Accelerated Partial Breast Irradiation With 3D-CRT and IMRT

Study Overview
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Brief Summary
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The purpose of this study is to determine in a phase II clinical trial whether accelerated partial breast irradiation after breast conserving surgery using 3 dimensional external beam radiotherapy (3D-CRT) and intensity modulated radiotherapy (IMRT) for low-risk invasive breast cancer patients is safe without causing serious late radiation side-effects.

Detailed Description
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It is a sequential phase II trial. Eligible patients after breast conserving surgery (BCS) are treated with accelerated partial breast irradiation (APBI) using three-dimensional conformal radiotherapy (3D-CRT) for the first 45 patients or intensity modulated radiotherapy (IMRT) for the second 45 patients. Primary end-point of the study: late radiation side-effects at 5 years. Early stopping criteria: Not used as primary end-point is late side-effects. Interim analysis: Not planned Secondary end-points: cosmetic results, quality of life, local recurrence-free survival, regional recurrence free survival, distant metastasis free survival, relapse free survival, overall survival, cancer specific survival. Null-hypothesis for primary end-point: The incidence of severe (>G2) late radiation side-effects after APBI using 3D-CRT or IMRT will not exceed 10%. Stratification: by treatment delivery: 3D-CRT - first 45 patients; IMRT - second 45 patients by bra capsize: Capsize A-B; C; and D-D+ Treatment intervention: 9 x 4.1 Gy APBI using 3D-CRT (first 45 patients) or IMRT (second 45 patients) delivered within 5 days, using twice-a-day fractionation. Clinical target volume (CTV) and Planning target volume (PTV) definition: CTV = excision cavity + 20 mm minus the actual pathological surgical margin in mm PTV = CTV + 5 mm in each direction Follow-up: ECOG PS, physical examination (inspection and palpation), registration of side-effects (RTOG (Radiation Therapy Oncology Group) EORTC (European Organization for Research and Treatment of Cancer)) early and late radiation morbidity scoring scheme) and cosmetic results (using the Harvard scale) : 7-14 days after RT, than in every 3 months for 2 years, and every 6 months for 5 years. Mammography: at 6, 12, 18, 24 months, and annually thereafter Quality of life questionnaire (QLQ) (e.g. EORTC (European Organization for Research and Treatment of Cancer) QLQ-30 and Breast (BR)-23) before RT, at 7-14 days after RT, at 3, 6, and 12 months, and annually thereafter digital photography: before treatment, at 7-14 days after treatment, and yearly thereafter

Official Title
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Accelerated Partial Breast Irradiation After Breast Conserving Surgery for Low-risk Invasive Breast Cancer: 3D Conformal Radiotherapy (3D-CRT) and Intensity Modulated Radiotherapy (IMRT) - Prospective Phase II Study

Conditions
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Breast Cancer, Radiation Toxicity, Side Effects

Intervention / Treatment
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* Radiation: accelerated partial breast irradiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: previous breast conserving surgery within 12 weeks (in case of adjuvant chemotherapy within 28 days after completion of chemotherapy) patient age > 40 years ECOG performance status: 0-1 life expectancy >5 years invasive ductal, papillary, mucinous, medullary or tubular carcinoma unifocal tumor pathological tumor size < or = 30 mm pathological negative axillary nodal status with axillary dissection or sentinel lymph node biopsy surgical clips in the tumor bed pathological surgical free margins of at least 2 mm written informed consent of patients Exclusion Criteria: Stage III-IV multifocal tumor extensive intraductal component (EIC) ductal or lobular carcinoma in situ (DCIS or LCIS) invasive lobular cancer (ILC) lymph-vascular invasion (LVI) contralateral breast cancer history of treatment for previous breast cancer lactation or breast feeding women Paget-disease of the nipple psychiatric disorder increased radiosensitivity (e.g. collagen vascular disease)

Ages Eligible for Study
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Minimum Age: 40 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Accelerated partial breast irradiation<br>Accelerated partial breast irradiation delivered by 3 dimensional conformal radiotherapy or intensity modulated radiotherapy | Radiation: accelerated partial breast irradiation<br>* 9 x 4.1 Gy accelerated partial breast irradiation delivered by 3D-CRT or IMRT over 5 consecutive days, using twice-a-day fractionation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| late radiation side-effect | Late radiation side-effects at 5 years scored by the RTOG (Radiation Therapy Oncology Group) EORTC (European Organization for Research and Treatment of Cancer) late radiation morbidity scoring scheme | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cosmetic results | cosmetic results at 5 years measured by the Harvard criteria | 5 years | 
| local tumor control | Local tumor control defined as reappearance of the tumor in the ipsilateral breast | 5 years | 
| regional tumor control | regional tumor control at 5 years | 5 years | 
| overall survival | overall survival at 5 years | 5 years | 
| disease free survival | disease free survival at 5 years | 5 years | 
| cancer specific survival | cancer specific survival at 5 years | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, breast conserving therapy, accelerated partial breast irradiation, 3D conformal radiotherapy, intensity modulated radiotherapy