RESUMO
Purpose.Present and validate an analytical model (AM) to calculate efficiency and spatial resolution of multi-parallel slit (MPS) and knife-edge slit (KES) cameras in the context of prompt gamma (PG) imaging in proton therapy, as well as perform a fair comparison between two prototypes of these cameras with their design specifications.Materials and methods.Monte Carlo (MC) simulations with perfect (ideal) conditions were performed to validate the proposed AM, as well as simulations in realistic conditions for the comparison of both prototypes. The spatial resolution obtained from simulations was derived from reconstructed PG profiles. The falloff retrieval precision (FRP) was quantified based on the variability of PG profiles from 50 different realizations.Results.The AM shows that KES and MPS designs fulfilling 'MPS-KES similar conditions' should have very close actual performances if the KES slit width corresponds to the half of the MPS slit width. Reconstructed PG profiles from simulated data with both cameras were used to compute the efficiency and spatial resolutions to compare against the model predictions. The FRP of both cameras was calculated with realistic detection conditions for beams with 107, 108and 109incident protons. A good agreement was found between the values predicted by the AM and those obtained from MC simulations (relative deviations of the order of 5%).Conclusion.The MPS camera outperforms the KES camera with their design specifications in realistic conditions and both systems can reach millimetric precision in the determination of the falloff position with 108or more initial protons.
Assuntos
Câmaras gama , Terapia com Prótons , Prótons , Método de Monte Carlo , Terapia com Prótons/métodos , Diagnóstico por Imagem , Raios gama , Imagens de FantasmasRESUMO
For real-time monitoring of the longitudinal position of the Bragg-peak during an ion therapy treatment, a novel non-invasive technique has been recently proposed that exploits the detection of prompt gamma-rays issued from nuclear fragmentation. Two series of experiments have been performed at the GANIL and GSI facilities with 95 and 305 MeV/u (12)C(6+) ion beams stopped in PMMA and water phantoms. In both experiments, a clear correlation was obtained between the carbon ion range and the prompt photon profile. Additionally, an extensive study has been performed to investigate whether a prompt neutron component may be correlated with the carbon ion range. No such correlation was found. The present paper demonstrates that a collimated set-up can be used to detect single photons by means of time-of-flight measurements, at those high energies typical for ion therapy. Moreover, the applicability of the technique both at cyclotron and at synchrotron facilities is shown. It is concluded that the detected photon count rates provide sufficiently high statistics to allow real-time control of the longitudinal position of the Bragg-peak under clinical conditions.
Assuntos
Radioterapia com Íons Pesados , Fótons , Radiometria/métodos , Nêutrons Rápidos , Análise Espectral , Fatores de TempoRESUMO
Compton cameras are gamma-ray imaging systems which have been proposed for a wide variety of applications such as medical imaging, nuclear decommissioning or homeland security. In the design and optimization of such a system Monte Carlo simulations play an essential role. In this work, we propose a generic module to perform Monte Carlo simulations and analyses of Compton Camera imaging which is included in the open-source GATE/Geant4 platform. Several digitization stages have been implemented within the module to mimic the performance of the most commonly employed detectors (e.g. monolithic blocks, pixelated scintillator crystals, strip detectors...). Time coincidence sorter and sequence coincidence reconstruction are also available in order to aim at providing modules to facilitate the comparison and reproduction of the data taken with different prototypes. All processing steps may be performed during the simulation (on-the-fly mode) or as a post-process of the output files (offline mode). The predictions of the module have been compared with experimental data in terms of energy spectra, angular resolution, efficiency and back-projection image reconstruction. Consistent results within a 3-sigma interval were obtained for the energy spectra except for low energies where small differences arise. The angular resolution measure for incident photons of 1275 keV was also in good agreement between both data sets with a value close to 13°. Moreover, with the aim of demonstrating the versatility of such a tool the performance of two different Compton camera designs was evaluated and compared.
