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We present a design of superconducting magnets, optimized for application in a gantry for proton therapy. We have introduced a new magnet design concept, called an alternating-gradient canted cosine theta (AG-CCT) concept, which is compatible with an achromatic layout. This layout allows a large momentum acceptance. The 15 cm radius of the bore aperture enables the application of pencil beam scanning in front of the SC-magnet. The optical and dynamic performance of a gantry based on these magnets has been analyzed using the fields derived (via Biot-Savart law) from the actual windings of the AG-CCT combined with the full equations of motion. The results show that with appropriate higher order correction, a large 3D volume can be rapidly scanned with little beam shape distortion. A very big advantage is that all this can be done while keeping the AG-CCT fields fixed. This reduces the need for fast field ramping of the superconducting magnets between the successive beam energies used for the scanning in depth and it is important for medical application since this reduces the technical risk (e.g., a quench) associated with fast field changes in superconducting magnets. For proton gantries the corresponding superconducting magnet system holds promise of dramatic reduction in weight. For heavier ion gantries there may furthermore be a significant reduction in size.

Each year, 500,000 patients are treated with radiotherapy for head and neck cancer, resulting in relatively high survival rates. However, in 40% of patients, quality of life is severely compromised because of radiation-induced impairment of salivary gland function and consequent xerostomia (dry mouth). New radiation treatment technologies enable sparing of parts of the salivary glands. We have determined the parts of the major salivary gland, the parotid gland, that need to be spared to ensure that the gland continues to produce saliva after irradiation treatment. In mice, rats, and humans, we showed that stem and progenitor cells reside in the region of the parotid gland containing the major ducts. We demonstrated in rats that inclusion of the ducts in the radiation field led to loss of regenerative capacity, resulting in long-term gland dysfunction with reduced saliva production. Then we showed in a cohort of patients with head and neck cancer that the radiation dose to the region of the salivary gland containing the stem/progenitor cells predicted the function of the salivary glands one year after radiotherapy. Finally, we showed that this region of the salivary gland could be spared during radiotherapy, thus reducing the risk of post-radiotherapy xerostomia.

Purpose: In proton therapy, the gantry, as the final part of the beamline, has a major effect on beam intensity and beam size at the isocenter. Most of the conventional beam optics of cyclotron‐based proton gantries have been designed with an imaging factor between 1 and 2 from the coupling point (CP) at the gantry entrance to the isocenter (patient location) meaning that to achieve a clinically desirable (small) beam size at isocenter, a small beam size is also required at the CP. Here we will show that such imaging factors are limiting the emittance which can be transported through the gantry. We, therefore, propose the use of large beam size and low divergence beam at the CP along with an imaging factor of 0.5 (2:1) in a new design of gantry beam optics to achieve substantial improvements in transmission and thus increase beam intensity at the isocenter. Methods: The beam optics of our gantry have been re‐designed to transport higher emittance without the need of any mechanical modifications to the gantry beamline. The beam optics has been designed using TRANSPORT, with the resulting transmissions being calculated using Monte Carlo simulations (BDSIM code). Finally, the new beam optics have been tested with measurements performed on our Gantry 2 at PSI. Results: With the new beam optics, we could maximize transmission through the gantry for a fixed emittance value. Additionally, we could transport almost four times higher emittance through the gantry compared to conventional optics, whilst achieving good transmissions through the gantry (>50%) with no increased losses in the gantry. As such, the overall transmission (cyclotron to isocenter) can be increased by almost a factor of 6 for low energies. Additionally, the point‐to‐point imaging inherent to the optics allows adjustment of the beam size at the isocenter by simply changing the beam size at the CP. Conclusion: We have developed a new gantry beam optics which, by selecting a large beam size and low divergence at the gantry entrance and using an imaging factor of 0.5 (2:1), increases the emittance acceptance of the gantry, leading to a substantial increase in beam intensity at low energies. We expect that this approach could easily be adapted for most types of existing gantries. [ABSTRACT FROM AUTHOR]

