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Purpose: The focus of this article is to describe the configuration, testing, and commissioning of a novel gantry-less synchrotron-based proton therapy (PT) facility. Materials and methods: The described PT system delivers protons with a water equivalent range between 4 and 38 cm in 1800 energy layers. The fixed beam delivery permits a maximum field size of 28 × 30 cm2. The patient positioning and imaging system includes a six-degree-of-freedom robotic arm, a convertible patient chair, a vertical 4DCT, and an orthogonal 2D X-ray imaging system. Results: The spot positioning reproducibility was consistent within ±1 mm. The width (σ) of the beam profile at the isocenter was energy dependent and ranged from 2.8 mm to 7.7 mm. Absolute dose reproducibility was measured and deviations were found to be <0.62% for all possible beam scenarios. The built-in dose monitoring system was successfully tested for its ability to generate interlocks under specific conditions (beam spot deviation ≥2 mm, individual spot dose ≥10% or ≥0.25 Gy, spot energy deviation ≥0.5 MeV). The robot positioning exhibited a consistent reproducibility within ±1 mm. All tested scenarios achieved laser-free initial 3D/3D image-guided positioning within ±5 mm. Subsequent 2D/3D positioning showed an accuracy of ±1 mm. A single 2D/3D image registration event corrected positions in all cases. Results of gamma analysis (3%, 3 mm) demonstrated pass rates greater than 95% for head and neck, thorax, abdomen treatment plans. Conclusions: We report on the performance of a novel single-room gantry-less PT system comprised of a compact synchrotron and an adjustable (from nearly horizontal to almost vertical) patient positioning system. The commissioning results show high accuracy and reproducibility of the main proton beam parameters and the patient positioning system. The new PT facility started patient treatments in March 2023, which were the first in Israel and the Middle Eastern region. [ABSTRACT FROM AUTHOR]

Background: Proton spatially fractionated RT (SFRT) can potentially synergize the unique advantages of using proton Bragg peak and SFRT peak‐valley dose ratio (PVDR) to reduce the radiation‐induced damage for normal tissues. Uniform‐target‐dose (UTD) proton GRID is a proton SFRT modality that can be clinically desirable and conveniently adopted since its UTD resembles target dose distribution in conventional proton RT (CONV). However, UTD proton GRID is not used clinically, which is likely due to the lack of an effective treatment planning method. Purpose: This work will develop a novel treatment planning method using scissor beams (SB) for UTD proton GRID, with the joint optimization of PVDR and dose objectives. Methods: The SB method for spatial dose modulation in normal tissues with UTD has two steps: (1) a primary beam (PB) is halved with interleaved beamlets, to generate spatial dose modulation in normal tissues; (2) a complementary beam (CB) is added to fill in previously valley‐dose positions in the target to generate UTD, while the CB is angled slightly from the PB, to maintain spatial dose modulation in normal tissues. A treatment planning method with PVDR optimization via the joint total variation and L1 (TVL1) regularization is developed to jointly optimize PVDR and dose objectives. The plan optimization solution is obtained using an iterative convex relaxation algorithm. Results: The new methods SB and SB‐TVL1 were validated in comparison with CONV. Compared to CONV of relatively homogeneous dose distribution, SB had modulated spatial dose pattern in normal tissues with UTD and comparable plan quality. Compared to SB, SB‐TVL1 further maximized PVDR, with comparable dose‐volume parameters. Conclusions: A novel SB method is proposed that can generate modulated spatial dose pattern in normal tissues to achieve UTD proton GRID. A treatment planning method with PVDR optimization capability via TVL1 regularization is developed that can jointly optimize PVDR and dose objectives for proton GRID. [ABSTRACT FROM AUTHOR]

Simple Summary: Adaptive proton therapy (APT) is an evolving approach to proton beam scanning treatment planning. We performed dosimetric study on two groups of head and neck (H&N) patients to evaluate the influence of plan adaptation on planning target volume (PTV) and organs at risk (OARs) doses, resulting from the changes in patient anatomy observed in control computed tomography (CT). The adapted treatment plans, which incorporated the changes observed in the control CT images, statistically improved mostly PTV coverage compared to initial plan. Study shows that applying adaptive procedures in clinical workflow may increased efficiency by controlling the proper irradiation of the treated area for H&N cancer patients. Applying a proton beam in radiotherapy enables precise irradiation of the tumor volume, but only for continuous assessment of changes in patient anatomy. Proton beam range uncertainties in the treatment process may originate not only from physical beam properties but also from patient-specific factors such as tumor shrinkage, edema formation and sinus filling, which are not incorporated in tumor volume safety margins. In this paper, we evaluated variations in dose distribution in proton therapy resulting from the differences observed in the control tomographic images and the dosimetric influence of applied adaptive treatment. The data from weekly computed tomography (CT) control scans of 21 patients, which serve as the basis for adaptive radiotherapy, were used for this study. Dosimetric analysis of adaptive proton therapy (APT) was performed on patients with head and neck (H&N) area tumors who were divided into two groups: patients with tumors in the sinus/nasal area and patients with tumors in the brain area. For this analysis, the reference treatment plans were forward-calculated using weekly control CT scans. A comparative evaluation of organ at risk (OAR) dose-volume histogram (DVH) parameters, as well as conformity and homogeneity indices, was conducted between the initial and recalculated dose distributions to assess the necessity of the adaptation process in terms of dosimetric parameters. Changes in PTV volume after replanning were observed in seventeen patient cases, showing a discrepancy of over 1 cm 3 in ten cases. In these cases, tumor progression occurred in 30% of patients, while regression was observed in 70%. The statistical analysis indicates that the use of the adaptive planning procedure results in a statistically significant improvement in dose distribution, particularly in the PTV area. The findings led to the conclusion that the adaptive procedure provides significant advantages in terms of dose distribution within the treated volume. However, when considering the entire patient group, APT did not result in a statistically significant dose reduction in OARs (α = 0.05). [ABSTRACT FROM AUTHOR]

Background: MR‐integrated proton therapy is under development. It consists of the unique challenge of integrating a proton pencil beam scanning (PBS) beam line nozzle with an magnetic resonance imaging (MRI) scanner. The magnetic interaction between these two components is deemed high risk as the MR images can be degraded if there is cross‐talk during beam delivery and image acquisition. Purpose: To create and benchmark a self‐consistent proton PBS nozzle model for empowering the next stages of MR‐integrated proton therapy development, namely exploring and de‐risking complete integrated prototype system designs including magnetic shielding of the PBS nozzle. Materials and Methods: Magnetic field (COMSOL Multiphysics${\text{Multiphysics}}$) and radiation transport (Geant4) models of a proton PBS nozzle located at OncoRay (Dresden, Germany) were developed according to the manufacturers specifications. Geant4 simulations of the PBS process were performed by using magnetic field data generated by the COMSOL Multiphysics${\text{Multiphysics}}$ simulations. In total 315 spots were simulated which consisted of a 40×30cm2$40\times 30\,{\text{cm}}^{2}$ scan pattern with 5 cm spot spacings and for proton energies of 70, 100, 150, 200, and 220 MeV. Analysis of the simulated deflection at the beam isocenter plane was performed to determine the self‐consistency of the model. The magnetic fringe field from a sub selection of 24 of the 315 spot simulations were directly compared with high precision magnetometer measurements. These focused on the maximum scanning setting of ±$\pm$ 20 cm beam deflection as generated from the second scanning magnet in the PBS for a proton beam energy of 220 MeV. Locations along the beam line central axis (CAX) were measured at beam isocenter and downstream of 22, 47, 72, 97, and 122 cm. Horizontal off‐axis positions were measured at 22 cm downstream of isocenter (±$\pm$ 50, ±$\pm$ 100, and ±$\pm$ 150 cm from CAX). Results: The proton PBS simulations had good spatial agreement to the theoretical values in all 315 spots examined at the beam line isocenter plane (0–2.9 mm differences or within 1.5 % of the local spot deflection amount). Careful analysis of the experimental measurements were able to isolate the changes in magnetic fields due solely to the scanning magnet contribution, and showed 1.9 ±$\pm$ 1.2 μT$\bf{\mu} {\text{T}}$–9.4 ±$\pm$ 1.2 μT$\bf{\mu} {\text{T}}$ changes over the range of measurement locations. Direct comparison with the equivalent simulations matched within the measurement apparatus and setup uncertainty in all but one measurement point. Conclusions: For the first time a robust, accurate and self‐consistent model of a proton PBS nozzle assembly has been created and successfully benchmarked for the purposes of advancing MR‐integrated proton therapy research. The model will enable confidence in further simulation based work on fully integrated designs including MRI scanners and PBS nozzle magnetic shielding in order to de‐risk and realize the full potential of MR‐integrated proton therapy. [ABSTRACT FROM AUTHOR]

Purpose: The time structures of proton spot delivery in proton pencil beam scanning (PBS) radiation therapy are essential in many clinical applications. This study aims to characterize the time structures of proton PBS delivered by both synchrotron and synchrocyclotron accelerators using a non‐invasive technique based on scattered particle tracking. Methods: A pixelated semiconductor detector, AdvaPIX‐Timepix3, with a temporal resolution of 1.56 ns, was employed to measure time of arrival of secondary particles generated by a proton beam. The detector was placed laterally to the high‐flux area of the beam in order to allow for single particle detection and not interfere with the treatment. The detector recorded counts of radiation events, their deposited energy and the timestamp associated with the single events. Individual recorded events and their temporal characteristics were used to analyze beam time structures, including energy layer switch time, magnet switch time, spot switch time, and the scanning speeds in the x and y directions. All the measurements were repeated 30 times on three dates, reducing statistical uncertainty. Results: The uncertainty of the measured energy layer switch times, magnet switch time, and the spot switch time were all within 1% of average values. The scanning speeds uncertainties were within 1.5% and are more precise than previously reported results. The measurements also revealed continuous sub‐milliseconds proton spills at a low dose rate for the synchrotron accelerator and radiofrequency pulses at 7 µs and 1 ms repetition time for the synchrocyclotron accelerator. Conclusion: The AdvaPIX‐Timepix3 detector can be used to directly measure and monitor time structures on microseconds scale of the PBS proton beam delivery. This method yielded results with high precision and is completely independent of the machine log files. [ABSTRACT FROM AUTHOR]

