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To investigate the dosimetric characteristics between an advanced proton pencil beam scanning (PBS) Bragg peak FLASH technique and conventional PBS planning technique in lung tumors. To evaluate the "FLASHness" of single-field in a multiple-field delivery scheme for a hypofractionation regimen and move a step forward to clinical application.Single-energy PBS Bragg peak FLASH treatment plans were optimized based on a novel Bragg peak tracking technique to enable Bragg peaks to stop at the distal edge of the target. Inverse treatment planning using multiple-field optimization (MFO) can achieve sufficient FLASH dose rate and intensity-modulated proton therapy (IMPT)-equivalent dosimetric quality. The dose rate of organs-at-risk (OARs) and the target were calculated under FLASH machine parameters. A group of 10 consecutive lung SBRT patients was optimized to 34 Gy/fraction using a standard treatment of PBS technique with multiple energy layers as references to the Bragg peak plans. The dosimetric quality was compared between Bragg peak FLASH and conventional plans based on RTOG0915 dose metrics. FLASH dose rate ratios (VFor higher dose thresholds, the Bragg peak plans achieved greater VHypofractionated lung Bragg peak plans can maintain comparable plan quality to conventional PBS while achieving sufficient FLASH dose rate coverage for major OARs for each field under the multiple-field delivery scheme. The novel Bragg peak FLASH technique has the potential to enhance lung cancer planning treatment outcomes compared to standard PBS treatment techniques.

Laser plasma accelerators (LPA) can produce very high-energy electrons (VHEE) with ultra-short bunch duration, which may facilitate the application of ultra-high dose rate radiotherapy (FLASH-RT) to treat deep-seated tumors. The study aims to evaluate the dose rate delivery by spot-scanning VHEE beams produced by LPA and to discuss the feasibility and beam specifications for FLASH-RT implementation. Various dose rate metrics, including averaged dose rate (ADR), dose-averaged dose rate (DADR), and dose-threshold dose rate (DTDR), are examined in the context of spot-scanning. Theoretical analysis and Monte Carlo simulations are employed to quantify the dose rate distribution for a water phantom and explore the impact of beam parameters. All the beam parameters are based on experimental results. With a lower pulse repetition rate of 5 Hz, ADR can only reach a dose rate in the order of 10−1Gy/s, while attaining the FLASH-RT dose rate of 40Gy/s necessitates the utilization of high-power lasers with a kilohertz working repetition rate. In contrast to ADR, DADR and DTDR remain independent of the scanning path and can reach the ultra-high dose rate surpassing 1014Gy/s at the phantom surface. Meanwhile, the ultrashort electron bunch can be stretched during scattering within the water, resulting in a dependence of DADR and DTDR on the penetration depth. Both the charge per shot and angular spread are important parameters in dose rate calculations. This investigation offers insights into practical beam parameters for preclinical applications and supplies guidance for designing the LPAs suitable for future spot-scanning VHEE FLASH-RT.

Experimental measurements of two-dimensional (2D) dose rate distributions in proton pencil beam scanning (PBS) FLASH radiation therapy (RT) are currently lacking. In this study, we characterize a newly designed 2D strip-segmented ionization chamber array (SICA) with high spatial and temporal resolution and demonstrate its applications in a modern proton PBS delivery system at both conventional and ultrahigh dose rates.A dedicated research beamline of the Varian ProBeam system was employed to deliver a 250-MeV proton PBS beam with nozzle currents up to 215 nA. In the research and clinical beamlines, the spatial, temporal, and dosimetric performances of the SICA were characterized and compared with measurements using parallel-plate ion chambers (IBA PPC05 and PTW Advanced Markus chamber), a 2D scintillator camera (IBA Lynx), Gafchromic films (EBT-XD), and a Faraday cup. A novel reconstruction approach was proposed to enable the measurement of 2D dose and dose rate distributions using such a strip-type detector.The SICA demonstrated a position accuracy of 0.12 ± 0.02 mm at a 20-kHz sampling rate (50 μs per event) and a linearity of RThe newly designed SICA demonstrated excellent spatial, temporal, and dosimetric performances and is well suited for commissioning, quality assurance, and a wide range of clinical applications in proton PBS clinical and FLASH-RT.

Purpose/Objective(s) Monte Carlo (MC) dose calculation has appeared in primary commercial treatment-planning systems and various in-house platforms. Dual-energy computed tomography (DECT) and metal artifact reduction (MAR) techniques complement MC capabilities. However, no publications have yet reported how proton therapy centers implement these new technologies, and a national survey is required to determine the feasibility of including MC and companion techniques in cooperative group clinical trials. Materials/Methods A 9-question survey was designed to query key clinical parameters: scope of MC utilization, validation methods for heterogeneities, clinical site-specific imaging guidance, proton range uncertainties, and how implants are handled. A national survey was distributed to all 29 operational US proton therapy centers on 13 May 2019. Results We received responses from 25 centers (86% participation). Commercial MC was most commonly used for primary plan optimization (16 centers) or primary dose evaluation (18 centers), while in-house MC was used more frequently for secondary dose evaluation (7 centers). Based on the survey, MC was used infrequently for gastrointestinal, genitourinary, gynecology and extremity compared with other more heterogeneous disease sites (P < .007). Although many centers had published DECT research, only 3/25 centers had implemented DECT clinically, either in the treatment-planning system or to override implant materials. Most centers (64%) treated patients with metal implants on a case-by-case basis, with a variety of methods reported. Twenty-four centers (96%) used MAR images and overrode the surrounding tissue artifacts; however, there was no consensus on how to determine metal dimension, materials density, or stopping powers. Conclusion The use of MC for primary dose calculation and optimization was prevalent and, therefore, likely feasible for clinical trials. There was consensus to use MAR and override tissues surrounding metals but no consensus about how to use DECT and MAR for human tissues and implants. Development and standardization of these advanced technologies are strongly encouraged for vendors and clinical physicists.

