Partial Breast Re-irradiation Using Ultra Hypofractionation: Phase 2 Multi-institutional Study (PRESERVE)
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Enrollment
- 171
- Locations
- 33
- Primary Endpoint
- Grade ≥3 toxicity associated with treatment
Study Overview
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 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).
Detailed Description
Most women affected by breast cancer are treated with breast-conserving surgery to remove the tumour, followed by radiation to reduce the risk of recurrence. Unfortunately, some women will experience recurrence of the cancer in the previously treated breast. These recurrences have historically been treated by removing the whole breast or a second breast-conserving surgery followed by 3 to 5 weeks of radiation. These treatments can negatively impact mental health and quality of life or lead to harmful side effects that could impact the skin, breast, ribs, heart and lungs.
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).
The target population for this study is women with localized recurrent or new primary breast cancer in the previously irradiated breast. This is a prospective single arm phase 2 trial of external beam rPBI using 26Gy in 5 fractions delivered daily over 1-week after a second lumpectomy for LR following prior BCS and adjuvant whole or partial breast irradiation. Using a multi-institutional and international network of comprehensive cancer centers, this study will advance global knowledge of how to optimally treat women with this disease.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 99 Years (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age > 18 years
- •In-breast recurrence or new primary (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 (prior nodal radiotherapy permitted)
- •Clinically node negative
- •Negative margins (no tumour on ink)
- •Recovered from surgery with the incision completely healed and no signs of infection
Exclusion Criteria
- •Multicentric disease (patients with multifocal breast cancer in the same quadrant are eligible)
- •Tumour histology limited to lobular carcinoma only
- •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
- •Current or prior diagnosis of bilateral breast cancer
Arms & Interventions
rPBI
26Gy in 5 daily fractions over 1-week
Intervention: rPBI (Radiation)
Outcomes
Primary Outcomes
Grade ≥3 toxicity associated with treatment
Time Frame: 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 Outcomes
- Percentage radiation-associated toxicity (acute)(3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI)
- Frequency radiation-associated toxicity (late)(3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI)
- Frequency radiation-associated toxicity (acute)(3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI)
- 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 local recurrence (out-of-field) (percentage)(3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI)
- Financial toxicity associated with treatment(Baseline, 3 months, 1 year, and 3 years post rPBI)
- Percentage radiation-associated toxicity (late)(3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI)
- Location of local recurrence (in-field) (percentage)(3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI)
- Risk of local recurrence (invasive and DCIS)(3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI)
- Risk of local recurrence after rPBI requiring mastectomy(3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI)
- Satisfaction with breasts(Baseline, 1 year, 3 years, and 5 years post rPBI)
- Location of local recurrence (in-field) (frequency)(3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI)
- Invasive breast cancer free survival(3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI)
- Overall survival(3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI)
- Risk of distant recurrence (invasive and DCIS)(3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI)