Daily adaptive proton therapy: challenges and clinical potential

Abstract

With proton therapy, highly conformal dose can be applied to the tumor while sparing the surrounding organs at risk. Protons are however sensitive to density changes in the beam path: If the patient anatomy is changing, the resulting dose is distorted. To restore the initial plan quality, the plan has to be adapted. In this thesis, the concept of daily adaptive proton therapy (DAPT) is investigated to react to daily anatomical changes and improve the overall treatment quality. With DAPT, a new plan is optimized based on a 3D image acquired directly (some minutes) before each fraction. The whole online workflow must be efficient, not exceeding 5 to 10 minutes, to not increase the occupancy time in the treatment room too much or decrease the patient comfort. DAPT has the potential to improve the treatment quality, but technical and workflow challenges have prevented its clinical integration so far. In this thesis, different aspects about the clinical benefit of DAPT and the sensitivity of DAPT to different uncertainties caused by simplifications in the DAPT workflow, such as analytical dose calculation or structure propagation, are investigated. Additionally, the uncertainties in the evaluation of the overall applied treatment dose and outcome are discussed and the dosimetric benefit of DAPT is shown in a phantom experiment. After a short introduction (chapter 1), more details about the clinical implementation of DAPT at the Paul Scherrer Institute (PSI) are discussed in chapter 2. The potential benefit of DAPT for patients treated in the paranasal sinuses is discussed in chapter 3. There it is shown how DAPT enables novel planning concepts and can reduce the integral dose to healthy tissue. Chapter 4 shows that DAPT brings a dosimetric benefit to the patients, even if the daily plan is optimized with analytical dose calculation algorithms in challenging anatomical sites such as the nose or the lung. Chapter 5 investigates how the use of propagated structures is affecting the dose distribution of the daily plan, because in the strict time span allowed for a DAPT treatment, there is no time for correcting the contours. For each fraction, there is only limited time to check the daily plan, which makes a careful offline dose review and monitoring of the treatment progress necessary. In chapter 6, the uncertainties of deformable image registration for the dose accumulation are investigated and in chapter 7 the effect of DAPT to the clinical outcome (e.g. tumor control, mortality or other side effects) is evaluated. Finally, the dosimetric benefit of the DAPT workflow implemented at PSI is shown in chapter 8 in an end-to-end test over multiple fractions with a newly developed anthropomorphic phantom with anatomical changes. The work described in this thesis puts the benefits of DAPT in relation to different uncertainties occurring during the DAPT workflow. In different planning studies and in an end-to-end experiment it was shown that the dosimetric benefits of DAPT are larger than the risks of the investigated uncertainties. It was also shown that the dosimetric benefit of DAPT can translate into an improved clinical outcome. The first patient treatment with the DAPT workflow tested in this project is planned for the beginning of next year, 2021.