NFB-04. Evaluating focal areas of signal intensity (FASI) in children with neurofibromatosis type-1 (NF1) treated with selumetinib on PBTC-029B

Abstract

BACKGROUND: Focal Areas of Signal Intensity (FASI) are T2 hyperintense benign lesions in children with NF1. They can mimic the appearance of low-grade glioma (LGG). Selumetinib has shown efficacy in treatment of NF1-associated LGG but treatment effects on FASI have not yet been described. METHODS: Patients with NF1-associated LGG treated with selumetinib on Stratum 3 of PBTC-029B were compared to age-matched untreated children with NF1-associated LGG at Cincinnati Children’s Hospital Medical. FASI were defined by published criteria as T2 hyperintense lesions lacking mass effect, enhancement or T1 hypointensity. Lesion size was determined by cross-product of perpendicular measures in LGG and 1-3 FASI per subject. When multiple FASI were present, the sum of FASI cross-products was used. Change between baseline and the latest available measure within 4 months of control was assessed, insuring that selumetinib-treated subjects were still receiving therapy. RESULTS: Fifteen age-matched pairs were assessed (2.8-16.9 years and 60% were male). Initial FASI size was not different between groups (p=0.98; median [IQR]: 138.7mm2 [88.4-182.0] for treated subjects versus 121.6mm2 [79.6-181.9] for untreated subjects). Lesion change was measured over mean follow up of 18.9 + 5.9 months. Spider plots show decreased LGG size over time during treatment, but there was no consistent change in size among treated or untreated FASI. Comparing FASI size between paired timepoints showed no difference in change from baseline for treated subjects versus for untreated subjects (two-sided test; p=0.08). In subjects who received selumetinib, there was no correlation between change in LGG and change in FASI (r=-0.04, p=0.88). Using RANO criteria for FASI lesions, 2/30 (6.7%) subjects had partial response, 26/30 (86.7%) subjects had stable disease, and 2/30 (6.7%) subjects had progressive disease. CONCLUSIONS: While the sample size was limited, treatment with selumetinib did not reduce overall FASI size in children with NF1 and LGG.