Particle arc therapy: Status and potential.

There is a rising interest in developing and utilizing arc delivery techniques with charged particle beams, e.g., proton, carbon or other ions, for clinical implementation. In this work, perspectives from the European Society for Radiotherapy and Oncology (ESTRO) 2022 physics workshop on particle arc therapy are reported. This outlook provides an outline and prospective vision for the path forward to clinically deliverable proton, carbon, and other ion arc treatments. Through the collaboration among industry, academic, and clinical research and development, the scientific landscape and outlook for particle arc therapy are presented here to help our community understand the physics, radiobiology, and clinical principles. The work is presented in three main sections: (i) treatment planning, (ii) treatment delivery, and (iii) clinical outlook.

Efficient proton arc optimization and delivery through energy layer pre-selection and post-filtering.

BACKGROUND: Proton arc therapy (PAT) has emerged as a promising approach for improving dose distribution, but also enabling simpler and faster treatment delivery in comparison to conventional proton treatments. However, the delivery speed achievable in proton arc relies on dedicated algorithms, which currently do not generate plans with a clear speed-up and sometimes even result in increased delivery time. PURPOSE: This study aims to address the challenge of minimizing delivery time through a hybrid method combining a fast geometry-based energy layer (EL) pre-selection with a dose-based EL filtering, and comparing its performance to a baseline approach without filtering. METHODS: Three methods of EL filtering were developed: unrestricted, switch-up (SU), and switch-up gap (SU gap) filtering. The unrestricted method filters the lowest weighted EL while the SU gap filtering removes the EL around a new SU to minimize the gantry rotation braking. The SU filtering removes the lowest weighted group of EL that includes a SU. These filters were combined with the RayStation dynamic proton arc optimization framework energy layer selection and spot assignment (ELSA). Four bilateral oropharyngeal and four lung cancer patients' data were used for evaluation. Objective function values, target coverage robustness, organ-at-risk doses and normal tissue complication probability evaluations, as well as comparisons to intensity-modulated proton therapy (IMPT) plans, were used to assess plan quality. RESULTS: The SU gap filtering algorithm performed best in five out of the eight cases, maintaining plan quality within tolerance while reducing beam delivery time, in particular for the oropharyngeal cohort. It achieved up to approximately 22% and 15% reduction in delivery time for oropharyngeal and lung treatment sites, respectively. The unrestricted filtering algorithm followed closely. In contrast, the SU filtering showed limited improvement, suppressing one or two SU without substantial delivery time shortening. Robust target coverage was kept within 1% of variation compared to the PAT baseline plan while organs-at-risk doses slightly decreased or kept about the same for all patients. CONCLUSIONS: This study provides insights to accelerate PAT delivery without compromising plan quality. These advancements could enhance treatment efficiency and patient throughput.

Very high-energy electron therapy as light-particle alternative to transmission proton FLASH therapy - An evaluation of dosimetric performances.

PURPOSE: Clinical translation of FLASH-radiotherapy (RT) to deep-seated tumours is still a technological challenge. One proposed solution consists of using ultra-high dose rate transmission proton (TP) beams of about 200-250 MeV to irradiate the tumour with the flat entrance of the proton depth-dose profile. This work evaluates the dosimetric performance of very high-energy electron (VHEE)-based RT (50-250 MeV) as a potential alternative to TP-based RT for the clinical transfer of the FLASH effect. METHODS: Basic physics characteristics of VHEE and TP beams were compared utilizing Monte Carlo simulations in water. A VHEE-enabled research treatment planning system was used to evaluate the plan quality achievable with VHEE beams of different energies, compared to 250 MeV TP beams for a glioblastoma, an oesophagus, and a prostate cancer case. RESULTS: Like TP, VHEE above 100 MeV can treat targets with roughly flat (within ± 20 %) depth-dose distributions. The achievable dosimetric target conformity and adjacent organs-at-risk (OAR) sparing is consequently driven for both modalities by their lateral beam penumbrae. Electron beams of 400[500] MeV match the penumbra of 200[250] MeV TP beams and penumbra is increased for lower electron energies. For the investigated patient cases, VHEE plans with energies of 150 MeV and above achieved a dosimetric plan quality comparable to that of 250 MeV TP plans. For the glioblastoma and the oesophagus case, although having a decreased conformity, even 100 MeV VHEE plans provided a similar target coverage and OAR sparing compared to TP. CONCLUSIONS: VHEE-based FLASH-RT using sufficiently high beam energies may provide a lighter-particle alternative to TP-based FLASH-RT with comparable dosimetric plan quality.

