title: EUD-based biological optimization for carbon ion therapy.
abstract: OBJECTIVE
  Treatment planning for carbon ion therapy requires an accurate modeling of the biological response of each tissue to estimate the clinical outcome of a treatment. The relative biological effectiveness (RBE) accounts for this biological response on a cellular level but does not refer to the actual impact on the organ as a whole. For photon therapy, the concept of equivalent uniform dose (EUD) represents a simple model to take the organ response into account, yet so far no formulation of EUD has been reported that is suitable to carbon ion therapy. The authors introduce the concept of an equivalent uniform effect (EUE) that is directly applicable to both ion and photon therapies and exemplarily implemented it as a basis for biological treatment plan optimization for carbon ion therapy.
  
  
  METHODS
  In addition to a classical EUD concept, which calculates a generalized mean over the RBE-weighted dose distribution, the authors propose the EUE to simplify the optimization process of carbon ion therapy plans. The EUE is defined as the biologically equivalent uniform effect that yields the same probability of injury as the inhomogeneous effect distribution in an organ. Its mathematical formulation is based on the generalized mean effect using an effect-volume parameter to account for different organ architectures and is thus independent of a reference radiation. For both EUD concepts, quadratic and logistic objective functions are implemented into a research treatment planning system. A flexible implementation allows choosing for each structure between biological effect constraints per voxel and EUD constraints per structure. Exemplary treatment plans are calculated for a head-and-neck patient for multiple combinations of objective functions and optimization parameters.
  
  
  RESULTS
  Treatment plans optimized using an EUE-based objective function were comparable to those optimized with an RBE-weighted EUD-based approach. In agreement with previous results from photon therapy, the optimization by biological objective functions resulted in slightly superior treatment plans in terms of final EUD for the organs at risk (OARs) compared to voxel-based optimization approaches. This observation was made independent of the underlying objective function metric. An absolute gain in OAR sparing was observed for quadratic objective functions, whereas intersecting DVHs were found for logistic approaches. Even for considerable under- or overestimations of the used effect- or dose-volume parameters during the optimization, treatment plans were obtained that were of similar quality as the results of a voxel-based optimization.
  
  
  CONCLUSIONS
  EUD-based optimization with either of the presented concepts can successfully be applied to treatment plan optimization. This makes EUE-based optimization for carbon ion therapy a useful tool to optimize more specifically in the sense of biological outcome while voxel-to-voxel variations of the biological effectiveness are still properly accounted for. This may be advantageous in terms of computational cost during treatment plan optimization but also enables a straight forward comparison of different fractionation schemes or treatment modalities.
authors.affiliation: Department of Radiation Oncology, Technische Universität München, Klinikum rechts der Isar, Ismaninger Str. 22, München 81675, Germany and Physik-Department, Technische Universität München, James-Franck-Str. 1, Garching 85748, Germany.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Brüningk
authors.affiliation: Department of Radiation Oncology, Technische Universität München, Klinikum rechts der Isar, Ismaninger Str. 22, München 81675, Germany and Physik-Department, Technische Universität München, James-Franck-Str. 1, Garching 85748, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Kamp
authors.affiliation: Department of Radiation Oncology, Technische Universität München, Klinikum rechts der Isar, Ismaninger Str. 22, München 81675, Germany and Physik-Department, Technische Universität München, James-Franck-Str. 1, Garching 85748, Germany.
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Wilkens
mesh_terms: D000465:Algorithms; D002244:Carbon; D003198:Computer Simulation; D004307:Dose-Response Relationship, Radiation; D063193:Heavy Ion Radiotherapy / Q000379:methods*; D020450:Heavy Ions; D006801:Humans; D008954:Models, Biological; D015233:Models, Statistical; D009369:Neoplasms / Q000503:physiopathology* / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*; D012062:Relative Biological Effectiveness
chemical_list: D002244:Carbon