Proton Beam Delivery Research Articles

Effects of spot size errors in DynamicARC pencil beam scanning proton therapy planning

Objective.Spot size stability is crucial in pencil beam scanning (PBS) proton therapy, and variations in spot size can disrupt dose distributions. Recently, a novel proton beam delivery method known as DynamicARC PBS scanning has been introduced. The current study investigates the dosimetric impact of spot size errors in DynamicARC proton therapy for head and neck (HNC), prostate, and lung cancers.Approach.Robustly optimized DynamicARC proton therapy plans were created for HNC (n= 4), prostate (n= 4), and lung (n= 4) cancer patients. Spot size errors of ±10%, ±15%, and ±20% were introduced, and their effects on target coverage (D95%andD99%), homogeneity index (HI), and organ-at-risk doses were analyzed across different cancer sites.Main Results.HNC and lung cancer plans showed greater vulnerability to spot size errors, with reductions in target coverage of up to 4.8% under -20% spot size errors. Dose homogeneity was also more affected in these cases, with HI degrading by 0.12 in lung cancer. Prostate cancer demonstrated greater resilience to spot size variations, even under errors of ±20%. For spot size errors ±10%, the oral cavity, parotid glands, and constrictor muscles experiencedDmeandeviations within ±1.2%, while deviations were limited to ±0.5% forD10%of the bladder and rectum and ±0.3% forV20 Gy(RBE)of the lungs. The robustness analysis indicated that lung cancer plans were most susceptible to robustness reductions caused by spot size errors, while HNC plans demonstrated moderate sensitivity. Conversely, prostate cancer plans demonstrated high robustness, experiencing only minimal reductions in target coverage.Significance.While the ±10% spot size tolerance is appropriate in majority of the cases, lung cancer plans may require more stringent criteria. As DynamicARC becomes clinically available, measuring spot size errors in practice will be essential to validate these findings and refine tolerance thresholds for clinical use.

Experimental Study and Quantitative Analysis of the Physical Parameters of the Proton Therapy Scanning Beam Delivery System

The development of proton therapy techniques imposes strict requirements for the accuracy of proton beam delivery. Existing methods for determining the planning target volume allow one to take into account only the influence of patient positioning errors before the start of irradiation. In this paper, the results of work on taking into account proton therapy system beam delivery errors for determining the planning target volume are presented. The technique for measuring the proton beam parameters and analyzing the measurement results is described. The calculation of the minimum required margin from the clinical target volume is carried out to guarantee its irradiation, taking into account the errors in beam delivery by the proton therapy system.

Time structures of proton pencil beam scanning delivery on a microsecond scale measured with a pixelated semiconductor detector Timepix3.

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

Delivery of High-Intensity Proton Beam for the Study of Flash-Effect in Radiotherapy

Flash-therapy is a rapidly developing field of radiology that has the potential to revolutionize future cancer treatment techniques. The method involves delivery the therapeutic radiation dose to the tumor volume at an ultra-high dose rate in the beam, several orders of magnitude higher than that usually used in conventional radiotherapy. In this mode of irradiation, the degree of damage to normal tissues surrounding the tumor and falling under the influence of radiation decreases, at the same time, the effect on cancer cells remains at the same level, which preserves the prospect of local control of the tumor with a lower frequency of side effects.
 The paper presents the results on the delivery of a high-intensity proton beam with an energy of 660 MeV from the Phasotron of the Joint Institute for Nuclear Research, Dubna, designed for radiobiological studies under flash therapy irradiation of cell cultures and small laboratory animals (mice, rats). In addition, the main design features and parameters of the created detectors for measuring the characteristics of this beam are presented.

Exploring beamline momentum acceptance for tracking respiratory variability in lung cancer proton therapy: a simulation study