Objective. To investigate the effects of respiratory motion on the delivered dose in the context of proton pencil beam scanning (PBS) transmission FLASH radiotherapy (FLASH-RT) by simulation and phantom measurements. Approach. An in-house simulation code was employed to perform in silico simulation of 2D dose distributions for clinically relevant proton PBS transmission FLASH-RT treatments. A moving simulation grid was introduced to investigate the impacts of various respiratory motion and treatment delivery parameters on the dynamic PBS dose delivery. A strip-ionization chamber array detector and an IROC motion platform were employed to perform phantom measurements of the 2D dose distribution for treatment fields similar to those used for simulation. Main results. Clinically relevant respiratory motion and treatment delivery parameters resulted in degradation of the delivered dose compared to the static delivery as translation and distortion. Simulation showed that the gamma passing rates (2 mm/2% criterion) and target coverage could drop below 50% and 80%, respectively, for certain scenarios if no mitigation strategy was used. The gamma passing rates and target coverage could be restored to more than 95% and 98%, respectively, for short beams delivered at the maximal inhalation or exhalation phase. The simulation results were qualitatively confirmed in phantom measurements with the motion platform. Significance. Respiratory motion could cause dose quality degradation in a clinically relevant proton PBS transmission FLASH-RT treatment if no mitigation strategy is employed, or if an adequate margin is not given to the target. Besides breath-hold, gated delivery can be an alternative motion management strategy to ensure high consistency of the delivered dose while maintaining minimal dose to the surrounding normal tissues. To the best of our knowledge, this is the first study on motion impacts in the context of proton transmission FLASH radiotherapy.

The transmission proton FLASH technique delivers high doses to the normal tissue distal to the target, which is less conformal compared to the Bragg peak technique. To investigate FLASH radiotherapy (RT) planning using single-energy Bragg peak beams with a similar beam arrangement as clinical intensity-modulated proton therapy (IMPT) in a liver stereotactic body radiation therapy (SBRT) and to characterize the plan quality, dose sparing of organs-at-risk (OARs), and FLASH dose rate percentage.An in-house platform was developed to enable inverse IMPT-FLASH planning using single-energy Bragg peaks. A universal range shifter and range compensators were utilized to effectively align the Bragg peak to the distal edge of the target. Two different minimum MU settings of 400 and 800 MU/spot (Bragg-400 MU and Bragg-800 MU) plans were investigated on 10 consecutive hepatocellular carcinoma patients previously treated by IMPT-SBRT to evaluate the FLASH dose and dose rate coverage for OARs. The IMPT-FLASH using single-energy Bragg peaks delivered 50 Gy in five fractions with similar or identical beam arrangement to the clinical IMPT-SBRT plans. NRG GI003 dose constraint metrics were used. Three dose rate calculation methods, including average dose rate (ADR), dose threshold dose rate (DTDR), and dose-ADR (DADR), were all studied.The novel spot map optimization can fulfill the inverse planning using single-energy Bragg peaks. All the Bragg peak FLASH plans achieved similar results for the liver-gross tumor volume (GTV) DSingle-energy Bragg peak IMPT-FLASH plans eliminate the exit dose in normal tissues, maintaining comparable dose metrics to the conventional IMPT-SBRT plans, while achieving a sufficient FLASH dose rate for liver cancers. This study demonstrates the feasibility of and sufficiently high dose rate when applying the Bragg peak FLASH treatment for a liver cancer hypofractionated FLASH therapy. The advancement of this novel method has the potential to optimize treatment for liver cancer patients.

Purpose A unique mantle cell lymphoma case with bilateral periorbital disease unresponsive to chemotherapy and with dosimetry not conducive to electron therapy was treated with pencil beam scanning (PBS) proton therapy. This patient presented treatment planning challenges due to the thin target, immediately adjacent organs at risk (OAR), and nonconformal orbital surface anatomy. Therefore, we developed a patient‐specific bolus and hypothesized that it would provide superior setup robustness, dose uniformity and dose conformity. Materials/Methods A blue‐wax patient‐specific bolus was generated from the patient's face contour to conform to his face and eliminate air gaps. A relative stopping power ratio (RSP) of 0.972 was measured for the blue‐wax, and the HUs were overridden accordingly in the treatment planning system (TPS). Orthogonal kV images were used for bony alignment and then to ensure positioning of the bolus through fiducial markers attached to the bolus and their contours in TPS. Daily CBCT was used to confirm the position of the bolus in relation to the patient's surface. Dosimetric characteristics were compared between (a) nonbolus, (b) conventional gel bolus and (c) patient‐specific bolus plans. An in‐house developed workflow for assessment of daily treatment dose based on CBCT images was used to evaluate inter‐fraction dose accumulation. Results The patient was treated to 24 cobalt gray equivalent (CGE) in 2 CGE daily fractions to the bilateral periorbital skin, constraining at least 50% of each lacrimal gland to under 20 Gy. The bolus increased proton beam range by adding 2–3 energy layers of different fields to help achieve better dose uniformity and adequate dose coverage. In contrast to the plan with conventional gel bolus, dose uniformity was significantly improved with patient‐specific bolus. The global maximum dose was reduced by 7% (from 116% to 109%). The max and mean doses were reduced by 6.0% and 7.7%, respectively, for bilateral retinas, and 3.0% and 13.9% for bilateral lacrimal glands. The max dose of the lens was reduced by 2.1%. The rigid shape, along with lightweight, and smooth fit to the patient face was well tolerated and reported as “very comfortable” by the patient. The daily position accuracy of the bolus was within 1 mm based on IGRT marker alignment. The daily dose accumulation indicates that the target coverage and OAR doses were highly consistent with the planning intention. Conclusion Our patient‐specific blue‐wax bolus significantly increased dose uniformity, reduced OAR doses, and maintained consistent setup accuracy compared to conventional bolus. Quality PBS proton treatment for periorbital tumors and similar challenging thin and shallow targets can be achieved using such patient‐specific bolus with robustness on both setup and dosimetry.