Background: Chordomas and chondrosarcomas of the skull base are rare, slowly growing malignant bone neoplasms. Despite their radioresistant properties, proton therapy has been successfully used as an adjunct to resection or as a definitive treatment. Herewith, we present our experience with robustly optimized intensity-modulated proton therapy (IMPT) and related toxicities in skull base chordoma and chondrosarcoma patients treated at HollandPTC, Delft, the Netherlands. Methods: Clinical data, treatment plans, and acute toxicities of patients treated between July 2019 and August 2021 were reviewed. CT and 3.0T MRI scans for treatment planning were performed in supine position in a thermoplastic mold. In total, 21 dose optimization and 28 dose evaluation scenarios were simulated. Acute toxicity was scored weekly before and during the treatment according to the CTCAE v4.0. Median follow-up was 35 months (range 12–36 months). Results: Overall, 9 chordoma and 3 chondrosarcoma patients with 1–3 resections prior to IMPT were included; 4 patients had titanium implants. Brainstem core and surface and spinal cord core and surface were used for nominal plan robust optimization in 11, 10, 8, and 7 patients, respectively. Middle ear inflammation, dry mouth, radiation dermatitis, taste disorder, and/or alopecia of grades 1–3 were noted at the end of treatment among 6 patients without similar complaints at inclusion; symptoms disappeared 3 months following the treatment. Conclusion: Robustly optimized IMPT is clinically feasible as a postoperative treatment for skull base chordoma and chondrosarcoma patients. We observed acceptable early toxicities (grade 1–3) that disappeared within the first 3 months after irradiation. [ABSTRACT FROM AUTHOR]

Simple Summary: Using the Proton Therapy Collaborative group registry, we describe the impact of pencil beam scanning (PBS) proton beam therapy (PBT) for Hodgkin lymphoma patients who require radiation to both mediastinal and axillary targets. We performed dosimetric comparisons between delivered PBS plans and photons with butterfly volumetric arc therapy (BVMAT). Compared to BVMAT, PBS had greater target coverage, better conformity, and lower dose heterogeneity while achieving a lower dose to the lungs and heart. Nearly half of the BVMAT plans exceeded the lung V5 constraint (>55%). PBS was well tolerated without any pneumonitis or grade 3+ acute toxicity. We show here that patients requiring both mediastinal and axillary treatment may be another subgroup of lymphoma patients who may benefit from PBT. Because proton beam therapy (PBT) can lower the dose of radiation to the heart, lungs, and breast, it is an established radiation modality for patients with Hodgkin lymphoma (HL). Pencil beam scanning (PBS) PBT facilitates the treatment of more extensive targets. This may be especially of value for lymphoma patients who require RT to both mediastinal and axillary targets, defined here as extended target RT (ETRT), given the target distribution and need to minimize the lung, heart, and breast dose. Using the Proton Collaborative Group registry, we identified patients with HL treated with PBT to both their mediastinum and axilla, for which DICOM-RT was available. All patients were treated with PBS. To evaluate the dosimetric impact of PBS, we compared delivered PBS plans with VMAT butterfly photon plans optimized to have the same target volume coverage, when feasible. Between 2016 and 2021, twelve patients (median 26 years) received PBS ETRT (median 30.6 Gy (RBE)). Despite the large superior/inferior (SI, median 22.2 cm) and left/right (LR, median 22.8 cm) extent of the ETRT targets, all patients were treated with one isocenter except for two patients (both with SI and LR > 30 cm). Most commonly, anterior beams, with or without posterior beams, were used. Compared to photons, PBS had greater target coverage, better conformity, and lower dose heterogeneity while achieving lower doses to the lungs and heart, but not to the breast. No acute grade 3+ toxicities were reported, including pneumonitis. Proton ETRT in this small cohort was safely delivered with PBS and was associated with an improved sparing of the heart and lungs compared to VMAT. [ABSTRACT FROM AUTHOR]

Purpose: The treatment of brain tumors in pregnant patients poses challenges, as the out‐of‐field dose exposure to the fetus can potentially be harmful. A pregnant patient with prior radiation treatment was presented with a brain tumor at our clinic. This work reports on our pre‐treatment study that compared fetal dose exposure between intensity‐modulated proton therapy (IMPT) using pencil beam scanning (PBS) and conventional photon 3D conformal radiation therapy (3DCRT) and volumetric‐modulated arc therapy (VMAT), and the subsequent pregnant patient's radiation treatment. Materials and methods: Pre‐treatment measurements of clinical plans, 3DCRT, VMAT, and IMPT, were conducted on a phantom. Measurements were performed using a device capable of neutron detections, closely following AAPM guidelines, TG158. For photon measurements, fetus shielding was utilized. On patient treatment days, which was determined to be proton treatment, shielding was used only during daily imaging for patient setup. Additionally, an in vivo measurement was conducted on the patient. Results: Measurements showed that IMPT delivered the lowest fetal dose, considering both photon and neutron out‐of‐field doses to the fetus, even when shielding was implemented for photon measurements. Additionally, the proton plans demonstrated superior treatment for the mother, a reirradiation case. Conclusion: The patient was treated with proton therapy, and the baby was subsequently delivered at full term with no complications. This case study supports previous clinical findings and advocates for the expanded use of proton therapy in this patient population. [ABSTRACT FROM AUTHOR]

Background: While minimizing plan delivery time is beneficial for proton therapy in terms of motion management, patient comfort, and treatment throughput, it often poses a tradeoff with optimizing plan quality. A key component of plan delivery time is the energy switching time, which is approximately proportional to the number of energy layers, that is, the cardinality. Purpose: This work aims to develop a novel optimization method that can efficiently compute the pareto surface between plan quality and energy layer cardinality, for the planner to navigate through this quality‐and‐efficiency tradeoff and select the appropriate plan of a balanced tradeoff. Methods: A new IMPT method CARD is proposed that (1) explicitly incorporates the minimization of energy layer cardinality as an optimization objective, and (2) automatically generates a set of plans sequentially with a descending order in number of energy layers. The energy layer cardinality is penalized through the l1,0‐norm regularization with an upper bound, and the upper bound is monotonically decreased to compute a series of treatment plans with gradually decreased energy layer cardinality on the quality‐and‐efficiency pareto surface. For any given treatment plan, the plan optimality is enforced using dose‐volume planning objectives and the plan deliverability is imposed through minimum‐monitor‐unit (MMU) constraints, with optimization solution algorithm based on iterative convex relaxation. Results: The new method CARD was validated in comparison with the benchmark plan of all energy layers (P0), and a state‐of‐the‐art method called MMSEL, using prostate, head‐and‐neck (HN), lung, pancreas, liver and brain cases. While labor‐intensive and time‐consuming manual parameter tuning was needed for MMSEL to generate plans of predefined energy layer cardinality, CARD automatically and efficiently computed all plans with sequentially decreasing predefined energy layer cardinality all at once. With the acceptable plan quality (i.e., no more than 110% of total optimization objective value from P0), CARD achieved the reduction of number of energy layers to 52% (from 77 to 40), 48% (from 135 to 65), 59% (from 85 to 50), 67% (from 52 to 35), 80% (from 50 to 40), and 30% (from 66 to 20), for prostate, HN, lung, pancreas, liver, and brain cases, respectively, compared to P0, with overall better plan quality than MMSEL. Moreover, due to the nonconvexity of the MMU constraint, CARD provided the similar or even smaller optimization objective than P0, at the same time with fewer number of energy layers, that is, 55 versus 77, 85 versus 135, 45 versus 52, and 25 versus 66 for prostate, HN, pancreas, and brain cases, respectively. Conclusions: We have developed a novel optimization algorithm CARD that can efficiently and automatically compute a series of treatment plans of any given energy layer sequentially, which allows the planner to navigate through the plan‐quality and energy‐layer‐cardinality tradeoff and select the appropriate plan of a balanced tradeoff. [ABSTRACT FROM AUTHOR]

Introduction: Daily quality assurance is an integral part of a radiotherapy workflow to ensure the dose is delivered safely and accurately to the patient. It is performed before the first treatment of the day and needs to be time and cost efficient for a multiple gantries proton center. In this study, we introduced an efficient method to perform QA for output constancy, range verification, spot positioning accuracy and imaging and proton beam isocenter coincidence with DailyQA3. Methods: A stepped acrylic block of specific dimensions is fabricated and placed on top of the DailyQA3 device. Treatment plans comprising of two different spread‐out Bragg peaks and five individual spots of 1.0 MU each are designed to be delivered to the device. A mathematical framework to measure the 2D distance between the detectors and individual spot is introduced and play an important role in realizing the spot positioning and centering QA. Lastly, a 5 months trends of the QA for two gantries are presented. Results: The outputs are monitored by two ion chambers in the DailyQA3 and a tolerance of ±3%$ \pm 3\% $ are used. The range of the SOBPs are monitored by the ratio of ion chamber signals and a tolerance of ±1mm$ \pm 1\ {\mathrm{mm}}$ is used. Four diodes at ±10cm$ \pm 10\ {\mathrm{cm}}$ from the central ion chambers are used for spot positioning QA, while the central ion chamber is used for imaging and proton beam isocenter coincidence QA. Using the framework, we determined the absolute signal threshold corresponding to the offset tolerance between the individual proton spot and the detector. A 1.5mm$1.5\ {\mathrm{mm}}$ tolerances are used for both the positioning and centering QA. No violation of the tolerances is observed in the 5 months trends for both gantries. Conclusion: With the proposed approach, we can perform four QA items in the TG224 within 10 min. [ABSTRACT FROM AUTHOR]

Simple Summary: Pencil beam scanning nozzles monitor the beam position in real time and record the results in log files. We cannot, however, place a beam position monitor at the isocenter during treatment, so accurate online beam position corrections and log file analyses rely on an algorithm to project the beam position from the nozzle to the isocentric plane. We present four generic algorithms and determined the accuracy of each approach in three example configurations and two nozzle lengths. Beam position uncertainties along the beam trajectory arise from the accelerator, beamline, and scanning magnets (SMs). They can be monitored in real time, e.g., through strip ionization chambers (ICs), and treatments can be paused if needed. Delivery is more reliable and accurate if the beam position is projected from monitored nozzle parameters to the isocenter, allowing for accurate online corrections to be performed. Beam position projection algorithms are also used in post-delivery log file analyses. In this paper, we investigate the four potential algorithms that can be applied to all pencil beam scanning (PBS) nozzles. For some combinations of nozzle configurations and algorithms, however, the projection uses beam properties determined offline (e.g., through beam tuning or technical commissioning). The best algorithm minimizes either the total uncertainty (i.e., offline and online) or the total offline uncertainty in the projection. Four beam position algorithms are analyzed (A1–A4). Two nozzle lengths are used as examples: a large nozzle (1.5 m length) and a small nozzle (0.4 m length). Three nozzle configurations are considered: IC after SM, IC before SM, and ICs on both sides. Default uncertainties are selected for ion chamber measurements, nozzle entrance beam position and angle, and scanning magnet angle. The results for other uncertainties can be determined by scaling these results or repeating the error propagation. We show the propagation of errors from two locations and the SM angle to the isocenter for all the algorithms. The best choice of algorithm depends on the nozzle length and is A1 and A3 for the large and small nozzles, respectively. If the total offline uncertainty is to be minimized (a better choice if the offline uncertainty is not stable), the best choice of algorithm changes to A1 for the small nozzle for some hardware configurations. Reducing the nozzle length can help to reduce the gantry size and make proton therapy more accessible. This work is important for designing smaller nozzles and, consequently, smaller gantries. This work is also important for log file analyses. [ABSTRACT FROM AUTHOR]

