Pencil Beam Scanning Proton Research Articles

5-Years Analysis of Effectivity and Toxicity of Ultra-Hypofractionated Proton Radiotherapy in the Treatment of Low- and Intermediate-Risk Prostate Cancer-A Retrospective Analysis.

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. 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. 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. 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.

Experimental validation of a 4D dynamic dose calculation model for proton pencil beam scanning without spot time stamp considering free-breathing motion.

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. 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 5.0mm. 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 6s) 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±0.08s) and spot scan speed. We evaluated the 2D gamma index and the absolute point doses between the calculated values and the measurements. 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%/3mm, 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%/2mm and 3%/3mm, 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%). Our 4DDD calculations under free-breathing conditions using amplitudes of less than 5.0mm were in good agreement with the measurements regardless of the starting phases, breathing curve patterns (between 3 and 6s 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.

Quality of Life, Clinical, and Patient-Reported Outcomes after Pencil Beam Scanning Proton Therapy Delivered for Intracranial Grade WHO 1-2 Meningioma in Children and Adolescents.

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). 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). 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. 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.

Characterisation of the UK high energy proton research beamline for high and ultra-high dose rate (FLASH) irradiation

Objective. This work sets out the capabilities of the high energy proton research beamline developed in the Christie proton therapy centre for Ultra-High Dose Rate (UHDR) irradiation and FLASH experiments. It also characterises the lower limits of UHDR operation for this Pencil Beam Scanning (PBS) proton hardware. Approach. Energy dependent nozzle transmission was measured using a Faraday Cup beam collector. Spot size was measured at the reference plane using a 2D scintillation detector. Integrated depth doses (IDDs) were measured. EBT3 Gafchromic film was used to compare UHDR and conventional dose rate spots. Our beam monitor calibration methodolgy for UHDR is described. A microDiamond detector was used to determine dose rates at zref. Instantaneous depth dose rates were calculated for 70–245 MeV. PBS dose rate distributions were calculated using Folkerts and Van der Water definitions. Main results. Transmission of 7.05 ± 0.1% is achieveable corresponding to a peak instantaneous dose rate of 112.7 Gy s−1. Beam parameters are comparable in conventional and UHDR mode with a spot size of σ x = 4.6 mm, σ y = 6.6 mm. Dead time in the beam monitoring electonics warrants a beam current dependent MU correction in the present configuration. Fast beam scanning of 26.4 m s−1 (X) and 12.1 m s−1 (Y) allows PBS dose rates of the order tens of Grays per second. Significance. UHDR delivery is possible for small field sizes and high energies enabling research into the FLASH effect with PBS protons at our facility. To our knowledge this is also the first thorough characterisation of UHDR irradiation using the hardware of this clinical accelerator at energies less than 250 MeV. The data set out in this publication can be used for designing experiments at this UK research facility and inform the possible future clinical translation of UHDR PBS proton therapy.

Requirements for dose calculation on an active scanned proton beamline for small, shallow fields

Introduction:A growing interest in using proton pencil beam scanning in combination with collimators for the treatment of small, shallow targets, such as ocular melanoma or pre-clinical research emerged recently. This study aims at demonstrating that the dose of a synchrotron-based PBS system with a dedicated small, shallow field nozzle can be accurately predicted by a commercial treatment planning system (TPS) following appropriate tuning of both, nozzle and TPS. Materials:A removable extension to the clinical nozzle was developed to modify the beam shape passively. Five circular apertures with diameters between 5 to 34mm, mounted 72cm downstream of a range shifter were used. For each collimator treatment plans with spread-out Bragg peaks (SOBP) with a modulation of 3 to 30mm were measured and calculated with GATE/Geant4 and the research TPS RayStation (RS11B-R). The dose grid, multiple coulomb scattering and block discretization resolution were varied to find the optimal balance between accuracy and performance. Results:For SOBPs deeper than 10mm, the dose in the target agreed within 1% between RS11B-R, GATE/Geant4 and measurements for aperture diameters between 8 to 34mm, but deviated up to 5% for smaller apertures. A plastic taper was introduced reducing scatter contributions to the patient (from the pipe) and improving the dose calculation accuracy of the TPS to a 5% level in the entrance region for large apertures. Conclusion:The commercial TPS and GATE/Geant4 can accurately calculate the dose for shallow, small proton fields using a collimator and pencil beam scanning.