Objective. Investigating the aspects of proton beam delivery to track organ motion with pencil beam scanning therapy. Considering current systems as a reference, specify requirements for next-generation units aiming at real-time image-guided treatments. Approach. Proton treatments for six non-small cell lung cancer (NSCLC) patients were simulated using repeated 4DCTs to model respiratory motion variability. Energy corrections required for this treatment site were evaluated for different approaches to tumour tracking, focusing on the potential for energy adjustment within beamline momentum acceptance (dp/p). A respiration-synchronised tracking, taking into account realistic machine delivery limits, was compared to ideal tracking scenarios, in which unconstrained energy corrections are possible. Rescanning and the use of multiple fields to mitigate residual interplay effects and dose degradation have also been investigated. Main results. Energy correction requirements increased with motion amplitudes, for all patients and tracking scenarios. Higher dose degradation was found for larger motion amplitudes, rescanning has beneficial effects and helped to improve dosimetry metrics for the investigated limited dp/p of 1.2% (realistic) and 2.4%. The median differences between ideal and respiratory-synchronised tracking show minimal discrepancies, 1% and 5% respectively for dose coverage (CTV V95) and homogeneity (D5-D95). Multiple-field planning improves D5-D95 up to 50% in the most extreme cases while it does not show a significant effect on V95. Significance. This work shows the potential of implementing tumour tracking in current proton therapy units and outlines design requirements for future developments. Energy regulation within momentum acceptance was investigated to tracking tumour motion with respiratory-synchronisation, achieving results in line with the performance of ideal tracking scenarios. ±5% Δp/p would allow to compensate for all range offsets in our NSCLC patient cohort, including breathing variability. However, the realistic momentum of 1.2% dp/p representative of existing medical units limitations, has been shown to preserve plan quality.

Early Impact of Proton Beam Therapy on Electrophysiological Characteristics in a Porcine Model.

Particle therapy is a noninvasive, catheter-free modality for cardiac ablation. We previously demonstrated the efficacy for creating ablation lesions in the porcine heart. Despite several earlier studies, the exact mechanism of early biophysical effects of proton and photon beam delivery on the myocardium remain incompletely resolved. Ten normal and 9 infarcted in situ porcine hearts received proton beam irradiation (40 Gy) delivered to the left ventricular myocardium with follow-up for 8 weeks. High-resolution electroanatomical mapping of the left ventricular was performed at baseline and follow-up. Bipolar voltage amplitude, conduction velocity, and connexin-43 were determined within the irradiated and nonirradiated areas. The irradiated area in normal hearts showed a significant reduction of bipolar voltage amplitude (10.1±4.9 mV versus 5.7±3.2, P<0.0001) and conduction velocity (85±26 versus 55±13 cm/s, P=0.03) beginning at 4 weeks after irradiation. In infarcted myocardium after irradiation, bipolar voltage amplitude of the infarct scar (2.0±2.9 versus 0.8±0.7 mV, P=0.008) was significantly reduced as well as the conduction velocity in the infarcted heart (43.7±15.7 versus 26.3±11.4 cm/s, P=0.02). There were no significant changes in bipolar voltage amplitude and conduction velocity in nonirradiated myocardium. Myocytolysis, capillary hyperplasia, and dilation were seen in the irradiated myocardium 8 weeks after irradiation. Active caspase-3 and reduction of connexin-43 expression began in irradiated myocardium 1 week after irradiation and decreased over 8 weeks. Irradiation of the myocardium with proton beams reduce connexin-43 expression, conduction velocity, and bipolar conducted electrogram amplitude in a large porcine model. The changes in biomarkers preceded electrophysiological changes after proton beam therapy.

