Clinical predictors and risk of optic pathway glioma (OPG) in Neurofibromatosis-1 (NF-1)

Abstract

9016 Background: NF-1 is a progressive disease with wide spectrum of phenotype and unpredictability in clinical course. NF-1 patients are at significantly increased risk for development of a variety of neoplasms that cause morbidity and limited mortality, including OPG. There are limited data identifying risk factors predictive of subsequent OPG development. Objective: To identify key early clinical features which predict subsequent risk for development of OPG. Methods: Case-control study of NF-1 patients with and without OPG from Cincinnati Children’s Hospital NF-1 and Cancer Registries. Predictor variables were clinical risk factors (age at diagnosis of NF-1, race/ethnicity, gender, and history of familial NF-1, macrocephaly, plexiform neurofibroma, developmental delay, seizure disorder,), and the dependent variable was development of OPG by imaging. Patients received screening head MRI at the time of presentation with NF-1. Odds ratios (O.R.) were calculated with 75 cases (NF-1 and OPG) and 215 controls (NF-1 only) and statistically/clinically significant factors were further analyzed by logistic regression method. Results: Prevalence of OPG in NF-1 was 15.6%. Almost half had familial NF-1. Median age at diagnosis of NF-1 was 1.6 yrs (cases) and 2.4 yrs (controls). OPG was diagnosed at median age 4 yrs. Patients with T2 hyperintense lesions on imaging (UBOs) and age 4 years or less at diagnosis of NF-1 were at significantly increased risk of developing OPG (O.R=3.1, p=0.006 and O.R=3.1, p=0.002 respectively). In addition, presence of seizure disorder and developmental delay were borderline significant (O.R=2.8, p=0.07 and O.R=1.7, p=0.04 respectively). Race (Caucasian) appeared to have disease modifying effect on development and progression of OPG. Conclusions: Patients with T2 lesions on presentation MRI, developmental delay, seizures, and age 4 years or less at NF-1 diagnosis appear to be at an increased risk of developing OPG. Caucasian race appears to have a modifying effect on disease progression. Patients with these risk factors may be stratified as “high risk” and may benefit from close surveillance for early detection of OPG. The association of developmental delay and seizures may suggest a pathophysiologic relationship. No significant financial relationships to disclose.