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PURPOSE: We developed and tested a novel method of creating intensity modulated proton arc therapy (IMPAT) plans that uses computing resources similar to those for regular intensity-modulated proton therapy (IMPT) plans and may offer a dosimetric benefit for patients with ependymoma or similar tumor geometries. METHODS: Our IMPAT planning method consists of a geometry-based energy selection step with major scanning spot contributions as inputs computed using ray-tracing and single-Gaussian approximation of lateral spot profiles. Based on the geometric relation of scanning spots and dose voxels, our energy selection module selects a minimum set of energy layers at each gantry angle such that each target voxel is covered by sufficient scanning spots as specified by the planner, with dose contributions above the specified threshold. Finally, IMPAT plans are generated by robustly optimizing scanning spots of the selected energy layers using a commercial proton treatment planning system (TPS). The IMPAT plan quality was assessed for four ependymoma patients. Reference three-field IMPT plans were created with similar planning objective functions and compared with the IMPAT plans. RESULTS: In all plans, the prescribed dose covered 95% of the clinical target volume (CTV) while maintaining similar maximum doses for the brainstem. While IMPAT and IMPT achieved comparable plan robustness, the IMPAT plans achieved better homogeneity and conformity than the IMPT plans. The IMPAT plans also exhibited higher relative biological effectiveness (RBE) enhancement than did the corresponding reference IMPT plans for the CTV in all four patients and brainstem in three of them. CONCLUSIONS: The proposed method demonstrated potential as an efficient technique for IMPAT planning and may offer a dosimetric benefit for patients with ependymoma or tumors in close proximity to critical organs. IMPAT plans created using this method had elevated RBE enhancement associated with increased linear energy transfer (LET) in both targets and abutting critical organs.
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Ependimoma , Terapia com Prótons , Radioterapia de Intensidade Modulada , Humanos , Terapia com Prótons/métodos , Prótons , Dosagem Radioterapêutica , Ependimoma/radioterapia , Radioterapia de Intensidade Modulada/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Órgãos em RiscoRESUMO
This paper summarizes clinical commissioning of the world's first commercial, clinically utilized installation of a compact, image-guided, pencil-beam scanning, intensity-modulated proton therapy system, the IBA Proteus® ONE, at the Willis-Knighton Cancer Center (WKCC) in Shreveport, LA. The Proteus® ONE is a single-room, compact-gantry system employing a cyclotron-generated proton beam with image guidance via cone-beam CT as well as stereoscopic orthogonal and oblique planar kV imaging. Coupling 220° of gantry rotation with a 6D robotic couch capable of in plane patient rotations of over 180° degrees allows for 360° of treatment access. Along with general machine characterization, system commissioning required: (a) characterization and calibration of the proton beam, (b) treatment planning system commissioning including CT-to-density curve determination, (c) image guidance system commissioning, and (d) safety verification (interlocks and radiation survey). System readiness for patient treatment was validated by irradiating calibration TLDs as well as prostate, head, and lung phantoms from the Imaging and Radiation Oncology Core (IROC), Houston. These results confirmed safe and accurate machine functionality suitable for patient treatment. WKCC also successfully completed an on-site dosimetry review by an independent team of IROC physicists that corroborated accurate Proteus® ONE dosimetry.
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Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias Pulmonares/radioterapia , Imagens de Fantasmas , Neoplasias da Próstata/radioterapia , Terapia com Prótons/instrumentação , Planejamento da Radioterapia Assistida por Computador/métodos , Tomografia Computadorizada de Feixe Cônico/métodos , Desenho de Equipamento , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Terapia com Prótons/métodos , Dosagem RadioterapêuticaRESUMO
This is a real case study to minimize the neutron dose equivalent (H) to a fetus using spot scanning proton beams with favorable beam energies and angles. Minimum neutron dose exposure to the fetus was achieved with iterative planning under the guidance of neutron H measurement. Two highly conformal treatment plans, each with three spot scanning beams, were planned to treat a 25-year-old pregnant female with aggressive recurrent chordoma of the base of skull who elected not to proceed with termination. Each plan was scheduled for delivery every other day for robust target coverage. Neutron H to the fetus was measured using a REM500 neutron survey meter placed at the fetus position of a patient simulating phantom. 4.1 and 44.1 µSv/fraction were measured for the two initial plans. A vertex beam with higher energy and the fetal position closer to its central axis was the cause for the plan that produced an order higher neutron H. Replacing the vertex beam with a lateral beam reduced neutron H to be comparable with the other plan. For a prescription of 70 Gy in 35 fractions, the total neutron H to the fetus was estimated to be 0.35 mSv based on final measurement in single fraction. In comparison, the passive scattering proton plan and photon plan had an estimation of 26 and 70 mSv, respectively, for this case. While radiation therapy in pregnant patients should be avoided if at all possible, our work demonstrated spot scanning beam limited the total neutron H to the fetus an order lower than the suggested 5 mSv regulation threshold. It is far superior than passive scattering beam and careful beam selection with lower energy and keeping fetus further away from beam axis are essential in minimizing the fetus neutron exposure.
