Portable tools to quantify stiffness as an outcome measure for cutaneous neurofibroma in NF1

Summary: Individuals with Neurofibromatosis Type 1 (NF1) share a clinically heterogeneous neurocutaneous disorder with >99% developing the hallmark tumor cutaneous neurofibroma (cNF). There is no effective drug therapy currently exists for cNF and mainstay treatment remains physical removal. However, clinical trials testing new drugs are ongoing, and quantitative techniques based on cNF biology are needed to measure changes in cNF following treatment. The cNF tumor bulk is composed of extracellular matrix, collagen and inflammatory cells that dictates their stiffness. No studies have reported measuring the stiffness change in neurofibromas, which would indicate shrinking of the tumor bulk. The goal of this study was to evaluate two different instruments: the Rex Gauge durometer (REX) and the Delfin SkinFibroMeter (DELFIN), in reproducibly measuring cNF stiffness. 97 neurofibromas from different skin areas of NF1 patients were measured at each of two visits about two weeks apart. The DELFIN had moderate within-tumor agreement (ICC = 0.607, 95% CI:0.512-0.691) and moderate within-visit agreement (ICC = 0.732, 95% CI:0.665-0.786), and the REX had moderate within-tumor agreement (ICC = 0.740, 95% CI:0.631-0.816) and excellent within-visit agreement (ICC = 0.937, 95% CI:0.913-0.953), while accounting for measurements clustered within a visit within a tumor within a patient. We found that both the Delfin SkinFibroMeter and the Rex Gauge Durometer are easy to use and reliable, providing consistent, objective quantification of cNF stiffness. Bahir Chamseddin², Renee McKay¹, Ruyun Jin³, Hong Zhu³, Lu Le^{1, 2} 1. Dermatology, University of Virginia School of Medicine, Charlottesville, VA, United States. 2. Dermatology, The University of Texas Southwestern Medical Center, Dallas, TX, United States. 3. Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA, United States. Clinical Research: Interventional Research