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Hadrontherapy is today an established modality in cancer radiation therapy. Based on the superior ballistic and radiobiological properties of accelerated ions, this discipline experienced a remarkable growth in the last 20 years. This paper reviews the history of hadrontherapy, from the early days to the most recent developments. In particular, the evolution of proton and carbon ion therapy is presented together with a glance at future solutions such as single-room facilities.

Charged particle applications for radiotherapy are motivated by their specific advantages in terms of dose delivery and biological effect. These advantages have to a large extent originated from the peculiarities of ion beam energy deposition patterns in the medium on a microscopic, down to a nanoscopic scale. A large amount of research was conducted in this direction, especially in the last two decades, profiting also from the parallel investigations going on in radiation protection for space exploration.

The main biophysical aspects of charged particles, which are relevant to hadrontherapy are shortly reviewed in the present contribution, namely focusing on relative biological effectiveness (RBE), oxygen enhancement ratio (OER) and combination with radiosensitizers. A summary of present major research direction on both microscopic and macroscopic assessment of the specific mechanism of radiation damage will be given, as well as several open challenges for a better understanding of the whole process, which still limit the full exploitation of ion beams for radiotherapy.

Proton computed tomography (pCT) is a diagnostic method capable of in situ imaging the three-dimensional density distribution in a patient before irradiation with charged particle beams. Proposed long time ago, this technology has been developed by several groups, and may become an essential tool for advanced quality assessment in hadrontherapy. We describe the basic principles of the method, its performance and limitations as well as provide a summary of experimental systems and of results achieved.

Segmented ionization chambers represent a good solution to monitor the position, the intensity and the shape of ion beams in hadrontherapy. Pixel and strip chambers have been developed for both passive scattering and active scanning dose delivery systems. In particular, strip chambers are optimal for pencil beam scanning, allowing for spatial and time resolutions below 0.1 mm and 1 ms, respectively. The MATRIX pixel and the Strip Accurate Monitor for Beam Applications (SAMBA) detectors are described in this paper together with the results of several beam tests and industrial developments based on these prototypes.

The information of the dose is not sufficiently describing the biological effects of ions on tissue since it does not express the radiation quality, i.e. the heterogeneity of the processes due to the slowing-down and the fragmentation of the particles when crossing a target. Depending on different circumstances, the radiation quality can be determined using measurements, calculations, or simulations. Microdosimeters are the primary tools used to provide the experimental information of the radiation quality and their role is becoming crucial for the recent clinical developments in particular with carbon ion therapy. Microdosimetry is strongly linked to the biological effectiveness of the radiation since it provides the physical parameters which explicitly distinguish the radiation for its capability of damaging cells. In the framework of ion-beam therapy microdosimetry can be used in the preparation of the treatment to complement radiobiological experiments and to analyze the modification of the radiation quality in phantoms. A more ambitious goal is to perform the measurements during the irradiation procedure to determine the non-targeted radiation and, more importantly, to monitor the modification of the radiation quality inside the patient. These procedures provide the feedback of the treatment directly beneficial for the single patient but also for the characterization of the biological effectiveness in general with advantages for all future treatment. Traditional and innovative tools are currently under study and an outlook of present experience and future development is presented here.

The use of radiofrequency linacs for hadrontherapy was proposed about 20 years ago, but only recently has it been understood that the high repetition rate together with the possibility of very rapid energy variations offers an optimal solution to the present challenge of hadrontherapy: "paint" a moving tumor target in three dimensions with a pencil beam. Moreover, the fact that the energy, and thus the particle range, can be electronically adjusted implies that no absorber-based energy selection system is needed, which, in the case of cyclotron-based centers, is the cause of material activation. On the other side, a linac consumes less power than a synchrotron. The first part of this article describes the main advantages of high frequency linacs in hadrontherapy, the early design studies, and the construction and test of the first high-gradient prototype which accelerated protons. The second part illustrates some technical issues relevant to the design of copper standing wave accelerators, the present developments, and two designs of linac-based proton and carbon ion facilities. Superconductive linacs are not discussed, since nanoampere currents are sufficient for therapy. In the last two sections, a comparison with circular accelerators and an overview of future projects are presented.