Treatment planning of scanned proton beams in RayStation.

The use of scanned proton beams in external beam radiation therapy has seen a rapid development over the past decade. This technique places new demands on treatment planning, as compared to conventional photon-based radiation therapy. In this article, several proton specific functions as implemented in the treatment planning system RayStation are presented. We will cover algorithms for energy layer and spot selection, basic optimization including the handling of spot weight limits, optimization of the linear energy transfer (LET) distribution, robust optimization including the special case of 4D optimization, proton arc planning, and automatic planning using deep learning. We will further present the Monte Carlo (MC) proton dose engine in RayStation to some detail, from the material interpretation of the CT data, through the beam model parameterization, to the actual MC transport mechanism. Useful tools for plan evaluation, including robustness evaluation, and the versatile scripting interface are also described. The overall aim of the paper is to give an overview of some of the key proton planning functions in RayStation, with example usages, and at the same time provide the details about the underlying algorithms that previously have not been fully publicly available.

Clinical evaluation of synthetic computed tomography methods in adaptive proton therapy of lung cancer patients.

Background and purpose: Efficient workflows for adaptive proton therapy are of high importance. This study evaluated the possibility to replace repeat-CTs (reCTs) with synthetic CTs (sCTs), created based on cone-beam CTs (CBCTs), for flagging the need of plan adaptations in intensity-modulated proton therapy (IMPT) treatment of lung cancer patients. Materials and methods: Forty-two IMPT patients were retrospectively included. For each patient, one CBCT and a same-day reCT were included. Two commercial sCT methods were applied; one based on CBCT number correction (Cor-sCT), and one based on deformable image registration (DIR-sCT). The clinical reCT workflow (deformable contour propagation and robust dose re-computation) was performed on the reCT as well as the two sCTs. The deformed target contours on the reCT/sCTs were checked by radiation oncologists and edited if needed. A dose-volume-histogram triggered plan adaptation method was compared between the reCT and the sCTs; patients needing a plan adaptation on the reCT but not on the sCT were denoted false negatives. As secondary evaluation, dose-volume-histogram comparison and gamma analysis (2%/2mm) were performed between the reCT and sCTs. Results: There were five false negatives, two for Cor-sCT and three for DIR-sCT. However, three of these were only minor, and one was caused by tumour position differences between the reCT and CBCT and not by sCT quality issues. An average gamma pass rate of 93% was obtained for both sCT methods. Conclusion: Both sCT methods were judged to be of clinical quality and valuable for reducing the amount of reCT acquisitions.

Partitioning of discrete proton arcs into interlaced subplans can bring proton arc advances to existing proton facilities.