Selecting Optimal Proton Pencil Beam Scanning Plan Parameters to Reduce Dose Discrepancy between Discrete Spot Plan and Continuous Scanning: A Proof-of-Concept Study.

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.

A portable primary-standard level graphite calorimeter for absolute dosimetry in clinical pencil beam scanning proton beams

Objective. To report the use of a portable primary standard level graphite calorimeter for direct dose determination in clinical pencil beam scanning proton beams, which forms part of the recommendations of the proposed Institute of Physics and Engineering in Medicine (IPEM) Code of Practice (CoP) for proton therapy dosimetry. Approach. The primary standard proton calorimeter (PSPC) was developed at the National Physical Laboratory (NPL) and measurements were performed at four clinical proton therapy facilities that use pencil beam scanning for beam delivery. Correction factors for the presence of impurities and vacuum gaps were calculated and applied, as well as dose conversion factors to obtain dose to water. Measurements were performed in the middle of 10 × 10 × 10 cm3 homogeneous dose volumes, centred at 10.0, 15.0 and 25.0 g·cm−2 depth in water. The absorbed dose to water determined with the calorimeter was compared to the dose obtained using PTW Roos-type ionisation chambers calibrated in terms of absorbed dose to water in 60Co applying the recommendations in the IAEA TRS-398 CoP. Main results. The relative dose difference between the two protocols varied between 0.4% and 2.1% depending on the facility. The reported overall uncertainty in the determination of absorbed dose to water using the calorimeter is 0.9% (k = 1), which corresponds to a significant reduction of uncertainty in comparison with the TRS-398 CoP (currently with an uncertainty equal or larger than 2.0% (k = 1) for proton beams). Significance. The establishment of a purpose-built primary standard and associated CoP will considerably reduce the uncertainty of the absorbed dose to water determination and ensure improved accuracy and consistency in the dose delivered to patients treated with proton therapy and bring proton reference dosimetry uncertainty in line with megavoltage photon radiotherapy.

Impact of Multiple Beams on the FLASH Effect in Soft Tissue and Skin in Mice

FLASH proton pencil beam scanning (p-PBS) showed a reduction in mouse skin toxicity and fibrosis when delivered as a single, uninterrupted, high-dose fraction. Clinical p-PBS treatment usually requires multiple beams to achieve good conformality, and these beams are separated by minutes to allow patient and equipment repositioning. We evaluate the impact of multibeam versus single-beam proton radiation on the FLASH sparing effect on skin toxicity. The right hind leg of 10-week-old female C57Bl/6j mice was irradiated using a Varian ProBeam proton beam scanning gantry system at conventional (1 Gy/s) or FLASH (100 Gy/s) average field dose rate. We scored the skin toxicity after different doses for 7 weeks. The treatment was delivered as 1, 2, or 3 equal beams with an interruption of 2 minutes. For each beam delivery, the equipment remained in the same position so that there was a full overlap of beams administered. Single-beam delivery confirmed a benefit for p-PBS FLASH in this model at 30, 35, and 40 Gy. At 30 and 35 Gy, a single beam interruption of 2 minutes (2×15 Gy or 2×17.5 Gy) reduced the FLASH sparing effect, which remained significant (P < .001). However, 2 interruptions (3×10 Gy or 3×11.6 Gy) abrogated the normal tissue sparing effect. Our results indicate that the FLASHsparing effect in areas of beam overlap can be compromised by interruptions in delivery time. Time gap between overlapping beams and spatial arrangement of the delivered beams are important parameters for FLASH studies. The effect of multibeam needs to be studied on different organs of interest.

FLASH Radiotherapy and the Use of Radiation Dosimeters.

