Phase IV Trial to Evaluate Breast Brachytherapy Using the Mammosite-Ml®

Study Overview
=================
Brief Summary
-----------------
This study will evaluate the local control rate, cosmetic results, and complication rates of breast brachytherapy delivered using the MammoSite-ML® when used as the sole method of radiation therapy or as a boost technique for patients with stage I-II carcinoma of the breast (< 3 cm), (non-lobular histology) treated with lumpectomy with histologically negative surgical margins by at least 2 mm, negative axillary lymph nodes, and DCIS. Hypotheses: For selected patients with stage I breast carcinoma and Ductal Carcinoma In Situ (DCIS), radiation therapy delivered with brachytherapy alone using the MammoSite-ML® is technically feasible and reproducible with acceptable complication rates. Cosmetic results after brachytherapy will be similar to that obtained after traditional whole breast external beam radiation therapy. Local tumor control rate in the breast after brachytherapy will be similar to that of conventional external beam radiation therapy, with less inconvenience and potentially less cost to the patient, given the selection criteria which minimize the risk of clinically significant multicentric or extensive residual carcinoma following lumpectomy.

Official Title
-----------------
Phase IV Trial to Evaluate Breast Brachytherapy Using the Mammosite-Ml® Radiation Therapy Delivery System as the Sole Method of Radiation Therapy or as a Boost for Early Stage Breast Cancer and Ductal Carcinoma In Situ of the Breast

Conditions
-----------------
Breast Cancer, Ductal Carcinoma in Situ

Intervention / Treatment
-----------------
* Device: Mammosite ML
* Device: Mammosite ML


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women,age of at least 45 years Zubrod performance status of 0-2 AJCC Stage I-II (T1-T2, N0 M0) breast cancer Maximum tumor dimension < 3 cm Invasive ductal, medullary, papillary, tubular, colloid (mucinous) histologies Unifocal breast cancer Unilateral breast cancer (no synchronous or previous contralateral breast cancer) Lumpectomy with negative surgical margins by at least 2 mm or re-excision specimen with negative surgical margins by at least 2 mm Ductal Carcinoma In-Situ Negative axillary lymph nodes for invasive breast cancer (sentinel node biopsy or standard level I-II dissection with > 6 nodes removed) Time interval from final breast surgery to brachytherapy loading less than 8 weeks At least 2 mm of breast tissue between the skin and the MammoSite® balloon surface(prefer > 5 mm) If chemotherapy is planned, it must begin no earlier that 2 weeks following completion of radiation therapy. If chemotherapy is first, a minimum of 2 weeks from the last cycle must elapse prior to the start of radiation therapy. Signed study-specific consent form Exclusion Criteria: Invasive lobular histology Non-epithelial breast malignancies such as sarcoma or lymphoma Multifocal or multicentric invasive carcinoma Extensive intraductal component (EIC) Paget's disease of the nipple Skin involvement by tumor, regardless of tumor size Positive axillary lymph nodes Distant metastases Collagen vascular disease (scleroderma) Pregnant or lactating women, due to potential exposure of the fetus to RT and unknown effects of RT on lactating females (negative pregnancy test for women of child-bearing age) Any previously treated or synchronous contralateral breast carcinoma Patients with psychiatric or addictive disorder that would preclude obtaining informed Consent Men

Ages Eligible for Study
-----------------
Minimum Age: 45 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sole method<br>patients will be treated with HDR brachytherapy using Mammosite ML as the sole method for radiation delivery after lumpectomy for breast cancer or DCIS | Device: Mammosite ML<br>* 34 Gy / 10 fractions (3.4 Gy per fraction) 2 fractions / day (separated by at least 6 hours) Delivered in 5 consecutive working days<br>* Other names: HDR Brachytherapy;|
| Experimental: Boost<br>patients will be treated with HDR brachytherapy using Mammosite ML as a boost technique prior to standard external beam radiation after lumpectomy for breast cancer or DCIS | Device: Mammosite ML<br>* 5-10.2 Gy / 2-3 fractions (3.4 Gy per fraction) 2 fractions / day (separated by at least 6 hours) Delivered in 1-2 days Followed by whole breast radiation (25-28 daily tx)<br>* Other names: HDR Brachytherapy;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ipsilateral Recurrence Rate | Local recurrence is defined as either invasive or non-invasive breast cancer recurrence within the target volume. Elsewhere recurrence is defined as either invasive or non-invasive breast cancer recurrence outside of the target volume. Local control rate will be evaluated by imaging techniques, physical exam and biopsy, if applicable. Measured as a count of participants experiencing recurrence, i.e. each subject experiencing ipsilateral tumor recurrence within 5 years = 1, and each subject with no ipsilateral tumor recurrence within 5 years = 0 | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cosmetic Results | Evaluation of cosmetic results as judged by the patient, surgeon, and radiation oncologist at stated follow up intervals. Serial photographs will be obtained. The cosmetic results will be assessed using the four category Harvard Scale definitions: Excellent - The treated breast looks essentially the same as the opposite breast Good - Minimal but identifiable effects of radiation on the treated breast Fair - Significant effects of radiation on the treated breast Poor - Severe normal tissue sequelae secondary to irradiation | 6 months after treatment, then annually for 5 years | 
| Toxicity Measured Through Adverse Event Incidence | The incidence of serious adverse events will be calculated. Adverse events reviewed for device harm/toxicity include skin redness, breast pain, infections, breast swelling, and rib fractures. | during therapy, 6 weeks after completion of therapy, and additionally as needed |