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Side effects of proton therapy are poorly studied. Moreover, the differences in the method of dose delivery on normal tissues are not taken into account when proton beams are scanned instead of being scattered. We proposed here to study the effects of both modalities of proton beam delivery on blood; skin; lung and heart in a murine model. In that purpose; C57BL/6 mice were total body irradiated by 190.6 MeV proton beams either by Double Scattering (DS) or by Pencil Beam Scanning (PBS) in the plateau phase before the Bragg Peak. Mouse survival was evaluated. Blood and organs were removed three months after irradiation. Biomarkers of genotoxicity; oxidative stress and inflammation were measured. Proton irradiation was shown to increase lymphocyte micronucleus frequency; lung superoxide dismutase activity; erythrocyte and skin glutathione peroxidase activity; erythrocyte catalase activity; lung; heart and skin oxidized glutathione level; erythrocyte and lung lipid peroxidation and erythrocyte protein carbonylation even 3 months post-irradiation. When comparing both methods of proton beam delivery; mouse survival was not different. However, PBS significantly increased lymphocyte micronucleus frequency; erythrocyte glutathione peroxidase activity and heart oxidized glutathione level compared to DS. These results point out the necessity to take into account the way of delivering dose in PT as it could influence late side effects.

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., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to disclose., (©Copyright 2023 The Author(s).)

Purpose: Fast energy switching is of fundamental importance to implement motion mitigation techniques in pencil beam scanning proton therapy, allowing efficient irradiation and high patient throughput. However, depending on magnet design, when switching between different energy layers, eddy currents arise in the bending magnets' yoke, damping the speed of the magnetic field change and lengthening the settling time of the magnetic field. In a proton therapy gantry, this can cause a temporary displacement of the beam trajectory and consequently an incorrect beam position in the bending direction, resulting in an unacceptable loss of position precision at isocenter. The precision can be recovered by either increasing the beam off time after an energy change (waiting until the magnetic field is fully settled) or by actively correcting for the misplacement. We studied the transient magnetic field effects at PSI Gantry 2 in order to develop a correction strategy for this beam position misplacement. Methods: We used position and proton range sensitive detectors (segmented strip chamber and multilayer ionization chambers respectively) to measure the difference between expected and actual proton beam position and range as a function of time. The detectors are automatically triggered, read out, and analyzed by the treatment control system. We studied the effects due to the magnets on the gantry and those upstream of the gantry separately, in order to identify which elements contribute the most to the beam position instability. We then designed a spot position algorithm to be applied with the gantry scanning magnets, to correct for the displacement observed as a function of time and achieve the PSI Gantry 2 clinical target of 1 mm precision at isocenter at all times, even after an energy change. Results: When switching energy layers in a field, we observed an exponentially decaying spot position displacement at isocenter. The effect increases with increasing energy difference between energy layers (ΔE). The initial residuals between expected and measured position are higher than 1 mm for most of the clinical cases at Gantry 2 and fall below 1 mm within about 1 s or more (depending on ΔE). We found no time dependence for the proton range, thus confirming that the displacement is purely due to a beam trajectory displacement resulting from the longer settling time of the magnetic field. A double exponential model, with two time constants and amplitudes depending on ΔE, fits the data and provides an easy model for the correction function. We implemented this correction as a spot position correction, applied by the scanning magnets during field application. After correction, the residuals were below 0.5 mm right after the energy change. Conclusions: We developed a spot position correction for PSI Gantry 2 which reduces the beam off time needed in current state‐of‐the‐art gantries to settle the magnetic fields in the bending magnets. Thanks to this correction, the spot position is stable within 100 ms of an energy change at Gantry 2. This is low enough to make possible efficient use of motion mitigation techniques. [ABSTRACT FROM AUTHOR]

Purpose: Fabricate an acrylic disk radiation sensor (ADRS) and characterize the photoluminescence signal generated from the optical device as basis for the development and evaluation of a new dosimetry system for pencil beam proton therapy. Methods: Based on the characteristics of the proposed optical dosimetry sensor, we established the relation between the photoluminescence output and the applied dose using an ionization chamber. Then, we obtained the relative integral depth dose profiles using the photoluminescence signal generated by pencil beam irradiation at energies of 99.9 and 162.1 MeV, and compared the results with the curve measured using a Bragg peak ionization chamber. Results: The relation between the photoluminescence output and applied dose was linear. In addition, the ADRS was dose independent for beam currents up to 6 Gy/min, and the calibration factor for energy was close to 1. Hence, the energy dependence on the optical device can be disregarded. The integral depth dose profiles obtained for the ADRS suitable agreed with the curve measured in the Bragg peak ionization chamber without requiring correction. Conclusions: These results suggest that the ADRS is suitable for dosimetry measurements in pencil beam scanning, and it will be employed as a low‐cost and versatile dosimetry sensor in upcoming developments. [ABSTRACT FROM AUTHOR]