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Feto/efeitos da radiação , Neoplasias Induzidas por Radiação/prevenção & controle , Nêutrons/efeitos adversos , Órgãos em Risco/efeitos da radiação , Terapia com Prótons , Radioterapia Conformacional/efeitos adversos , Neoplasias Cranianas/radioterapia , Adulto , Feminino , Humanos , Neoplasias Induzidas por Radiação/etiologia , Gravidez , Proteção Radiológica , Dosagem Radioterapêutica , Espalhamento de RadiaçãoRESUMO
The delivery of accurate proton dose for clinical trials requires that the appropriate conversion function from Hounsfield unit (HU) to relative linear stopping power (RLSP) be used in proton treatment planning systems (TPS). One way of verifying that the TPS is calculating the correct dose is an end-to-end test using an anthropomorphic phantom containing tissue equivalent materials and dosimeters. Many of the phantoms in use for such end-to-end tests were originally designed using tissue-equivalent materials that had physical characteristics to match patient tissues when irradiated with megavoltage photon beams. The aim of this study was to measure the RLSP of materials used in the phantoms, as well as alternative materials to enable modifying phantoms for use at proton therapy centers. Samples of materials used and projected for use in the phantoms were measured and compared to the HU assigned by the treatment planning system. A percent difference in RLSP of 5% was used as the cutoff for materials deemed acceptable for use in proton therapy (i.e., proton equivalent). Until proper tissue-substitute materials are identified and incorporated, institutions that conduct end-to-end tests with the phantoms are instructed to override the TPS with the measured stopping powers we provide. To date, the RLSPs of 18 materials have been measured using a water phantom and/or multilayer ion chamber (MLIC). Nine materials were identified as acceptable for use in anthropomorphic phantoms. Some of the failing tissue substitute materials are still used in the current phantoms. Further investigation for additional appropriate tissue substitute materials in proton beams is ongoing. Until all anthropomorphic phantoms are constructed of appropriate materials, a unique HU-RLSP phantom has been developed to be used during site visits to verify the proton facility's treatment planning HU-RLSP calibration curve.
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Imagens de Fantasmas , Terapia com Prótons/instrumentação , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia/instrumentação , Antropometria , Calibragem , Humanos , Terapia com Prótons/métodos , Garantia da Qualidade dos Cuidados de Saúde , Controle de Qualidade , Radioterapia/métodos , Dosagem Radioterapêutica , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND: Current fiducial markers (FMs) in external-beam radiotherapy (EBRT) for prostate cancer (PCa) cannot be positively visualized on magnetic resonance imaging (MRI) and create dose perturbation and significant imaging artifacts on computed tomography (CT) and MRI. We report our initial experience with clinical imaging of a novel multimodality FM, NOVA. METHODS: We tested Gold Anchor [G-FM], BiomarC [carbon, C-FM], and NOVA FMs in phantoms imaged with kilovoltage (kV) X-rays, transrectal ultrasound (TRUS), CT, and MRI. Artifacts of the FMs on CT were quantified by the relative streak artifacts level (rSAL) metric. Proton dose perturbations (PDPs) were measured with Gafchromic EBT3 film, with FMs oriented either perpendicular to or parallel with the beam axis. We also tested the performance of NOVA-FMs in a patient. RESULTS: NOVA-FMs were positively visualized on all 4 imaging modalities tested. The rSAL on CT was 0.750 ± 0.335 for 2-mm reconstructed slices. In F-tests, PDP was associated with marker type and depth of measurement (p < 10-6); at 5-mm depth, PDP was significantly greater for the G-FM (12.9%, p = 10-6) and C-FM (6.0%, p = 0.011) than NOVA (4.5%). EBRT planning with MRI/CT image co-registration and daily alignments using NOVA-FMs in a patient was feasible and reproducible. CONCLUSIONS: NOVA-FMs were positively visible and produced less PDP than G-FMs or C-FMs. NOVA-FMs facilitated MRI/CT fusion and identification of regions of interest.
