Adjuvant Regional Nodal Radiation Therapy for One Week in Breast Cancer

Study Overview
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Brief Summary
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The purpose of this trial is to investigate the toxicities and efficacy of hypofractionated regional nodal radiotherapy (RNI) for one week in breast cancer patients treated with mastectomy or breast conserving surgery. Hypofractionated radiotherapy will be delivered to chest wall or whole breast and regional lymph regions (including supraclavicular/infraclavicular region, internal mammary nodes, and any part of the axillary bed at risk). Eligible breast cancer patients will be followed for at least 1 years to evaluate the acute and late radiation-induced toxicities, locoregional recurrence, over survival, distant metastasis, and quality of life.

Detailed Description
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Eligible breast cancer patients will receive hypofractionated radiotherapy of 5.2 Gy in 5 fractions within one week and a sequential tumor bed boost of 5.2 Gy in 2 fractions to the conserved breast. The dose is prescribed to ipsilateral chest wall or whole breast and regional lymph regions (including supraclavicular/infraclavicular region, internal mammary nodes, and any part of the axillary bed at risk). All patients are treated with intensity modulated radiation therapy (IMRT) technique. The primary endpoint is ≥2 grade any acute radiation induced toxicity event. patients will be followed for at least 1 years to evaluate the acute and late radiation-induced toxicity, locoregional recurrence, over survival, distant metastasis, and quality of life. Calculation of the required number of cases based on an alpha of 0.05 and a power of 80% with a maximal tolerable toxicity difference of 10% during and within 6 months after RNI comparing to conventional radiotherapy and lost rate of follow up of 10%. In total 197 patients are needed to be recruited.

Official Title
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One-week Hypofractionated Radiotherapy in Breast Cancer Patients With an Indication for Regional Nodal Irradiation: Prospective, Single-arm Trial

Conditions
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Breast Cancer

Intervention / Treatment
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* Radiation: External Beam radiotherapy using IMRT technique


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged >18 years old Underwent radical surgery with either mastectomy or breast conserving surgery and axillary lymph node dissection (ALND) Ipsilateral clinically diagnosed and histologically confirmed invasive breast cancer T1-3 >=1 pathologically positive axillary lymph nodes Karnofsky Performance Status scoring ≥80, and anticipative overall survival >5 years Surgery wound healed without infection Negative pathologically surgical margin ER (estrogen-receptor), PR (progesterone-receptor), HER2 (human epidermal growth factor receptor 2) and Ki67 testing can be performed on the primary breast tumor Women of child-bearing potential must agree to use adequate contraception for up to 1 month before study treatment and the duration of study participation Ability to understand and willingness to participate the research and sign the consent forms Exclusion Criteria: Pathologically positive ipsilateral supraclavicular lymph node Pathologically or radiologically confirmed involvement of ipsilateral internal mammary lymph nodes Pregnant or lactating women Severe non-neoplastic medical comorbidities History of non-breast malignancy within 5 years with the exception of lobular carcinoma in situ, basal cell carcinoma of the skin, carcinoma in situ of skin, Adenocarcinoma in situ of the lung and carcinoma in situ of the cervix simultaneous contralateral breast cancer Previous radiotherapy to the neck, chest and/or ipsilateral axillary region Active collagen vascular disease Definitive pathological or radiologic evidence of distant metastatic disease Primary T4 tumor Interval between radical surgery (mastectomy or breast conserving surgery) and radiotherapy was more than 12 weeks or interval between last dose of adjuvant chemotherapy and radiotherapy was more than 8 weeks

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Hypofractionated radiotherapy<br>Patients with an indication for regional nodal irradiation will receive 5.2 Gy in 5 fractions to chest wall or whole breast and regional lymph regions (including supraclavicular/infraclavicular region, internal mammary nodes, and any part of the axillary bed at risk) and a sequential tumor bed boost of 5.2 Gy in 2 fractions to the conserved breast. | Radiation: External Beam radiotherapy using IMRT technique<br>* 2600cGy/ 5 fractions / 1 weeks to ipsilateral chest wall or whole breast and regional lymph regions and a sequential tumor bed boost of 5.2 Gy in 2 fractions to the conserved breast<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative complication rate of ≥Grade 2 Acute Radiation-induced Toxicity | Within time from the beginning of radiotherapy to 6 months after completion of radiotherapy, any acute radiation-induced toxicities will be assessed and recorded after the last fraction using the Common Terminology Criteria for Adverse Events (CTCAE) 3.0. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative complication rate of ≥Grade 2 Late Radiation-induced Toxicity | Within time from 6 months after completion of radiotherapy to 5 years after completion of radiotherapy, any late toxicity will be assessed and recorded using the Radiation Therapy Oncology Group (RTOG) /European Organization for Research on Treatment of Cancer (EORTC) Late Radiation Morbidity Scoring Schema and CTCAE 3.0 | 5 years | 
| Number of Participants with excellent or good Cosmetic outcomes following breast conserving surgery-Harvard/ NSABP/RTOG scoring scale | The cosmetic outcomes will be evaluated at 6 months after last fractions. The cosmetic outcomes are evaluated based on the Allegheny General Modification of the Harvard/National Surgical Adjuvant Breast and Bowel Project (NSABP)/ RTOG scoring scale which graded patients into the following four classifications: excellent, when compared to the untreated breast, there is a minimal or no difference in the size or shape of the treated breast; good, slight difference in the size or shape of the treated breast; fair, obvious difference in the size or shape of the treated breast; and poor, marked change in the size or shape of the treated breast | 6 months | 
| Number of Participants with excellent or good Cosmetic outcomes following breast conserving surgery-Harvard/ NSABP/RTOG scoring scale | The cosmetic outcomes will be evaluated at 5 years after last fractions. The cosmetic outcomes are evaluated based on the Allegheny General Modification of the Harvard/National Surgical Adjuvant Breast and Bowel Project (NSABP)/ RTOG scoring scale which graded patients into the following four classifications: excellent, when compared to the untreated breast, there is a minimal or no difference in the size or shape of the treated breast; good, slight difference in the size or shape of the treated breast; fair, obvious difference in the size or shape of the treated breast; and poor, marked change in the size or shape of the treated breast | 5 years | 
| Locoregional recurrence | any first recurrence confirmed by histology or cytology within the ipsilateral chest wall and/or regional nodes area(including supraclavicular, infraclavicular or internal mammary lymph nodes) | 5 years | 
| Distant metastasis free survival (DMFS) | The time from the date of enrollment to any recurrence of tumor at distant sites or death from any cause | 5 years | 
| Invasive recurrence-free survival (IRFS) | The time from the date of enrollment to any invasive recurrence of tumor or death from any cause | 5 years | 
| Over survival (OS) | The time from the date of enrollment to the date of death from any cause | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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regional nodal irradiation, IMRT, Hypofractionated radiotherapy for one week