BACKGROUND: Proton arcs have shown potential to reduce the dose to organs at risks (OARs) by delivering the protons from many different directions. While most previous studies have been focused on dynamic arcs (delivery during rotation), an alternative approach is discrete arcs, where step-and-shoot delivery is used over a large number of beam directions. The major advantage of discrete arcs is that they can be delivered at existing proton facilities. However, this advantage comes at the expense of longer treatment times. PURPOSE: To exploit the dosimetric advantages of proton arcs, while achieving reasonable delivery times, we propose a partitioning approach where discrete arc plans are split into subplans to be delivered over different fractions in the treatment course. METHODS: For three oropharyngeal cancer patients, four different arc plans have been created and compared to the corresponding clinical IMPT plan. The treatment plans are all planned to be delivered in 35 fractions, but with different delivery approaches over the fractions. The first arc plan (1×30) has 30 directions to be delivered every fraction, while the others are partitioned into subplans with 10 and 6 beam directions, each to be delivered every third (3×10), fifth fraction (5×6), or seventh fraction (7×10). All plans are assessed with respect to delivery time, target robustness over the treatment course, doses to OARs and NTCP for dysphagia and xerostomia. RESULTS: The delivery time (including an additional delay of 30 s between the discrete directions to simulate manual interaction with the treatment control system) is reduced from on average 25.2 min for the 1×30 plan to 9.2 min for the 3×10 and 7×10 plans and 5.7 min for the 5×6 plans. The delivery time for the IMPT plan is 7.9 min. When accounting for the combination of delivery time, target robustness, OAR sparing, and NTCP reduction, the plans with 10 directions in each fraction are the preferred choice. Both the 3×10 and 7×10 plans show improved target robustness compared to the 1×30 plans, while keeping OAR doses and NTCP values at almost as low levels as for the 1×30 plans. For all patients the NTCP values for dysphagia are lower for the partitioned plans with 10 directions compared to the IMPT plans. NTCP reduction for xerostomia compared to IMPT is seen in two of the three patients. The best results are seen for the first patient, where the NTCP reductions for the 7×10 plan are 1.6 p.p. (grade 2 xerostomia) and 1.5 p.p. (grade 2 dysphagia). The corresponding NTCP reductions for the 1×30 plan are 2.7 p.p. (xerostomia, grade 2) and 2.0 p.p. (dysphagia, grade 2). CONCLUSIONS: Discrete proton arcs can be implemented at any proton facility with reasonable treatment times using a partitioning approach. The technique also makes the proton arc treatments more robust to changes in the patient anatomy.

Parameter based 4D dose calculations for proton therapy.

Background and purpose Retrospective log file-based analysis provides the actual dose delivered based on the patient's breathing and the daily beam-delivery dynamics. To predict the motion sensitivity of the treatment plan on a patient-specific basis before treatment start a prospective tool is required. Such a parameter-based tool has been investigated with the aim to be used in clinical routine. Materials and Methods 4D dose calculations (4DDC) were performed for seven cancer patients with small breathing motion treated with scanned pulsed proton beams. Validation of the parameter-based 4DDC (p-4DDC) method was performed with an anthropomorphic phantom and patient data employing measurements and a log file-based 4DDC tool. The dose volume histogram parameters (Dx%) were investigated for the target and the organs at risk, compared to static and the file-based approach. Results The difference between the measured and the p-4DDC dose was within the deviation of the measurements. The maximum deviation was 0.4Gy. For the planning target volume D98% varied up to 15% compared to the static scenario, while the results from the log file and p-4DDC agreed within 2%. For the liver patients, D33%liver deviated up to 35% compared to static and 10% comparing the two 4DDC tools, while for the pancreas patients the D1%stomach varied up to 45% and 11%, respectively. Conclusion The results showed that p-4DDC could be used prospectively. The next step will be the clinical implementation of the p-4DDC tool, which can support a decision to either adapt the treatment plan or apply motion mitigation strategies.

Patient Breathing Motion and Delivery Specifics Influencing the Robustness of a Proton Pancreas Irradiation.