PurposeThe focus of this article is to describe the configuration, testing, and commissioning of a novel gantry-less synchrotron-based proton therapy (PT) facility.Materials and methodsThe described PT system delivers protons with a water equivalent range between 4 and 38 cm in 1800 energy layers. The fixed beam delivery permits a maximum field size of 28 × 30 cm2. The patient positioning and imaging system includes a six-degree-of-freedom robotic arm, a convertible patient chair, a vertical 4DCT, and an orthogonal 2D X-ray imaging system.ResultsThe spot positioning reproducibility was consistent within ±1 mm. The width (σ) of the beam profile at the isocenter was energy dependent and ranged from 2.8 mm to 7.7 mm. Absolute dose reproducibility was measured and deviations were found to be

Purpose: Experimental patient‐specific QA (PSQA) is a time and resource‐intensive process, with a poor sensitivity in detecting errors. Radiation therapy facilities aim to substitute it by means of independent dose calculation (IDC) in combination with a comprehensive beam delivery QA program. This paper reports on the commissioning of the IDC software tool myQA iON (IBA Dosimetry) for proton therapy and its clinical implementation at the MedAustron Ion Therapy Center. Methods: The IDC commissioning work included the validation of the beam model, the implementation and validation of clinical CT protocols, and the evaluation of patient treatment data. Dose difference maps, gamma index distributions, and pass rates (GPR) have been reviewed. The performance of the IDC tool has been assessed and clinical workflows, simulation settings, and GPR tolerances have been defined. Results: Beam model validation showed agreement of ranges within ± 0.2 mm, Bragg‐Peak widths within ± 0.1 mm, and spot sizes at various air gaps within ± 5% compared to physical measurements. Simulated dose in 2D reference fields deviated by ‐0.3% ± 0.5%, while 3D dose distributions differed by 1.8% on average to measurements. Validation of the CT calibration resulted in systematic differences of 2.0% between IDC and experimental data for tissue like samples. GPRs of 99.4 ± 0.6% were found for head, head and neck, and pediatric CT protocols on a 2%/2 mm gamma criterion. GPRs for the adult abdomen protocol were at 98.9% on average with 3%/3 mm. Root causes of GPR outliers, for example, implants were identified and evaluated. Conclusion: IDC has been successfully commissioned and integrated into the MedAustron clinical workflow for protons in 2021. IDC has been stepwise and safely substituting experimental PSQA since February 2021. The initial reduction of proton experimental PSQA was about 25% and reached up to 90% after 1 year. [ABSTRACT FROM AUTHOR]

Objective. Clinical outcomes after proton therapy have shown some variability that is not fully understood. Different approaches have been suggested to explain the biological outcome, but none has yet provided a comprehensive and satisfactory rationale for observed toxicities. The relatively recent transition from passive scattering (PS) to pencil beam scanning (PBS) treatments has significantly increased the voxel-wise dose rate in proton therapy. In addition, the dose rate distribution is no longer uniform along the cross section of the target but rather highly heterogeneous, following the spot placement. We suggest investigating dose rate as potential contributor to a more complex proton RBE model. Approach. Due to the time structure of the PBS beam delivery the instantaneous dose rate is highly variable voxel by voxel. Several possible parameters to represent voxel-wise dose rate for a given clinical PBS treatment plan are detailed. These quantities were implemented in the scripting environment of our treatment planning system, and computations experimentally verified. Sample applications to treated patient plans are shown. Main results. Computed dose rates we experimentally confirmed. Dose rate maps vary depending on which method is used to represent them. Mainly, the underlying time and dose intervals chosen determine the topography of the resultant distributions. The maximum dose rates experienced by any target voxel in a given PBS treatment plan in our system range from ∼100 to ∼450 Gy(RBE)/min, a factor of 10–100 increase compared to PS. These dose rate distributions are very heterogeneous, with distinct hot spots. Significance. Voxel-wise dose rates for current clinical PBS treatment plans vary greatly from clinically established practice with PS. The exploration of different dose rate measures to evaluate potential correlations with observed clinical outcomes is suggested, potentially adding a missing component in the understanding of proton relative biological effectiveness (RBE). [ABSTRACT FROM AUTHOR]

In pencil-beam-scanning proton therapy, the dose is painted spot-by-spot, layer-by-layer, allowing for significantly more control compared to conventional radiation. This work intends to showcase the impressive ability of intensity-modulated proton therapy (IMPT) to shape complex dose distributions by recreating some of history's most renowned artworks as treatment plans. Five (5) well-recognized paintings were recreated in our clinical treatment planning system using a water phantom as a "canvas" and radiation dose as "paint." For each "painting," colors were assigned to various isodose levels, and the treatment plans were inversely optimized to achieve the desired tones. Using the above methods, we were able to recreate The Starry Night by Vincent Van Gogh, Girl with a Pearl Earring by Johannes Vermeer, and The Scream by Edvard Munch, among others. The results of this work have potential applications in patient education, medical education, and medical physics education by providing a unique and interesting platform for learning. [ABSTRACT FROM AUTHOR]

This study explores the feasibility and potential dosimetric and time efficiency benefit of proton Pencil Beam Scanning (PBS) craniospinal irradiation with a single posterior-anterior (SPA) brain field. The SPA approach was compared to our current clinical protocol using Bilateral Posterior Oblique brain fields (BPO). Ten consecutive patients were simulated in the head-first supine position on a long BOS frame and scanned using 3 mm CT slice thickness. A customized thermoplastic mask immobilized the patient's head, neck, and shoulders. A vac-lock was used to secure the legs. PBS proton plans were robustly optimized with 3mm setup errors and 3.5% range uncertainties in the Eclipse V15.6 treatment planning system (n = 12 scenarios). In order to achieve a smooth gradient dose match at the junction area, at least 5 cm overlap region was maintained between the segments and 5 mm uncertainty along the cranial-cauda direction was applied to each segment independently as additional robust optimization scenarios. The brain doses were planned by SPA or BPO fields. All spine segments were planned with a single PA field. Dosimetric differences between the BPO and SPA approaches were compared, and the treatment efficiency was analyzed according to timestamps of beam delivery. Results: The maximum brain dose increases to 111.1 ± 2.1% for SPA vs. 109.0 ± 1.7% for BPO (p < 0.01). The dose homogeneity index (D5/D95) in brain CTV was comparable between techniques (1.037 ± 0.010 for SPA and 1.033 ± 0.008 for BPO). Lens received lower maximum doses by 2.88 ± 1.58 Gy (RBE) (left) and 2.23 ± 1.37 Gy (RBE) (right) in the SPA plans (p < 0.01). No significant cochlea dose change was observed. SPA reduced the treatment time by more than 4 minutes on average and ranged from 2 to 10 minutes, depending on the beam waiting and allocation time. SPA is dosimetrically comparable to BPO, with reduced lens doses at the cost of slightly higher dose inhomogeneity and hot spots. Implementation of SPA is feasible and can help to improve the treatment efficiency of PBS CSI treatment. [ABSTRACT FROM AUTHOR]

Proton therapy offers unique physical properties that make it an excellent choice for treating metastatic breast cancer, particularly when recurrent disease occurs near previously irradiated tissues. This case study demonstrates the dosimetric benefits of proton therapy in patients with metastatic breast cancer to the skin. The case consists of one patient with 5 separate areas treated with Pencil Beam Scanning (PBS) proton therapy over a period of 2 years using Monte Carlo calculation and robust optimization. The results demonstrate that proton therapy effectively spared healthy tissues while delivering the prescribed dose to the tumor. This case demonstrates the feasibility of developing effective radiation plans for skin metastases using proton therapy, highlighting its dosimetric advantages and minimal impact on nearby organs. [ABSTRACT FROM AUTHOR]

This study evaluated the dose distributions of proton pencil beam scanning (PBS) with/without a multileaf collimator (MLC) compared to passive scattering (PS) for stage I/II lung cancers. Collimated/uncollimated (PBS+/PBS-) and PS plans were created for 20 patients. Internal-clinical-target-volumes (ICTVs) and planning-target-volumes (PTVs) with a 5 mm margin were defined on the gated CTs. Organs-at-risk (OARs) are defined as the normal lungs, spinal cord, esophagus, and heart. The prescribed dose was 66 Gy relative-biological-effectiveness (RBE) in 10 fractions at the isocenter and 50% volume of the ICTVs for the PS and PBS, respectively. We compared the target and OAR dose statistics from the dose volume histograms. The PBS+ group had a significantly better mean PTV conformity index than the PBS- and PS groups. The mean dose sparing for PBS+ was better than those for PBS- and PS. Only the normal lung doses of PBS- were worse than those of PS. The overall performance of the OAR sparing was in the order of PBS+, PBS-, and PS. The PBS+ plan showed significantly better target homogeneity and OAR sparing than the PBS- and PS plans. PBS requires collimating systems to treat lung cancers with the most OAR sparing while maintaining the target coverage. [ABSTRACT FROM AUTHOR]

Proton therapy (PT) is an advancing radiotherapy modality increasingly integrated into clinical settings, transitioning from research facilities to hospital environments. A critical aspect of the commissioning of a proton pencil beam scanning delivery system is the acquisition of experimental beam data for accurate beam modelling within the treatment planning system (TPS). These guidelines describe in detail the acquisition of proton pencil beam modelling data. First, it outlines the intrinsic characteristics of a proton pencil beam—energy distribution, angular-spatial distribution and particle number. Then, it lists the input data typically requested by TPSs. Finally, it describes in detail the set of experimental measurements recommended for the acquisition of proton pencil beam modelling data—integrated depth-dose curves, spot maps in air, and reference dosimetry. The rigorous characterization of these beam parameters is essential for ensuring the safe and precise delivery of proton therapy treatments.

