title: Spatial mapping of the biologic effectiveness of scanned particle beams: towards biologically optimized particle therapy.
abstract: The physical properties of particles used in radiation therapy, such as protons, have been well characterized, and their dose distributions are superior to photon-based treatments. However, proton therapy may also have inherent biologic advantages that have not been capitalized on. Unlike photon beams, the linear energy transfer (LET) and hence biologic effectiveness of particle beams varies along the beam path. Selective placement of areas of high effectiveness could enhance tumor cell kill and simultaneously spare normal tissues. However, previous methods for mapping spatial variations in biologic effectiveness are time-consuming and often yield inconsistent results with large uncertainties. Thus the data needed to accurately model relative biological effectiveness to guide novel treatment planning approaches are limited. We used Monte Carlo modeling and high-content automated clonogenic survival assays to spatially map the biologic effectiveness of scanned proton beams with high accuracy and throughput while minimizing biological uncertainties. We found that the relationship between cell kill, dose, and LET, is complex and non-unique. Measured biologic effects were substantially greater than in most previous reports, and non-linear surviving fraction response was observed even for the highest LET values. Extension of this approach could generate data needed to optimize proton therapy plans incorporating variable RBE.
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, U.S.A.
authors.forename: Fada
authors.initials: F
authors.lastname: Guan
authors.affiliation: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, U.S.A.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Bronk
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, U.S.A.
authors.forename: Uwe
authors.initials: U
authors.lastname: Titt
authors.affiliation: 1] Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, U.S.A [2] Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, U.S.A.
authors.forename: Steven H
authors.initials: SH
authors.lastname: Lin
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, U.S.A.
authors.forename: Dragan
authors.initials: D
authors.lastname: Mirkovic
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, U.S.A.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Kerr
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, U.S.A.
authors.forename: X Ronald
authors.initials: XR
authors.lastname: Zhu
authors.affiliation: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, U.S.A.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Dinh
authors.affiliation: Center for Translational Cancer Research, Texas A&M Health Science Center, Institute of Biosciences and Technology, Houston, Texas, U.S.A.
authors.forename: Mary
authors.initials: M
authors.lastname: Sobieski
authors.affiliation: Center for Translational Cancer Research, Texas A&M Health Science Center, Institute of Biosciences and Technology, Houston, Texas, U.S.A.
authors.forename: Clifford
authors.initials: C
authors.lastname: Stephan
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, U.S.A.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Peeler
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, U.S.A.
authors.forename: Reza
authors.initials: R
authors.lastname: Taleei
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, U.S.A.
authors.forename: Radhe
authors.initials: R
authors.lastname: Mohan
authors.affiliation: 1] Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, U.S.A [2] Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, U.S.A.
authors.forename: David R
authors.initials: DR
authors.lastname: Grosshans
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D004601:Elementary Particles; D006801:Humans; D009010:Monte Carlo Method; D011878:Radiotherapy; D012062:Relative Biological Effectiveness