Retrospective Multicentric Study on Non-Optic CNS Tumors in Children and Adolescents with Neurofibromatosis Type 1

Abstract

The natural history of non-optic central nervous system (CNS) tumors in neurofibromatosis type 1 (NF1) is largely unknown. Here, we describe prevalence, clinical presentation, treatment, and outcome of 49 non-optic CNS tumors observed in 35 pediatric patients (0–18 years). Patient- and tumor-related data were recorded. Overall survival (OS) and progression-free survival (PFS) were evaluated. Eighteen patients (51%) harbored an optic pathway glioma (OPG) and eight (23%) had multiple non-optic CNS lesions. The majority of lesions (37/49) were managed with a wait-and-see strategy, with one regression and five reductions observed. Twenty-one lesions (42.9%) required surgical treatment. Five-year OS was 85.3%. Twenty-four patients progressed with a 5-year PFS of 41.4%. Patients with multiple low-grade gliomas progressed earlier and had a lower 5-year PFS than those with one lesion only (14.3% vs. 57.9%), irrespective of OPG co-presence. Non-optic CNS tumors are common in young patients with NF1. Neither age and symptoms at diagnosis nor tumor location influenced time to progression in our series. Patients with multiple lesions tended to have a lower age at onset and to progress earlier, but with a good OS.

ERN GENTURIS tumour surveillance guidelines for individuals with neurofibromatosis type 1

“… 45 , 46 , 47 LGGs can be seen concurrently with OPGs in children (50%–60%). 46 , 48 As most LGGs develop in childhood, 46 , 49 adults with NF1 are more likely to develop high-grade gliomas (HGGs), and even rarely glioblastomas (GBMs) ( Table 5 ). 48 Predictors for treatment include: symptomatic tumours; thalamic, cerebellar and frontal location; multiple and diffuse lesions.…”

“… 46 , 48 As most LGGs develop in childhood, 46 , 49 adults with NF1 are more likely to develop high-grade gliomas (HGGs), and even rarely glioblastomas (GBMs) ( Table 5 ). 48 Predictors for treatment include: symptomatic tumours; thalamic, cerebellar and frontal location; multiple and diffuse lesions. 45 When feasible, complete resection of the lesion is the best therapeutic option for a symptomatic or progressive LGG ( Table 4 , Table 5 ).…”

Diencephalic Syndrome Due to Optic Pathway Gliomas in Pediatric Patients: An Italian Multicenter Study

“…During MRI surveillance, patient 8 (NF1 positive and PTPN11 mutated) developed three metachronous LGGs, one of which, in the frontal lobe, was successfully treated with LITT [17]. She was diagnosed with CPP at 3 years of age and treated with a GnRH analogue until the age of 10 years.…”

Non-Oncological Neuroradiological Manifestations in NF1 and Their Clinical Implications

“…NF1 patients are known to be prone to CNS tumor development, and the natural history of optic pathway glioma as well as non-optic tumors has been largely described in the literature [ 8 , 9 , 10 , 11 ]. Besides tumor-related manifestations, NF1 is also characterized by a wide spectrum of CNS alterations, with variable impacts on functioning and life quality, which can be observed to varying degrees in up to 70% patients [ 12 , 13 ].…”