SBRT for Breast Cancer

Overseen By Danny Vesprini, MD, FRCPC

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Toronto Sunnybrook Regional Cancer Centre

Must not be taking: Chemotherapy

Disqualifiers: Multifocal tumors, Supraclavicular disease, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

24 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a prospective, single institution, phase I-II study of stereotactic body radiotherapy (SBRT) for unresected breast cancer. Twenty-four patients with advanced breast cancer who are not candidates for surgery (metastatic disease, unresectable, medically inoperable) or decline surgery will be enrolled in a prospective study using SBRT (4 fractions of radiation therapy over 12-15 days) as the primary treatment modality.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does allow concurrent endocrine therapy (hormone treatment). You cannot have received chemotherapy within 3 weeks before starting the trial.

What data supports the effectiveness of the treatment SBRT for breast cancer?

Research shows that stereotactic ablative radiotherapy (SABR), also known as SBRT, is effective for treating oligometastatic breast cancer, which is when cancer has spread to a few other parts of the body. SABR is also a standard treatment for early-stage lung cancer, suggesting its potential effectiveness in precisely targeting and treating cancer in other areas, like the breast. ^{1 2 3 4 5}

Is stereotactic body radiation therapy (SBRT) generally safe for humans?

Stereotactic body radiation therapy (SBRT), also known as stereotactic ablative radiotherapy (SABR), has been used to treat various cancers, including lung cancer. While it shows promise in controlling tumors, some serious complications have been reported, and strategies are needed to reduce these risks. Overall, the probability of severe side effects is low, but long-term management may be required for some patients. ^{6 7 8 9 10}

How is the treatment SBRT different from other treatments for breast cancer?

SBRT (Stereotactic Body Radiation Therapy) is unique because it delivers high doses of radiation precisely to the tumor in fewer sessions compared to traditional radiation therapy, which uses smaller doses over a longer period. This approach can be particularly effective for targeting specific areas like oligometastases (small, limited spread of cancer) in breast cancer, potentially improving outcomes while sparing healthy tissue. ^{1 4 11 12 13}

Research Team

Danny Vesprini, MD

Principal Investigator

Sunnybrook Health Sciences Centre, University of Toronto

Eligibility Criteria

This trial is for adults with advanced breast cancer who can't have surgery due to metastasis, inoperability, or personal choice. They must not have had chemotherapy within the last 3 weeks but can be on endocrine therapy. Participants need a confirmed diagnosis of invasive non-lobular breast carcinoma and must commit to attending all treatment sessions and follow-ups.

Inclusion Criteria

Primary breast and axillary surgery not recommended/performed due to any of the following: distant metastatic disease, unresectable T4 disease and/or medically inoperable and/or patient declined breast surgery Stages T1-T4, N1-N2, M0-M1 disease

Ability to attend radiation planning and therapy, able to attend for follow-up care

Able to provide written informed consent.

Exclusion Criteria

Received chemotherapy within 3 weeks prior to breast SBRT. (Concurrent endocrine therapy is permitted)

Multifocal or multicentric tumours.

Ipsilateral supraclavicular or infraclavicular nodal disease >= 1cm size that is at the level of or superior to the brachial plexus

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive stereotactic body radiotherapy (SBRT) for breast cancer, consisting of 4 fractions of radiation therapy over 12-15 days

2-3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of acute toxicity and tumor response rate

12 weeks

Long-term follow-up

Participants' quality of life, pain levels, and breast symptoms are monitored using questionnaires and scales

2 years

Treatment Details

Interventions

• SBRT

Trial Overview The study tests Stereotactic Body Radiation Therapy (SBRT) as a primary treatment for unresectable breast cancer. It involves giving patients four high-dose radiation treatments over approximately two weeks to see how effective it is against their cancer.

Participant Groups

Group I: SBRT to the Primary Breast Tumour Experimental Treatment 1 Intervention

SBRT to the breast using 4 sequentially escalating dose levels from 9Gy to 12 Gy.

SBRT is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as SBRT for:

• Prostate cancer
• Lung cancer
• Liver cancer
• Pancreatic cancer
• Spinal tumors

Approved in European Union as SBRT for:

• Prostate cancer
• Lung cancer
• Liver cancer
• Pancreatic cancer
• Spinal tumors
• Bone metastases

Approved in Canada as SBRT for:

• Prostate cancer
• Lung cancer
• Liver cancer
• Pancreatic cancer
• Spinal tumors

Approved in Japan as SBRT for:

• Prostate cancer
• Lung cancer
• Liver cancer
• Pancreatic cancer

Who Is Running the Clinical Trial?