Radiotherapy (RT) using ultra-high dose rate (UHDR) radiation, known as FLASH RT, has shown promising results in reducing normal tissue toxicity while maintaining tumor control. However, implementing FLASH RT in clinical settings presents technical challenges, including limited depth penetration and complex treatment planning. Monte Carlo (MC) simulation is a valuable tool for dose calculation in RT and has been investigated for optimizing FLASH RT. Various MC codes, such as EGSnrc, DOSXYZnrc, and Geant4, have been used to simulate dose distributions and optimize treatment plans. Accurate dosimetry is essential for FLASH RT, and radiation detectors play a crucial role in measuring dose delivery. Solid-state detectors, including diamond detectors such as microDiamond, have demonstrated linear responses and good agreement with reference detectors in UHDR and ultra-high dose per pulse (UHDPP) ranges. Ionization chambers are commonly used for dose measurement, and advancements have been made to address their response nonlinearities at UHDPP. Studies have proposed new calculation methods and empirical models for ion recombination in ionization chambers to improve their accuracy in FLASH RT. Additionally, strip-segmented ionization chamber arrays have shown potential for the experimental measurement of dose rate distribution in proton pencil beam scanning. Radiochromic films, such as GafchromicTM EBT3, have been used for absolute dose measurement and to validate MC simulation results in high-energy X-rays, triggering the FLASH effect. These films have been utilized to characterize ionization chambers and measure off-axis and depth dose distributions in FLASH RT. In conclusion, MC simulation provides accurate dose calculation and optimization for FLASH RT, while radiation detectors, including diamond detectors, ionization chambers, and radiochromic films, offer valuable tools for dosimetry in UHDR environments. Further research is needed to refine treatment planning techniques and improve detector performance to facilitate the widespread implementation of FLASH RT, potentially revolutionizing cancer treatment.

CBCT-Based Dose Monitoring and Adaptive Planning Triggers in Head and Neck PBS Proton Therapy.

To investigate the feasibility of using cone-beam computed tomography (CBCT)-derived synthetic CTs to monitor the daily dose and trigger a plan review for adaptive proton therapy (APT) in head and neck cancer (HNC) patients. For 84 HNC patients treated with proton pencil-beam scanning (PBS), same-day CBCT and verification CT (vfCT) pairs were retrospectively collected. The ground truth CT (gtCT) was created by deforming the vfCT to the same-day CBCT, and it was then used as a dosimetric baseline and for establishing plan review trigger recommendations. Two different synthetic CT algorithms were tested; the corrected CBCT (corrCBCT) was created using an iterative image correction method and the virtual CT (virtCT) was created by deforming the planning CT to the CBCT, followed by a low-density masking process. Clinical treatment plans were recalculated on the image sets for evaluation. Plan review trigger criteria for adaptive therapy were established after closely reviewing the cohort data. Compared to the vfCT, the corrCBCT and virtCT reliably produced dosimetric data more similar to the gtCT. The average discrepancy in D99 for high-risk clinical target volumes (CTV) was 1.1%, 0.7%, and 0.4% and for standard-risk CTVs was 1.8%, 0.5%, and 0.5% for the vfCT, corrCBCT, and virtCT, respectively. Streamlined APT has been achieved with the proposed plan review criteria and CBCT-based synthetic CT workflow.

Proton Bragg Peak FLASH Enables Organ Sparing and Ultra-High Dose-Rate Delivery: Proof of Principle in Recurrent Head and Neck Cancer.

