About this trial

The goal of this phase III randomized controlled trial (PRADAIIBE) is to assess if preoperative radiation therapy (Preop-RT) combined with immediate breast reconstruction (IBR) can safely improve both aesthetic and quality of life outcomes in breast cancer patients, compared to the standard of care (SoC) therapy consisting of post-mastectomy radiation therapy (PMRT) and delayed/immediate breast reconstruction, in a population of breast cancer patients with an indication of mastectomy and PMRT.

The following hypotheses and outcomes will be assessed at the primary endpoint of 1 year of follow-up:

* Efficacy: Does Preop-RT+IBR lead to a higher BREAST-Q satisfaction with breasts score (primary endpoint), EQ-5D-5L VAS score , EQ-5D-5L Index score, AIS-Total Aesthetic Score, or a shorter treatment duration compared to SoC? * Safety: Does Preop-RT+IBR lead to an increase in adverse events (general or surgical), a lower rate of pathologic Complete Response (pCR), or worse survival outcomes compared to SoC? \[Note: this study was not powered as a non-inferiority trial, all outcomes will be pooled internationally with parallel studies\]

Eligible and consenting participants will undergo screening and baseline assessments. They will then be randomised between experimental (Preop-RT+IBR) and control (SoC) groups, in a 1:1 stratified variable block size design. Follow-up will take place at 3 months, 1, 2, 5, and 10 years after the last study treatment. At baseline and during each follow-up visit each participant will complete the Breast Q 'satisfaction with breasts' and EQ-5D-5L scales, photographs will be taken. During follow-up pCR will be assessed if applicable, adverse events will be registered, and oncological follow-up will be recorded.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

c. have a wish for a breast reconstruction

An Eastern Cooperative Oncology Group (ECOG) performance status grade ≤ 2

Participant is able and willing to provide written informed consent, which includes compliance with and ability to undergo all study procedures, and attend the scheduled follow-up visit(s) per protocol.

Disqualifiers

A previous history of breast cancer or irradiation of the chest wall for any other indication, on the other side (ipsilateral). A bilateral SSM/NSM + reconstruction (e.g. in case of a contralateral prophylactic SSM/NSM), or previous contralateral breast cancer disease/treatment, do not fall under this criterium and are thus allowed.

Collagen synthesis disease

Ongoing pregnancy

Actively breastfeeding

Trial design

Design model

Parallel

Treatments tested in this trial

Preoperative radiotherapy
Radiation
In this study patients assigned to the experimental treatment arm will receive preoperative radiation therapy instead of postoperative radiation therapy (PMRT). This preoperative radiation therapy will be administered according to the standard of care (SoC) principles for PMRT and Whole Breast Radiation Therapy (WBRT) as defined by international guidelines.
Postoperative radiotherapy
Radiation
Standard of care (SoC) postoperative radiotherapy, as defined by international guidelines.
Immediate breast reconstruction
Procedure/Surgery
In the experimental arm of the PRADAIIBE, the participants will undergo immediate breast reconstruction surgery. This is defined as breast reconstruction taking place at the same time as oncological surgery. Using one of the following primary techniques: 1) Autologous tissue reconstruction ; 2) Breast implant based reconstruction; 3) Combined autologous tissue and breast implant reconstruction. These techniques can take place in a single phase, or in a two-phased (tissue expander) approach. Adjuvant techniques (e.g.: lipofilling, mesh, ADM etc.) could be added.
Immediate or delayed breast reconstruction
Procedure/Surgery
In the standard arm of the PRADAIIBE, the participants will undergo immediate or delayed breast reconstruction surgery. This is defined as breast reconstruction taking place at the same time as oncological surgery (immediate), or at a later time (delayed). Using one of the following primary techniques: 1) Autologous tissue reconstruction ; 2) Breast implant based reconstruction; 3) Combined autologous tissue and breast implant reconstruction. These techniques can take place in a single phase, or in a two-phased (tissue expander) approach. Adjuvant techniques (e.g.: lipofilling, mesh, ADM etc.) could be added.

Treatment groups

180 Participants

are divided into 2 treatment groups

Group A: Standard treatment arm (SoC; PostOperative RT)Active comparator 2 interventions

Group B: Experimental treatment arm (PreOperative RT)Experimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Patient's satisfaction with breasts.

Operationalisation (measurement variable): The satisfaction with breasts outcome variable is operationalised through the "satisfaction with breasts" scale from the BREAST-Q (v2) 'Reconstruction', 'Breast Conserving Treatment', or 'Mastectomy' modules (as applicable). The answers from the questionnaire are then transformed into a 'BREAST-Q Score', using the provided conversion scales.(3) The BREAST-Q score can range from 0 to100. Analysis metric: The transformed value of the BREAST-Q score will be used for analysis. Method of aggregation: Mean, SD, median, IQR, and range will be reported. For comparisons and estimands, please refer to the SAP.