Purpose Proton therapy for the treatment of breast cancer is acquiring increasing interest, due to the potential reduction of radiation-induced side effects such as cardiac and pulmonary toxicity. While several in silico studies demonstrated the gain in plan quality offered by pencil beam scanning (PBS) compared to passive scattering techniques, the related dosimetric uncertainties have been poorly investigated so far. Methods Five breast cancer patients were planned with Raystation 6 analytical pencil beam (APB) and Monte Carlo (MC) dose calculation algorithms. Plans were optimized with APB and then MC was used to recalculate dose distribution. Movable snout and beam splitting techniques (i.e. using two sub-fields for the same beam entrance, one with and the other without the use of a range shifter) were considered. PTV dose statistics were recorded. The same planning configurations were adopted for the experimental benchmark. Dose distributions were measured with a 2D array of ionization chambers and compared to APB and MC calculated ones by means of a γ analysis (agreement criteria 3%, 3 mm). Results Our results indicate that, when using proton PBS for breast cancer treatment, the Raystation 6 APB algorithm does not allow obtaining sufficient accuracy, especially with large air gaps. On the contrary, the MC algorithm resulted into much higher accuracy in all beam configurations tested and has to be recommended. Conclusions Centers where a MC algorithm is not yet available should consider a careful use of APB, possibly combined with a movable snout system or in any case with strategies aimed at minimizing air gaps. [ABSTRACT FROM AUTHOR]

Purpose: GRID therapy is an effective treatment for bulky tumors. Linear accelerator (Linac)‐produced photon beams collimated through blocks or multileaf collimators (MLCs) are the most common methods used to deliver this therapy. Utilizing the newest proton delivery method of pencil beam scanning (PBS) can further improve the efficacy of GRID therapy. In this study, we developed a method of delivering GRID therapy using proton PBS, evaluated the dosimetry of this novel technique and applied this method in two clinical cases. Materials/Methods: In the feasibility study phase, a single PBS proton beam was optimized to heterogeneously irradiate a shallow 20 × 20 × 12 cm3 target volume centered at a 6 cm depth in a water phantom. The beam was constrained to have an identical spot pattern in all layers, creating a “beamlet” at each spot position. Another GRID treatment using PBS was also performed on a deep 15 × 15 × 8 cm3 target volume centered at a 14 cm depth in a water phantom. Dosimetric parameters of both PBS dose distributions were compared with typical photon GRID dose distributions. In the next phase, four patients have been treated at our center with this proton GRID technique. The planning, dosimetry, and measurements for two representative patients are reported. Results: For the shallow phantom target, the depth–dose curve of the PBS plan was uniform within the target (variation < 5%) and dropped quickly beyond the target (50% at 12.9 cm and 0.5% at 14 cm). The lateral profiles of the PBS plan were comparable to those of photon GRID in terms of valley‐to‐peak ratios. For the deep phantom target, the PBS plan provided smaller valley‐to‐peak ratios than the photon GRID technique. Pretreatment dose verification QA showed close agreement between the measurements and the plan (pass rate > 95% with a gamma index criterion of 3%/3 mm). Patients tolerated the treatment well without significant skin toxicity (radiation dermatitis grade ≤ 1). Conclusions: Proton GRID therapy using a PBS delivery method was successfully developed and implemented clinically. Proton GRID therapy offers many advantages over photon GRID techniques. The use of protons provides a more uniform beamlet dose within the tumor and spares normal tissues located beyond the tumor. This new PBS method will also reduce the dose to proximal organs when treating a deep‐seated tumor. [ABSTRACT FROM AUTHOR]