Purpose: While transmission proton beams have been demonstrated to achieve ultra-high dose rate FLASH therapy delivery, they are unable to spare normal tissues distal to the target. This study aims to compare FLASH treatment planning using single energy Bragg peak proton beams versus transmission proton beams in lung tumors and to evaluate Bragg peak plan optimization, characterize plan quality, and quantify organ-at-risk (OAR) sparing. Materials and Methods: Both Bragg peak and transmission plans were optimized using an in-house platform for 10 consecutive lung patients previously treated with proton stereotactic body radiation therapy (SBRT). To bring the dose rate up to the FLASH-RT threshold, Bragg peak plans with a minimum MU/spot of 1200 and transmission plans with a minimum MU/spot of 400 were developed. Two common prescriptions, 34 Gy in 1 fraction and 54 Gy in 3 fractions, were studied with the same beam arrangement for both Bragg peak and transmission plans (n = 40 plans). RTOG 0915 dosimetry metrics and dose rate metrics based on different dose rate calculations, including average dose rate (ADR), dose-averaged dose rate (DADR), and dose threshold dose rate (DTDR), were investigated. We then evaluated the effect of beam angular optimization on the Bragg peak plans to explore the potential for superior OAR sparing. Results: Bragg peak plans significantly reduced doses to several OAR dose parameters, including lung V7.4Gy and V7Gy by 32.0% (p &lt, 0.01) and 30.4% (p &lt, 0.01) for 34Gy/fx plans, respectively, and by 40.8% (p &lt, 0.01) and 41.2% (p &lt, 0.01) for 18Gy/fx plans, respectively, compared with transmission plans. Bragg peak plans have ~3% less in DADR and ~10% differences in mean OARs in DTDR and DADR relative to transmission plans due to the larger portion of lower dose regions of Bragg peak plans. With angular optimization, optimized Bragg peak plans can further reduce the lung V7Gy by 20.7% (p &lt, 0.01) and V7.4Gy by 19.7% (p &lt, 0.01) compared with Bragg peak plans without angular optimization while achieving a similar 3D dose rate distribution. Conclusion: The single-energy Bragg peak plans achieve superior dosimetry performances in OARs to transmission plans with comparable dose rate performances for lung cancer FLASH therapy. Beam angle optimization can further improve the OAR dosimetry parameters with similar 3D FLASH dose rate coverage.

Radiation therapy (RT) is an integral component of potentially curative management of esophageal cancer (EC). However, RT can cause significant acute and late morbidity due to excess radiation exposure to nearby critical organs, especially the heart and lungs. Sparing these organs from both low and high radiation dose has been demonstrated to achieve clinically meaningful reductions in toxicity and may improve long-term survival. Accruing dosimetry and clinical evidence support the consideration of proton beam therapy (PBT) for the management of EC. There are critical treatment planning and delivery uncertainties that should be considered when treating EC with PBT, especially as there may be substantial motion-related interplay effects. The Particle Therapy Co-operative Group Thoracic and Gastrointestinal Subcommittees jointly developed guidelines regarding patient selection, treatment planning, clinical trials, and future directions of PBT for EC.

To quantitatively assess target and organs-at-risk (OAR) dose rate based on three proposed proton PBS dose rate metrics and study FLASH intensity-modulated proton therapy (IMPT) treatment planning using transmission beams. An in-house FLASH planning platform was developed to optimize transmission (shoot-through) plans for nine consecutive lung cancer patients previously planned with proton SBRT. Dose and dose rate calculation codes were developed to quantify three types of dose rate calculation methods (dose-averaged dose rate (DADR), average dose rate (ADR), and dose-threshold dose rate (DTDR)) based on both phantom and patient treatment plans. Two different minimum MU/spot settings were used to optimize two different dose regimes, 34-Gy in one fraction and 45-Gy in three fractions. The OAR sparing and target coverage can be optimized with good uniformity (hotspot &lt, 110% of prescription dose). ADR, accounting for the spot dwelling and scanning time, gives the lowest dose rate, DTDR, not considering this time but a dose-threshold, gives an intermediate dose rate, whereas DADR gives the highest dose rate without considering any time or dose-threshold. All three dose rates attenuate along the beam direction, and the highest dose rate regions often occur on the field edge for ADR and DTDR, whereas DADR has a better dose rate uniformity. The differences in dose rate metrics have led a large variation for OARs dose rate assessment, posing challenges to FLASH clinical implementation. This is the first attempt to study the impact of the dose rate models, and more investigations and evidence for the details of proton PBS FLASH parameters are needed to explore the correlation between FLASH efficacy and the dose rate metrics.

