Preoperative Radiation Schedules for Breast Cancer

Overseen By Benjamin D. Smith, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Recurrent breast cancer, Scleroderma, Pregnancy, 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

Compensation: Varies

Number of Visits: Unknown

126 Participants Needed

Trial Summary

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 effectiveness of preoperative radiation schedules for breast cancer treatment?

Research shows that hypofractionated radiotherapy, which involves giving higher doses of radiation over fewer sessions, is a safe and effective treatment for breast cancer, as seen in large trials. It has been shown to provide good control of the disease and is already a standard practice in many centers. ^{1 2 3 4 5}

Is preoperative hypofractionated radiation therapy safe for breast cancer patients?

Research shows that hypofractionated radiation therapy, which uses fewer but larger doses, is generally safe for breast cancer patients, with similar safety and effectiveness compared to traditional methods. Studies have found no significant increase in adverse effects, making it a viable option for many patients. ^{3 6 7 8 9}

How does preoperative radiation therapy for breast cancer differ from other treatments?

Preoperative radiation therapy for breast cancer, particularly hypofractionated schedules, involves giving fewer but larger doses of radiation over a shorter period, which can be more convenient and may have similar effectiveness compared to traditional longer schedules. This approach is being studied to see if it can be as effective in reducing the risk of cancer returning, while potentially causing fewer side effects and being more convenient for patients. ^{1 2 3 10 11}

What is the purpose of this trial?

To compare the outcomes of and responses to 2 different radiation therapy schedules (the standard radiation amount and number of doses versus less radiation and fewer doses) that are being given before having breast cancer surgery (cancer removal and reconstruction).

Research Team

Benjamin D. Smith, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults over 18 with invasive breast cancer who plan to have tissue-based reconstruction after mastectomy. It's open to those with certain advanced stages of cancer, including T3-T4c or N1-N3 and even stage T4d in specific cases. Patients must not have had previous radiation in the affected area, be pregnant, or have recurrent breast cancer or active scleroderma.

Inclusion Criteria

After chemotherapy, my ultrasound showed improvement in my breast and nearby lymph nodes without any suspicious nodes in the chest area.

I plan to have breast reconstruction using my own tissue.

My breast cancer is HER2 positive and I've had chemotherapy before surgery.

Exclusion Criteria

Patients who are pregnant

I have active scleroderma.

I have had radiation therapy on my breast, lower neck, or chest area.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preoperative Radiation

Participants receive either hypofractionated or conventionally fractionated preoperative radiation therapy

6-8 weeks

Surgery

Participants undergo mastectomy with immediate autologous breast reconstruction

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment, including evaluation of oncologic and surgical outcomes

18 months

Treatment Details

Interventions

• Group 1 (preoperative radiation hypofractionated)
• Group 2 (preoperative radiation conventionally fractionated)

Trial Overview The TOPAz trial compares two preoperative radiation schedules before breast surgery: a hypofractionated course (less radiation in fewer doses) versus a conventionally fractionated one (standard amount and number of doses). The goal is to see which method works better for patients undergoing mastectomy followed by immediate autologous reconstruction.

Participant Groups

Group I: Group 2 (preoperative radiation conventionally fractionated) Experimental Treatment 2 Interventions

Participants will receive the standard number of radiation treatment doses

Group II: Group 1 (preoperative radiation hypofractionated) Experimental Treatment 2 Interventions

Participants will receive the standard number of radiation treatment doses

Group 1 (preoperative radiation hypofractionated) is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Hypofractionated Radiation Therapy for:

• Breast cancer

Approved in European Union as Hypofractionated Radiation Therapy for:

• Breast cancer

Approved in Canada as Hypofractionated Radiation Therapy for:

• Breast cancer

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Artidis

Collaborator

Trials

1

Recruited

130+

Artidis

Industry Sponsor

Trials

5

Recruited

600+

Findings from Research

A multicenter randomized controlled trial in India is testing whether a 1-week (5 fractions) regimen of hypofractionated radiotherapy is non-inferior to the standard 3-week (15 fractions) schedule for breast cancer patients, with a target sample size of 2100 participants.

If successful, the 1-week regimen could improve access to radiotherapy and reduce treatment costs, while also ensuring safety and efficacy in patients with advanced disease requiring regional nodal radiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated radiation therapy comparing a standard radiotherapy schedule (over 3 weeks) with a novel 1-week schedule in adjuvant breast cancer: an open-label randomized controlled study (HYPORT-Adjuvant)-study protocol for a multicentre, randomized phase III trial. Chatterjee, S., Chakraborty, S.[2021]

Recent advancements in radiation therapy for non-metastatic breast cancer, particularly hypofractionation and partial breast irradiation, have led to optimized treatment approaches that consider both patient and tumor characteristics.

