RARE-03 CENTRAL NERVOUS SYSTEM TUMORS IN CHILDREN WITH NEUROFIBROMATOSIS TYPE 1, A COHORT FROM A NATIONAL PEDIATRIC ONCOLOGY CENTER

Abstract

Abstract Approximately 15% of the children with Neurofibromatosis type 1 (NF1) develop a central nervous system (CNS) tumor, predominantly optic pathway glioma. However, other brain tumor types are also frequent, resulting in a heterogenous population regarding tumor type, symptoms and treatment. Even though many tumors are indolent, clinical deterioration or radiological progression requires surveillance and treatment. Pediatric oncology care in the Netherlands has been centralized into the Princess Máxima Center since June 2018, providing care for the majority of Dutch NF1 CNS tumor patients. This retrospective cohort study describes the course of disease in NF1 patients with a CNS tumor diagnosed between 2005–2020, based on data from patient files. The population consisted of 95 patients (48 males), median age at diagnosis 4.3 (range 0.8–17.2) and 12.6 (range 2.9–19.9) years at follow up, 27% familiar NF1, mostly nonsense or frameshift mutations. Neurological and/or visual symptoms were present in 64 (67.4%) patients. 63.6% of the tumors was in the optic pathway, 9.1% in the cerebellum. Biopsy in 19/95 revealed 1 ependymoma and 18 low grade glioma, with rarely additional molecular changes besides NF1. Kaplan Meier median PFS was 24 months (range 3–174.5, n=65) in symptomatic presenting patients, 34 months (range 5–165, n=20) in asymptomatic patients with abnormal ophthalmological and/or neurological exam and 67.3 months (range 7–130, n=10) in asymptomatic patients without abnormalities at exam. Treatment was indicated in 53 (55.8%), predominantly chemotherapy (n=49), with substantial toxicity. Carboplatin allergy was seen in 29/44 (65.9%) patients, peripheral neuropathy in 21/46 (45.7%) patients receiving vincristine, and 5/10 patients receiving irinotecan and bevacizumab ended treatment early due to toxicity. In conclusion: analysis of our extensive cohort of NF1 patients with a CNS tumor indicates the relevance of regular screening of NF1 patients without complaints and critical surveillance and systematical documentation of treatment toxicity.