Motion compensation strategies in particle therapy depend on the anatomy, motion amplitude and underlying beam delivery technology. This retrospective study on pancreas patients with small moving tumours analysed existing treatment concepts and serves as a basis for future treatment strategies for patients with larger motion amplitudes as well as the transition towards carbon ion treatments. The dose distributions of 17 hypofractionated proton treatment plans were analysed using 4D dose tracking (4DDT). The recalculation of clinical treatment plans employing robust optimisation for mitigating different organ fillings was performed on phased-based 4D computed tomography (4DCT) data considering the accelerator (pulsed scanned pencil beams delivered by a synchrotron) and the breathing-time structure. The analysis confirmed the robustness of the included treatment plans concerning the interplay of beam and organ motion. The median deterioration of D50% (ΔD50%) for the clinical target volume (CTV) and the planning target volume (PTV) was below 2%, while the only outlier was observed for ΔD98% with -35.1%. The average gamma pass rate over all treatment plans (2%/ 2 mm) was 88.8% ± 8.3, while treatment plans for motion amplitudes larger than 1 mm performed worse. For organs at risk (OARs), the median ΔD2% was below 3%, but for single patients, essential changes, e.g., up to 160% for the stomach were observed. The hypofractionated proton treatment for pancreas patients based on robust treatment plan optimisation and 2 to 4 horizontal and vertical beams showed to be robust against intra-fractional movements up to 3.7 mm. It could be demonstrated that the patient's orientation did not influence the motion sensitivity. The identified outliers showed the need for continuous 4DDT calculations in clinical practice to identify patient cases with more significant deviations.

Spot scanning proton arc therapy reduces toxicity in oropharyngeal cancer patients.

BACKGROUND: Proton arc technology has recently shown dosimetric gains for various treatment indications. The increased number of beams and energy layers (ELs) in proton arc plans, increases the degrees of freedom in plan optimization and thereby flexibility to spare dose in organs at risk (OARs). A relationship exists between dosimetric plan quality, delivery efficiency, the number of ELs -and beams in a proton arc plan. PURPOSE: This work aims to investigate the effect of the number of beams and ELs in a proton arc plan, on toxicity and delivery time for oropharyngeal cancer patients (OPC) selected for intensity modulated proton therapy (IMPT) based on the Dutch model-based approach. METHODS: The EL reduction algorithm iteratively selects ELs from beams equidistantly spaced over a 360° arc. The beams in the final plan may contain multiple ELs, making them suited for static delivery on the studied treatment machine. The produced plans can therefore be called "step and shoot" proton arc plans. The number of beams and ELs were varied to determine the relationship with the planning cost function value, normal tissue complication probability (NTCP) and delivery time. Proton arc plans with robust target coverage and optimal energy layer reduction (ELR) settings to reduce NTCP, were generated for 10 OPC patients. Proton arc plans were compared to clinical volumetric modulated arc therapy (VMAT) and IMPT plans in terms of integral dose, OAR dose, NTCP for xerostomia and dysphagia and delivery time. Furthermore, dose-weighted average linear energy transfer (LETd ) distributions were compared between the IMPT and proton arc plans. A dry run delivery of a plan containing 20 beams and 360 ELs was performed to evaluate delivery time and accuracy. RESULTS: We found 360 ELs distributed over 30 beams generated proton arc plans with near minimal expected plan toxicity. Relative to corresponding IMPT and VMAT plans, an average reduction of 21 ± 3% and 58 ± 10% in integral dose was observed. D m e a n $_{mean}$ was reduced most in the pharyngeal constrictor muscle (PCM) medius structure, with on average 9.0 ± 4.2 Gy(RBE) (p = 0.0002) compared to the clinical IMPT plans. The average NTCP for grade≥2 and grade≥3 xerostomia at 6 months after treatment significantly decreased with 4.7 ± 1.8% (p = 0.002) and 1.7 ± 0.8% (p = 0.002), respectively, while the average NTCP for grade≥2 and grade≥3 dysphagia decreased with 4.4 ± 2.9% (p = 0.002) and 0.9 ± 0.4% (p = 0.002), respectively, increasing the benefit of protons relative to VMAT. For a "step and shoot" proton arc delivery with auto beam sequencing the estimated delivery time is 11 min, similar to the delivery time of a 6-field IMPT treatment. Gamma analysis between the planned and delivered dose distribution resulted in a 99.99% pass rate using 1mm/1% dose difference/distance to agreement criteria. CONCLUSIONS: "Step and shoot" proton arc demonstrates potential to further reduce toxicity compared to IMPT and VMAT in OPC treatment. By employing 360 ELs and 30 beams in the proposed ELR method, delivery time can reach clinically acceptable levels without compromising plan toxicity when automatic beam sequencing is available.

