American Lebanese Syrian Associated Charities, St Jude Children's Research Hospital, NCI Cancer Center, Alexander and Margaret Stewart Trust, Sontag Foundation, and American Association for Cancer Research.

Background. Proton therapy offers superior low and intermediate radiation dose distribution compared with photonbased 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 identifi ed prognostic variables. Material and methods. All patients Ͻ 18 years old with tumors of the brain or skull base treated from 2007 to 2013 were reviewed; 313 who received Ͼ 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% Ϯ 1.1%. The two-year cumulative incidence of grade 3 ϩ toxicity was 2.1% Ϯ 0.9%. Univariate analysis identifi ed age Ͻ 5 years, posterior fossa tumor location and specifi c dosimetric parameters as factors associated with an increased risk of toxicity. Conclusion. 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.

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Brainstem injury is a rare complication of radiation therapy for both photons and protons. Substantial dosimetric data have been collected for brainstem injury after proton therapy, and established guidelines to allow for safe delivery of proton radiation have been defined. Increased capability exists to incorporate LET optimization; however, further research is needed to fully explore the capabilities of LET- and RBE-based planning.