Systematically Assessing Changes in Plexiform Neurofibroma Related Disfigurement From Photographs of Subjects With Neurofibromatosis Type 1 on a Phase 2 Clinical Trial

Background: Up to 50% of subjects with Neurofibromatosis Type 1 (NF1) will develop histologically benign plexiform neurofibromas (PN). One of the most common morbidities associated with PN is a disfigurement that has the potential to pose formidable obstacles to the medical and psychosocial well-being of subjects with NF1. The phase 2 trial of the MEK inhibitor selumetinib for inoperable PN (NCT01362803) have shown volumetric shrinkage of PN in approximately 74% of subjects with at least one PN morbidity, with most of the responsive tumors decreasing in size by 20-50% volume from baseline. Both trials have completed enrollment and primary study objectives. In this selumetinib trial, standardized photography of visible PN was performed over time to assess for changes in disfigurement over time. This trial did not include criteria to measure changes in disfigurement and no validated criteria for measurement of PN-related disfigurement exist. We developed a scale to rate the extent of a disfigurement from NF1 PN and will apply this scale to photographs obtained on the phase II selumetinib trial. Objective: To determine if selumetinib treatment is associated with improvement in PN-related disfigurement, as determined by raters reviewing photographs before treatment and just prior to cycle 13 of treatment. Eligibility: Four groups of adult raters to rate disfigurement who are not directly involved in the conduct of the selumetinib treatment study (NCT01362803), who are not NIH employees, and can read and write in English. Design: -Methods Photographs of consenting individuals with PN, who may or may not have received selumetinib will be reviewed. Raters will be presented pre and post treatment photographs of persons who received selumetinib as well as control photographs of persons not receiving selumetinib. Each rater is presented with the same set of photographs though placement and order may differ. Each rater will look at photographs of each individual with PN for at least 10 seconds, then with photos still visible, raters will verbally answer a questionnaire. The rater will be asked questions at the end of the session to assess the feasibility of the questionnaire. Session will be repeated by some raters approximately six months later on a subset of the photographs. -Statistical Analysis In each cohort of raters, for each subject s slide set evaluated at a time point, the mean of the raters scores for each subject will be formed. For each person with PN that received selumetinib, the paired difference between baseline and pre-cycle 13 of these mean scores will be determined. For the full set of approximately 35 paired scores, the difference will be assessed for statistical importance by means of a paired t-test, or a Wilcoxon signed rank test.