapy in patients with inoperable advanced stage non-small cell lung cancer. [2018]

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

Hypofractionated radiation therapy in the treatment of early-stage breast cancer. [2021]

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

Hypofractionated Radiation Therapy (HFRT) of Breast/Chest Wall and Regional Nodes in Locally Advanced Breast Cancer: Toxicity Profile and Survival Outcomes in Retrospective Monoistitutional Study. [2022]

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

Hypofractionated Regional Nodal Irradiation for Women With Node-Positive Breast Cancer. [2022]

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

Journey to hypofractionation in radiotherapy for breast cancer: critical reviews for recent updates. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Large scale experience of two ultrahypofractionated 5 fractions regimes after breast conserving surgery from a single centre. [2023]

7. France pubmed.ncbi.nlm.nih.gov

[Extreme hypofractionation: New indications for breast cancer radiotherapy]. [2021]

8. Poland pubmed.ncbi.nlm.nih.gov

Hypofractionated radiotherapy in breast cancer: a 10-year single institution experience. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

What are the minimal standards of radiotherapy planning and dosimetry for "hypofractionated" radiotherapy in breast cancer? [2018]