Partial Breast Re-irradiation Using Ultra Hypofractionation (PRESERVE)

Not Applicable

Recruiting

• Conditions: Breast Cancer; Breast Cancer Recurrent
• Interventions: Radiation: rPBI

• Registration Number: NCT05592938
• Lead Sponsor: University Health Network, Toronto

Brief Summary

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 they can accrue sufficient patient with rPBI who will be treated using 26 Gray(Gy) in 5 daily fractions over 1-week. Planned interim analysis after the 15 recruited patients for early toxicity evaluation with stopping rule for unacceptable toxicity.

Detailed Description

Breast cancer is the leading cause of cancer in women worldwide, with over 2 million cases diagnosed every year. Although advances in treatment have led to an overall reduction in breast cancer mortality, survivors continue to have an ongoing risk of disease recurrence. For women who experience breast recurrence, mastectomy has historically been the only treatment approach offered. However, it has been associated with negative health outcomes, including reduced quality of life, depression and anxiety, and impaired sexual functioning. Fear of mastectomy has also been associated with delays in seeking appropriate and timely management of disease. As a result, there is increasing interest to identify treatment options that include breast preservation.

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. However, previously published studies have used long fractionation regimens for rPBI delivered over 3 to 5 weeks, which can present a challenge for both patients and health systems. This is particularly true in low- and middle-income countries, where more than half of new breast cancer cases now occur.

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 they can accrue sufficient patient with rPBI who will be treated using 26Gy in 5 daily fractions over 1-week. Planned interim analysis after the 15 recruited patients for early toxicity evaluation with stopping rule for unacceptable toxicity.

Using an international network of comprehensive cancer centers, this study will advance global knowledge of how to optimally treat woman with this disease.

Study Timeline

• Study First Submitted: 2022-10-14
• Study First Submitted QC: 2022-10-21
• Study First Posted: 2022-10-25
• Study Start: 2023-06-27
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-12
• Last Update Posted: 2024-07-16
• Primary Completion: 2027-06-27
• Study Completion: 2027-06-27

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 171

Inclusion Criteria

• Age > 18 years
• In-breast recurrence (ductal carcinoma in situ (DCIS) or invasive carcinoma)
• Tumour <3.0 cm in greatest diameter on pathologic examination, including both invasive and non-invasive components
• >5 years after completion of prior adjuvant whole or partial breast radiotherapy
• Clinically node negative
• Negative margins (no tumour on ink)
• Recovered from surgery with the incision completely healed and no signs of infection

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Exclusion Criteria

• Multicentric disease (patients with multifocal breast cancer in the same quadrant are eligible)
• Extensive intraductal component
• T4 disease
• Node positive or distant metastatic disease
• Serious non-malignant disease (cardiovascular, pulmonary, systemic lupus erythematosus, scleroderma), which would preclude radiation treatment
• Currently pregnant or lactating
• Presence of an ipsilateral breast implant or pacemaker
• Unable to commence radiation within 16 weeks of breast-conserving surgery (or last surgical procedure on the breast) or within 12 weeks from last cycle of adjuvant chemotherapy
• Unable to clearly define the surgical cavity (oncoplastic procedures are permitted provided the tumor bed is well delineated with surgical clips).
• Psychiatric disorders which would preclude obtaining informed consent or adherence to protocol
• Grade II or more late skin toxicity from prior radiation evaluated and graded using CTCAE v5.0

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
rPBI	rPBI	26Gy in 5 daily fractions over 1-week

Primary Outcome Measures

Name	Time	Method
Grade ≥3 toxicity associated with treatment	During accrual period, up to 3 years	TThe primary endpoint, grade ≥3 toxicity associated with treatment will be summarized using frequency and percentage with 95% Clopper-Pearson confidence intervals by grade at each scheduled follow up.

Secondary Outcome Measures

Name	Time	Method
Percentage radiation-associated toxicity (acute)	3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI	Radiation-associated toxicities (acute) will be graded according to CTCAE v5.0 by physicians. Toxicity associated with treatment will be summarized using percentage with 95% Clopper-Pearson confidence intervals by grade at each scheduled follow up.
Frequency radiation-associated toxicity (late)	3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI	Radiation-associated toxicities (late) will be graded according to CTCAE v5.0 by physicians. Toxicity associated with treatment will be summarized using frequency with 95% Clopper-Pearson confidence intervals by grade at each scheduled follow up.
Frequency radiation-associated toxicity (acute)	3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI	Radiation-associated toxicities (acute) will be graded according to CTCAE v5.0 by physicians. Toxicity associated with treatment will be summarized using frequency with 95% Clopper-Pearson confidence intervals by grade at each scheduled follow up.
Location of local recurrence (out-of-field) (frequency)	3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI	Location of recurrence will be summarized by frequency.
Location of local recurrence (out-of-field) (percentage)	3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI	Location of recurrence will be summarized by percentage
Financial toxicity associated with treatment	Baseline, 3 months, 1 year, and 3 years post rPBI	Quality of life questionnaire will be used to obtain scores and will summarized using mean and standard deviation at baseline and follow up. Change in score compared to baseline will be summarized using mean and standard deviation, and assessed with paired t-test. Number and proportion of patients with a minimal clinically important difference will be calculated.
Percentage radiation-associated toxicity (late)	3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI	Radiation-associated toxicities (late) will be graded according to CTCAE v5.0 by physicians. Toxicity associated with treatment will be summarized using percentage with 95% Clopper-Pearson confidence intervals by grade at each scheduled follow up.
Location of local recurrence (in-field) (percentage)	3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI	Location of recurrence will be summarized by percentage.
Risk of local recurrence (invasive and DCIS)	3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI	Cumulative incidence function will be used to estimate local recurrence with death as a competing risk.
Risk of local recurrence after rPBI requiring mastectomy	3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI	Cumulative incidence function will be used to estimate local recurrence after rPBI requiring mastectomy with death as a competing risk
Satisfaction with breasts	Baseline, 1 year, 3 years, and 5 years post rPBI	Quality of life questionnaire will be used to obtain scores and will summarized using mean and standard deviation at baseline and follow up. Change in score compared to baseline will be summarized using mean and standard deviation, and assessed with paired t-test. Number and proportion of patients with a minimal clinically important difference will be calculated.
Location of local recurrence (in-field) (frequency)	3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI	Location of recurrence will be summarized by frequency.
Invasive breast cancer free survival	3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI	Kaplan-Meier method will be used to estimate invasive breast cancer free survival
Overall survival	3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI	Kaplan-Meier method will be used to estimate overall survival
Risk of distant recurrence (invasive and DCIS)	3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI	Cumulative incidence function will be used to estimate distant recurrence and distance recurrence with death as a competing risk.

Trial Locations

Locations (1)

Princess Margaret Cancer Centre; 🇨🇦 Toronto, Ontario, Canada