Transmission beams have been proposed for ultra-high dose (or FLASH) proton planning, limiting the organ sparing potentials of proton therapy. By pulling back the ranges of the highest energy proton beams and compensating proton ranges to adapt to the target distally, the exit dose of proton beams can be eliminated to better protect organs at risk while still preserving FLASH dose rate delivery.An inverse planning tool was developed to optimize intensity modulated proton therapy using a single-energy layer for FLASH radiation therapy planning. The range pull-backs were calculated to stop single-energy proton beams at the distal edge of the target. The spot map and weights of each field were optimized to achieve a sufficient dose rate using proton beam Bragg peaks. A C-shape target in phantom, along with 6 consecutive lung cancer patients previously treated using proton stereotactic body radiation therapy were planned using this novel Bragg Peak method and also transmission technique. Dosimetry characteristics and 3-dimensional dose rate were investigated.The minimum monitor units (MU) for transmission and Bragg peak plans were 400 MU/spot and 1200 MU/spot, respectively, corresponding to spot peak dose rates of 670 GyRBE (relative biological effectiveness) per second and 1950 GyRBE per second. Bragg peak plans yield a generally comparable target uniformity while significantly reducing dose spillage volume from the low to medium dose level. For all the 6 lung cases delivery of 34 GyRBE in 1 fraction, assessing Radiation Therapy Oncology Group 0915 constraints, the lung VThis first proof-of-concept study has demonstrated this novel method of combining range pull-back and powerful inverse optimization capable of achieving FLASH dose rate based on currently available machine parameters using a single-energy Bragg peak. Similar target coverage and uniformity can be maintained by Bragg peak FLASH plans while substantially improving the sparing of organs at risk compared with transmission plans.

The Daily Quality Assurance (DQA) for a proton modality is not standardized. The modern pencil beam scanning proton system is becoming a trend and an increasing number of proton centers with PBS are either under construction or in planning. The American Association of Physicists in Medicine has a Task Group 224 report published in 2019 for proton modality routine QA. Therefore, there is a clinical need to explore a DQA procedure to meet the TG 224 guideline. The MatriXX PT and a customized phantom were used for the dosimetry constancy checking. An OBI box was used for imaging QA. The MyQA(TM) software was used for logging the dosimetry results. An in‐house developed application was applied to log and auto analyze the DQA results. Another in‐house developed program "DailyQATrend" was used to create DQA databases for further analysis. All the functional and easy determined tasks passed. For dosimetry constancy checking, the outputs for four gantry rooms were within ±3% with room to room baseline differences within ±1%. The energy checking was within ±1%. The spot location checking from the baseline was within 0.63 mm and the spot size checking from the baseline was within −1.41 ± 1.27 mm (left–right) and −0.24 ± 1.27 mm (in–out) by averaging all the energies. We have found that there was also a trend for the beam energies of two treatment rooms slowly going down (0.76% per month and 0.48 per month) after analyzing the whole data trend with linear regression. A DQA program for a PBS proton system has been developed and fully implemented into the clinic. The DQA program meets the TG 224 guideline and has web‐based logging and auto treading functions. The clinical data show the DQA program is efficient and has the potential to identify the PBS proton system potential issue.

Monte Carlo (MC)-based dose calculations are generally superior to analytical dose calculations (ADC) in modeling the dose distribution for proton pencil beam scanning (PBS) treatments. The purpose of this paper is to present a methodology for commissioning and validating an accurate MC code for PBS utilizing a parameterized source model, including an implementation of a range shifter, that can independently check the ADC in commercial treatment planning system (TPS) and fast Monte Carlo dose calculation in opensource platform (MCsquare). The source model parameters (including beam size, angular divergence and energy spread) and protons per MU were extracted and tuned at the nozzle exit by comparing Tool for Particle Simulation (TOPAS) simulations with a series of commissioning measurements using scintillation screen/CCD camera detector and ionization chambers. The range shifter was simulated as an independent object with geometric and material information. The MC calculation platform was validated through comprehensive measurements of single spots, field size factors (FSF) and three-dimensional dose distributions of spread-out Bragg peaks (SOBPs), both without and with the range shifter. Differences in field size factors and absolute output at various depths of SOBPs between measurement and simulation were within 2.2%, with and without a range shifter, indicating an accurate source model. TOPAS was also validated against anthropomorphic lung phantom measurements. Comparison of dose distributions and DVHs for representative liver and lung cases between independent MC and analytical dose calculations from a commercial TPS further highlights the limitations of the ADC in situations of highly heterogeneous geometries. The fast MC platform has been implemented within our clinical practice to provide additional independent dose validation/QA of the commercial ADC for patient plans. Using the independent MC, we can more efficiently commission ADC by reducing the amount of measured data required for low dose “halo” modeling, especially when a range shifter is employed. © 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine

For lung tumors with large motion amplitudes, the use of proton pencil beam scanning (PBS) can produce large dose errors. In this study, we assess under what circumstances PBS can be used to treat lung cancer patients who exhibit large tumor motion, based on the quantification of tumor motion and the dose interplay.PBS plans were optimized on average 4DCT datasets using a beam-specific PTV method for 10 consecutive patients with locally advanced non-small-cell-lung-cancer (NSCLC) treated with proton therapy to 6660/180 cGy. End inhalation (CT0) and end exhalation (CT50) were selected as the two extreme scenarios to acquire the relative stopping power ratio difference (Δrsp) for a respiration cycle. The water equivalent difference (ΔWET) per radiological path was calculated from the surface of patient to the iCTV by integrating the Δrsp of each voxel. The magnitude of motion of voxels within the target follows a quasi-Gaussian distribution. A motion index (MI (5mm WET)), defined as the percentage of target voxels with an absolute integral ΔWET larger than 5 mm, was adopted as a metric to characterize interplay. To simulate the treatment process, 4D dose was calculated by accumulating the spot dose on the corresponding respiration phase to the reference phase CT50 by deformable image registration based on spot timing and patient breathing phase.The study indicated that the magnitude of target underdose in a single fraction plan is proportional to the MI (p .001), with larger motion equating to greater dose degradation and standard deviations. The target homogeneity, minimum, maximum and mean dose in the 4D dose accumulations of 37 fractions varied as a function of MI.This study demonstrated that MI can predict the level of dose degradation, which potentially serves as a clinical decision tool to assess whether lung cancer patients are potentially suitable to receive PBS treatment.

Purpose To determine whether individual liver tumor patients can be safely treated with pencil beam scanning proton therapy. This study reports a planning preparation workflow that can be used for beam angle selection and the evaluation of the efficacy of abdominal compression (AC) to mitigate motion. Methods Four-dimensional computed tomography scans (4DCT) with and without AC were available from 10 liver tumor patients with fluoroscopy-proven motion reduction by AC, previously treated using photons. For each scan, the motion amplitudes and the motion-induced variation of water-equivalent thickness (ΔWET) in each voxel of the target volume were evaluated during treatment plan preparation. Optimal proton beam angles were selected after volume analysis of the respective beam-specific planning target volume (BSPTV). M⊥80 and ΔWET80 derived from the 80th percentiles of perpendicular motion amplitude (M⊥) and ΔWET were compared with and without AC. Proton plans were created on the average CT to achieve target coverage similar to that of the conventional photon treatments. 4D dynamic dose calculation was performed postplan by synchronizing proton beam delivery timing patterns to the 4DCT phases to assess interplay and fractionation effects, and to determine motion criteria for subsequent patient treatment. Results Selected coplanar beam angles ranged between 180° and 39°, primarily from right lateral (oblique) and posterior (oblique) directions. While AC produced a significant reduction in mean Liver-GTV dose, any reduction in mean heart dose was patient dependent and not significant. Similarly, AC resulted in reductions in M⊥, ΔWET, and BSPTV volumes and improved dose degradation (ΔD95 and ΔD1) within the CTV. For small motion (M⊥80 10 mm or ΔWET80 > 7 mm), AC and/or some other form of mitigation strategies were required. Conclusion A workflow for screening patients’ motion characteristics and optimizing beam angle selection was established for the pencil beam scanning proton therapy treatment of liver tumors. Abdominal compression was found to be useful at mitigation of moderate and large motion.

Purpose Treatment planning systems (TPSs) from different vendors can involve different implementations of Monte Carlo dose calculation (MCDC) algorithms for pencil beam scanning (PBS) proton therapy. There are currently no guidelines for validating non-water materials in TPSs. Furthermore, PBS-specific parameters can vary by 1-2 orders of magnitude among different treatment delivery systems (TDSs). This paper proposes a standardized framework on the use of commissioning data and steps to validate TDS-specific parameters and TPS-specific heterogeneity modeling to potentially reduce these uncertainties. Methods A standardized commissioning framework was developed to commission the MCDC algorithms of RayStation 8A and Eclipse AcurosPT v13.7.20 using water and non-water materials. Measurements included Bragg peak depth-dose and lateral spot profiles and scanning field outputs for Varian ProBeam. The phase-space parameters were obtained from in-air measurements and the number of protons per MU from output measurements of 10 × 10 cm2 square fields at a 2 cm depth. Spot profiles and various PBS field measurements at additional depths were used to validate TPS. Human tissues in TPS, Gammex phantom materials, and artificial materials were used for the TPS benchmark and validation. Results The maximum differences of phase parameters, spot sigma, and divergence between MCDC algorithms are below 4.5 µm and 0.26 mrad in air, respectively. Comparing TPS to measurements at depths, both MC algorithms predict the spot sigma within 0.5 mm uncertainty intervals, the resolution of the measurement device. Beam Configuration in AcurosPT is found to underestimate number of protons per MU by ~2.5% and requires user adjustment to match measured data, while RayStation is within 1% of measurements using Auto model. A solid water phantom was used to validate the range accuracy of non-water materials within 1% in AcurosPT. Conclusions The proposed standardized commissioning framework can detect potential issues during PBS TPS MCDC commissioning processes, and potentially can shorten commissioning time and improve dosimetric accuracies. Secondary MCDC can be used to identify the root sources of disagreement between primary MCDC and measurement.

