Constructing a database of alien plants in the Himalaya to test patterns structuring diversity.

Differences in the number of alien plant species in different locations may reflect climatic and other controls that similarly affect native species and/or propagule pressure accompanied with delayed spread from the point of introduction. We set out to examine these alternatives for Himalayan plants, in a phylogenetic framework. We build a database of alien plant distributions for the Himalaya. Focusing on the well-documented regions of Jammu & Kashmir (west) and Bhutan (east) we compare alien and native species for (1) richness patterns, (2) degree of phylogenetic clustering, (3) the extent to which species-poor regions are subsets of species-rich regions and (4) continental and climatic affinities/source. We document 1470 alien species (at least 600 naturalised), which comprise ~14% of the vascular plants known from the Himalaya. Alien plant species with tropical affinities decline in richness with elevation and species at high elevations form a subset of those at lower elevations, supporting location of introduction as an important driver of alien plant richness patterns. Separately, elevations which are especially rich in native plant species are also rich in alien plant species, suggesting an important role for climate (high productivity) in determining both native and alien richness. We find no support for the proposition that variance in human disturbance or numbers of native species correlate with alien distributions. Results imply an ongoing expansion of alien species from low elevation sources, some of which are highly invasive.

Distribution, Chemical Constituents and Biological Properties of Genus Malaxis.

The genus Malaxis (family Orchidaceae), comprises nearly 183 species available across the globe. The plants of this genus have long been employed in traditional medical practices because of their numerous biological properties, like the treatment of infertility, hemostasis, burning sensation, bleeding diathesis, fever, diarrhea, dysentery, febrifuge, tuberculosis, etc. Various reports highlight their phytochemical composition and biological activities. However, there is a lack of systematic review on the distribution, phytochemistry, and biological properties of this genus. Hence, this study aims to conduct a thorough and critical review of Malaxis species, covering data published from 1965 to 2022 with nearly 90 articles. Also, it examines different bioactive compounds, their chemistry, and pharmacotherapeutics as well as their traditional uses. A total of 189 unique compounds, including the oil constituents were recorded from Malaxis species. The highest active ingredients were obtained from Malaxis acuminata (103) followed by Malaxis muscifera (49) and Malaxis rheedei (33). In conclusion, this review offers an overview of the current state of knowledge on Malaxis species and highlights prospects for future research projects on them. Additionally, it recommends the promotion of domestication studies for rare medicinal orchids like Malaxis and the prompt implementation of conservation measures.

Feasibility study of utilizing Sphinx Compact for quality assurance in uniform scanning proton therapy.

PURPOSE: To investigate the feasibility of utilizing the Sphinx Compact detector for quality assurance in a uniform scanning proton therapy system. METHOD: The Sphinx Compact detector was used to measure various dosimetric parameters of uniform scanning proton beam at the Oklahoma Proton Center: distal range, distal-fall-off, collinearity, field symmetry, flatness, and field size for four different beams. A specially designed brass aperture was used to perform the required measurements. The Sphinx Compact measurement results were validated against the measurement results from the well-established detectors in proton therapy: IBA Zebra, IBA MatriXX-PT, EBT3 films, and Logos XRV-124. The data collected using the Sphinx Compact was analyzed in myQA software. RESULTS: Based on the data analysis performed, the Sphinx Compact measurements were within acceptable accuracy to the results from the detectors mentioned in the Method section. Specifically, the lateral penumbra was within ±0.4 mm, collinearity was within ± 0.5 mm, flatness was within ±0.6 %, symmetry within ±1.6 %, distal range was within ±0.5 mm, distal-fall-off was <0.9 mm, and field size was within ±1 mm. The reproducibility of the Sphinx Compact was tested for range and collinearity, and the results were within ±0.1 mm. CONCLUSION: The sphinx Compact detector could potentially replace multiple detectors utilized for monthly QA in uniform scanning proton therapy. In a multi-room center, performing the QA with one detector compared to using multiple detectors dramatically reduces total QA time and the complexity of the QA process.

Feasibility Study of Using XRV-124 Scintillation Detector for Collinearity Measurement in Uniform Scanning Proton Therapy.

