Accelerated Partial Breast Irradiation Versus Standard or Hypofractionated Whole-Breast Irradiation, in Early Breast Cancer, After Breast-conserving Surgery

Study Overview
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Brief Summary
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Radiotherapy has been confirmed as an important treatment breast-conserving surgery reducing the risk of any recurrence of breast cancer and breast cancer-related mortality in patients with early breast cancer. There are no comparative data on the ideal radiotherapy treatment regimen for patients with early stage breast cancer who underwent conservative surgery in the Brazilian population.

Detailed Description
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The investigators propose a prospective, randomized, pilot study, with active control, to evaluate the viability and safety of accelerated partial breast irradiation, in 5 fractions, comparing with the radiotherapy regimens of the whole breast in 15 and 5 fractions, in patients with breast cancer, in initial stage, who underwent conservative surgery.

Official Title
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Clinical Trial, Randomized, Open Label, With an Active Comparator to Assess the Efficacy and Safety of Using Accelerated Partial Irradiation Versus Standard or Hypofractionated Irradiation of the Entire Breast in Patients With Initial Breast Cancer After Conservative Surgery

Conditions
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Malignant Neoplasm of Breast

Intervention / Treatment
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* Radiation: Active Comparator: Standard
* Radiation: Experimental 1: Hypofractionated radiotherapy
* Radiation: Experimental 2: Accelerated Partial Breast Irradiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Information to the patient and signed informed consent; Women aged ≥50 years Breast conserving surgery Pathologic tumor size < 3 cm (maximum microscopic diameter of the invasive component) Invasive adenocarcinoma (except classic invasive lobular carcinoma) Unifocal disease Histopathologic grades I or II Eastern Cooperative Oncology Group (ECOG) 0-1 Lymphovascular invasion absent Negative axillary lymph nodes Minimum microscopic margins of non-cancerous tissue of 2mm (excluding deep margin when in deep fascia) No prior breast or mediastinal radiotherapy No hematogenous metastases Exclusion Criteria: Previous malignancy (except non-melanomatous skin cancer) Mastectomy Classical-Type Invasive Lobular Carcinoma Neoadjuvant chemotherapy Human Epidermal growth factor Receptor-type 2 positive (HER2+) Triple-negative breast cancers Intravascular lymphoma present Contraindications to radiotherapy. No geographical, social or psychologic reasons that would prevent study follow

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 90 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Comparator: Standard<br>Whole breast Radiotherapy, 40 Gray (40Gy) fractions | Radiation: Active Comparator: Standard<br>* Radiation: Whole Breast Irradiation + Boost Whole breast, either 40Gy, in 15 fractions, in 3 weeks<br>|
| Experimental: Experimental 1: Hypofractionated radiotherapy<br>Whole breast Radiotherapy, 26 Gray (26Gy) in 5 fractions | Radiation: Experimental 1: Hypofractionated radiotherapy<br>* Radiation: Hypofractionated irradiation Whole Breast Irradiation 26Gy in 5 fractions in one week<br>|
| Experimental: Experimental 2: Accelerated Partial Breast Irradiation<br>Partial Breast Irradiation 26 Gray (26Gy) to the tumor bed in 5 fractions. | Radiation: Experimental 2: Accelerated Partial Breast Irradiation<br>* Radiation: Accelerated partial breast irradiation Tumor bed 26Gy in 5 fractions, in 5 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of local recurrence | To estimate and compare the rate of local recurrence between the experimental and control arms. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to occurrence of distant metastases | Distant tumor time is defined as number of days from randomization until occurrence of distant metastases, death without prior distant progression, or end of follow-up. | 5 years | 
| Disease-free survival | Disease-free survival, defined as number of days from randomization until the first occurrence of local recurrence, distant metastases, tumor-related death, death without prior progression, or end of follow-up. | 5 years | 
| Overall survival | Overall survival time, defined as number of days from randomization until death or end of follow-up. | 5 years | 
| Medico-economic study | To evaluate and compared the cost between Accelerated Partial Breast Irradiation with Standard and Hypofractionated irradiation | Baseline and 3 months, 6 months, 12 months, 2 years, 5 years after treatment end | 
| Health-related Quality of Life | To evaluate the patients quality of life with the help of the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). This questionnaire was designed to be cancer specific, multidimensional in structure, suitable for self-administration (brief and easy to complete), and applicable in a wide range of cultural contexts. The scores in each dimension are uniformly transformed to dimensions ranging from 0 to 100, with 0 denoting the negative (low functioning, high symptom burden) and 100 the positive end (high functioning, low symptom burden) of the continuum. | Baseline and 3 months, 6 months, 12 months, 2 years, 5 years after treatment end | 
| Evaluation of quality of life change by European Organization for Research and Treatment of Cancer Breast-Cancer-Specific Quality of Life Questionnaire (EORTC QLQ-BR23) | To evaluate the patient quality of life with the help of the European Organization for Research and Treatment of Cancer Breast-Cancer-Specific Quality of Life Questionnaire (EORTC QLQ-BR23). The 23-item EORTC QLQ BR23 contains two breast cancer specific functional scales (body image and sexuality) and three symptom scales evaluating arm symptoms, breast symptoms, and systemic therapy symptoms. The minimum and maximum values are 0 and 100, and higher scores mean a better outcome. | Baseline and 3 months, 6 months, 12 months, 2 years, 5 years after treatment end | 
| Fatigue Questionnaire (Functional Assessment of Cancer Therapy-Fatigue - FACT-F) | To evaluate the patient quality of life with the help of the Functional Assessment of Cancer Therapy-Fatigue (FACT-F). Scores are interpreted according to the guidelines of the Scoring Manual. The higher the number of points, the better the quality of life. To obtain the score, the negative questions are reverted; then the answers of the domains are added up, and a proportional average is carried out in case of non answered items. | Baseline and 3 months, 6 months, 12 months, 2 years, 5 years after treatment end | 
| Measurement Satisfaction of Body Image of the participants | To evaluate the patient quality of life and patient satisfaction with the help of the Body Image Scale (BIS). Scores are interpreted according to the guidelines of the Scoring Manual. The Body Image Scale (BIS) is a self-assessment scale designed to assess cancer patients' perceptions of their appearance and identify any changes to those perceptions resulting from a disease or a treatment. The total score ranges from 0 to 30. A higher score means a higher level of body image disturbance. | Baseline and 3 months, 6 months, 12 months, 2 years, 5 years after treatment end | 
| Changes in anxiety and depression | To evaluate the patient quality of life and patient satisfaction with the help of the Hospital Anxiety and Depression Scale (HADS). Scores for each sub scale (depression and anxiety) are summed-up and range from 0 to 21. Values from 0-7 indicate normal levels, 8-10 are border values and values from 11-21 are considered to be pathological. | Baseline and 3 months, 6 months, 12 months, 2 years, 5 years after treatment end | 
| Early and late adverse effects in normal tissues | To evaluate the results reported by patient and evaluated by doctors, as well as, photographic assessments. | 5 years | 
| Late adverse effects | To evaluate if the patient had symptoms of swelling or edema in the arm, breast shrinkage, hardness, pigmentation, necrosis, pain and tenderness in the breast. | 5 years | 
| Acute toxicity rate | To evaluate acute toxicity rate. The maximum grade for acute toxicity will be recorded for each patient at each treatment evaluation using Common Terminology Criteria for Adverse Events. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer, Radiotherapy, Hypofractionated, Breast-conserving surgery