Short-Course Radiation Therapy for Breast Cancer

(PRESERVE Trial)

Recruiting at 8 trial locations

Overseen By Anne Koch, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Disqualifiers: Multicentric disease, Lobular carcinoma, Node positive, others

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: Unknown

Duration: 1 week

171 Participants Needed

Trial Summary

What is the purpose of this trial?

Breast-conserving surgery followed by re-irradiation with partial breast irradiation (rPBI) has recently been found to be a safe alternative to mastectomy for women who have undergone prior whole breast radiation. By reducing the volume of tissue receiving radiation, rPBI has been associated with less toxicity and improved cosmetic outcomes. For many women with early-stage breast cancer, shorter 1-week (5-fraction) courses of breast radiation (ultra-fractionation) have been found to be equivalent to longer fractionation schedules in the upfront treatment setting. These 1-week schedules are more convenient for patients, with fewer treatments and shorter overall treatment time. The investigators hypothesize that a 1-week ultra-hypofractionated rPBI regimen following breast-conserving surgery (BCS) for local recurrence or new primary breast cancer in the previously irradiated breast (LR) will be associated with acceptable toxicity at 1 year (\<13% grade \>3 toxicity).

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 the treatment rPBI, Partial Breast Irradiation, rPBI, Ultra Hypofractionation for breast cancer?

Recent studies show that partial breast irradiation (PBI) and ultra-hypofractionated radiation are effective and safe for certain breast cancer patients, offering similar or better outcomes compared to traditional methods, with fewer side effects and shorter treatment times. ^{1 2 3 4 5}

Is short-course radiation therapy for breast cancer safe?

Research shows that short-course radiation therapy, including ultra-hypofractionation and partial breast irradiation, is generally safe for breast cancer patients. Studies have demonstrated low toxicity and good tolerance, making it a safe option for suitable patients. ^{1 6 7 8 9}

How does the treatment rPBI differ from other breast cancer treatments?

The treatment rPBI (Partial Breast Irradiation) is unique because it focuses radiation only on the part of the breast where the tumor was, rather than the whole breast, and it uses a shorter treatment schedule of 1-2 weeks instead of the usual 3-6 weeks. This makes it more convenient and potentially less costly for patients, while still being effective and safe for those with early-stage breast cancer. ^{1 2 7 10 11}

Research Team

Danielle Rodin, MD

Principal Investigator

Princess Margaret Cancer Centre

Anne Koch, MD

Principal Investigator

Princess Margaret Cancer Centre

Eligibility Criteria

This trial is for women over 18 with early-stage breast cancer who've had prior radiation and surgery, are clinically node negative, have a tumor under 3.0 cm without distant metastases or severe late skin toxicity from previous treatments. It excludes those with multifocal disease, implants or pacemakers near the chest, recent chemotherapy, certain psychiatric disorders, specific non-malignant diseases, or current pregnancy.

Inclusion Criteria

My cancer has not spread to my lymph nodes.

It has been over a year since I finished breast radiotherapy.

I am older than 18 years.

Exclusion Criteria

I do not have serious heart, lung, lupus, or scleroderma diseases that would prevent radiation treatment.

Currently pregnant or lactating

I couldn't start radiation within the required time after my breast surgery or chemotherapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 26Gy in 5 daily fractions over 1-week of re-irradiation with partial breast irradiation (rPBI) following breast-conserving surgery

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments of toxicity and quality of life

5 years

Treatment Details

Interventions

• rPBI

Trial Overview The PRESERVE trial tests a shorter course of re-irradiation called rPBI (26 Gray in 5 daily fractions over one week) after breast-conserving surgery to see if it's safe and effective as an alternative to mastectomy for women who previously received whole breast radiation.

Participant Groups

Group I: rPBI Experimental Treatment 1 Intervention

26Gy in 5 daily fractions over 1-week

rPBI is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Partial Breast Irradiation for:

• Early-stage breast cancer
• Re-irradiation after prior whole breast radiation

Approved in United States as rPBI for:

• Early-stage breast cancer
• Re-irradiation after prior whole breast radiation

Approved in Japan as Ultra Hypofractionation for:

• Early-stage breast cancer
• Node-negative tumors not requiring boost irradiation

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

CHU de Quebec (Université Laval)

Collaborator

Trials

1

Recruited

170+

l'Hopital Maisonneuve-Rosemont

Collaborator

Trials

1

Recruited

170+

L'Institut de recherche du Centre universitaire de sante McGill

Collaborator

Trials

1

Recruited

170+

NYU Langone Health

Collaborator

Trials

1,431

Recruited

838,000+

Centre hospitalier de l'Université de Montréal (CHUM)

Collaborator

Trials

389

Recruited

143,000+

Peter MacCallum Cancer Centre, Australia

Collaborator

Trials

102

Recruited

23,700+

Sunnybrook Health Sciences Centre

Collaborator

Trials

693

Recruited

1,569,000+

Royal Victoria Regional Health Centre

Collaborator

Trials

3

Recruited

1,400+

AC Camargo Cancer Center

Collaborator

Trials

30

Recruited

8,400+

Findings from Research

Partial breast irradiation (PBI) and ultra-hypofractionated whole breast irradiation (uWBI) are effective alternatives to traditional radiation therapy, reducing treatment time from 3-6 weeks to just 1-2 weeks for select patients, which enhances convenience and access to care.

Recent long-term studies indicate that PBI and accelerated PBI (APBI) are safe and effective for low-risk patients with specific breast cancer characteristics, showing similar or improved outcomes in local recurrence and toxicity compared to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modern radiation techniques in early stage breast cancer for the breast radiologist. Jones, BM., Green, S.[2021]

Accelerated partial breast irradiation (APBI) is an advanced form of hypofractionated external beam radiation therapy (HERT) that allows for faster treatment due to targeting a smaller area, which may improve patient convenience and comfort.

Both APBI and HERT are currently being tested in randomized trials, highlighting their potential as effective treatment options for breast cancer, although they are still considered investigational.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated partial breast irradiation: an advanced form of hypofractionation. Budrukkar, A.[2019]

Adopting hypofractionated whole breast irradiation and accelerated partial breast irradiation (APBI) can lead to improved survival rates and a higher likelihood of remaining disease-free for women undergoing breast cancer treatment, with a 4% increase in survival and a 7% increase in disease-free status at 15 years compared to conventional schedules.

In women who had lumpectomies, the hypofractionation model showed a 62% chance of remaining alive with an intact breast, compared to 54% in the conventional model, highlighting the potential benefits of shorter radiation schedules in improving patient outcomes in emerging economies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nation-Scale Adoption of Shorter Breast Radiation Therapy Schedules Can Increase Survival in Resource Constrained Economies: Results From a Markov Chain Analysis. Khan, AJ., Rafique, R., Zafar, W., et al.[2018]

Recent studies support the use of shorter radiotherapy courses for early-stage breast cancer, with ultra-hypofractionated regimens allowing treatment in as few as 5 sessions, which can reduce the burden on patients.

Breast cancer is increasingly recognized as a low alpha-beta ratio malignancy, suggesting that larger doses per fraction may be more effective, leading to a shift towards hypofractionated and ultra-hypofractionated treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early-stage Breast Cancer: Tailored External Beam Fractionation Approaches for Treatment of the Whole or Partial Breast. Prionas, ND., Stephens, SJ., Blitzblau, RC.[2022]

In a study of 158 patients undergoing weekly hypofractionated breast irradiation (WHBI) after breast-conserving surgery, the rate of ipsilateral breast tumor recurrence was very low at 1.3%, indicating strong efficacy in preventing local cancer recurrence.

The 3-year disease-free survival rate was 97.5%, and the overall survival rate was 96.2%, with most patients experiencing only mild acute toxicities, suggesting that WHBI is a safe and effective treatment option for early-stage breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First Results of a Phase 2 Trial of Once-Weekly Hypofractionated Breast Irradiation (WHBI) for Early-Stage Breast Cancer. Dragun, AE., Ajkay, NJ., Riley, EC., et al.[2018]

In a study of 157 older patients with low-risk breast cancer, both accelerated partial breast irradiation (APBI) and ultra-APBI (uAPBI) showed similar oncologic outcomes, with no significant differences in local or regional recurrence rates, disease-free survival, or overall survival.