PURPOSE To present and discuss beam characteristics and commissioning process of the first gantry-mounted accelerator single room pencil beam scanning (PBS) proton system. METHODS The Mevion HYPERSCAN employs a design configuration with a synchrocyclotron mounted on the gantry to eliminate the traditional beamline and a nozzle that contains the dosimetry monitoring chambers, the energy modulator (Energy Selector (ES)), and an Adaptive Aperture (AA). To characterize the beam, we measured the integrated depth dose (IDDs) for 12 energies, from highest energy of 227 MeV down to 28 MeV with a range difference ~ 2 cm between the adjacent energies, using a large radius Bragg peak chamber; single-spot profiles in air at five locations along the beam central axis using radiochromic EBT3 film and cross compared with a scintillation detector; and determined the output using a densely packed spot map. To access the performance of AA, we measured interleaf leakage and the penumbra reduction effect. Monte Carlo simulation using TOPAS was performed to study spot size variation along the beam path, beam divergence, and energy spectrum. RESULTS This proton system is calibrated to deliver 1 Gy dose at 5 cm depth in water using the highest beam energy by delivering 1 MU/spot to a 10 × 10 cm2 map with a 2.5 mm spot spacing. The spot size in air varies from 4 mm to 26 mm from 227 MeV to 28 MeV at the isocenter plane with the nozzle retracted 23.6 cm from isocenter. The beam divergence of 28 MeV beam is ~ 52.7 mrad, which is nearly 22 times that of 227 MeV proton beam. The binary design of the ES has resulted in shifts of the effective SSD toward the isocenter as the energy is modulated lower. The peaks of IDD curves have a constant 80%-80% width of 8.4 mm at all energies. The interleaf leakage of the AA is less than 1.5% at the highest energy; and the AA can reduce the penumbra by 2 mm to 13 mm for the 227 and 28 MeV energies at isocenter plane in air. CONCLUSIONS The unique design of the HYPERSCAN proton system has yielded beam characteristics significantly different from that of other proton systems in terms of the Bragg peak shapes, spot sizes, and the penumbra sharpening effect of the AA. The combination of the ES and AA has made PBS implementation possible without using beam transport line and range shifter devices. Different considerations may be required in treatment planning optimization to account for different design and beam characteristics.

Purpose: Monte Carlo (MC) dose calculation is generally superior to analytical dose calculation (ADC) used in commercial TPS to model the dose distribution especially for heterogeneous sites, such as lung and head/neck patients. The purpose of this study was to provide a validated, fast, and open-source MC code, MCsquare, to assess the impact of approximations in ADC on clinical pencil beam scanning (PBS) plans covering various sites. Methods: First, MCsquare was validated using tissue-mimicking IROC lung phantom measurements as well as benchmarked with the general purpose Monte Carlo TOPAS for patient dose calculation. Then a comparative analysis between MCsquare and ADC was performed for a total of 50 patients with 10 patients per site (including liver, pelvis, brain, head-and-neck, and lung). Differences among TOPAS, MCsquare, and ADC were evaluated using four dosimetric indices based on the dose-volume histogram (target Dmean, D95, homogeneity index, V95), a 3D gamma index analysis (using 3%/3 mm criteria), and estimations of tumor control probability (TCP). Results: Comparison between MCsquare and TOPAS showed less than 1.8% difference for all of the dosimetric indices/TCP values and resulted in a 3D gamma index passing rate for voxels within the target in excess of 99%. When comparing ADC and MCsquare, the variances of all the indices were found to increase as the degree of tissue heterogeneity increased. In the case of lung, the D95s for ADC were found to differ by as much as 6.5% from the corresponding MCsquare statistic. The median gamma index passing rate for voxels within the target volume decreased from 99.3% for liver to 75.8% for lung. Resulting TCP differences can be large for lung (≤10.5%) and head-and-neck (≤6.2%), while smaller for brain, pelvis and liver (≤1.5%). Conclusions: Given the differences found in the analysis, accurate dose calculation algorithms such as Monte Carlo simulations are needed for proton therapy, especially for disease sites with high heterogeneity, such as head-and-neck and lung. The establishment of MCsquare can facilitate patient plan reviews at any institution and can potentially provide unbiased comparison in clinical trials given its accuracy, speed and open-source availability. © 2018 American Association of Physicists in Medicine

Purpose: The purpose of this paper is to demonstrate the utility of a comprehensive test pattern in validating calculation models that include the halo component (low-dose tails) of proton pencil beam scanning (PBS) spots. Such a pattern has been used previously for quality assurance purposes to assess spot shape, position, and dose. Methods: In this study, a scintillation detector was used to measure the test pattern in air at isocenter for two proton beam energies (115 and 225 MeV) of two IBA universal nozzles (UN #1 and UN #2). Planar measurements were compared with calculated dose distributions based on the weighted superposition of location-independent (UN #1) or location-dependent (UN #2) spot profiles, previously measured using a pair-magnification method and between two nozzles. Results: Including the halo component below 1% of the central dose is shown to improve the gamma-map comparison between calculation and measurement from 94.9% to 98.4% using 2 mm/2% criteria for the 115 MeV proton beam of UN #1. In contrast, including the halo component below 1% of the central dose does not improve the gamma agreement for the 115 MeV proton beam of UN #2, due to the cutoff of the halo component at off-axis locations. When location-dependent spot profiles are used for calculation instead of spot profiles at central axis, the gamma agreement is improved from 98.0% to 99.5% using 2 mm/2% criteria. The two nozzles clearly have different characteristics, as a direct comparison of measured data shows a passing rate of 89.7% for the 115 MeV proton beam. At 225 MeV, the corresponding gamma comparisons agree better between measurement and calculation, and between measurements in the two nozzles. Conclusions: In addition to confirming the primary component of individual PBS spot profiles, a comprehensive test pattern is useful for the validation of the halo component at off-axis locations, especially for low energy protons.