Wenna Zhang,1– 3 Xin Cai,1– 3 Jiayao Sun,2– 4 Weiwei Wang,2– 4 Jingfang Zhao,2– 4 Qing Zhang,1– 3 Guoliang Jiang,1– 3,5 Zheng Wang1– 3,5 1Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Radiation Oncology (20dz2261000), Shanghai, People’s Republic of China; 3Shanghai Engineering Research Center of Proton and Heavy Ion Radiation Therapy, Shanghai, People’s Republic of China; 4Department of Medical Physics, Shanghai Proton and Heavy Ion Center, Shanghai, People’s Republic of China; 5Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital, Shanghai, People’s Republic of ChinaCorrespondence: Guoliang Jiang; Zheng Wang, Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital, No. 4365 Kangxin Road, Pudong, Shanghai, 201315, People’s Republic of China, Email guoliang.jiang@sphic.org.cn; zheng.wang@sphic.org.cnPurpose: Carbon ion radiotherapy (CIRT) has emerged as a promising treatment modality for hepatocellular carcinoma (HCC). However, evidence of using the pencil beam scanning (PBS) technique to treat moving liver tumors remains lacking. The present study investigated the efficacy and toxicity of PBS CIRT in patients with HCC.Methods: Between January 2016 and October 2021, 90 consecutive HCC patients treated with definitive CIRT in our center were retrospectively analyzed. Fifty-eight patients received relative biological effectiveness-weighted doses of 50– 70 Gy in 10 fractions, and 32 received 60– 67.5 Gy in 15 fractions, which were determined by the tumor location and normal tissue constraints. Active motion-management techniques and necessary strategies were adopted to mitigate interplay effects efficiently. Oncologic outcomes and toxicities were evaluated.Results: The median follow-up time was 28.6 months (range 5.7– 74.6 months). The objective response rate was 75.0% for all 90 patients with 100 treated lesions. The overall survival rates at 1-, 2- and 3-years were 97.8%, 83.3% and 75.4%, respectively. The local control rates at 1-, 2- and 3-years were 96.4%, 96.4% and 93.1%, respectively. Radiation-induced liver disease was not documented, and 4 patients (4.4%) had their Child–Pugh score elevated by 1 point after CIRT. No grade 3 or higher acute non-hematological toxicities were observed. Six patients (6.7%) experienced grade 3 or higher late toxicities.Conclusion: The active scanning technique was clinically feasible to treat HCC by applying necessary mitigation measures for interplay effects. The desirable oncologic outcomes as well as favorable toxicity profiles presented in this study will be a valuable reference for other carbon-ion centers using the PBS technique and local effect model-based system, and add to a growing body of evidence about the role of CIRT in the management of HCC.Keywords: hepatocellular carcinoma, carbon ion radiotherapy, pencil beam scanning, local effect model

Simple Summary: As the technology of the pencil beam scanning system advances, achieving higher accuracy in converting CT Hounsfield to proton-stopping power becomes imperative. Recently, the dual-energy computer tomography (DECT) technique has emerged as a superior technique to single-energy computer tomography in estimating SPR. However, such a technique is not widely adopted clinically. One of the reasons is that the optimization process on the DECT scanners involves a wide range of parameters, one of which is spectral pair. It is generally accepted that the larger separation of the spectra pair could yield a better estimation of SPR. However, it is not validated under a scenario of scanning objects deviating from calibration conditions. In this simulation study, we are examining the performance of variations of spectra pairs on SPR prediction. Our study aims to quantify the impact of spectral separation on achieved theoretical prediction accuracy of proton-stopping power when the volume discrepancy between calibration phantom and scanned object is observed. Such discrepancy can be commonly seen in our CSI pediatric patients. One of the representative image-domain DECT models is employed on a virtual phantom to derive electron density and effective atomic number for a total of 34 ICRU standard human tissues. The spectral pairs used in this study are 90 kVp/140 kVp, without and with 0.1 mm to 0.5 mm additional tin filter. The two DECT images are reconstructed via a conventional filtered back projection algorithm (FBP) on simulated noiseless projection data. The best-predicted accuracy occurs at a spectral pair of 90 kVp/140 kVp with a 0.3 mm tin filter, and the root-mean-squared average error is 0.12% for tissue substitutes. The results reveal that the selected image-domain model is sensitive to spectral pair deviation when there is a discrepancy between calibration and scanning conditions. This study suggests that an optimization process may be needed for clinically available DECT scanners to yield the best proton-stopping power estimation. [ABSTRACT FROM AUTHOR]

Simple Summary: The currently documented outcomes of proton therapy for patients with localized prostate cancer are based on passive scattering (PS). In this study, we compared the dose distribution of the line scanning (LS) method, one of the pencil beam scanning (PBS) techniques, with that of PS and volumetric modulated arc therapy (VMAT) in 30 patients. The results showed that LS could significantly reduce the wide range of rectal and bladder doses compared to the PS and VMAT while upholding the requisite target dose. The results suggest that proton therapy for prostate cancer with the PBS method may have the potential to reduce toxicities further while preserving therapeutic efficacies. Background: The proton irradiation modality has transitioned from passive scattering (PS) to pencil beam scanning. Nevertheless, the documented outcomes predominantly rely on PS. Methods: Thirty patients diagnosed with prostate cancer were selected to assess treatment planning across line scanning (LS), PS, and volumetric modulated arc therapy (VMAT). Dose constraints encompassed clinical target volume (CTV) D98 ≥ 73.0 Gy (RBE), rectal wall V65 < 17% and V40 < 35%, and bladder wall V65 < 25% and V40 < 50%. The CTV, rectal wall, and bladder wall dose volumes were calculated and evaluated using the Freidman test. Results: The LS technique adhered to all dose limitations. For the rectal and bladder walls, 10 (33.3%) and 21 (70.0%) patients in the PS method and 5 (16.7%) and 1 (3.3%) patients in VMAT, respectively, failed to meet the stipulated requirements. The wide ranges of the rectal and bladder wall volumes (V10-70) were lower with LS than with PS and VMAT. LS outperformed VMAT across all dose–volume rectal and bladder wall indices. Conclusion: The LS method demonstrated a reduction in rectal and bladder doses relative to PS and VMAT, thereby suggesting the potential for mitigating toxicities. [ABSTRACT FROM AUTHOR]

Purpose: We developed a 4‐dimensional dynamic dose (4DDD) calculation model for proton pencil beam scanning (PBS). This model incorporates the spill start time for all energies and uses the remaining irradiated spot time model instead of irradiated spot time logs. This study aimed to validate the calculation accuracy of a log file‐based 4DDD model by comparing it with dose measurements performed under free‐breathing conditions, thereby serving as an alternative approach to the conventional log file‐based system. Methods: Three cubic verification plans were created using a heterogeneous block phantom; these plans were created using 10 phase 4D‐CT datasets of the phantom. The CIRS dynamic platform was used to simulate motion with amplitudes of 2.5, 3.75, and 5.0 mm. These plans consisted of eight‐ and two‐layered rescanning techniques. The lateral profiles were measured using a 2D ionization chamber array (2D‐array) and EBT3 Gafchromic films at four starting phases, including three sinusoidal curves (periods of 3, 4, and 6 s) and a representative patient curve during actual treatment. 4DDDs were calculated using in‐house scripting that assigned a time stamp to each spot and performed dose accumulation using deformable image registration. Furthermore, to evaluate the impact of parameter selection on our 4DDD model calculations, simulations were performed assuming a ±10% change in irradiation time stamp (0.8 ± 0.08 s) and spot scan speed. We evaluated the 2D gamma index and the absolute point doses between the calculated values and the measurements. Results: The 2D‐array measurements revealed that the gamma scores for the static plans (no motion) and 4DDD plans exceeded 97.5% and 93.9% at 3%/3 mm, respectively. The average gamma score of the 4DDD plans was at least 96.1%. When using EBT3 films, the gamma scores of the 4DDD model exceeded 92.4% and 98.7% at 2%/2 mm and 3%/3 mm, respectively. Regarding the 4DDD point dose differences, more than 95% of the dose regions exhibited discrepancies within ±5.0% for 97.7% of the total points across all plans. The spot time assignment accuracy of our 4DDD model was acceptable even with ±10% sensitivity. However, the accuracy of the scan speed, when varied within ±10% sensitivity, was not acceptable (minimum gamma scores of 82.6% and maximum dose difference of 12.9%). Conclusions: Our 4DDD calculations under free‐breathing conditions using amplitudes of less than 5.0 mm were in good agreement with the measurements regardless of the starting phases, breathing curve patterns (between 3 and 6 s periods), and varying numbers of layered rescanning. The proposed system allows us to evaluate actual irradiated doses in various breathing periods, amplitudes, and starting phases, even on PBS machines without the ability to record spot logs. [ABSTRACT FROM AUTHOR]

Simple Summary: Ultra-high dose rate (UHDR) irradiation in proton therapy has mostly been performed using a cyclotron system so far. In this study, we present our approach to achieve an ultra-high dose rate for a clinical synchrotron proton therapy system and its dosimetric specifications. We demonstrated that it is feasible to adapt an existing clinical synchrotron-based proton therapy system and reach ~100 nA nozzle beam. UHDR dose rate (>40 Gy/s) was reached with the tested spot scanning patterns. The maximum dose per spill depends on the field size and is limited by the maximum charge extraction per spill. A beam monitoring ion chamber is currently being incorporated into the beam control system to improve system reproducibility and expand the irradiation area. Background: This study aims to present the feasibility of developing a synchrotron-based proton ultra-high dose rate (UHDR) pencil beam scanning (PBS) system. Methods: The RF extraction power in the synchrotron system was increased to generate 142.4 MeV pulsed proton beams for UHDR irradiation at ~100 nA beam current. The charge per spill was measured using a Faraday cup. The spill length and microscopic time structure of each spill was measured with a 2D strip transmission ion chamber. The measured UHDR beam fluence was used to derive the spot dwell time for pencil beam scanning. Absolute dose distributions at various depths and spot spacings were measured using Gafchromic films in a solid-water phantom. Results: For proton UHDR beams at 142.4 MeV, the maximum charge per spill is 4.96 ± 0.10 nC with a maximum spill length of 50 ms. This translates to an average beam current of approximately 100 nA during each spill. Using a 2 × 2 spot delivery pattern, the delivered dose per spill at 5 cm and 13.5 cm depth is 36.3 Gy (726.3 Gy/s) and 56.2 Gy (1124.0 Gy/s), respectively. Conclusions: The synchrotron-based proton therapy system has the capability to deliver pulsed proton UHDR PBS beams. The maximum deliverable dose and field size per pulse are limited by the spill length and extraction charge. [ABSTRACT FROM AUTHOR]

Background: Very high‐energy electrons (VHEE) radiotherapy, in the energy range of 100–200 MeV is currently considered a promising technique for the future of radiation therapy and could benefit from the promises of ultra‐high dose rate FLASH therapy. However, to our knowledge, no analytical calculation models have been tested for this type of application and the approximations proposed for multiple scattering with electron beams have not been extensively evaluated at these high energies. Purpose: In this work, we discuss the derivation of a simple and fast algorithm based on the Fermi‐Eyges theory of multiple Coulomb scattering for fast dose calculation for VHEE beams (up to 200 MeV). Similar to the Gaussian pencil beam models used for electron or proton beams, this pencil beam kernel is separated into a central and an off‐axis term. Monte Carlo simulations are performed to compare the analytical calculations with simulations and to determine the parametrizations used in the model at the highest electron energies. Methods: The normalized electron planar fluence distribution is described in water according to the Fermi‐Eyges theory of multiple Coulomb scattering and a double Gaussian distribution model. The main quantities used in the model and their calculation (mass angular scattering power, mean energy, range straggling) are discussed and tested for electron energies up to 200 MeV. The TOPAS/Geant4 Monte Carlo (MC) toolkit is used to compare analytical calculations with MC simulations for a theoretical pencil beam irradiation and to find the best parameters describing the range straggling. The model is then tested on a realistic simulation of a pencil beam scanning beamline with treatment field dimensions up to 15 × 15 cm2 and for deep‐seated targets. Results: Radial dose distributions of a pencil beam in water were calculated with the model and compared with the results of a complete Monte Carlo simulation. A good agreement (within 2%/2 mm gamma passing rate superior to 90%, and a mean deviation between calculated and simulated pencil beam radial spread smaller than 0.6 mm) was observed between analytical dose distributions and simulations for energies up to 200 MeV and field sizes up to 15 × 15 cm2. Conclusions: A parameterization of an electron source and an analytical pencil beam model were proposed in this work, thereby allowing a suitable reproduction of the lateral fluence of a VHEE beam and good agreement between calculations and simulated data. Further improvement of the method would require the consideration of a model describing the large‐angle scattering of the electrons. The results of this work could support future research into VHEE radiotherapy and might be of interest for use together with VHEE broad beams produced by scanned narrow pencil beams. [ABSTRACT FROM AUTHOR]