Fast robust optimization of proton PBS arc therapy plans using early energy layer selection and spot assignment.

Objective.Proton pencil-beam scanning arcs (PBS arcs) have gained much attention during the past years, due to its potential for increased clinical benefit compared to conventional proton therapy. Previous studies on PBS arcs have primarily been focused on plan quality, and lately efforts have been made to reduce the delivery time. However, the methods presented so far suffer from slow optimization processes.Approach.We present a new method for fast robust optimization of PBS arc plans. The new method assigns a single energy layer per discretized direction prior to spot weight optimization and reduces the number of initial spots considerably compared to conventional methods. We used the new method for three prostate cancer patients with a prescribed dose to the CTV of 77 GyRBEin 35 fractions. For each of the patients, four plans were created: 2-beam IMPT (2IMPT), 1-beam PBS arc (1Arc), 1-beam PBS arc without focus on reducing upward energy jumps (1Arc_unseq) and two-beam PBS arc (2Arc).Main results.All PBS arc plans show a reduced integral dose compared to their respective 2IMPT plans. In the nominal case, the average CTV D98 and D2 metrics over the three patients were best for the 2Arc, followed by 2IMPT (D98¯/D2¯:7523/7986 cGyRBE(2IMPT), 7478/7984 cGy (1Arc), 7486/7951 cGy (1Arc_unseq), 7531/7951 cGyRBE(2Arc)). The average robust target coverage in terms of V95 of the voxelwise minimum dose distribution (evaluated over 42 scenarios) was: 98.0% (2IMPT), 88.6% (1Arc), 92.5% (1Arc_unseq), 97.3% (2Arc). The optimization time, including spot selection and spot dose computation, is longest for the 2Arc plan, but is below 6 min for all patients. The maximum estimated delivery time for all types of arc plans is just above 5 minSignificance.The ability for efficient treatment planning constitutes an important step towards clinical introduction of proton PBS arcs.

Mitigation of motion effects in pencil-beam scanning - Impact of repainting on 4D robustly optimized proton treatment plans for hepatocellular carcinoma.

Proton fields delivered by the active scanning technique can be interfered with the intrafractional motion. This in-silico study seeks to mitigate the dosimetric impacts of motion artifacts, especially its interplay with the time-modulated dose delivery. Here four-dimensional (4d) robust optimization and dose repainting, which is the multiple application of the same field with reduced fluence, were combined. Two types of repainting were considered: layered and volumetric repainting. The time-resolved dose calculation, which is necessary to quantify the interplay effect, was integrated into the treatment planning system and validated. Nine clinical cases of hepatocellular carcinoma (HCC) showing motion in the range of 0.4-1.5cm were studied. It was found that the repainted delivery of 4D robustly optimized plans reduced the impact of interplay effect as quantified by the homogeneity index within the clinical target volume (CTV) to a tolerable level. Similarly, the fractional over- and underdosage was reduced sufficiently for some HCC cases to achieve the purpose of motion management. This holds true for both investigated types of repainting with small dosimetric advantages of volume repainting over layered repainting. Volume repainting, however, cannot be applied clinically in proton centers with slow energy changes. Thus, it served as a reference in the in-silico evaluation. It is recommended to perform the dynamic dose calculation for individual cases to judge if robust optimization in conjunction with repainting is sufficient to keep the interplay effect within bounds.

Clinical validation of a GPU-based Monte Carlo dose engine of a commercial treatment planning system for pencil beam scanning proton therapy.

