Experimental and computational characterisation of the secondary fragment field in clinical proton therapy beams using microdosimetry

Hadron therapy, including protons and carbon-ions, is increasingly used in clinical oncology due to its enhanced biological effectiveness and precision in targeting tumour tissues. While the role of secondary fragments is well recognized in carbon-ion therapy, their contribution in proton therapy remains understudied. This is mainly due to their low frequency of occurrence and limited impact on the physical dose. However, the secondary fragments generated by protons traversing a target material are heavier ions produced by target fragmentation. These interact differently with biological tissue, producing denser ionization clusters and much higher LET. Even though rare, they may substantially affect radiation quality and biological response. This work aims to characterise the secondary fragment field generated by a typical clinical proton beam using microdosimetry, and to evaluate how different detector types influence their measurement and the interpretation of their radiation quality. To this purpose, we performed experiments at the Trento Proton Therapy Centre using a 70.2 MeV proton beam moderated by 70 mm of lung-equivalent material. Microdosimetric spectra were acquired with two diamond detectors (0.85 and 12 µm sensitive volumes) and a spherical tissue-equivalent proportional counter (TEPC). Measurements were complemented by Geant4-based Monte Carlo simulations using a custom microdosimetry toolkit that focuses on the secondaries characterization. Microdosimetric spectra were analysed by classifying events according to their volume of origin and particle type, providing detailed insights into the contribution of secondary fragments. Despite accounting for less than 0.5% of total events, secondary fragments contributed up to 2.6% of the frequency-mean lineal energy ( y ¯ F ȳF ) and over 60% of the dose-mean lineal energy ( y ¯ D ȳD ), underscoring their relevance. Detector geometry and composition critically influenced spectral shape and sensitivity. Thinner detectors were better suited for target fragment detection. However, while solid-state microdosimeters produced self-fragments from their own structure, which are not representative of the irradiated medium, the TEPC's walls screened most of the fragments produced in the target material. These intrinsic experimental artefacts highlight the necessity of detector-specific interpretation of spectra when used for biological modelling. The custom Geant4-based microdosimetry toolkit developed proved to be a reliable tool for such interpretation. Overall, our results demonstrate the significant influence of secondary fragments on microdosimetric quantities in proton therapy and stress the importance of fragment-aware, detector-specific approaches for accurate assessment of radiation quality and prediction of biological outcomes.