Hypofractionated Radiotherapy for Breast Cancer

(RHEAL Trial)

Not currently recruiting at 23 trial locations

Overseen By Solomon Daryl, RN

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Ontario Clinical Oncology Group (OCOG)

Must not be taking: Neoadjuvant endocrine therapy

Disqualifiers: Age < 18, T4/N3 stages, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

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

Compensation: Varies

Number of Visits: 5

Duration: 1-3 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a faster, one-week radiation schedule is as effective as the usual three-week plan for treating breast cancer in patients who have undergone surgery. It focuses on women with breast cancer that has spread to nearby lymph nodes but not to other parts of the body. Participants should have recently been diagnosed, had surgery, and require locoregional radiation treatment to the breast area. This trial suits those without widespread cancer or conditions that would interfere with the treatment. As a Phase 3 trial, it represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications to join the trial?

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that hypofractionated radiotherapy, which involves delivering higher doses of radiation over a shorter period, is generally safe for breast cancer patients. Studies have found that this method results in low rates of immediate side effects, meaning patients experience fewer problems right after treatment. For instance, one study noted only minor changes in skin appearance and mild side effects among patients.

Another study examined different therapy schedules and found it was well-tolerated over time, indicating that patients did not encounter many serious issues during or after treatment. Research across various settings has demonstrated that hypofractionated radiotherapy is effective and safe in the long term.

In summary, current research suggests that hypofractionated radiotherapy is a safe option for many breast cancer patients. It requires fewer treatment sessions but maintains safety comparable to traditional methods that extend treatment over a longer period. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

Researchers are excited about hypofractionated radiotherapy for breast cancer because it offers a faster and potentially more convenient treatment option compared to conventional radiotherapy. Unlike the standard approach, which involves smaller doses over several weeks, hypofractionation delivers larger doses in fewer sessions, reducing the overall treatment time. This not only makes the process quicker for patients but may also improve access to care and reduce healthcare costs. Additionally, early studies suggest that it could be just as effective and safe as traditional methods, which is promising for enhancing patient quality of life.

What evidence suggests that hypofractionated radiotherapy might be an effective treatment for breast cancer?

Research has shown that hypofractionated radiotherapy, which involves larger doses of radiation over a shorter period, is as effective as traditional longer treatment schedules for breast cancer. In this trial, participants will be assigned to either the hypofractionated radiotherapy arm or the conventional fractionation arm. Studies have found that the hypofractionated approach is equally effective at preventing cancer recurrence in the treated area. Specifically, one study found that 98.7% of patients experienced no cancer spread around the breast area after three years. Additionally, this treatment tends to have low rates of side effects and changes in appearance. These findings suggest that hypofractionated radiotherapy could be a convenient and effective option for treating breast cancer. ^{2 4 5 6 7}

Who Is on the Research Team?

Timothy J. Whelan

Principal Investigator

Juravinski Cancer Centre, McMaster University, Hamilton

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed node-positive breast cancer who've had surgery and need radiotherapy, but haven't spread to other body parts. It's not for those with recent non-breast cancers (except certain skin cancers), previous chest radiation, severe diseases like scleroderma or serious heart/lung conditions, under 18s, advanced tumor stages T4/N3, arm swelling after surgery, pregnant/breastfeeding women, or if they can't follow up for 5 years.

Inclusion Criteria

My cancer has not spread to other parts of my body.

I have recently been diagnosed with breast cancer and have undergone surgery.

I am eligible for targeted radiation therapy after my surgery.

Exclusion Criteria

I have had breast cancer or DCIS on the same side treated with radiation before.

My cancer is at an advanced stage, affecting nearby tissues or lymph nodes.

I haven't had cancer other than non-melanoma skin cancer or treated in-situ carcinoma in the last 5 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either conventional or hypofractionated locoregional radiotherapy

1-3 weeks

5-15 visits (in-person)

Follow-up

Participants are monitored for lymphedema, radiation toxicity, and other outcomes

5 years

Annual visits (in-person)

Long-term follow-up

Participants are assessed for breast cancer recurrence, new second cancers, and overall survival

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Locoregional radiation treatment

Trial Overview The study compares two ways of giving radiotherapy: the standard method over 3 weeks versus a shorter one-week course. The goal is to see if the short course works just as well without making patients come in for treatment as often.

How Is the Trial Designed?