PURPOSE: To perform the validation of the GPU-based (Graphical Processing Unit based) proton Monte Carlo (MC) dose engine implemented in a commercial TPS (RayStation 10B) and to report final dose calculation times for clinical cases. MATERIALS AND METHODS: 440 patients treated at the Proton Therapy Center of Trento, Italy, between 2018 and 2019 were selected for this study. 636 approved plans with 3361 beams computed with the clinically implemented CPU-MC dose engine (version 4.2 and 4.5), were used for the validation of the new algorithm. For each beam, the dose was recalculated using the new GPU-MC dose engine with the initial CPU computation settings and compared to the original CPU-MC dose. Beam dose difference distributions were studied to ensure that the two dose distributions were equal within the expected fluctuations of the MC statistical uncertainty (s) of each computation. Plan dose distributions were compared with respect to the dosimetric indices D98, D50 and D1 of all ROIs defined as targets. A complete assessment of the computation time as a function of s and dose grid voxel size was done. RESULTS: The median over all mean beam dose differences between CPU- and GPU-MC was -0.01% and the median of the corresponding standard deviations was close to (√2s) both for simulations with an s of 0.5% and 1.0% per beam. This shows that the two dose distributions can be considered equal. All the DVH indices showed an average difference below 0.04%. About half of the plans were computed with 1.0% statistical uncertainty on a 2 mm dose calculation grid, for which the median computation time was 5.2 s. The median computational speed for all plans in the study was 8.4 million protons/second. CONCLUSION: A validation of a clinical MC algorithm running on GPU was performed on a large pool of patients treated with pencil beam scanning proton therapy. We demonstrated that the differences with the previous CPU-based MC were only due to the intrinsic statistical fluctuations of the MC method, which translated to insignificant differences on plan dose level. The significant increase in dose calculation speed is expected to facilitate new clinical workflows.

Technical Note: Investigating interplay effects in pencil beam scanning proton therapy with a 4D XCAT phantom within the RayStation treatment planning system.

PURPOSE: Pencil beam scanning (PBS) for moving targets is known to be impacted by interplay effects. Four-dimensional computed tomography (4DCT)-based motion evaluation is crucial for understanding interplay and developing mitigation strategies. Availability of high-quality 4DCTs with variable breathing traces is limited. Purpose of this work is the development of a framework for interplay analysis using 4D-XCAT phantoms in conjunction with time-resolved irradiation patterns in a commercial treatment planning system (TPS). Four-dimensional dynamically accumulated dose distributions (4DDDs) are simulated in an in-silico study for a PBS liver treatment. METHODS: An XCAT phantom with 50 phases, varying linearly in amplitude each by 1 mm, was combined with the RayStation TPS (7.99.10). Deformable registration was used with time-resolved dose calculation, mapping XCAT phases to motion signals. To illustrate the applicability of the method a two-field liver irradiation plan was used. A variety sin4 type motion signals, varying in amplitude (1-20 mm), period (1.6-5.2 s) and phase (0-2π) were applied. Either single variable variations or random combinations were selected. The interplay effect within a clinical target (5 cm diameter) was characterized in terms of homogeneity index (HI5), with and without five paintings. In total 2092 scenarios were analyzed within RayStation. RESULTS: A framework is presented for interplay research, allowing for flexibility in determining motion management techniques, increasing reproducibility, and enabling comparisons of different methods. A case study showed the interplay effect was correlated with amplitude and strongly affected by the starting phase, leading to large variance. The average of all scenarios (single fraction) resulted in HI5 of 0.31 (±0.11), while introduction of five times layered repainting reduced this to 0.11(±0.03). CONCLUSION: The developed framework, which uses the XCAT phantom and RayStation, allows detailed analysis of motion in context of PBS with comparable results to clinical cases. Flexibility in defining motion patterns for detailed anatomies in combination with time-resolved dose calculation, facilitates investigation of optimal treatment and motion mitigation strategies.

Robust radiation therapy optimization using simulated treatment courses for handling deformable organ motion.