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Background: Proton therapy (PT) has unique biologic properties with excellent clinical outcomes for the management of localized prostate cancer. Here, we aim to characterize the toxicity of PT for patients with localized prostate cancer and propose mitigation strategies using a large institutional database. Methods: We reviewed medical records of 2772 patients with localized prostate cancer treated with definitive PT between May 2006 through January 2020. Disease risk was stratified according to National Comprehensive Cancer Network guidelines as low [LR, n = 640]; favorable-intermediate [F-IR, n = 849]; unfavorable-intermediate [U-IR, n = 851]; high [HR, n = 315]; or very high [VHR, n = 117]. Descriptive statistics and Kaplan-Meier estimates assessed toxicity and freedom from biochemical relapse (FFBR). Results: Median follow-up was 7.0 years. The median dose was 78 Gy(RBE)(range: 72-79.2 Gy) in 2.0 Gy(RBE) fractions; 63 % of patients received 78 Gy(RBE) in 39 fractions, and 29 % received 76 Gy(RBE) in 38 fractions. Overall rates of late grade ≥3 GU and GI toxicity were 0.87 % and 1.01 %, respectively. Two patients developed grade 4 late GU toxicity and seven patients with grade 4 late GI toxicity. All patients experiencing severe late grade 4 toxicities were treated to 78 Gy(RBE) in 39 fractions with 80 Gy(RBE) dose to the anterior rectal wall and/or bladder neck. The 10-year FFBR rates for patients with LR to U-IR disease were compared between those treated with 76 and 78 Gy(RBE); the rates were 94.5 % (95 % confidence interval [CI] 92.4-96.0 %) and 93.2 % (95 % CI 91.3-95.7 %), respectively (log-rank p = 0.22). Conclusions: Proton therapy is associated with low rates of late grade ≥3 GU and GI toxicity. While rare, late grade 4 toxicities occurred in nine (0.3 %) patients. De-escalation to a total dose of 76 Gy(RBE) yields excellent clinical outcomes for patients with LR to U-IR disease with the potential for significant reductions in grade ≥3 late toxicity.
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EBT-XD model of Gafchromic™ films has a broader optimal dynamic dose range, up to 40 Gy, compared to its predecessor models. This characteristic has made EBT-XD films suitable for high-dose applications such as stereotactic body radiotherapy and stereotactic radiosurgery, as well as ultra-high dose rate FLASH radiotherapy. The purpose of the current study was to characterize the dependence of EBT-XD film response on linear energy transfer (LET) and dose rate of therapeutic protons from a synchrotron. A clinical spot-scanning proton beam was used to study LET dependence at three dose-averaged LET (LETd) values of 1.0 keV/µm, 3.6 keV/µm, and 7.6 keV/µm. A research proton beamline was used to study dose rate dependence at 150 Gy/second in the FLASH mode and 0.3 Gy/second in the non-FLASH mode. Film response data from LETd values of 0.9 keV/µm and 9.0 keV/µm of the proton FLASH beam were also compared. Film response data from a clinical 6 MV photon beam were used as a reference. Both gray value method and optical density (OD) method were used in film calibration. Calibration results using a specific OD calculation method and a generic OD calculation method were compared. The four-parameter NIH Rodbard function and three-parameter rational function were compared in fitting the calibration curves. Experimental results showed that the response of EBT-XD film is proton LET dependent but independent of dose rate. Goodness-of-fit analysis showed that using the NIH Rodbard function is superior for both protons and photons. Using the "specific OD + NIH Rodbard function" method for EBT-XD film calibration is recommended.
