title: Bioinformatics methods for learning radiation-induced lung inflammation from heterogeneous retrospective and prospective data.
abstract: Radiotherapy outcomes are determined by complex interactions between physical and biological factors, reflecting both treatment conditions and underlying genetics. Recent advances in radiotherapy and biotechnology provide new opportunities and challenges for predicting radiation-induced toxicities, particularly radiation pneumonitis (RP), in lung cancer patients. In this work, we utilize datamining methods based on machine learning to build a predictive model of lung injury by retrospective analysis of treatment planning archives. In addition, biomarkers for this model are extracted from a prospective clinical trial that collects blood serum samples at multiple time points. We utilize a 3-way proteomics methodology to screen for differentially expressed proteins that are related to RP. Our preliminary results demonstrate that kernel methods can capture nonlinear dose-volume interactions, but fail to address missing biological factors. Our proteomics strategy yielded promising protein candidates, but their role in RP as well as their interactions with dose-volume metrics remain to be determined.
authors.affiliation: Department of Radiation Oncology, Washington University Medical School, Saint Louis, MO 63110, USA.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Spencer
authors.forename: Damian Almiron
authors.initials: DA
authors.lastname: Bonnin
authors.forename: Joseph O
authors.initials: JO
authors.lastname: Deasy
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Bradley
authors.forename: Issam
authors.initials: I
authors.lastname: El Naqa
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000532:radiotherapy*; D019295:Computational Biology / Q000379:methods*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D008954:Models, Biological; D025341:Principal Component Analysis; D011446:Prospective Studies; D040901:Proteomics / Q000379:methods; D017564:Radiation Pneumonitis / Q000209:etiology* / Q000378:metabolism; D011878:Radiotherapy / Q000009:adverse effects; D012189:Retrospective Studies
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