Purpose: The purpose of this work is to study the feasibility of using an XRV-124 scintillation detector in measuring the collinearity of the x-ray system and uniform scanning proton beam. Methods: A brass aperture for Snout 10 was manufactured. The center of the aperture had an opening of 1 cm in diameter (4 cm for the film measurements). The 2D kV x-ray images of the XRV-124 were acquired such that the marker inside the detector is aligned to the imaging isocenter. After obtaining the optimal camera settings, a uniform scanning proton beam was delivered for various ranges (12 g/cm2 to 28 g/cm2 in step size of 2 g/cm2). For each range, 10 monitor units (MU) of the first layer were delivered to the XRV-124 detector. Collinearity tests were repeated by using EDR2 and EBT3 films following our current quality assurance protocol in practice. The results from the XRV-124 measurements were compared against the collinearity results from EDR2 and EBT3 films. Results and Discussion: The collinearity results were evaluated in the horizontal (x) and vertical (y) directions. The average deviation in collinearity in the x-direction was -0.24 ± 0.30 mm, 0.57 ± 0.39 mm, and -0.27 ± 0.14 mm for EDR2, EBT3, and XRV-124, respectively. In the y-direction, the average deviation was 0.39 ± 0.07 mm, 0.29 ± 0.14 mm, and 0.39 ± 0.03 mm for EDR2, EBT3, and XRV-124, respectively. Conclusion: The measurement results from the XRV-124 and films are in good agreement. Compared to film, the use of the XRV-124 detector for collinearity measurements in uniform scanning protons is more efficient and provides results in real time.

Potential toxicity of nickel nano and microparticles on the reproductive system of female rats: A comparative time-dependent study.

Increased application of engineered nanoparticles in different sectors viz. agriculture, commerce, industry, and medicine has raised serious public health issues. Nanoparticles of nickel have been increasingly used as catalysts, conductive pastes, adhesives, nanowires, and nanofilters. Human and animal exposure to these particles may cause toxicity in different organs/systems. Studies made in the past had demonstrated their toxicity in liver, kidney, and lungs. However, their reproductive effects remain poorly understood. Therefore, the present study on reproductive toxicity of nickel nanoparticles (<30 nm) was executed in female Wistar rats. A comparison of results obtained in nickel microparticle-treated rats was also made. Rats were administered nano and microparticles through gavage at a dosage of 5 mg/kg body weight each for two exposure periods; that is, 15 and 30 days. Ovaries removed from these rats were analyzed to study the effects of nickel bioaccumulation on synthesis of steroid hormones, lipid peroxidation, apoptosis, and oxidative stress. Structural changes were monitored through histopathological and ultrastructural observations. The present study showed exposure time-dependent differences in the toxicity of nickel nano and microparticles in the ovary of rats. Nano nickel was cumulative in the ovaries. It affected steroidogenesis. Further, increased generation of reactive oxygen species and enhanced oxidative stress may have contributed to cytotoxicity. It was concluded that exposure to nano nickel might induce irreversible damage in the ovaries of rat.

Quantitative analysis of dose-averaged linear energy transfer (LETd ) robustness in pencil beam scanning proton lung plans.

PURPOSE: The primary objective of our study was to perform a quantitative robustness analysis of the dose-averaged linear energy transfer (LETd ) and related RBE-weighted dose in robustly optimized (in terms of the range and set up uncertainties) pencil beam scanning (PBS) proton lung cancer plans. METHODS: In this study, we utilized the 4DCT dataset of six anonymized lung patients. PBS lung plans were generated using a robust optimization technique (range uncertainty: ±3.5% and setup errors: ±5 mm) on the CTV for a total dose of 5000 cGy (RBE) in five fractions using the RBE of 1.1. For each patient, the LETd distributions were calculated for the nominal plan and three groups. Group 1: two plan robustness scenarios for range uncertainties of ±3.5%; Group 2: twelve plan robustness scenarios (range uncertainty (±3.5%) in conjunction with setup errors (±5 mm)); and Group 3: ten different breathing phases of the 4DCT dataset. The RBE-weighted dose to the OARs was evaluated for all robustness scenarios and breathing phases. The variation (∆) in the mean LETd and mean RBE-weighted dose from each group was recorded. RESULTS: The mean LETd in the CTV of nominal PBS lung plans among six patients ranged from 2.2 to 2.6 keV/µm. On average, for the combined range and setup uncertainties, the ∆ in the mean LETd among 12 scenarios of all six patients was 0.6 keV/µm, which is slightly higher than when only the range uncertainties were considered (0.4 keV/µm). The ∆ in the mean LETd in a patient was ≤1.7 keV/µm in the heart and ≤1.2 keV/µm in the esophagus and total lung. The ∆ in the mean RBE-weighted dose in a patient was up to 79 cGy for the total lung, 165 cGy for the heart, and 258 cGy for the esophagus. For ten breathing phases, the ∆ in the mean LETd in a patient was ≤0.3 keV/µm in the CTV, ≤0.5 keV/µm in the heart, ≤0.4 keV/µm in the esophagus, and ≤0.7 keV/µm in the total lung. CONCLUSION: The addition of setup errors to the range uncertainties resulted in slightly less homogeneous LETd distributions. The variations in the mean LETd among the ten breathing phases were slightly larger in the total lung than in the heart and esophagus. The combination of setup and range uncertainties had a greater impact than the effect of breathing phases on the variations in the mean RBE-weighted dose to the OARs. Overall, the LETd distributions in the CTV were less sensitive than those in the OARs to setup errors, range uncertainties, and breathing phases for robustly optimized (in terms of range and setup uncertainities) PBS proton lung cancer plans.

