Partial Breast Irradiation for Recurrent Breast Cancer

Recruiting at 1 trial location

Overseen By Janice Lyons, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Case Comprehensive Cancer Center

Disqualifiers: Metastatic disease, Lobular carcinoma, Multicentric carcinoma, others

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

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 16

55 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial allows hormonal therapy and HER2 directed therapy to be taken during radiation. If you are on chemotherapy, it must be scheduled at least 2 weeks apart from radiation. The protocol does not specify other medication restrictions.

What data supports the effectiveness of the treatment Partial Breast Irradiation for Recurrent Breast Cancer?

Research shows that modern radiation techniques, including partial breast irradiation, have improved over the years, reducing complications and improving survival rates. Intraoperative radiotherapy (IORT), a form of partial breast irradiation, has shown promise in reducing local recurrence and improving quality of life for patients with early-stage breast cancer. ^{1 2 3 4 5}

Is partial breast irradiation using intraoperative radiotherapy safe for humans?

Intraoperative radiotherapy (IORT) for partial breast irradiation has been shown to be safe in large studies involving thousands of women with early-stage breast cancer. It generally has favorable safety profiles, meaning it causes fewer side effects compared to other methods, and is convenient for patients. ^{1 6 7 8 9}

How is partial breast irradiation for recurrent breast cancer different from other treatments?

Partial breast irradiation focuses radiation only on the area around the original tumor site, which can reduce side effects and shorten treatment time compared to whole breast radiation. This approach is particularly useful for patients who have had a recurrence of breast cancer in the same breast after initial treatment. ^{3 4 10 11 12}

What is the purpose of this trial?

The standard treatment for participants whose cancer has returned after breast conserving surgery is radiation given twice daily (separated by at least 6 hours) for a total of 30 treatments. The purpose of this study is to find out if giving radiation once a day for 15 treatments after repeat breast conserving surgery works as well as giving it the standard way.

Research Team

Janice Lyons, MD

Principal Investigator

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Rahul Tendulkar, MD

Principal Investigator

Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults over 18 with a specific breast cancer recurrence that's small (<3cm), treated surgically without spread to lymph nodes or distant organs. Participants must be in good health, understand the study, and consent to join. It excludes those with certain other breast cancers, genetic mutations like BRCA, systemic diseases affecting skin/connective tissue, pregnant/lactating women, and anyone unable to consent.

Inclusion Criteria

I had a small tumor removed from my breast and no signs of cancer in my underarm lymph nodes.

My surgery removed all visible cancer with clear margins.

My breast cancer recurrence is of a specific type, confirmed by a biopsy.

Exclusion Criteria

I have multiple breast tumors or suspicious lymph nodes that are not confirmed cancerous.

My cancer has spread to lymph nodes or other parts of my body.

I have Paget's disease of the nipple.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Repeat Breast Conserving Surgery

Participants undergo repeat breast conserving surgery to remove recurrent tumor

1 week

1 visit (in-person)

Radiation Therapy

Participants receive daily partial breast irradiation for 15 fractions

3 weeks

15 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Quarterly visits (in-person)

Long-term Follow-up

Participants are monitored for long-term outcomes such as recurrence and survival

10 years

Treatment Details

Interventions

• Radiation Therapy

Trial Overview The study tests if radiation therapy once daily for 15 treatments after repeat surgery is as effective as the standard twice-daily radiation for 30 treatments. The goal is to see if fewer sessions can still prevent cancer from returning while potentially reducing inconvenience and side effects.

Participant Groups

Group I: Radiation Therapy(RT) Experimental Treatment 1 Intervention

There will be one treatment cohort. Radiation therapy will be delivered daily for 15 daily fractions, 2.67Gy per fraction, delivered using a 3-D or IMRT(Intensity Modulate Radiation Therapy) plan. For participants with high-risk features deemed by the radiation oncologist who would otherwise be a candidate for a boost (age \<50, high grade, poor biology, close margins), 48 Gy delivered in fifteen fractions of 3.2 Gy is allowed.

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

Approved in European Union as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in United States as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Canada as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Japan as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in China as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Switzerland as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Who Is Running the Clinical Trial?

