Hypofractionated Radiotherapy in Breast Cancer Patients With Prosthetic Reconstruction

Study Overview
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Brief Summary
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RATIONALE: Radiotherapy (RT) can be indicated to patients submitted to breast-conserving surgery, but, despite the benefits, adjuvant RT can cause contracture generated by tissue fibrosis in patients with immediate prosthetic reconstruction, which could cause prosthesis loss. The biological explanation of this outcome is not fully understood, but recent advances in the analysis of patient-derived blood can contribute to establishing a connection of molecular alterations related to this clinical outcome. There is not a consensus about using hypofractionated RT schemes for patients with BCS and breast reconstruction since no studies had investigated the reasons why some patients lose the prosthesis. PURPOSE: This study will evaluate G3 toxicity rate in breast cancer patients with immediate prosthetic reconstruction, submitted to hypofractionated radiotherapy, analyzing capsular contracture, leakage, infection, and bad positioning in order to demonstrate the noninferiority of Hypo-RT with the conventional RT. Additionally, the molecular profile of blood samples will be investigated in order to find biomarkers related to inflammations processes and response to treatment.

Detailed Description
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General aim: To evaluated if hypofractionated accelerated radiotherapy in patients with breast cancer undergoing immediate breast implant reconstruction surgery is non inferior to conventional radiotherapy. Aim 1 (Primary objective): Assess the G3 toxicity rate - loss of the prosthesis (complication that requires surgical intervention: capsular contracture, leakage, infection, malpositioning). Aim 2 (Specific secondary objectives): Compare local recurrence rate between two groups; Compare quality of life index between two groups using EORTC QLQ-C30 / EORTC QLQ-BR45 scales during treatment, after 6 and 12 months after treatment ending; Compare self-image differences between groups; Compare acute and late radiodermatitis rates by CTCAE 4.0; Analyse dosimetric planning differences considering the volumes of all breast and breast without prosthesis; Study inflammation molecular markers, which may indicate an increased risk of fibrosis; Evaluate the change in the profile of extracellular vesicles in patients treated with RT hypofractionated and conventional; Evaluate the change in EV collagen production after in vitro irradiation, using co-culture experiments with breast cells and fibroblasts.

Official Title
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Randomized Phase III Clinical Trial of Hypofractionated Radiotherapy in Breast Cancer Patients With Immediate Prosthetic Reconstruction: PROMART Trial

Conditions
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Breast Cancer

Intervention / Treatment
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* Radiation: Hypofractionation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women with confirmed histological diagnosis of invasive ductal carcinoma and lobular breast carcinoma; Radical mastectomy with immediate reconstruction with a prosthesis; Patients indicated for adjuvant RT; Any lymph node status; With or without adjuvant chemotherapy; ECOG performance status from 0-2; > 18 years old; Informed Consent Form applied before any study-specific procedure. Exclusion Criteria: Another histological diagnosis than invasive ductal carcinoma or lobular carcinoma; Previous history of neoplasm and/or radiotherapy and/ or quimiotherapy before this study; Distant metastatic disease; Palliative treatment; Patients with scleroderma / systemic lupus erythematosus.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Arm Experimental: Post Mastectomy Hypofractionated Radiotherapy Arm No Intervention: Post Mastectomy Conventional Radiotherapy
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Post Mastectomy Hypofractionated Radiotherapy Arm<br>Post Mastectomy Hypofractionated Radiotherapy Arm | Radiation: Hypofractionation<br>* Hypofractionation scheme will comprise 40 Gy in 15 fractions<br>|
| No Intervention: Post Mastectomy Conventional Radiotherapy<br>Post Mastectomy Conventional Radiotherapy | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the G3 toxicity rate | loss of the prosthesis (complication that requires surgical intervention: capsular contracture, leakage, infection, malpositioning) | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local recurrence | Compare local recurrence rate between two groups | 5 years | 
| Assessment of quality of life through the EORTC Questionnaires European Organization for Research and Treatment of Cancer, where a high or low score may suggest good quality of life depending on the domain of the questionnaire | Compare quality of life index between two groups using EORTC scales during treatment, after 6 and 12 months after treatment ending | 2 years | 
| Comparison of self-image using the EORTC Questionnaires European Organization for Research and Treatment of Cancer, where a high or low score may suggest good quality of life depending on the domain of the questionnaire | Compare self-image differences between groups | 5 years | 
| Compare acute and late radiodermatitis rates by Common Terminology Criteria for Adverse Events (CTCAE) 4.0 | Acute and late radiodermatitis rateswill be evaluated by CTCAE 4.0 scale, using the adverse event (AE) reporting. A grading (severity) scale is provided for each AE term. | 2 years | 
| Dosimetric analysis | Analyze dosimetric planning differences considering the volumes of all breast and breast without prosthesis | 5 years | 
| Inflammation markers screening - detection of cytokines with the CBA panel | Study inflammation molecular markers, which may indicate an increased risk of fibrosis. The cytokines present in the plasma will be evaluated using the Cytometric Beads Array technique with the CBA panel - Human Th1/Th2/Th17CBAKit which, through beads, is able to identify the expression of cytokines expressed by Th1, Th2 standard lymphocytes and Th17, including IL-2, IL-4, IL-6, IL-10, IL-17A, TNF e IFN-γ. After proper labeling, the immunophenotypic analyzes will be performed in a BD FAC Symphony flow cytometer. | 3 years | 
| Extracellular vesicles isolation and characterization | Evaluate the change in the profile of extracellular vesicles in patients treated with RT hypofractionated and conventional | 4 years | 
| Evaluate extracellular vesicles molecular profile | Evaluate the change in EV collagen production after in vitro irradiation, using co-culture experiments with breast cells and fibroblasts | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, radiation therapy, hypofractionated, biomarkers