We describe a radiation therapy treatment plan optimization method that explicitly considers the effects of interfraction organ motion through optimization on the clinical target volume (CTV), and investigate how it compares to conventional planning using a planning target volume (PTV). The method uses simulated treatment courses generated using patient images created by a deformable registration algorithm to replicate the effects of interfraction organ motion, and performs robust optimization aiming to achieve CTV coverage under all simulated treatment courses. The method was applied to photon-mediated treatments of three prostate cases and compared to conventional, PTV-based planning with margins selected to achieve similar CTV coverage as the robustly optimized plans. Clinical goals for the CTV and healthy tissue were used in comparison between the two types of plans. Out of the two clinical goals for overdosage of the CTV, the three robustly optimized plans violated respectively 2, 2, and 0 goals in the mean over the scenarios, whereas none of the PTV plans violated these goals. Of the ten clinical goals for rectum, bladder, anal canal, and bulbus, the robustly optimized plans violated respectively 0, 1, and 1 goals in the mean, whereas the PTV plans violated 5, 7, and 4 goals. Compared to PTV-based planning, the inclusion of treatment course scenarios in the optimization has the potential to reduce the dose to healthy tissues while retaining a high probability of target coverage. This may reduce the need for adaptive replanning.

Implementation of proton therapy treatments with pencil beam scanning of targets with limited intrafraction motion.

PURPOSE: To report on the implementation, validation and results of the first two proton therapy PBS treatments of limited amplitudes moving targets performed at our center. METHODS AND MATERIALS: A real time optical tracking system was used to monitor the patient surface during the CT scan and treatment. This system is also able to trigger the beam during the treatment. A 4DCT (10 phases) and a Free-Breathing CT (FBCT) were used for the planning. The physician used the 4DCT for ITV delineation, while planning was performed on the FBCT. The approved plan was evaluated in two ways:The largest breathing amplitude recorded during 4DCT scan was used as gating safety threshold during treatment delivery. This planning and treatment workflow was then applied for two patients affected by thoracic thymoma. RESULTS: The dosimetric evaluation of the plan showed no interplay effect. The second patient showed an overdosage to the coronary and Left Anterior Descending area in the worst case scenario but it was below the constraints. Duty Cycle together with number of beam interruptions gave information about the patient compliance to the treatment: the first patient breath is stable and within thresholds, whilst the second patient had more variations, causing multiple beam interruptions. CONCLUSION: We defined and used for two patients a protocol for the treatment of small amplitude moving targets. The planning and delivery of the treatments gave very good results in terms of coverage, OARs sparing, 4D dose evaluation of the plan and interplay effect assessment.

Motion effects in proton treatments of hepatocellular carcinoma-4D robustly optimised pencil beam scanning plans versus double scattering plans.

Pencil beam scanning (PBS) proton therapy enables better dose conformality for complex anatomical geometries than passive proton scattering techniques, but is more susceptible to organ motion. This becomes an issue when treating moving tumours in the thorax or abdomen. Novel four-dimensional treatment planning approaches have been developed to increase the robustness of PBS plans against motion. However, their efficacy still needs to be examined by means of 4D dynamically accumulated dose (4DDD) analyses. This study investigates the potential use of 4D robust optimisation to maintain sufficient target coverage in the presence of organ motion, while sparing surrounding healthy tissue, for hepatocellular carcinoma (HCC). The liver is particularly suited to study motion interplay effects since the treatment region exhibits smaller density gradients and more homogeneous tissue than targets in the thorax, making it less prone to range errors. A facility-specific beam time model, developed and experimentally validated previously, was used for the clinical evaluation. 4DDD analyses of eleven target volumes did not show a significant improvement of the target coverage using 4D robust optimisation, but a reduction of the dose to close-by organs at risk. Interplay effects were averaged out for the applied fractionation scheme of 15 fractions. Contrary to PBS, passive double scattering (DS) plans yielded homogeneous 4DDD dose distributions in a single fraction. But, in some cases, they exceeded organ at risk dose limits, which were only satisfied in PBS. The average normal liver dose could be decreased by almost 6% compared to non-robustly optimised PBS plans and by 16% compared to DS plans when implementing 4D robust optimisation. Except for some very small tumours with large motion amplitudes, 4D robustly optimised PBS plans were found to be clinically acceptable even without supplementary motion mitigation techniques.