Small spot size versus large spot size: Effect on plan quality for lung cancer in pencil beam scanning proton therapy.

PURPOSE: The purpose of the current study was to evaluate the impact of spot size on the interplay effect, plan robustness, and dose to the organs at risk for lung cancer plans in pencil beam scanning (PBS) proton therapy METHODS: The current retrospective study included 13 lung cancer patients. For each patient, small spot (∼3 mm) plans and large spot (∼8 mm) plans were generated. The Monte Carlo algorithm was used for both robust plan optimization and final dose calculations. Each plan was normalized, such that 99% of the clinical target volume (CTV) received 99% of the prescription dose. Interplay effect was evaluated for treatment delivery starting in two different breathing phases (T0 and T50). Plan robustness was investigated for 12 perturbed scenarios, which combined the isocenter shift and range uncertainty. The nominal and worst-case scenario (WCS) results were recorded for each treatment plan. Equivalent uniform dose (EUD) and normal tissue complication probability (NTCP) were evaluated for the total lung, heart, and esophagus. RESULTS: In comparison to large spot plans, the WCS values of small spot plans at CTV D95% , D96% , D97% , D98% , and D99% were higher with the average differences of 2.2% (range, 0.3%-3.7%), 2.3% (range, 0.5%-4.0%), 2.6% (range, 0.6%-4.4%), 2.7% (range, 0.9%-5.2%), and 2.7% (range, 0.3%-6.0%), respectively. The nominal and WCS mean dose and EUD for the esophagus, heart, and total lung were higher in large spot plans. The difference in NTCP between large spot and small spot plans was up to 1.9% for the total lung, up to 0.3% for the heart, and up to 32.8% for the esophagus. For robustness acceptance criteria of CTV D95% ≥ 98% of the prescription dose, seven small spot plans had all 12 perturbed scenarios meeting the criteria, whereas, for 13 large spot plans, there were ≥2 scenarios failing to meet the criteria. Interplay results showed that, on average, the target coverage in large spot plans was higher by 1.5% and 0.4% in non-volumetric and volumetric repainting plans, respectively. CONCLUSION: For robustly optimized PBS lung cancer plans in our study, a small spot machine resulted in a more robust CTV against the setup and range errors when compared to a large spot machine. In the absence of volumetric repainting, large spot PBS lung plans were more robust against the interplay effect. The use of a volumetric repainting technique in both small and large spot PBS lung plans led to comparable interplay target coverage.

Attributes of oxidative stress in the reproductive toxicity of nickel oxide nanoparticles in male rats.

The nanoparticles of nickel are now being widely used in industrial, commercial, and biomedical applications. In recent years, health safety issues posed by them have aroused concerns among health scientists. The aim of the present study was to investigate the role of oxidative stress in male reproductive toxicity induced by nickel oxide nanoparticles in rats. Male Wistar rats (140-170 g) were administered with nickel oxide nanoparticles (NiONPs) (particles size <30 nm) (5 mg/kg body weight) by gavage for 30 days. Its effects on different parameters, viz., sperm count, motility, and morphology, were investigated. DNA damage in sperms was monitored through comet assay. All these observations indicated a spermicidal effect of NiONPs. Results on lipid peroxidation (MDA, H2O2, and NO) and oxidative stress (GSH, GPx, and catalase) thus studied in testes exhibited adverse effects of NiONPs. Histopathological results on male reproductive organs, viz., testis, epididymis, vas deferens, seminal vesicles, and prostate also demonstrated moderate to severe toxicity. A comparison of these results with those obtained on nickel oxide microparticle (NiOMP)-treated rats showed that NiONPs are more toxic than NiOMPs. Furthermore, NiONPs could create an imbalance between oxidants and antioxidants in the testes. It is concluded that redox imbalance in testes constitutes a major mechanism of NiONP-induced reproductive toxicity.

Impact of errors in spot size and spot position in robustly optimized pencil beam scanning proton-based stereotactic body radiation therapy (SBRT) lung plans.