PO-03-067 POTENTIAL NEGATIVE IMPACT OF IN SITU LARGE LESION FORMATION IN PORCINE AND CANINE ANIMALS

A significant amount of information regarding large lesion formation has emerged over the last 5 – 6 years. Extensive studies have been performed with needle electrode, PFA ablation and protons. The consequence of large lesions have not been analyzed in the intact heart in situ. This study aim was to compare how large lesions were created by needle and proton beam ablation in animal models, and to establish adequate energy power. Twenty-two dogs underwent ablation with a needle electrode. The effect of large lesions from proton therapy was also examined in 28 pigs. The lesion size, potential myocardial disruption, or perforation were examined in each of these animal sets. Similarly, findings from PFA ablation were considered. Of these animals, 35 had normal myocardium, while 15 had undergone prior infarction creation. The target location for needle electrode ablation was established by ultrasound, CT and MR, while CT and MR were utilized for establishing the dose response range and targets for proton therapy. These were examined ultimately by an MR study immediately before animal euthanasia, where upon the lesion size was established. In the animals with normal myocardium, the lesions were largely confined to the desired target. Lesions were of substantial size with 1038 ± 887 mm3 from needle electrodes, and 3500 ± 2100 mm3 from protons. In contrast, with myocardial infarction, there was a ven overlap between the lesion created by myocardial infarction and that created by either needle or proton deliveries. The needle electrode and proton delivery large lesions were seen in the table. The large lesions were confined to the area of the infarct in those animals. There was relatively little scatter of demonstrable lesions in the residual myocardium at risk. There were regions around both needle electrode and proton beam deliveries consistent with lower outputs in both cases. In needle electrode deliveries was significant edema farfield around the major lesion, while there was some penumbral proton effect at levels of 10-20 Gy. Both needle, proton, and PFA deliveries create very large lesions in ventricular myocardium. While this could be of substantial risk, the overall lesions are confined to the target dose of needle/PFA and proton targets. This indicates there is relatively little damage to residual myocardium at risk without negative of decreased myocardial contraction. This must be carefully determined, in setting temperature, radiation, and PFA dosing.Tabled 1Table (PO-03-067)Needle normal tissueNeedle infarct tissueProton normal tissueProton infarct tissuePower40 W/50 s50 W/60 s40 W/50 s30 Gy40 Gy40 GyLesion volume (mm3)983±9061093±8681052±5432500±8005900±9003476±1018Width (mm)17.3±5.823.6±14.914.0±3.722.4±3.432.1±7.825.1±3.6Length (mm)14.9±5.914.7±4.217.1±5.413.3±2.114.9±3.613.8±3.4Depth (mm)13.4±2.913.4±3.315.3±2.213.7±2.515.5±3.714.3±2.8Depth at maximum width (mm)7.6±2.18.3±2.37.9±1.79.4±3.19.1±2.49.2±2.0 Open table in a new tab

Comprehensive investigation of lateral dose profile and output factor measurements in small proton fields from different delivery techniques.

As a part of the commissioning and quality assurance in proton beam therapy, lateral dose profiles and output factors have to be acquired. Such measurements can be performed with point detectors and are especially challenging in small fields or steep lateral penumbra regions as the detector's volume effect may lead to perturbations. To address this issue, this work aims to quantify and correct for such perturbations of six point detectors in small proton fields created via three different delivery techniques. Lateral dose profile and output measurements of three proton beam delivery techniques (pencil beam scanning, pencil beam scanning combined with collimators, passive scattering with collimators) were performed using high-resolution EBT3 films, a PinPoint 3D 31022 ionization chamber, a microSilicon diode 60023 and a microDiamond detector 60019 (all PTW Freiburg, Germany). Detector specific lateral dose response functions K(x,y) acting as the convolution kernel transforming the undisturbed dose distribution D(x,y) into the measured signal profiles M(x,y) were applied to quantify perturbations of the six investigated detectors in the proton fields and correct the measurements. A signal theoretical analysis in Fourier space of the dose distributions and detector's K(x,y) was performed to aid the understanding of the measurement process with regard to the combination of detector choice and delivery technique. Quantification of the lateral penumbra broadening and signal reduction at the fields center revealed that measurements in the pencil beam scanning fields are only compromised slightly even by large volume ionization chambers with maximum differences in the lateral penumbra of 0.25mm and 4% signal reduction at the field center. In contrast, radiation techniques with collimation are not accurately represented by the investigated detectors as indicated by a penumbra broadening up to 1.6mm for passive scattering with collimators and 2.2mm for pencil beam scanning with collimators. For a 3mm diameter collimator field, a signal reduction at field center between 7.6% and 60.7% was asserted. Lateral dose profile measurements have been corrected via deconvolution with the corresponding K(x,y) to obtain the undisturbed D(x,y). Corrected output ratios of the passively scattered collimated fields obtained for the microDiamond, microSilicon and PinPoint 3D show agreement better than 0.9% (one standard deviation) for the smallest field size of 3mm. Point detector perturbations in small proton fields created with three delivery techniques were quantified and found to be especially pronounced for collimated small proton fields with steep dose gradients. Among all investigated detectors, the microSilicon diode showed the smallest perturbations. The correction strategies based on detector's K(x,y) were found suitable for obtaining unperturbed lateral dose profiles and output factors. Approximation of K(x,y) by considering only the geometrical averaging effect has been shown to provide reasonable prediction of the detector's volume effect. The findings of this work may be used to guide the choice of point detectors in various proton fields and to contribute toward the development of a code of practice for small field proton dosimetry.