Assuntos
Simulação por Computador , Câmaras gama , Radiografia/métodos , Método de Monte Carlo , Fótons , Radiografia/instrumentaçãoRESUMO
In order to fully exploit the ballistic potential of particle therapy, we propose an online range monitoring concept based on time-of-flight (TOF)-resolved prompt gamma (PG) detection in a single proton counting regime. In a proof of principle experiment, different types of monolithic scintillating gamma detectors are read in time coincidence with a diamond-based beam hodoscope, in order to build TOF spectra of PG generated in a target presenting an air cavity of variable thickness. Since the measurement was carried out at low beam currents (< 1 proton/bunch) it was possible to reach excellent coincidence time resolutions, of the order of 100 ps (σ). Our goal is to detect possible deviations of the proton range with respect to treatment planning within a few intense irradiation spots at the beginning of the session and then carry on the treatment at standard beam currents. The measurements were limited to 10 mm proton range shift. A Monte Carlo simulation study reproducing the experiment has shown that a 3 mm shift can be detected at 2σ by a single detector of â¼1.4 × 10-3 absolute detection efficiency within a single irradiation spot (â¼108 protons) and an optimised experimental set-up.
Assuntos
Terapia com Prótons/métodos , Raios gama , Humanos , Método de Monte Carlo , Imagens de FantasmasRESUMO
PURPOSE: Targeted radiation therapy has seen an increased interest in the past decade. In vitro and in vivo experiments showed enhanced radiation doses due to gold nanoparticles (GNPs) to tumors in mice and demonstrated a high potential for clinical application. However, finding a functionalized molecular formulation for actively targeting GNPs in tumor cells is challenging. Furthermore, the enhanced energy deposition by secondary electrons around GNPs, particularly by short-ranged Auger electrons is difficult to measure. Computational models, such as Monte Carlo (MC) radiation transport codes, have been used to estimate the physical quantities and effects of GNPs. However, as these codes differ from one to another, the reliability of physical and dosimetric quantities needs to be established at cellular and molecular levels, so that the subsequent biological effects can be assessed quantitatively. METHODS: In this work, irradiation of single GNPs of 50 nm and 100 nm diameter by X-ray spectra generated by 50 and 100 peak kilovoltages was simulated for a defined geometry setup, by applying multiple MC codes in the EURADOS framework. RESULTS: The mean dose enhancement ratio of the first 10 nm-thick water shell around a 100 nm GNP ranges from 400 for 100 kVp X-rays to 600 for 50 kVp X-rays with large uncertainty factors up to 2.3. CONCLUSIONS: It is concluded that the absolute dose enhancement effects have large uncertainties and need an inter-code intercomparison for a high quality assurance; relative properties may be a better measure until more experimental data is available to constrain the models.
Assuntos
Ouro/química , Nanopartículas Metálicas/química , Radioterapia/métodos , Animais , Simulação por Computador , Elétrons , Humanos , Imageamento Tridimensional , Técnicas In Vitro , Camundongos , Método de Monte Carlo , Neoplasias/diagnóstico por imagem , Controle de Qualidade , Radiometria , Reprodutibilidade dos Testes , Água , Raios XRESUMO
No established second-line chemotherapy is available for patients with advanced gastric cancer failing to respond or progressing to first-line chemotherapy. However, 20-40% of these patients commonly receive second-line chemotherapy. We evaluated the influence of clinico-pathologic factors on the survival of 175 advanced gastric cancer patients, who received second-line chemotherapy at three oncology departments. Univariate and multivariate analyses found five factors which were independently associated with poor overall survival: performance status 2 (hazard ratio (HR), 1.79; 95% CI, 1.16-2.77; P=0.008), haemoglobin =11.5 g l(-1) (HR, 1.48; 95% CI, 1.06-2.05; P=0.019), CEA level >50 ng ml(-1) (HR, 1.86; 95% CI, 1.21-2.88; P=0.004), the presence of greater than or equal to three metastatic sites of disease (HR, 1.72; 95% CI, 1.16-2.53; P=0.006), and time-to-progression under first-line chemotherapy =6 months (HR, 1.97; 95% CI, 1.39-2.80; P<0.0001). A prognostic index was constructed dividing patients into low- (no risk factor), intermediate- (one to two risk factors), or high- (three to five risk factors) risk groups, and median survival times for each group were 12.7 months, 7.1 months, and 3.3 months, respectively (P<0.001). In the absence of data deriving from randomised trials, this analysis suggests that some easily available clinical factors may help to select patients with advanced gastric cancer who could derive more benefit from second-line chemotherapy.
