title: Incidence and dosimetric parameters of pediatric brainstem toxicity following proton therapy.
abstract: BACKGROUND
  Proton therapy offers superior low and intermediate radiation dose distribution compared with photon-based radiation for brain and skull base tumors; yet tissue within and adjacent to the target volume may receive a comparable radiation dose. We investigated the tolerance of the pediatric brainstem to proton therapy and identified prognostic variables.
  
  
  METHODS
  All patients < 18 years old with tumors of the brain or skull base treated from 2007 to 2013 were reviewed; 313 who received > 50.4 CGE to the brainstem were included in this study. Brainstem toxicity was graded according to the NCI Common Terminology Criteria for Adverse Events v4.0.
  
  
  RESULTS
  The three most common histologies were ependymoma, craniopharyngioma, and low-grade glioma. Median patient age was 5.9 years (range 0.5-17.9 years) and median prescribed dose was 54 CGE (range 48.6-75.6 CGE). The two-year cumulative incidence of toxicity was 3.8% ± 1.1%. The two-year cumulative incidence of grade 3 + toxicity was 2.1% ± 0.9%. Univariate analysis identified age < 5 years, posterior fossa tumor location and specific dosimetric parameters as factors associated with an increased risk of toxicity.
  
  
  CONCLUSIONS
  Utilization of current national brainstem dose guidelines is associated with a low risk of brainstem toxicity in pediatric patients. For young patients with posterior fossa tumors, particularly those who undergo aggressive surgery, our data suggest more conservative dosimetric guidelines should be considered.
authors.affiliation: Department of Radiation Oncology, University of Florida , Jacksonville, Florida , USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Indelicato
authors.forename: Stella
authors.initials: S
authors.lastname: Flampouri
authors.forename: Ronny L
authors.initials: RL
authors.lastname: Rotondo
authors.forename: Julie A
authors.initials: JA
authors.lastname: Bradley
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Morris
authors.forename: Philipp R
authors.initials: PR
authors.lastname: Aldana
authors.forename: Eric
authors.initials: E
authors.lastname: Sandler
authors.forename: Nancy P
authors.initials: NP
authors.lastname: Mendenhall
mesh_terms: D000293:Adolescent; D001932:Brain Neoplasms / Q000532:radiotherapy*; D001933:Brain Stem / Q000528:radiation effects*; D002648:Child; D002675:Child, Preschool; D003397:Craniopharyngioma / Q000532:radiotherapy; D004806:Ependymoma / Q000532:radiotherapy; D005910:Glioma / Q000532:radiotherapy; D006801:Humans; D015994:Incidence; D007223:Infant; D015192:Infratentorial Neoplasms / Q000532:radiotherapy*; D061766:Proton Therapy / Q000009:adverse effects*; D011832:Radiation Injuries; D011836:Radiation Tolerance; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D019292:Skull Base Neoplasms / Q000532:radiotherapy*