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Surface modification of yttria-stabilized tetragonal zirconia polycrystals (Y-TZP) using lasers for adhesion enhancement with resin-matrix cement has been increasingly explored. However, Y-TZP is chemically inert and non-reactive, demanding surface modification using alternative approaches to enhance its bond strength to resin-matrix cements. The main aim of this study was to conduct an integrative review on the influence of ultrashort pulse laser patterning of zirconia (3Y-TZP) for enhanced bonding to resin-matrix cements. An electronic search was performed on web of science, SCOPUS, Pubmed/Medline, Google Scholar and EMBASE using a combination of the following search items: zirconia, 3Y-TZP, surface modification, laser surface treatment, AND laser, ultrashortpulse laser, bonding, adhesion, and resin cement. Articles published in the English language, up to January 2022, were included regarding the influence of surface patterning on bond strength of Y-TZP to resin-matrix cements. Out of the 12 studies selected for the present review 10 studies assessed femtosecond lasers while 2 studies assessed picosecond lasers. Ultrashort pulsed laser surface patterning successfully produced different surface morphological aspects without damaging the bulk properties of zirconia. Contrarily, defects such as micro-cracks occurs after surface modification using traditional methods such as grit-blasting or long-pulsed laser patterning. Ultrashort pulsed laser surface patterning increase bond strength of zirconia to resin-matrix cements and therefore such alternative physical method should be considered in dentistry. Also, surface defects were avoided using ultrashort pulsed laser surface patterning, which become the major advantage when compared with traditional physical methods or long pulse laser patterning.
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Colagem Dentária , Cimentos de Resina , Propriedades de Superfície , Cimentos de Resina/química , Teste de Materiais , Lasers , Zircônio/química , Ítrio/química , Resistência ao Cisalhamento , OdontologiaRESUMO
Our randomized clinical study comparing stereotactic body radiotherapy (SBRT) and stereotactic body proton therapy (SBPT) for early stage non-small cell lung cancer (NSCLC) was closed prematurely owing to poor enrollment, largely because of lack of volumetric imaging and difficulty in obtaining insurance coverage for the SBPT group. In this article, we describe technology improvements in our new proton therapy center, particularly in image guidance with cone beam CT (CBCT) and CT on rail (CTOR), as well as motion management with real-time gated proton therapy (RGPT) and optical surface imaging. In addition, we have a treatment planning system that provides better treatment plan optimization and more accurate dose calculation. We expect to re-start the SBPT program, including for early stage NSCLC as well as for other disease sites soon after starting patient treatment at our new proton therapy center.
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The combination of radiation therapy (RT) and immunotherapy has emerged as a promising treatment option in oncology. Historically, x-ray radiation (XRT) has been the most commonly used form of RT. However, proton beam therapy (PBT) is gaining recognition as a viable alternative, as it has been shown to produce similar outcomes to XRT while minimizing off-target effects. The effects of PBT on the antitumor immune response have only just begun to be described, and to our knowledge no studies to date have examined the effect of PBT as part of a combinatorial immunoradiotherapeutic strategy. Here, using a 2-tumor model of lung cancer in mice, we show that PBT in tandem with an anti-PD1 antibody substantially reduced growth in both irradiated and unirradiated tumors. This was accompanied by robust activation of the immune response, as evidenced by whole-tumor and single-cell RNA sequencing showing upregulation of a multitude of immune-related transcripts. This response was further significantly enhanced by the injection of the tumor to be irradiated with NBTXR3 nanoparticles. Tumors of mice treated with the triple combination exhibited increased infiltration and activation of cytotoxic immune cells. This triple combination eradicated both tumors in 37.5% of the treated mice and showed robust long-term immunity to cancer.
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Neoplasias Pulmonares , Nanopartículas , Animais , Camundongos , Radioimunoterapia , Prótons , Neoplasias Pulmonares/radioterapia , ImunoterapiaRESUMO
PURPOSE: Optically stimulated luminescent detectors (OSLDs) have a number of advantages in radiation dosimetry making them excellent dosimeters for quality assurance and patient dose verification. Although the dosimeters have been investigated in several modalities, relatively little work has been done in examining the dosimeters for use in clinical proton beams. This study examined a number of characteristics of the response of the dosimeters in the spread-out Bragg peak (SOBP) region of clinical proton beams. METHODS: Optically stimulated luminescence (OSL) dosimeters from Landauer, Inc., specifically the nanoDot dosimeter, were investigated. These dosimeters were placed in a special phantom with a recess to fit the dosimeters without an air gap. Beams with nominal energies of 160, 200, and 250 MeV were used in the passively-scattered proton beam at the MD Anderson Cancer Center Proton Therapy Center. Dosimetric properties including linearity, field size dependence, energy dependence, residual signal as a function of cumulative dose, and postirradiation fading were investigated by taking measurements at the center of SOBPs. RESULTS: The dosimeters showed 1% supralinearity at 200 cGy and 5% supralinearity at 1000 cGy. No noticeable field size dependence of the detector was found for field sizes from 2 × 2 cm(2) to 18 × 18 cm(2). Residual signal as a function of cumulative dose showed a small increase for measurements up to 1000 cGy. Readout signal depletion of the dosimeters after consecutive readings showed a slightly larger depletion in protons for doses up to 500 cGy but not by a clinically significant amount. Within the center of various SOBP widths and proton energies the variation in response was less than 2%. An average beam quality factor of 1.089 with experimental standard deviation of 0.007 was determined and applied to the data such that the results were within 1.2% of ion chamber data. CONCLUSIONS: The nanoDot OSL dosimeter characteristics were studied in the SOBP region of clinical proton beams. To achieve accurate dosimetric readings, corrections to the dosimeter response were applied. Corrections tended to be minimal or broadly consistent. The nanoDot OSLD was found to be an acceptable dosimeter for measurement in the SOBP region for a range of clinical proton beams.