Verification of Uniformity of Dosimetric Characteristics of Couch Tops in Proton Radiation Therapy

In proton therapy the couches used for patient positioning and alignment can affect the uncertainty in the dose distribution from the applied proton beam. In order to limit the additional uncertainty of the proton range, it is necessary to know the determined water equivalent thickness (WET) of the couch top and carefully reflect it in the calculations of the dosimetry planning system. The method presented in this article is based on the difference in the measured depth of the proton beam detected by the multilayer ionization chamber with the beam passing through the couch top and without passing through it.&#x0D; A range shifter (proton beam modifier) installed in the nozzle with the known WET for evaluating couch tops before commissioning was used in this research work. A nozzle is a proton beam delivery system consisting of quadrupole magnets, ionization chambers and an X-ray tube. CT scans were also acquired to evaluate the internal homogeneity of the test couch tops.&#x0D; Several kVue couch inserts Proton one (Qfix Systems, Avondale, PA) were evaluated in this study. The results show that the inserts are largely interchangeable for this type of design and the use of the range shifter during treatment, using gantry angles with the proton beam passing through the couch top, does not affect its WET, adding a deflection of approximately 0.1 mm. It was also determined that the reproducibility of the WET determination method has a deviation less than ±0.03 mm. In conclusion, the described above method of couch top testing before commissioning in proton therapy can also be applied to other patient immobilization systems.

Ionoacoustic application of an optical hydrophone to detect proton beam range in water.

Proton range uncertainty has been the main factor limiting the ability of proton therapy to concentrate doses to tumors to their full potential. Ionoacoustic (IA) range verification is an approach to reducing this uncertainty by detecting thermoacoustic waves emitted from an irradiated volume immediately following a pulsed proton beam delivery; however, the signal weakness has been an obstacle to its clinical application. To increase the signal-to-noise ratio (SNR) with the conventional piezoelectric hydrophone (PH), the detector-sensitive volume needs to be large, but it could narrow the range of available beam angles and disturb real-time images obtained during beam delivery. To prevent this issue, we investigated a millimeter-sized optical hydrophone (OH) that exploits the laser interferometric principle. For two types of IA waves [γ-wave emitted from the Bragg peak (BP) and a spherical IA wave with resonant frequency (SPIRE) emitted from the gold fiducial marker (GM)], comparisons were made with PH in terms of waveforms, SNR, range detection accuracy, and signal intensity robustness against the small detector misalignment, particularly for SPIRE. A 100-MeV proton beam with a 27 ns pulse width and 4 mm beam size was produced using a fixed-field alternating gradient accelerator and was irradiated to the water phantom. The GM was set on the beam's central axis. Acrylic plates of various thicknesses, up to 12mm, were set in front of the phantoms to shift the proton range. OH was set distal and lateral to the beam, and the range was estimated using the time-of-flight method for γ-wave and by comparing with the calibration data (SPIRE intensity versus the distance between the GM and BP) derived from an IA wave transport simulation for SPIRE. The BP dose per pulse was 0.5-0.6Gy. To measure the variation in SPIRE amplitude against the hydrophone misalignment, the hydrophone was shifted by±2mm at a maximum in lateral directions. Despite its small size, OH could detect γ-wave with a higher SNR than the conventional PH (diameter, 29mm), and a single measurement was sufficient to detect the beam range with a submillimeter accuracy in water. In the SPIRE measurement, OH was far more robust against the detector misalignment than the focused PH (FPH) used in our previous study [5%/mm (OH) versus 80%/mm (FPH)], and the correlation between the measured SPIRE intensity and the distance between the GM and BP agreed well with the simulation results. However, the OH sensitivity was lower than the FPH sensitivity, and about 5.6-Gy dose was required to decrease the intensity variation among measurements to less than 10%. The miniature OH was found to detect weak IA signals produced by proton beams with a BP dose used in hypofractionated regimens. The OH sensitivity improvement at the MHz regime is worth exploring as the next step.

