Assessment of biological effects of primary and secondary irradiations in proton therapy by dosimetric measurements and simulations

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The high dose conformity and enhanced normal tissue sparing have made proton therapy an effective treatment for cancer. Nonetheless, the biophysical characterization of the radiation field at all dose levels remains challenging. The adoption of a generic RBE value of 1.1 in current clinical practice may be inadequate due to its variation with numerous parameters including a strong correlation with the particle's LET. Both quantities vary across the treatment volume with a substantial increase towards the distal edge, which is concerning due to the presence or proximity of OARs in those regions. Accurately calculating the LET is necessary to predict and improve the biological outcomes, but measuring LET experimentally is difficult and simulation parameters can influence the results, which also hinder the clinical implementation of LET-based RBE models. To mitigate the range uncertainties and potentially higher RBE at the distal edge, the lateral field edge is typically used to spare adjacent OARs. However, the substantial spot size in proton PBS along with scattering events result in a larger lateral penumbra compared to collimated broad divergent beams, particularly at shallow depths and large air gaps. Studies have demonstrated dosimetric advantages by combining PBS with apertures, but the biophysical effects of this configuration are not well understood with some studies suggesting an increase in the LET at the lateral edges. Considering the importance of sparing OARs, a detailed biophysical characterization and comparison of collimated and uncollimated fields in PBS is crucial. Furthermore, the characterization of the secondary radiation field in PT remains challenging due to the mixture of particles with a wide energy range and a major contribution from neutrons associated with a high RBE. These challenges were addressed in this work, by combining measurements with a Timepix-based detector, MC simulations and biophysical models. A model was developed to overcome Timepix limitations in high-resolution directional detection and LET calculation. The model can be used for precise incident angle and LET calculation of protons over a full field-of-view using a compact single-layer Timepix detector, based on a detailed track analysis of registered pixel clusters. The model was further coupled with a methodology for converting proton LETF from silicon to water. Building upon this work, a systematic approach to calculate the total and particle-specific absorbed dose and dose equivalent in water was also presented. This work was the first to demonstrate the feasibility of estimating different dose quantities in a mixed radiation field using a hybrid sensor in single-event mode with sufficient accuracy, validated with MC simulations and TLD measurements. These methods were exploited in different proton therapy applications. First, we demonstrated the feasibility of using a compact detector for a precise directional detection and LET estimation (average values and distributions), known to be a good surrogate of RBE. Second, a biophysical characterization and comparison of collimated and uncollimated fields using measurements and simulations coupled with biophysical models revealed a lower dose, higher LET and lower DNA damage induction, for collimated PBS fields relative to uncollimated ones. The highest impact was found at the lateral field edges, extending up to a few centimeters, and was more pronounced at lower energies. Third, a detailed analysis of the secondary radiation field in a 5-year-old phantom anthropomorphic phantom receiving a clinical PBS treatment for a pediatric brain tumor was carried out. The results showed that various dose quantities in mixed radiation fields can be measured using a Timepix detector with good accuracy, potentially eliminating the need to combine multiple detector systems or to run full MC simulations. The methods and results presented in this work can be extended to other clinical indications and to more intricate scenarios where the particle-specific dose and LET distributions may vary. Proton therapy can offer important benefits for patients, especially with PBS and IMPT techniques, but further research is needed to improve clinical outcomes. Timepix-based detectors along with the methods developed in this work have shown to be a valuable tool for PT applications. A detailed biophysical characterization of the radiation field at various dose levels may open new perspectives for treatment optimization and improved radiation protection, and potentially allowing more patients to benefit from PT.
Original languageEnglish
QualificationDoctor of Science
Awarding Institution
  • KU Leuven
  • Sterpin, Edmond, Supervisor, External person
  • Van Hoey, Olivier, SCK CEN Mentor
  • Tabury, Kevin, SCK CEN Mentor
Date of Award24 May 2023
StatePublished - 24 May 2023

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