Hypofractionated Vs Conventional Fractionated Radiotherapy After Breast Conserving Surgery

Study Overview
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Brief Summary
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The study was designed to investigate whether hypofractionated radiotherapy(HF-RT) is noninferior to conventionally fractionated radiotherapy (CF-RT) in terms of tumor loco-regional control for patients after breast conserving surgery

Detailed Description
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Eligible patients after breast conserving surgery will be randomized 1:1 into hypofractionated radiotherapy (HF-RT) group or conventionally fractionated radiotherapy (CF-RT) group. Patients in HF-RT group will receive 40 Gy/15 fractions irradiation to the whole breast with/without regional lymphnodes within 3 weeks and the tumor bed is boosted to 48 Gy/15 fractions simutaneously. Patients in CF-RT group will receive 50 Gy/ 25 fractions irradiation to whole breast with/without regional lymphnodes within 5 weeks and the tumor bed is boosted to 60 Gy/30 fractions sequentially. The primary endpoint is loco-regional recurrence. Other cancer related events and acute/late radiation morbidities will also be evaluated. The patients will be followed for 10 years. It is hypothesized that hypofractionated radiotherapy is non inferior to conventional fractionated radiotherapy in terms of tumor loco-regional control for patients after breast conserving surgery.

Official Title
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Hypofractionated Versus Conventional Fractionated Radiotherapy After Breast Conserving Surgery：a Multi-center Phase III Randomized Clinical Trial