Case Comprehensive Cancer Center

Lead Sponsor

Trials

472

Recruited

33,400+

Findings from Research

Intraoperative radiotherapy (IORT) for early-stage breast cancer significantly improves radiation-related quality of life (QoL) parameters, with patients reporting less pain and better functioning compared to those receiving external beam radiotherapy (EBRT).

In a study of 230 women, those treated with IORT alone experienced fewer breast and arm symptoms and better overall role functioning, indicating that IORT may be a more patient-friendly option than traditional EBRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation-related quality of life parameters after targeted intraoperative radiotherapy versus whole breast radiotherapy in patients with breast cancer: results from the randomized phase III trial TARGIT-A. Welzel, G., Boch, A., Sperk, E., et al.[2021]

Radiation therapy is crucial in breast cancer treatment, significantly reducing local recurrence and improving survival rates, especially with advancements in techniques since the late 1980s.

Shorter courses of radiation therapy (3-4 weeks) are generally as effective as longer ones, and modern techniques like volumetric modulated arc therapy (VMAT) help minimize complications while enhancing treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolution of radiotherapy techniques in breast conservation treatment. Boyages, J., Baker, L.[2020]

Adjuvant radiotherapy is crucial for reducing local recurrences in early breast cancer, with moderate hypofractionated whole-breast irradiation being the standard treatment.

Recent advancements in irradiation techniques allow for shorter and more personalized treatment plans, making therapy more tolerable and potentially leading to de-escalation of treatment intensity based on individual patient risk profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adjuvant radiation therapy for breast cancer]. Lange, T., Knöchelmann, AC., Bremer, M.[2023]

In a study of 82 patients with early-stage breast cancer treated with intraoperative radiotherapy (IORT), 72% of those who underwent 21-gene recurrence testing were classified as low risk, indicating that IORT may be suitable for a majority of these patients.

The study highlights a need for further research on the long-term clinical outcomes and safety of IORT, as most patients selected for this treatment were low risk based on their recurrence scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

21-gene recurrence assay in patients receiving intraoperative radiotherapy: are "favorable" characteristics a surrogate for low recurrence? Oppong, BA., Sen Gupta, S., Gary, M., et al.[2022]

Intraoperative radiotherapy (IORT) was used in a study involving 1367 patients with 1400 tumors, showing a 5-year local recurrence rate of 5.98% for those receiving IORT only, which is comparable to other IORT studies but higher than standard whole breast radiation therapy (WBRT).

IORT offers benefits such as convenience and low complication rates, making it a viable option for patients meeting specific criteria, although the addition of WBRT was found to significantly reduce the risk of local recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrence and Survival Rates for 1400 Early Breast Tumors Treated with Intraoperative Radiation Therapy (IORT). Silverstein, MJ., Epstein, MS., Chen, P., et al.[2022]

Intraoperative radiotherapy (IORT) for early-stage breast cancer has been shown to be safe and effective, with two large randomized trials confirming its efficacy in thousands of women, allowing for targeted treatment of high-risk tissue during surgery.

IORT offers several advantages, including reduced treatment time, lower toxicity, and improved patient convenience, but it may require additional whole breast radiation if final pathology reveals unexpected findings, which could limit some of its benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative Radiotherapy for Breast Cancer. Harris, EER., Small, W.[2020]

In a study of 80 head and neck rhabdomyosarcoma (HNRMS) survivors with a median follow-up of 10.5 years, 63% experienced at least one severe adverse event (AE), and 76% had five or more AEs, highlighting the significant impact of treatment-related complications.

Survivors treated with the innovative AMORE approach had a lower risk of severe AEs compared to those treated with standard external beam radiotherapy (EBRT), while overall survival rates were similar between the two groups, suggesting that AMORE may be a safer alternative.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of local treatment in long-term head and neck rhabdomyosarcoma survivors after external beam radiotherapy or AMORE treatment. Schoot, RA., Slater, O., Ronckers, CM., et al.[2015]

Radiotherapy is generally considered a safe treatment, but national reporting of serious incidents is crucial for identifying potential harm and improving safety culture in healthcare.

