Intraoperative Radiation Therapy for Breast Cancer

Not currently recruiting at 26 trial locations

Overseen By Michael Alvarado

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: University of California, San Francisco

Must not be taking: Chemotherapy, Hormone therapy

Disqualifiers: Lymph node positive, BRCA1/2, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 15-40 minutes

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method of delivering radiation therapy to breast cancer patients immediately after surgery. The aim is to determine if delivering radiation directly to the tumor area during surgery can effectively eliminate remaining cancer cells, potentially matching the effectiveness of traditional radiation therapy. It targets patients with early-stage breast cancer undergoing breast-conserving surgery, with tumors less than 3.5 cm in size. This approach may benefit those with a small, localized breast tumor who have not previously had cancer in that breast. As an unphased trial, it provides a unique opportunity to explore innovative treatments that could improve recovery and outcomes for early-stage breast cancer patients.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are undergoing primary systemic treatment (hormones or chemotherapy) as initial treatment, you are not eligible for the trial.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are undergoing primary systemic treatment like hormones or chemotherapy, you may not be eligible for the trial.

What is the safety track record for intraoperative radiation therapy?

Research shows that intraoperative radiation therapy (IORT) is generally well-tolerated by breast cancer patients. Studies have found that IORT usually causes fewer immediate skin side effects compared to traditional external beam radiation, with some patients experiencing milder skin reactions.

However, long-term effects such as breast fibrosis, where breast tissue becomes thicker and scarred, can occur. These long-term effects are still under study to gain a full understanding.

Overall, IORT tends to have fewer complications after radiation and is known for better cosmetic results. The treatment is effective and safe for many, but individual experiences can vary based on factors like age and tumor size. Patients should discuss any concerns with their healthcare provider to determine if IORT is the right choice. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Intraoperative Radiation Therapy (IORT) is unique because it delivers radiation directly to the tumor site during a lumpectomy, all in one go. This is different from the standard external beam radiation therapy, which usually requires multiple sessions over several weeks. Researchers are excited about IORT because it targets cancer cells more precisely, potentially reducing damage to surrounding healthy tissue and shortening the overall treatment time. This approach could make recovery quicker and more convenient for patients, which is a big win in cancer care.

What evidence suggests that intraoperative radiation therapy is effective for breast cancer?

Research has shown that intraoperative radiation therapy (IORT), which participants in this trial will receive, can effectively treat early-stage breast cancer. In the TARGIT-A trial, the chance of cancer returning in the same breast within five years was 3.3% with IORT. Although this is slightly higher than the 1.3% risk with whole breast radiation, IORT remains promising, especially for patients with lower risk. Additionally, IORT has been linked to fewer deaths from causes other than breast cancer. Long-term data indicates high survival rates and a good chance of avoiding further surgery, such as a mastectomy. Overall, these findings suggest IORT could be a suitable option for some patients. ^{1 2 6 7 8}

Who Is on the Research Team?

Michael D. Alvarado

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for individuals with early stage breast cancer (T1 and T2, no larger than 3.5 cm, no spread to lymph nodes or other parts of the body) who are suitable for breast-conserving surgery. It's not open to those under 50, with tumors over 3 cm, estrogen receptor negative cancers, HER2 positive status, high-grade tumors or extensive intraductal component.

Inclusion Criteria

I am a candidate for surgery that will not remove my entire breast.

My cancer is small (under 3.5 cm) and has not spread to lymph nodes or other parts of my body.

Exclusion Criteria

Unable to determine if the edges of the tissue removed during surgery are clear of cancer.

I was diagnosed with cancer in both breasts at the same time.

My breast cancer has spread to the lymph nodes under my arm.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo intraoperative radiation therapy (IORT) in a single fraction over 15-40 minutes during breast-conserving surgery

15-40 minutes

1 visit (in-person, during surgery)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits every 6 months for 3 years and yearly for 2 additional years

5 years

Every 6 months for 3 years, then yearly for 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Intraoperative Radiation Therapy

Trial Overview The study is testing intraoperative radiation therapy given one time during surgery where the tumor was removed. The goal is to see if this method can effectively kill any remaining tumor cells and compare its effectiveness against standard radiation treatments in patients with early-stage breast cancer.

How Is the Trial Designed?