Purpose: The primary fluence of a proton pencil beam exiting the accelerator is enveloped by a region of secondaries, commonly called “spray”. Although small in magnitude, this spray may affect dose distributions in pencil beam scanning mode e.g., in the calculation of the small field output, if not modelled properly in a treatment planning system (TPS). The purpose of this study was to dosimetrically benchmark the Monte Carlo (MC) dose engine of the RayStation TPS (v.10A) in small proton fields and systematically compare single Gaussian (SG) and double Gaussian (DG) modeling of initial proton fluence providing a more accurate representation of the nozzle spray. Methods: The initial proton fluence distribution for SG/DG beam modeling was deduced from two-dimensional measurements in air with a scintillation screen with electronic readout. The DG model was either based on direct fits of the two Gaussians to the measured profiles, or by an iterative optimization procedure, which uses the measured profiles to mimic in-air scan-field factor (SF) measurements. To validate the DG beam models SFs, i.e. relative doses to a 10 × 10 cm2 field, were measured in water for three different initial proton energies (100MeV, 160MeV, 226.7MeV) and square field sizes from 1×1cm2 to 10×10cm2 using a small field ionization chamber (IBA CC01) and an IBA ProteusPlus system (universal nozzle). Furthermore, the dose to the center of spherical target volumes (diameters: 1cm to 10cm) was determined using the same small volume ionization chamber (IC). A comprehensive uncertainty analysis was performed, including estimates of influence factors typical for small field dosimetry deduced from a simple two-dimensional analytical model of the relative fluence distribution. Measurements were compared to the predictions of the RayStation TPS. Results: SFs deviated by more than 2% from TPS predictions in all fields

Purpose: To assess clinical outcomes of adolescents and young adults (AYAs) with head and neck sarcomas (HNSs) treated with pencil beam scanning proton therapy (PBSPT) and to report quality of life (QoL). Materials and Methods: Twenty-eight AYAs (aged 15 to 39 years) with HNS treated between January 2001 and July 2022 at our institution were included. The median age was 21.6 years. Rhabdomyosarcoma (39.3%), Ewing sarcoma (17.9%), chondrosarcoma (14.3%), and osteosarcoma (14.3%) were the most frequent diagnoses. Three (10.7%) patients were metastatic before PBSPT and 13 (46.4%) patients had a tumor with intracranial extension. The median total radiation dose was 63 GyRBE (range, 45 to 74 GyRBE). Thirteen (46.4%) patients received concomitant chemotherapy. Toxicity was reported according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US National Institutes of Health, Bethesda, Maryland). Survival was estimated using the Kaplan-Meier method. QoL was assessed using a PEDQOL (Pediatric Quality of Life Questionnaire) questionnaire. Self-reported outcomes were assessed using institutional questionnaires. Results: With a median follow-up of 57 months (range, 3.7 to 243 months), 5 patients (17.8%) had local failure (LF) only, 2 (7.1%) experienced distant failure (DF) only, and 2 (7.1%) had LF and DF. The estimated 5-year local control (LC) and distant control (DC) rates were 71.8% and 80.5%, respectively. The median times to LF and DF were 13.4 and 22.2 months, respectively. Four (14.3%) patients died, all but one from their HNS. Estimated 5-year overall survival was 90.7%. Six (21.4%) patients developed nonocular grade ≥3 toxicity, which consisted of otitis media (n = 2), hearing impairment (n = 2), osteoradionecrosis (n = 1), and sinusitis (n = 1). Four (14.3%) patients developed cataracts that required surgery. The 5-year freedom from nonocular grade 3 toxicity was 91.1%. No grade 4 or higher toxicity was observed. Adolescents rated their quality of life before treatment worse than their parents did. Conclusion: Excellent outcomes with acceptable late-toxicity rates were observed for AYAs with HNS after PBSPT.

The primary fluence of a proton pencil beam exiting the accelerator is enveloped by a region of secondaries, commonly called "spray". Although small in magnitude, this spray may affect dose distributions in pencil beam scanning mode e.g., in the calculation of the small field output, if not modelled properly in a treatment planning system (TPS). The purpose of this study was to dosimetrically benchmark the Monte Carlo (MC) dose engine of the RayStation TPS (v.10A) in small proton fields and systematically compare single Gaussian (SG) and double Gaussian (DG) modeling of initial proton fluence providing a more accurate representation of the nozzle spray. The initial proton fluence distribution for SG/DG beam modeling was deduced from two-dimensional measurements in air with a scintillation screen with electronic readout. The DG model was either based on direct fits of the two Gaussians to the measured profiles, or by an iterative optimization procedure, which uses the measured profiles to mimic in-air scan-field factor (SF) measurements. To validate the DG beam models SFs, i.e. relative doses to a 10 × 10 cm2 field, were measured in water for three different initial proton energies (100 M e V , 160 M e V , 226.7 M e V) and square field sizes from 1 × 1 c m 2 to 10 × 10 c m 2 using a small field ionization chamber (IBA CC01) and an IBA ProteusPlus system (universal nozzle). Furthermore, the dose to the center of spherical target volumes (diameters: 1 c m to 10 c m) was determined using the same small volume ionization chamber (IC). A comprehensive uncertainty analysis was performed, including estimates of influence factors typical for small field dosimetry deduced from a simple two-dimensional analytical model of the relative fluence distribution. Measurements were compared to the predictions of the RayStation TPS. SFs deviated by more than 2 % from TPS predictions in all fields < 4 × 4 c m 2 with a maximum deviation of 5.8 % for SG modeling. In contrast, deviations were smaller than 2 % for all field-sizes and proton energies when using the directly fitted DG model. The optimized DG model performed similarly except for slightly larger deviations in the 1 × 1 c m 2 scan-fields. The uncertainty estimates showed a significant impact of pencil beam size variations (± 5 %) resulting in up to 5.0 % standard uncertainty. The point doses within spherical irradiation volumes deviated from calculations by up to 3.3 % for the SG model and 2.0 % for the DG model. Properly representing nozzle spray in RayStation's MC-based dose engine using a DG beam model was found to reduce the deviation to measurements in small spherical targets to below 2 %. A thorough uncertainty analysis shows a similar magnitude for the combined standard uncertainty of such measurements. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the oncological outcomes and safety of carbon ion re-irradiation with pencil beam scanning (PBS) delivery technique for previously irradiated and unresectable locally recurrent rectal cancer (LRRC). Between June 2017 and September 2021, 24 patients of unresectable LRRC with prior pelvic photon radiotherapy who underwent carbon ion re-irradiation at our institute were retrospectively analyzed. Carbon ion radiotherapy was delivered by raster scanning with a median relative biological effectiveness-weighted dose of 72 Gy in 20 fractions. Weekly CT reviews were carried out, and offline adaptive replanning was performed whenever required. The median follow-up duration was 23.8 months (range, 6.2–47.1 months). At the last follow-up, two patients had a local disease progression, and 11 patients developed distant metastases. The 1- and 2-year local control, progression-free survival and overall survival rates were 100 and 93.3%, 70.8 and 45.0% and 86.7 and 81.3%, respectively. There were no Grade 3 or higher acute toxicities observed. Three patients developed Grade 3 late toxicities, one each with gastrointestinal toxicity, skin reaction and pelvic infection. In conclusion, definitive carbon ion re-irradiation with PBS provided superior oncologic results with tolerable toxicities and may be served as a curative treatment strategy in unresectable LRRC. [ABSTRACT FROM AUTHOR]

Purpose: An accurate estimation of range uncertainties is essential to exploit the potential of proton therapy. According to Paganetti's study, a value of 2.4% (1.5 standard deviation) is currently recommended for planning robust treatments with Monte Carlo dose engines. This number is based on a dominant contribution from the mean excitation energy of tissues. However, it was recently shown that expressing tissues as a mixture of water and "dry" material in the CT calibration process allowed for a significant reduction of this uncertainty. We thus propose an adapted framework for pencil beam scanning robust optimization. First, we move towards a spot‐specific range uncertainty (SSRU) determination. Second, we use the water‐based formalism to reduce range uncertainties and, potentially, to spare better the organs at risk. Methods: The stoichiometric calibration was adapted to provide a molecular decomposition (including water) of each voxel of the CT. The SSRU calculation was implemented in MCsquare, a fast Monte Carlo dose engine dedicated to proton therapy. For each spot, a ray‐tracing method was used to propagate molecular I‐values uncertainties and obtain the corresponding effective range uncertainty. These were then combined with other sources of range uncertainties, according to Paganetti's study of 2012. The method was then assessed on three head‐and‐neck patients. Two plans were optimized for each patient: the first one with the classical 2.4% flat range uncertainty (FRU), the second one with the variable range uncertainty. Both plans were then compared in terms of target coverage and OAR mean dose reduction. Robustness evaluations were also performed, using the SSRU for both plans in order to simulate errors as realistically as possible. Results: For patient 1, it was found that the median SSRU was 1.04% (1.5 standard deviation), yielding, therefore, a very large reduction from the 2.4% FRU. All three SSRU plans were found to have a very good robustness level at a 90% confidence interval while sparing OAR better than the classical plan. For instance, in nominal cases, average reductions in the mean dose of 15.7, 8.4, and 13.2% were observed in the left parotid, right parotid, and pharyngeal constrictor muscle, respectively. As expected, the classical plans showed a higher but unnecessary level of robustness. Conclusions: Promising results of the SSRU framework were observed on three head‐and‐neck cases, and more patients should now be considered. The method could also benefit to other tumor sites and, in the long run, the variable part of the range uncertainty could be generalized to other sources of uncertainty in order to move towards more and more patient‐specific treatments. [ABSTRACT FROM AUTHOR]

