Comparison of Acute Toxicity and Cost Between Whole Breast Irradiation With Sequential Boost and Simultaneous Integrated Boost After Breast Conserving Surgery.

Study Overview
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Brief Summary
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Whole breast irradiation (WBI) after breast conserving surgery for early-stage breast cancer halves the recurrence risk and reduces the breast cancer death by about one sixth. A sequential boost (SeqB) dose to the tumour bed further improves local control, but also increases the risk of late skin toxicity and cosmetic changes. At Ghent University Hospital WBI is prescribed in 15 fractions of 2.67 Gy according to the START-B hypofractionation scheme. A sequential boost is typically given in 4 to 8 extra fractions which prolongs the overall treatment time. The boost dose can also be delivered within the 15 fractions of WBI, the so-called simultaneous integrated boost (SIB). SIB shortens the overall treatment time which is convenient for the patient and the radiotherapy department. In this study we wish to test the hypothesis of acceptable skin toxicity and reduced cost with SIB using hypofractionated prone intensity modulation radiotherapy IMRT with topographical dose painting, a technique recently developed in our group. Patients are randomized between SeqB and SIB.

Official Title
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Comparison of Acute Toxicity and Cost Between Whole Breast Irradiation With Sequential Boost and Simultaneous Integrated Boost After Breast Conserving Surgery

Conditions
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Radiotherapy After Breast Conserving Surgery

Intervention / Treatment
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* Radiation: sequential boost (15 x 2.67 Gy WBI + 4 x 2.5 Gy boost)
* Radiation: SIB (15 x 2.67 Gy WBI and SIB 15 x 2.67-3.12 Gy)
* Radiation: sequential boost (15 x 2.67 Gy WBI + 6 x 2.48 Gy boost)
* Radiation: SIB (15 x 2.67 Gy WBI and SIB 15 x 2.67-3.33 Gy)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Female patients AND breast conserving surgery AND multidisciplinary decision of adjuvant WBI with a boost to the tumor bed AND age ≥ 18 years AND informed consent obtained, signed and dated before specific protocol procedures Exclusion criteria Mastectomy Need for lymph node irradiation No boost Bilateral breast irradiation Patient not able to reach or maintain the prone position Pregnant or breastfeeding Mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study Patient unlikely to comply with the protocol; i.e. uncooperative attitude, inability to return for follow-up visits, and unlikely to complete the study

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: Minimal surgical margin 1 mm, conventional arm: seq boost<br>Minimal surgical margin of 1 mm, conventional arm with sequential boost (15 x 2.67 Gy WBI + 4 x 2.5 Gy boost). | Radiation: sequential boost (15 x 2.67 Gy WBI + 4 x 2.5 Gy boost)<br>* Minimal surgical margin of 1 mm, conventional arm with sequential boost (15 x 2.67 Gy WBI + 4 x 2.5 Gy boost)<br>|
| Experimental: Minimal surgical margin of 1 mm, experimental arm with SIB<br>Minimal surgical margin of 1 mm, experimental arm with SIB (15 x 2.67 Gy WBI and SIB 15 x 2.67-3.12 Gy) | Radiation: SIB (15 x 2.67 Gy WBI and SIB 15 x 2.67-3.12 Gy)<br>* Minimal surgical margin of 1 mm, experimental arm with SIB (15 x 2.67 Gy WBI and SIB 15 x 2.67-3.12 Gy)<br>|
| Active Comparator: Minimal surgical margin <1 mm, conventional arm: seq boost<br>Minimal surgical margin < 1 mm, conventional arm with sequential boost (15 x 2.67 Gy WBI + 6 x 2.48 Gy boost) | Radiation: sequential boost (15 x 2.67 Gy WBI + 6 x 2.48 Gy boost)<br>* Minimal surgical margin < 1 mm, conventional arm with sequential boost (15 x 2.67 Gy WBI + 6 x 2.48 Gy boost)<br>|
| Experimental: Minimal surgical margin < 1 mm, experimental arm with SIB.<br>Minimal surgical margin < 1 mm, experimental arm with SIB (15 x 2.67 Gy WBI and SIB 15 x 2.67-3.33 Gy) | Radiation: SIB (15 x 2.67 Gy WBI and SIB 15 x 2.67-3.33 Gy)<br>* Minimal surgical margin < 1 mm, experimental arm with SIB (15 x 2.67 Gy WBI and SIB 15 x 2.67-3.33 Gy)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Degree of acute moist desquamation during or in the first 2 weeks after radiotherapy. | Clinical inspection of the treated breast. | weekly during radiotherapy, 2 weeks after the end of radiotherapy. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Degree of acute skin toxicity. | Clinical inspection. | Weekly during radiotherapy and 2 weeks after the end of radiotherapy. | 
| Degree of chronic skin toxicity and cosmesis after radiotherapy. | Inspection, clinical evaluation, digital photographs. | 2 weeks, 1 year, 2 years and 5 years after radiotherapy. | 
| Quality of life after radiotherapy. | QLQ C30 and QLQ BR23 quality of life questionnaires. | 2 weeks, 1 year, 2 years and 5 years after radiotherapy. | 
| Biomarker analysis. | Blood sample | Blood sample within 1 week before the start of radiotherapy | 
| Measurement of costs for the patient for the full treatment. | Activity based costing models. | Over the period of radiotherapy treatment, with a maximum of 5 weeks. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Radiotherapy