Effects of Neoadjuvant Chemotherapy and Radiotherapy on Flap Perfusion in a Novel Mouse Model Using Standard Clinical Assessment and Near-Infrared Fluorescence Angiography

Abstract

IntoductionThe clinical management of locally advanced cancers of the head and neck pose a signifi cant therapeutic challenge [1]. Despite advances in the fi eld, including the routine use of microvascular free tissue transfers in the reconstruction of defects, fl ap failure persists as a troublesome complication 2 . The underlying factors that infl uence the development of fl ap failure are varied and complex, including comorbid systemic diseases, positive surgical margins, lymph node metastases, and prior radiotherapy and/or chemotherapy [1][2][3].Radiation and chemotherapy are often administered neoadjuvantly, or prior to surgical intervention, to gauge Abstract Purpose: Minimizing surgical morbidity after local fl ap reconstruction is important in the management of cutaneous defects. Controversy exists in current literature regarding the effects of radiation and chemotherapy on fl ap perfusion. Neoadjuvant treatments can damage the microvasculature of the surgical bed through fi brosis, endothelial cell damage, and reduced cell proliferation, which collectively increase the likelihood of postoperative fl ap failure. The aim of this study is to examine the effects of neoadjuvant radiation and chemotherapy on skin fl ap perfusion.Methods: Animals were divided into three groups: control (no treatment, n=4), radiation group (36-Gy administered to dorsal skin, n=4), and chemotherapy group (2 mg/kg IP cisplatin, n=4). Treatments were performed 15 days prior to random-pattern dorsal fl ap surgery, with a fl ap length-to-width ratio of 4:1 (4x1cm2). Flap perfusion was assessed via laser-assisted (Luna, Novadaq) indocyanine green dye angiography and standard clinical assessment. Results:Fluorescence imaging was used to quantify fl ap perfusion as a fraction of healthy skin perfusion. Chemotherapy group fl aps had poorer distal end perfusion than radiation or control group fl aps (56% vs. 69% and 71%, respectively) on post-operative day (POD) 1. Clinical assessment of fl ap perfusion by experienced surgeons on POD2 found chemotherapy group fl aps to be least viable. By POD5, 100% of chemotherapy group fl aps had experienced complete fl ap loss as measured by clinical evaluation and perfusion imaging. Conclusion:Flaps receiving neoadjuvant chemotherapy performed worse than those receiving local radiotherapy or no treatment. We demonstrate the detrimental effect of neoadjuvant chemotherapy on fl ap viability in this preclinical murine model.

Multidisciplinary Practice Variations of Anti-Thrombotic Strategies for Free Tissue Transfers

“…Thus, there is no definitive conclusion if preoperative chemotherapy and radiation are risk factors for flap viability. 12,14,[32][33][34][35][36][37][38][39][40] Surgeons may have rated radiation and chemotherapy as less of a risk factor than hematologists because they routinely use flaps in oncologic patients receiving adjuvant therapy.…”