Assuntos
Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno Carcinoembrionário/análise , Progressão da Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Neoplasias Gástricas/mortalidadeRESUMO
The primary end point of the study was the analysis of associations between polymorphisms with putative influence on 5-fluorouracil/irinotecan activity and progression-free survival (PFS) of patients with advanced colorectal cancer treated with first-line FOLFIRI chemotherapy. Peripheral blood samples from 146 prospectively enrolled patients were used for genotyping polymorphisms in thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR), excision repair cross-complementation group-1 (ERCC 1) xeroderma pigmentosum group-D (XPD), X-ray cross-complementing-1 (XRCC 1), X-ray cross-complementing-3 (XRCC 3) and uridine diphosphate-glucuronosyltransferases-A1 (UGT1 A1). TS 3'-UTR 6+/6+ and XRCC3-241 C/C genotypes were associated with adverse PFS. Hazard ratio for PFS achieved 2.89 (95% confidence interval=1.56-5.80; P=0.002) in 30 patients (20%) with both risk genotypes. Risk for Grade III-IV neutropenia was significantly associated with UGT1A1*28 7/7 genotype. These promising findings deserve further investigations and their validation in independent prospective studies.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Perfilação da Expressão Gênica/métodos , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Camptotecina/análogos & derivados , Camptotecina/farmacologia , Camptotecina/uso terapêutico , Intervalo Livre de Doença , Feminino , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Genótipo , Humanos , Irinotecano , Leucovorina/farmacologia , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Farmacogenética/métodos , Polimorfismo Genético/efeitos dos fármacos , Polimorfismo Genético/genética , Estudos ProspectivosRESUMO
The level of blood pressure, the type of antihypertensive treatment and the prevalence of resistant hypertension at the first examination were evaluated in 6254 patients referred to a hospital Hypertension Unit from 1989 to 2003. From 1989-1993 to 1999-2003, we observed a reduced prevalence of grade 2 and grade 3 hypertension, and an increase in the prevalence of grade 1 hypertension, the proportion of treated subjects, the average number of antihypertensive drugs per patient and the prevalence of resistant hypertension.
Assuntos
Hipertensão/epidemiologia , Anti-Hipertensivos , Pressão Sanguínea , Feminino , Unidades Hospitalares , Humanos , Hipertensão/tratamento farmacológico , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
Particle therapy is increasingly attractive for the treatment of tumors and the number of facilities offering it is rising worldwide. Due to the well-known enhanced effectiveness of ions, it is of utmost importance to plan treatments with great care to ensure tumor killing and healthy tissues sparing. Hence, the accurate quantification of the relative biological effectiveness (RBE) of ions, used in the calculation of the biological dose, is critical. Nevertheless, the RBE is a complex function of many parameters and its determination requires modeling. The approaches currently used have allowed particle therapy to thrive, but still show some shortcomings. We present herein a short description of a new theoretical framework, NanOx, to calculate cell survival in the context of particle therapy. It gathers principles from existing approaches, while addressing some of their weaknesses. NanOx is a multiscale model that takes the stochastic nature of radiation at nanometric and micrometric scales fully into account, integrating also the chemical aspects of radiation-matter interaction. The latter are included in the model by means of a chemical specific energy, determined from the production of reactive chemical species induced by irradiation. Such a production represents the accumulation of oxidative stress and sublethal damage in the cell, potentially generating non-local lethal events in NanOx. The complementary local lethal events occur in a very localized region and can, alone, lead to cell death. Both these classes of events contribute to cell death. The comparison between experimental data and model predictions for the V79 cell line show a good agreement. In particular, the dependence of the typical shoulders of cell survival curves on linear energy transfer are well described, but also the effectiveness of different ions, including the overkill effect. These results required the adjustment of a number of parameters compatible with the application of the model in a clinical scenario thereby showing the potential of NanOx. Said parameters are discussed in detail in this paper.
