Plastic Surgery Research Council

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Successful Reduction of Radiation Associated Skin Injury Utilizing Topical DFO in a Murine Breast Reconstruction Model
Alicia Snider, MD1, Alexis Donneys, MD2, Noah Nelson, MS3, Russell Ettinger, MD2, Kavitha Ranganathan, MD2, Jeremy Lynn, BS2, Daniel Fergle, BS2, Mark Banazak Holl, PhD2, Geoffrey Guertner, MD4, Steven Buchman, MD2.
1University of South Carolina, Columbia, SC, USA, 2University of Michigan, Ann Arbor, MI, USA, 3University of South Carolina, Ann Arbor, MI, USA, 4Stanford University, Stanford, CA, USA.

Successful Reduction of Radiation Associated Skin Injury Utilizing Topical DFO in a Murine Breast Reconstruction Model
Alicia Snider, MD; Alexis Donneys, MD; Noah Nelson, BS; Kavitha Ranganathan, MD; Jeremy Lynn, BS; Daniel Fergel; Mark Banaszak Holl, PhD; Geoffrey Gurtner, MD, Steven Buchman, MD
Background: Breast cancer is the most common cancer in the US, and the most prevalent treatment algorithm partner's surgery with adjuvant radiation (XRT). Despite the many oncologic benefits of XRT, it has detrimental effects on the normal surrounding tissues leading to prohibitive complications which limit candidacy for expander-based reconstruction. In order to mitigate the pernicious effects of radiation, we posited that the use of topical deferoxamine (DFO) would reduce cutaneous injury, boost post-XRT skin healing, and improve dermal type I collagen organization.
Methods: Female Sprague-Dawley rats (n=15) were divided into 3 groups (n= 5 per group): 1) Expander placement (Control); 2) Expander placement + XRT (XRT); 3) Expander + XRT+ DFO patch (DFO). Expanders were surgically placed in a sub-musculocutaneous plane in the right upper back with a subsequent 15 cc fill volume. Control specimens received no additional intervention, XRT group received a breast cancer human-equivalent dose of radiation, and the DFO group had topical application of DFO for a total of 10 days following XRT. After a 20 day recovery period an Image J analysis was utilized to quantify skin ulceration Atomic force microscopy (AFM) was used on tissue sections to identify dermal type I collagen organizational structure.
Results: Image J evaluation of the XRT group demonstrated a significant increase in skin ulceration when compared to the Control group (p=0.001). Post-radiation treatment with DFO patch application was associated with improved healing outcomes with a significant reduction in ulceration when compared to the XRT group (p=0.002). SPM images of the XRT group exhibited a significant increase in collagen fibril disorganization when compared to Control (p=0.001) and DFO (p=0.000). There were no statistical differences between Control and DFO groups as both had a greater percentage of more parallel, organized collagen sheets.
Conclusions: Topical DFO mitigated cutaneous injury and boosted post-XRT skin healing as demonstrated by a significant reduction in skin ulceration and a significant improvement in type I collagen fibril organization in a murine model of expander based breast reconstruction. If these exciting findings can be extended into the clinical realm then utilizing DFO to reduce radiation skin injury holds the promise of increasing the number of reconstructive candidates, improving surgical outcomes, and dramatically improving quality of life for this nation's largest cancer population.


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