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Dispositivos Ópticos , Dosimetria Termoluminescente/instrumentação , Desenho Assistido por Computador , Desenho de Equipamento , Análise de Falha de Equipamento , Luz , Terapia com Prótons , Doses de Radiação , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
PURPOSE: Planar integral spot dose (PISD) of proton pencil beam spots (PPBSs) is a required input parameter for beam modeling in some treatment planning systems used in proton therapy clinics. The measurement of PISD by using commercially available large area ionization chambers, like the PTW Bragg peak chamber (BPC), can have large uncertainties due to the size limitation of these chambers. This paper reports the results of our study of a novel method to determine PISD values from the measured lateral dose profiles and peak dose of the PPBS. METHODS: The PISDs of 72.5, 89.6, 146.9, 181.1, and 221.8 MeV energy PPBSs were determined by area integration of their planar dose distributions at different depths in water. The lateral relative dose profiles of the PPBSs at selected depths were measured by using small volume ion chambers and were investigated for their angular anisotropies using Kodak XV films. The peak spot dose along the beam's central axis (D(0)) was determined by placing a small volume ion chamber at the center of a broad field created by the superposition of spots at different locations. This method allows eliminating positioning uncertainties and the detector size effect that could occur when measuring it in single PPBS. The PISD was then calculated by integrating the measured lateral relative dose profiles for two different upper limits of integration and then multiplying it with corresponding D(0). The first limit of integration was set to radius of the BPC, namely 4.08 cm, giving PISD(RBPC). The second limit was set to a value of the radial distance where the profile dose falls below 0.1% of the peak giving the PISD(full). The calculated values of PISD(RBPC) obtained from area integration method were compared with the BPC measured values. Long tail dose correction factors (LTDCFs) were determined from the ratio of PISD(full)∕PISD(RBPC) at different depths for PPBSs of different energies. RESULTS: The spot profiles were found to have angular anisotropy. This anisotropy in PPBS dose distribution could be accounted in a reasonable approximate manner by taking the average of PISD values obtained using the in-line and cross-line profiles. The PISD(RBPC) values fall within 3.5% of those measured by BPC. Due to inherent dosimetry challenges associated with PPBS dosimetry, which can lead to large experimental uncertainties, such an agreement is considered to be satisfactory for validation purposes. The PISD(full) values show differences ranging from 1 to 11% from BPC measured values, which are mainly due to the size limitation of the BPC to account for the dose in the long tail regions of the spots extending beyond its 4.08 cm radius. The dose in long tail regions occur both for high energy beams such as 221.8 MeV PPBS due to the contributions of nuclear interactions products in the medium, and for low energy PPBS because of their larger spot sizes. The calculated LTDCF values agree within 1% with those determined by the Monte Carlo (MC) simulations. CONCLUSIONS: The area integration method to compute the PISD from PPBS lateral dose profiles is found to be useful both to determine the correction factors for the values measured by the BPC and to validate the results from MC simulations.
