Study On The Techniques Related To Dealing With The Uncertainty Of Intensity Modulated Heavy-Ion Radiotherapy

Due to the inverted depth dose distribution characteristics of heavy-ion beam,intensity-modulated particle therapy（IMPT）with carbon ions can not only produce conformal dose distributions to the target volume,but also reduce the dose to normal tissues and organs around the target.However,the dose distributions generated by IMPT are comparatively susceptible to various uncertainties occurring in the process of radiotherapy,resulting in a difference between the final dose distribution received by patients and the planned dose distributions.Therefore,reducing the influences of uncertainties on carbon-ion IMPT is the main objectives of current ion beam radiotherapy research.In this paper,RBE weighted dose is taken as the entry point to study the impact of robust optimization method on carbon-ion IMPT planning in view of setup uncertainty,range uncertainty and target positioning uncertainty caused by respiratory motion.The main research contents are listed as follows:1)A robust optimization method for computing RBE-weighted dose based on the mixed beam model was proposed to reduce the impact of range and setup uncertainties on dose distribution in carbon-ion radiotherapy.Firstly,a probabilistic robust model was established and the objective function was expressed using the quadratic function.Then two treatment plans were designed regarding to physical absorbed dose and RBE-weighted dose.Finally,the conjugate gradient method was adopted to find the respective optimal solutions so as to make the actual dose received by the target volume and organ at risk（OAR）decrease under the disturbance of range and setup deviation.The prescription for CTV was 1Gy（RBE）with dose constraints of 0.3Gy（RBE）for OAR.The TG119 model was utilized to evaluate the effectiveness of the robust optimization method for computing RBE-weighted dose based on the mixed beam model.2)Based on the open-source treatment planning system---mat Rad,the PTV-based optimization method,the RP-4DRO method and the EP-4DRO method are implemented in this study aiming at setup uncertainty,range uncertainty and the target positioning uncertainty caused by respiratory motion on carbon-ion IMPT.A minmax robust model was established to make carbon-ion IMPT treatment planning,and five lung cancer patients were employed to evaluate the clinical application potential of both the 4DRO methods.The main results are listed as follows:1)Compared with the conventional dose optimization method based on the planning target volume（PTV）,the robust treatment planning based on physical absorbed dose made（?）_95%reduce 10.0c Gy in the clinical target volume（CTV）,and the（?）D_5%and（?）D_max parameters of the OAR decreased by 21.50c Gy and 35.97c Gy respectively,indicating that the robustness of the plans has been greatly improved.Besides,the robust treatment planning based on RBE-weighted dose showed that（?）_95%reduced by 14.00c Gy（RBE）in the CTV while（?）_5%and（?）₈（6）in the OAR reduced by 19.00c Gy（RBE）and 26.28c Gy（RBE）,respectively.These results illustrate that the robust optimization method not only reduced the variation of biological dose in the CTV,but also reduced the hot spots of biological dose in the OAR.Collectively,the robust optimization method for RBE-weighted dose based on the mixed beam model could effectively enhance the robustness of carbon-ion radiotherapy treatment planning while sparing OAR simultaneously.2)In lung cancer data testing,different cancer patients respond to the various optimization methods differently.In comparison to the PTV-based optimization method,the EP-4DRO method provided better robustness and plan quality of clinical target volume（CTV）in individual respiratory phase,while the RP-4DRO method just guaranteed the robustness in accumulated dose distributions.Besides,in individual respiratory phase,the EP-4DRO method showed superior dose homogeneity inside the target boundaries compared to the RP-4DRO and PTV-based optimization methods.Both the 4DRO methods performed better in the dose distribution conformity and sparing of OARs compared to the PTV-based optimization.Moreover,an important finding was that the RP-4DRO method showed a better performance than the EP-4DRO method in protecting the OARs。In conclusion,the study showed that in comparison with the PTV-based optimization method,the robust optimization methods can better alleviate the disturbance of dose distributions caused by range uncertainty,setup uncertainty and target positioning uncertainty due to respiratory motion,and reduce the dose of OAR in carbon-ion IMPT.The study provided a theoretical basis for updating the next domestic heavy-ion treatment planning system.