title: Clinical evidence of variable proton biological effectiveness in pediatric patients treated for ependymoma.
abstract: A constant relative biological effectiveness (RBE) is used for clinical proton therapy; however, experimental evidence indicates that RBE can vary. We analyzed pediatric ependymoma patients who received proton therapy to determine if areas of normal tissue damage indicated by post-treatment image changes were associated with increased biological dose effectiveness.
  
  
  
  Fourteen of 34 children showed T2-FLAIR hyperintensity on post-treatment magnetic resonance (MR) images. We delineated regions of treatment-related change and calculated dose and linear energy transfer (LET) distributions with Monte Carlo. Voxel-level image change data were fit to a generalized linear model incorporating dose and LET. Cross-validation was used to determine model parameters and for receiver operating characteristic curve analysis. Tolerance dose (TD50; dose at which 50% of patients would experience toxicity) was interpolated from the model.
  
  
  
  Image changes showed dependence on increasing LET and dose. TD50decreased with increasing LET, indicating an increase in biological dose effectiveness. The cross-validated area under the curve for the model was 0.91 (95% confidence interval 0.88-0.94).
  
  
  
  Our correlation of changes on MR images after proton therapy with increased LET constitutes the first clinical evidence of variable proton biological effectiveness.
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, United States; The University of Texas Graduate School of Biomedical Sciences at Houston, United States.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Peeler
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, United States.
authors.forename: Dragan
authors.initials: D
authors.lastname: Mirkovic
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, United States.
authors.forename: Uwe
authors.initials: U
authors.lastname: Titt
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States; Gustave Roussy, Université Paris-Saclay, Department of Radiation Oncology, Villejuif, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Blanchard
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States.
authors.forename: Jillian R
authors.initials: JR
authors.lastname: Gunther
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States.
authors.forename: Anita
authors.initials: A
authors.lastname: Mahajan
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, United States.
authors.forename: Radhe
authors.initials: R
authors.lastname: Mohan
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States. Electronic address: dgrossha@mdanderson.org.
authors.forename: David R
authors.initials: DR
authors.lastname: Grosshans
mesh_terms: D002648:Child; D002675:Child, Preschool; D004806:Ependymoma / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D007223:Infant; D018499:Linear Energy Transfer; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D009010:Monte Carlo Method; D058958:Organs at Risk / Q000528:radiation effects; D011446:Prospective Studies; D061766:Proton Therapy / Q000009:adverse effects / Q000379:methods*; D011879:Radiotherapy Dosage; D012062:Relative Biological Effectiveness
keywords: Biological effectiveness; Pediatric; Proton therapy