PURPOSE: The purpose of the current study was threefold: (a) investigate the impact of the variations (errors) in spot sizes in robustly optimized pencil beam scanning (PBS) proton-based stereotactic body radiation therapy (SBRT) lung plans, (b) evaluate the impact of spot sizes and position errors simultaneously, and (c) assess the overall effect of spot size and position errors occurring simultaneously in conjunction with either setup or range errors. METHODS: In this retrospective study, computed tomography (CT) data set of five lung patients was selected. Treatment plans were regenerated for a total dose of 5000 cGy(RBE) in 5 fractions using a single-field optimization (SFO) technique. Monte Carlo was used for the plan optimization and final dose calculations. Nominal plans were normalized such that 99% of the clinical target volume (CTV) received the prescription dose. The analysis was divided into three groups. Group 1: The increasing and decreasing spot sizes were evaluated for ±10%, ±15%, and ±20% errors. Group 2: Errors in spot size and spot positions were evaluated simultaneously (spot size: ±10%; spot position: ±1 and ±2 mm). Group 3: Simulated plans from Group 2 were evaluated for the setup (±5 mm) and range (±3.5%) errors. RESULTS: Group 1: For the spot size errors of ±10%, the average reduction in D99% for -10% and +10% errors was 0.7% and 1.1%, respectively. For -15% and +15% spot size errors, the average reduction in D99% was 1.4% and 1.9%, respectively. The average reduction in D99% was 2.1% for -20% error and 2.8% for +20% error. The hot spot evaluation showed that, for the same magnitude of error, the decreasing spot sizes resulted in a positive difference (hotter plan) when compared with the increasing spot sizes. Group 2: For a 10% increase in spot size in conjunction with a -1 mm (+1 mm) shift in spot position, the average reduction in D99% was 1.5% (1.8%). For a 10% decrease in spot size in conjunction with a -1 mm (+1 mm) shift in spot position, the reduction in D99% was 0.8% (0.9%). For the spot size errors of ±10% and spot position errors of ±2 mm, the average reduction in D99% was 2.4%. Group 3: Based on the results from 160 plans (4 plans for spot size [±10%] and position [±1 mm] errors × 8 scenarios × 5 patients), the average D99% was 4748 cGy(RBE) with the average reduction of 5.0%. The isocentric shift in the superior-inferior direction yielded the least homogenous dose distributions inside the target volume. CONCLUSION: The increasing spot sizes resulted in decreased target coverage and dose homogeneity. Similarly, the decreasing spot sizes led to a loss of target coverage, overdosage, and degradation of dose homogeneity. The addition of spot size and position errors to plan robustness parameters (setup and range uncertainties) increased the target coverage loss and decreased the dose homogeneity.

Impact of spot positional errors in robustly optimized intensity-modulated proton therapy plan of craniospinal irradiation.

We investigated the influence of random spot positioning errors (SPEs) on dosimetric outcomes of robustly optimized intensity-modulated proton therapy (RB-IMPT) plans in craniospinal irradiation (CSI). Six patients with CSI treated using the RB-IMPT technique were selected. An in-house MATLAB code was used to simulate a random SPE of 1 mm in positive, negative, and both directions for 25%, 50%, and 75% of the total spot positions in the nominal plan. The percentage dose variation (ΔD%) in the six nominal and 54 error-introduced plans was evaluated using standard dose-volume indices, line dose difference, and 3D gamma analysis method. The introduction of a random SPE of 1 mm resulted in a reduction in D99%, D98%, and D95% of both CTVs and PTVs by < 2% compared with the corresponding nominal plans. However, this leads to an increase in D1% of the lens by up to 16.9%. The line dose in the junction region showed ΔD% < 2% for the brain and upper spine and < 4% for the upper and lower spine. The 3D gamma values for 3% at 3 mm and 2% at 2 mm were above 99% and 95%, respectively, in all 54 error-introduced plans. The worst decrease in gamma values was observed for 1% at 1 mm, with values ranging from 64 to 78% for all types of SPE. The RB-IMPT plan for CSI investigated in this study is robust enough for target coverage, even if there are random SPEs of 1 mm. However, this leads to an increase in the dose to the critical organ located close to the target.

Impact of proton dose calculation algorithms on the interplay effect in PBS proton based SBRT lung plans.

Purpose. The purpose of the current study was to investigate the impact of RayStation analytical pencil beam (APB) and Monte Carlo (MC) algorithms on the interplay effect in pencil beam scanning (PBS) proton-based stereotactic body radiation therapy (SBRT) lung plans.Methods. The currentin-silicoplanning study was designed for a total dose of 5000 cGy(RBE) with a fractional dose of 1000 cGy(RBE). First, three sets of nominal plans were generated for each patient: (a) APB optimization followed by APB dose calculation (PB-PB), (b) APB optimization followed by MC dose calculation (PB-MC), and (c) MC optimization followed by MC dose calculation (MC-MC). Second, for each patient, two sets of volumetric repainting plans (five repaintings) - PB-MCVR5and MC-MCVR5were generated based on PB-MC and MC-MC, respectively. Dosimetric differences between APB and MC algorithms were calculated on the nominal and interplay dose-volume-histograms (DVHs).Results. Interplay evaluation in non-volumetric repainting plans showed that APB algorithm overestimated the target coverage by up to 8.4% for D95%and 10.5% for D99%, whereas in volumetric repainting plans, APB algorithm overestimated by up to 5.3% for D95%and 7.0% for D99%. Interplay results for MC calculations showed a decrease in D95%and D99%by average differences of 3.5% and 4.7%, respectively, in MC-MC plans and by 1.8% and 3.0% in MC-MCVR5plans.Conclusion. In PBS proton-based SBRT lung plans, the combination of APB algorithm and interplay effect reduced the target coverage. This may result in inferior local control. The use of MC algorithm for both optimization and final dose calculations in conjunction with the volumetric repainting technique yielded superior target coverage.