Purpose: In proton therapy, the potential of using high‐dose rates in the cancer treatment is being explored. High‐dose rates could improve efficiency and throughput in standard clinical practice, allow efficient utilization of motion mitigation techniques for moving targets, and potentially enhance normal tissue sparing due to the so‐called FLASH effect. However, high‐dose rates are difficult to reach when lower energy beams are applied in cyclotron‐based proton therapy facilities, because they result in large beam sizes and divergences downstream of the degrader, incurring large losses from the cyclotron to the patient position (isocenter). In current facilities, the emittance after the degrader is reduced using circular collimators; however, this does not provide an optimal matching to the acceptance of the following beamline, causing a low transmission for these energies. We, therefore, propose to use a collimation system, asymmetric in both beam size and divergence, resulting in symmetric emittance in both beam transverse planes as required for a gantry system. This new emittance selection, together with a new optics design for the following beamline and gantry, allows a better matching to the beamline acceptance and an improvement of the transmission. Methods: We implemented a custom method to design the collimator sizes and shape required to select high emittance, to be transported by the following beamline using new beam optics (designed with TRANSPORT) to maximize acceptance matching. For predicting the transmission in the new configuration (new collimators + optics), we used Monte Carlo simulations implemented in BDSIM, implementing a model of PSI Gantry 2 which we benchmarked against measurements taken in the current clinical scenario (circular collimators + clinical optics). Results: From the BDSIM simulations, we found that the new collimator system and matching beam optics results in an overall transmission from the cyclotron to the isocenter for a 70 MeV beam of 0.72%. This is an improvement of almost a factor of 6 over the current clinical performance (0.13% transmission). The new optics satisfies clinical beam requirements at the isocenter. Conclusions: We developed a new emittance collimation system for PSI's PROSCAN beamline which, by carefully selecting beam size and divergence asymmetrically, increases the beam transmission for low‐energy beams in current state‐of‐the‐art cyclotron‐based proton therapy gantries. With these improvements, we could predict almost 1% transmission for low‐energy beams at PSI's Gantry 2. Such a system could easily be implemented in facilities interested in increasing dose rates for efficient motion mitigation and FLASH experiments alike. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this work was to provide a flexible platform for FLASH research with protons by adapting a former clinical pencil beam scanning gantry to irradiations with ultra‐high dose rates. Methods: PSI Gantry 1 treated patients until December 2018. We optimized the beamline parameters to transport the 250 MeV beam extracted from the PSI COMET accelerator to the treatment room, maximizing the transmission of beam intensity to the sample. We characterized a dose monitor on the gantry to ensure good control of the dose, delivered in spot‐scanning mode. We characterized the beam for different dose rates and field sizes for transmission irradiations. We explored scanning possibilities in order to enable conformal irradiations or transmission irradiations of large targets (with transverse scanning). Results: We achieved a transmission of 86% from the cyclotron to the treatment room. We reached a peak dose rate of 9000 Gy/s at 3 mm water equivalent depth, along the central axis of a single pencil beam. Field sizes of up to 5 × 5 mm2 were achieved for single‐spot FLASH irradiations. Fast transverse scanning allowed to cover a field of 16 × 1.2 cm2. With the use of a nozzle‐mounted range shifter, we are able to span depths in water ranging from 19.6 to 37.9 cm. Various dose levels were delivered with precision within less than 1%. Conclusions: We have realized a proton FLASH irradiation setup able to investigate continuously a wide dose rate spectrum, from 1 to 9000 Gy/s in single‐spot irradiation as well as in the pencil beam scanning mode. As such, we have developed a versatile test bench for FLASH research. [ABSTRACT FROM AUTHOR]

In proton therapy, the last part of the beam transport system is installed on a rotatable gantry, so that the beam can be aimed at the tumor from different angles. Since such a gantry system consists of many dipole and quadrupole magnets, it is typically a 100–200 tons device of more than 10 m in diameter. The use of superconducting (SC) magnets for proton therapy allows gantries to be significantly lighter and potentially smaller, which is attractive for this medical application. In addition to that, SC combined function magnets enable beam optics with a very large momentum acceptance. The latter can be advantageous for patient treatment, since the irradiation time can then be significantly reduced by avoiding magnet current changes. To design such an achromatic system, we performed precise high-order calculations. To reach the required accuracy and to check consistency of the obtained results, we have used different simulation tools in our iterative design approach. Here, we will describe our beam optics calculations in the code COSY Infinity and particle tracking using OPAL (open source software from PSI) in 3D field maps obtained from detailed magnet calculations performed in Opera. Our method has shown to be advantageous in a complicated beam optics study and it reduces the risk of systematic errors in a design. [ABSTRACT FROM AUTHOR]