Development and validation of an optimal GATE model for proton pencil-beam scanning delivery

ObjectiveTo develop and validate a versatile Monte Carlo (MC)-based dose calculation engine to support MC-based dose verification of treatment planning systems (TPSs) and quality assurance (QA) workflows in proton therapy. MethodsThe GATE MC toolkit was used to simulate a fixed horizontal active scan-based proton beam delivery (SIEMENS IONTRIS). Within the nozzle, two primary and secondary dose monitors have been designed to enable the comparison of the accuracy of dose estimation from MC simulations with respect to physical QA measurements. The developed beam model was validated against a series of commissioning measurements using pinpoint chambers and 2D array ionization chambers (IC) in terms of lateral profiles and depth dose distributions. Furthermore, beam delivery module and treatment planning has been validated against the literature deploying various clinical test cases of the AAPM TG‐119 (c-shape phantom) and a prostate patient. ResultsMC simulations showed excellent agreement with measurements in the lateral depth-dose parameters and spread-out Bragg peak (SOBP) characteristics within a maximum relative error of 0.95 mm in range, 1.83% in entrance to peak ratio, 0.27% in mean point-to-point dose difference, and 0.32% in peak location. The mean relative absolute difference between MC simulations and measurements in terms of absorbed dose in the SOBP region was 0.93% ± 0.88%. Clinical phantom studies showed a good agreement compared to research TPS (relative error for TG-119 planning target volume PTV-D95 ∼ 1.8%; and for prostate PTV-D95 ∼ −0.6%). ConclusionWe successfully developed a MC model for the pencil beam scanning system, which appears reliable for dose verification of the TPS in combination with QA information, prior to patient treatment.

Comparative assessment of passive scattering and active scanning proton therapy techniques using Monte Carlo simulations

Background: in this study, two proton beam delivery designs, i.e. passive scattering proton therapy (PSPT) and pencil beam scanning (PBS), were quantitatively compared in terms of dosimetric indices. The GATE Monte Carlo (MC) particle transport code was used to simulate the proton beam system; and the developed simulation engines were benchmarked with respect to the experimental measurements. Method: a water phantom was used to simulate system energy parameters using a set of depth-dose data in the energy range of 120–235 MeV. To compare the performance of PSPT against PBS, multiple dosimetric parameters including Bragg peak width (BP W50), peak position, range, peak-to-entrance dose ratio, penumbra(90-10)%, penumbra(80-20)%, M 95% and dose volume histogram have been analyzed under the same conditions. Furthermore, the clinical test cases introduced by AAPM TG-119 were simulated in both beam delivery modes to compare the relevant clinical values obtained from Dose Volume Histogram (DVH) analysis. Results: the parametric comparison in the water phantom between the two techniques revealed that the value of peak-to-entrance dose ratio in PSPT is considerably higher than that from PBS by a factor of 8%. In addition, the BP_W50, penumbra(90-10)%, penumbra(80-20)%, and M 95% in PSPT was increased by a factor of 7, 51, 37, and 2.7%, respectively compared to the corresponding value obtained from PBS model. TG-119 phantom simulations showed that the difference of PTV mean dose between PBS and PSPT techniques are up to 1.8% while the difference of max dose to organ at risks (OARs) exceeds 50%. Conclusion: the results of this simulation show that although the passive scattering design method has a slightly higher ability to adjust the dose in target volume, but the active scanning proton therapy systems was superior in dose painting, and lower out-of-field dose compared to passive scattering design.

Impedance minimization of the CERN Super Proton Synchrotron cavities using the generalized coupled S -parameter method

In the context of the Large Hadron Collider (LHC) injector upgrade, components with high contribution to the beam coupling impedance of the injector chain have to be identified and optimized to ensure the delivery of high-intensity proton beams to the LHC. The Super Proton Synchrotron (SPS) is the last accelerator in the LHC injector chain. In the existing design, the longitudinal beam coupling impedance of the SPS cavities limits the increase of the beam intensity in the SPS ring. Since the 200 MHz traveling wave cavities are one of the main contributors to the overall beam coupling budget of the SPS machine, different types of higher-order mode (HOM) couplers are used in the long 33-cell and 44-cell cavities for the damping of various HOMs. The location of the HOM couplers in the cavity, as well as their shape, affects the damping of HOMs. Finding a suitable arrangement of the HOM couplers requires solving a discrete optimization problem. The repetitive calculation of the beam coupling impedance by the conventional time-domain wakefield solvers in the optimization is hindered by the large size of the SPS cavities. The generalized coupled $S$-parameter method is a domain decomposition method for the calculation of the $S$ parameters and beam coupling impedance of large structures. In this paper, this method is employed to calculate the beam coupling impedance of the SPS cavities. Then, an optimization method is proposed to find an optimal arrangement of the HOM couplers in the cavities. The article presents the geometrical details of the SPS cavities, a short description of the generalized coupled $S$-parameter method, and a discrete optimization method applied to the SPS cavities.

