Spatially Fractionated Radiation Therapy (SFRT) is a radiotherapy approach characterised by spatially inhomogeneous dose distributions. It was introduced to minimise damages to the healthy tissues in conventional photon-based cancer treatments, with similar or even enhanced tumour control rates. When proton beam therapy emerged, offering its own advantages in terms of reduced toxicity, their combination was investigated. This research, conducted at the University of Birmingham, focused on proton microbeams, the latter being a specific SFRT configuration. The aim was to perform a physical and dosimetric evaluation using a Complementary Metal Oxide Semiconductor (CMOS) detector to estimate relevant dosimetric parameters as a function of distance in different materials. They included peak and valley doses, as well as Peak-to-Valley Dose Ratios (PVDRs). Furthermore, in vitro irradiations of tumoural cells were performed at various dose levels. Given the project’s time frame, the objective was narrowed down to focus on observing the DNA damages and irradiation patterns with both broad beam and microbeam geometries. Damages in the form of Double Strand Breaks (DSBs) were tracked via γH2AX staining. Assessments with the CMOS yielded PVDRs reaching as high as 27.84 ± 0.44 in air, while irradiations effectively revealed distinct patterns. According to available literature, there does not appear to be any study on tumoural cells involving a similar pattern of proton microbeams. Furthermore, as the latter have never been employed in irradiations at the University of Birmingham before, this research represents a promising starting point for future investigations, possibly on more structured targets in which the biological effects of SFRT can be validated.
La radioterapia spazialmente frazionata (SFRT) è un approccio radioterapico caratterizzato da distribuzioni di dose spazialmente non omogenee. È stata introdotta per minimizzare i danni ai tessuti sani nei trattamenti contro il cancro basati sull’utilizzo dei fotoni, mantenendo gli stessi tassi di controllo tumorale o addirittura migliorandoli. Quando è emersa la terapia con fasci di protoni, offrendo essa stessa vantaggi in termini di minore tossicità, si è esplorata la possibilità di combinare le tecniche. Questa ricerca, condotta presso l'Università di Birmingham, si è concentrata sui microfasci di protoni. I microfasci sono una specifica forma di SFRT. L'obiettivo era condurre una valutazione fisica e dosimetrica utilizzando un rivelatore CMOS (Complementary Metal Oxide Semiconductor) per stimare alcuni parametri dosimetrici in funzione della distanza in diversi materiali. In particolare, sono state valutate le dosi di picco e di valle e i loro rapporti, noti come PVDR (Peak-to-Valley Dose Ratio). Inoltre, sono stati effettuati irraggiamenti di cellule tumorali in vitro a varie dosi. Data la durata del progetto, l’obiettivo è stato riformulato per concentrarsi sull’osservazione dei danni al DNA e dei pattern di irraggiamento in seguito all’esposizione ad un fascio di protoni non collimato ed ai microfasci. I danni, sottoforma di rotture a doppia elica del DNA (DSBs), sono stati evidenziati attraverso la fluorescenza dell’istone γH2AX. La valutazione con il CMOS ha restituito valori di PVDR fino a 27.84 ± 0.44 in aria, mentre gli irraggiamenti hanno evidenziato in maniera efficace la formazione di diversi pattern. Stando alle fonti disponibili, non sembra esistere in letteratura nessuno studio su cellule tumorali con una simile configurazione di microfasci di protoni. Inoltre, all’Università di Birmingham, non erano mai stati impiegati prima in irraggiamenti, per cui questa ricerca rappresenta un promettente punto di partenza per future indagini, possibilmente su bersagli più strutturati in cui gli effetti biologici della SFRT possano essere dimostrati.
Dosimetric assessment of proton microbeams and in vitro irradiation of tumoural cells
GAZZERA, ELISA
2022/2023
Abstract
Spatially Fractionated Radiation Therapy (SFRT) is a radiotherapy approach characterised by spatially inhomogeneous dose distributions. It was introduced to minimise damages to the healthy tissues in conventional photon-based cancer treatments, with similar or even enhanced tumour control rates. When proton beam therapy emerged, offering its own advantages in terms of reduced toxicity, their combination was investigated. This research, conducted at the University of Birmingham, focused on proton microbeams, the latter being a specific SFRT configuration. The aim was to perform a physical and dosimetric evaluation using a Complementary Metal Oxide Semiconductor (CMOS) detector to estimate relevant dosimetric parameters as a function of distance in different materials. They included peak and valley doses, as well as Peak-to-Valley Dose Ratios (PVDRs). Furthermore, in vitro irradiations of tumoural cells were performed at various dose levels. Given the project’s time frame, the objective was narrowed down to focus on observing the DNA damages and irradiation patterns with both broad beam and microbeam geometries. Damages in the form of Double Strand Breaks (DSBs) were tracked via γH2AX staining. Assessments with the CMOS yielded PVDRs reaching as high as 27.84 ± 0.44 in air, while irradiations effectively revealed distinct patterns. According to available literature, there does not appear to be any study on tumoural cells involving a similar pattern of proton microbeams. Furthermore, as the latter have never been employed in irradiations at the University of Birmingham before, this research represents a promising starting point for future investigations, possibly on more structured targets in which the biological effects of SFRT can be validated.È consentito all'utente scaricare e condividere i documenti disponibili a testo pieno in UNITESI UNIPV nel rispetto della licenza Creative Commons del tipo CC BY NC ND.
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https://hdl.handle.net/20.500.14239/16422