title: Interpretation of proton relative biological effectiveness using lesion induction, lesion repair, and cellular dose distribution.
abstract: Phenomenological biophysical models have been successfully used to estimate the relative biological effectiveness (RBE) of ions. The predictive power of these models is limited because they require measured dose-response data that are not necessarily available for all clinically relevant end points. Furthermore, input parameters often lack mechanistic interpretation. In order to link RBE to more fundamental biological parameters we combine the concepts of two well-established biophysical models, i.e., the phenomenological "track structure" model and the more mechanistic "lethal lesion/potentially lethal lesion" (LPL) model. We parametrize a relation between RBE, dose homogeneity in the cell nucleus and induction rates for different lesion types. The macroscopic dose-response relationship is described in the LPL model and the microscopic, subcellular, relationship is determined by the local dose deposition pattern. The formalism provides a framework for a mechanistic interpretation of RBE values.
authors.affiliation: Northeast Proton Therapy Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. hpaganetti@partners.org
authors.forename: H
authors.initials: H
authors.lastname: Paganetti
mesh_terms: D002470:Cell Survival / Q000528:radiation effects*; D003198:Computer Simulation; D004249:DNA Damage; D004260:DNA Repair / Q000528:radiation effects; D004273:DNA, Neoplasm / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D018499:Linear Energy Transfer; D008954:Models, Biological; D009369:Neoplasms / Q000503:physiopathology* / Q000532:radiotherapy*; D061766:Proton Therapy; D011874:Radiometry / Q000379:methods*; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D012062:Relative Biological Effectiveness; D014407:Tumor Cells, Cultured
chemical_list: D004273:DNA, Neoplasm