title: Clinical outcomes and late endocrine, neurocognitive, and visual profiles of proton radiation for pediatric low-grade gliomas.
abstract: OBJECTIVE
  Primary low-grade gliomas are common brain tumors of childhood, many of which require radiation therapy (RT) as definitive treatment. Increased conformality of RT could decrease the incidence and severity of late effects. We report our experience with 32 pediatric patients treated with proton RT.
  
  
  METHODS
  Thirty-two pediatric patients with low-grade gliomas of the brain or spinal cord were treated with proton RT from 1995 to 2007. Sixteen patients received at least 1 regimen of chemotherapy before definitive RT. The median radiation dose was 52.2 GyRBE (48.6-54 GyRBE).
  
  
  RESULTS
  The median age at treatment was 11.0 years (range, 2.7-21.5 years), with a median follow-up time of 7.6 years (range, 3.2-18.2 years). The 6-year and 8-year rates of progression-free survival were 89.7% and 82.8%, respectively, with an 8-year overall survival of 100%. For the subset of patients who received serial neurocognitive testing, there were no significant declines in Full-Scale Intelligence Quotient (P=.80), with a median neurocognitive testing interval of 4.5 years (range, 1.2-8.1 years) from baseline to follow-up, but subgroup analysis indicated some significant decline in neurocognitive outcomes for young children (<7 years) and those with significant dose to the left temporal lobe/hippocampus. The incidence of endocrinopathy correlated with a mean dose of ≥40 GyRBE to the hypothalamus, pituitary, or optic chiasm. Stabilization or improvement of visual acuity was achieved in 83.3% of patients at risk for radiation-induced injury to the optic pathways.
  
  
  CONCLUSIONS
  This report of late effects in children with low-grade gliomas after proton RT is encouraging. Proton RT appears to be associated with good clinical outcome, especially when the tumor location allows for increased sparing of the left temporal lobe, hippocampus, and hypothalamic-pituitary axis.
authors.affiliation: Harvard Medical School, Boston, Massachusetts.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Greenberger
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Margaret B
authors.initials: MB
authors.lastname: Pulsifer
authors.affiliation: Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: David H
authors.initials: DH
authors.lastname: Ebb
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: MacDonald
authors.affiliation: Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts; Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Robin M
authors.initials: RM
authors.lastname: Jones
authors.affiliation: Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: William E
authors.initials: WE
authors.lastname: Butler
authors.affiliation: Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Mary S
authors.initials: MS
authors.lastname: Huang
authors.affiliation: Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Marcus
authors.affiliation: Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Oberg
authors.affiliation: Harvard Medical School, Boston, Massachusetts; Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Tarbell
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts. Electronic address: tyock@partners.org.
authors.forename: Torunn I
authors.initials: TI
authors.lastname: Yock
mesh_terms: D000293:Adolescent; D000367:Age Factors; D001932:Brain Neoplasms / Q000150:complications / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D002648:Child; D002675:Child, Preschool; D003071:Cognition / Q000528:radiation effects; D018572:Disease-Free Survival; D005910:Glioma / Q000150:complications / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D006624:Hippocampus / Q000528:radiation effects; D006801:Humans; D007360:Intelligence / Q000528:radiation effects; D060787:Neoplasm Grading; D009897:Optic Chiasm; D058958:Organs at Risk / Q000528:radiation effects; D010902:Pituitary Gland / Q000528:radiation effects; D061766:Proton Therapy / Q000009:adverse effects* / Q000379:methods*; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects / Q000379:methods; D012189:Retrospective Studies; D013120:Spinal Cord Neoplasms / Q000150:complications / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D013702:Temporal Lobe / Q000528:radiation effects; D016896:Treatment Outcome; D055815:Young Adult