A multi-institutional study of brainstem gliomas in children with neurofibromatosis type 1

Abstract

Objective: To define the clinical and radiologic features of brainstem gliomas (BSGs) in children with neurofibromatosis type 1 (NF1).

Methods: We performed a retrospective cross-sectional study of 133 children with NF1 and concurrent BSGs cared for at 4 NF1 referral centers. BSG was determined using radiographic criteria. Age at diagnosis, tumor location and appearance, clinical symptoms, treatment, and presence of a concurrent optic pathway glioma were assessed.

Results: The average age at BSG diagnosis was 7.2 years, and tumors occurred most often in the midbrain and medulla (66%). The majority of children with NF1-BSGs were asymptomatic (54%) and were not treated (88%). Only 9 of the 72 asymptomatic children received treatment because of progressive tumor enlargement. In contrast, 61 children presented with clinical signs/symptoms attributable to their BSG; these individuals were older and more often had focal lesions. Thirty-one patients underwent treatment for their tumor, and 14 received CSF diversion only. Progression-free survival was ∼3 years shorter for children receiving tumor-directed therapy relative to those who had either no treatment or CSF diversion only. Overall survival was 85% for the tumor-directed therapy group, whereas no deaths were reported in the untreated or CSF diversion groups.

Conclusions: Unlike children with sporadically occurring BSGs, most children with NF1-BSGs were asymptomatic, and few individuals died from complications of their tumor. Those requiring tumor-directed treatment tended to be older children with focal lesions, and had clinically more aggressive disease relative to those who were not treated or underwent CSF diversion only.

Figure 1. Age distribution of individuals with neurofibromatosis type 1 (NF1) presenting with brainstem glioma (BSG)

The number of individuals with NF1-BSG is represented as a function of age (years).

Figure 2. Location of brainstem gliomas in individuals with neurofibromatosis type 1

The number and percentage of tumors arising in specific locations within the brainstem.

Figure 3. Progression-free survival (PFS)

(A) All participants (n = 133): PFS was reduced for children with neurofibromatosis type 1 (NF1)–brainstem glioma (BSG) who received tumor-directed therapy (red line; n = 40; 41.33 ± 7.51 months) relative to those who received no treatment or underwent CSF diversion only (black line; n = 93; 76.69 ± 6.07 months); p = 0.01. (B) Symptomatic participants (n = 31): PFS was reduced for symptomatic children with NF1-BSG who received tumor-directed therapy (red line; n = 31; 45.68 ± 8.76 months) relative to those who received no treatment or underwent CSF diversion (black line; n = 30; 78.29 ± 12.84 months); p = 0.02.