Group I: Treatment (IORT) Experimental Treatment 2 Interventions

Patients undergo IORT in a single fraction over 15-40 minutes at the time of standard of care lumpectomy.

Intraoperative Radiation Therapy is already approved in United States, European Union for the following indications:

Approved in United States as Keytruda for:

• Head and neck squamous cell carcinoma (HNSCC)
• Melanoma
• Lung cancer

Approved in European Union as Keytruda for:

• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Head and neck squamous cell carcinoma (HNSCC)

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Carl Zeiss Meditec AG

Industry Sponsor

Trials

43

Recruited

7,800+

Published Research Related to This Trial

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab, a monoclonal antibody targeting PD-1, showed significant efficacy in treating a 79-year-old patient with advanced squamous cell lung cancer, leading to a complete response after just 3 cycles of treatment.

However, the patient developed acute myelomonocytic leukemia after starting pembrolizumab, highlighting a potential safety concern that warrants further investigation into the drug's effects on blood cell production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. Kim, HB., Park, SG., Hong, R., et al.[2020]

Radiation therapy not only helps eliminate cancer cells but also modifies the tumor microenvironment, potentially enhancing the body's immune response against tumors.

Combining radiation with immune checkpoint inhibitors has shown promise in early clinical trials for breast cancer, suggesting a synergistic effect that could improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in Combining Radiation and Immunotherapy in Breast Cancer. Nguyen, AT., Shiao, SL., McArthur, HL.[2021]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab (Keytruda) is approved for treating advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient, specifically for patients whose disease has progressed after previous treatments.

This approval is significant for patients who are not candidates for curative surgery or radiation, providing a new therapeutic option for a challenging stage of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Approved Use for Keytruda. Aschenbrenner, DS.[2022]

In a study involving 8 patients with hormone receptor-positive metastatic breast cancer, combining pembrolizumab with palliative radiation therapy did not result in any objective responses, leading to the study's closure.

The median progression-free survival was only 1.4 months and overall survival was 2.9 months, indicating limited efficacy of this treatment combination in heavily pre-treated patients, although the treatment was generally safe with only one significant adverse event reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Study of Pembrolizumab in Combination With Palliative Radiotherapy for Hormone Receptor-positive Metastatic Breast Cancer. Barroso-Sousa, R., Krop, IE., Trippa, L., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11493767/

Comparative long-term oncological outcomes of ... At a median follow-up of 64.6 months, IORT demonstrated 11 locoregional recurrences (LRR), 1 metastasis, and 1 death, compared to 4 LRR, 5 ...

2. astro.org astro.org/news-and-publications/news-and-media-center/news-releases/2025/astro-corrects-media-misinformation-on-breast-cancer-treatment-options

ASTRO corrects media misinformation on breast cancer ... Higher Recurrence Rates: The ELIOT trial showed significantly higher local recurrence rates with IORT compared to WBI, even when re-analyzed for ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2405630825000904

IORT for early-stage, low-risk breast cancer IORT has been associated with lower non–breast cancer mortality, as reported in the long-term results of the TARGIT-A trial[3], which observed fewer deaths ...

4. breast-cancer-research.biomedcentral.com breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-024-01936-0

Intraoperative radiotherapy versus ... - Breast Cancer Research The results of the TARGIT-A trial showed that the five-year risk of local recurrence in the ipsilateral breast was 3.3% for IORT versus 1.3% for ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1155/2024/6207762

Outcomes From Real‐World Data on Intraoperative ... With a median follow-up of 66.6 months, the overall survival and mastectomy-free rates were 95.66% and 90.65%, respectively; this demonstrates ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0360301625030536

Efficacy and Safety of Intraoperative Radiotherapy (IORT) ... Conclusion. IORT followed by postoperative EBRT is generally effective and safe in Chinese breast cancer patients. Age and tumor size significantly affect ...

7. spandidos-publications.com spandidos-publications.com/10.3892/ol.2025.15092

Long‑term follow‑up outcomes of intraoperative ... However, the long‑term outcomes and safety of IORT in patients with breast cancer remain incompletely understood.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10849931/

Outcomes and complications of intraoperative radiotherapy ... IORT is considered to have lower post‐radiation complications and better cosmetic outcomes in breast cancer patients.