|Program and Abstracts
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Amifostine Prophylaxis Ameliorates Radiation-induced Injury In A Murine Model Of Expander-based Breast Reconstruction
Yekaterina Polyatskaya, MD, Noah S. Nelson, BS, Jose J. Rodriguez, MD, Alexander R. Zheutlin, BS, Sagar S. Deshpande, BS, Peter A. Felice, MD, Alexis Donneys, MD, MS, Steven R. Buchman, MD.
University of Michigan, Ann Arbor, MI, USA.
AMIFOSTINE PROPHYLAXIS AMELIORATES RADIATION-INDUCED INJURY IN A MURINE MODEL OF EXPANDER-BASED BREAST RECONSTRUCTION
Polyatskaya Y, Nelson NS, Rodriguez JJ, Zheutlin AR,
Deshpande SS, Felice PA, Donneys A, Buchman SR
Purpose: Although expander-based breast reconstruction is the most commonly used method of reconstruction worldwide, it continues to be plagued with complication rates as high as 60% when adjuvant radiotherapy is implemented. One of the key ways that radiation exerts its damage is by induction of vascular and inflammatory changes in the soft tissue. Amifostine is the most widely cited cytoprotectant currently on formulary for prophylaxis against radiation-induced mucositis and xerostomia. We hypothesized that quantitative measures of radiotherapy-induced vascular injury can be mitigated by utilizing Amifostine prophylaxis in this clinically relevant murine model of expander-based breast reconstruction.
Methods: 30 Sprague Dawley rats were divided into three experimental groups: expander placement (Control), expander placement followed by radiotherapy (XRT), and expander placement followed by radiotherapy with amifostine prophylaxis (AMF/XRT). All groups underwent placement of a sub-latissimus tissue expander and subsequent expansion to a 15cc fill volume. The Control group underwent no further intervention. The two groups receiving radiotherapy were administered a fractionated dose of radiation of 28Gy over 5 days, equivalent to a human dose of 50-60Gy used in breast cancer patients. Animals then underwent a 45-day recovery period. All groups underwent vascular perfusions with Microfil following the recovery period. The specimens were analyzed with micro-CT. Analysis of the microvasculature was performed using qualifying and quantitative radiomorphometrics.
Results: Micro-CT analysis was used to calculate vessel volume fraction (VVF), vessel number (VN), and vessel separation (VSp). A significant increase in VN was seen in the XRT group as compared to the Control group (p=0.021) and the AMF/XRT group (p=0.027). There was no significant difference between the Control and AMF/XRT (p=0.862). VVF was significantly higher in the XRT group than either the Control group (p=0.043) and AMF/XRT group (p=0.040), however no significant difference was seen between the Control and AMF/XRT groups (p=0.980). VSp of XRT group was smaller when compared to both the Control and AMF/XRT specimens (p=0.05 and p=0.048, respectively), and no difference was seen between the Control and AMF/XRT groups (p=0.339).
Conclusions: In this study, amifostine administered prior to radiotherapy preserved vascular metrics similar to those of non-radiated specimens. Elevated vascularity demonstrated within the XRT group was not seen in either the Control or AMF/XRT groups. These results indicate that amifostine prophylaxis protects soft tissue in a murine model of expander-based breast reconstruction from inflammatory-induced pathologic vascular response initiated by radiation. These findings also demonstrate the capacity of Amifostine as a protective therapeutic which can potentially be utilized for women undergoing radiotherapy. Our hope is to translate our findings from the bench to the bedside in an attempt to decrease the overall morbidity of breast reconstruction and increase the number of restorative treatment options available for women afflicted with breast cancer.
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