Assuntos
Sobrevivência Celular/efeitos da radiação , Partículas Elementares/uso terapêutico , Fibroblastos/efeitos da radiação , Pulmão/efeitos da radiação , Modelos Teóricos , Animais , Células Cultivadas , Cricetinae , Cricetulus , Fibroblastos/citologia , Transferência Linear de Energia , Pulmão/citologia , Eficiência Biológica RelativaRESUMO
Single photon emission computed tomography (SPECT) is at present one of the major techniques for non-invasive diagnostics in nuclear medicine. The clinical routine is mostly based on collimated cameras, originally proposed by Hal Anger. Due to the presence of mechanical collimation, detection efficiency and energy acceptance are limited and fixed by the system's geometrical features. In order to overcome these limitations, the application of Compton cameras for SPECT has been investigated for several years. In this study we compare a commercial SPECT-Anger device, the General Electric HealthCare Infinia system with a High Energy General Purpose (HEGP) collimator, and the Compton camera prototype under development by the French collaboration CLaRyS, through Monte Carlo simulations (GATE-GEANT4 Application for Tomographic Emission-version 7.1 and GEANT4 version 9.6, respectively). Given the possible introduction of new radio-emitters at higher energies intrinsically allowed by the Compton camera detection principle, the two detectors are exposed to point-like sources at increasing primary gamma energies, from actual isotopes already suggested for nuclear medicine applications. The Compton camera prototype is first characterized for SPECT application by studying the main parameters affecting its imaging performance: detector energy resolution and random coincidence rate. The two detector performances are then compared in terms of radial event distribution, detection efficiency and final image, obtained by gamma transmission analysis for the Anger system, and with an iterative List Mode-Maximum Likelihood Expectation Maximization (LM-MLEM) algorithm for the Compton reconstruction. The results show for the Compton camera a detection efficiency increased by a factor larger than an order of magnitude with respect to the Anger camera, associated with an enhanced spatial resolution for energies beyond 500 keV. We discuss the advantages of Compton camera application for SPECT if compared to present commercial Anger systems, with particular focus on dose delivered to the patient, examination time, and spatial uncertainties.
Assuntos
Câmaras gama , Tomografia Computadorizada de Emissão de Fóton Único/instrumentação , Algoritmos , Benchmarking , Humanos , Método de Monte Carlo , Imagens de Fantasmas , Fótons , ProbabilidadeRESUMO
Ion beam therapy enables a highly accurate dose conformation delivery to the tumor due to the finite range of charged ions in matter (i.e. Bragg peak (BP)). Consequently, the dose profile is very sensitive to patients anatomical changes as well as minor mispositioning, and so it requires improved dose control techniques. Proton interaction vertex imaging (IVI) could offer an online range control in carbon ion therapy. In this paper, a statistical method was used to study the sensitivity of the IVI technique on experimental data obtained from the Heidelberg Ion-Beam Therapy Center. The vertices of secondary protons were reconstructed with pixelized silicon detectors. The statistical study used the [Formula: see text] test of the reconstructed vertex distributions for a given displacement of the BP position as a function of the impinging carbon ions. Different phantom configurations were used with or without bone equivalent tissue and air inserts. The inflection points in the fall-off region of the longitudinal vertex distribution were computed using different methods, while the relation with the BP position was established. In the present setup, the resolution of the BP position was about 4-5 mm in the homogeneous phantom under clinical conditions (106 incident carbon ions). Our results show that the IVI method could therefore monitor the BP position with a promising resolution in clinical conditions.
Assuntos
Radioterapia com Íons Pesados/métodos , Radioterapia Assistida por Computador/métodos , Humanos , Imagens de Fantasmas , Prótons , Dosagem RadioterapêuticaRESUMO
BACKGROUND: Elderly patients have been often excluded from or underrepresented in the study populations of combination chemotherapy trials. The primary end point of this study was to determine the response rate and the toxicity of the weekly oxaliplatin, 5-fluorouracil and folinic acid (OXALF) regimen in elderly patients with advanced gastric cancer. The secondary objective was to measure the time to disease progression and the survival time. METHODS: Chemotherapy-naive patients with advanced gastric cancer aged 70 or older were considered eligible for study entry. Patients received weekly oxaliplatin 40 mg/m2, fluorouracil 500 mg/m2 and folinic acid 250 mg/m2. All drugs were given intravenously on a day-1 schedule. RESULTS: A total of 42 elderly patients were enrolled. Median age was 73 years and all patients had metastatic disease. The response rate according to RECIST criteria was 45.2% (95% CIs: 30%-56%) with two complete responses, 17 partial responses, 13 stable diseases and 10 progressions, for an overall tumor rate control of 76.2% (32 patients). Toxicity was generally mild and only three patients discontinued treatment because of treatment related adverse events. The most common treatment-related grade 3/4 adverse events were fatigue (7.1%), diarrhoea (4.8%), mucositis (2.4%), neurotoxicity (2.4%) and neutropenia (4.8%). The median response duration was 5.3 months (95% CIs: 2.13 - 7.34), the median time to disease progression was 5.0 months (95% CIs: 3.75 - 6.25) and the median survival time was 9.0 months (95% CIs: 6.18 - 11.82). CONCLUSION: OXALF represents an active and well-tolerated treatment modality for elderly patients with locally advanced and metastatic gastric cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/secundário , Taxa de SobrevidaRESUMO
Blood pressure measurement is the cornerstone for the diagnosis, the treatment and the research on arterial hypertension, and all of the decisions about one of these single aspects may be dramatically influenced by the accuracy of the measurement. Over the past 20 years or so, the accuracy of the conventional Riva-Rocci/Korotkoff technique of blood pressure measurement has been questioned and efforts have been made to improve the technique with automated devices. In the same period, recognition of the phenomenon of white coat hypertension, whereby some individuals with an apparent increase in blood pressure have normal, or reduced, blood pressures when measurement is repeated away from the medical environment, has focused attention on methods of measurement that provide profiles of blood pressure behavior rather than relying on isolated measurements under circumstances that may in themselves influence the level of blood pressure recorded. These methodologies have included repeated measurements of blood pressure using the traditional technique, self-measurement of blood pressure in the home or work place, and ambulatory blood pressure measurement using innovative automated devices. The purpose of this review to serve as a source of practical information about the commonly used methods for blood pressure measurement: the traditional Riva-Rocci method and the automated methods.
