Regenerative Tissue Matrix for Breast Reconstruction
Condition: Breast Cancer
Study type: Interventional

Summary: 
      The purpose of this study is to evaluate the role of Alloderm tissue regenerative matrix used
      in many breast reconstruction operations. When this material is used in the abdomen it often
      stretches and sometimes needs to be replaced. Although we see good clinical results when used
      for breast reconstruction, there is no research regarding if or how the material changes in
      this location. The Alloderm is placed in the breast at the time the expander is placed,
      post-mastectomy. The expansion is started at the time of surgery and completed during a
      series of office visit. This process stretches the skin, underlying muscle and presumably the
      Alloderm. The goal of this study is to better understand the natural history of this material
      when used for breast reconstruction.

      Our objective is to measure changes in the dimension of the tissue matrix material after it
      has been placed in the breast. These objective findings will be supplemented with a patient
      questionnaire specifically designed for breast surgery patients.

      All patients will receive the standard preoperative work up, intraoperative procedures, and
      postoperative care indicated for patients undergoing implant breast reconstruction after
      mastectomy. Some of these patients will require use of the Alloderm to reconstruct the lower
      half of the breast pocket. This is already being done by plastic surgeons here at Henry Ford
      Hospital. The difference will be that the Alloderm tissue matrix used to reconstruct the
      lower part of the breast pocket for the study patients will have 4 millimeter metallic clips
      placed in it. Postoperatively these clips will be tracked by ultrasound done in the clinic.
      As the breast implant is normally expanded by adding saline, we believe the Alloderm matrix
      will stretch. The movement of these imperceptible clips will be tracked and measured to map
      the expansion of the matrix in response to the underlying implant stretching the overlying
      breast pocket and the skin envelope. The pattern of expansion will allow us to develop a
      mathematical model to describe the stretch pattern of Alloderm matrix used in breast
      reconstruction. This information will be supplemented with a validated questionnaire
      specifically designed by breast surgery patients. This will give us both an objective
      dimensional change in the breast reconstruction as well as a patient-centered evaluation of
      the reconstruction process.
    

Detailed description: 
      1. Describe the experimental design/methodology.Prospective consecutive case series.

        2. Outline the protocol, corresponding it to the specific aims; identify the data or
           endpoints to be analyzed to reach the specific aims.

             1. The first 3 candidates will serve as the prototypes for the model. There may be
                some unanticipated modifications to the setup, patient care, imaging or data
                analysis. We plan to follow these 3 cases more deliberately and not proceed until
                all 3 are followed for at least 3 months. After these 3 cases, we anticipate the
                rest will proceed more smoothly. Placement of the clips to provide the most data is
                the primary question for these 3 cases.

                The above schematic shows the presumed change is Alloderm size and shape post
                expansion and corresponding change in location of the vessel clips. The inferior
                borders is the fixed point. By positioning the clips at regular intervals along the
                top border, we can measure transverse and horizontal changes. The timing of
                ultrasound studies is designed to coincide with when these changes are most likely
                to be visualized during the postoperative period. We may change the dates of the
                studies. We do not anticipate the the total number of studies will increase because
                changes after full expansion (completed by postoperative week 4) are slower and
                smaller in magnitude.

             2. 30 patients enrolled in the study will be studied for position of the metallic
                markers on postoperative day 1, week 4, month 6, month 12. The location of each
                clip relative to the fixed anchor point will be recorded and each timepoint. The
                fixed anchor point is the medial-inner attachment point of the Alloderm® to the
                chest wall fascia. This is the most inferior/medial point of the Alloderm® tissue
                matrix. With expansion of the breast expander the chest wall fascia does not move.
                Only the overlying skin, pectoralis muscle and Alloderm stretch in response to
                breast prosthesis expansion. We can therefore track movement of the clips embedded
                in the matrix over time. For each clip we can develop a best fit curve for the 30
                subjects studied. This will allow us to develop a mathematical model of the final
                position and shape of the reconstructed breast at one year out. This model will be
                compared to existing mathematical models for breast tissue expanders (Mentor Corp.

             3. A standardized validated questionnaire Breast-Q is a patient reported outcomes data
                instrument. The Breast-Q is conceptually grounded in patient perceptions, able to
                span the continuum of impact of surgery or validated against appropriate
                psychometric benchmarks. It allows for quantification of patient satisfaction and
                health-related quality of life experienced by women undergoing breast surgery. The
                questionnaire will be administered preoperative, one month postoperative and one
                year postoperative.

           The BREAST-Q scoring software, QScore, gives clinicians and researchers a simple and
           accurate way to analyze their data. It features a powerful scoring engine based on RUMM
           2020; a data analyzing program developed by Rasch Unidimensional Measurement Models
           Laboratory in Perth, Australia.

           Each pre and postoperative BREAST-Q module comes with a Microsoft Excel template. The
           templates help to organize your data for import into the QScore program. Once imported,
           QScore automatically transforms your raw data into summary scores ranging from 0 (very
           dissatisfied) to 100 (very satisfied) for each scale.

        3. Discuss potential limitations and difficulties in the protocol. Potential limitations
           include displacement of the vessel clips. If this happens, the patient's results and
           aesthetic outcome are not compromised. The clips do not cause any harm. These patients
           will be followed by standard of care protocol but removed from the study.

        4. Provide a tentative schedule for conducting and completing this project and, if
           applicable, the multicenter study.

           The patients will be seen in the office at study enrollment and post surgery at one
           week, one month, six months and one years for evaluation ultrasound study. The Breast Q
           questionnaire will be completed preoperatively and then after surgery at one month and
           one year. one month and one year post surgery. We anticipated all patients enrolled
           within 6 months of study initiation. Total project should less than 2 years after last
           patient enrolled.

        5. Data collection: Submit a copy of the data collection tool or list the data fields to be
           collected (review IRB policy, Access to Medical Records for Research on intranet at
           http://henry.hfhs.org).

      Data entry points that will be collected include: The patient's name, age, history of steroid
      use, past medical history, date of surgery, size of graft used, thickness of the graft used.
      Also implant size, pre-surgery bra size, distance from each clip to inferiolateral anchor
      point on ultrasound.

      7. DATA ANALYSIS: Describe the analysis of the data and relate this to the specific aims.
      Describe the statistical analysis in detail (referral to analysis by a multicenter sponsor is
      not acceptable). The Committee recommends free consultation with the Division of
      Biostatistics and Research Epidemiology.

      There are two types of outcome measurements: the alloderm increased size and stardardized
      validated questionnaire. We will compare the difference between baseline and each time point
      after implant. For the alloderm increased size, the student paired-t statistic wil be used to
      test if there is any stretch in size. For questionnaire outcome, one-sample wilcoxon rank sum
      test will be used to test the difference in patient satisfication. Bonferrnoi correction is
      used for multiple comparison and the familywise type I error rate is set at 0.05.
    

Intervention name(s): 5 mm vessel clips
Intervention type(s): Other
Intervention description(s): evenly placed vessel clips placed at surgery and tracked by ultrasound
Other intervention name(s): Alloderm; acellular regenerative tissue matrix
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: breast reconstruction; tissue expander; Alloderm; tissue matrix