Simple Summary: This retrospective study presents the clinical outcomes of the largest cohort of patients (853 patients) with low-, favorable intermediate-, and unfavorable intermediate-risk prostate cancer treated with ultra-hypofractionated proton beam radiotherapy (36.25 GyE/five fractions). The median follow-up time was 62.7 months. Ultra-hypofractionated proton beam radiotherapy is an effective treatment for low- and favorable intermediate-risk prostate cancer, with long-term bDFS rates comparable to other techniques. It is promising for unfavorable intermediate-risk prostate cancer and has acceptable long-term GI and favorable GU toxicity. Background: We retrospectively analyzed the 5-year biochemical disease-free survival (bDFS) and occurrence of late toxicity in prostate cancer patients treated with pencil beam scanning (PBS) proton radiotherapy. Methodology: In the period from January 2013 to June 2018, 853 patients with prostate cancer were treated with an ultra-hypofractionated schedule (36.25 GyE/five fractions). The mean PSA value was 6.7 (0.7–19.7) µg/L. There were 318 (37.3%), 314 (36.8%), and 221 (25.9%) patients at low (LR), favorable intermediate (F-IR), and unfavorable intermediate risk (U-IR), respectively. Neoadjuvant hormonal therapy was administered to 197 (23.1%) patients, and 7 (0.8%) patients had adjuvant hormonal therapy. The whole group of patients reached median follow-up time at 62.7 months, and their mean age was 64.8 (40.0–85.7) years. The bDFS rates and late toxicity profile were evaluated. Results: Median treatment time was 10 (7–38) days. Estimated 5-year bDFS rates were 96.5%, 93.7%, and 91.2% for low-, favorable intermediate-, and unfavorable intermediate-risk groups, respectively. Cumulative late toxicity (CTCAE v4.0) of G2+ was as follows: gastrointestinal (GI)—G2: 9.1%; G3: 0.5%; genitourinary (GU)—G2: 4.3%, and no G3 toxicity was observed. PSA relapse was observed in 58 (6.8%) patients: 16 local, 22 lymph node, 4 bone recurrences, and 10 combined sites of relapse were detected. Throughout the follow-up period, 40 patients (4.7%) died, though none due to prostate cancer. Conclusion: Ultra-hypofractionated proton beam radiotherapy is an effective treatment for low- and favorable intermediate-risk prostate cancer, with long-term bDFS rates comparable to other techniques. It is promising for unfavorable intermediate-risk prostate cancer and has acceptable long-term GI and favorable GU toxicity. [ABSTRACT FROM AUTHOR]

Simple Summary: Meningioma is a rare entity in the pediatric and adolescent population. While maximal resection remains the established standard of care, the role of radiation therapy remains unclear. The aim of this retrospective study was to report the clinical and patient-reported outcomes of a cohort of 10 children and adolescents with intracranial meningioma treated with Pencil Beam Scanning Proton Therapy (PBS-PT) at the Paul Scherrer Institute between 1996 and 2022. The local control rates at three and five years were modest, yet overall survival remained excellent. Some patients reported functional status limitation during first year and 2 years after PBS-PT, with only one reporting limitation after 3 years. The good tolerance of the treatment in terms of acute toxicity and the absence of severe long-term side effects support the safety of the treatment and viability of PBS-PT as a suitable therapeutic option for intracranial meningioma in the pediatric and adolescent population. Purpose: The purpose of this study was to report the clinical and patient-reported outcomes of children and adolescents with intracranial meningioma treated with pencil beam scanning proton therapy (PBS-PT). Material and methods: Out of a total cohort of 207 intracranial meningioma patients treated with PBS-PT between 1999 and 2022, 10 (4.8%) were children or adolescents aged < 18 years. Median age was 13.9 years (range, 3.2–17.2). Six (60%) children were treated as primary treatment (postoperative PT, n = 4; exclusive PT, n = 2) and four (40%) at the time of tumor recurrence. Acute and late toxicities were registered according to Common Terminology Criteria of Adverse Events (CTCAE). Quality of life (QoL) before PBS-PT was assessed using PEDQOL questionnaires. Educational, functional, and social aspects after PT were assessed through our in-house developed follow-up surveys. Median follow-up time was 71.1 months (range, 2.5–249.7), and median time to last questionnaire available was 37.6 months (range, 5.75–112.6). Results: Five (50%) children developed local failure (LF) at a median time of 32.4 months (range, 17.7–55.4) after PBS-PT and four (80%) were considered in-field. One patient died of T-cell lymphoma 127.1 months after PBS-PT. Estimated 5-year local control (LC) and overall survival (OS) rates were 19.4% and 100.0%, respectively. Except for one patient who developed a cataract requiring surgery, no grade ≥3 late toxicities were reported. Before PT, patients rated their QoL lower than their parents in most domains. During the first year after PT, one child required educational support, one needed to attend to a special school, one had social problems and another three children required assistance for daily basic activities (DBA). Three years after PT, only one child required assistance for DBA. Conclusions: The outcome of children with intracranial meningioma treated with PBS-PT is in line with other centers who have reported results of radiation therapy delivered to this particular patient group. This therapy provides acceptable functional status profiles with no high-grade adverse radiation-induced events. [ABSTRACT FROM AUTHOR]

Simple Summary: Proton beam therapy delivered via pencil beam scanning is an advanced method for treating cancer. Two types of scanning modes are available for this method: discrete spot scanning (DSS) and continuous scanning. Continuous scanning has some advantages over DSS including improved proton beam delivery efficiency and reduced delivery time. However, continuous scanning delivers a dose between consecutive spots, and currently commercially available treatment planning systems do not account for this. Consequently, the continuous scanning delivered dose is inherently different from the planned one, which is discrete spot based. We conducted a proof-of-concept study of the ability of a prediction model to reduce the dose discrepancy between continuous scanning and discrete spot plan. Our findings suggest that selecting planning parameters with the prediction model reduces the dose discrepancy and therefore may permit relaxed dose delivery constraint, which further improves the benefits of continuous scanning. Pencil beam scanning delivered with continuous scanning has several advantages over conventional discrete spot scanning. Such advantages include improved beam delivery efficiency and reduced beam delivery time. However, a move dose is delivered between consecutive spots with continuous scanning, and current treatment planning systems do not take this into account. Therefore, continuous scanning and discrete spot plans have an inherent dose discrepancy. Using the operating parameters of the state-of-the-art particle therapy system, we conducted a proof-of-concept study in which we systematically generated 28 plans for cubic targets with different combinations of plan parameters and simulated the dose discrepancies between continuous scanning and a planned one. A nomograph to guide the selection of plan parameters was developed to reduce the dose discrepancy. The effectiveness of the nomograph was evaluated with two clinical cases (one prostate and one liver). Plans with parameters guided by the nomograph decreased dose discrepancy than those used standard plan parameters. Specifically, the 2%/2 mm gamma passing rate increased from 96.3% to 100% for the prostate case and from 97.8% to 99.7% for the liver case. The CTV DVH root mean square error decreased from 2.2% to 0.2% for the prostate case and from 1.8% to 0.9% for the liver case. The decreased dose discrepancy may allow the relaxing of the delivery constraint for some cases, leading to greater benefits in continuous scanning. Further investigation is warranted. [ABSTRACT FROM AUTHOR]

Background: Electrons with kinetic energy up to a few hundred MeV, also called very high energy electrons (VHEE), are currently considered a promising technique for the future of radiation therapy (RT) and in particular ultra‐high dose rate (UHDR) therapy. However, the feasibility of a clinical application is still being debated and VHEE therapy remains an active area of research for which the optimal conformal technique is also yet to be determined. Purpose: In this work, we will apply two existing formalisms based on analytical Gaussian multiple‐Coulomb scattering theory and Monte Carlo (MC) simulations to study and compare the electron and bremsstrahlung photon dose distributions arising from two beam delivery systems (passive scattering with or without a collimator or active scanning). Methods: We therefore tested the application of analytical and MC models to VHEE beams and assessed their performance and parameterization in the energy range of 6–200 MeV. The optimized electron beam fluence, the bremsstrahlung, an estimation of central‐axis and off‐axis x‐ray dose at the practical range and neutron contributions to the total dose, along with an extended parameterization for the photon dose model were developed, together with a comparison between double scattering (DS) and pencil beam scanning (PBS) techniques. MC simulations were performed with the TOPAS/Geant4 toolkit to verify the dose distributions predicted by the analytical calculations. Results: The results for the clinical energy range (between 6 and 20 MeV) as well as for higher energies (VHEE range between 20 and 200 MeV) and for two treatment field sizes (5 × 5 and 10 × 10 cm2) are reported, showing a reasonable agreement with MC simulations with mean differences below 2.1%. The relative contributions of photons generated in the medium or by the scattering system along the central‐axis (up to 50% of the total dose) are also illustrated, along with their relative variations with electron energy. Conclusions: The fast analytical models parametrized in this study allow an estimation of the amount of photons produced behind the practical range by a DS system with an accuracy lower than 3%, providing important information for the eventual design of a VHEE system. The results of this work could support future research on VHEE radiotherapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Meningiomas are one of the most common primary brain tumors. The current standard therapy for symptomatic or growing lesions includes surgery and/or radiotherapy. Pencil Beam Scanning Proton Therapy (PBS PT) is an alternative to conventional radiotherapy with unique dose deposition pattern and improved conformality. In this retrospective study, we assess the clinical outcome including the quality of life (QoL) of patients with intracranial meningiomas treated with PBS PT between 1997 and 2022 at the Centre for Proton Therapy of the Paul Scherrer Institute. In 200 patients, we observed a high local control and survival, especially in patients with grade 1 tumors as well as a low rate of high-grade toxicity and stable QoL over the years after treatment. This study shows that PBS PT is an adequate alternative to conventional radiotherapy in meningioma treatment. The aim of this study was to assess the clinical outcome, including QoL, of patients with intracranial meningiomas WHO grade 1–3 who were treated with Pencil Beam Scanning Proton Therapy (PBS PT) between 1997 and 2022. Two hundred patients (median age 50.4 years, 70% WHO grade 1) were analyzed. Acute and late side effects were classified according to CTCAE version 5.0. Time to event data were calculated. QoL was assessed descriptively by the EORTC-QLQ-C30 and BN20 questionnaires. With a median follow-up of 65 months (range: 3.8–260.8 months) the 5 year OS was 95.7% and 81.8% for WHO grade 1 and grade 2/3, respectively (p < 0.001). Twenty (10%) local failures were observed. Failures occurred significantly (p < 0.001) more frequent in WHO grade 2 or 3 meningioma (WHO grade 1: n = 7, WHO grade 2/3: n = 13), in patients with multiple meningiomas (p = 0.005), in male patients (p = 0.005), and when PT was initiated not as upfront therapy (p = 0.011). There were no high-grade toxicities in the majority (n = 176; 88%) of patients. QoL was assessed for 83 (41.5%) patients and for those patients PT did not impacted QoL negatively during the follow-up. In summary, we observed very few local recurrences of meningiomas after PBS PT, a stable QoL, and a low rate of high-grade toxicity. [ABSTRACT FROM AUTHOR]

