Hypofractionation With Simultaneous Integrated Boost vs. Standard Fractionation in Early Breast Cancer

Study Overview
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Brief Summary
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Hypofractionation with simultaneous integrated boost has been investigated in a few trials and appears to be safe and feasible. Investigators initiated this multicenter two-armed phase III prospective trial to analyse the non-inferiority of hypofractionation with simultaneous integrated boost in patients with early breast cancer in comparison to standard fractionation.

Detailed Description
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Control Arm: Conventionaly fractionated radiotherapy of the breast 28 × 1.8 Gy = 50.4 Gy followed by a tumor bed boost sequentially 5 to 8 × 2.0 Gy = 10.0 Gy to 16.0 Gy, total dose 60.4 Gy to 66.4 Gy. or Conventionaly fractionated radiotherapy of the breast 28 × 1.8 Gy = 50.4 Gy with simultaneous integrated boost to the tumor bed, total dose 28 × 0.3 Gy or 0.45 Gy= 8.4 Gy or 12,6 Gy, total dose 58,8 Gy to 63.0 Gy. or Hypofractionated radiotherapy of the breast 16 × 2.66 Gy = 42.56 Gy followed by a tumor bed boost sequentially 5 to 8 × 2.0 Gy = 10.0 Gy to 16.0 Gy, total dose 52.56 Gy to 58.56 Gy. Experimental Arm: Hypofractionated radiotherapy of the breast 16 × 2.50 Gy with simultaneous integrated boost to the tumor bed, total dose within the boost volume 16 × 3.00 Gy.

Official Title
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Adjuvant Radiotherapy After Breast-conserving Surgery in Early Breast Cancer: Hypofractionation With Simultaneous Integrated Boost vs. Standard Fractionation

Conditions
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Early-Stage Breast Carcinoma

Intervention / Treatment
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* Radiation: Standard Radiation
* Radiation: Hypofractionation with SIB


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histopathologically confirmed breast cancer operated by breast conserving surgery with clear margins independently of further risk factors (positive or high-risk negative lymph node status, estrogen- or progesterone receptor status, Her-2/neu status uPA/PAI-1 criteria) and postoperative systemic therapy (chemotherapy, endocrine, antibody or bisphosphonate therapy were permitted when indicated) Indication to adjuvant radiotherapy including boost radiotherapy Clearly identified primary tumor region preferably by radiopaque clips Primary wound healing after breast conserving therapy without signs of infection Age ≥ 18 years ECOG ≤ 2 Performance Status Written informed consent Compliance regarding treatment appointments and toxicity Linguistic and cognitive ability to understand the questionnaires Exclusion Criteria: Patients operated by mastectomy No indication for boost radiation (e.g. status after IORT) double sided breast cancer Resection margins positive for disease or insufficient identification of the boost volume Indication for radiotherapy of the regional lymph nodes History of prior breast or thoracic radiotherapy Extended postoperative seroma at the beginning of radiotherapy Previously administered radiotherapy not allowing the required dose Pregnant or lactating patients and woman of child bearing potential, who lacked effective contraception treatment history of other cancer or participation in another clinical trial testing radiotherapy or drugs within 4 weeks of the start of treatment. Patients with serious, uncontrolled, physical or cerebrovascular disorders(e.g. myocardial infarction within the last 12 months) or neurologiy or psychiatric disorders thought to adversly affect treatment compliance

Ages Eligible for Study
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Minimum Age: 18 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: Standard radiation<br>Conventionally fractionated radiotherapy of the breast followed by a tumor bed boost sequentially or Conventionally fractionated radiotherapy of the breast with simultaneous integrated boost to the tumor bed or Hypofractionated radiotherapy of the breast followed by a tumor bed boost sequentially | Radiation: Standard Radiation<br>* Conventionally fractionated radiotherapy of the breast followed by a tumor bed boost sequentially or Conventionally fractionated radiotherapy of the breast with simultaneous integrated boost to the tumor bed or Hypofractionated radiotherapy of the breast followed by a tumor bed boost sequentially<br>|
| Experimental: Hypofractionation with SIB<br>Hypofractionated radiotherapy of the breast with simultaneous integrated boost to the tumor bed | Radiation: Hypofractionation with SIB<br>* Hypofractionated radiotherapy of the breast with simultaneous integrated boost to the tumor bed<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | any local or regional recurrence or distant metastasis or death | 3 to 6 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to occurence of local recurrence | ipsilateral in-breast recurrence | 3 to 6 years | 
| Overall survival | death | 3 to 6 years | 
| Safety and side effects (Number of Patients with Adverse Events) | Number of Patients with Adverse Events | 3 to 6 years | 
| Acute and chronic toxicity (NCI-CTCAE) | All dimensions of NCI-CTCAE | 1 day, 7 days, end of radiation (last day of radiation and closing visite), 3 months, 6 months, 12 months, 18 months, 24 months, 30 months, 36 months, 42 months, 48 months, 54 months, 60 months, 66 months, 72 months | 
| Cosmetic results (NCI-CTCAE) | NCI-CTCAE | 1 day, end of radiation (last day of radiation and closing visite), 3 months, 12 months, 24 months, 36 months, 48 months, 60 months, 72 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast cancer, Hypofractionation with SIB, Non-inferiority, adjuvant radiotherapy with simultaneous integrated boost