Preoperative Radiation Therapy and Immediate Breast Reconstruction

Not Applicable

Recruiting

• Conditions: Breast Neoplasms; Breast Carcinoma; Breast Adenocarcinoma; Cancer; Neoplasm

• Registration Number: NCT06739655
• Lead Sponsor: Cancer Research Antwerp

Brief Summary

The PRADAIIBE study is a multicentric phase 3 clinical trial, investigating the effects of radiotherapy timing on breast reconstruction results, in breast cancer patients.

This study will be recruiting Belgian breast cancer patients. They can participate if there is an indication for both surgical removal of the complete breast tissue, in the form of a skin or nipple sparing mastectomy (SSM/NSM) and postoperative radiotherapy treatment, as well as a wish for breast reconstruction.

During the screening visit the eligibility criteria are checked, demographic information is collected, a baseline assessment is performed and the participant will be randomly assigned to either the control or intervention group.

Those assigned to the control group will follow the standard of care treatment in the classic sequence of oncological surgery followed by radiotherapy. The breast reconstruction surgery will take place either at the same time (mostly tissue expander implantation) as the oncological surgery, or at a delayed moment.

Patients assigned to the intervention group will receive the same standard of care treatments, with the difference that the radiotherapy is administered before the oncological surgery (preoperative radiotherapy). In this arm of the study, the breast reconstruction is performed at the same time as the oncological surgery (Immediate Breast Reconstruction).

After the treatment is finished the patients will return for follow up visits at 3 months, 1 year, 2 years, 5 years and 10 years after finishing the study treatments. An additional visit is provided at 3 months after the last session of radiotherapy for patients undergoing delayed reconstruction.

During these baseline and follow-up visits, 2 questionnaires (BREAST-Q v2; EQ5D5L) will be completed, photographs of the breasts will be taken, adverse events will be recorded and oncological recurrence will be evaluated.

The key result (primary outcome) is breast satisfaction (BREAST-Q v2, BQ-score) at 1 year follow-up. Secondary outcomes are defined as BREAST-Q-scores, EQ5D5L-scores, photograph evaluations (AIS-TAS), adverse events, treatment pathway duration, and pathological complete response rates. These are assessed per follow-up visit. The tertiary outcome follows oncological recurrence.

With the results from this study the goal is to improve patient satisfaction, QoL and aesthetic results of breast reconstruction after breast cancer treatment, as well as reduce postoperative complications and treatment duration.

Detailed Description

The PRADAIIBE study is a multicentric phase 3 clinical trial, investigating the effects of radiotherapy timing on breast reconstruction results, in breast cancer patients.

This study will be recruiting Belgian breast cancer patients. They can participate if there is an indication for both surgical removal of the complete breast tissue, in the form of a skin or nipple sparing mastectomy (SSM/NSM) and postoperative radiotherapy treatment, as well as a wish for breast reconstruction.

After informed consent is signed, patients will be screened. If they meet the study inclusion criteria and do not meet the exclusion criteria, they will be included in the study as a participant. If they are not found to be eligible, they will be registered as a 'screen failure'.

After study inclusion, baseline assessments will be taken, this includes two questionnaires, the first one is focussed on satisfaction with the patient's own breasts (BREAST-Q v2, BQ-score) and the second one on their perception of their quality of life (EQ5D5L, VAS-score, Index-score). Next, 4 photographs of the exposed breast area will be taken. These photographs will be assessed by an expert panel (Aesthetic Item Scale (AIS), TAS-score).

Next, the eligible participant will be randomized using the central eCRF randomization tool (Caster EDC). At randomization, participants will be stratified based on study site. They will be randomly assigned to one of the following treatment arms:

* Standard treatment arm: SSM/NSM, immediate or delayed breast reconstruction, and postoperative radiation therapy (postop-RT).

* Experimental treatment arm: preoperative radiotherapy (preop-RT) followed by SSM/NSM combined with an immediate breast reconstruction.

Those assigned to the control group will follow the standard of care treatment in the classic sequence of oncological surgery followed by radiotherapy. The breast reconstruction surgery will take place either at the same time (mostly tissue expander implantation) as the oncological surgery, or at a delayed moment.

Patients assigned to the intervention group will receive the same standard of care treatments, with the difference that the radiotherapy is administered before the oncological surgery. This allows that the breast reconstruction is performed at the same time as the oncological surgery (Immediate Breast Reconstruction). In the treatment arm breast reconstruction will always be performed immediately (during oncological surgery).

In the unexpected event of tumour downstaging due to preoperative treatment, changing the indication from SSM/NSM to breast conserving surgery/treatment (BCS/BCT), while the patient has already been included and randomized in this trial, a separate pathway is foreseen. In this case the patient should receive the treatment and surgery which is most indicated, being BCS/BCT. The same follow up will be provided, using a BREAST-Q questionnaire tailored to BCT follow up. They will be analysed following the 'Intention To Treat' (ITT) principle, but will be filtered out in the 'Per Protocol Analysis' (PPA).

