Partial Breast Re-irradiation Using Ultra Hypofractionation (PRESERVE)

Study Overview
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Brief Summary
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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
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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.

Official Title
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Partial Breast Re-irradiation Using Ultra Hypofractionation: Phase 2 Multi-institutional Study (PRESERVE)

Conditions
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Breast Cancer, Breast Cancer Recurrent

Intervention / Treatment
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* Radiation: rPBI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years In-breast recurrence confirmed as unicentric Tumour <3.0 cm in greatest diameter on pathologic examination, including both invasive and non-invasive components >1 year 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 Negative metastatic work-up (no evidence of distant metastases on bone scan, and computerized tomography (CT) scans of the thorax, abdomen, and pelvis; or using (FDG) Positron emission tomography (PET)-CT). Exclusion Criteria: Infiltrating Lobular Carcinoma Multifocal or multicentric disease 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 (Level I 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rPBI<br>26Gy in 5 daily fractions over 1-week | Radiation: rPBI<br>* External beam partial breast reirradiation (rPBI) using 26Gy in 5 fractions delivered daily over 1-week<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants accrued to the trial | The primary endpoint will be determined by the ability to complete accrual of 15 patients to the study in 2 years. | During accrual period, up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency radiation-associated toxicity (acute) | 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. | 3 months, 1 year, and 3 years post rPBI | 
| Percentage radiation-associated toxicity (acute) | 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. | 3 months, 1 year, and 3 years post rPBI | 
| Frequency radiation-associated toxicity (late) | 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. | 3 months, 1 year, and 3 years post rPBI | 
| Percentage radiation-associated toxicity (late) | 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. | 3 months, 1 year, and 3 years post rPBI | 
| Risk of local recurrence (invasive and DCIS) | Cumulative incidence function will be used to estimate local recurrence with death as a competing risk. | 3 months, 1 year, and 3 years post rPBI | 
| Risk of distant recurrence (invasive and DCIS) | Cumulative incidence function will be used to estimate distant recurrence and distance recurrence with death as a competing risk. | 3 months, 1 year, and 3 years post rPBI | 
| Location of local recurrence (in-field) (frequency) | Location of recurrence will be summarized by frequency. | 3 months, 1 year, and 3 years post rPBI | 
| Location of local recurrence (in-field) (percentage) | Location of recurrence will be summarized by percentage. | 3 months, 1 year, and 3 years post rPBI | 
| Location of local recurrence (out-of-field) (frequency) | Location of recurrence will be summarized by frequency. | 3 months, 1 year, and 3 years post rPBI | 
| Location of local recurrence (out-of-field) (percentage) | Location of recurrence will be summarized by percentage | 3 months, 1 year, and 3 years post rPBI | 
| Risk of local recurrence after rPBI requiring mastectomy | Cumulative incidence function will be used to estimate local recurrence after rPBI requiring mastectomy with death as a competing risk | 3 months, 1 year, and 3 years post rPBI | 
| Invasive breast cancer free survival | Kaplan-Meier method will be used to estimate invasive breast cancer free survival | 3 months, 1 year, and 3 years post rPBI | 
| Overall survival | Kaplan-Meier method will be used to estimate overall survival | 3 months, 1 year, and 3 years post rPBI | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypofractionated