Journal
RADIOTHERAPY AND ONCOLOGY
Volume 121, Issue 3, Pages 395-401Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.radonc.2016.11.001
Keywords
Proton therapy; Biological effectiveness; Pediatric
Funding
- National Cancer Institute at the National Institutes of Health [2U19CA021239-35, 5R21CA187484-02, P30CA016672]
- Cancer Prevention and Research Institute of Texas [RP160232]
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Background and purpose: 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. Material and methods: 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. Results: Image changes showed dependence on increasing LET and dose. TD50 decreased 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). Conclusions: Our correlation of changes on MR images after proton therapy with increased LET constitutes the first clinical evidence of variable proton biological effectiveness. (C) 2016 Elsevier Ireland Ltd.
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