A multi-institutional study of brainstem gliomas in children with neurofibromatosis type 1.
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.
From the Departments of Neurology (J.M., S.M.M., D.H.G.) and Radiology (R.C.M.), Washington University School of Medicine, St. Louis, MO; Division of Oncology (A.C.S., M.J.F.), Children's Hospital of Philadelphia, PA; Center for Neuroscience of Behavioral Medicine (A.S., R.J.P.), Children's National Medical Center, Washington, DC; Division of Academic General Pediatrics (R.L.), Feinberg School of Medicine, Northwestern University, Ann & Robert H. Lurie Children's Hospital of Chicago, IL; and Department of Pediatrics (M.J.F.), The Perelman School of Medicine at The University of Pennsylvania, Philadelphia.
Jasia
J
Mahdi
From the Departments of Neurology (J.M., S.M.M., D.H.G.) and Radiology (R.C.M.), Washington University School of Medicine, St. Louis, MO; Division of Oncology (A.C.S., M.J.F.), Children's Hospital of Philadelphia, PA; Center for Neuroscience of Behavioral Medicine (A.S., R.J.P.), Children's National Medical Center, Washington, DC; Division of Academic General Pediatrics (R.L.), Feinberg School of Medicine, Northwestern University, Ann & Robert H. Lurie Children's Hospital of Chicago, IL; and Department of Pediatrics (M.J.F.), The Perelman School of Medicine at The University of Pennsylvania, Philadelphia.
Amish C
AC
Shah
From the Departments of Neurology (J.M., S.M.M., D.H.G.) and Radiology (R.C.M.), Washington University School of Medicine, St. Louis, MO; Division of Oncology (A.C.S., M.J.F.), Children's Hospital of Philadelphia, PA; Center for Neuroscience of Behavioral Medicine (A.S., R.J.P.), Children's National Medical Center, Washington, DC; Division of Academic General Pediatrics (R.L.), Feinberg School of Medicine, Northwestern University, Ann & Robert H. Lurie Children's Hospital of Chicago, IL; and Department of Pediatrics (M.J.F.), The Perelman School of Medicine at The University of Pennsylvania, Philadelphia.
Aimee
A
Sato
From the Departments of Neurology (J.M., S.M.M., D.H.G.) and Radiology (R.C.M.), Washington University School of Medicine, St. Louis, MO; Division of Oncology (A.C.S., M.J.F.), Children's Hospital of Philadelphia, PA; Center for Neuroscience of Behavioral Medicine (A.S., R.J.P.), Children's National Medical Center, Washington, DC; Division of Academic General Pediatrics (R.L.), Feinberg School of Medicine, Northwestern University, Ann & Robert H. Lurie Children's Hospital of Chicago, IL; and Department of Pediatrics (M.J.F.), The Perelman School of Medicine at The University of Pennsylvania, Philadelphia.
Stephanie M
SM
Morris
From the Departments of Neurology (J.M., S.M.M., D.H.G.) and Radiology (R.C.M.), Washington University School of Medicine, St. Louis, MO; Division of Oncology (A.C.S., M.J.F.), Children's Hospital of Philadelphia, PA; Center for Neuroscience of Behavioral Medicine (A.S., R.J.P.), Children's National Medical Center, Washington, DC; Division of Academic General Pediatrics (R.L.), Feinberg School of Medicine, Northwestern University, Ann & Robert H. Lurie Children's Hospital of Chicago, IL; and Department of Pediatrics (M.J.F.), The Perelman School of Medicine at The University of Pennsylvania, Philadelphia.
Robert C
RC
McKinstry
From the Departments of Neurology (J.M., S.M.M., D.H.G.) and Radiology (R.C.M.), Washington University School of Medicine, St. Louis, MO; Division of Oncology (A.C.S., M.J.F.), Children's Hospital of Philadelphia, PA; Center for Neuroscience of Behavioral Medicine (A.S., R.J.P.), Children's National Medical Center, Washington, DC; Division of Academic General Pediatrics (R.L.), Feinberg School of Medicine, Northwestern University, Ann & Robert H. Lurie Children's Hospital of Chicago, IL; and Department of Pediatrics (M.J.F.), The Perelman School of Medicine at The University of Pennsylvania, Philadelphia.
Robert
R
Listernick
From the Departments of Neurology (J.M., S.M.M., D.H.G.) and Radiology (R.C.M.), Washington University School of Medicine, St. Louis, MO; Division of Oncology (A.C.S., M.J.F.), Children's Hospital of Philadelphia, PA; Center for Neuroscience of Behavioral Medicine (A.S., R.J.P.), Children's National Medical Center, Washington, DC; Division of Academic General Pediatrics (R.L.), Feinberg School of Medicine, Northwestern University, Ann & Robert H. Lurie Children's Hospital of Chicago, IL; and Department of Pediatrics (M.J.F.), The Perelman School of Medicine at The University of Pennsylvania, Philadelphia.
Roger J
RJ
Packer
From the Departments of Neurology (J.M., S.M.M., D.H.G.) and Radiology (R.C.M.), Washington University School of Medicine, St. Louis, MO; Division of Oncology (A.C.S., M.J.F.), Children's Hospital of Philadelphia, PA; Center for Neuroscience of Behavioral Medicine (A.S., R.J.P.), Children's National Medical Center, Washington, DC; Division of Academic General Pediatrics (R.L.), Feinberg School of Medicine, Northwestern University, Ann & Robert H. Lurie Children's Hospital of Chicago, IL; and Department of Pediatrics (M.J.F.), The Perelman School of Medicine at The University of Pennsylvania, Philadelphia.
Michael J
MJ
Fisher
From the Departments of Neurology (J.M., S.M.M., D.H.G.) and Radiology (R.C.M.), Washington University School of Medicine, St. Louis, MO; Division of Oncology (A.C.S., M.J.F.), Children's Hospital of Philadelphia, PA; Center for Neuroscience of Behavioral Medicine (A.S., R.J.P.), Children's National Medical Center, Washington, DC; Division of Academic General Pediatrics (R.L.), Feinberg School of Medicine, Northwestern University, Ann & Robert H. Lurie Children's Hospital of Chicago, IL; and Department of Pediatrics (M.J.F.), The Perelman School of Medicine at The University of Pennsylvania, Philadelphia. gutmannd@wustl.edu.
David H
DH
Gutmann
D000293:Adolescent; D000367:Age Factors; D001933:Brain Stem / Q000000981:diagnostic imaging; D020295:Brain Stem Neoplasms / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005910:Glioma / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000628:therapy; D006801:Humans; D007223:Infant; D008297:Male; D009456:Neurofibromatosis 1 / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000628:therapy; D012189:Retrospective Studies; D055815:Young Adult