Group I: Experimental Experimental Treatment 1 Intervention

Hypofractionation for locoregional radiotherapy

Group II: Control Active Control 1 Intervention

Conventional fractionation for locoregional radiotherapy

Locoregional radiation treatment is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Locoregional Radiation Therapy for:

• Breast cancer
• Node-positive breast cancer

Approved in United States as Locoregional Radiation Therapy for:

• Breast cancer
• Node-positive breast cancer

Approved in Canada as Locoregional Radiation Therapy for:

• Breast cancer
• Node-positive breast cancer

Who Is Running the Clinical Trial?

Ontario Clinical Oncology Group (OCOG)

Lead Sponsor

Trials

65

Recruited

42,000+

Published Research Related to This Trial

In a study of 257 breast cancer patients treated with hypofractionated radiation therapy (HFRT), the 5-year overall survival rate was 86.6%, indicating that HFRT is effective for patients with breast cancer and nodal involvement.

The treatment was associated with manageable side effects, with no serious complications like cardiac issues or pneumonitis reported, although some patients experienced mild to moderate skin changes and lymphedema.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated Regional Nodal Irradiation for Women With Node-Positive Breast Cancer. Bellefqih, S., Elmajjaoui, S., Aarab, J., et al.[2022]

In a study of 2309 breast cancer patients, those receiving hypofractionated radiotherapy experienced significantly less acute skin reactions and pain compared to those receiving conventional fractionation, indicating a safer treatment option.

Hypofractionation also resulted in lower levels of patient-reported symptoms like burning, swelling, and fatigue during treatment, suggesting it may enhance patient comfort without compromising long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differences in the Acute Toxic Effects of Breast Radiotherapy by Fractionation Schedule: Comparative Analysis of Physician-Assessed and Patient-Reported Outcomes in a Large Multicenter Cohort. Jagsi, R., Griffith, KA., Boike, TP., et al.[2022]

In a study of 81 patients with localized breast cancer treated with hypofractionated radiotherapy (HFRT), the treatment was well-tolerated, with low rates of late toxicities such as chest pain (11%) and limb pain (12%).

The five-year overall survival rate was 76.5%, and there were no locoregional recurrences, indicating that HFRT is effective in controlling the disease while minimizing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of toxicities and outcomes in patients with breast cancer treated with hypofractionated radiotherapy. Sindhu, M., Malik, M., Ahmed, SF., et al.[2022]

Long-term randomized trials have confirmed that hypofractionated radiotherapy, delivering about 2.6 Gy per fraction for a total of 40-42.6 Gy over 3 weeks, is both safe and effective for treating early breast cancer post-surgery.

While most studies focused on breast-only treatment, hypofractionated locoregional radiation is now considered standard care in the UK and parts of Canada, indicating its growing acceptance in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of hypofractionated radiotherapy in breast locoregional radiation. Caudrelier, JM., Truong, PT.[2018]

The use of hypofractionated radiation therapy (RT) for breast cancer treatment increased from 3.8% in 2006 to 13.6% by 2009-2010 among low-risk older patients, indicating a growing acceptance of this more convenient and cost-effective treatment option.

Despite the increase in hypofractionation use, it remained low overall, especially among patients over 80 years old, while the adoption of intensity-modulated RT (IMRT) rose significantly during the same period, highlighting a disparity in the uptake of these two treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoption of hypofractionated radiation therapy for breast cancer after publication of randomized trials. Jagsi, R., Falchook, AD., Hendrix, LH., et al.[2022]

In a study of 1,010 breast cancer patients, hypofractionated radiotherapy (HFRT) showed similar locoregional recurrence-free survival (LRRFS) and disease-free survival (DFS) rates compared to conventionally fractionated radiotherapy (CFRT) after a median follow-up of 49.5 months.

While HFRT was effective across various nodal stages and molecular subtypes, it tended to show lower DFS in N2-3 patients with triple-negative breast cancer compared to CFRT, indicating a need for further investigation in this specific group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Practice of Hypofractionated Radiotherapy in Patients With Invasive Breast Cancer. Chen, F., Hui, TSK., Ma, L., et al.[2022]

Hypofractionated radiotherapy is gaining popularity for breast cancer treatment in the UK and Canada, but there are concerns about potential increased toxicity associated with this approach.

