Short-Course Radiation for Breast Cancer

(TRIO Trial)

Overseen By Muriel Brackstone, MD PhD

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Disqualifiers: Metastatic disease, Collagen vascular disease, Recurrent breast cancer, others

Stay on Your Current Meds You can continue your current medications while participating

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

40 Participants Needed

Trial Summary

What is the purpose of this trial?

Patients with high risk breast cancers (any locally advanced breast cancer patient defined as Stages IIB-III \[excluding inflammatory breast cancer\] with stage IIA being eligible for triple negative and HER2-positive breast cancers) will receive neoadjuvant radiation to any portion of their tumour in three fractions in order to act as an immune primer. Radiation will be delivered to a portion of the tumour in three fractions. The patient will be positioned prone as per the SIGNAL 2.0 protocol. The patient will then go on to standard of care treatment (neoadjuvant chemotherapy and surgery) followed by whole-breast radiation as needed. Pathologic complete response will be the primary outcome. Immune markers will also be evaluated.

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

The trial protocol does not specify whether you need to stop taking your current medications. However, since the trial involves neoadjuvant chemotherapy and radiation, it's best to discuss your current medications with the trial team to ensure there are no interactions.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the idea that Short-Course Radiation for Breast Cancer is an effective treatment?

The available research shows that preoperative short-course radiation therapy for breast cancer is becoming more common and is seen as a promising approach. It is part of a shift in treatment strategies that aim to improve outcomes by using radiation before surgery. This approach can lead to more conservative surgeries and potentially increase the chances of patients living longer without the disease returning. Advances in technology and understanding of how radiation works have made this treatment more precise and effective, allowing it to be safely combined with other cancer-fighting methods. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment Neoadjuvant radiotherapy, Preoperative radiotherapy, Neoadjuvant radiotherapy for breast cancer?

Research suggests that using radiotherapy before surgery in breast cancer can help improve control and survival rates, similar to its use in rectal cancer. Advances in technology and understanding of radiotherapy have made it more precise and effective, potentially allowing for more conservative surgeries and better outcomes. ^{1 2 3 4 5}

What safety data exists for short-course radiation treatment for breast cancer?

The safety data for short-course radiation treatment for breast cancer includes findings from a Canadian randomized trial, which showed no statistical differences in efficacy or adverse effects between conventional and short-course radiotherapy. However, this trial only included patients with favorable prognoses and excluded those with carcinoma involving the inked margin of excision. The trial also did not use additional boost irradiation and had a low percentage of patients treated with systemic chemotherapy. There is a concern that large fraction doses may cause more severe late toxicities in normal breast tissue. Further clinical studies are recommended to confirm the feasibility of this method for broader patient groups. ^{6 7 8 9 10}

Is short-course radiation for breast cancer safe?

Short-course radiation for breast cancer has been studied and found to have similar safety profiles to conventional radiotherapy, with no significant differences in adverse effects. However, it may cause more severe late skin reactions, and further studies are needed to confirm its safety for all patient groups. ^{6 7 8 9 10}

Is neoadjuvant radiotherapy a promising treatment for breast cancer?

Yes, neoadjuvant radiotherapy, also known as short-course radiotherapy, is a promising treatment for breast cancer. It offers a shorter treatment time, which can be more convenient for patients, and has been shown to be as effective as traditional long-term radiotherapy. This approach can improve the quality of life for patients by reducing treatment costs and saving medical resources. ^{1 2 9 11 12}

How is short-course radiation treatment for breast cancer different from other treatments?

Short-course radiation treatment for breast cancer is unique because it shortens the treatment period by increasing the daily dose of radiation, making it more convenient and less costly compared to conventional long-term radiotherapy. This approach is already used in Canada and parts of Europe and has shown similar effectiveness and safety to traditional methods, although further studies are needed to confirm its feasibility in different populations. ^{1 2 9 11 12}

Research Team

Brian Yaremko, MD

Principal Investigator

London Health Sciences Centre/London Regional Cancer Program

Muriel Brackstone, MD, PhD

Principal Investigator

London Health Sciences Centre/Lawson Health Research Institute

Michael Lock, MD

Principal Investigator

London Health Sciences Centre/London Regional Cancer Program

Eligibility Criteria

This trial is for adults over 18 with high-risk, non-inflammatory breast cancer at stages IIB-III (IIA if triple negative or HER2-positive). Participants must be able to undergo MRI scans, tolerate needle biopsies, and have not received prior treatment for their current breast cancer. They should also plan to receive standard neoadjuvant chemotherapy.

Inclusion Criteria

I am scheduled for chemotherapy before surgery.

My breast cancer is at an advanced stage but not the most severe form.

My breast cancer is not lobular, sarcomatous, metaplastic, or has lobular features.

Exclusion Criteria

You cannot handle having a core needle biopsy.

Pregnant or lactating

I have health conditions that prevent me from receiving standard cancer treatments.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive 3 doses of stereotactic radiotherapy to act as an immune primer

1 week

3 visits (in-person)

Chemotherapy

Participants undergo standard neoadjuvant chemotherapy (anthracycline and taxane based)

12-16 weeks

Surgery

Participants undergo standard surgery (breast conserving or lumpectomy)

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Routine follow-up appointments, including yearly mammography

Treatment Details

Interventions

• Neoadjuvant radiotherapy

Trial Overview The study tests whether three fractions of radiation before standard care can prime the immune system in patients with advanced breast cancer. The primary goal is to see if this leads to a complete response where no signs of cancer are found after treatment.

Participant Groups

Group I: Neoadjuvant radiotherapy Experimental Treatment 1 Intervention

3 doses of stereotactic radiotherapy administered prior to neoadjuvant chemotherapy in high-risk breast cancers.

Neoadjuvant radiotherapy is already approved in United States, European Union, China for the following indications:

Approved in United States as Neoadjuvant radiotherapy for:

• Locally advanced breast cancer (LABC)
• T4 breast cancer

Approved in European Union as Preoperative radiotherapy for:

• Locally advanced breast cancer (LABC)
• T4 breast cancer

Approved in China as Neoadjuvant radiotherapy for:

• Locally advanced breast cancer (LABC)
• T4 breast cancer

Who Is Running the Clinical Trial?

London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

686

Recruited

427,000+

London Health Sciences Centre OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

668

Recruited

424,000+

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

678

Recruited

421,000+

Lawson Health Research Institute

Lead Sponsor

Trials

684

Recruited

432,000+

Findings from Research

Delaying surgery for more than four weeks after short-course neoadjuvant radiotherapy in rectal cancer patients may lead to better tumor downstaging and fewer postoperative complications, but there are concerns about increased local recurrence rates in this group.

Current evidence does not show a significant impact of different surgery timing on overall survival, indicating a need for further high-quality studies to clarify the optimal timing for surgery after radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What is the optimal timing of surgery after short-course radiotherapy for rectal cancer? Donnelly, SM., Wyatt, J., Powell, SG., et al.[2023]

In a study of 155 patients with locally advanced rectal cancer, preoperative short-course radiotherapy followed by surgery showed a low complete pathological response rate of only 2.2%, but 28% of patients experienced downstaging, indicating some effectiveness in tumor size reduction.

The research suggests that waiting more than 20 days after radiotherapy before surgery may improve the chances of achieving a free circumferential resection margin, particularly in patients with mesorectal fascia involvement, which is crucial for reducing the risk of cancer recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response to treatment and interval to surgery after preoperative short-course radiotherapy in rectal cancer. García-Cabezas, S., Rodríguez-Liñán, M., Otero-Romero, AM., et al.[2017]

Recent advancements in breast cancer treatment are shifting towards administering systemic therapy before surgery, which can lead to more effective treatment outcomes and potentially higher rates of disease-free and overall survival.

The evolving approach to radiotherapy includes considering its use before surgery, supported by improved radiobiological knowledge and technology, allowing for safer and more effective combinations with other treatments like antitumor drugs or immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative Radio(Chemo)Therapy in Breast Cancer: Time to Switch the Perspective? Montero, A., Ciérvide, R.[2023]

Unconventional radiation therapy, which delivers larger doses over fewer days, does not increase the risk of local recurrence or negatively impact breast appearance in women with early breast cancer after breast-conserving surgery, based on a review of four trials involving 7095 participants.

This approach also significantly reduces acute skin toxicity, making it a safer option for selected patients, although long-term follow-up is needed to fully understand its effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fraction size in radiation treatment for breast conservation in early breast cancer. James, ML., Lehman, M., Hider, PN., et al.[2020]

In a study of 210 rectal cancer patients treated with preoperative short-course radiotherapy followed by surgery, the 5-year overall survival rate was 66.4%, indicating effective long-term outcomes.

The treatment resulted in excellent local control with a locoregional relapse-free survival rate of 91.7%, and the associated treatment-induced toxicity was low, with severe side effects occurring in only 1% of patients early and 7.6% late.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative short-course radiotherapy in rectal cancer patients: results and prognostic factors. Skóra, T., Nowak-Sadzikowska, J., Martynów, D., et al.[2022]

In a trial involving 67 breast cancer patients undergoing neo-adjuvant therapy, pre-operative chemotherapy showed low side effects, with 79% of patients experiencing no hair loss and 74% reporting no gastrointestinal issues, despite the use of five different cytotoxic agents.

Response rates to pre-operative chemotherapy included 4% complete remission and 38% partial remission, indicating that while the treatment was generally well-tolerated, the effectiveness varied, and the study aims to identify which patients would benefit most from subsequent post-operative treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective randomized clinical trial: protoadjuvant chemotherapy vs. protoadjuvant radiotherapy in breast cancer stages T3/4, N+/-, M0. Rainer, H.[2007]

In a randomized trial comparing short-course (SC) and long-course (LC) preoperative radiotherapy for rectal cancer, the LC group experienced significantly higher rates of acute adverse events (AEs) at 99.4% compared to 72.3% in the SC group, indicating that SC may be safer in terms of immediate treatment-related toxicity.