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Algoritmos , Prótons , Radiometria/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Alta Energia/métodos , Dosagem Radioterapêutica , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
PURPOSE: The main purpose of this work was to generate and validate the dosimetric accuracy of proton beams of dimensions that are appropriate for in vivo small animal and in vitro ultrahigh dose rate (FLASH) radiotherapy experiments using a synchrotron-based treatment delivery system. This study was performed to enable future investigations of the relevance of a spread-out Bragg peak (SOBP) under FLASH conditions. METHODS: The spill characteristics of the small field fixed horizontal beam line were modified to deliver accelerated protons in times as short as 2 ms and to control the dose delivered. A Gaussian-like transverse beam profile was transformed into a square uniform one at FLASH dose rates, while avoiding low-dose regions, a crucial requirement to protect normal tissue during FLASH irradiation. Novel beam-shaping devices were designed using Monte Carlo techniques to produce up to about 6 cm3 of uniform dose in SOBPs while maximizing the dose rate. These included a scattering foil, a conical flattening filter to maximize the flux of protons into the region of interest, energy filters, range compensators, and collimators. The shapes, sizes, and positions of the components were varied to provide the required field sizes and SOBPs. RESULTS: The designed and fabricated devices were used to produce 10-, 15-, and 20-mm diameter, circular field sizes and 10-, 15-, and 20-mm SOBP modulation widths at uniform physical dose rates of up to 375 Gy/s at the center of the SOBP and a minimum dose rate of about 255 Gy/s at the entrance, respectively, in cylindrical volumes. The flatness of lateral dose profiles at the center could be adjusted to within ±1.5% at the center of the SOBP. Assessment of systematic uncertainties, such as impact of misalignments and positioning uncertainties, was performed using simulations, and the results were used to provide appropriate adjustments to ensure high-accuracy FLASH beam delivery for both in vitro and in vivo preclinical experiments. CONCLUSIONS: It is feasible to use synchrotron-generated proton beams of sufficient dimensions for FLASH radiobiology experiments. We expect to use the system we developed to acquire in vitro and in vivo small animal FLASH radiobiology data as a function of dose, dose rate, oxygen content, and linear energy transfer to help us understand the underlying mechanisms of the FLASH phenomenon.
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Terapia com Prótons , Prótons , Animais , Método de Monte Carlo , Dosagem Radioterapêutica , SíncrotronsRESUMO
This study aimed to compare the predictive performance of different modeling methods in developing normal tissue complication probability (NTCP) models for predicting radiation-induced esophagitis (RE) in non-small cell lung cancer (NSCLC) patients receiving proton radiotherapy. The dataset was composed of 328 NSCLC patients receiving passive-scattering proton therapy and 41.6% of the patients experienced ≥ grade 2 RE. Five modeling methods were used to build NTCP models: standard Lyman-Kutcher-Burman (sLKB), generalized LKB (gLKB), multivariable logistic regression using two variable selection procedures-stepwise forward selection (Stepwise-MLR), and least absolute shrinkage and selection operator (LASSO-MLR), and support vector machines (SVM). Predictive performance was internally validated by a bootstrap approach for each modeling method. The overall performance, discriminative ability, and calibration were assessed using the Negelkerke R2, area under the receiver operator curve (AUC), and Hosmer-Lemeshow test, respectively. The LASSO-MLR model showed the best discriminative ability with an AUC value of 0.799 (95% confidence interval (CI): 0.763-0.854), and the best overall performance with a Negelkerke R2 value of 0.332 (95% CI: 0.266-0.486). Both of the optimism-corrected Negelkerke R2 values of the SVM and sLKB models were 0.301. The optimism-corrected AUC of the gLKB model (0.796) was higher than that of the SVM model (0.784). The sLKB model had the smallest optimism in the model variation and discriminative ability. In the context of classification and probability estimation for predicting the NTCP for radiation-induced esophagitis, the MLR model developed with LASSO provided the best predictive results. The simplest LKB modeling had similar or even better predictive performance than the most complex SVM modeling, and it was least likely to overfit the training data. The advanced machine learning approach might have limited applicability in clinical settings with a relatively small amount of data.