Toronto Sunnybrook Regional Cancer Centre

Lead Sponsor

Trials

10

Recruited

950+

Findings from Research

Stereotactic ablative body radiotherapy (SABR) is a feasible and well-tolerated treatment for patients with bone-only oligometastatic breast cancer, with 80% of patients successfully receiving treatment and no severe (grade 3 or 4) toxicities reported.

The treatment showed promising efficacy, with a 100% local progression-free survival (LPFS) and 67% distant progression-free survival (DPFS) at two years, suggesting that SABR could be a viable option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative body radiotherapy (SABR) for bone only oligometastatic breast cancer: A prospective clinical trial. David, S., Tan, J., Savas, P., et al.[2020]

Stereotactic ablative radiation therapy (SABR) was found to be effective for treating pulmonary metastases, with a median follow-up of 23 months showing improved overall survival (OS) for patients with 3 or fewer metastases compared to those with more (74.2% vs. 59.3% at 24 months).

Patients with less responsive primary tumors (like adrenal or pancreatic cancers) had higher local failure rates, suggesting that higher doses of SABR or surgical options may be necessary for these cases to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiation therapy for pulmonary metastases: Improving overall survival and identifying subgroups at high risk of local failure. Pasalic, D., Lu, Y., Betancourt-Cuellar, SL., et al.[2021]

Stereotactic ablative body radiotherapy (SABR) is now the standard treatment for early-stage non-small-cell lung cancer (NSCLC) in patients who cannot undergo surgery, highlighting its efficacy in this patient population.

The review also discusses the safety profile of SABR, including reported toxicity rates, and explores its potential use in combination with other therapies for improved outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of outcomes following stereotactic ablative radiotherapy in the treatment of early-stage primary lung cancer. Murray, P., Franks, K., Hanna, GG.[2022]

Stereotactic ablative radiotherapy (SABR) shows high effectiveness for oligometastatic breast cancer, achieving local control rates of 97% at 1 year and 90% at 2 years, based on a meta-analysis of 10 studies involving 467 patients.

SABR is associated with a low toxicity rate, with only 4.1% of patients experiencing grade 2 or 3 side effects, indicating it is a safe treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy to treat breast cancer oligometastases: A systematic review with meta-analysis. Viani, GA., Gouveia, AG., Louie, AV., et al.[2021]

Stereotactic ablative radiotherapy (SABR) is an effective treatment for early-stage non-small cell lung cancers (NSCLCs) that are medically inoperable, providing local control and toxicity levels comparable to surgical resection.

SABR is gaining interest as a noninvasive treatment option for patients with borderline resectable lung cancers, although further randomized studies are needed to evaluate its survival benefits in operable patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy (SABR) for non-small cell lung cancer. Iyengar, P., Westover, K., Timmerman, RD.[2013]

Stereotactic ablative radiotherapy (SABR) has rapidly expanded in clinical use for treating various primary and metastatic tumors, demonstrating promising results in tumor control.

Despite its effectiveness, SABR can lead to serious complications, highlighting the need for strategies to reduce these risks and improve the safety of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious complications associated with stereotactic ablative radiotherapy and strategies to mitigate the risk. Lo, SS., Sahgal, A., Chang, EL., et al.[2018]

In a study of 40 patients with central and ultracentral non-small cell lung cancer (NSCLC) treated with stereotactic ablative radiotherapy (SABR), those with ultracentral tumors experienced worse overall survival (OS) and progression-free survival (PFS) compared to those with central tumors, indicating a need for careful consideration in treatment planning.

The incidence of severe treatment-related toxicities (grade ≥3) was higher in the ultracentral group, with 12.5% of patients experiencing significant complications, including severe bronchial obstruction and esophageal perforation, highlighting the potential risks associated with SABR in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes in patients with central and ultracentral non-small cell lung cancer treated with stereotactic body radiotherapy: single-institution experience. Song, X., Zhao, L., Jiang, N., et al.[2023]

In a study of 500 patients treated with stereotactic ablative body radiotherapy (SABR) for stage I non-small cell lung cancer, severe chest wall pain (CWP) occurred in only 2% of patients, indicating that serious toxicity is rare with this treatment.

The study found that larger treatment volumes and closer tumor-chest wall distances were associated with increased risk of CWP and rib fractures, suggesting that careful planning of radiation doses can help minimize these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and risk factors for chest wall toxicity after risk-adapted stereotactic radiotherapy for early-stage lung cancer. Bongers, EM., Haasbeek, CJ., Lagerwaard, FJ., et al.[2022]

The TROG 13.01/ALTG 13.001 clinical trial is investigating the safety and efficacy of single versus multi-fraction stereotactic ablative body radiotherapy (SABR) for lung tumors in 84 patients with up to three metastases, aiming to determine the best treatment approach for pulmonary oligometastases.