Simple Summary: Intensity modulated proton therapy provides unparalleled normal tissue sparing for the treatment of pediatric cancers such as medulloblastoma using craniospinal irradiation. However, proton delivery systems have a minimum deliverable energy and depth, requiring range shifter devices for the treatment of shallow targets and/or small anatomy. Standard range shifters are mounted to the treatment nozzle and introduce lateral scatter which, unfortunately, increases normal tissue dose. In this study we designed, manufactured, and characterized a range shifter board which rests directly under the patient during treatment to maintain a shallow treatment depth while minimizing lateral scatter, similar to previously proposed designs but optimized for our synchrotron-based delivery system. We present the dosimetric measurements we performed to characterize the device for treatment planning including severity of artifacts in on-board images. We compared the standard and range shifter board planning approaches in an anthropomorphic phantom and delivered the treatment plans to confirm the dosimetric differences. Finally, we compared treatment plans from two previously treated pediatric patients, demonstrating the ability to significantly reduce lung and kidney dose using this device compared to a standard range shifter. This device is now in routine use at our clinic. Purpose: To report our design, manufacturing, commissioning and initial clinical experience with a table-mounted range shifter board (RSB) intended to replace the machine-mounted range shifter (MRS) in a synchrotron-based pencil beam scanning (PBS) system to reduce penumbra and normal tissue dose for image-guided pediatric craniospinal irradiation (CSI). Methods: A custom RSB was designed and manufactured from a 3.5 cm thick slab of polymethyl methacrylate (PMMA) to be placed directly under patients, on top of our existing couch top. The relative linear stopping power (RLSP) of the RSB was measured using a multi-layer ionization chamber, and output constancy was measured using an ion chamber. End-to-end tests were performed using the MRS and RSB approaches using an anthropomorphic phantom and radiochromic film measurements. Cone beam CT (CBCT) and 2D planar kV X-ray image quality were compared with and without the RSB present using image quality phantoms. CSI plans were produced using MRS and RSB approaches for two retrospective pediatric patients, and the resultant normal tissue doses were compared. Results: The RLSP of the RSB was found to be 1.163 and provided computed penumbra of 6.9 mm in the phantom compared to 11.8 mm using the MRS. Phantom measurements using the RSB demonstrated errors in output constancy, range, and penumbra of 0.3%, −0.8%, and 0.6 mm, respectively. The RSB reduced mean kidney and lung dose compared to the MRS by 57.7% and 46.3%, respectively. The RSB decreased mean CBCT image intensities by 86.8 HU but did not significantly impact CBCT or kV spatial resolution providing acceptable image quality for patient setup. Conclusions: A custom RSB for pediatric proton CSI was designed, manufactured, modeled in our TPS, and found to significantly reduce lateral proton beam penumbra compared to a standard MRS while maintaining CBCT and kV image-quality and is in routine use at our center. [ABSTRACT FROM AUTHOR]

Purpose: Indians have a higher incidence of cardiovascular diseases, often at a younger age, than other ethnic groups. This higher baseline risk requires consideration when assessing additional cardiac morbidity of breast cancer treatment. Superior cardiac sparing is a critical dosimetric advantage of proton therapy in breast cancer radiotherapy. We report here the heart and cardiac-substructure doses and early toxicities in breast cancer patients treated post-operatively with proton therapy in India's first proton therapy center. Materials and Methods: We treated twenty breast cancer patients with intensity-modulated proton therapy (IMPT) from October 2019 to September 2022, eleven after breast conservation, nine following mastectomy, and appropriate systemic therapy, when indicated. The most prescribed dose was 40 GyE to the whole breast/chest wall and 48 GyE by simultaneous integrated boost to the tumor bed and 37.5 GyE to appropriate nodal volumes, delivered in 15 fractions. Results: Adequate coverage was achieved for clinical target volume (breast/chest wall), i.e., CTV40, and regional nodes, with 99% of the targets receiving 95% of the prescribed dose (V95% > 99%). The mean heart dose was 0.78 GyE and 0.87 GyE for all and left breast cancer patients, respectively. The mean left anterior descending artery (LAD) dose, LAD D0.02cc, and left ventricle dose were 2.76, 6.46, and 0.2 GyE, respectively. Mean ipsilateral lung dose, V20Gy, V5Gy, and contralateral breast dose (Dmean) were 6.87 GyE, 14.6%, 36.4%, and 0.38 GyE, respectively. Conclusion: The dose to heart and cardiac substructures is lower with IMPT than published photon therapy data. Despite the limited access to proton therapy at present, given the higher cardiovascular risk and coronary artery disease prevalence in India, the cardiac sparing achieved using this technique merits consideration for wider adoption in breast cancer treatment. [ABSTRACT FROM AUTHOR]

This study aimed to examine the dosimetric effect of intensity-modulated proton therapy (IMPT) with a multi-leaf collimator (MLC) in treating malignant glioma. We compared the dose distribution of IMPT with or without MLC (IMPT MLC+ or IMPT MLC- , respectively) using pencil beam scanning and volumetric-modulated arc therapy (VMAT) in simultaneous integrated boost (SIB) plans for 16 patients with malignant gliomas. High- and low-risk target volumes were assessed using D 2% , V 90% , V 95% , homogeneity index (HI), and conformity index (CI). Organs at risk (OARs) were evaluated using the average dose (D mean) and D 2%. Furthermore, the dose to the normal brain was evaluated using from V 5Gy to V 40Gy at 5 Gy intervals. There were no significant differences among all techniques regarding V 90% , V 95% , and CI for the targets. HI and D 2% for IMPT MLC+ and IMPT MLC- were significantly superior to those for VMAT (p < 0.01). The D mean and D 2% of all OARs for IMPT MLC+ were equivalent or superior to those of other techniques. Regarding the normal brain, there was no significant difference in V 40Gy among all techniques whereas V 5Gy to V 35Gy in IMPT MLC+ were significantly smaller than those in IMPT MLC- (with differences ranging from 0.45% to 4.80%, p < 0.05) and VMAT (with differences ranging from 6.85% to 57.94%, p < 0.01). IMPT MLC+ could reduce the dose to OARs, while maintaining target coverage compared to IMPT MLC- and VMAT in treating malignant glioma. [ABSTRACT FROM AUTHOR]

Background: Pencil beam scanning (PBS) proton therapy allows for far superior dose conformality compared with passive scattering techniques. However, one drawback of PBS is that the beam delivery time can be long, particularly when treating superficial disease. Minimizing beam delivery time is important for patient comfort and precision of treatment delivery. Mini-ridge filters (MRF) have been shown to reduce beam delivery time for synchrotron-based PBS. Given that cyclotron systems are widely used in proton therapy it is necessary to investigate the potential clinical benefit of mini-ridge filters in such systems. Purpose: To demonstrate the clinical benefit of using a MRF to reduce beam delivery time for patients with large target volumes and superficial disease in cyclotron-based PBS proton therapy. Methods: A MRF beam model was generated by simulating the effect of a MRF on our clinical beam data assuming a fixed snout position relative to the isocenter. The beam model was validated with a series of measurements. The model was used to optimize treatment plans in a water phantom and on six patient DICOM datasets to further study the effect of the MRF and for comparison with physician-approved clinical treatment plans. Beam delivery time was measured for six plans with and without the MRF to demonstrate the reduction achievable. Plans with and without MRF were reviewed to confirm clinical acceptability by a radiation oncologist. Patient-specific QA measurements were carried out with a two-dimensional ionization chamber array detector for one representative patient’s plan optimized with the MRF beam model. Results: Results show good agreement between the simulated beam model and measurements with mean and maximum deviations of 0.06 mm (0.45%) and 0.61 mm (4.9%). The increase in Bragg peak width (FWHM) ranged from 2.7 mm at 226 MeV to 6.1 mm at 70 MeV. The mean and maximum reduction in beam delivery time observed per field was 29.1 s (32.2%) and 79.7 s (55.3%). Conclusion: MRFs can be used to reduce treatment time in cyclotron-based PBS proton therapy without sacrificing plan quality. This is particularly beneficial for patients with large targets and superficial disease such as in breast cancer where treatment times are generally long, as well as patients treated with deep inspiration breath hold (DIBH). [ABSTRACT FROM AUTHOR]

This study evaluates the feasibility of the pencil beam scanning technique of carbon ion radiotherapy (CIRT) in the setting of hepatocellular carcinoma (HCC) and establishes the maximum tolerated dose (MTD) calculated by the Local Effect Model version I (LEM‐I) with a dose escalation plan. The escalated relative biological effectiveness‐weighted dose levels included 55, 60, 65, and 70 Gy in 10 fractions. Active motion management techniques were employed, and several measures were applied to mitigate the interplay effect induced by a moving target. CIRT was planned with the LEM‐I‐based treatment planning system and delivered by raster scanning. Offline PET/CT imaging was used to verify the beam range. Offline adaptive replanning was performed whenever required. Twenty‐three patients with a median tumor size of 4.3 cm (range, 1.7–8.5 cm) were enrolled in the present study. The median follow‐up time was 56.1 months (range, 5.7–74.4 months). No dose limiting toxicity was observed until 70 Gy, and MTD had not been reached. No patients experienced radiation‐induced liver disease within 6 months after the completion of CIRT. The overall survival rates at 1, 3, and 5 years were 91.3%, 81.9%, and 67.1% after CIRT, respectively. The local progression‐free survival and progression‐free survival rates at 1, 3 and 5 years were 100%, 94.4%, and 94.4% and 73.6%, 59.2%, and 37.0%, respectively. The raster scanning technique could be used to treat HCC. However, caution should be exercised to mitigate the interplay effect. CIRT up to 70 Gy in 10 fractions over 2 weeks was safe and effective for HCC. [ABSTRACT FROM AUTHOR]

Background: Pencil beam scanning (PBS) proton therapy can provide highly conformal target dose distributions and healthy tissue sparing. However, proton therapy of hepatocellular carcinoma (HCC) is prone to dosimetrical uncertainties induced by respiratory motion. This study aims to develop intra-treatment tumor motion monitoring during respiratory gated proton therapy and combine it with motion-including dose reconstruction to estimate the delivered tumor doses for individual HCC treatment fractions. Methods: Three HCC-patients were planned to receive 58 GyRBE (n=2) or 67.5 GyRBE (n=1) of exhale respiratory gated PBS proton therapy in 15 fractions. The treatment planning was based on the exhale phase of a 4-dimensional CT scan. Daily setup was based on cone-beam CT (CBCT) imaging of three implanted fiducial markers. An external marker block (RPM) on the patient’s abdomen was used for exhale gating in free breathing. This study was based on 5 fractions (patient 1), 1 fraction (patient 2) and 6 fractions (patient 3) where a post-treatment control CBCT was available. After treatment, segmented 2D marker positions in the post-treatment CBCT projections provided the estimated 3D motion trajectory during the CBCT by a probability-based method. An external-internal correlation model (ECM) that estimated the tumor motion from the RPM motion was built from the synchronized RPM signal and marker motion in the CBCT. The ECM was then used to estimate intra-treatment tumor motion. Finally, the motion-including CTV dose was estimated using a dose reconstruction method that emulates tumor motion in beam’s eye view as lateral spot shifts and in-depth motion as changes in the proton beam energy. The CTV homogeneity index (HI) The CTV homogeneity index (HI) was calculated as D2% − D98%/D50% ×100%. Results: The tumor position during spot delivery had a root-mean-square error of 1.3 mm in left-right, 2.8 mm in cranio-caudal and 1.7 mm in anterior-posterior directions compared to the planned position. On average, the CTV HI was larger than planned by 3.7%-points (range: 1.0-6.6%-points) for individual fractions and by 0.7%-points (range: 0.3-1.1%-points) for the average dose of 5 or 6 fractions. Conclusions: A method to estimate internal tumor motion and reconstruct the motion-including fraction dose for PBS proton therapy of HCC was developed and demonstrated successfully clinically. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to determine the integral depth-dose curves and assess the geometric collection efficiency of different detector diameters in proton pencil beam scanning. Materials and Methods: The Varian ProBeam Compact spot scanning system was used for this study. The integral depth-dose curves with a proton energy range of 130 to 220 MeV were acquired with 2 types of Bragg peak chambers: 34070 with 8-cm diameter and 34089 with 15-cm diameter (PTW), multi-layer ionization chamber with 12-cm diameter (Giraffe, IBA Dosimetry), and PeakFinder with 8-cm diameter (PTW). To assess geometric collection efficiency, the integral depth-dose curves of 8- and 12-cm chamber diameters were compared to a 15-cm chamber diameter as the largest detector. Results: At intermediate depths of 130, 150, 190, and 220 MeV, PTW Bragg peak chamber type 34089 provided the highest integral depth-dose curves followed by IBA Giraffe, PTW Bragg peak chamber type 34070, and PTW PeakFinder. Moreover, PTW Bragg peak chamber type 34089 had increased geometric collection efficiency up to 3.8%, 6.1%, and 3.1% when compared to PTW Bragg peak chamber type 34070, PTW PeakFinder, and IBA Giraffe, respectively. Conclusion: A larger plane-parallel ionization chamber could increase the geometric collection efficiency of the detector, especially at intermediate depths and high-energy proton beams.

