Intensity Modulated Radiotherapy (IMRT) vs. 3D-conformal Accelerated Partial Breast Irradiation (APBI) for Early Stage Breast Cancer After Lumpectomy

Study Overview
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Brief Summary
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In the setting of radiotherapy as part of breast-conservation therapy for patients with early stage breast cancer, the novel planning and delivery method of intensity modulated radiotherapy is an effective and safe alternative to the commonly-used standard 3D-conformal external beam radiotherapy, spares more normal breast and lung tissue, and may lead to improved clinical outcomes.

Official Title
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A Phase III Randomized Study Comparing Intensity Modulated Planning Versus 3-Dimensional Planning for Accelerated Partial Breast Radiotherapy

Conditions
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Breast Cancer

Intervention / Treatment
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* Radiation: accelerated partial breast irradiation - 3D-conformal planning
* Radiation: accelerated partial breast irradiation - IMRT planning


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed disease (AJC Classification): Tis, T1, T2 (≤ 3.0 cm), N0, M0. Microscopic multifocal disease is only allowed when the entire span of identified disease measures 3.0 cm or less. Negative surgical margins ( ≥ 0.2 cm) after final surgery. Subjects with infiltrating lobular histologies or high nuclear grade DCIS will be required to have breast MRI scanning as part of the initial staging to verify localized disease. Subjects with DCIS will be included in the study only if they had an MRI prior to lumpectomy. Findings on MRI scanning revealing relevant suspicion of disease outside of planned lumpectomy volume should be further evaluated by ultrasound and, if necessary biopsy, to exclude multicentric/multifocal disease. Subjects with malignant calcifications on mammography will be required to have repeat mammography after surgery to ensure removal of all malignant calcifications. Willing to complete additional screening requirements and meet eligibility criteria as defined in protocol Sec. 4.4. Successful placement of fiducial markers for IGRT requiring nonmigrating fiducials. PTV to ipsilateral breast ratio (IBR) ≤ 25 %. Radiotherapy anticipated to begin within 10 weeks of lumpectomy or re-excision of margins. Exclusion Criteria: Pregnancy or breast-feeding. Have collagen-vascular disease. Inadequate surgical margins ( < 0.2 cm) after final surgery. Subjects with persistent malignant/suspicious micro-calcifications. Gross multifocal disease and microscopic disease greater than 3.0 cm.

Ages Eligible for Study
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Minimum Age: 40 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IMRT<br>Intensity modulated radiotherapy, 38.5 Gy, 10 fractions over 5 days | Radiation: accelerated partial breast irradiation - IMRT planning<br>* 38.5 Gy, 10 fractions over 5 days<br>* Other names: EBRT;|
| Active Comparator: 3D-CRT<br>Three dimensional conformal external radiotherapy, 38.5 Gy, 10 fractions over 5 days | Radiation: accelerated partial breast irradiation - 3D-conformal planning<br>* 38.5 Gy, 10 fractions over 5 days<br>* Other names: EBRT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of breast pain after Accelerated Partial Breast Radiotherapy (APBI) | Assessment by both treating investigators and by subjective patient outcomes questionnaires filled out at each follow-up visit | 5 years | 
| Prevalence of chest wall pain after Accelerated Partial Breast Radiotherapy (APBI) | Assessment by both treating investigators and by subjective patient outcomes questionnaires filled out at each follow-up visit | 2-5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dosimetric comparison | Comparison of treatment plans and actual doses received between comparable patients treated with 3D-CRT and IMRT with regard to treatment target and normal tissue | 5-10 days | 
| Acute skin reactions | Radiation-induced dermatitis | 6 months | 
| Cosmetic outcomes after APBI | Assesed by both treating investigators and subjective patient questionnaires filled out at each follow-up visit | 2-5 years | 
| Ipsilateral breast event | Track occurrence and patterns of local treatment failures or new primaries within the treated breast (efficacy outcome measure) | 5-15 years | 
| Cause specific survival | Track survival status and the specific cause(s) of death if applicable for study participants (efficacy outcome measure) | 5-15 years | 
| Disease free survival | Track breast-cancer free survival status of study participants (efficacy outcome measure) | 5-15 years | 
| Overall survival | Track the overall survival status of all study participants (efficacy outcome measure) | 5-15 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast-conservation, adjuvant radiotherapy, breast cancer, early-stage breast cancer, DCIS, lumpectomy, accelerated partial breast irradiation, APBI, three dimensional conformal external radiotherapy, intensity modulated radiotherapy, 3D CRT, IMRT