Accelerated ion beams with therapeutically relevant energy result in a narrow and sharp Bragg peak. For treating tumors of different sizes and shapes, the narrow peak should be broadened to cover the clinical target. Two methods have been introduced for this problem: a beam scattering method and a beam scanning method. Conventionally, a passive beam shaping device has been used to broaden the beam profile transversely and extend the Bragg peak dose from the distal to the proximal end of the target volume, respectively. Although conventional passive beam irradiation requires relatively simple treatment planning, there is one disadvantage which is the significantly excessive doses delivered to the normal tissues along the entrance to the target. Layer stacking was proposed to reduce this excessive dose and to achieve higher dose conformation with passive beam [19,20]. Fig. 5 illustrates the principle layer-stacking method. This technique uses a fine ridge filter, a range shifter, and MLC. The target is subdivided into regions with a 2.5 mm layer along the beam direction. By changing the MLC opening, the beam field size is defined to fit the respective subdivided regions. However, passive beam delivery techniques still have disadvantages as follows. The efficiency of beam utilization is low, 10%–30%, resulting in a relatively large neutron contamination and high beam intensity; the beam shaping devices such as the compensator and MLC are required. Nevertheless, a PBS method still has more advantages than a broad-beam method as follows. For irregularly shaped tumors, the dose distribution is more conformal; the efficiency of beam utilization is almost 100%; the amount of radiation shielding, thus, can be less than that in broad-beam method; secondary neutron can be significantly reduced. GSI developed the hybrid scanning system with a pencil beam [21]. Both HIT and CNAO used it in routine treatment [22,23]; however, PBS was not robust against the position and profile errors of the beam, and further, the risk of dose degradation increased by interplay with organ motion. Therefore, the PBS method was not generally applied for respiratory moving targets. In 2006, NIRS initiated a project to construct the New Particle Therapy Research Facility (NPTRF) for carbon ion beam scanning delivery. The scanning systems of NPTRF directly followed a developed and tested prototype [24]. The scanning speed of 100 m/s was achieved on the isocenter plane painting each layer quickly [24]. In 2007, Furukawa et al. [25] proposed the respiratory phase-controlled rescanning method in order to apply PBS to the respiratory moving target. In 2012, the energy was rapidly changed one after another with a range shifter during beam delivery by multienergy extended-flattop extraction [26]. After the commissioning of 200 energy steps in 2015 [27], the full energy scanning mode without range shifting was introduced for clinical operation in 2017 [28]. Recent PBS methods have been developed with two sets of scanning magnets to scan the beam in a plane within the target volume. There are two ways to scan the beam spot: dynamic (or continuous) scanning method in a raster or line pattern, where the scan speed, beam intensity, or both are varied to produce the prescribed intensity distribution by treatment planning; discrete spot scanning method, where the beam is cut off between spots and the dose at each spot is varied to achieve the prescribed dose pattern. The continuous raster scanning is utilized to save the beam on/off time during beam movement between spot positions instead of discrete spot scanning. Pencil beam 3D scanning is an irradiation method where a pencil beam is laterally scanned to make a lateral irradiation field with orthogonal scanning dipole magnets and then longitudinally scanned by either a range shifter or energy change. The 3D scanning method incorporated with a rotating gantry can achieve higher treatment accuracy applying intensity-modulated particle therapy with multiple fields [29]. The advanced PBS technique will be further developed to achieve faster scanning speeds, smaller spot size, and more accurate spot positioning.

The rotating gantry can irradiate the tumor from several angles. Conventionally, the supine position is used because it minimizes the displacement of internal organs and is the most comfortable position for the patient. The gantry system offers more flexibility when selecting beam directions than the fixed beam. By choosing the most adequate beam incidence, the sensitive organs and the complex density heterogeneities can be avoided in the patient’s body.

In 1990, the first proton beam radiotherapy facility with a rotating gantry was built by Loma Linda (Fermilab), whereas, In 2009, the first facility with a 360° rotating gantry for CIRT was constructed in HIT; its characteristics were as follows: length, 25 m; radius, 6.5 m; weight, about 600 tons. HIT used only normal conducting magnets for the gantry, whereas NIRS installed a second rotating gantry for CIRT in 2017, which was the first rotating gantry with superconducting magnets with a significantly reduced size (length, 13 m; radius, 5.5 m) and weight (about 300 tons). The current developed superconducting rotating gantry is being installed at Yamagata University, Japan, with a length of approximately 25 m, a radius of approximately 5.5 m, and a weight of about 200 tons. By increasing the magnetic field strength produced by the superconducting magnet, the gantry size of 40% was achieved.

The most innovative feature for CIRT is the superconducting rotating gantry, allowing a compact small-sized and lightweight gantry design. Furthermore, when energy modulation is conducted upstream, the associated fast changes in magnet and on their power supplies. Recently, Kim et al. [30] presented a very compact gantry design for CIRT, where the gantry’s length and radius were 9.74 m and 3.17 m, respectively, reduced by using 5-T superconducting bending magnets for C⁶⁺ ion beam of 400 MeV/u. It can transport an asymmetric beam and yields a beam with a full width at half maximum of 4 mm at the isocenter regardless of the rotating angle. Upstream parallel scanning covers a 20×20 cm² field size at the isocenter.