Time frame

Measured at 3 months, 1year, 2 years, 5 years and 10 years after last locoregional treatment. Primary endpoint: 1 year after LST.

Secondary outcomes

1

Quality of Life (EQ-5D-5L VAS score)

Operationalisation (measurement variable): 'Quality of Life' will be assessed using the EQ-5D-5L questionnaire. Deriving the VAS-score from the VAS-scale Range EQ-5D-5L VAS-score: 0-100 Analysis metric: The VAS-score will be used as recorded. Method of aggregation: Mean, SD, median, IQR, and range will be reported. For comparisons and estimands, please refer

Time frame

A baseline assessment is performed during the screening visit, followed by repeated measurements during the IMFU (if applicable), 3M, 1Y, 2Y, 5Y, and 10Y follow-up visits.

2

Quality of Life (Index score)

Operationalisation (measurement variable): 'Quality of Life' will be assessed using the EQ-5D-5L questionnaire. The index score is calculated from the Likert-scale answers, using a formula validated in the Belgian population. Range EQ-5D-5L Index-score: -0.533-0.962. Analysis metric: The Index-score will be transformed to a scale between 0 and 1, proportional to its original distribution using the following formula: F(IS) = (IS+0.533)/1.495 The rationale for this transformation, is to adhere to the scale proposed by the EQ-5D-5L documentation, and improve interpretability. Method of aggregation: Mean, SD, median, IQR, and range will be reported. For comparisons and estimands, please refer

Time frame

A baseline assessment is performed during the screening visit, followed by repeated measurements during the IMFU (if applicable), 3M, 1Y, 2Y, 5Y, and 10Y follow-up visits.

3

Breast cosmesis, objective assessment (AIS - TAS)

Operationalisation (measurement variable): 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. This set will consist of 4 2D digital photographs. The AIS has 5 items, each are scored from 1 to 5. These items are then summed to derive the 'Total Aesthetic Score' (TAS). The TAS can range from 5 to 25. Analysis metric: The derived value of the Total Aesthetic Score (TAS) from each assessor will be averaged to derive the TAS of each set of photos. Method of aggregation: Mean, SD, median, IQR, and range will be reported. For comparisons and estimands, please refer to the SAP.

Time frame

Photographs are taken during the screening visit, followed by repeated photographs during the IMFU (if applicable), 3M, 1Y, 2Y, 5Y, and 10Y follow-up visits. Expert panel assessment will take place at a later moment.

4

Frequency and severity of adverse events (General AEs)

During the study all adverse events (AEs) codes and grades will be recorded in the eCRF, based on the 'National Cancer Institute Common Terminology Criteria for Adverse Events' (NCI-CTCAE) v5.0 reporting system. Analysis metric: Tabulation of AE frequency, type and severity. As well as the highest grade AE for each participant. Method of aggregation: AEs will be aggregated based on their grades. Two composite measures will be reported, consisting of 1) any AE vs. no AE, and 2) grade \> 3 AEs vs. no or grade \<3 AEs. Tables presenting both frequency and proportions of each grade and the composite measures will be presented. Proportions will be reported as AEs compared to 'highest grade per patient', and to 'total set of AEs'. For comparisons and estimands, please refer to the SAP.

Time frame

AEs will be assessed and recorded continuously, with explicit querying during all follow-up visits.

Other outcomes

1

Oncological survival and time-to-event data

Operationalisation (measurement variable): The oncological survival and TTE data are operationalised as time-to-event intervals for the events of interest listed below. These events are recorded according to the 2015 DATECAN consensus. The following TTE/survival metrics will be reported according to the 2015 DATECAN consensus: Overall Survival (OS), Breast Cancer-Specific Survival (BCSS), Relapse-Free Survival (RFS), Locoregional Relapse-Free Survival (L-RFS), and Distant-Relapse Free Survival (D-RFS). Analysis metric: The TTE data is registered in days from randomisation (Rz). Censoring will be used for participants without events at the end of their follow up. Method of aggregation: KM-estimates with derived estimates for central tendency and spread, as well as proportions free from events at follow-up visit timepoints will be reported. The non-aggregated data will be used for survival analysis. For comparisons and estimands, please refer to the SAP.

Time frame

Oncological TTE data will be registered at 1, 2, 5, and 10 years of follow-up after the last study treatment (LST). However, the exact dates of diagnosis/death will be used.

Preoperative Radiation Therapy and Immediate Breast Reconstruction

About this trial

Eligibility criteria

Qualifiers

Disqualifiers

Trial design

Treatments tested in this trial

Treatment groups

Trial outcomes

Primary outcomes

Secondary outcomes

Other outcomes

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