Conditions
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Breast Cancer

Intervention / Treatment
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* Radiation: Hypofractionated Radiotherapy
* Radiation: Conventional fractionated Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female Age18-70 years Imaging examination confirmed single lesion. if the tumor is multiple, it needs to be removed by single quadrantectomy Receive breast conserving surgery with negative margins Axillary lymph nodes treatment: Sentinel lymph node biopsy or level I/II axillary lymph node dissection. If the sentinel lymph node is negative, the axillary lymph node dissection can be omitted. If it is positive, level I/II axillary lymph node dissection with or more than 10 lymph nodes is needed. The tumor bed is labeled with clips and it can be drawn on the treatment planning system. Pathologically confirmed invasive breast cancer Pathologically stage is T1-3N0-3M0 Immunohistochemical examination is conducted to determine the status of ER, PR, HER2, Ki67 after surgery No distant metastases No supraclavicular or internal mammary nodes metastases No neoadjuvant chemotherapy Fit for postoperative radiotherapy. No contraindications to radiotherapy KPS≥80 Signed informed consent Exclusion Criteria: T4 or M1 breast cancer Supraclavicular or internal mammary nodes metastases Pathologically confirmed DCIS only without an invasive component Bilateral breast cancer or historically confirmed contralateral invasive breast cancer Treated with neoadjuvant chemotherapy or neoadjuvant endocrine therapy Multiple lesions can not be removed by single quadrantectomy Suspicious unresected and microcalcification, densities, or palpable abnormalities (in the ipsilateral or contralateral breast) KPS ≤ 70 Patients with severe non-malignant comorbidity in cardiovascular or respiration system Concurrent or previous malignancy excluding basal or squamous cell carcinoma of the skin Previous radiotherapy to the chest wall or regional lymph node areas Patients with medical contraindication for radiotherapy: systemic lupus erythematosus, cirrhosis Pregnant or lactating Conditions indicating that the patient cannot go through the radiation therapy or follow up Unable or unwilling to sign informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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 |
| --- | --- |
| Experimental: Hypofractionated Radiotherapy<br>40 Gy/15 fractions irradiation is delivered to the whole breast, 2.67 Gy per fraction, 5 fractions weekly. Tumor bed is boosted to 48 Gy simultaneously, 3.2 Gy per fraction, 5 fractions weekly. | Radiation: Hypofractionated Radiotherapy<br>* daily fractions, 2.66 Gy/3.2 Gy per fraction to whole breast/tumor bed, five fractions per week<br>* Other names: Experimental Arm;|
| Active Comparator: Conventional Irradiation<br>50 Gy/25 fractions irradiation is delivered to the whole breast, 2 Gy per fraction, 5 fractions weekly. Additional 10 Gy/5 fractions is boosted to tumor bed sequentially, 2 Gy per fraction, 5 fractions weekly. | Radiation: Conventional fractionated Radiotherapy<br>* daily fractions, 2 Gy per fraction, five fractions per week<br>* Other names: Standard Arm;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Loco-regional recurrence (LRR) | Defined as any clinical and biopsy-proven tumor recurrence involving the ipsilateral chest wall and/or regional nodes (including axillary, supraclavicular, infraclavicular, or internal mammary nodes). | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Distant metastasis free survival (DMFS) | Distant metastasis is defined as clinical detection of metastatic disease beyond the chest wall and/or regional lymph nodes or death or last visit. Distant metastasis free survival (DMFS) is defined as the interval starting from the date of randomization until to the event. | every 3 months during the first 2 years after the last fraction received, every 6 months during 3-5 years, every year during 6-10 years | 
| Disease free survival (DFS) | Defined as the interval from the date of randomization to any disease recurrence or death or last visit. | every 3 months during the first 2 years after the last fraction received, every 6 months during 3-5 years, every year during 6-10 years | 
| Overall survival (OS) | Defined as the interval from the date of randomization to death or last visit. | every 3 months during the first 2 years after the last fraction received, every 6 months during 3-5 years, every year during 6-10 years | 
| Number of patients with radiation-induced acute toxicity assesses by CTCAE4.03 | Acute toxicity (development of radiation dermatitis, pruritus, pain, radiation esophagitis, and radiation pneumonitis) will be assessed according to toxicity criteria of CTCAE version 4.03 before treatment, during treatment (after 8 fractions irradiation for HF-RTgroup and 15 fractions for CF-RT group) and the end of treatment (15 fractions irradiation for HF-RTgroup and 30 fractions for CF-RT group), 2 weeks and 3 months after the last fraction received. | before treatment, after 8 fractions (HF-RTgroup) and 15 fractions (CF-RT and HF-RT groups) and 30 fractions（CF-RT group) irradiation, 2 weeks and 3 months after the irradiation finished | 
| Number of patients with radiation-induced late toxicity assesses by CTCAE4.03 | Late toxicity (change of skin in irradiated area，impaired shoulder movement ，impaired shoulder movement, brachial plexopathy,ischemic heart disease) will be assessed according to toxicity criteria of CTCAE version 4.03 | before treatment, every year after the last fraction received through 10 years | 
| Number of patients with radiation-induced late toxicity assesses by LENT-SOMA Toxicity Assessment | Development of dyspigmentation, telangiectasia in irradiated area and radiation pulmonary fibrosis will be assessed according to toxicity criteria of LENT-SOMA | before treatment, every year after the last fraction received through 10 years | 
| Harvard/NSABP/RTOG Breast Cosmesis Grades of patients | The cosmetic outcomes will be evaluated by radiation oncologists, nurses and patients using digital photographs and Harvard/NSABP/RTOG Breast Cosmesis Grading Scale. Harvard/NSABP/RTOG Breast Cosmesis Grading Scale classifies the overall aesthetic results in four categories from excellent, good, fair to poor. | before treatment, every year after the last fraction received through 10 years | 
| Quality of Life Score assessed by EORTC-QLQ-C30 (version 3) | Patients' quality of life will be assessed using self-administered questionnaire EORTC-QLQ-C30 (version 3) | before treatment, after 15 fractions (HF-RTgroup) or 30 fractions (CF-RT group) irradiation，every year after the treatment finished through 10 years | 
| Quality of Life Score assessed by EORTC breast-cancer module (BR23) | Patients' quality of life will be assessed using self-administered questionnaire EORTC breast-cancer module (BR23) | before treatment, after 15 fractions (HF-RTgroup) or 30 fractions (CF-RT group) irradiation, every year after the last fraction received through 10 years | 
| Number and percentage of peripheral blood lymphocytes | peripheral blood lymphocytes will be assessed before, during treatment (after 8 fractions irradiation for HF-RTgroup and 15 fractions for CF-RT group) and the end of treatment (15 fractions irradiation for HF-RTgroup and 30 fractions for CF-RT group). The number and percentage of peripheral blood lymphocytes will be assessed the correlation with the grade of acute toxicity assessed by CTCAE 4.03 | before treatment, after 8 fractions (HF-RTgroup) and 15 fractions (CF-RT and HF-RT groups) and 30 fractions（CF-RT group) irradiation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypofractionated radiotherapy, Breast Conserving Surery