Clinically, field size and dose rate are important irradiation parameters. Field size is the distance between the 50% points of the maximum dose value, measured along the line perpendicular to the beam central axis, on the isocenter plane in the air. The maximum field sizes for scanned beams of ions are currently smaller than those for passive beams because the high magnetic field requires fast deflection of the high-energy ion beams. The maximum field size for the scanned beam at HIT is 20×20 cm², whereas, at HIMAC, the maximum field sizes with the scanned beam are 22×22 cm² and 20×20 cm² for the fixed beam and gantry, respectively. Using translations of the treatment table may facilitate the treatment of larger fields. Clinically, a larger field size is required for CIRT, which can be increased by downsizing a scanning magnet, in other words, shortening the source-to-axis distance. The maximum field size of 25×25 cm² is being installed at Yamagata University, Japan.

The dose escalation studies of hypofractionated CIRT were conducted by the Japan group. At NIRS, Clinical trials were carried out with a hypofractionated schedule, and favorable results were obtained. The dose rate is another major parameter influencing the quality of treatment by determining the treatment time and affecting the radiobiological properties. Using passive beam methods, the typical dose rate required for treatment is about 5 GyE/min (roughly equal to a physical dose of 2 Gy) to 1 L volume corresponding to beam intensity of 10⁹ particles per second (pps), under a beam utilization efficacy of about 20% to 30%. Therefore, in PBS, the beam intensity can be decreased because the beam utilization efficacy increases to almost 100%. In the scanning beam methods, the typical dose rate required for treatment is about 2 Gy/min to 1 L volume corresponding to around 10⁸ pps. The higher dose rate could be achieved by modifying the dose monitor and control system. The extracted particle number per second will increase by increasing the dose monitor dynamic range. However, for continuous beam scanning with a high dose rate (e.g., 4 Gy/min/L), the amount of extra dose during beam moving between positions should be evaluated because the beam is not turned off.

In the last few decades, proton and carbon ion particle therapies have been developed and their clinical applications have proved to be feasible and effective. Other ion beams, such as helium, oxygen, and neon, have been investigated and applied in treating tumors with different radiation sensitivities against different ion species. At LBL, helium and neon ions have been examined in clinical trials [31,32]. Between 1977 and 1994, around 2,000 patients were treated with helium ions using passive beam delivery at LBL [33]. Recent studies suggest that helium ions will be used as a potential treatment beam for further particle therapy improvement due to their favorable physical characteristics [34 -37]. Helium ions show a low-dose fragmentation tail compared to carbon ions and exhibit less lateral beam spread and a higher LET than protons. From the biological point of view, helium RBE is closer to that of protons and certainly lower than that of carbon ions. HIT studied helium ion beams using measurements and Monte Carlo simulation in terms of dose distributions with single pencil beam, SOBP plans, and nuclear fragmentation [37 -40]. In 2020, the first European clinical program using helium ions by the raster-scanning method will be launched by HIT. Moreover, the beam delivery of multiple ion species has been investigated to maximize the therapeutic effects of charged particle beam in a single treatment session [41,42]. Inaniwa et al. [41] introduced the intensity-modulated composite particle therapy using two or more ion species in one treatment session, which enables the optimization of the dose and the LET distribution. The planning target volume (PTV) has higher LET than that of OARs while keeping the dose to PTV uniform. Recently, the European group developed the combined ion beam with constant RBE particle therapy in single field arrangements [43]; they reported that biophysically robust particle therapy treatments are feasible when combining heavy and light ions in a single treatment field, yielding uniform effective dose, RBE, and, in turn, physical dose distributions within the target. Through comprehensive dosimetric and in vitro study, multi-ion particle therapy will provide great clinical advantages.

Respiratory motions are significantly important when treating moving target, especially in the treatment of lung cancer, which may be reduced in two primary ways as follows: (1) beam gating, where the beam is turned off after the target has moved out of the calculated treatment position; (2) repainting layers or treatment volume (i.e., repainting means to scan two or more times). In 2007, Furukawa et al. [25] developed a respiratory phase-controlled rescanning method to apply PBS to the respiratory moving target. A rescanning technique can be employed to average the effect of the irradiation at different breathing phases. This technique compensates for the interplay effects due to the residual motion of the target. Since rescanning does not involve any specific hardware, margins related to technical complexity will be low and comparable to stationary irradiation. The scanning speed is typically assumed to be sufficient using scanner magnets. The treatment control system mainly requires for rescanning. Gating requires a beam control system for pausing and resuming the beam based on the motion surrogate. Given the technical development and the current situation, motion mitigation reply on rescanning technique. However, studying the beam tracking method for motion mitigation can be a research topic to maximize target conformation and minimize treatment time. By selecting the appropriate motion mitigation technique, the best target coverage and conformation will be achieved with far less treatment time.