Systemic treatment (Chemotherapy, endocrine therapy, etc.) will be administered per standard of care, according to the discretion of the treating physician(s). It will be registered in the study, but it is not considered as part of the study treatments.

After the treatment period is finished (last radiotherapy treatment or surgery), the patients will be followed-up at 3 months, 1 year, 2 years, 5 years and 10 years after finishing the treatment. An additional visit is provided at 3 months after conclusion of radiotherapy (intermediate follow up visit) for patients/participants undergoing delayed reconstruction, as these patients typically have to wait 6-12 months before reconstructive surgery is performed.

During these follow-up visits the BREAST-Q and EQ5D5L questionnaires, photographic assessment (expert panel using AIS), adverse events, pathologic response, treatment period duration and oncological recurrence (from the +1 year visit onwards) will be recorded. During the intermediate follow up visit, photographs and the EQ5D5L questionnaire will be taken, and adverse events will be assessed.

The research question of the PRADAIIBE trial is to investigate whether preop-RT followed by SSM/NSM combined with an immediate breast reconstruction (implant based or autologous) improves patient satisfaction with the breast reconstruction and overall quality of life, when compared to standard of care treatment i.e.: post-mastectomy radiation therapy (PMRT) and delayed breast reconstruction.

The primary objective is to determine if there is improvement in patient satisfaction with breasts at 1 year after last locoregional treatment (as measured using the pre-operative and post-operative satisfaction with Breasts scale from the BREAST-Q Reconstruction Module Version 2 questionnaire). This is operationalised through determining the median/mean BREAST-Q score at 1 year after last locoregional treatment, as well as the mean/median difference in the BREAST-Q score between baseline and at 1 year after last locoregional treatment.

For the secondary outcomes, the BREAST-Q, EQ5D5L, AIS, AE, treatment duration, and pathological response will be assessed during follow-up visits.

For the tertiary outcomes, the tumour recurrence (local, regional, metastatic and death), progression, and survival will be monitored. This data will be shared and aggregated with similar international studies, as coordinate by the PRADA-Consortium.

Study Timeline

• Study First Submitted: 2024-12-02
• Study First Submitted QC: 2024-12-17
• Study First Posted: 2024-12-18
• Study Start: 2025-02-20
• Status Verified: 2025-07
• Last Update Submitted: 2025-08-11
• Last Update Posted: 2025-08-14
• Primary Completion: 2029-02-20
• Study Completion: 2038-02-20

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 180

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Patient's satisfaction with breasts.	Measured at 1 year after last locoregional treatment.	Operationalisation (measurement variable): The satisfaction with breasts outcome variable is operationalised through the "satisfaction with breasts" scale from the BREAST-Q (v2) 'Reconstruction' or 'Breast Conserving Treatment' Module questionnaires (as applicable). The answers from the questionnaire are then transformed into a 'BREAST-Q Score'. The BREAST-Q score can range from 0 to 100.; Analysis metric: BREAST-Q score absolute value will be used for analysis.; Method of aggregation: The mean, median, standard deviation and IQR will be reported.; Time point(s): A baseline assessment is performed during the screening visit. The primary endpoint is assessed at 1 year of follow-up after the last study treatment (LST).