Development and validation of the Dynamic Collimation Monte Carlo simulation package for pencil beam scanning proton therapy.

PURPOSE: The aim of this work was to develop and experimentally validate a Dynamic Collimation Monte Carlo (DCMC) simulation package specifically designed for the simulation of collimators in pencil beam scanning proton therapy (PBS-PT). The DCMC package was developed using the TOPAS Monte Carlo platform and consists of a generalized PBS source model and collimator component extensions. METHODS: A divergent point-source model of the IBA dedicated nozzle (DN) at the Miami Cancer Institute (MCI) was created and validated against on-axis commissioning measurements taken at MCI. The beamline optics were mathematically incorporated into the source to model beamlet deflections in the X and Y directions at the respective magnet planes. Off-axis measurements taken at multiple planes in air were used to validate both the off-axis spot size and divergence of the source model. The DCS trimmers were modeled and incorporated as TOPAS geometry extensions that linearly translate and rotate about the bending magnets. To validate the collimator model, a series of integral depth dose (IDD) and lateral profile measurements were acquired at MCI and used to benchmark the DCMC performance for modeling both pristine and range shifted beamlets. The water equivalent thickness (WET) of the range shifter was determined by quantifying the shift in the depth of the 80% dose point distal to the Bragg peak between the range shifted and pristine uncollimated beams. RESULTS: A source model of the IBA DN system was successfully commissioned against on- and off-axis IDD and lateral profile measurements performed at MCI. The divergence of the source model was matched through an optimization of the source-to-axis distance and comparison against in-air spot profiles. The DCS model was then benchmarked against collimated IDD and in-air and in-phantom lateral profile measurements. Gamma analysis was used to evaluate the agreement between measured and simulated lateral profiles and IDDs with 1%/1 mm criteria and a 1% dose threshold. For the pristine collimated beams, the average 1%/1 mm gamma pass rates across all collimator configurations investigated were 99.8% for IDDs and 97.6% and 95.2% for in-air and in-phantom lateral profiles. All range shifted collimated IDDs passed at 100% while in-air and in-phantom lateral profiles had average pass rates of 99.1% and 99.8%, respectively. The measured and simulated WET of the polyethylene range shifter was determined to be 40.9 and 41.0 mm, respectively. CONCLUSIONS: We have developed a TOPAS-based Monte Carlo package for modeling collimators in PBS-PT. This package was then commissioned to model the IBA DN system and DCS located at MCI using both uncollimated and collimated measurements. Validation results demonstrate that the DCMC package can be used to accurately model other aspects of a DCS implementation via simulation.

Investigating volumetric repainting to mitigate interplay effect on 4D robustly optimized lung cancer plans in pencil beam scanning proton therapy.

PURPOSE: The interplay effect between dynamic pencil proton beams and motion of the lung tumor presents a challenge in treating lung cancer patients in pencil beam scanning (PBS) proton therapy. The main purpose of the current study was to investigate the interplay effect on the volumetric repainting lung plans with beam delivery in alternating order ("down" and "up" directions), and explore the number of volumetric repaintings needed to achieve acceptable lung cancer PBS proton plan. METHOD: The current retrospective study included ten lung cancer patients. The total dose prescription to the clinical target volume (CTV) was 70 Gy(RBE) with a fractional dose of 2 Gy(RBE). All treatment plans were robustly optimized on all ten phases in the 4DCT data set. The Monte Carlo algorithm was used for the 4D robust optimization, as well as for the final dose calculation. The interplay effect was evaluated for both the nominal (i.e., without repainting) as well as volumetric repainting plans. The interplay evaluation was carried out for each of the ten different phases as the starting phases. Several dosimetric metrics were included to evaluate the worst-case scenario (WCS) and bandwidth based on the results obtained from treatment delivery starting in ten different breathing phases. RESULTS: The number of repaintings needed to meet the criteria 1 (CR1) of target coverage (D95%  ≥ 98% and D99%  ≥ 97%) ranged from 2 to 10. The number of repaintings needed to meet the CR1 of maximum dose (ΔD1%  < 1.5%) ranged from 2 to 7. Similarly, the number of repaintings needed to meet CR1 of homogeneity index (ΔHI < 0.03) ranged from 3 to 10. For the target coverage region, the number of repaintings needed to meet CR1 of bandwidth (<100 cGy) ranged from 3 to 10, whereas for the high-dose region, the number of repaintings needed to meet CR1 of bandwidth (<100 cGy) ranged from 1 to 7. Based on the overall plan evaluation criteria proposed in the current study, acceptable plans were achieved for nine patients, whereas one patient had acceptable plan with a minor deviation. CONCLUSION: The number of repaintings required to mitigate the interplay effect in PBS lung cancer (tumor motion < 15 mm) was found to be highly patient dependent. For the volumetric repainting with an alternating order, a patient-specific interplay evaluation strategy must be adopted. Determining the optimal number of repaintings based on the bandwidth and WCS approach could mitigate the interplay effect in PBS lung cancer treatment.