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

Background: Spot size σ (in air at isocenter), interspot spacing d, and spot charge q influence dose delivery efficiency and plan quality in Intensity Modulated Proton Therapy (IMPT) treatment planning. The choice and range of parameters varies among different manufacturers. The goal of this work is to demonstrate the influence of the spot parameters on dose quality and delivery in IMPT treatment plans, to show their interdependence, and to make practitioners aware of the spot parameter values for a certain facility. Our study could help as a guideline to make the trade‐off between treatment quality and time in existing PBS centers and in future systems. Methods: We created plans for seven patients and a phantom, with different tumor sites and volumes, and compared the effect of small‐, medium‐, and large‐spot widths (σ = 2.5, 5, and 10 mm) and interspot distances (1σ, 1.5σ, and 1.75σ) on dose, spot charge, and treatment time. Moreover, we quantified how postplanning charge threshold cuts affect plan quality and the total number of spots to deliver, for different spot widths and interspot distances. We show the effect of a minimum charge (or MU) cutoff value for a given proton delivery system. Results: Spot size had a strong influence on dose: larger spots resulted in more protons delivered outside the target region. We observed dose differences of 2–13 Gy (RBE) between 2.5 mm and 10 mm spots, where the amount of extra dose was due to dose penumbra around the target region. Interspot distance had little influence on dose quality for our patient group. Both parameters strongly influence spot charge in the plans and thus the possible impact of postplanning charge threshold cuts. If such charge thresholds are not included in the treatment planning system (TPS), it is important that the practitioner validates that a given combination of lower charge threshold, interspot spacing, and spot size does not result in a plan degradation. Low average spot charge occurs for small spots, small interspot distances, many beam directions, and low fractional dose values. Conclusions: The choice of spot parameters values is a trade‐off between accelerator and beam line design, plan quality, and treatment efficiency. We recommend the use of small spot sizes for better organ‐at‐risk sparing and lateral interspot distances of 1.5σ to avoid long treatment times. We note that plan quality is influenced by the charge cutoff. Our results show that the charge cutoff can be sufficiently large (i.e., 106 protons) to accommodate limitations on beam delivery systems. It is, therefore, not necessary per se to include the charge cutoff in the treatment planning optimization such that Pareto navigation (e.g., as practiced at our institution) is not excluded and optimal plans can be obtained without, perhaps, a bias from the charge cutoff. We recommend that the impact of a minimum charge cut impact is carefully verified for the spot sizes and spot distances applied or that it is accommodated in the TPS. [ABSTRACT FROM AUTHOR]

This study describes the development of a beam monitoring system for the verification of entrance dose map in pencil beam scanning (PBS) proton therapy based on fiber optic radiation sensors (FORS) and the validation of this system through a feasibility study. The beam monitoring system consisted of 128 optical fibers optically coupled to photo-multiplier tubes. The performance of the beam monitoring system based on FORS was verified by comparing 2D dose maps of square-shaped fields of various sizes, which were obtained using conventional dosimeters such as MatriXX and EBT3 film, with those measured using FORS. The resulting full-width at half maximum and penumbra were compared for PBS proton beams, with a ≤2% difference between each value, indicating that measurements using the conventional dosimetric tool corresponded to measurements based on FORS. For irregularly-shaped fields, a comparison based on the gamma index between 2D dose maps obtained using MatriXX and EBT3 film and the 2D dose map measured by the FORS showed passing rates of 96.9 ± 1.3% and 96.2 ± 1.9%, respectively, confirming that FORS-based measurements for PBS proton therapy agreed well with those measured using the conventional dosimetric tools. These results demonstrate that the developed beam monitoring system based on FORS is good candidate for monitoring the entrance dose map in PBS proton therapy. [ABSTRACT FROM AUTHOR]

A mini-ridge filter is often used to widen the Bragg peak in the longitudinal direction at low energies but not high energies. To facilitate the clinical use of a mini-ridge filter, we performed a planning study for the feasibility of a mini-ridge filter as an integral part of the synchrotron nozzle (IMRF). Dose models with and without IMRF were commissioned in a commercial Treatment planning system (TPS). Dosimetric characteristics in a homogenous water phantom were compared between plans with and without IMRF for a fixed spread-out Bragg peak width of 4 cm with distal ranges varying from 8 to 30 g/cm². Six clinical cases were then used to compare the plan quality between plans. The delivery efficiency was also compared between plans in both the phantom and the clinical cases. The Bragg peak width was increased by 0.18 cm at the lowest energy and by only about 0.04 cm at the highest energy. The IMRF increased the spot size (σ) by up to 0.1 cm at the lowest energy and by only 0.02 cm at the highest energy. For the phantom, the IMRF negligibly affected dose at high energies but increased the lateral penumbra by up to 0.12 cm and the distal penumbra by up to 0.06 cm at low energies. For the clinical cases, the IMRF slightly increased dose to the organs at risk. However, the beam delivery time was reduced from 18.5% to 47.1% for the lung, brain, scalp, and head and neck cases, and dose uniformities of target were improved up to 2.9% for these cases owing to the reduced minimum monitor unit effect. In conclusion, integrating a mini-ridge filter into a synchrotron nozzle is feasible for improving treatment efficiency without significantly sacrificing the plan quality. [ABSTRACT FROM AUTHOR]