The need to accurately and efficiently verify both output and dose profiles creates significant challenges in quality assurance of pencil beam scanning (PBS) proton delivery. A system for PBS QA has been developed that combines a new two-dimensional ionization chamber array in a waterproof housing that is scanned in a water phantom. The MatriXX PT has the same detector array arrangement as the standard math formula but utilizes a smaller 2 mm plate spacing instead of 5 mm. Because the bias voltage of the MatriXX PT and Evolution cannot be changed, PPC40 and FC65-G ionization chambers were used to assess recombination effects. The PPC40 is a parallel plate chamber with an electrode spacing of 2 mm, while the FC65-G is a Farmer chamber FC65-G with an electrode spacing of 2.8 mm. Three bias voltages (500, 200, and 100 V) were used for both detectors to determine which radiation type (continuous, pulse or pulse-scanned beam) could closely estimate math formula from the ratios of charges collected. In comparison with the math formula, a significant improvement in measurement of absolute dose with the MatriXX PT was observed. While dose uncertainty of the math formula can be up to 4%, it is math formula for the MatriXX PT. Therefore the math formula should not be used for QA of PBS for conditions in which ion recombination is not negligible. Farmer chambers should be used with caution for measuring the absolute dose of PBS beams, as the uncertainty of math formula can be math formula; chambers with an electrode spacing of 2 mm or smaller are recommended. PACS number: 87.53.Qc OA gold

This analysis was designed to compare dosimetric parameters among different fixed-field intensity-modulated radiation therapy (IMRT) solutions and volumetric-modulated arc therapy (VMAT) to identify which can achieve the lowest risk of organs at risk (OARs) and treatment delivery efficiently. A total of 16 patients (8 male and 8 female) with early-stage primary mediastinal large B-cell lymphoma (PMBCL) were enrolled with planned gross tumor volume (PGTV) 45 Gy and planning target volume (PTV) 40 Gy. Four different plans were generated: 5-, 7, 9-field IMRT, and VMAT. The dose distributions for PGTV and PTV OARs (lungs, left ventricle, heart, thyroid gland, and breasts) were compared. The monitor units (MUs) and treatment delivery time were also evaluated. Mean conformity index (CI) and homogeneity index (HI) for PGTV in 5F-, 7F-, 9F-IMRT, and VMAT were 1.01 and 1.10, 1.01 and 1.10, 1.01 and 1.10, and 1.01 and 1.11 ( p = 0.963 and 0.843), whereas these 2 indices for PTV were 1.04 and 1.22, 1.03 and 1.19, 1.03 and 1.17, and 1.08 and 1.14 ( p = 0.964 and 0.969), respectively. D mean (Gy), V4 (%), D50 (Gy), and D80 (Gy) to the left and right breasts increased by 0.7 Gy and 0.1 Gy, 6.8% and 7.7%, 0.9 Gy and 1.7 Gy, and 1.0 Gy and 1.5 Gy in VMAT, respectively. The 9-beam IMRT plan had the highest MUs (25,762.4 MUs) and the longest treatment delivery time (10.7 minutes); whereas, the VMAT had the lowest MUs (13,345.0) and the shortest treatment delivery time (5.9 minutes). Seven- and 9-field IMRT and VMAT provide improved tumor coverage compared with 5F-IMRT, whereas VMAT shows higher treatment delivery efficiency than IMRT technique. Seven- and 9-field IMRT slightly reduce the low dose radiation exposure of breasts compared with VMAT technique. The 7- and 9-field IMRT and VMAT techniques both can be safely and efficiently delivered to patients with PMBCL.

Background The importance of the thoracic radiation therapy (TRT) dose has not been clearly defined in extensive stage small-cell lung cancer (ES-SCLC) and it is unclear whether improved TRT dose translates into a survival benefit. Methods 306 patients with ES-SCLC were retrospectively reviewed, of which 170 received IMRT/CRT fractionation RT after ChT, and 136 received chemotherapy (ChT) alone. We adopted the time-adjusted BED (tBED) for effective dose fractionation calculation. Due to the nonrandomized nature of this study, we compared the ChT + RT with ChT groups that matched on possible confounding variables. Results Patients achieved 2-year OS, PFS and LC rates of 19.7%, 10.7% and 28.4%, respectively. After propensity score matching, (113 cases for each group), the rates of OS, PFS and LC at 2 years were 21.4%, 7.7% and 34.5% for ChT + TRT, and 10.3% ( p 0.001 ), 4.6% ( p 0.001 ) and 6.3% for ChT only ( p 0.001 ), respectively. Among propensity score matching patients, 56 cases for each group received the high dose (tBED > 50 Gy) TRT and received low dose (tBED ≤ 50 Gy) TRT. Two-year OS, PFS and LC rates were 32.3%, 15.3% and 47.1% for the high dose compared with 17.0% ( p p = 0.097) and 34.7% ( p = 0.029) for low dose radiotherapy. Conclusions TRT added to ChT improved ES-SCLC patient OS. High dose TRT improved OS over lower doses. Our results suggest that high-dose thoracic radiation therapy may be a reasonable consideration in select patients with ES-SCLC.