Despite strong level-1 evidence supporting hypofractionation, its adoption in routine practice has been slow, prompting the AIRO Breast Cancer Group to issue position statements aimed at standardizing postoperative radiation therapy practices based on current evidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Italian Association for Radiotherapy and Clinical Oncology (AIRO) position statements for postoperative breast cancer radiation therapy volume, dose, and fractionation. Meattini, I., Palumbo, I., Becherini, C., et al.[2023]

Accelerated hypofractionation in radiotherapy for breast cancer may benefit low-risk patients by delivering a higher dose in a shorter time while targeting a smaller volume, which is currently under intensive clinical research.

Advanced techniques like intensity-modulated radiotherapy and gating improve safety by reducing side effects such as skin damage and protecting critical organs like the lungs and heart during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Impact of radiotherapy modalities on local control and survival in adjuvant breast cancer treatment]. Azria, D., Hennequin, C.[2018]

In a study of 393 breast cancer patients treated with moderately hypofractionated radiotherapy (HYPO-RT) over a median follow-up of 5.7 years, the overall survival rates were high at 96.0% at 5 years and 79.3% at 10 years, indicating the efficacy of this treatment.

HYPO-RT demonstrated excellent local control with only 4.3% local recurrences and low toxicity rates, with severe acute dermatitis occurring in just 0.9% of patients, highlighting its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated radiotherapy in breast cancer: a 10-year single institution experience. Najas, GF., Stuart, SR., Marta, GN., et al.[2022]

Hypofractionated radiation therapy is an effective treatment option for selected early breast cancer patients after breast-conserving surgery, allowing for higher doses in fewer sessions.

The optimal timing, fractionation, and total dose for delivering the tumor bed boost in hypofractionated schedules are still being researched, indicating a need for further studies to refine treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor Bed Boost Integration during Whole Breast Radiotherapy: A Review of the Current Evidence. Franco, P., Cante, D., Sciacero, P., et al.[2020]

Randomized trials indicate that hypofractionation using 2.67 Gy fractions for adjuvant whole breast radiotherapy does not compromise local tumor control or increase late adverse effects, suggesting it is a safe treatment option.

There is potential for even fewer larger fractions to be safely administered, but ongoing research is needed to determine the effectiveness and safety of a 5-fraction schedule, especially considering the volume of breast tissue treated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pushing the limits of hypofractionation for adjuvant whole breast radiotherapy. Yarnold, J., Haviland, J.[2018]

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 whole breast radiation therapy (RT) after breast conserving surgery has been shown to provide equivalent local control and cosmetic outcomes compared to traditional RT methods, based on four randomized trials with 5-10 year follow-up.

Given its similar effectiveness and added benefits of patient convenience and reduced healthcare utilization, hypofractionated RT should be considered the new standard treatment following breast conserving surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionation should be the new 'standard' for radiation therapy after breast conserving surgery. Holloway, CL., Panet-Raymond, V., Olivotto, I.[2018]

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]

In a study of 339 breast cancer patients receiving hypofractionated radiotherapy, the majority experienced mild to moderate acute skin toxicity, with only 4% reporting severe reactions, indicating a generally well-tolerated treatment.

Radiation pneumonitis occurred in 3.2% of patients, primarily those receiving regional lymphatics radiotherapy, suggesting that while hypofractionated schedules are effective, careful monitoring is needed for specific side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated radiotherapy for breast cancer patients treated by breast-conserving surgery: short-term morbidity and preliminary results. Plataniotis, GA., Theofanopoulou, MA., Sotiriadou, K., et al.[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]

References

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

Hypofractionated radiation therapy comparing a standard radiotherapy schedule (over 3 weeks) with a novel 1-week schedule in adjuvant breast cancer: an open-label randomized controlled study (HYPORT-Adjuvant)-study protocol for a multicentre, randomized phase III trial. [2021]

2. Italy pubmed.ncbi.nlm.nih.gov

The Italian Association for Radiotherapy and Clinical Oncology (AIRO) position statements for postoperative breast cancer radiation therapy volume, dose, and fractionation. [2023]

3. France pubmed.ncbi.nlm.nih.gov

[Impact of radiotherapy modalities on local control and survival in adjuvant breast cancer treatment]. [2018]

4. Poland pubmed.ncbi.nlm.nih.gov

Hypofractionated radiotherapy in breast cancer: a 10-year single institution experience. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Tumor Bed Boost Integration during Whole Breast Radiotherapy: A Review of the Current Evidence. [2020]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Pushing the limits of hypofractionation for adjuvant whole breast radiotherapy. [2018]

7. Australia pubmed.ncbi.nlm.nih.gov

Hypofractionated radiation treatment in early breast cancer: Results in a New Zealand setting. [2018]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Hypofractionation should be the new 'standard' for radiation therapy after breast conserving surgery. [2018]

9. India pubmed.ncbi.nlm.nih.gov

Assessment of toxicities and outcomes in patients with breast cancer treated with hypofractionated radiotherapy. [2022]

10. Japan pubmed.ncbi.nlm.nih.gov

Hypofractionated radiotherapy for breast cancer patients treated by breast-conserving surgery: short-term morbidity and preliminary results. [2018]

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

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