Proton pencil-beam scanning (PBS) Bragg peak FLASH combines ultra-high dose rate delivery and organ-at-risk (OAR) sparing. This proof-of-principle study compared dosimetry and dose rate coverage between PBS Bragg peak FLASH and PBS transmission FLASH in head and neck reirradiation. PBS Bragg peak FLASH plans were created via the highest beam single energy, range shifter, and range compensator, and were compared to PBS transmission FLASH plans for 6 GyE/fraction and 10 GyE/fraction in eight recurrent head and neck patients originally treated with quad shot reirradiation (14.8/3.7 CGE). The 6 GyE/fraction and 10 GyE/fraction plans were also created using conventional-rate intensity-modulated proton therapy techniques. PBS Bragg peak FLASH, PBS transmission FLASH, and conventional plans were compared for OAR sparing, FLASH dose rate coverage, and target coverage. All FLASH OAR V40 Gy/s dose rate coverage was 90-100% at 6 GyE and 10 GyE for both FLASH modalities. PBS Bragg peak FLASH generated dose volume histograms (DVHs) like those of conventional therapy and demonstrated improved OAR dose sparing over PBS transmission FLASH. All the modalities had similar CTV coverage. PBS Bragg peak FLASH can deliver conformal, ultra-high dose rate FLASH with a two-millisecond delivery of the minimum MU per spot. PBS Bragg peak FLASH demonstrated similar dose rate coverage to PBS transmission FLASH with improved OAR dose-sparing, which was more pronounced in the 10 GyE/fraction than in the 6 GyE/fraction. This feasibility study generates hypotheses for the benefits of FLASH in head and neck reirradiation and developing biological models.

Commissioning dose computation model for proton source in pencil beam scanning therapy by convolution neural networks

Objective. Proton source model commissioning (PSMC) is critical for ensuring accurate dose calculation in pencil beam scanning (PBS) proton therapy using Monte Carlo (MC) simulations. PSMC aims to match the calculated dose to the delivered dose. However, commissioning the ‘nominal energy’ and ‘energy spread’ parameters in PSMC can be challenging, as these parameters cannot be directly obtained from solving equations. To efficiently and accurately commission the nominal energy and energy spread in a proton source model, we developed a convolution neural network (CNN) named ‘PSMC-Net.’ Methods. The PSMC-Net was trained separately for 33 energies (E, 70–225 MeV with a step of 5 MeV plus 226.09 MeV). For each E, a dataset was generated consisting of 150 source model parameters (15 nominal energies ∈ [E, E + 1.5 MeV], ten spreads ∈ [0, 1]) and the corresponding 150 MC integrated depth doses (IDDs). Of these 150 data pairs, 130 were used for training the network, 10 for validation, and 10 for testing. Results. The source model, built by 33 measured IDDs and 33 PSMC-Nets (cost 0.01 s), was used to compute the MC IDDs. The gamma passing rate (GPRs, 1 mm/1%) between MC and measured IDDs was 99.91 ± 0.12%. However, when no commissioning was made, the corresponding GPR was reduced to 54.11 ± 22.36%, highlighting the tremendous significance of our CNN commissioning method. Furthermore, the MC doses of a spread-out Bragg peak and 20 patient PBS plans were also calculated, and average 3D GPRs (2 mm/2% with a 10% threshold) were 99.89% and 99.96 ± 0.06%, respectively. Significance. We proposed a nova commissioning method of the proton source model using CNNs, which made the PSMC process easy, efficient, and accurate.

Definition of dose rate for FLASH pencil-beam scanning proton therapy: A comparative study.