BackgroundPencil beam scanning (PBS) proton therapy can provide highly conformal target dose distributions and healthy tissue sparing. However, proton therapy of hepatocellular carcinoma (HCC) is prone to dosimetrical uncertainties induced by respiratory motion. This study aims to develop intra-treatment tumor motion monitoring during respiratory gated proton therapy and combine it with motion-including dose reconstruction to estimate the delivered tumor doses for individual HCC treatment fractions.MethodsThree HCC-patients were planned to receive 58 GyRBE (n=2) or 67.5 GyRBE (n=1) of exhale respiratory gated PBS proton therapy in 15 fractions. The treatment planning was based on the exhale phase of a 4-dimensional CT scan. Daily setup was based on cone-beam CT (CBCT) imaging of three implanted fiducial markers. An external marker block (RPM) on the patient’s abdomen was used for exhale gating in free breathing. This study was based on 5 fractions (patient 1), 1 fraction (patient 2) and 6 fractions (patient 3) where a post-treatment control CBCT was available. After treatment, segmented 2D marker positions in the post-treatment CBCT projections provided the estimated 3D motion trajectory during the CBCT by a probability-based method. An external-internal correlation model (ECM) that estimated the tumor motion from the RPM motion was built from the synchronized RPM signal and marker motion in the CBCT. The ECM was then used to estimate intra-treatment tumor motion. Finally, the motion-including CTV dose was estimated using a dose reconstruction method that emulates tumor motion in beam’s eye view as lateral spot shifts and in-depth motion as changes in the proton beam energy. The CTV homogeneity index (HI) The CTV homogeneity index (HI) was calculated as D2% − D98%D50% ×100%.ResultsThe tumor position during spot delivery had a root-mean-square error of 1.3 mm in left-right, 2.8 mm in cranio-caudal and 1.7 mm in anterior-posterior directions compared to the planned position. On average, the CTV HI was larger than planned by 3.7%-points (range: 1.0-6.6%-points) for individual fractions and by 0.7%-points (range: 0.3-1.1%-points) for the average dose of 5 or 6 fractions.ConclusionsA method to estimate internal tumor motion and reconstruct the motion-including fraction dose for PBS proton therapy of HCC was developed and demonstrated successfully clinically.

Purpose: Stereotactic body proton therapy (SBPT) is an emerging treatment strategy for lung tumors that aims to combine the excellent local control benefits of ultra-hypofractionation with the physical advantages of protons, which reduce the integral dose to organs at risk (OARs) compared to photons. To date, however, very little data delivering SBPT in 5 or fewer fractions to lung tumors have been reported. Given that photon stereotactic body radiation therapy can struggle to deliver ablative doses to high-risk tumors (i.e., central/ultra-central location, prior in-field radiation, tumor size >5 cm, or the presence of severe pulmonary comorbidities) while adhering to OAR dose constraints, we hypothesized that SBPT would be an effective alternative for patients with high-risk tumors. Methods and Materials: Twenty-seven high-risk patients with 29 lung tumors treated with SBPT at the New York Proton Center between December 2019 and November 2022 were retrospectively identified. Patients were divided into three major subgroups: early-stage non-small cell lung cancer (NSCLC), locally recurrent NSCLC, and metastatic cancer from lung cancer or other histologies. Patient characteristics were reported using descriptive statistics, actuarial methods were used to quantify disease control rates, and toxicities were scored using CTCAE v 5.0. Results: The most common high-risk indications for SBPT were central/ultra-central tumor location (69.0%), severe COPD (48.1%), reirradiation (44.4%), significant pulmonary fibrosis (22.2%), and large tumor size > 5 cm (18.5%). In total, 96.6% of tumors were fully covered by the prescription dose without compromising target coverage. Three-year actuarial rates of local control for early-stage NSCLC, locally recurrent NSCLC, and metastatic patients were 89%, 100%, and 43%, respectively. Three-year actuarial rates of regional control were 89%, 67%, and 86%. Three-year actuarial rates of distant metastasis-free survival were 79%, 100%, and 0%. Two patients (7.4%), both of whom had clinically significant baseline interstitial lung disease and pre-treatment continuous oxygen demand, experienced grade =2 pulmonary toxicity (1 grade 3, 1 grade 5). There were no acute or late grade =2 toxicities related to esophagitis, cardiac injury, airway injury, pulmonary fibrosis, bronchopulmonary hemorrhage or brachial plexopathy. Conclusions: In the largest study of proton SBRT reported to date, SBPT has a favorable toxicity profile while being an effective approach for treating most high-risk tumors without requiring dose de-escalation or compromising tumor coverage and warrants further investigation. [ABSTRACT FROM AUTHOR]

Background: Proton beam therapy (PBT) is a non-surgical treatment that spares adjacent tissues compared to photon radiation and useful for Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). We present a single center experience in HCC and iCCA treated with Pencil Beam Scanning (PBS) PBT. Methods: Forty-four consecutive patients (22 patients in each group) receiving PBT were included and reviewed. PBT was delivered with hypofractionated or stereotactic body radiation therapy (SBRT) using PBS. Tumor size was approximated by clinical target volume (CTV). Outcomes were evaluated with Kaplan-Meier and liver toxicity was determined by MELD-Na and albumin-bilirubin (ALBI) grade. Results: Median follow up was 38.7 months, fourteen (35%) had multifocal disease and median CTV was 232.5cc. Four (9%) and 40 (91%) patients received SBRT and hypofractionated radiation, respectively. Two year overall survival was statistically higher for HCC (entire group: 68.9% months [95% CI: 61.3 - 76.3%]; iCCA: 49.8% [95% CI: 38.5% - 61.1%]; HCC: 89.4% [95% CI: 82.3 - 96.5%]; P <0.005). There was no statistical difference in progression-free survival or freedom from local failure. Biologically Equivalent Dose (BED) was greater than or equal to 80.5Gy in 37 (84%) patients. All iCCA patients had stable or improved ALBI grade following treatment. ALBI effecgrade was stable in 83% of HCC patients and average MELD-Na score remained stable. Tumor size, pretreatment liver function, and total radiation dose were not associated with liver toxicity. Conclusions: PBT for unresectable HCC and iCCA is safe and effective, even for large and multifocal tumors. Liver function was preserved even in those with baseline cirrhosis in this advanced population with large tumors. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the clinical beam commissioning results and lateral penumbra characteristics of our new pencil beam scanning (PBS) proton therapy using a multi‐leaf collimator (MLC) calculated by use of a commercial Monte Carlo dose engine. Eighteen collimated uniform dose plans for cubic targets were optimized by the RayStation 9A treatment planning system (TPS), varying scan area, modulation widths, measurement depths, and collimator angles. To test the patient‐specific measurements, we also created and verified five clinically realistic PBS plans with the MLC, such as the liver, prostate, base‐of‐skull, C‐shape, and head‐and‐neck. The verification measurements consist of the depth dose (DD), lateral profile (LP), and absolute dose (AD). We compared the LPs and ADs between the calculation and measurements. For the cubic plans, the gamma index pass rates (γ‐passing) were on average 96.5% ± 4.0% at 3%/3 mm for the DD and 95.2% ± 7.6% at 2%/2 mm for the LP. In several LP measurements less than 75 mm depths, the γ‐passing deteriorated (increased the measured doses) by less than 90% with the scattering such as the MLC edge and range shifter. The deteriorated γ‐passing was satisfied by more than 90% at 2%/2 mm using uncollimated beams instead of collimated beams except for three planes. The AD differences and the lateral penumbra width (80%–20% distance) were within ±1.9% and ± 1.1 mm, respectively. For the clinical plan measurements, the γ‐passing of LP at 2%/2 mm and the AD differences were 97.7% ± 4.2% on average and within ±1.8%, respectively. The measurements were in good agreement with the calculations of both the cubic and clinical plans inserted in the MLC except for LPs less than 75 mm regions of some cubic and clinical plans. The calculation errors in collimated beams can be mitigated by substituting uncollimated beams. [ABSTRACT FROM AUTHOR]

• Automation of beam delivery accuracy evaluation using ML models and log files. • Analysis of all spots in a treatment field to ensure accurate beam delivery. • Aapplication of Machine learning models for predicting spot size of all spots in a treatment field. • Tool for quick evaluation of machine performance in actual treatment angle. Comprehensive Quality Assurance (QA) protocols are necessary for complex beam delivery systems like Pencil Beam Scanning (PBS) proton therapy. This study focuses on automating the evaluation of beam delivery accuracy using irradiation log files and machine learning (ML) models. Irradiation log files of 935 clinical treatment fields and routine QA beams were analysed to evaluate spot parameters and Monitor Unit (MU) accuracy. ML models predicted spot size along the X, Y, major, and minor axes. In-house scripts automated log file analysis and spot size predictions. Predicted spot sizes were compared with expected baselines, and the accuracy of spot position, symmetry, and MU for each spot in the beam was evaluated. More than 99.5 % of spot positions were accurate within a 1 mm. The mean and Standard Deviation (SD) of X positional error were −0.021 mm (SD: 0.181 mm), and for Y positional error, they were −0.002 mm (SD: 0.132 mm). ML models accurately predicted spot sizes, with over 95 % of spots demonstrating size variations within 10 % of the baseline. The Root Mean Squared Error (RMSE) of X and Y spot size differences were 0.15 mm and 0.16 mm, respectively. Spot symmetry was within 10 %, and MU accuracy showed 95 % of spots with MU per spot variation less than 2 %. This method can validate the vendor's beam delivery safety interlock system and serve as a quick alternative to patient-specific QA in adaptive treatment, where time is limited, as well as for routine QA spot parameter evaluations. [ABSTRACT FROM AUTHOR]