A color scintillation detector for relative dose distribution measurement was developed at PSI. The system consists of a gadolinium-based scintillating screen mounted perpendicularly to the beam axis and coupled with a color CMOS camera in a light-tight box. The camera is equipped with an iris (aperture) controller to remotely adjust the number of photons reaching the image sensor. To improve the measurement accuracy and decrease the image artifacts, we investigated different methods for spatial calibration and optimized the internal light reflection by adjusting the detector structure. The response dependence on camera working distance, iris setting, and color channels was assessed. The depth-dose curves of the gadolinium-based scintillator in three RGB channels were compared with reference curves measured by an Advanced Markus plane-parallel ion chamber. The quenching effect of the ▪ screen measured with this system amounts to about 10% in the Bragg peak region of a 150 MeV proton beams. The shape of the emission spectrum was observed to be independent of the ionization density. Preliminary investigations showed that it is possible to correlate the ratio of the detector response in different color channels with the proton ionization density. • A color scintillation detector was developed and characterized in clinical proton beams. • Two methods for spatial calibration were evaluated and results benchmarked against a commercial detector. • The developed detector can be used to evaluate the quenching of different scintillating probes in RGB channels. • Preliminary investigation on the possibility to correlate the color response to the residual proton energy. [ABSTRACT FROM AUTHOR]

In the last few years, the use of ions in radiation therapy is gaining interest and it is being considered medically necessary for a growing subset of tumours. Concurrently, the technologies involved in a particle therapy treatment are rapidly evolving, as well as the accuracy in the dose delivery in spite of the increased complexity. Since nowadays, the pencil beam scanning technique is showing very interesting features in terms of dose conformation and overall treatment outcome, the present review is intended to summarize the main procedures, detectors and tools adopted for the clinical dose verification. A list of dose measurements is provided, with the aim of being a valuable guidance for starting and future particle therapy facilities. Absorbed dose to water, relative dose, fluence and surrogates of the delivered dose are the main quantities measured by means of different detectors, specifically developed for point-like, 1D or 2D measurements. The dosimetric procedures are here categorized according to their purpose, distinguishing between system commissioning and clinical quality assurance. A separate discussion is dedicated to patient specific, in vivo and 4D dose verification, which aim at assessing the actual delivered dose. Together with the description of the currently used methods, challenges and perspectives toward an increasingly accurate and fast dose verification strategy are discussed. [ABSTRACT FROM AUTHOR]

Purpose The IAEA TRS-398 code of practice details the reference conditions for reference dosimetry of proton beams using ionization chambers and the required beam quality correction factors (kQ). Pencil beam scanning ( PBS) systems cannot approximate reference conditions using a single spot. However, dose distributions requested in TRS-398 can be reproduced with PBS using a combination of spots. This study aims to demonstrate, using Monte Carlo ( MC) simulations, that kQ factors computed/measured for broad beams can be used with scanned beams for similar reference dose distributions with no additional significant uncertainty. Methods We consider the Alfonso formalism13 usually employed for nonstandard photon beams. To approach reference conditions similar as IAEA TRS-398 and the associated dose distributions, PBS must combine many pencil beams with range or energy modulation and shaping techniques that differ from those used in passive systems (broad beams). In order to evaluate the impact of these differences on kQ factors, ionization chamber responses are computed with MC (Geant4 9.6) in three different proton beams, with their corresponding quality factors (Q), producing a 10 × 10 cm2 field with a flat dose distribution for (a) a dedicated scanned pencil beam (Qpbs), (b) a hypothetical proton source (Qhyp), and (c) a double-scattering beam (Qds). The tested ionization chamber cavities are a 2 × 2 × 0.2 mm³ air cavity, a Roos-type ionization chamber, and a Farmer-type ionization chamber. Results and Discussion Ranges of Qpbs, Qhyp, and Qds are consistent within 0.4 mm. Flatnesses of dose distributions are better than 0.5%. Calculated [ABSTRACT FROM AUTHOR]

A ridge filter (RGF), a beam energy modulation device, is usually used for particle radiotherapy with a pencil beam scanning system. The conventional RGF has a one-dimensional (1D) periodic laterally stepped structure in orthogonal plane with a central beam direction. The energy of a beam passing through the different thicknesses of the stepped RGF is modulated. Although the lateral pencil beam size is required to cover the several stepped RGF units to modulate its energy as designed, the current trend is to decrease lateral beam size to improve the scanning system. As a result, the beam size becomes smaller than the size of the individual RGF unit. The aim of this study was to develop a new RGF with two-dimensional (2D) honeycomb geometry to simultaneously achieve both a decrease in lateral beam size and the desired energy modulation. The conventional 1D-RGF and the 2D-RGF with honeycomb geometry were both designed so that the Bragg peak size of a 79 MeV/u carbon ion pencil beam in water was 1 mm RMS in the beam direction. To validate the design of the 2D-RGF, we calculated depth dose distributions in water using a simplified Monte Carlo method. In the calculations, we decreased the lateral pencil beam size at the entrance of the RGF and investigated the threshold of lateral beam size with which the pencil beam can reproduce the desired Bragg peak size for each type of RGF. In addition, we calculated lateral dose distributions in air downstream from the RGF and evaluated the inhomogeneity of the lateral dose distributions. Using the 2D-RGF, the threshold of lateral beam size with which the pencil beam can reproduce the desired Bragg peak size was smaller than that using the 1D-RGF. Moreover, the distance from the RGF at which the lateral dose distribution becomes uniform was shorter using the 2D-RGF than that using the 1D-RGF. These results indicate that when the periodic length of both RGFs is the same, the 2D-RGF allows use of a pencil beam with smaller lateral beam size and a shorter distance from the RGF to the target, resulting in improvement in the conformity of dose distribution in a tumor. [ABSTRACT FROM AUTHOR]

