The Study On The Clinical Techniques To Deal With The Uncertainty Of Intensity Modulated Proton Therapy For Lung Cancer

Compared with traditional photon radiotherapy,the energy loss rate of proton beam will form a peak at the end of its range while passing through the material,called Bragg peak,and the dose will quickly drop to zero after the peak.Due to the unique physical advantage of proton beam,broadening the Bragg peak of proton beam to the focus of the tumor will further increase the dose delivered to the tumor while minimizing that delivered to surrounding healthy organs.Nowadays,the pencil beam scanning technology is a promising methods of broadening Bragg peak,which is so-called intensity-modulated proton therapy(IMPT)in clinical planning.Dosimetric studies have demonstrated that proton therapy,especially IMPT,can reduce the dose to critical normal tissues relative to photon radiotherapy for patients with early-stage non-small cell lung cancer(NSCLC).Although IMPT has obvious dosimetric advantages,the following uncertainties must be dealt with in order to make full use of the advantage of IMPT:(1)Uncertainties from patient setup errors.(2)Range uncertainty resulting from the uncertainty in the Hounsfield units(HUs)of computed tomography images and the values of stopping powers.(3)The interplay effect between the motion of the scanning beam and target motion.(4)High LET value in healthy tissue caused by the RBE model uncertainties.These uncertainties compromise the accuracy of IMPT to a greater extent that the actual dose will be different from the planned dose.Here,current papers performed studies of both theoretical studies and clinical application for the pursuit of a doctoral dissertation.Finally,the main research work is list as bellow:First,the author introduced the concept of ITV based robust planning to compare the conventional approach,i.e.PTV based planning,in regards to range uncertainty and patients setup uncertainty for lung cancers.In order to evaluate objectively,current paper developed specific index for robustness in terms of setup and range uncertainties,which provide a clinical basis for recommendation the usage of ITV in the conceptual of ITV based robust planning.Moreover,to improve the plan efficiency of ITV based robust plan,an automated ITV based robust planning methods was proposed based on the similar sharpness dose characteristics of Stereotactic body radiotherapy(SBRT)and IMPT.The results showed that the target gradient could be increased,the dose of total lung could be further reduced as well as planning times,which provided an alternative plan for the design of IMPT for lung cancer.Secondly,in order to handle the interplay effect caused by the tumor motion during the plan delivery,current paper assessed interplay effect of IMPT plan systematically using a commercial proton device and treatment planning system and proposed the several repainting schemes of iso-energetic layer to obtain the optimal times based on our proposed quantitative metrics for interplay effect.The results demonstrated that the interplay effect led to the deterioration of the dose in the target,and the layer repainting method can mitigated the interplay effect.Therefore,it was recommended to use the interplay metrics in clinical practice to select the optimal times of repainting based on the characteristics of patients.Thirdly,in order to cope with the uncertainty of relative biological effect(RBE),the paper evaluated the variation trend of the dosimetric index and the LET index of target area and organs at risk with the number of fields quantitatively using the lung cancer data,based on the current variable RBE model and the LET model.The results showed that the maximum LET value of organ at risk decreased with the increasing number of proton beams,while the plan robustness increased.In summary,to handle the impact of uncertainties in IMPT planning for lung cancer: Firstly,all patients were scanned with 4DCT,and the maximum tumor motion was assessed quantitatively by the DVL formula;secondly,for the patients with less than specific motion range level(for example,5mm),patient setup,and range should be considered using ITV based robust IMPT plan.Moreover,for the patients with more than specific motion range level,CTV based robust optimization should be used to handle the interplay effect based on 4DCT image and our proposed interplay metrics should be used to decide if iso-energetic layer repainting method to use to mitigate the interplay effect.Furthermore,for the patient with organ at risk is close to the target,the recalculated dose distribution should be using variable RBE model and LET model,which show us to investigated if needed to use multi-field method to reduce the higher LET for organ at risk.Thirdly,as well as variable RBE model dose distribution and LET distribution should be calculated for multi-field method selection.At last,for the selected plan with layer repainting strategy to mitigate the interplay effect,the quantitatively interplay metrics was reused to decide the optimal number of layer rescanning,which mitigated interplay effect best.In the process of robust planning,the developed automated robust plan methods was used to improve plan quality and efficiency.