Biological dose optimization incorporating intra-tumoural cellular radiosensitivity heterogeneity in ion-beam therapy treatment planning.


Treatment plans of charged-particle therapy have been made under an assumption that all cancer cells within a tumour equally respond to a given radiation. However, an intra-tumoural cellular radiosensitivity heterogeneity clearly exists, and it may lead to an overestimation of therapeutic effects of the radiation. The purpose of this study was to develop a biological model that can incorporate the radiosensitivity heterogeneity into biological optimization for charged-particle therapy treatment planning.
Approach. The radiosensitivity heterogeneity was modeled as the variability of a cell-line specific parameter in the microdosimetric kinetic model following the gamma distribution. To validate the developed intra-tumoural-radiosensitivity-heterogeneity-incorporated microdosimetric kinetic (HMK) model, a treatment plan with H-ion beams was made for a chordoma case assuming a radiosensitivity heterogeneous region within the tumour. To investigate the effects of the radiosensitivity heterogeneity on the biological effectiveness of H-, He-, C-, O-, and Ne-ion beams, the relative biological effectiveness (RBE)-weighted dose distributions were planned to a cuboid target with the stated ion beams without considering the heterogeneity. The planned dose distributions were then recalculated by taking the heterogeneity into account.
Main results:
The cell survival fraction and corresponding RBE weighted dose w- ere formulated basedon the HMK model. The first derivative of the RBE-weighted dose distribution was also derived,which is needed for fast biological optimization. For the patient plan, the biological optimization increasedthe dose to the radiosensitivity heterogeneous region to compensate for the heterogeneity-inducedreduction in biological effectiveness of the H-ion beams. The reduction in biological effectiveness dueto the heterogeneity waspronouncedfor low-LET beams but moderate for high-LET beams. The RBE-weighted dose in the cuboid target decreased by 7.6% for the H-ion beam, while it decreased by just 1.4% for the Ne-ion beam.
Significance. The optimal treatment plans that consider the intra-tumoural cellular radiosensitivity heterogeneity can be devised using the HMK model.&#xD.

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