In a radiotherapy center, daily quality assurance (QA) measurements are performed to ensure that the equipment can be safely used for patient treatment on that day. In a pencil beam scanning (PBS) proton therapy center, spot positioning, spot size, range, and dose output are usually verified every day before treatments. We designed, built, and tested a new, reliable, sensitive, and inexpensive phantom, coupled with an array of ionization chambers, for daily QA that reduces the execution times while preserving the reliability of the test. The phantom is provided with 2 pairs of wedges to sample the Bragg peak at different depths to have a transposition on the transverse plane of the depth dose. Three “boxes” are used to check spot positioning and delivered dose. The box thickness helps spread the single spot and to fit a Gaussian profile on a low resolution detector. We tested whether our new QA solution could detect errors larger than our action levels: 1 mm in spot positioning, 2 mm in range, and 10% in spot size. Execution time was also investigated. Our method is able to correctly detect 98% of spots that are actually in tolerance for spot positioning and 99% of spots out of 1 mm tolerance. All range variations greater than the threshold (2 mm) were correctly detected. The analysis performed over 1 month showed a very good repeatability of spot characteristics. The time taken to perform the daily quality assurance is 20 minutes, a half of the execution time of the former multidevice procedure. This “in-house build” phantom substitutes 2 very expensive detectors (a multilayer ionization chamber [MLIC] and a strip chamber, reducing by 5 times the cost of the equipment. We designed, built, and validated a phantom that allows for accurate, sensitive, fast, and inexpensive daily QA procedures in proton therapy with PBS. [ABSTRACT FROM AUTHOR]

Background We performed a survey using the modified EORTC Facility questionnaire (pFQ) to evaluate the human, technical and organizational resources of particle centers in Europe. Material and methods The modified pFQ consisted of 235 questions distributed in 11 sections accessible on line on an EORTC server. Fifteen centers from 8 countries completed the pFQ between May 2015 and December 2015. Results The average number of patients treated per year and per particle center was 221 (range, 40–557). The majority (66.7%) of centers had pencil beam or raster scanning capability. Four (27%) centers were dedicated to eye treatment only. An increase in the patients-health professional FTE ratio was observed for eye tumor only centers when compared to other centers. All centers treated routinely chordomas/chondrosarcomas, brain tumors and sarcomas but rarely breast cancer. The majority of centers treated pediatric cases with particles. Only a minority of the queried institutions treated non-static targets. Conclusions As the number of particle centers coming online will increase, the experience with this treatment modality will rise in Europe. Children can currently be treated in these facilities in a majority of cases. The majority of these centers provide state of the art particle beam therapy. [ABSTRACT FROM AUTHOR]

Purpose Proton therapy with Pencil Beam Scanning (PBS) has the potential to improve radiotherapy treatments. Unfortunately, its promises are jeopardized by the sensitivity of the dose distributions to uncertainties, including dose calculation accuracy in inhomogeneous media. Monte Carlo dose engines (MC) are expected to handle heterogeneities better than analytical algorithms like the pencil-beam convolution algorithm (PBA). In this study, an experimental phantom has been devised to maximize the effect of heterogeneities and to quantify the capability of several dose engines (MC and PBA) to handle these. Methods An inhomogeneous phantom made of water surrounding a long insert of bone tissue substitute (1 × 10 × 10 cm 3 ) was irradiated with a mono-energetic PBS field (10 × 10 cm 2 ). A 2D ion chamber array (MatriXX, IBA Dosimetry GmbH) lied right behind the bone. The beam energy was such that the expected range of the protons exceeded the detector position in water and did not attain it in bone. The measurement was compared to the following engines: Geant4.9.5, PENH, MCsquare, as well as the MC and PBA algorithms of RayStation (RaySearch Laboratories AB). Results For a γ-index criteria of 2%/2 mm, the passing rates are 93.8% for Geant4.9.5, 97.4% for PENH, 93.4% for MCsquare, 95.9% for RayStation MC, and 44.7% for PBA. The differences in γ-index passing rates between MC and RayStation PBA calculations can exceed 50%. Conclusion The performance of dose calculation algorithms in highly inhomogeneous media was evaluated in a dedicated experiment. MC dose engines performed overall satisfactorily while large deviations were observed with PBA as expected. [ABSTRACT FROM AUTHOR]