Background: This study aimed at evaluating spatially varying instantaneous dose rates for different intensity-modulated proton therapy (IMPT) planning strategies and delivery scenarios, and comparing these with FLASH dose rates (>40 Gy/s). Material and methods: In order to quantify dose rates in three-dimensions, we proposed the 'dose-averaged dose rate' (DADR) metric, defined for each voxel as the dose-weighted mean of the instantaneous dose rates of all spots (i.e., pencil beams). This concept was applied to four head-and-neck cases, each planned with clinical (4 fields) and various spot-reduced IMPT techniques: 'standard' (4 fields), 'arc' (120 fields) and 'arc-shoot-through' (120 fields; 229 MeV only). For all plans, different delivery scenarios were simulated: constant beam intensity, variable beam intensity for a clinical Varian ProBeam system, varied per energy layer or per spot, and theoretical spot-wise variable beam intensity (i.e., no monitor/safety limitations). DADR distributions were calculated assuming 2-Gy or 6-Gy fractions. Results: Spot-reduced plans contained 17–52 times fewer spots than clinical plans, with no deterioration of plan quality. For the clinical plans, the mean DADR in normal tissue for 2-Gy fractionation was 1.7 Gy/s (median over all patients) at maximum, whereas in standard spot-reduced plans it was 0.7, 4.4, 7.1, and 12.1 Gy/s, for the constant, energy-layer-wise, spot-wise, and theoretical spot-wise delivery scenarios, respectively. Similar values were observed for arc plans. Arc-shoot-through planning resulted in DADR values of 3.0, 6.0, 14.1, and 24.4 Gy/s, for the abovementioned scenarios. Hypofractionation (3×) generally resulted in higher dose rates, up to 73.2 Gy/s for arc-shoot-through plans. The DADR was inhomogeneously distributed with highest values at beam entrance and at the Bragg peak. Conclusion: FLASH dose rates were not achieved for conventional planning and clinical spot-scanning machines. As such, increased spot-wise beam intensities, spot-reduced planning, hypofractionation and arc-shoot-through plans were required to achieve FLASH compatible dose rates. [ABSTRACT FROM AUTHOR]

In recent years there has been increasing interest in the more extensive application of proton therapy in a clinical and preferably hospital-based environment. However, broader adoption of proton therapy has been hindered by the costs of treatment, which are still much higher than those in advanced photon therapy. This article presents an overview of on-going technical developments, which have a reduction of the capital investment or operational costs either as a major goal or as a potential outcome. Developments in instrumentation for proton therapy, such as gantries and accelerators, as well as facility layout and efficiency in treatment logistics will be discussed in this context. Some of these developments are indeed expected to reduce the costs. The examples will show, however, that a dramatic cost reduction of proton therapy is not expected in the near future. Although current developments will certainly contribute to a gradual decrease of the treatment costs in the coming years, many steps will still have to be made to achieve a much lower cost per treatment. [ABSTRACT FROM AUTHOR]

The goal of this work is to increase the beam transmission from the cyclotron to the patient location of ocular tumor treatment facility Optis 2 at the Paul Scherrer Institute and thus to reduce the patient treatment times. The examined options for such transmission increase were the installation of local degraders in the patient treatment room and modification of the energy selection collimator settings. The experiments have shown that an improvement of the beam transmission is possible to achieve, however on a cost of an increase in lateral or distal penumbra of the beam. The benefits and drawbacks of the examined options are discussed. [ABSTRACT FROM AUTHOR]

An increasing number of proton therapy facilities are being planned and built at hospital based centers. Most facilities are employing traditional dose delivery methods. A second generation of dose application techniques, based on pencil beam scanning, is slowly being introduced into the commercially available proton therapy systems. New developments in accelerator physics are needed to accommodate and fully exploit these new techniques. At the same time new developments such as the development of small cyclotrons, Dielectric Wall Accelerator (DWA) and laser driven systems, aim for smaller, single room treatment units. In general the benefits of proton therapy could be exploited optimally when achieving a higher level in accuracy, beam energy, beam intensity, safety and system reliability. In this review an overview of the current developments will be given followed by a discussion of upcoming new technologies and needs, like increase of energy, on-line MRI and proton beam splitting for independent uses of treatment rooms. [ABSTRACT FROM AUTHOR]

Purpose: To test the hypothesis that heart irradiation increases the risk of a symptomatic radiation-induced loss of lung function (SRILF) and that this can be well-described as a modulation of the functional reserve of the lung. Methods and Materials: Rats were irradiated with 150-MeV protons. Dose–response curves were obtained for a significant increase in breathing frequency after irradiation of 100%, 75%, 50%, or 25% of the total lung volume, either including or excluding the heart from the irradiation field. A significant increase in the mean respiratory rate after 6–12 weeks compared with 0–4 weeks was defined as SRILF, based on biweekly measurements of the respiratory rate. The critical volume (CV) model was used to describe the risk of SRILF. Fits were done using a maximum likelihood method. Consistency between model and data was tested using a previously developed goodness-of-fit test. Results: The CV model could be fitted consistently to the data for lung irradiation only. However, this fitted model failed to predict the data that also included heart irradiation. Even refitting the model to all data resulted in a significant difference between model and data. These results imply that, although the CV model describes the risk of SRILF when the heart is spared, the model needs to be modified to account for the impact of dose to the heart on the risk of SRILF. Finally, a modified CV model is described that is consistent to all data. Conclusions: The detrimental effect of dose to the heart on the incidence of SRILF can be described by a dose dependent decrease in functional reserve of the lung. [Copyright &y& Elsevier]

