Targeted Intra-Operative Radiotherapy for the Management of Ductal Carcinoma In-Situ of the Breast

Study Overview
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Brief Summary
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We hypothesize that the combination of mammography and CE-MRI will improve the surgeon and radiologist's ability to define extent of disease prior to surgical resection, improve the odds of obtaining clear surgical margins, and increase the efficacy of IORT delivered immediately after initial surgical resection. In this investigation, we will determine whether or not patients deemed eligible for 'immediate IORT based on mammography and CE-MRI can be successfully treated without the need for re-excision or additional radiotherapy due to inadequate surgical margins.

Official Title
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Targeted Intra-Operative Radiotherapy for the Management of Ductal Carcinoma In-Situ of the Breast (TARGIT-DCIS Trial): Use of Mammography and Breast MRI to Identify Candidates for IORT.

Conditions
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Breast Cancer

Intervention / Treatment
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* Radiation: Intraoperative radiotherapy
* Device: Intraoperative radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with biopsy-proven DCIS, mammographic and CE-MRI evidence of DCIS measuring great then equal to 4cm, and a desire to receive breast conserving therapy, will be considered for participation in this study. Patient history, physical examination findings, and demographics (sex, age, height, weight, bra size, etc.) will be performed and documented. Inclusion Criteria for Initial Registration (all patients cohorts): All cohorts Signed informed consent and HIPAA documents Female sex Age great then equal to 40 years Localized ductal carcinoma in situ Clinically and/or histologically negative axillary lymph nodes No imaging or clinical findings suggestive of invasive carcinoma. Cohort 1 (Immediate IORT group) Localized DCIS measuring less then equal to 4 cm on preoperative imaging. Cohort 2 (Delayed IORT group) Localized DCIS measuring less then equal to4 cm or less on surgical pathology Delayed IORT could be performed for the explicit purpose of administering IORT or performed following re-excision of a previously operated breast to achieve clear surgical margins. This cohort includes patients who were excluded from immediate IORT based on pre-operative imaging suggesting ineligibility for immediate IORT, but who are subsequently found to meet histological criteria (localized DCIS less then equal to 4 cm and no invasive cancer) for IORT based on surgical pathology. Unifocal microinvasive (T1mic or invasive focus less then equal to 1mm in maximal diameter) is allowed following initial WLE if surgical pathology margins were less then equal to2 mm for both the invasive and non-invasive components. Delayed IORT must be performed within 3 months of initial WLE. Cohort 3 Subjects who received IORT at the time of initial WLE but whose surgical pathology showed them to be unsuitable candidates for IORT alone on the basis of: DCIS measuring greater than 5 cm on surgical pathology. T1a (less than 1 mm) or larger invasive carcinoma associated with extensive DCIS. Surgical margins width less than1 mm. Exclusion Criteria: Male sex Age less than 40 DCIS associated with any evidence of microinvasion or invasive carcinoma on pre-operative imaging or core biopsy of the breast or axillary nodes. DCIS that is multicentric in the ipsilateral breast. Multicentricity will be defined at 2 or more lesions separated by more than 3 cm in the same breast. Non-epithelial breast malignancies such as sarcoma or lymphoma DCIS associated with diffuse suspicious or indeterminate microcalcifications Pregnancy or lactation Collagen vascular diseases, including Systemic lupus erythematosus, Systemic sclerosis (scleroderma), CREST Syndrome (calcinosis, Raynaud phenomenon, esophageal dysfunction, sclerodactyly, telangiectasia, and the presence of anticentromere antibodies), polymyositis, dermatomyositis with a CPK level above normal or with an active skin rash, inclusion-body myositis, or amyloidosis Serious psychiatric or addictive disorders

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 |
| --- | --- |
| Other: 1<br>Patients will receive IORT | Radiation: Intraoperative radiotherapy<br>* 20Gy to surface of tumor bed and 5Gy at depth of 1cm from surface of tumor bed<br>* Other names: Intrabeam Photon Radiosurgery System and Applicators;Device: Intraoperative radiotherapy<br>* 20gy to tumor bed, 5gy at depth of 1cm from surface of tumor bed<br>* Other names: Intrabeam Photon Radiosurgery;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility. The primary efficacy endpoint will be reoperation (re-excision or mastectomy) rates following WLE or IORT |  | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety endpoints: The overall serious adverse event rate will be assessed for all patients at stated follow-up periods. Complications associated with each of the following setting will be documented and reported separately |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DCIS, To evaluate Preoperative mammagraphy and MRI to select candiates with DCIS for IORT