Research On Uncertainties Of Intensity Modulated Proton Therapy

Compared with conventional radiotherapy and passive scattering proton therapy,intensity-modulated proton therapy（IMPT）has a greater potential to utilize the Bragg peak characteristic of the proton beam to deliver highly conformal dose to targets while minimizing dose in nearby organs-at-risk.Due to its technical characteristic,IMPT is more sensitive to various uncertainties occurring in the process of radiotherapy,resulting in a deviation between the actual dose distribution received by patients and the planned dose distribution.Currently,reducing the influences of uncertainties on IMPT is the main research direction of precision proton therapy.In this paper,robust optimization of IMPT and collection efficiency of monitor parallel plate ionization chambers were studied,and new strategies were proposed to mitigate the impact of range uncertainty,set-up uncertainty,and dose delivery control accuracy effect in IMPT.The main research works are listed as follows:1.A new robust optimization method called modified worst case method was proposed,which enables users to control the trade-off between nominal plan quality and plan robustness.In each iteration of the optimization process,the dose value of each voxel in n scenarios（n was set to 9 in this study）,including a nominal scenario and eight perturbed scenarios with range or set-up uncertainties,were calculated and the maximum of deviations of each scenario voxel dose from that of the nominal scenario was included as an additive robust optimization term in the objective function.A weighting factor P_robust was used to this robust optimization term to balance the nominal plan quality and plan robustness.The robust optimization methods were implemented and results were compared using an in-house developed robust optimization module.2.The collection efficiency of monitor parallel plate ionization chambers is the main uncertainty in the beam control of pencil beam scanning systems.In this study,Boag’s theory was applied to a proton pencil beam scanning system.The transverse distribution of charge density in the ionization chamber was considered to be a Gaussian function and an analytical solution was derived to calculate collection efficiency in the beam spot area.This calculation method is called the integral method and was used to investigate the effects of beam parameters on collection efficiency.The beam sizes of Shanghai Advanced Proton Therapy（SAPT）facility were simulated by Geant4 and the constraints of collection efficiency on beam parameters at the SAPT were investigated.The main results are listed as follows:1.In the study of the robust optimization method of IMPT,the C-shape water model in the TG-119 Report was used,and three fixed irradiation fields were set with the angles of 0°,90°and 270°,respectively.The results showed that when P_robust was set to 0.8,compared with conventional optimization,the robustness index D₉₅ of CTV was reduced from 9.8 Gy to 7.6Gy.When P_robustobust was reduced from 1 to 0,D₉₅ was increased from 7.0 Gy to 9.8 Gy,while CTV’s D_max,and OARs’D₅,D_max in the nominal scenario were reduced.The proposed modified worst case method can effectively improve the robustness of the plan to range and set-up uncertainties.Besides,it was shown that the weighting factor P _robust in this method can be used to control the trade-off between nominal plan quality and plan robustness.2.In the study of the collection efficiency of a monitor parallel plate ionization chamber,it was proved that collection efficiency is positively correlated with applied voltage,beam size,and beam energy,but negatively correlated with beam current intensity.Additionally,it was confirmed that collection efficiency was improved when the air filling the monitor parallel plate ionization chamber was replaced by nitrogen.Using Geant4 to simulate the beam parameters,when the applied voltage is 1500 V and filling gas is air,if the beam current intensity is 3 n A,the variation of collection efficiencies corresponding to the 94 proton beam energies is negligible.The beam current intensities of 94 energy proton beams were calculated when the collection efficiency was set to 0.99,of which 70.6 Me V proton beam current intensity was 7.4n A and 150.4 MeV was 5.69 nA.The modified worst case method proposed in this paper can effectively improve the robustness of the IMPT plan to the range and set-up uncertainties.It was shown that the weighting factor P_robust in this method can be used to control the trade-off between nominal plan quality and plan robustness.After further evaluation using clinical patient cases,this method is expected to become a new method to improve the quality of IPMT plans.In the theoretical study of the collection efficiency of a monitor parallel plate ionization chamber,the results can be used as a reference for the beam commissioning of the SAPT facility to improve the accuracy of dose delivery control.