FLASH proton therapy has the potential to reduce side effects of conventional proton therapy by delivering a high dose of radiation in a very short period of time. However, significant progress is needed in the development of FLASH proton therapy. Increasing the dose rate while maintaining dose conformality may involve the use of advanced beam-shaping technologies and specialized equipment such as 3D patient-specific range modulators, to take advantage of the higher transmission efficiency at the highest energy available. The dose rate is an important factor in FLASH proton therapy, but its definition can vary because of the uneven distribution of the dose over time in pencil-beam scanning (PBS). Highlight the distinctions, both in terms of concept and numerical values, of the various definitions that can be established for the dose rate in PBS protontherapy. In an insilico study, five definitions of the dose rate, namely the PBS dose rate, the percentile dose rate, the maximum percentile dose rate, the average dose rate, and the dose averaged dose rate (DADR) were analyzed first through theoretical comparison, and then applied to a head and neck case. To carry out this study, a treatment plan utilizing a single energy level and requiring the use of a patient-specific range modulator was employed. The dose rate values were compared both locally and by means of dose rate volume histograms (DRVHs). The PBS dose rate, the percentile dose rate, and the maximum percentile dose are definitions that are specifically designed to take into account the time structure of the delivery of a PBS treatment plan. Although they may appear similar, our study shows that they can vary locally by up to 10%. On the other hand, the DADR values were approximately twice as high as those of the PBS, percentile, and maximum percentile dose rates, since the DADR disregards the periods when a voxel does not receive any dose. Finally, the average dose rate can be defined in various ways, as discussed in this paper. The average dose rate is found to be lower by a factor of approximately 1/2 than the PBS, percentile, and maximum percentile doserates. We have shown that using different definitions for the dose rate in FLASH proton therapy can lead to variations in calculated values ranging from a few percent to a factor of two. Since the dose rate is a critical parameter in FLASH radiation therapy, it is essential to carefully consider the choice of definition. However, to make an informed decision, additional biological data and models areneeded.

FLASH dose rate calculation based on log files in proton pencil beam scanning therapy.

In radiation therapy, irradiating healthy normal tissues in the beam trajectories is inevitable. This unnecessary dose means that patients undergoing treatment risk developing side effects. Recently, FLASH radiotherapy delivering ultra-high-dose-rate beams has been re-examined because of its normal-tissue-sparing effect. To confirm the mean and instantaneous dose rates of the FLASH beam, stable and accurate dosimetry is required. Detailed verification of the FLASH effect requires dosimeters and a method to measure the average and instantaneous dose rate stably for 2- or 3-dimensional dose distributions. To verify the delivered FLASH beam, we utilized machine log files from the built-in monitor chamber to develop a dosimetry method to calculate the dose and average/instantaneous dose rate distributions in two or three dimensions in a phantom. To create a spread-out Bragg peak (SOBP) and deliver a uniform dose in a target, a mini-ridge filter was created with a 3D printer. Proton pencil beam line scanning plans of 2×2 cm2 , 3×3 cm2 , 4×4 cm2 , and round shapes with 2.3cm diameter patterns delivering 230 MeV energy protons were created. The absorbed dose in the solid water phantom of each plan was measured using a PPC05 ionization chamber (IBA Dosimetry, Virginia, USA) in the SOBP region, and the log files for each plan were exported from the treatment control system console. Using these log files, the delivered dose and average dose rate were calculated using two methods: a direct method and a Monte Carlo (MC) simulation method that uses log file information. The computed and average dose rates were compared with the ionization chamber measurements. Additionally, instantaneous dose rates in user-defined volumes were calculated using the MC simulation method with a temporal resolution of 5ms. Compared to ionization chamber dosimetry, 10 of 12 cases using the direct calculation method and 9 of 11 cases using the MC method had a dose difference below ±3%.Nine of 12 cases using the direct calculation method and 8 of 11 cases using the MC method had dose rate differences below ±3%.The average and maximum dose differences for the direct calculation and MC method were-0.17, +0.72%, and -3.15, +3.32%, respectively. For the dose rate difference, the average and maximum for the direct calculation and MC method were +1.26, +1.12%, and +3.75, +3.15%, respectively. In the instantaneous dose rate calculation with the MC simulation, a large fluctuation with a maximum of 163Gy/s and a minimum of 4.29Gy/s instantaneous dose rate was observed in a specific position, whereas the mean dose rate was 62Gy/s. We successfully developed methods in which machine log files are used to calculate the dose and the average and instantaneous dose rates for FLASH radiotherapy and demonstrated the feasibility of verifying the delivered FLASH beams.

PETRA: A pencil beam trimming algorithm for analytical proton therapy dose calculations with the dynamic collimation system.