Investigating the utilization of beam-specific apertures for the intensity-modulated proton therapy (IMPT) head and neck cancer plans.

Intensity-modulated proton therapy (IMPT) planning for the head and neck (HN) cancer often requires the use of the range shifter, which can increase the lateral penumbrae of the pencil proton beam in the patient, thus leading to an increase in unnecessary dose to the organs at risks (OARs) in proximity to the target volumes. The primary goal of the current study was to investigate the dosimetric benefits of utilizing beam-specific apertures for the IMPT HN cancer plans. The current retrospective study included computed tomography datasets of 10 unilateral HN cancer patients. The clinical target volume (CTV) was divided into low-risk CTV1 and high-risk CTV2. Total dose prescriptions to the CTV1 and CTV2 were 54 Gy(RBE) and 70 Gy(RBE), respectively, with a fractional dose of 2 Gy(RBE). All treatment plans were robustly optimized (patient setup uncertainty = 3 mm; range uncertainty = 3.5%) on the CTVs. For each patient, 2 sets of plans were generated: (1) without beam-specific aperture (WOBSA), and (2) with beam-specific aperture (WBSA). Specifically, both the WOBSA and WBSA of the given patient used identical beam angles, air gap, optimization structures, optimization constraints, and optimization settings. Target coverage and homogeneity index were comparable in both the WOBSA and WBSA plans with no statistical significance (p > 0.05). On average, the mean dose in WBSA plans was reduced by 12.1%, 2.9%, 3.0%, 3.8%, and 5.2% for the larynx, oral cavity, parotids, superior pharyngeal constrictor muscle, and inferior pharyngeal constrictor muscle, respectively. The dosimetric results of the OARs were found to be statistically significant (p < 0.05). The use of the beam-specific apertures did not deteriorate the coverage and homogeneity in the target volume and allowed for a reduction in mean dose to the OARs with an average difference up to 12.1%.

Investigating beam matching for multi-room pencil beam scanning proton therapy.

The purpose of this study was to investigate the proton beam matching for a multi-room ProteusPLUS pencil beam scanning (PBS) proton therapy system and quantify the agreement among three beam-matched treatment rooms (GTR1, GTR2, and GTR3). In-air spot size measurements were acquired using a 2D scintillation detector at various gantry angles. Range and absolute dose measurements were performed in water at gantry angle 0°. Patient-specific quality assurance (QA) plans of four different disease sites (brain, mediastinum, sacrum, and prostate) and machine QA fields with uniform dose were delivered for various beam conditions. The results from GTR1 were considered as reference values. The average difference in spot sizes between GTR2 and GTR1 was - 0.3% ± 2.2% (range, - 5.9 to 5.8%). For GTR3 vs. GTR1, the average difference in spot sizes was 0.6% ± 1.7% (range, - 4.8 to 4.6%). The spot symmetry was found to be ≤ 4.4%. For proton range, the difference among three rooms was within ± 0.5 mm. On average, the difference in absolute dose was - 0.1 ± 0.7% (range, - 1.3 to 2.1%) for GTR2 vs. GTR1 and 0.7 ± 0.6% (range, - 0.1 to 2.1%) for GTR3 vs. GTR1. The average gamma passing rate of patient-specific QA measurements (n = 29) was ≥ 98.6%. The average gamma passing rate of machine QA fields was 99.9%. In conclusion, proton beam matching was quantified for three beam-matched rooms of an IBA ProteusPLUS system with a PBS dedicated nozzle. It is feasible to match the spot size and absolute dose within ± 5% and ± 2%, respectively. Proton range can be matched within ± 0.5 mm.

Impact of magnetic field regulation in conjunction with the volumetric repainting technique on the spot positions and beam range in pencil beam scanning proton therapy.

