Partial Breast Re-irradiation Using Ultra Hypofractionation (PRESERVE)
- Conditions
- Breast CancerBreast 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 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 171
- 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
- Multicentric disease (patients with multifocal breast cancer in the same quadrant are eligible)
- Tumour histology limited to lobular carcinoma only
- 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
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 (11)
A.C.Camargo Cancer Center
🇧🇷São Paulo, SP, Brazil
Verspeeten Family Cancer Centre
🇨🇦London, Ontario, Canada
NYU Langone Health
🇺🇸New York, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Odette Cancer Centre
🇨🇦Toronto, Ontario, Canada
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
CHU de Québec-Université Laval
🇨🇦Montreal, Quebec, Canada
Hôpital Maisonneuve-Rosemont - CIUSSS de l'Est-de-l'Île-de-Montréal
🇨🇦Montreal, Quebec, Canada
Centre hospitalier de l'Université de Montréal
🇨🇦Montreal, Quebec, Canada
King Hussein Cancer Centre
🇯🇴Amman, Jordan