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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new preparation method for breast cancer treatment. It involves administering short doses of radiation (neoadjuvant radiotherapy) to part of the tumor before the usual chemotherapy and surgery. The researchers aim to determine if this approach boosts the immune system and enhances treatment effectiveness. Women with certain types of high-risk breast cancer, who have not yet started treatment and whose cancer has not spread, might be suitable candidates for this trial. As an unphased trial, this study provides a unique opportunity to contribute to innovative research that could improve future breast cancer treatments.

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 prior data suggests that this neoadjuvant radiotherapy is safe for high-risk breast cancer patients?

Research has shown that neoadjuvant radiotherapy, which involves radiation given before other treatments, is generally safe. One study found that this approach led to good results without major safety concerns at the doses used. Patients in various studies handled the treatment well, and the risk of complications remained low. This treatment has been tested for different types of cancer, and findings suggest it is well-tolerated in most cases.

Overall, evidence supports the safety of neoadjuvant radiotherapy. This treatment aims to shrink tumors before surgery and other treatments, potentially enhancing their effectiveness. For those considering joining a trial, existing research provides a reassuring picture of safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard of care for high-risk breast cancer, which often involves weeks of conventional radiation therapy followed by chemotherapy, the neoadjuvant radiotherapy under study is unique because it delivers just three doses of stereotactic radiotherapy before chemotherapy. This shorter course aims to be just as effective while significantly reducing treatment time, potentially allowing for quicker progression to subsequent therapies. Researchers are excited about this approach because it targets the tumor with high precision, minimizing damage to surrounding healthy tissue and possibly improving patient outcomes and quality of life.

What evidence suggests that neoadjuvant radiotherapy might be an effective treatment for high-risk breast cancer?

Research has shown that administering radiation therapy before the main treatment, known as neoadjuvant radiotherapy, can improve outcomes for breast cancer patients. In this trial, participants will receive neoadjuvant radiotherapy, which involves three doses of stereotactic radiotherapy before neoadjuvant chemotherapy in high-risk breast cancers. One study found that this approach increased the number of patients achieving a pathologic complete response (pCR), with about 38% experiencing this positive outcome. This method can also enhance patient satisfaction and reduce overall treatment times. Some studies have reported impressive survival rates, with approximately 70.9% of patients living beyond 13 years. These findings suggest that neoadjuvant radiotherapy is a promising option for those with high-risk breast cancer. ^{1 2 3 5 6}

Who Is on the 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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

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]

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 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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8534073/

Long-Term Results of a Prospective Phase II Trial Overall survival at 13 years was 70.9% (95%CI: 59.6–84.2) (Figure 1). Twenty patients had died, including 17 patients who died from breast cancer. Univariate ...

2. thegreenjournal.com thegreenjournal.com/article/S0167-8140(25)04495-0/fulltext

A systematic review of literature of the last decade This review indicates that NART followed by IBR may result in higher patient satisfaction, lower complication rates and shorter total treatment time compared ...

3. nature.com nature.com/articles/s41598-024-59961-0

Neoadjuvant radiochemotherapy is safe and feasible for ... This study aimed to evaluate the survival outcomes of neoadjuvant radiochemotherapy (NARCT) for early breast cancer.

4. bmrat.org bmrat.org/index.php/BMRAT/article/view/944

Evaluating the efficacy of preoperative radiotherapy in ... This study demonstrated that PRT for non-complete responder patients improves pCR rates in the breast and axilla, allowing almost 38% of patients to have ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0167814025052405

ESTRO recommendations on preoperative radiation ... Radiological response was evaluated in four trials, with response rates ranging from 17 % to 100 %. Pathological response data were available in ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2468294225001200

Comparing the oncologic outcomes of breast-conserving ... Five-year overall survival rates are similar for BCS with or without neoadjuvant chemotherapy. •. Recurrence rates and distant metastasis are increased ...