Purpose: The dose–response relationship for a relatively short length (4 mm) of rat spinal cord has been shown to be significantly modified by adjacent low-dose fields. In an additional series of experiments, we have now established the dose–volume dependence of this effect. Methods and Materials: Wistar rats were irradiated on the cervical spinal cord with single doses of unmodulated protons (150 MeV) to obtain sharp lateral penumbras, by use of the shoot-through technique, which employs the plateau of the depth-dose profile rather than the Bragg peak. Three types of inhomogeneous dose distributions were administered: Twenty millimeters of cervical spinal cord were irradiated with variable subthreshold (= bath) doses (4 and 18 Gy). At the center of the 20-mm segment, a short segment of 2 mm or 8 mm (= shower) was irradiated with variable single doses. These inhomogeneous dose distributions are referred to as symmetrical bath-and-shower experiments. An asymmetrical dose distribution was arranged by irradiation of 12 mm (= bath) of spinal cord with a dose of 4 Gy. The caudal 2 mm (= shower) of the 12-mm bath was additionally irradiated with variable single doses. This arrangement of inhomogeneous dose distribution is referred to as asymmetrical bath-and-shower experiment. The endpoint for estimation of the dose–response relationships was paralysis of the fore limbs or hind limbs and confirmation by histology. Results: The 2-mm bath-and-shower experiments with a 4-Gy bath dose showed a large shift of the dose–response curves compared with the 2-mm single field, which give lower ED50 values of 61.2 Gy and 68.6 Gy for the symmetrical and asymmetrical arrangement, respectively, compared with an ED50 of 87.8 Gy after irradiation of a 2-mm field only. If the bath dose is increased to 18 Gy, the ED50 value is decreased further to 30.9 Gy. For an 8-mm field, addition of a 4-Gy bath dose did not modify the ED50 obtained for an 8-mm field only (23.2 and 23.1 Gy). Conclusions: The spinal cord tolerance of relatively small volumes (shower) is strongly affected by low-dose irradiation (= bath) of adjacent tissue. The results of all bath-and-shower experiments show the effect of a low bath dose to be highest for a field of 2 mm, less for 4 mm, and absent for 8 mm. Adding a 4-Gy bath to only 1 side of a 2-mm field still showed a large effect. Because glial progenitor cells are known to migrate over at least 2 to 3 mm, this observation indicates that interference with stem cell migration is not the most likely mechanism of a bath effect. [Copyright &y& Elsevier]

Purpose: To evaluate several existing dose–volume effect models for their ability to describe the occurrence of white matter necrosis in rat spinal cord after irradiation with small proton beams. Methods and materials: A large number of dose–volume effect models has been fitted to data on the occurrence of white matter necrosis after irradiation with small proton beams. The fitting was done with the maximum likelihood method. For each model, the goodness of fit was calculated. An empirical tolerance dose–volume (eTDV) model was designed to describe data obtained after uniform irradiation. Results: The eTDV model, the critical element model, and critical volume model with inclusion of the repair-by-migration principle described by Shirato, were able to describe the data obtained after irradiation with uniform dose distributions of varying sizes. However, none of the models under investigation was able to describe all the data. Extension of the developed empirical model with a repair mechanism with a limited range resulted in a good description of the tolerance doses. Conclusions: In the rat spinal cord, a nonlocal repair mechanism, acting from nonirradiated to irradiated tissue, plays an important role in the (prevention of the) occurrence of white matter necrosis after irradiation. Models that take into account this effect need to be developed. [Copyright &y& Elsevier]

In many thoracic cancers, the radiation dose that can safely be delivered to the target volume is limited by the tolerance dose of the surrounding lung tissue. It has been hypothesized that irradiation of the heart may be an additional risk factor for the development of early radiation-induced lung morbidity. In the current study, the dependence of lung tolerance dose on heart irradiation is determined. Fifty percent of the rat lungs were irradiated either including or excluding the heart. Proton beams were used to allow very accurate and conformal dose delivery. Lung function toxicity was scored using a breathing rate assay. We confirmed that the tolerance dose for early lung function damage depends not only on the lung region that is irradiated but also that concomitant irradiation of the heart severely reduces the tolerance of the lung. This study for the first time shows that the response of an organ to irradiation does not necessarily depend on the dose distribution in that organ alone.