The study will compare a single high dose of 28Gy to a total of 48Gy delivered in four fractions, assessing not only safety but also quality of life, survival rates, and potential cost implications of each treatment method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised phase II trial of Stereotactic Ablative Fractionated radiotherapy versus Radiosurgery for Oligometastatic Neoplasia to the lung (TROG 13.01 SAFRON II). Siva, S., Kron, T., Bressel, M., et al.[2022]

In a study of 102 patients treated with stereotactic ablative radiation therapy (SABR) for early-stage non-small-cell lung cancer, a significant correlation was found between higher Biological Equivalent Doses (BED) over 300 Gy and the development of radiological changes such as organizing pneumonia and lung affectation over a 2-year follow-up.

Radiological changes were more pronounced in patients receiving BEDs greater than 300 Gy to healthy lung volumes of at least 30 cc, suggesting that these findings could inform future radiotherapy dose constraints to minimize pulmonary toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biological equivalent dose is associated with radiological toxicity after lung stereotactic ablative radiation therapy. Cases, C., Benegas, M., Sánchez, M., et al.[2023]

Stereotactic body radiation therapy (SBRT) is a preferred treatment for early-stage non-small cell lung cancer (NSCLC) patients who cannot undergo surgery, but accurate lymph node staging is crucial for optimal patient selection.

Current staging methods like PET/CT and EBUS have limited sensitivity in detecting lymph node metastases, which can lead to undetected cancer spread and poorer outcomes; thus, invasive staging procedures are often necessary to improve detection and potentially enhance survival with adjuvant therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Undetected lymph node metastases in presumed early stage NSCLC SABR patients. Cerra-Franco, A., Diab, K., Lautenschlaeger, T.[2017]

In a study of 39 patients with 45 lung lesions treated with stereotactic ablative body radiotherapy (SBRT), local progression-free survival rates were high, with 90.5% at 1 year and 80.5% at 2 years, indicating effective tumor control.

The treatment was well-tolerated with only mild acute side effects, suggesting that the moderate dose schedules of 35 Gy (5 fractions) or 37.5 Gy (3 fractions) are safe and effective for managing non-small cell lung cancer and metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy for small lung tumors with a moderate dose. Favorable results and low toxicity. Duncker-Rohr, V., Nestle, U., Momm, F., et al.[2022]

Stereotactic ablative body radiosurgery (SABR) and stereotactic body radiation therapy (SBRT) deliver high doses of radiation precisely to tumors, which may improve treatment outcomes compared to conventional low-dose radiation therapy (1.8-2Gy).

These advanced techniques not only enhance tumor ablation but also interact beneficially with biological and immunologic therapies, while incorporating methods to protect normal tissues, making them suitable for various types of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative body radiosurgery (SABR) or Stereotactic body radiation therapy (SBRT). Folkert, MR., Timmerman, RD.[2022]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Stereotactic ablative body radiotherapy (SABR) for bone only oligometastatic breast cancer: A prospective clinical trial. [2020]

2. Ireland pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiation therapy for pulmonary metastases: Improving overall survival and identifying subgroups at high risk of local failure. [2021]

3. England pubmed.ncbi.nlm.nih.gov

A systematic review of outcomes following stereotactic ablative radiotherapy in the treatment of early-stage primary lung cancer. [2022]

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

Stereotactic body radiotherapy to treat breast cancer oligometastases: A systematic review with meta-analysis. [2021]

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

Stereotactic ablative radiotherapy (SABR) for non-small cell lung cancer. [2013]

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

Serious complications associated with stereotactic ablative radiotherapy and strategies to mitigate the risk. [2018]

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

Long-term outcomes in patients with central and ultracentral non-small cell lung cancer treated with stereotactic body radiotherapy: single-institution experience. [2023]

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

Incidence and risk factors for chest wall toxicity after risk-adapted stereotactic radiotherapy for early-stage lung cancer. [2022]

9. England pubmed.ncbi.nlm.nih.gov

A randomised phase II trial of Stereotactic Ablative Fractionated radiotherapy versus Radiosurgery for Oligometastatic Neoplasia to the lung (TROG 13.01 SAFRON II). [2022]

10. Ireland pubmed.ncbi.nlm.nih.gov

Biological equivalent dose is associated with radiological toxicity after lung stereotactic ablative radiation therapy. [2023]

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

Undetected lymph node metastases in presumed early stage NSCLC SABR patients. [2017]

12. Germany pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy for small lung tumors with a moderate dose. Favorable results and low toxicity. [2022]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Stereotactic ablative body radiosurgery (SABR) or Stereotactic body radiation therapy (SBRT). [2022]