Single-dose Preoperative Partial Breast Irradiation in Low-risk Breast Cancer Patients

Study Overview
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Brief Summary
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In this ABLATIVE-2 trial, low-risk breast cancer patients will be treated with MRI-guided single dose preoperative partial breast radiotherapy to assess the rate of pathologic complete response after an interval of six to twelve months between radiotherapy and surgery. Response monitoring will be assessed using MRI and markers in blood and tumor tissue to enable prediction of pathologic response.

Detailed Description
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Patients will receive single-dose preoperative radiotherapy followed by breast conserving surgery (BCS) at 12 months after radiotherapy, as long as follow-up MRI scans show a complete radiologic response. In case of incomplete radiologic response, BCS will be performed at 6 months after radiotherapy. BCS is performed earlier when progressive disease is found on MRI. In the follow-up period between radiotherapy and surgery, tumor response will be monitored using MRI every 3 months. After surgery, patients will be followed up until 10 years after radiotherapy treatment to assess oncological outcomes, toxicity, cosmetic outcome and quality of life.

Official Title
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Single-dose Preoperative Partial Breast Irradiation in Low-risk Breast Cancer Patients

Conditions
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Breast Cancer

Intervention / Treatment
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* Radiation: Single dose ablative radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: WHO performance scale ≤2. Females at least 50 years of age with unifocal cT1N0 breast cancer on mammography, ultrasound and MRI. Patients with an indication for chemotherapy or HER2-targeted therapy according to Dutch National Oncoline Guidelines or own hospital protocols are not eligible. Patients with an indication for endocrine therapy are eligible. Tumor size as assessed on MRI. On tumor biopsy: Bloom-Richardson grade 1 or 2. Non-lobular invasive histological type carcinoma. LCIS or (non-extensive) DCIS is accepted. ER positive tumor receptor. HER2 negative tumor. Tumor-negative sentinel node (excluding isolated tumor cells). Adequate communication and understanding skills of the Dutch language. Exclusion Criteria: Legal incapacity. BRCA1, BRCA2 or CHEK2 gene mutation. Distant metastasis. Previous history of breast cancer or DCIS. Other type of malignancy within 5 years before breast cancer diagnosis. Patients with adequately treated malignancy longer than 5 years before breast cancer diagnosis are eligible for inclusion. For adequately treated carcinoma in situ of the cervix or basal cell carcinoma of the skin no specific time span to breast cancer diagnosis is required for inclusion. Collagen synthesis disease. Signs of extensive DCIS component on histological biopsy or on imaging (e.g. no extensive calcifications on mammography). Invasive lobular carcinoma. MRI absolute contraindications as defined by the Department of Radiology. Nodal involvement with cytological or histological confirmation. Indication for treatment with (neo-)adjuvant chemotherapy. Non-feasible dosimetric RT plan.

Ages Eligible for Study
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Minimum Age: 50 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pre-operative single dose partial breast irradiation<br> | Radiation: Single dose ablative radiotherapy<br>* Patients will receive a single dose of 20Gy/15Gy on the gross tumor volume and clinical tumor volume respectively, in the context of pre-operative partial breast irradiation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic complete response | pCR is defined as the absence of residual invasive cancer on resected breast specimen | 12 months after radiotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiologic complete response | Radiologic complete response (rCR) is defined as complete absence of pathologic contrast enhancement in the original tumor bed and complete absence of pathologic ADC (apparent diffusion coefficient) reduction in the original tumor bed. rCR is reported according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines. | at baseline, 2 weeks, 3, 6, 9, and 12 months after radiotherapy | 
| Treatment-related adverse events | Number of participants with treatment-related adverse events as assessed by the Common Terminology Criteria Adverse Events version 5.0 | at baseline, 2 weeks, 3, 6, 9, 12 months, 2, 3, 4, 5, 6, 8 and 10 years after radiotherapy | 
| Patient quality of life | PROMs are assessed using the European Organization for Research and Treatment of Cancer core-30 quality of life questionnaire (EORTC QLQ-C30) | at baseline, 2 weeks, 3, 6, 9, 12 months, 2, 3, 4, 5, 6, 8 and 10 years after radiotherapy | 
| Breast cancer specific quality of life | PROMs are assessed using the European Organization for Research and Treatment of Cancer breast cancer-specific quality of life questionnaire (EORTC QLQ-BR23) | at baseline, 2 weeks, 3, 6, 9, 12 months, 2, 3, 4, 5, 6, 8 and 10 years after radiotherapy | 
| Patient distress | PROMs are assessed using the Hospital Anxiety and Depression Scale (HADS) questionnaire | at baseline, 2 weeks, 3, 6, 9, 12 months, 2, 3, 4, 5, 6, 8 and 10 years after radiotherapy | 
| Physician reported cosmetic outcome | Cosmetic outcome is assessed by the physician using a questionnaire | at baseline, 2 weeks, 3, 6, 9, 12 months, 2, 3, 4, 5, 6, 8 and 10 years after radiotherapy | 
| Patient reported cosmetic outcome | Cosmetic outcome is assessed by the patient using the BREAST-Q questionnaire. . | at baseline, 2 weeks, 3, 6, 9, 12 months, 2, 3, 4, 5, 6, 8 and 10 years after radiotherapy | 
| Objective cosmetic outcome | Cosmetic outcome is assessed objectively using images captured using the VECTRA XT 3D-imaging system. This three-dimensional surface-imaging system uses stereophotogrammetry to estimate x, y, z coordinates of the imaged surface. These coordinates will be used to calculate the volume-shape-symmetry measure. | at baseline, 2 weeks, 3, 6, 9, 12 months, 2, 3, 4, 5, 6, 8 and 10 years after radiotherapy | 
| Local, regional and distant relapse rates | A local recurrence is defined as disease occurrence in the ipsilateral breast. A regional recurrence is defined as nodal occurrence in the ipsilateral axilla, internal mammary, infraclavicular or supraclavicular region. A distant metastasis defined as disease occurrence in the contralateral breast or contralateral breast nodal region or another organ than breast involvement. | Day of radiotherapy till end of follow-up of 10 years | 
| Overall survival | Overall survival will be calculated from the date of the radiotherapy treatment until the time of breast-cancer related death or breast-cancer unrelated death. | Day of radiotherapy till end of follow-up of 10 years | 
| Radiotherapy-associated immune response markers | Immune response markers as CD3, CD4, CD8 and FOXP3 will be assessed in tumor tissue after surgery. | 12 months after radiotherapy | 
| Radiotherapy-associated biomarkers | ctDNA will be assessed in blood samples taken between radiotherapy and surgery. | at baseline, 2 weeks, 3, 6, 9, and 12 months after radiotherapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Partial breast irradiation, Low-risk breast cancer, Early stage breast cancer, Pre-operative radiotherapy, Pre-operative single dose radiation, pathologic complete response, cosmetic outcome, survival, toxicity, quality of life, neo-adjuvant radiotherapy, oncological outcomes