title: Biologically optimized helium ion plans: calculation approach and its in vitro validation.
abstract: Treatment planning studies on the biological effect of raster-scanned helium ion beams should be performed, together with their experimental verification, before their clinical application at the Heidelberg Ion Beam Therapy Center (HIT). For this purpose, we introduce a novel calculation approach based on integrating data-driven biological models in our Monte Carlo treatment planning (MCTP) tool. Dealing with a mixed radiation field, the biological effect of the primary (4)He ion beams, of the secondary (3)He and (4)He (Z  =  2) fragments and of the produced protons, deuterons and tritons (Z  =  1) has to be taken into account. A spread-out Bragg peak (SOBP) in water, representative of a clinically-relevant scenario, has been biologically optimized with the MCTP and then delivered at HIT. Predictions of cell survival and RBE for a tumor cell line, characterized by [Formula: see text] Gy, have been successfully compared against measured clonogenic survival data. The mean absolute survival variation ([Formula: see text]) between model predictions and experimental data was 5.3%  ±  0.9%. A sensitivity study, i.e. quantifying the variation of the estimations for the studied plan as a function of the applied phenomenological modelling approach, has been performed. The feasibility of a simpler biological modelling based on dose-averaged LET (linear energy transfer) has been tested. Moreover, comparisons with biophysical models such as the local effect model (LEM) and the repair-misrepair-fixation (RMF) model were performed. [Formula: see text] values for the LEM and the RMF model were, respectively, 4.5%  ±  0.8% and 5.8%  ±  1.1%. The satisfactorily agreement found in this work for the studied SOBP, representative of clinically-relevant scenario, suggests that the introduced approach could be applied for an accurate estimation of the biological effect for helium ion radiotherapy.
authors.affiliation: Medical Physics Unit, CNAO Foundation, Via Strada Campeggi 53, I-27100 Pavia, Italy. Heidelberg Ion Beam Therapy Center, Im Neuenheimer Feld 450, D-69120 Heidelberg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Mairani
authors.forename: I
authors.initials: I
authors.lastname: Dokic
authors.forename: G
authors.initials: G
authors.lastname: Magro
authors.forename: T
authors.initials: T
authors.lastname: Tessonnier
authors.forename: F
authors.initials: F
authors.lastname: Kamp
authors.forename: D J
authors.initials: DJ
authors.lastname: Carlson
authors.forename: M
authors.initials: M
authors.lastname: Ciocca
authors.forename: F
authors.initials: F
authors.lastname: Cerutti
authors.forename: P R
authors.initials: PR
authors.lastname: Sala
authors.forename: A
authors.initials: A
authors.lastname: Ferrari
authors.forename: T T
authors.initials: TT
authors.lastname: Böhlen
authors.forename: O
authors.initials: O
authors.lastname: Jäkel
authors.forename: K
authors.initials: K
authors.lastname: Parodi
authors.forename: J
authors.initials: J
authors.lastname: Debus
authors.forename: A
authors.initials: A
authors.lastname: Abdollahi
authors.forename: T
authors.initials: T
authors.lastname: Haberer
mesh_terms: D000465:Algorithms; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D006371:Helium / Q000627:therapeutic use*; D006801:Humans; D011868:Radioisotopes / Q000627:therapeutic use*; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*; D012062:Relative Biological Effectiveness
chemical_list: D011868:Radioisotopes; D006371:Helium