Secondary Outcome Measures

Name	Time	Method
Patient's satisfaction with breasts	Measured at 3 months, 2 years, 5 years and 10 years after last locoregional treatment.	Operationalisation (measurement variable): The satisfaction with breasts outcome variable is operationalised through the "satisfaction with breasts" scale from the BREAST-Q (v2) 'Reconstruction' or 'Breast Conserving Treatment' Module questionnaires (as applicable). The answers from the questionnaire are then transformed into a 'BREAST-Q Score'. The BREAST-Q score can range from 0 to 100.; Analysis metric: BREAST-Q score absolute value will be used for analysis.; Method of aggregation: The mean, median, standard deviation and IQR will be reported.; Time point(s): A baseline assessment is performed during the screening visit. The secondary endpoint of 'Satisfaction with breasts' is assessed at 3 months, 2, 5, and 10 years of follow-up after the last study treatment (LST).
Patient quality of life (QoL)	Measured at 3 months, 1 year, 2 years, 5 years and 10 years after last locoregional treatment.	Operationalisation (measurement variable): 'Quality of Life' will be assessed through the EQ-5D-5L questionnaire. From the answers on this questionnaire the VAS-score and Index-score (using the Belgian population validated transformation formula) will be calculated and used. The EQ-5D-5L VAS-score can range from 0 to 100, while the Index-score can range from -0.533 to 0.962.; Analysis metric: The VAS-score and Index-score absolute values will both be used for analysis.; Method of aggregation: The mean, median, standard deviation and IQR will be reported.; Time point(s): A baseline assessment is performed during the screening visit. The secondary endpoint of 'Quality of Life' is assessed at 3 months, 1, 2, 5, and 10 years of follow-up after the last study treatment (LST). An additional assessment of the 'Quality of Life' is performed in the group receiving delayed breast reconstruction, which will then take place at 3 months after postoperative radiotherapy.
Breast cosmetic outcome of the treated breast compared to the untreated breast	Measured at 3 months, 1 year, 2 years, 5 years and 10 years after last locoregional treatment.	Breast cosmesis will be assessed through a blinded panel of experts, using the 'Aesthetic Items Scale' to score a set of photographs taken during study visits (cfr. infra, timepoints). The summed score from all 5 AIS items is used to derive the 'Total Aesthetic Score' (TAS). The TAS can range from 5 to 25.; Analysis metric: The TAS absolute value will be used for analysis.; Method of aggregation: The mean, median, standard deviation and IQR will be reported.; Time point(s): At baseline, a set of 4 (2D, digital) photographs will be taken during the screening visit. Follow-up photographs are taken during all follow-up visits at 3 months, 1, 2, 5, and 10 years after the last study treatment (LST). An additional set of photographs is taken during the extra follow-up visit (IMFU) in the group receiving delayed breast reconstruction. Assessment is performed by a blinded expert panel.
Adverse events	Measured at 3 months, 1 year, 2 years, 5 years and 10 years after last locoregional treatment.	Operationalisation (measurement variable): During the study all adverse events (AEs) are monitored and collected in the eCRF, based on the 'National Cancer Institute Common Terminology Criteria for Adverse Events' (NCI-CTCAE) v5.0 reporting system. The AE codes and grades will be recorded in the eCRF and used as variables.; Analysis metric: Tabulation of AE type and severity will be used for analysis.; Method of aggregation: The highest grade per participant and proportion of participants experiencing no AE or a grade 1 AE vs. a grade 2 or more AE, as well as the frequency of each grade will be used.; Time point(s): AEs will be assessed and recorded continuously, with explicit querying during all follow-up visits. These outcome variables will be reported during interim- and final analyses.
Surgical complications	Measured at 3 months, 1 year, 2 years, 5 years and 10 years after last locoregional treatment.	Operationalisation (measurement variable): During the study all surgical adverse events (AEs) are monitored and collected in the eCRF, based on the 'National Cancer Institute Common Terminology Criteria for Adverse Events' (NCI-CTCAE) v5.0 reporting system. The AE codes and grades will be recorded in the eCRF and used as variables.; Analysis metric: Tabulation of surgical AE type and severity will be used for analysis.; Method of aggregation: The highest grade per participant and proportion of participants experiencing no AE vs. an AE of any grade, as well as the frequency of each grade will be used.; Time point(s): AEs will be assessed and recorded continuously, with explicit querying during all follow-up visits. These outcome variables will be reported during interim- and final analyses.
Treatment pathway times (Rz to LST)	Measured at 3 months after last locoregional treatment.	Operationalisation (measurement variable): The dates of diagnostic, study, and treatment milestones will be recorded in the eCRF. Time intervals expressed in days, will be assessed for: - Randomisation to last study treatment (LST).; Analysis metric: Time interval between events/milestones, expressed in days.; Method of aggregation: The mean, median, standard deviation and IQR will be reported.; Time point(s): These outcome variables will be reported during interim- and final analyses, including a summary of the proportion of participants that have completed the respective milestones, in case of interim analysis.
Pathological complete response rate	Measured at 3 months after last locoregional treatment.	Operationalisation (measurement variable): Patients receiving preoperative chemotherapy undergo pathological response assessment of the removed breast tissues (SoC assessment). The reported response or 'No preoperative (systemic/chemo/radio)therapy' will be recorded in the eCRF.; Analysis metric: Tabulation of the reported response will be used for analysis.; Method of aggregation: The frequency and proportion of the response category will be used.; Time point(s): This outcome variable will be assessed after the pathological report of the removed breast tissues (source document) is available. This is checked intermittently during the treatment phase, or at least at the 3 months follow-up visit. This outcome variables will also be reported during interim analyses.

Trial Locations

Locations (5)

Universitair Ziekenhuis Antwerpen (UZA); 🇧🇪 Edegem, Antwerpen, Belgium

Universitair Ziekenhuis Gent (UZGent); 🇧🇪 Gent, Oost Vlaanderen, Belgium

AZ Groeninge; 🇧🇪 Kortrijk, West Vlaanderen, Belgium

CHU Namur; 🇧🇪 Namur, Belgium

Ziekenhuis aan de stroom; 🇧🇪 Wilrijk, Antwerpen, Belgium