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. Neurofibromatosis type 1 (NF1) is a common cancer predisposition syndrome in which affected children and adults develop benign and malignant nervous system tumors.1 WHO grade I gliomas (pilocytic astrocytomas [PAs]), including those involving the optic pathway and brainstem, predominate in children with NF1. Optic pathway gliomas (OPGs), the most frequently encountered of these low-grade gliomas, are seen in 15%-20% of children with NF1. These tumors typically come to medical attention in young preschool children (mean age, 4.5 years) who present with reduced visual acuity or precocious puberty, or who are incidentally discovered on screening neuroimaging. 2,3While OPGs represent 66%-75% of all CNS tumors in children with NF1, 4 the second most common brain tumor is the brainstem glioma (BSG), representing approximately 18% of NF1-associated brain neoplasms.4,5 Unlike NF1-OPG, NF1-BSGs tend to arise at a slightly older ageFrom the

Neurofibromatosis 1 French national guidelines based on an extensive literature review since 1966

“…The second most frequently encountered brain tumor in individuals with NF1 is the BSG [240]. These are indolent tumors that arise in slightly older children and are often discovered incidentally on neuroimaging studies [241][242][243]. Similar to OPGs, these tumors are usually pilocytic astrocytomas.…”

“…Similar to OPGs, these tumors are usually pilocytic astrocytomas. They might come to medical attention with headache, nausea, vomiting, cranial neuropathies, and ataxia [241]. Observation is recommended for asymptomatic children.…”

“…Observation is recommended for asymptomatic children. These tumors might cause obstructive hydrocephalus requiring ventriculoperitoneal shunt placement or an endoscopic ventriculostomy [241]. Treatment with carboplatin and vincristine chemotherapy is reserved for those with progressive or worsening symptoms [139].…”

Neurofibromatosis type 1 and optic pathway glioma: Molecular interplay and therapeutic insights

“…11 Brainstem gliomas represent the second most common brain tumor in children with NF1 and tend to occur at an older age and are often indolent and asymptomatic. 12 Less commonly, gliomas may arise in cerebellum, cortex, and basal ganglia, where they are usually asymptomatic at time of diagnosis. They are more prevalent in adolescents and adults.…”

Favorable prognosis in pediatric brainstem low‐grade glioma: Report from the German SIOP‐LGG 2004 cohort

“…On the other hand, radiologic diagnosis was broadly accepted for LGG in the past, especially for NF1‐associated tumors of the visual pathways, and radiologic criteria to discriminate DIPG from LGG were established . Within our cohort, more than a third of those with radiologic diagnosis were NF1‐patients for whom radiologic diagnosis of brainstem LGG has been accepted . Two‐thirds of the histologies were PA, and glioneuronal tumors had a share of 20% comparable to other series .…”