Nanodosimetric Track Structure Studies for Applications in Particle Therapy

Compared to the conventional photon therapy, the irradiation with charged particles allows achieving a superior dose conformity to the tumor, a lower integral dose to the patient, and an enhanced biological effectiveness (for heavy ions). These attractive features have encouraged a rapid diffusion of particle therapy centers over the last decade. However, due to the lack of extensive clinical data and epidemiological studies, the assessment of the biological outcome of this relatively new technique is subject to large uncertainties. Moreover, the standard dosimetric quantities are unable to resolve the differences in the radiation biological effects caused by the features of the track structure produced by particles of different types and energies. On the other hand, the capability of nanodosimetry to describe the radiation track structure produced in biological tissue – or in water as a surrogate of biological tissue – through measurements in low pressure gas, has the potential to overcome the limitations of the standard dosimetric approach. In this thesis, the use of nanodosimetry to address the radiobiological challenges of particle therapy has been proposed. Monte Carlo simulations have been performed to study the introduction of the nanodosimetric approach for the characterization of the track structure of the mixed radiation fields produced in the patient inside and outside the treatment fields. The radiation tracks simulated in a water phantom irradiated with either protons or carbon ions have been analyzed to obtain quantities related to the radiation-induced damage to DNA. Such quantities have been used to quantify the damage caused by secondary radiation of proton beams relatively to the damage caused by photon irradiation. Moreover, biologically weighted treatments have been obtained by optimizing the fluences of the particle beams in order to create a mixed radiation field with given nanodosimetric parameters within the target volume. The second step of the work has been the development of an experimental device for nanodosimetric measurements in the clinical environment. Experimental measurements have been performed to study the working principle of a novel track imaging detector (TIDe) and to characterize the detector performance. Ions produced by low energy alpha particles in low pressure gas have been successfully detected with a TIDe prototype. However, a low ion detection efficiency – of the order of few percent – has been observed. Further work has been performed to enhance the detector performance by varying the detector geometry and building materials. This work has demonstrated that the nanodosimetric approach allows the characterization of the complex radiation fields produced in particle therapy with measurable quantities, directly related to the induction of biological damage. Furthermore, the first stages of the development of a detector for the measurements of such quantities have been performed. Finally, the next steps, both theoretical and experimental, necessary for the implementation of the approach in the clinical practice of particle therapy have been identified.