The overall goal of this project is to improve the proton therapy dose distributions that can confidently bedelivered. The improvements are expected to be threefold: (1) the use with confidence of tighter marginsaround the target volume, thus reducing normal tissue complications, (2) reduced uncertainty in treatmentplanning and delivery through techniques such as image-guided interventions and robust optimization, and(3) confidence that the dose distribution which is delivered agrees, within explicit bounds, with what wasplanned. While proton therapy has been practiced for several decades with success, there remain a numberof uncertainties and limitations that can compromise the benefit of protons, either by requiring undesirablylarge margins around the clinical target volume (with concomitant over irradiation of normal tissues) or bypreventing the use of protons or limiting their optimal application in some important sites (e.g., lung). Thehypothesis of this project is that improved accuracy in treatment planning and delivery methods and theapplication of intensity-modulated proton therapy (IMPT) and optimization techniques will lead to reductionsin margins and in the difference between planned and delivered dose distributions; also that these reductionswill be by a factor of at least 2 compared with the current values. To test this hypothesis, we will (1) quantifythe impact of current uncertainties and the gains made possible with strategies to reduce uncertainties, (2)evaluate the potential of IMPT and optimization techniques for reducing margins and mitigating the impact ofuncertainties, and (3) quantify the confidence limits on the planned dose distributions and verify that thedifferences between planned and delivered dose distributions are within confidence limits. The significanceof the proposed research is that it should lead to reductions in margins, greater sparing of normal tissues,and greater potential for dose intensification. Additionally, it should lead to greater confidence that theplanned and delivered proton therapy dose distributions are very nearly the same. The significance is furtherheightened by the need to minimize the possibility of suboptimal application of this very powerful modalitywhose use is rapidly proliferating around the world.
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