Introduction. Because the specific proton beam dose distribution (i.e. the so-called 'Bragg curve’), proton radiotherapy ensures that the high-dose region is precisely confined to the target volume while minimizing the dose delivered to healthy tissues/critical organs surrounding the tumour or to those lying in the path of the proton beam. This method has been used for patients in Kraków since November 2016. Aim. To report the early tolerance outcomes to proton radiotherapy in patients completing their treatment just before the end of August 2017. Materials and methods. Study subjects were 47 patients who had completed their treatment before the end of August 2017 with a mean age of 41.6 years (range: 16-76, median: 40). The most frequent diagnoses were skull base tumours (22 pts. — 46.8%) and brain G1 or G2 gliomas (17 pts. — 36.2%), whereas the most frequent histological types were chordomas (17 pts. — 36.2%). Proton radiotherapy was administered by pencil beam scanning and consisted of using the intensity modulated proton therapy (IMPT) technique. The total dose given per cancer type averaged as follows: (i) 70 and 74 Gy(RBE), for respectively chodrosarcomas and chordomas, (ii) 54 Gy(RBE) for brain gliomas and (iii) 70 Gy(RBE) for paranasal sinuses tumours. Early tolerance was prospectively evaluated and measured according to the CTCAE scale, version 4.03. Results. In all, 91 side effects (SE) were recorded in 44 patients. The intensity of SEs were as following: 62 SEs (68.1%) were of grade 1 intensity, 21 SEs (23.1%) were of grade 2 and 8 SEs (8.8%) were of grade 3. The most frequently developed SEs were skin reactions (29 pts. — 61.7%) or oral/pharyngeal mucositis (20 pts. — 42.6%). Because the patient follow-up period was short, presented results only describes the early tolerance to this therapy. Our findings of mild intensities for the most early side effects, at (grades 1 or 2) are consistent with other published studies. [ABSTRACT FROM AUTHOR]

Background and purpose Systematic investigation of the energy and angular dependence of secondary neutron fluence energy distributions and ambient dose equivalents values (H*(10)) inside a pencil beam scanning proton therapy treatment room using a gantry. Materials and methods Neutron fluence energy distributions were measured with an extended-range Bonner sphere spectrometer featuring ³He proportional counters, at four positions at 0°, 45°, 90°, and 135° with respect to beam direction and at a distance of 2 m from the isocenter. The energy distribution of secondary neutrons was investigated for initial proton beam energies of 75 MeV, 140 MeV, and 200 MeV, respectively, using a 2D scanned irradiation field of 11 × 11 cm² delivered to a 30 × 30 × 30 cm³ PMMA phantom. Additional measurements were performed at a proton energy of 118 MeV including a 5 cm range-shifter ( PMMA), yielding a Bragg peak position similar to that of 75 MeV protons. Results Ambient dose equivalent values from 0.3 μSv/Gy (75 MeV; 90°) to 24 μSv/Gy (200 MeV; 0°) were measured inside the treatment room at a distance of 2 m from the isocenter. H*(10) values were lower (by factors of up to 7.2 (at 45°)) at 75 MeV compared to those at 118 MeV with the 5 cm range-shifter. At 0° and 45°, an evaporation peak was found in the measured neutron fluence energy distributions, at neutron energies around MeV, which contributes about 50% to total H*(10) values, for all investigated proton beam energies. Conclusions This study showed a pronounced increase of secondary neutron H*(10) values inside the proton treatment room with increasing proton energy without beam modifiers. For example, in beam direction this increase was about a factor of 50 when protons of 75 MeV and 200 MeV were compared. The existence of a peak of secondary neutrons in the MeV region was demonstrated in beam direction (0°). This peak is due to evaporation neutrons produced in the existing surrounding materials such as those used for the gantry. Therefore, any simulation of the secondary neutrons within a proton treatment room must take these materials into account. In addition, the results obtained here show that the use of a range-shifter increases the production of secondary neutrons inside the treatment room. Using a range-shifter, the higher neutron doses observed mainly result from the higher incident proton energy (118 MeV instead of 75 MeV when no range-shifter was used), due to higher neutron production cross-sections. [ABSTRACT FROM AUTHOR]

Abstract: 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. [ABSTRACT FROM AUTHOR]

