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Amifostine Reduces Radiation-Induced Complications in a Murine Model of Expander-Based Breast Reconstruction
Peter A. Felice, M.D., M.S., Noah S. Nelson, B.S., Erin E. Page, B.S., Sagar S. Deshpande, B.S., Alexis Donneys, M.D., M.S., José Rodriguez, M.D., Steven R. Buchman, M.D..
University of Michigan Medical School, Ann Arbor, MI, USA.
Immediate expander-based breast reconstruction is a prevalent option for many women after mastectomy. For patients undergoing treatment regimens requiring adjuvant radiation, however, complication rates as high as 60% have been reported and often preclude the use of this reconstructive technique. Amifostine is a cytoprotectant on formulary for prophylaxis against radiation-induced mucositis and xerostomia. We hypothesize that this protective capacity of Amifostine can be extended to reduce radiation-induced soft tissue complications in the breast, thus promoting expander-based reconstructive options for women battling this devastating disease.
56 Sprague Dawley rats were divided into two experimental groups, Operative Expander Placement (Expander) and Operative Sham (Sham). Expander specimens underwent placement of a sub-latissimus tissue expander and subsequent expansion to a 15cc fill volume, while Sham specimens underwent identical operative intervention without expander placement. Each experimental group was further divided into three subgroups; Control specimens received no further intervention, XRT specimens received a human-equivalent dose of radiation alone, and AMF-XRT specimens received both Amifostine pre-treatment and a human-equivalent dose of radiation. Animals then underwent a 45-day recovery period, during which interval photo documentation, clinical examination, and ImageJ analysis were used to evaluate for surgical site complications.
In the Sham group, 0 of 10 Control specimens, 0 of 10 XRT specimens, and 0 of 10 AMF-XRT specimens showed signs of skin or soft tissue complication. For the Expander animals, AMF-XRT specimens (4 of 13, 30%) demonstrated significantly fewer substantial gross skin and soft tissue complications compared to XRT specimens (9 of 13, 69%; p = 0.041) (Figure). ImageJ evaluation also demonstrated a significant difference for mean percentage of necrosis for XRT specimens at 12.94%, compared with 6.96% of Amifostine pre-treated animals (p = 0.019). The lack of complications demonstrated in Sham specimens is noteworthy in that expansion, radiation administration, and prophylactic Amifostine administration were thus isolated as the main determinants of complication and remediation. An Expander Control group was not included in this study, as it would not serve to answer our hypothesis with respect to radiation and Amifostine pre-treatment administration.
In the Expander specimens, Amifostine pre-treatment significantly reduced skin and soft-tissue complications from 69% to 30%. ImageJ analysis also demonstrated a significantly reduced rate of necrosis by almost 50% in Expander AMF-XRT specimens compared with Expander XRT specimens. Since no complications were seen in Sham specimens, we concluded that the operative procedure itself was not responsible for skin and soft tissue injury. These findings demonstrate that Amifostine prophylaxis provides substantial and significant protection against radiation-induced skin and soft tissue injury in a murine model of expander-based breast reconstruction. 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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