Definitive treatment for early-stage breast cancer with FLASH proton therapy

Dosimetric feasibility and optimization with intensity-modulated ridge filtered beams and toxicity-model endpoints

More Info


The aim of this thesis is to study the dosimetric feasibility of FLASH proton therapy for early-stage breast cancer patients. The biological effect of FLASH is seen under ultra-high dose-rates conditions and is beneficial in the damage to healthy tissue. The FLASH effect could enable the clinical feasibility of definitive radiotherapy for low-risk early-stage breast cancer patients. Some of these patients can not receive surgery for medical reasons and definitive conventional radiotherapy carries a high risk of toxicities. FLASH proton therapy could be a viable option for these patients. The biological FLASH effect enables to reduce the risk of toxicities by sparing healthy tissue and proton therapy enables to deliver dose to the cancer cells effectively.
This thesis proposes a pencil beam scanning (PBS) ridge filter simulation set-up to achieve ultra-high dose-rates. The ridge filter generates spread-out Bragg peak (SOBP) beams that cover a broader depth of the tumor, avoiding the time-consuming energy switching of conventional PBS. An optimization is performed with intensity-modulated ridge filtered beams. SOBP beams with a width of 3 cm are implemented in the in-house treatment planning software Erasmus-iCycle to generate ridge filter treatment plans for two patients.
In this study, the dosimetric feasibility is determined by comparing the ridge filter treatment plans to conventional intensity-modulated proton therapy (IMPT) treatment plans. The clinical acceptability of the treatment plans is assessed by dose uniformity and dose coverage. Furthermore, toxicity-model endpoints for fat necrosis and fibrosis are used to evaluate the treatment plans. The generated ridge filter treatment plans outperform the generated IMPT treatment plans for a FLASH enhancement ratio between 1.19-1.39 for one of the patients. The other patient required a FER in the order of magnitude of 2.0.
The results of the study suggest that it is feasible to generate ridge filter treatment plans with the proposed set-up. However, the dosimetric feasibility comes with limitations in the tumor characteristics (size and position) and needs further investigation. More knowledge is needed of the optimal ridge filter, the optimization of SOBP beams, and the FLASH effect before clinically acceptable FLASH-compatible ridge filter treatment plans can be achieved.