Late toxicity and cosmetic results were also comparable between the two treatment methods, suggesting that uAPBI, which uses a single fraction of brachytherapy, is a safe and effective option for reducing treatment intensity in older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

APBI Versus Ultra-APBI in the Elderly With Low-Risk Breast Cancer: A Comparative Analysis of Oncological Outcome and Late Toxicity. Hannoun-Lévi, JM., Montagne, L., Sumodhee, S., et al.[2021]

In a study involving 396 patients treated with ultra-hypofractionated breast radiotherapy, the five-year local-relapse free survival (LRFS) rate was an impressive 98.8%, indicating high efficacy in controlling breast cancer.

While ultra-hypofractionated radiotherapy showed excellent tumor control, certain regimens, particularly the 5.7 Gy weekly fraction and tumor bed boost, were linked to a higher risk of acute and late skin toxicities, highlighting the need for careful treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Large scale experience of two ultrahypofractionated 5 fractions regimes after breast conserving surgery from a single centre. Sauvage, LM., Loap, P., Vu-Bezin, J., et al.[2023]

The UK-FAST-Forward study indicated that ultra-hypofractionated whole-breast irradiation (ultra-HF-WBI) is not inferior to traditional high-fractionated whole-breast irradiation, but safety concerns have prevented its use in Japan.

A new phase II trial involving 98 patients aims to assess the safety of ultra-HF-WBI after breast-conserving surgery, focusing on the occurrence of late adverse events over 3 years, which could influence future treatment guidelines in Japan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-institutional phase II study of ultra-hypofractionated whole-breast irradiation after breast-conserving surgery for breast cancer in Japan: Kyoto Radiation Oncology Study Group (UPBEAT study). Mitsuyoshi, T., Ono, Y., Ashida, R., et al.[2023]

In a phase II trial involving 73 early-stage breast cancer patients, the external beam partial breast irradiation (PBI) regimen of 35 Gy in 7 daily fractions was found to be well-tolerated, with no Grade 3 toxicity reported and only minor side effects observed.

The treatment demonstrated high efficacy, achieving a 98% local control rate and a 96.7% rate of freedom from distant metastases over a median follow-up of 40 months, indicating it is a safe and effective option for patients aged 60 and older.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Seven fractions to deliver partial breast irradiation: the toxicity is Low. Trovo, M., Avanzo, M., Vinante, L., 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]

Hypofractionated whole breast irradiation (WBI) has been shown to produce outcomes comparable to conventional radiation in early-stage breast cancer patients, suggesting it is a safe and effective treatment option.

Current trials, including a phase III study by the Radiation Therapy Oncology Group, are investigating the feasibility and effectiveness of adding a concurrent tumor bed boost to hypofractionated WBI, which may enhance treatment outcomes and broaden its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated fractionation with a concurrent boost for early stage breast cancer. Freedman, GM., White, JR., Arthur, DW., et al.[2022]

References

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

Modern radiation techniques in early stage breast cancer for the breast radiologist. [2021]

2. India pubmed.ncbi.nlm.nih.gov

Accelerated partial breast irradiation: an advanced form of hypofractionation. [2019]

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

Nation-Scale Adoption of Shorter Breast Radiation Therapy Schedules Can Increase Survival in Resource Constrained Economies: Results From a Markov Chain Analysis. [2018]

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

Early-stage Breast Cancer: Tailored External Beam Fractionation Approaches for Treatment of the Whole or Partial Breast. [2022]

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

First Results of a Phase 2 Trial of Once-Weekly Hypofractionated Breast Irradiation (WHBI) for Early-Stage Breast Cancer. [2018]

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

APBI Versus Ultra-APBI in the Elderly With Low-Risk Breast Cancer: A Comparative Analysis of Oncological Outcome and Late Toxicity. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Large scale experience of two ultrahypofractionated 5 fractions regimes after breast conserving surgery from a single centre. [2023]

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

Multi-institutional phase II study of ultra-hypofractionated whole-breast irradiation after breast-conserving surgery for breast cancer in Japan: Kyoto Radiation Oncology Study Group (UPBEAT study). [2023]

9. England pubmed.ncbi.nlm.nih.gov

Seven fractions to deliver partial breast irradiation: the toxicity is Low. [2018]

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

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

11. Ireland pubmed.ncbi.nlm.nih.gov

Accelerated fractionation with a concurrent boost for early stage breast cancer. [2022]