Adjuvant Partial-breast Irradiation Using Stereotactic Body Radiation Therapy

Study Overview
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Brief Summary
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The adjuvant radiotherapy (RT) of the early-stage breast cancer patients as local treatment aims to eliminate the potential microscopic residual disease in the surgery bed or satellites in its neighborhood. Nowadays accelerated partial breast irradiation (APBI) is recommended for highly selected patients. This prospective randomized study compares the targeted external beam APBI with commonly used accelerated whole-breast irradiation (WBI) in terms of feasibility, safety, tolerance, and cosmetic effects. It is designed as non-inferiority trial and its aim is to increase the level of evidence for establishment of external beam APBI in indicated patients into daily clinical practice.

Detailed Description
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Early-stage breast cancer patients after partial mastectomy are screened for eligibility. The inclusion criteria are age ˃ 50 years, non-lobular carcinoma histology, size ≤ 2 cm, negative margins ≥ 2 mm, L0, ER-positive, HER-2 negative. Enrolled patients are equally randomized into two arms according to radiotherapeutic regiment - external beam APBI (5× 6 Gy) and accelerated whole breast irradiation with the boost (15× 2,67Gy + 5× 2Gy). The follow-up visits are planned at the end of RT and 1, 3, 6, 9, and 12 months after radiation, in the second year every 4 months and then every 6 months. Cosmetics results and toxicity are evaluated using questionnaires, CTCAE criteria, and photodocumentation of the irradiated chest. The main objective of presented study is to evaluate the feasibility, safety, tolerance, and cosmetic effects of SBRT irradiation to the surgery bed in five fractions. In addition to standard clinical examination and evaluation of acute and late side effects, patients together with clinicians and nurses will independently complete a questionnaire on the impact of irradiation on the cosmetic effect. The technique of targeted external beam APBI should demonstrate better feasibility and less toxicity than the standard regimen in the adjuvant setting in treating early-stage breast cancer patients. Consequently, the presented study should increase the level of evidence for RT-indicated patients to the establishment of external APBI into daily clinical practice.

Official Title
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Adjuvant Partial-breast Irradiation of Early-stage Breast Cancer Using Stereotactic Body Radiation Therapy

Conditions
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Early-stage Breast Cancer

Intervention / Treatment
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* Radiation: APBI
* Radiation: WBI


Participation Criteria
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Eligibility Criteria
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Patients referred to medical attention for adjuvant radiotherapy of early-stage breast cancer at the Department of Radiation Oncology, Masaryk Memorial Cancer Institute (MMCI) were screened for eligibility. If all inclusion/exclusion criteria will be met, they were invited to participate in the present study. Inclusion Criteria: Age ≥50 years Karnofsky index > 70 Partial mastectomy (breast-conserving surgery) DCIS G1/2 ≤ 2.5 cm with negative margins (≥ 3 mm) or invasive (non-lobular) luminal-like HER2 negative carcinoma ≤ 2 cm with negative margins (≥ 2 mm) without LVI In the case of invasive carcinoma, performing of axillary dissection (≥6 negative lymph nodes) or negative sentinel node biopsy Exclusion Criteria: Prior to other chest or breast surgery (including breast reconstruction), the absence of surgical clips in the tumor bed Prior ipsilateral chest or breast radiotherapy Neoadjuvant systemic therapy Adjuvant chemotherapy Multifocal or multicentric involvement BRCA 1 or 2 mutations or known mutations in other high penetrance genes Any systemic illness (collagen vascular diseases) or unstable medical condition that might pose additional risks for the performance of radiotherapy including claustrophobia or jactation Any other factors that, in the opinion of the site investigators, would interfere with adherence to study requirements Pregnancy or breastfeeding Inability or unwillingness of the subject to sign written informed consent

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The trial is designed as binary outcome parallel group non-inferiority trial.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: APBI, accelerated partial breast irradiation<br>The APBI group will be irradiated with a dose of 30Gy in 5 fractions in 5 working days. | Radiation: APBI<br>* accelerated partial breast irradiation to the surgery bed (5 x 6,0 Gy; in 5 working days)<br>|
| Active Comparator: WBI, whole breast irradiation<br>The control group of patients will be irradiated with a standard accelerated mode within 20 working days. | Radiation: WBI<br>* accelerated whole breast irradiation with the boost to tumor bed (15x 2,67 Gy + 5x 2,0 Gy, every working day)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| APBI vs. WBI - toxicity | Comparison of acute and late toxicity of the APBI of the early stage breast cancer with accelerated irradiation regimen. | 44 months | 
| APBI vs. WBI - cosmetic effects | Comparison of cosmetic effects of the APBI of the early stage breast cancer with accelerated irradiation regimen. Cosmetic effects independently evaluated by patient, physician, and nurse scored using Harvard scale (4-point Likert scale). The scale contains 4 values - nearly identical as untreated (the best outcome), slightly different, clearly different, seriously distorted (the worst outcome) | 44 months | 
| APBI - feasibility | Evaluation of feasibility of the APBI regimen based on the proportion of patients who completed radiation in a total of 10 days and the proportion of patients who were irradiated exactly according to technical guidelines. | 44 months | 
| APBI vs. WBI - tolerance | Comparison of tolerance of the APBI of the early stage breast cancer with accelerated irradiation regimen. The toxicity was evaluated by CTCAE criteria (Common Terminology Criteria for Adverse Events). The outcome to define the tolerance a safety was CTCAE grade II or greater skin toxicity. | 44 months | 
| APBI vs. WBI - safety | Comparison of safety of the APBI of the early stage breast cancer with accelerated irradiation regimen. The toxicity was evaluated by CTCAE criteria (Common Terminology Criteria for Adverse Events). The outcome to define the tolerance a safety was CTCAE grade II or greater skin toxicity. | 44 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life C30 | Quality of Life assessment using the standardized European Organisation for Research and Treatment of Cancer (EORTC) questionnaire QLQ-C30. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems. | 44 months | 
| Quality of life BR45 | Quality of Life assessment using the standardized European Organisation for Research and Treatment of Cancer (EORTC) questionnaire with special module for patients with breast cancer (Breast QLQ-BR45). All of the scales and single item measures range in score from 0 to 100. A high score for the functional scales and functional single items represents a high/healthy level of functioning, whereas a high score for the symptom scales and symptom item represents a high level of symptomatology or problems. | 44 months | 
| Effectivity | Assessment of effectivity of the treatment method by evaluating subsequent endpoints such as LC (local control) and OS (overall survival). Overall survival (OS) is defined as the time from randomization to death from any cause. Local control (LC) is defined as the time from randomization to the first local recurrence. | 44 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, adjuvant radiotherapy, accelerated partial breast irradiation, surgical bed