There has been no previous study on the efficacy of the thoracic radiotherapy (TRT) in oligometastatic or polymetastatic extensive stage small-cell lung cancer (ES-SCLC) to the overall survival (OS). In a group of 270 ES-SCLC cases retrospective study, 78 patients (28.9%) had oligometastases and 192 (71.1%) had polymetastases, among which 51 oligometastatic patients (65.4%) and 93 polymetastatic patients (51.6%) received TRT. Propensity score matching (PSM) was utilized. The 2-year OS, progression free survival (PFS) and local control (LC) in oligometastatic and polymetastatic patients were 22.8% and 4.5% (p

The presence of a low-dose envelope, or 'halo', in the fluence profile of a proton spot can increase the output of a pencil beam scanning field by over 10%. This study evaluated whether the Monte Carlo simulation code, TOPAS 1.0-beta 8, based on Geant4.9.6 with its default physics list, can predict the spot halo at depth in phantom by incorporating a halo model within the proton source distribution. Proton sources were modelled using three 2D Gaussian functions, and optimized until simulated spot profiles matched measurements at the phantom surface out to a radius of 100 mm. Simulations were subsequently compared with profiles measured using EBT3 film in Solidwater® phantoms at various depths for 100, 115, 150, 180, 210 and 225 MeV proton beams. Simulations predict measured profiles within a 1 mm distance to agreement for 2D profiles extending to the 0.1% isodose, and within 1 mm/1% Gamma criteria over the integrated curve of spot profile as a function of radius. For isodose lines beyond 0.1% of the central spot dose, the simulated primary spot sigma is smaller than the measurement by up to 15%, and can differ by over 1 mm. The choice of particle interaction algorithm and phantom material were found to cause ~1 mm range uncertainty, a maximal 5% (0.3 mm) difference in spot sigma, and maximal 1 mm and ~2 mm distance to agreement in isodoses above and below the 0.1% level, respectively. Based on these observations, therefore, the selection of physics model and the application of Solidwater® as water replacement material in simulation and measurement should be used with caution.

As an injector for the Separated Function RFQ (SFRFQ) accelerator, the Integral Split Ring Radio Frequency Quadrupole (ISR RFQ) accelerator was upgraded to achieve a higher beam current. The experiments on the RFQ accelerator indicated that the maximum accelerated O+ beam current could exceed 3.2 mA with an energy of 1.03 MeV and energy spread (FWHM) of 3.1%. The resultant beam is then transported through a 1-m-long magnetic triplet and finally accelerated to 1.654 MeV by the SFRFQ cavity. The beam conditions of the RFQ accelerator were carefully optimized to satisfy the requirements of the SFRFQ accelerator, and the combined accelerator was able to deliver 0.53 mA of O+ beam to the end of the beam line, which has sufficiently demonstrated the feasibility of the SFRFQ cavity.

AcurosPT is a Monte Carlo algorithm in the Eclipse 13.7 treatment planning system, which is designed to provide rapid and accurate dose calculations for proton therapy. Computational run‐time in minimized by simplifying or eliminating less significant physics processes. In this article, the accuracy of AcurosPT was benchmarked against both measurement and an independent MC calculation, TOPAS. Such a method can be applied to any new MC calculation for the detection of potential inaccuracies. To validate multiple Coulomb scattering (MCS) which affects primary beam broadening, single spot profiles in a Solidwater® phantom were compared for beams of five selected proton energies between AcurosPT, measurement and TOPAS. The spot Gaussian sigma in AcurosPT was found to increase faster with depth than both measurement and TOPAS, suggesting that the MCS algorithm in AcurosPT overestimates the scattering effect. To validate AcurosPT modeling of the halo component beyond primary beam broadening, field size factors (FSF) were compared for multi‐spot profiles measured in a water phantom. The FSF for small field sizes were found to disagree with measurement, with the disagreement increasing with depth. Conversely, TOPAS simulations of the same FSF consistently agreed with measurement to within 1.5%. The disagreement in absolute dose between AcurosPT and measurement was smaller than 2% at the mid‐range depth of multi‐energy beams. While AcurosPT calculates acceptable dose distributions for typical clinical beams, users are cautioned of potentially larger errors at distal depths due to overestimated MCS and halo implementation.

Separated Function Radio Frequency Quadrupole (SFRFQ) accelerator is a new structure where diaphragms are loaded onto the quadrupole electrodes to form accelerating gaps, while the unmodulated RF quadrupole electric field provides transverse focusing. SFRFQ promises a higher accelerating efficiency than the conventional RFQ for heavy ions at low frequencies. In order to reduce reverse field and avoid RF sparking, an asymmetrical electrode and diaphragms designs were adopted. After simulation and RF design, a full scale SFRFQ prototype cavity with 14 βλ /2 cells has been constructed as a post-accelerator of the Peking University Integral Split Ring (ISR) RFQ. Beam commissioning was carried out to verify its feasibility. It accelerates O + beam from 64 to 103 keV/ u with a beam current exceeding 0.53 mA and the experimental results agree well with the simulation predictions by SFRFQCODEV1.0 [Z. Wang, J.E. Chen, Y.R. Lu, et al., Nucl. Instr. and Meth. A, 572, (2007) 596].