The Dynamic Collimation System (DCS) has been shown to produce superior treatment plans to uncollimated pencil beam scanning (PBS) proton therapy using an in-house treatment planning system (TPS) designed for research. Clinical implementation of the DCS requires the development and benchmarking of a rigorous dose calculation algorithm that accounts for pencil beam trimming, performs monitor unit calculations to produce deliverable plans at all beam energies, and is ideally implemented with a commercially available TPS. To present an analytical Pencil bEam TRimming Algorithm (PETRA) for the DCS, with and without its range shifter, implemented in the Astroid TPS (.decimal, Sanford, Florida, USA). PETRA was derived by generalizing an existing pencil beam dose calculation model to account for the DCS-specific effects of lateral penumbra blurring due to the nickel trimmers in two different planes, integral depth dose variation due to the trimming process, and the presence and absence of the range shifter. Tuning parameters were introduced to enable agreement between PETRA and a measurement-validated Dynamic Collimation Monte Carlo (DCMC) model of the Miami Cancer Institute's IBA Proteus Plus system equipped with the DCS. Trimmer position, spot position, beam energy, and the presence or absence of a range shifter were all used as variables for the characterization of the model. The model was calibrated for pencil beam monitor unit calculations using procedures specified by International Atomic Energy Agency Technical Report Series 398 (IAEA TRS-398). The integral depth dose curves (IDDs) for energies between 70 MeV and 160 MeV among all simulated trimmer combinations, with and without the ranger shifter, agreed between PETRA and DCMC at the 1%/1mm 1-D gamma criteria for 99.99% of points. For lateral dose profiles, the median 2-D gamma pass rate for all profiles at 1.5%/1.5mm was 99.99% at the water phantom surface, plateau, and Bragg peak depths without the range shifter and at the surface and Bragg peak depths with the range shifter. The minimum 1.5%/1.5mm gamma pass rates for the 2-D profiles at the water phantom surface without and with the range shifter were 98.02% and 97.91%, respectively, and, at the Bragg peak, the minimum pass rates were 97.80% and 97.5%, respectively. The PETRA model for DCS dose calculations was successfully defined and benchmarked for use in a commercially available TPS.

Automated treatment planning for proton pencil beam scanning using deep learning dose prediction and dose-mimicking optimization.

The purpose of this study is to investigate the use of a deep learning architecture for automated treatment planning for proton pencil beam scanning (PBS). A 3-dimensional (3D) U-Net model has been implemented in a commercial treatment planning system (TPS) that uses contoured regions of interest (ROI) binary masks as model inputs with a predicted dose distribution as the model output. Predicted dose distributions were converted to deliverable PBS treatment plans using a voxel-wise robust dose mimicking optimization algorithm. This model was leveraged to generate machine learning (ML) optimized plans for patients receiving proton PBS irradiation of the chest wall. Model training was carried out on a retrospective set of 48 previously-treated chest wall patient treatment plans. Model evaluation was carried out by generating ML-optimized plans on a hold-out set of 12 contoured chest wall patient CT datasets from previously treated patients. Clinical goal criteria and gamma analysis were used to compare dose distributions of the ML-optimized plans against the clinically approved plans across the test patients. Statistical analysis of mean clinical goal criteria indicates that compared to the clinical plans, the ML optimization workflow generated robust plans with similar dose to the heart, lungs, and esophagus while achieving superior dosimetric coverage to the PTV chest wall (clinical mean V95=97.6% vs. ML mean V95=99.1%, p<0.001) across the 12 test patients. ML-based automated treatment plan optimization using the 3D U-Net model can generate treatment plans of similar clinical quality compared to human-driven optimization.

Long Term Outcome and Quality of Life of Intracranial Meningioma Patients Treated with Pencil Beam Scanning Proton Therapy

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 &lt; 0.001). Twenty (10%) local failures were observed. Failures occurred significantly (p &lt; 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.