Despite the higher AEs in the LC group, there were no significant differences in overall postoperative complication rates between the two groups, suggesting that while LC may lead to more acute side effects, it does not necessarily result in worse surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute Adverse Events and Postoperative Complications in a Randomized Trial of Preoperative Short-course Radiotherapy Versus Long-course Chemoradiotherapy for T3 Adenocarcinoma of the Rectum: Trans-Tasman Radiation Oncology Group Trial (TROG 01.04). Ansari, N., Solomon, MJ., Fisher, RJ., et al.[2022]

In a study of 177 patients with resectable rectal cancer, short-course preoperative radiotherapy (25 Gy in five fractions) was linked to a 38% complication rate within 3 months, highlighting the need to identify patients who may not benefit from this treatment.

Factors such as an overall treatment time (OTT) exceeding 13 days, older age, and longer radiotherapy fields were associated with a higher risk of postoperative complications, suggesting that optimizing treatment protocols could reduce acute toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective study of acute toxicity following short-course preoperative radiotherapy. Hartley, A., Giridharan, S., Gray, L., et al.[2004]

Short-course radiotherapy for the whole breast after surgery is a promising alternative to conventional long-term radiotherapy, offering a more convenient treatment option for breast cancer patients, as it shortens the treatment duration by increasing the daily dose.

A Canadian trial showed no significant differences in efficacy or adverse effects between short-course and conventional radiotherapy, but it had limitations, such as excluding patients with more severe cases and not using boost irradiation, indicating the need for further studies to confirm its safety and effectiveness, especially for Japanese women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-course radiotherapy for the whole breast after breast conserving surgery. Nozaki, M., Kawashima, M.[2008]

Implementing a radiation dermatitis (RD) prevention protocol significantly improved oncology nurses' confidence in assessing and managing RD in breast cancer patients, as shown by surveys completed by 11 nurses before and after an education session.

The protocol led to a statistically significant increase in the use of topical steroids for RD prophylaxis, which is expected to help reduce the incidence of dermatologic adverse events during radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation Dermatitis: A Prevention Protocol for Patients With Breast Cancer. Lucas, AS., Lacouture, M., Schneider, SM.[2019]

Short-course radiation therapy (5 × 5 Gy) for resectable rectal cancer has been shown to have fewer early adverse effects compared to long-course chemoradiation, based on two randomized studies involving a total of 638 participants.

Both treatment regimens resulted in similar long-term oncologic outcomes and late toxicity rates, making short-course radiation a more convenient and cost-effective option, especially for patients who cannot undergo chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Point: short-course radiation therapy is preferable in the neoadjuvant treatment of rectal cancer. Bujko, K., Bujko, M.[2022]

Hypofractionated radiotherapy (HFRT) after breast-conserving surgery is a safe and effective alternative to conventional radiotherapy, providing similar survival rates and local tumor control while significantly reducing treatment time.

HFRT not only saves medical resources and costs but also enhances the quality of life for patients by shortening the overall treatment duration compared to standard radiotherapy, which typically lasts 5 to 7 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progress of clinical study on hypofractionated radiotherapy after breast-conserving surgery. Wei, NN., Li, F., Cai, P., et al.[2020]

References

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

What is the optimal timing of surgery after short-course radiotherapy for rectal cancer? [2023]

2. Spain pubmed.ncbi.nlm.nih.gov

Response to treatment and interval to surgery after preoperative short-course radiotherapy in rectal cancer. [2017]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Preoperative Radio(Chemo)Therapy in Breast Cancer: Time to Switch the Perspective? [2023]

4. England pubmed.ncbi.nlm.nih.gov

Fraction size in radiation treatment for breast conservation in early breast cancer. [2020]

5. Germany pubmed.ncbi.nlm.nih.gov

Preoperative short-course radiotherapy in rectal cancer patients: results and prognostic factors. [2022]

6. Austria pubmed.ncbi.nlm.nih.gov

Prospective randomized clinical trial: protoadjuvant chemotherapy vs. protoadjuvant radiotherapy in breast cancer stages T3/4, N+/-, M0. [2007]

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

Acute Adverse Events and Postoperative Complications in a Randomized Trial of Preoperative Short-course Radiotherapy Versus Long-course Chemoradiotherapy for T3 Adenocarcinoma of the Rectum: Trans-Tasman Radiation Oncology Group Trial (TROG 01.04). [2022]

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

Retrospective study of acute toxicity following short-course preoperative radiotherapy. [2004]

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

Short-course radiotherapy for the whole breast after breast conserving surgery. [2008]

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

Radiation Dermatitis: A Prevention Protocol for Patients With Breast Cancer. [2019]

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

Point: short-course radiation therapy is preferable in the neoadjuvant treatment of rectal cancer. [2022]

12. China pubmed.ncbi.nlm.nih.gov

Progress of clinical study on hypofractionated radiotherapy after breast-conserving surgery. [2020]