PURPOSE: The objective of this study was to evaluate the impact of the magnetic field regulation in conjunction with the volumetric repainting technique on the spot positions and range in pencil beam scanning proton therapy. METHODS: "Field regulation" - a feature to reduce the switching time between layers by applying a magnetic field setpoint (instead of a current setpoint) has been implemented on the proton beam delivery system at the Miami Cancer Institute. To investigate the impact of field regulation for the volumetric repainting technique, several spot maps were generated with beam delivery sequence in both directions, that is, irradiating from the deepest layer to the most proximal layer ("down" direction) as well as irradiating from the most proximal layer to the deepest layer ("up" direction). Range measurements were performed using a multi-layer ionization chamber array. Spot positions were measured using two-dimensional and three-dimensional scintillation detectors. For range and central-axis spot position, spot maps were delivered for energies ranging from 70-225 MeV. For off-axis spot positions, the maps were delivered for high-, medium, and low-energies at eight different gantry angles. The results were then compared between the "up" and "down" directions. RESULTS: The average difference in range for given energy between "up" and "down" directions was 0.0 ± 0.1 mm. The off-axis spot position results showed that 846/864 of the spots were within ±1 mm, and all off-axis spot positions were within ±1.2 mm. For spots (n = 126) at the isocenter, the evaluation between "up" and "down" directions for given energy showed the spot position difference within ±0.25 mm. At the nozzle entrance, the average differences in X and Y positions for given energy were 0.0 ± 0.2 mm and -0.0 ± 0.4 mm, respectively. At the nozzle exit, the average differences in X and Y positions for given energy were 0.0 ± 0.1 mm and -0.1 ± 0.1 mm, respectively. CONCLUSION: The volumetric repainting technique in magnetic field regulation mode resulted in acceptable spot position and range differences for our beam delivery system. The range differences were found to be within ±1 mm (TG224). For the spot positions (TG224: ±1 mm), the central axis measurements were within ±1 mm, whereas for the off-axis measurements, 97.9% of the spots were within ±1 mm, and all spots were within ±1.2 mm.

Parametrization of in-air spot size as a function of energy and air gap for the ProteusPLUS pencil beam scanning proton therapy system.

The purpose of this study was to parametrize the in-air one sigma spot size for various energies and air gaps in pencil beam scanning (PBS) proton therapy. The current study included range shifters with a water equivalent thickness (WET) of 40 mm (RS40) and 75 mm (RS75). For RS40, the spot sizes were measured for energies ranging from 80 to 225 MeV in increments of 2.5 MeV, whereas the air gap was varied from 5 to 25 cm in increments of 2.5 cm. For RS75, the spot sizes were measured for energies ranging from 120 to 225 MeV in increments of 2.5 MeV, whereas the air gap was varied from 5 to 35 cm in increments of 2.5 cm. For both RS40 and RS75, all measurements (n = 1090) were acquired at the isocenter using a Lynx 2D scintillation detector. For RS40, the spot sizes increased from 3.1 mm to 10.4 mm, whereas the variation in spot sizes for RS75 ranged from 3.3 mm to 13.1 mm. For each range shifter, an analytical equation demonstrating the relationship of the spot size with the proton energy and air gap was obtained. The best parametrization results were obtained with the 3rd degree polynomial fits of the energy and air gap parameters. The average difference between the modeled and measured spot sizes was 0.0 ± 0.1 mm (range, - 0.24-0.21 mm) for RS40, and 0.0 ± 0.1 mm (range, - 0.23-0.15 mm) for RS75. In conclusion, the analytical model agrees within ± 0.25 mm of the measured spot sizes on a ProteusPLUS PBS proton system with a PBS dedicated nozzle.

Determination of machine-specific tolerances using statistical process control analysis of long-term uniform scanning proton machine QA results.

PURPOSE: The purpose of this study was twofold: (a) report the long-term monthly quality assurance (QA) dosimetry results of the uniform scanning beam delivery system, and (b) derive the machine-specific tolerances based on the statistic process control (SPC) methodology and compare them against the AAPM TG224 recommended tolerances. METHODS: The Oklahoma Proton Center has four treatment rooms (TR1, TR2, TR3, and TR4) with a cyclotron and a universal nozzle. Monthly QA dosimetry results of four treatment rooms over a period of 6 yr (Feb 2014-Jan 2020) were retrieved from the QA database. The dosimetry parameters included dose output, range, flatness, and symmetry. The monthly QA results were analyzed using the SPC method, which included individuals and moving range (I-MR) chart. The upper control limit (UCL) and lower control limit (LCL) were set at 3σ above and below the mean value, respectively. RESULTS: The mean difference in dose output was -0.3% (2σ = ±0.9% and 3σ = ±1.3%) in TR1, 0% (2σ = ±1.4% and 3σ = ±2.1%) in TR2, -0.2% (2σ = ±1.0% and 3σ = ±1.6%) in TR3, and -0.5% (2σ = ±0.9% and 3σ = ±1.3%) in TR4. The mean flatness and symmetry differences of all beams among the four treatment rooms were within ±1.0%. The 3σ for the flatness difference ranged from ±0.5% to ±1.2%. The 3σ for the symmetry difference ranged from ±0.4% to ±1.4%. The SPC analysis showed that the 3σ for range 10 cm (R10), R16, and R22 were within ±1 mm, whereas the 3σ for R28 exceeded ±1 mm in two rooms (3σ = ±1.9 mm in TR2 and 3σ = ±1.3 mm in TR3). CONCLUSION: The 3σ of the dose output, flatness, and symmetry differences in all four rooms were comparable to the TG224 tolerance (±2%). For the uniform scanning system, if the measured range is compared against the requested range, it may not always be possible to achieve the range difference within ±1 mm (TG224) for all the ranges.