Treatment planning for Flash radiotherapy: General aspects and applications to proton beams.

The increased radioresistence of healthy tissues when irradiated at very high dose rates (known as the Flash effect) is a radiobiological mechanism that is currently investigated to increase the therapeutic ratio of radiotherapy treatments. To maximize the benefits of the clinical application of Flash, a patient-specific balance between different properties of the dose distribution should be found, that is, Flash needs to be one of the variables considered in treatment planning. We investigated the Flash potential of three proton therapy planning and beam delivery techniques, each on a different anatomical region. Based on a set of beam delivery parameters, on hypotheses on the dose and dose rate thresholds needed for the Flash effect to occur, and on two definitions of Flash dose rate, we generated exemplary illustrations of the capabilities of current proton therapy equipment to generate Flash dose distributions. All techniques investigated could both produce dose distributions comparable with a conventional proton plan and reach the Flash regime, to an extent that was strongly dependent on the dose per fraction and the Flash dose threshold. The beam current, Flash dose rate threshold, and dose rate definition typically had a more moderate effect on the amount of Flash dose in normal tissue. A systematic estimation of the impact of Flash on different patient anatomies and treatment protocols is possible only if Flash-specific treatment planning features become readily available. Planning evaluation tools such as a voxel-based dose delivery time structure, and the inclusion in the optimization cost function of parameters directly associated with Flash (e.g., beam current, spot delivery sequence, and scanning speed), are needed to generate treatment plans that are taking full advantage of the potential benefits of the Flasheffect.

Simulation Study of a 3-D Multislit Prompt Gamma Imaging System for Proton Therapy Monitoring

The Bragg peak phenomenon empowers proton therapy in targeted dose delivery in principle and also critically demands high accuracy of proton beam’s dispatch track in practice. To ensure the accuracy, prompt gamma imaging (PGI) systems were studied for monitoring the delivery of proton beams in real time. In this work, a dual-head PGI system was proposed and optimized with multislit collimators and BGO scintillators. The dual-head system was then assessed through a contrast recovery coefficient (CRC)-variance approach to identify a preferred setup. The performance of the PGI system was evaluated in terms of detection efficiency, spatial resolution, and positioning accuracy through a series of Monte Carlo simulations. Simulation results show that the detection efficiency of the system is 0.53% at the center of the FOV for 4.44 MeV prompt gamma, and the spatial resolution is better than 2 mm across the FOV. The positioning accuracy defined as the most distal edge position (MDEP) error is less than 2 mm along the beam incident direction at a relatively low number of detected events ( <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$5 \times 10^{4}$ </tex-math></inline-formula> ) in the dual-head system corresponding to a beam spot of <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$10 ^{8}$ </tex-math></inline-formula> incident protons. The system design is feasible for the real-time proton therapy monitoring.

The effects of Compton camera data acquisition and readout timing on PG imaging for proton range verification.

The purpose of this study was to determine how the characteristics of the data acquisition (DAQ) electronics of a Compton camera (CC) affect the quality of the recorded prompt gamma (PG) interaction data and the reconstructed images, during clinical proton beam delivery. We used the Monte-Carlo-plus-Detector-Effect (MCDE) model to simulate the delivery of a 150 MeV clinical proton pencil beam to a tissue-equivalent plastic phantom. With the MCDE model we analyzed how the recorded PG interaction data changed as two characteristics of the DAQ electronics of a CC were changed: (1) the number of data readout channels; and (2) the active charge collection, readout, and reset time. As the proton beam dose rate increased, the number of recorded PG single-, double-, and triple-scatter events decreased by a factor of 60× for the current DAQ configuration of the CC. However, as the DAQ readout channels were increased and the readout/reset timing decreased, the number of recorded events decreased by <5× at the highest clinical dose rate. The increased number of readout channels and reduced readout/reset timing also resulted in higher quality recorded data. That is, a higher percentage of the recorded double- and triple-scatters were "true" events (caused by a single incident gamma) and not "false" events (caused by multiple incident gammas). The increase in the number and the quality of recorded data allowed higher quality PG images to be reconstructed even at the highest clinical dose rates.