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 (4 DCT) 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 (Δ WET) 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 Δ WET80 derived from the 80th percentiles of perpendicular motion amplitude (M⊥) and Δ WET 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 4 DCT 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⊥, Δ WET, and BSPTV volumes and improved dose degradation (ΔD95 and ΔD1) within the CTV. For small motion (M⊥80 < 7 mm and Δ WET80 < 5 mm), motion mitigation was not needed. For moderate motion (M⊥80 7-10 mm or Δ WET80 5-7 mm), AC produced a modest improvement. For large motion (M⊥80 > 10 mm or Δ WET80 > 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. [ABSTRACT FROM AUTHOR]

Introduction Pencil beam scanning technique used at CNAO requires beam characteristics to be carefully assessed and periodically checked to guarantee patient safety. This study aimed at characterizing the Lynx® detector (IBA Dosimetry) for commissioning and periodic quality assurance (QA) for proton and carbon ion beams, as compared to EBT3 films, currently used for QA checks. Methods and materials The Lynx® is a 2-D high-resolution dosimetry system consisting of a scintillating screen coupled with a CCD camera, in a compact light-tight box. The scintillator was preliminarily characterized in terms of short-term stability, linearity with number of particles, image quality and response dependence on iris setting and beam current; Lynx® was then systematically tested against EBT3 films. The detector response dependence on radiation LET was also assessed. Results Preliminary results have shown that Lynx is suitable to be used for commissioning and QA checks for proton and carbon ion scanning beams; the cross-check with EBT3 films showed a good agreement between the two detectors, for both single spot and scanned field measurements. The strong LET dependence of the scintillator due to quenching effect makes Lynx® suitable only for relative 2-D dosimetry measurements. Conclusion Lynx® appears as a promising tool for commissioning and periodic QA checks for both protons and carbon ion beams. This detector can be used as an alternative of EBT3 films, allowing real-time measurements and analysis, with a significant time sparing. [ABSTRACT FROM AUTHOR]

This work tackles the commissioning and validation of a novel combination of a synchrotron-based proton beam therapy system (Hitachi, Ltd.) for use with a Monte Carlo treatment planning system (TPS). Four crucial aspects in this configuration have been investigated: (1) Monte Carlo-based correction performed by the TPS to the measured integrated depth-dose curves (IDD), (2) circular spot modelling with a single Gaussian function to characterize the synchrotron physical spot, which is elliptical, (3) the modelling of the range shifter that enables using only one set of measurements in open beams, and (4) the Monte Carlo dose calculation model in small fields. Integrated depth-dose curves were measured with a PTW Bragg peak chamber and corrected, with a Monte Carlo model, to account for energy absorbed outside the detector. The elliptical spot was measured by IBA Lynx scintillator, EBT3 films and PTW microDiamond. The accuracy of the TPS (RayStation, RaySearch Laboratories) at spot modelling with a circular Gaussian function was assessed. The beam model was validated using spread-out Bragg peak (SOBP) fields. We took single-point doses at several depths through the central axis using a PTW Farmer chamber, for fields between 2 × 2cm and 30 × 30cm. We checked the range-shifter modelling from open-beam data. We tested clinical cases with film and an ionization chamber array (IBA Matrix). Sigma differences for spots fitted using 2D images and 1D profiles to elliptical and circular Gaussian models were below 0.22 mm. Differences between SOBP measurements at single points and TPS calculations for all fields between 5 × 5 and 30 × 30cm were below 2.3%. Smaller fields had larger differences: up to 3.8% in the 2 × 2cm field. Mean differences at several depths along the central axis were generally below 1%. Differences in range-shifter doses were below 2.4%. Gamma test (3%, 3 mm) results for clinical cases were generally above 95% for Matrix and film. Approaches for modelling synchrotron proton beams have been validated. Dose values for open and range-shifter fields demonstrate accurate Monte Carlo correction for IDDs. Elliptical spots can be successfully modelled using a circular Gaussian, which is accurate for patient calculations and can be used for small fields. A double-Gaussian spot can improve small-field calculations. The range-shifter modelling approach, which reduces clinical commissioning time, is adequate. • Novel configuration: synchrotron-based proton therapy system with a Monte Carlo TPS. • The Monte Carlo-based correction applied by the TPS to the measured IDD is validated. • The single Gaussian modelling for the synchrotron physical spot is investigated. • Modelling of the range shifter with one set of measurements in open beams is checked. • The Monte Carlo dose calculation model performance in small fields is studied. [ABSTRACT FROM AUTHOR]

