Alfredo Ferrari

(1) Background: Cancer ion therapy is constantly growing thanks to its increased precision and, for heavy ions, its increased biological effectiveness (RBE) with respect to conventional photon therapy. The complex dependence of RBE on many factors demands biophysical modeling. Up to now, only the Local Effect Model (LEM), the Microdosimetric Kinetic Model (MKM), and the “mixed-beam” model are used in clinics. (2) Methods: In this work, the BIANCA biophysical model, after extensive benchmarking in vitro, was applied to develop a database predicting cell survival for different ions, energies, and doses. Following interface with the FLUKA Monte Carlo transport code, for the first time, BIANCA was benchmarked against in vivo data obtained by C-ion or proton irradiation of the rat spinal cord. The latter is a well-established model for CNS (central nervous system) late effects, which, in turn, are the main dose-limiting factors for head-and-neck tumors. Furthermore, these data have been considered to validate the LEM version applied in clinics. (3) Results: Although further benchmarking is desirable, the agreement between simulations and data suggests that BIANCA can predict RBE for C-ion or proton treatment of head-and-neck tumors. In particular, the agreement with proton data may be relevant if the current assumption of a constant proton RBE of 1.1 is revised. (4) Conclusions: This work provides the basis for future benchmarking against patient data, as well as the development of other databases for specific tumor types and/or normal tissues.

Helium (4He) ion beam therapy provides favorable biophysical characteristics compared to currently administered particle therapies, i.e., reduced lateral scattering and enhanced biological damage to deep-seated tumors like heavier ions, while simultaneously lessened particle fragmentation in distal healthy tissues as observed with lighter protons. Despite these biophysical advantages, raster-scanning 4He ion therapy remains poorly explored e.g., clinical translational is hampered by the lack of reliable and robust estimation of physical and radiobiological uncertainties. Therefore, prior to the upcoming 4He ion therapy program at the Heidelberg Ion-beam Therapy Center (HIT), we aimed to characterize the biophysical phenomena of 4He ion beams and various aspects of the associated models for clinical integration. Characterization of biological effect for 4He ion beams was performed in both homogenous and patient-like treatment scenarios using innovative models for estimation of relative biological effectiveness (RBE) in silico and their experimental validation using clonogenic cell survival as the gold-standard surrogate. Towards translation of RBE models in patients, the first GPU-based treatment planning system (non-commercial) for raster-scanning 4He ion beams was devised in-house (FRoG). Our data indicate clinically relevant uncertainty of ±5–10% across different model simulations, highlighting their distinct biological and computational methodologies. The in vitro surrogate for highly radio-resistant tissues presented large RBE variability and uncertainty within the clinical dose range. Existing phenomenological and mechanistic/biophysical models were successfully integrated and validated in both Monte Carlo and GPU-accelerated analytical platforms against in vitro experiments, and tested using pristine peaks and clinical fields in highly radio-resistant tissues where models exhibit the greatest RBE uncertainty. Together, these efforts mark an important step towards clinical translation of raster-scanning 4He ion beam therapy to the clinic.

Due to their favorable physical and biological properties, helium ion beams are increasingly considered a promising alternative to proton beams for radiation therapy. Hence, this work aims at comparing in-silico the treatment of brain and ocular meningiomas with protons and helium ions, using for the first time a dedicated Monte Carlo (MC) based treatment planning engine (MCTP) thoroughly validated both in terms of physical and biological models. Starting from clinical treatment plans of four patients undergoing proton therapy with a fixed relative biological effectiveness (RBE) of 1.1 and a fraction dose of 1.8 Gy(RBE), new treatment plans were optimized with MCTP for both protons (with variable and fixed RBE) and helium ions (with variable RBE) under the same constraints derived from the initial clinical plans. The resulting dose distributions were dosimetrically compared in terms of dose volume histograms (DVH) parameters for the planning target volume (PTV) and the organs at risk (OARs), as well as dose difference maps. In most of the cases helium ion plans provided a similar PTV coverage as protons with a consistent trend of superior OAR sparing. The latter finding was attributed to the ability of helium ions to offer sharper distal and lateral dose fall-offs, as well as a more favorable differential RBE variation in target and normal tissue. Although more studies are needed to investigate the clinical potential of helium ions for different tumour entities, the results of this work based on an experimentally validated MC engine support the promise of this modality with state-of-the-art pencil beam scanning delivery, especially in case of tumours growing in close proximity of multiple OARs such as meningiomas.

EPJ Web of Conferences, open-access proceedings in physics and astronomy

The measured fluxes of secondary particles produced by the interactions of cosmic rays with the astronomical environment represent a powerful tool to infer some properties of primary cosmic rays. In this work we investigate the production of secondary particles in inelastic hadronic interactions between several cosmic rays species of projectiles and different target nuclei of the interstellar medium. The yields of secondary particles have been calculated with the FLUKA simulation package, that provides with very good accuracy the energy distributions of secondary products in a large energy range. An application to the propagation and production of secondaries in the Galaxy is presented.

The physics foundations of hadronic interactions as implemented in most Monte Carlo codes are presented together with a few practical examples. The description of the relevant physics is presented schematically split into the major steps in order to stress the different approaches required for the full understanding of nuclear reactions at intermediate and high energies. Due to the complexity of the problem, only a few semi-qualitative arguments are developed in this paper. The description will be necessarily schematic and somewhat incomplete, but hopefully it will be useful for a first introduction into this topic. Examples are shown mostly for the high energy regime, where all mechanisms mentioned in the paper are at work and to which perhaps most of the readers are less accustomed. Examples for lower energies can be found in the references