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Carcinoma Pulmonar de Células não Pequenas , Esofagite , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Esofagite/diagnóstico , Esofagite/etiologia , Humanos , Neoplasias Pulmonares/radioterapia , Probabilidade , PrótonsRESUMO
Objective. Irradiation with ultra-high dose rates (>40 Gy s-1), also known as FLASH irradiation, has the potential to shift the paradigm of radiation therapy because of its reduced toxicity to normal tissues compared to that of conventional irradiations. The goal of this study was to (1) achieve FLASH irradiation conditions suitable for pre-clinicalin vitroandin vivobiology experiments using our synchrotron-based proton beamline and (2) commission the FLASH irradiation conditions achieved.Approach. To achieve these suitable FLASH conditions, we made a series of adaptations to our proton beamline, including modifying the spill length and size of accelerating cycles, repurposing the reference monitor for dose control, and expanding the field size with a custom double-scattering system. We performed the dosimetric commissioning with measurements using an Advanced Markus chamber and EBT-XD films as well as with Monte Carlo simulations.Main results. Through adaptations, we have successfully achieved FLASH irradiation conditions, with an average dose rate of up to 375 Gy s-1. The Advanced Markus chamber was shown to be appropriate for absolute dose calibration under our FLASH conditions with a recombination factor ranging from 1.002 to 1.006 because of the continuous nature of our synchrotron-based proton delivery within a spill. Additionally, the absolute dose measured using the Advanced Markus chamber and EBT-XD films agreed well, with average and maximum differences of 0.32% and 1.63%, respectively. We also performed a comprehensive temporal analysis for FLASH spills produced by our system, which helped us identify a unique relationship between the average dose rate and the dose in our FLASH irradiation.Significance.We have established a synchrotron-based proton FLASH irradiation platform with accurate and precise dosimetry that is suitable for pre-clinical biology experiments. The unique time structure of the FLASH irradiation produced by our synchrotron-based system may shed new light onto the mechanism behind the FLASH effect.
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Terapia com Prótons , Prótons , Terapia com Prótons/métodos , Radiometria , Dosagem Radioterapêutica , SíncrotronsRESUMO
PURPOSE: Optically stimulated luminescent detectors (OSLDs) are quickly gaining popularity as passive dosimeters, with applications in medicine for linac output calibration verification, brachytherapy source verification, treatment plan quality assurance, and clinical dose measurements. With such wide applications, these dosimeters must be characterized for numerous factors affecting their response. The most abundant commercial OSLD is the InLight/OSL system from Landauer, Inc. The purpose of this study was to examine the angular dependence of the nanoDot dosimeter, which is part of the InLight system. METHODS: Relative dosimeter response data were taken at several angles in 6 and 18 MV photon beams, as well as a clinical proton beam. These measurements were done within a phantom at a depth beyond the build-up region. To verify the observed angular dependence, additional measurements were conducted as well as Monte Carlo simulations in MCNPX. RESULTS: When irradiated with the incident photon beams parallel to the plane of the dosimeter, the nanoDot response was 4% lower at 6 MV and 3% lower at 18 MV than the response when irradiated with the incident beam normal to the plane of the dosimeter. Monte Carlo simulations at 6 MV showed similar results to the experimental values. Examination of the results in Monte Carlo suggests the cause as partial volume irradiation. In a clinical proton beam, no angular dependence was found. CONCLUSIONS: A nontrivial angular response of this OSLD was observed in photon beams. This factor may need to be accounted for when evaluating doses from photon beams incident from a variety of directions.
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Medições Luminescentes/instrumentação , Nanotecnologia/instrumentação , Dispositivos Ópticos , Radiometria/instrumentação , Desenho de Equipamento , Análise de Falha de Equipamento , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
PURPOSE: To evaluate patient census, equipment clinical availability, maximum daily treatment capacity, use factor for major beam delivery parameters, and treatment process time for actual treatments delivered by proton therapy systems. METHODS: The authors have been recording all beam delivery parameters, including delivered dose, energy, range, spread-out Bragg peak widths, gantry angles, and couch angles for every treatment field in an electronic medical record system. We analyzed delivery system downtimes that had been recorded for every equipment failure and associated incidents. These data were used to evaluate the use factor of beam delivery parameters, the size of the patient census, and the equipment clinical availability of the facility. The duration of each treatment session from patient walk-in and to patient walk-out of the treatment room was measured for 82 patients with cancers at various sites. RESULTS: The yearly average equipment clinical availability in the last 3 yrs (June 2007-August 2010) was 97%, which exceeded the target of 95%. Approximately 2200 patients had been treated as of August 2010. The major disease sites were genitourinary (49%), thoracic (25%), central nervous system (22%), and gastrointestinal (2%). Beams have been delivered in approximately 8300 treatment fields. The use factor for six beam delivery parameters was also evaluated. Analysis of the treatment process times indicated that approximately 80% of this time was spent for patient and equipment setup. The other 20% was spent waiting for beam delivery and beam on. The total treatment process time can be expressed by a quadratic polynomial of the number of fields per session. The maximum daily treatment capacity of our facility using the current treatment processes was estimated to be 133 +/- 35 patients. CONCLUSIONS: This analysis shows that the facility has operated at a high performance level and has treated a large number of patients with a variety of diseases. The use factor of beam delivery parameters varies by disease site. Further improvements in efficiency may be realized in the equipment- and patient-related processes of treatment.