The article emphasizes the importance of careful planning and dosimetry in hypofractionated radiotherapy to ensure effective treatment while minimizing risks, and it provides recommendations for both planning and monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What are the minimal standards of radiotherapy planning and dosimetry for "hypofractionated" radiotherapy in breast cancer? MacLeod, N., McIntyre, A., Canney, PA.[2018]

Hypofractionated radiation therapy (HFRT) for locally advanced breast cancer showed excellent overall survival rates of 100% at 1 year and 90% at 3 years, indicating its efficacy as a treatment option.

The treatment had a low toxicity profile, with only 1.6% of patients experiencing local recurrence and manageable rates of skin toxicity and lymphedema, suggesting it is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated Radiation Therapy (HFRT) of Breast/Chest Wall and Regional Nodes in Locally Advanced Breast Cancer: Toxicity Profile and Survival Outcomes in Retrospective Monoistitutional Study. De Matteis, S., Facondo, G., Valeriani, M., et al.[2022]

In a study of 274 early breast cancer patients treated with hypofractionated radiation treatment (HFRT) over a median follow-up of 7 years, the local recurrence-free survival rate was very high at 97.2%, indicating that HFRT is effective in preventing local cancer recurrence.

The acute toxicity associated with HFRT was generally low, with most patients experiencing less than grade 3 side effects, suggesting that HFRT is a safe treatment option for eligible patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated radiation treatment in early breast cancer: Results in a New Zealand setting. James, ML., Dehn, G., Robinson, BA.[2018]

Hypofractionated radiation therapy, which delivers fewer but larger doses of radiation over a shorter period, has shown comparable outcomes to conventional radiation in treating breast cancer, suggesting it could be an effective alternative.

Ongoing phase 3 trials are investigating hypofractionated whole breast irradiation and accelerated partial breast irradiation, which may lead to broader acceptance of these methods for early-stage breast cancer, although concerns about patient selection and late toxicity remain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated radiation therapy in the treatment of early-stage breast cancer. Freedman, GM.[2021]

Hypofractionation for whole-breast irradiation is safe and effective, providing similar local control and cosmetic outcomes compared to traditional methods, as supported by recent randomized trials.

There is growing interest in using hypofractionation for partial-breast irradiation, with early studies showing promising local control and manageable side effects, while larger randomized trials are currently being conducted to further evaluate its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience using hypofractionated radiation schedules in breast cancer. Whelan, TJ., Kim, DH., Sussman, J.[2022]

Hypofractionated radiotherapy is gaining importance in breast cancer treatment, suggesting a shift towards more efficient radiation delivery methods.

The introduction of simultaneous integrated boost techniques allows for targeted treatment of the primary tumor region, potentially improving treatment outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging Role of Hypofractionated Radiotherapy with Simultaneous Integrated Boost in Modern Radiotherapy of Breast Cancer. Nitsche, M., Dunst, J., Carl, UM., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10955656/

Ultra-hypofractionated one-week locoregional radiotherapy ... Regional node irradiation (RNI) reduces breast cancer death risk by 1 to 5 %, varying with lymph node status [1]. Moderately hypofractionated ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa0906260

Long-Term Results of Hypofractionated Radiation Therapy ... We conducted a study to determine whether a hypofractionated 3-week schedule of whole-breast irradiation is as effective as a 5-week schedule.

3. ascopubs.org ascopubs.org/doi/10.1200/GO-24-00277

Phase II Evaluation of Ultra-Hypofractionated ... The study found that ultra-hypofractionated radiation therapy in patients with breast cancer had low rates of acute toxicity and cosmesis changes.

4. sciencedirect.com sciencedirect.com/science/article/pii/S1526820921002664

Hypofractionated Radiation Therapy (HFRT) of Breast ... Randomized trials with a long follow-up have shown that hypofractionated radiotherapy (HFRT) leads to similar results in terms of local control and cosmetic ...

5. thebreastonline.com thebreastonline.com/article/S0960-9776(25)00652-6/fulltext

Once-Weekly Ultra-Hypofractionated Radiation Therapy for ... Three-year locoregional control was 98.7%, and three-year overall survival, disease-free survival and cause-specific survival were 90%, 94.4% ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10845660/

Efficacy and safety analysis of hypofractionated and ... In this meta-analysis, we conducted a comparative analysis of the safety and efficacy of hypofractionated and conventional fractionated ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2405630824000417

Ultra-hypofractionated one-week locoregional radiotherapy ... Regional node irradiation (RNI) reduces breast cancer death risk by 1 to 5 %, varying with lymph node status [1]. Moderately hypofractionated radiation therapy ...