4D robust optimization including uncertainties in time structures can reduce the interplay effect in proton pencil beam scanning radiation therapy.

PURPOSE: Interplay effects in proton radiotherapy can create large distortions in the dose distribution and severely degrade the plan quality. Standard methods to mitigate these effects include abdominal compression, gating, and rescanning. We propose a new method to include the time structures of the delivery and organ motion in the framework of four-dimensional (4D) robust optimization to generate plans that are robust against interplay effects. METHODS: The method considers multiple scenarios reflecting the uncertainties in the delivery and in the organ motion. In each scenario, the pencil beam scanning spots are distributed to different phases of the breathing cycle according to each individual spot time stamp, and a partial beam dose is calculated for each phase. The partial beam doses are accumulated on a reference phase through deformable image registrations. Minimax optimization is performed to take all scenarios into account simultaneously. For simplicity, the uncertainties in this proof of concept study are limited to variations in the breathing pattern. The method is evaluated for three different nonsmall cell lung cancer patients and compared to plans using conventional 4D robust optimization both with and without rescanning. We assess the ability of the method to mitigate distortions from the interplay effect over multiple evaluation scenarios using 4D dose calculations. This interplay evaluation is performed in an experimentally validated framework, which is independent of the optimization in the plan generation step. RESULTS: For the three studied patients, 4D optimization including time structures is efficient, especially for large tumor motions, where rescanning of conventional 4D robustly optimized plans is not sufficient to mitigate the interplay effect. The most efficient approach of the new method is achieved when it is combined with rescanning. For the patient with the largest motion, the mean V95% is 99.2% and mean V107% is 3.65% for the best rescanned 4D plan optimized with time structure. This can be compared to conventional 4D optimized plans with mean V95% of 92.7% and mean V107% of 13.1%. CONCLUSIONS: The current study shows the potential of reducing interplay effects in proton pencil beam scanning radiotherapy by incorporating organ motion and delivery characteristics in a 4D robust optimization.

Experimental validation of a 4D dose calculation routine for pencil beam scanning proton therapy.

Respiratory induced organ motion poses a major challenge for high-precision radiotherapy such as pencil beam scanning proton therapy (PBS). In order to employ PBS for target regions affected by respiratory motion, the implementation of dedicated motion mitigation techniques should be considered and residual uncertainties need to be assessed. For the latter purpose, a routine simulating the delivery of a scanned proton beam to a moving target was developed and implemented in the commercial treatment planning system RayStation. The time structure of the beam delivery was extracted from electronic irradiation protocols of the delivery system. Alternatively to electronic irradiation protocols, an empirical time model of the beam delivery was created to allow for prospective estimations of interplay effects between target motion and pencil beam scanning. The experimental validation of the routine was performed using a two-dimensional ionization chamber array and a dynamic phantom. A 4D CT data set, including 10 respiratory phases, provided the spatial temporal information about the phantom motion. The dosimetric comparison of the measured and the calculated dose distribution yielded gamma pass rates above 96% using a 3% dose difference and a 3mm distance to agreement criterion. Thus, a tool for the evaluation of interplay effects is available in a clinical software environment and patient-specific quality assurance can be extended to dynamic treatment scenarios.

Thin composite palladium and palladium/alloy membranes for hydrogen separation.

Dense composite Pd and Pd/alloy membranes are currently being extensively investigated. The synthesis and characterization of these membranes, with a special emphasis on Pd/alloy membranes, are reviewed in this paper. Experimental results on Pd/Cu membranes supported on porous stainless steel exhibited good thermal stability and reasonable hydrogen flux. Furthermore, optical micrographs showed the formation of the dense palladium layer was unaffected by the topological features of the porous stainless steel, although the surface of the support directs the topology of the final Pd layer.