Proceedings to the 7th Annual Conference of the Particle Therapy Cooperative Group North America (PTCOG-NA)

Proceedings to the 7th Annual Conference of the Particle Therapy Cooperative Group North America (PTCOG-NA)

Ultra-Hypofractionated Proton Therapy in Localized Prostate Cancer: Passive Scattering versus Intensity-Modulated Proton Therapy

Few studies have directly compared passive scattering (PS) to intensity-modulated proton therapy (IMPT) in the delivery of ultra-hypofractionated proton beams to the localized prostate cancer (PCa). In this preliminary study involving five patients previously treated with CyberKnife, treatment plans were created for PS and IMPT (36.25 CGE in five fractions with two opposing fields) to compare the dosimetric parameters to the planning target volume (PTV) and organs-at-risk (OAR: rectum, bladder, femoral heads). Both plans met the acceptance criteria. Significant differences were observed in the minimum and maximum doses to the PTV. The mean dose to the PTV was lower for PS (35.62 ± 0.26 vs. 37.18 ± 0.14; p = 0.002). Target coverage (D98%) was better for IMPT (96.79% vs. 99.10%; p = 0.004). IMPT resulted in significantly lower mean doses to the rectum (16.75 CGE vs. 6.88 CGE; p = 0.004) and bladder (17.69 CGE vs. 5.98 CGE p = 0.002). High dose to the rectum (V36.25 CGE) were lower with PS, but not significantly opposite to high dose to the bladder. No significant differences were observed in mean conformity index values, with a non-significant trend towards higher mean homogeneity index values for PS. Non-significant differences in the gamma index for both fields were observed. These findings suggest that both PS and IMPT ultra-hypofractionated proton therapy for PCa are highly precise, offering good target coverage and sparing of normal tissues and OARs.

Secondary Particle Interactions in a Compton Camera Designed for in vivo Range Verification of Proton Therapy.

The purpose of this study was to determine the types, proportions, and energies of secondary particle interactions in a Compton camera (CC) during the delivery of clinical proton beams. The delivery of clinical proton pencil beams ranging from 70 to 200 MeV incident on a water phantom was simulated using Geant4 software (version 10.4). The simulation included a CC similar to the configuration of a Polaris J3 CC designed to image prompt gammas (PGs) emitted during proton beam irradiation for the purpose of in vivo range verification. The interaction positions and energies of secondary particles in each CC detector module were scored. For a 150-MeV proton beam, a total of 156,688(575) secondary particles per 108 protons, primarily composed of gamma rays (46.31%), neutrons (41.37%), and electrons (8.88%), were found to reach the camera modules, and 79.37% of these particles interacted with the modules. Strategies for using CCs for proton range verification should include methods of reducing the large neutron backgrounds and low-energy non-PG radiation. The proportions of interaction types by module from this study may provide information useful for background suppression.

Differential normal skin transcriptomic response in total body irradiated mice exposed to scattered versus scanned proton beams

Proton therapy allows to avoid excess radiation dose on normal tissues. However, there are some limitations. Indeed, passive delivery of proton beams results in an increase in the lateral dose upstream of the tumor and active scanning leads to strong differences in dose delivery. This study aims to assess possible differences in the transcriptomic response of skin in C57BL/6 mice after TBI irradiation by active or passive proton beams at the dose of 6 Gy compared to unirradiated mice. In that purpose, total RNA was extracted from skin samples 3 months after irradiation and RNA-Seq was performed. Results showed that active and passive delivery lead to completely different transcription profiles. Indeed, 140 and 167 genes were differentially expressed after active and passive scanning compared to unirradiated, respectively, with only one common gene corresponding to RIKEN cDNA 9930021J03. Moreover, protein–protein interactions performed by STRING analysis showed that 31 and 25 genes are functionally related after active and passive delivery, respectively, with no common gene between both types of proton delivery. Analysis showed that active scanning led to the regulation of genes involved in skin development which was not the case with passive delivery. Moreover, 14 ncRNA were differentially regulated after active scanning against none for passive delivery. Active scanning led to 49 potential mRNA-ncRNA pairs with one ncRNA mainly involved, Gm44383 which is a miRNA. The 43 genes potentially regulated by the miRNA Gm44393 confirmed an important role of active scanning on skin keratin pathway. Our results demonstrated that there are differences in skin gene expression still 3 months after proton irradiation versus unirradiated mouse skin. And strong differences do exist in late skin gene expression between scattered or scanned proton beams. Further investigations are strongly needed to understand this discrepancy and to improve treatments by proton therapy.