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Neoplasias/epidemiologia , Neoplasias/radioterapia , Radioterapia de Alta Energia/estatística & dados numéricos , Estudos de Tempo e Movimento , Humanos , Terapia com Prótons , TexasRESUMO
BACKGROUND AND PURPOSE: To determine rates of xerostomia after intensity-modulated radiotherapy (IMRT) or intensity-modulated proton therapy (IMPT) for oropharyngeal cancer (OPC) and identify dosimetric factors associated with xerostomia risk. MATERIALS AND METHODS: Patients with OPC who received IMRT (n = 429) or IMPT (n = 103) from January 2011 through June 2015 at a single institution were studied retrospectively. Every 3 months after treatment, each patient completed an eight-item self-reported xerostomia-specific questionnaire (XQ; summary XQ score, 0-100). An XQ score of 50 was selected as the demarcation value for moderate-severe (XQs ≥ 50) and no-mild (XQs < 50) xerostomia. The mean doses and percent volumes of organs at risk receiving various doses (V5-V70) were extracted from the initial treatment plans. The dosimetric variables and xerostomia risk were compared using an independent-sample t-test or chi-square test. RESULTS: The median follow-up time was 36.2 months. The proportions of patients with moderate-severe xerostomia were similar in the two treatment groups up to 18 months after treatment. However, moderate-severe xerostomia was less common in the IMPT group than in the IMRT group at 18-24 months (6% vs. 20%; p = 0.025) and 24-36 months (6% vs. 20%; p = 0.01). During the late xerostomia period (24-36 months), high dose/volume exposures (V25-V70) in the oral cavity were associated with high proportions of patients with moderate-severe xerostomia (all p < 0.05), but dosimetric variables regarding the salivary glands were not associated with late xerostomia. CONCLUSION: IMPT was associated with less late xerostomia than was IMRT in OPC patients. Oral cavity dosimetric variables were related to the occurrence of late xerostomia.
Assuntos
Neoplasias Orofaríngeas , Terapia com Prótons , Radioterapia de Intensidade Modulada , Xerostomia , Humanos , Neoplasias Orofaríngeas/radioterapia , Terapia com Prótons/efeitos adversos , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/efeitos adversos , Estudos Retrospectivos , Xerostomia/epidemiologia , Xerostomia/etiologia , Xerostomia/prevenção & controleRESUMO
Proton therapy is an expanding radiotherapy modality in the United States and worldwide. With the number of proton therapy centers treating patients increasing, so does the need for consistent, high-quality clinical commissioning practices. Clinical commissioning encompasses the entire proton therapy system's multiple components, including the treatment delivery system, the patient positioning system, and the image-guided radiotherapy components. Also included in the commissioning process are the x-ray computed tomography scanner calibration for proton stopping power, the radiotherapy treatment planning system, and corresponding portions of the treatment management system. This commissioning report focuses exclusively on intensity-modulated scanning systems, presenting details of how to perform the commissioning of the proton therapy and ancillary systems, including the required proton beam measurements, treatment planning system dose modeling, and the equipment needed.
Assuntos
Terapia com Prótons , Radioterapia de Intensidade Modulada , Calibragem , Humanos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por ComputadorRESUMO
PURPOSE: To provide a series of suggestions for other Medical Physics practices to follow in order to provide effective radiation therapy treatments during the COVID-19 pandemic. METHODS AND MATERIALS: We reviewed our entire Radiation Oncology infrastructure to identify a series of workflows and policy changes that we implemented during the pandemic that yielded more effective practices during this time. RESULTS: We identified a structured list of several suggestions that can help other Medical Physics practices overcome the challenges involved in delivering high quality radiotherapy services during this pandemic. CONCLUSIONS: Our facility encompasses 4 smaller Houston Area Locations (HALs), a main campus with 8 distinct services based on treatment site (ie. Thoracic, Head and Neck, Breast, Gastrointestinal, Gynecology, Genitourinary, Hematologic Malignancies, Melanoma and Sarcoma and Central Nervous System/Pediatrics), a Proton Center facility, an MR-Linac, a Gamma Knife clinic and an array of brachytherapy services. Due to the scope of our services, we have gained experience in dealing with the rapidly changing pandemic effects on our clinical practice. Our paper provides a resource to other Medical Physics practices in search of workflows that have been resilient during these challenging times.