Dosimetric comparison of breath-hold and free-breathing techniques in left-sided breast cancer patients treated with proton pencil beam scanning

Dosimetric comparison of breath-hold and free-breathing techniques in left-sided breast cancer patients treated with proton pencil beam scanning

A motion model-guided 4D dose reconstruction for pencil beam scanned proton therapy

Objective. 4D dose reconstruction in proton therapy with pencil beam scanning (PBS) typically relies on a single pre-treatment 4DCT (p4DCT). However, breathing motion during the fractionated treatment can vary considerably in both amplitude and frequency. We present a novel 4D dose reconstruction method combining delivery log files with patient-specific motion models, to account for the dosimetric effect of intra- and inter-fractional breathing variability. Approach. Correlation between an external breathing surrogate and anatomical deformations of the p4DCT is established using principal component analysis. Using motion trajectories of a surface marker acquired during the dose delivery by an optical tracking system, deformable motion fields are retrospectively reconstructed and used to generate time-resolved synthetic 4DCTs (‘5DCTs’) by warping a reference CT. For three abdominal/thoracic patients, treated with respiratory gating and rescanning, example fraction doses were reconstructed using the resulting 5DCTs and delivery log files. The motion model was validated beforehand using leave-one-out cross-validation (LOOCV) with subsequent 4D dose evaluations. Moreover, besides fractional motion, fractional anatomical changes were incorporated as proof of concept. Main results. For motion model validation, the comparison of 4D dose distributions for the original 4DCT and predicted LOOCV resulted in 3%/3 mm gamma pass rates above 96.2%. Prospective gating simulations on the p4DCT can overestimate the target dose coverage V95% by up to 2.1% compared to 4D dose reconstruction based on observed surrogate trajectories. Nevertheless, for the studied clinical cases treated with respiratory-gating and rescanning, an acceptable target coverage was maintained with V95% remaining above 98.8% for all studied fractions. For these gated treatments, larger dosimetric differences occurred due to CT changes than due to breathing variations. Significance. To gain a better estimate of the delivered dose, a retrospective 4D dose reconstruction workflow based on motion data acquired during PBS proton treatments was implemented and validated, thus considering both intra- and inter-fractional motion and anatomy changes.

Postmastectomy Intensity Modulated Proton Therapy: 5-Year Oncologic and Patient-Reported Outcomes

To report oncologic, physician-assessed, and patient-reported outcomes (PROs) for a group of women homogeneously treated with modern, skin-sparing multifield optimized pencil-beam scanning proton (intensity modulated proton therapy [IMPT]) postmastectomy radiation therapy (PMRT). We reviewed consecutive patients who received unilateral, curative-intent, conventionally fractionated IMPT PMRT between 2015 and 2019. Strict constraints were applied to limit the dose to the skin and other organs at risk. Five-year oncologic outcomes were analyzed. Patient-reported outcomes were evaluated as part of a prospective registry at baseline, completion of PMRT, and 3 and 12 months after PMRT. A total of 127 patients were included. One hundred nine (86%) received chemotherapy, among whom 82 (65%) received neoadjuvant chemotherapy. The median follow-up was 4.1 years. Five-year locoregional control was 98.4% (95% CI, 93.6-99.6), and overall survival was 87.9% (95% CI, 78.7-96.5). Acute grade 2 and 3 dermatitis was seen in 45% and 4% of patients, respectively. Three patients (2%) experienced acute grade 3 infection, all of whom had breast reconstruction. Three late grade 3 adverse events occurred: morphea (n=1), infection (n=1), and seroma (n=1). There were no cardiac or pulmonary adverse events. Among the 73 patients at risk for PMRT-associated reconstruction complications, 7 (10%) experienced reconstruction failure. Ninety-five patients (75%) enrolled in the prospective PRO registry. The only metrics to increase by >1 point were skin color (mean change: 5) and itchiness (2) at treatment completion and tightness/pulling/stretching (2) and skin color (2) at 12 months. There was no significant change in the following PROs: bleeding/leaking fluid, blistering, telangiectasia, lifting, arm extension, or bending/straightening the arm. With strict dose constraints to skin and organs at risk, postmastectomy IMPT was associated with excellent oncologic outcomes and PROs. Rates of skin, chest wall, and reconstruction complications compared favorably to previous proton and photon series. Postmastectomy IMPT warrants further investigation in a multi-institutional setting with careful attention to planning techniques.