• Our solution converts a commercial IBA high energy scanning beamline to allow for ocular proton therapy. An ocular applicator that fits a commercial proton snout with an upstream range shifter to allow for treatments with sharp lateral penumbra is described. The validation of the ocular applicator consisted of a comparison of range, depth doses (Bragg peaks and spread out Bragg peaks), point doses, and 2-D lateral profiles. Measurements were made for three field sizes, 1.5, 2, and 3 cm, resulting in 15 beams. Distal and lateral penumbras were simulated in the treatment planning system for seven range-modulation combinations for beams typical of ocular treatments and a field size of 1.5 cm, and penumbra values were compared to published literature. All the range errors were within 0.5 mm. The maximum averaged local dose differences for Bragg peaks and SOBPs were 2.6% and 1.1%, respectively. All the 30 measured point doses were within +/-3% of the calculated. The measured lateral profiles, analyzed through gamma index analysis and compared to the simulated, had pass rates greater than 96% for all the planes. The lateral penumbra increased linearly with depth, from 1.4 mm at 1 cm depth to 2.5 mm at 4 cm depth. The distal penumbra ranged from 3.6 to 4.4 mm and increased linearly with the range. The treatment time for a single 10 Gy (RBE) fractional dose ranged from 30 to 120 s, depending on the shape and size of the target. The ocular applicator's modified design allows lateral penumbra similar to dedicated ocular beamlines while enabling planners to use modern treatment tools such as Monte Carlo and full CT-based planning with increased flexibility in beam placement. [ABSTRACT FROM AUTHOR]

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.

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., (© 2023 Institute of Physics and Engineering in Medicine.)

Background and purpose Retrospective log file-based analysis provides the actual dose delivered based on the patient's breathing and the daily beam-delivery dynamics. To predict the motion sensitivity of the treatment plan on a patient-specific basis before treatment start a prospective tool is required. Such a parameter-based tool has been investigated with the aim to be used in clinical routine. Materials and Methods 4D dose calculations (4DDC) were performed for seven cancer patients with small breathing motion treated with scanned pulsed proton beams. Validation of the parameter-based 4DDC (p-4DDC) method was performed with an anthropomorphic phantom and patient data employing measurements and a log file-based 4DDC tool. The dose volume histogram parameters ( D x % ) were investigated for the target and the organs at risk, compared to static and the file-based approach. Results The difference between the measured and the p-4DDC dose was within the deviation of the measurements. The maximum deviation was 0.4Gy. For the planning target volume D 98 % varied up to 15% compared to the static scenario, while the results from the log file and p-4DDC agreed within 2%. For the liver patients, D 33 % liver deviated up to 35% compared to static and 10% comparing the two 4DDC tools, while for the pancreas patients the D 1 % stomach varied up to 45% and 11%, respectively. Conclusion The results showed that p-4DDC could be used prospectively. The next step will be the clinical implementation of the p-4DDC tool, which can support a decision to either adapt the treatment plan or apply motion mitigation strategies., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: E.E. reports a relationship with RaySearch Laboratories AB that includes employment., (© 2023 The Author(s).)

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 cm 2 ) 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., (© 2023 American Association of Physicists in Medicine.)

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., Competing Interests: The authors declare no conflict of interest.

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.

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., Competing Interests: Conflict of Interest The authors have no conflicts of interest to declare., (Copyright © 2023 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Purpose The aim of this work was the commissioning of delivery procedures for the treatment of moving targets in scanning pencil beam hadrontherapy. Methods EBT3 films fixed to the Anzai Respiratory Phantom were exposed to carbon ion scanned homogeneous fields (E = 332 MeV/u). To evaluate the interplay effect, field size and flatness for 3 different scenarios were compared to static condition: gated irradiation or repainting alone and combination of both. Respiratory signal was provided by Anzai pressure sensor or optical tracking system (OTS). End-exhale phase and 1 s gating window were chosen (2.5 mm residual motion). Dose measurements were performed using a PinPoint ionization chamber inserted into the Brainlab ET Gating Phantom. A sub-set of tests was also performed using proton beams. Results The combination of gating technique and repainting (N = 5) showed excellent results (6.1% vs 4.3% flatness, identical field size and dose deviation within 1.3%). Treatment delivery time was acceptable. Dose homogeneity for gated irradiation alone was poor. Both Anzai sensor and OTS appeared suitable for providing respiratory signal. Comparisons between protons and carbon ions showed that larger beam spot sizes represent more favorable condition for minimizing motion effect. Conclusion Results of measurements performed on different phantoms showed that the combination of gating and layered repainting is suitable to treat moving targets using scanning ion beams. Abdominal compression using thermoplastic masks, together with multi-field planning approach and multi-fractionation, have also been assessed as additional strategies to mitigate the effect of patient respiration in the clinical practice. [ABSTRACT FROM AUTHOR]