New UK legislation will expand the focus of reporting to include not only overexposures but also underexposures and positioning errors, highlighting the need for clear definitions and practical approaches to minimize these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unintended doses in radiotherapy-over, under and outside? Eaton, DJ., Byrne, JP., Cosgrove, VP., et al.[2019]

Recent legal requirements in France mandate the reporting of significant incidents in radiotherapy, leading to increased awareness of accidents related to ionizing radiation.

The paper highlights that many serious radiotherapy incidents stem from technical dysfunctions, human errors, and organizational weaknesses, emphasizing the need for improved dosimetric practices to prevent future occurrences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lessons from recent accidents in radiation therapy in France. Derreumaux, S., Etard, C., Huet, C., et al.[2022]

A prospective study involving 13 patients with ipsilateral breast tumor recurrences showed that accelerated partial breast irradiation (APBI) using intraoperative radiation therapy (IORT) achieved a high local control rate of 92% after a median follow-up of 7.8 years.

Patients reported high satisfaction with their treatment experience and maintained good cosmetic outcomes, indicating that APBI may be a well-tolerated alternative to mastectomy for patients with recurrent breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Partial Breast Reirradiation for Patients With Ipsilateral Breast Tumor Recurrence After Initial Treatment With Breast Conservation for Early Stage Breast Cancer. Pisano, CE., Kharouta, MZ., Harris, EE., et al.[2022]

Partial breast irradiation is being explored as a less invasive alternative to the standard whole breast radiation therapy (50 Gy plus a boost of 10 to 16 Gy) after breast-conserving surgery, aiming to reduce treatment time and side effects.

This approach targets the area around the original tumor site, where most recurrences occur, and can be delivered through various methods such as intraoperative radiotherapy, brachytherapy, or 3D conformal radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Accelerated partial breast irradiation following breast conservative surgery. A review of the literature]. Calais, G.[2007]

Intraoperative radiotherapy (IORT) delivered to women with early-stage breast cancer showed a high breast cancer-specific survival rate of 100% and a local control rate of 94.8% after 3.5 years, based on a study of 71 women.

However, the study raised concerns about the local control rate, as 8% of patients experienced ipsilateral breast recurrence, suggesting the need for improvements in imaging and treatment techniques to enhance outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local control following single-dose intraoperative radiotherapy prior to surgical excision of early-stage breast cancer. Kimple, RJ., Klauber-DeMore, N., Kuzmiak, CM., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Radiation-related quality of life parameters after targeted intraoperative radiotherapy versus whole breast radiotherapy in patients with breast cancer: results from the randomized phase III trial TARGIT-A. [2021]

2. China (Republic : 1949- ) pubmed.ncbi.nlm.nih.gov

Evolution of radiotherapy techniques in breast conservation treatment. [2020]

3. Germany pubmed.ncbi.nlm.nih.gov

[Adjuvant radiation therapy for breast cancer]. [2023]

4. China (Republic : 1949- ) pubmed.ncbi.nlm.nih.gov

21-gene recurrence assay in patients receiving intraoperative radiotherapy: are "favorable" characteristics a surrogate for low recurrence? [2022]

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

Recurrence and Survival Rates for 1400 Early Breast Tumors Treated with Intraoperative Radiation Therapy (IORT). [2022]

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

Intraoperative Radiotherapy for Breast Cancer. [2020]

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

Adverse events of local treatment in long-term head and neck rhabdomyosarcoma survivors after external beam radiotherapy or AMORE treatment. [2015]

8. England pubmed.ncbi.nlm.nih.gov

Unintended doses in radiotherapy-over, under and outside? [2019]

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

Lessons from recent accidents in radiation therapy in France. [2022]

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

Partial Breast Reirradiation for Patients With Ipsilateral Breast Tumor Recurrence After Initial Treatment With Breast Conservation for Early Stage Breast Cancer. [2022]

11. France pubmed.ncbi.nlm.nih.gov

[Accelerated partial breast irradiation following breast conservative surgery. A review of the literature]. [2007]

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

Local control following single-dose intraoperative radiotherapy prior to surgical excision of early-stage breast cancer. [2021]