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BEST IN PHYSICS (THERAPY): Nano-Dosimetric Kinetic Model for Variable Relative Biological Effectiveness of Proton and Ion Beams

R Abolfath

R Abolfath1*, L Bronk1 , Y Helo2 , J Schuemann3 , U. Titt1 , D Grosshans1 , R Mohan1 , (1) The University of Texas MD Anderson Cancer Center, Houston, TX, (2) University College London, London, UK (3) Massachusetts General Hospital, Boston, MA


WE-H-BRA-1 (Wednesday, August 3, 2016) 4:30 PM - 6:00 PM Room: Ballroom A

Purpose: Recent clonogenic cell survival and γH2AX studies suggest proton relative biological effectiveness (RBE) may be a non-linear function of linear energy transfer (LET) in the distal edge of the Bragg peak and beyond. We sought to develop a multiscale model to account for non-linear response phenomena to aid in the optimization of intensity-modulated proton therapy.

Methods: The model is based on first-principle simulations of proton track structures, including secondary ions, and an analytical derivation of the dependence on particle LET of the linear-quadratic (LQ) model parameters α and β. The derived formulas are an extension of the microdosimetric kinetic (MK) model that captures dissipative track structures and non-Poissonian distribution of DNA damage at the distal edge of the Bragg peak and beyond. Monte Carlo simulations were performed to confirm the non-linear dose-response characteristics arising from the non-Poisson distribution of initial DNA damage.

Results: In contrast to low LET segments of the proton depth dose, from the beam entrance to the Bragg peak, strong deviations from non-dissipative track structures and Poisson distribution in the ionization events in the Bragg peak distal edge govern the non-linear cell response and result in the transformation α=(1+c_1 L) α_x+2(c_0 L+c_2 L^2 )(1+c_1 L) β_x and β=(1+c_1 L)^2 β_x. Here L is the charged particle LET, and c_0,c_1, and c_2 are functions of microscopic parameters and can be served as fitting parameters to the cell-survival data. In the low LET limit c_1, and c_2 are negligible hence the linear model proposed and used by Wilkins-Oelfke for the proton treatment planning system can be retrieved. The present model fits well the recent clonogenic survival data measured recently in our group in MDACC.

Conclusion: The present hybrid method provides higher accuracy in calculating the RBE-weighted dose in the target and normal tissues.

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