Since 1990, when the world's first hospital-based proton therapy center opened in Loma Linda, California, interest in dedicated proton and carbon ion therapy facilities has been growing steadily. Today, many proton therapy centers are in operation, but the number of centers offering carbon ion therapy is still very low. This difference reflects the fact that protons are well accepted by the medical community, whereas radiotherapy with carbon ions is still experimental. Furthermore, accelerators for carbon ions are larger, more complicated and more expensive than those for protons only. This article describes the accelerator performance required for hadrontherapy and how this is realized, with particular emphasis on carbon ion synchrotrons.

Superconductivity is playing an increasingly important role in advanced medical technologies. Compact superconducting cyclotrons are emerging as powerful tools for external beam therapy with protons and carbon ions, and offer advantages of cost and size reduction in isotope production as well. Superconducting magnets in isocentric gantries reduce their size and weight to practical proportions. In diagnostic imaging, superconducting magnets have been crucial for the successful clinical implementation of magnetic resonance imaging. This article introduces each of those areas and describes the role which superconductivity is playing in them.

The evaluation of nuclear fragmentation contribution on the delivered dose during particle therapy treatment is still an open point. The FOOT (FragmentatiOn Of Target) experiment aims to improve the actual knowledge of nuclear physics by measuring the differential cross section as a function of the energy and angle of the fragments produced when an external particle beam interacts with patent tissues during hadrontherapy treatment. Depending on the beam energy, the purpose of the measurements is dual: in the range of 150–400 MeV/u, they will be used to evaluate the side effects of the nuclear fragmentation in the hadrontherapy treatment, while in the range of 700–1000 MeV/u (typical of cosmic galactic rays) they will be used to optimize the shielding of the spaceship for long term space missions. The FOOT detector includes a pre-target region with a first plastic scintillator for time of flight (TOF) and trigger purpose, and a beam monitor drift chamber to evaluate the beam direction (necessary for the inverse kinematic approach); a magnetic spectrometer to measure the momentum of fragments; and finally a second plastic scintillator for deposited energy (ΔE) and TOF measurements, and a scintillating crystal calorimeter to measure the kinetic energy of fragments. These measurements will be combined to accurately identify the charge and mass of fragments. The experiment, funded by the INFN since September 2017, is in the construction phase. It has performed several test beams, while the full detector data taking is scheduled in the next few years. A full description of the different setups together with the performances obtained with the latest geometry studies are reported here.

The use of radiofrequency linacs for hadrontherapy was proposed about 20 years ago, but only recently has it been understood that the high repetition rate together with the possibility of very rapid energy variations offers an optimal solution to the present challenge of hadrontherapy: “paint” a moving tumor target in three dimensions with a pencil beam. Moreover, the fact that the energy, and thus the particle range, can be electronically adjusted implies that no absorber-based energy selection system is needed, which, in the case of cyclotron-based centers, is the cause of material activation. On the other side, a linac consumes less power than a synchrotron. The first part of this article describes the main advantages of high frequency linacs in hadrontherapy, the early design studies, and the construction and test of the first high-gradient prototype which accelerated protons. The second part illustrates some technical issues relevant to the design of copper standing wave accelerators, the present developments, and two designs of linac-based proton and carbon ion facilities. Superconductive linacs are not discussed, since nanoampere currents are sufficient for therapy. In the last two sections, a comparison with circular accelerators and an overview of future projects are presented.

Since 1990, when the world's first hospital-based proton therapy center opened in Loma Linda, California, interest in dedicated proton and carbon ion therapy facilities has been growing steadily. Today, many proton therapy centers are in operation, but the number of centers offering carbon ion therapy is still very low. This difference reflects the fact that protons are well accepted by the medical community, whereas radiotherapy with carbon ions is still experimental. Furthermore, accelerators for carbon ions are larger, more complicated and more expensive than those for protons only. This article describes the accelerator performance required for hadrontherapy and how this is realized, with particular emphasis on carbon ion synchrotrons.

Superconductivity is playing an increasingly important role in advanced medical technologies. Compact superconducting cyclotrons are emerging as powerful tools for external beam therapy with protons and carbon ions, and offer advantages of cost and size reduction in isotope production as well. Superconducting magnets in isocentric gantries reduce their size and weight to practical proportions. In diagnostic imaging, superconducting magnets have been crucial for the successful clinical implementation of magnetic resonance imaging. This article introduces each of those areas and describes the role which superconductivity is playing in them.