Design of a focused collimator for proton therapy spot scanning using Monte Carlo methods.

PURPOSE: When designing a collimation system for pencil beam spot scanning proton therapy, a decision must be made whether or not to rotate, or focus, the collimator to match beamlet deflection as a function of off-axis distance. If the collimator is not focused, the beamlet shape and fluence will vary as a function of off-axis distance due to partial transmission through the collimator. In this work, we quantify the magnitude of these effects and propose a focused dynamic collimation system (DCS) for use in proton therapy spot scanning. METHODS: This study was done in silico using a model of the Miami Cancer Institute's (MCI) IBA Proteus Plus system created in Geant4-based TOPAS. The DCS utilizes rectangular nickel trimmers mounted on rotating sliders that move in synchrony with the pencil beam to provide focused collimation at the edge of the target. Using a simplified setup of the DCS, simulations were performed at various off-axis locations corresponding to beam deflection angles ranging from 0° to 2.5°. At each off-axis location, focused (trimmer rotated) and unfocused (trimmer not rotated) simulations were performed. In all simulations, a 4 cm water equivalent thickness range shifter was placed upstream of the collimator, and a voxelized water phantom that scored dose was placed downstream, each with 4 cm airgaps. RESULTS: Increasing the beam deflection angle for an unfocused trimmer caused the collimated edge of the beamlet profile to shift 0.08-0.61 mm from the baseline 0° simulation. There was also an increase in low-dose regions on the collimated edge ranging from 14.6% to 192.4%. Lastly, the maximum dose, D max , was 0-5% higher for the unfocused simulations. With a focused trimmer design, the profile shift and dose increases were all eliminated. CONCLUSIONS: We have shown that focusing a collimator in spot scanning proton therapy reduces dose at the collimated edge compared to conventional, unfocused collimation devices and presented a simple, mechanical design for achieving focusing for a range of source-to-collimator distances.

Impact of Air Gap on Intensity-Modulated Proton Therapy Breast Plans.

OBJECTIVE: The primary purpose of this study was to investigate the impact of an air gap (AG) on breast cancer plans that are generated using the intensity-modulated proton therapy technique. METHODS: In this retrospective study, we have included a total of ten female patients with left breast cancer. A total clinical target volume (CTV_Total) was generated by combining breast or chest wall, axillary level I-III nodes, internal mammary nodes, and supraclavicular nodes. Monte Carlo algorithm used within RayStation was used for both the robust plan optimization and dose computation. For each case, intensity-modulated proton therapy breast plan with a 4 cm AG was considered as the base plan. To test the impact of the AG, the base plan (AG = 4 cm) of a given case was copied and recalculated for additional AG of 6, 8, 10, 12, and 14 cm. RESULTS: An increase in the AG yielded a decrease in the dosimetric and tumor control probability (TCP) values in all ten patients. As the AG increased from 4 cm to 14 cm, the impact of the AG on the dosimetric indices was the most severe for the target volume received by 95% of the prescription dose (CTV_Total V95%) and dose received by 99% of the target volume (CTV_Total D99%), which showed the average reduction of 7% ± 3% and 6.3% ± 2.8%, respectively. Similarly, the average decrease in dose received by 99% of the volume (CTV_Total D95%), CTV_Total mean dose, Homogeneity Index of CTV_Total, and TCP of CTV_Total were 4.7% ± 1.8%, 2.1% ± 0.6%, 0.03 ± 0.02, and 1.3% ± 0.4%, respectively. CONCLUSIONS: In the present study, an increase in 2 cm AG provided a reduction in the dosimetric and TCP results by ≤1%. An increment of the AG by 4 cm (ie, from 4 cm to 8 cm) resulted in a loss of ≤2% and ≤0.6% in the dosimetric and TCP results, respectively. There was no distinct trend between organ at risk results and variation in the AG.