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A pharmacodynamic model was developed to describe the radiation\u2010induced tumor shrinkage and overall survival in mice bearing DIPG. CD1\u2010nude mice were implanted in the brain cortex with luciferase\u2010labeled patient\u2010derived orthotopic xenografts of DIPG (SJDIPGx7 <jats:italic>H3F3A<jats:sup>WT<\/jats:sup><\/jats:italic><jats:sup>\/<\/jats:sup><jats:italic><jats:sup>K27\u00a0M<\/jats:sup><\/jats:italic> and SJDIPGx37\u00a0<jats:italic>H3F3A<jats:sup>K27M<\/jats:sup><\/jats:italic><jats:sup>\/<\/jats:sup><jats:italic><jats:sup>K27M<\/jats:sup><\/jats:italic>). Mice were treated with image\u2010guided whole\u2010brain RT at 1 or 2\u00a0Gy\/fraction 5\u2010days\u2010on 2\u2010days\u2010off for a cumulative dose of 20 or 54\u00a0Gy. Tumor progression was monitored with bioluminescent imaging (BLI). A mathematical model describing BLI and overall survival was developed with data from mice receiving 2\u00a0Gy\/fraction and validated using data from mice receiving 1\u00a0Gy\/fraction. BLI data were adequately fitted with a logistic tumor growth function and a signal distribution model with linear radiation\u2010induced killing effect. A higher tumor growth rate in SJDIPGx37 versus SJDIPGx7 xenografts and a killing effect decreasing with higher tumor baseline (<jats:italic>p\u00a0<\/jats:italic>&lt;\u00a00.0001) were identified. Cumulative radiation dose was suggested to inhibit the tumor growth rate according to a Hill function. Survival distribution was best described with a Weibull hazard function in which the hazard baseline was a continuous function of tumor BLI. Significant differences were further identified between DIPG cell lines and untreated versus treated mice. The model was adequately validated with mice receiving 1\u00a0Gy\/fraction and will be useful in guiding future preclinical trials incorporating radiation and to support systemic combination therapies with RT.<\/jats:p>","DOI":"10.1002\/psp4.12627","type":"journal-article","created":{"date-parts":[[2021,5,3]],"date-time":"2021-05-03T16:56:39Z","timestamp":1620060999000},"page":"599-610","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Model\u2010based evaluation of image\u2010guided fractionated whole\u2010brain radiation therapy in pediatric diffuse intrinsic pontine glioma xenografts"],"prefix":"10.1002","volume":"10","author":[{"given":"Hillary R.","family":"Husband","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences St. Jude Children\u2019s Research Hospital Memphis TN USA"},{"name":"College of Engineering and Science Louisiana Tech University Ruston LA 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