Assuntos
Determinação da Pressão Arterial/métodos , Determinação da Pressão Arterial/instrumentação , Humanos , Visita a Consultório Médico , Reprodutibilidade dos Testes , AutocuidadoRESUMO
The purpose of this review is to summarize the current knowledge regarding metabolic syndrome prevalence and features in primary aldosteronism. We will also discuss the link between aldosterone and the different metabolic changes typical of the metabolic syndrome. Hypertensive patients have a high prevalence of obesity, dyslipidemia and hyperglycaemia. These are risk factors for the metabolic syndrome, and are associated with an increased cardiovascular risk profile. In particular, insulin resistance seems to be the major alteration in patients affected by primary aldosteronism. We will then describe the experimental and clinical evidences of the role of aldosterone in the pathogenesis of insulin resistance. Higher rates of cardiovascular events have been recently reported in primary aldosteronism: they could be partly due to the increased prevalence of the metabolic syndrome in this disorder.
Assuntos
Aldosterona/fisiologia , Síndrome Metabólica/etiologia , Humanos , Hiperaldosteronismo/complicações , Hiperaldosteronismo/etiologia , Hiperaldosteronismo/metabolismo , Resistência à Insulina , Síndrome Metabólica/metabolismo , Obesidade/complicações , Obesidade/metabolismoRESUMO
The present study was undertaken in an attempt to elucidate the mechanism(s) underlying transferrin (TRF) receptor expression in human erythroleukemic (K562 and HEL) lines during the exponential and the plateau phase of growth. TRF receptor synthesis is enhanced when stationary cells are subcultured at low density in fresh medium. This rise occurs in either the presence or the absence of serum, which is associated with cell proliferation or quiescence, respectively. In the presence of serum, it is not inhibited by the addition of hydroxyurea (i.e., an agent blocking DNA synthesis). Thus, the receptor synthesis is enhanced not only in subcultures of actively proliferating cells (in the presence of serum), but also in subcultures of quiescent elements (in the absence of serum or upon the addition of serum plus hydroxyurea). Conversely, the ferritin content is markedly decreased when stationary cells are subcultured at low density, in either the presence or the absence of serum. These results suggest that stationary cells subcultured in fresh medium undergo a depletion of their intracellular iron pool, which in turn may represent the stimulus triggering TRF receptor synthesis. This hypothesis is supported by two observations: both the depletion of this pool and the rise in TRF receptor synthesis are more marked in the absence than in the presence of serum; addition of excess exogenous iron fully inhibits the rise of TRF receptor synthesis in cells subcultured with fresh medium and serum.
Assuntos
Leucemia Eritroblástica Aguda/metabolismo , Receptores da Transferrina/biossíntese , Fenômenos Fisiológicos Sanguíneos , Divisão Celular , Linhagem Celular , Ferritinas/análise , Humanos , Ferro/análise , Leucemia Eritroblástica Aguda/patologia , Receptores da Transferrina/análiseRESUMO
The expression of transferrin receptors (TrfRs) was investigated in acute T-cell leukemia (T-ALL) blasts at the molecular, biochemical, immunological, and functional level. TrfRs, although not detected on quiescent T-cells from normal adults, are constitutively expressed at high level on the blasts from all T-ALL patients and bind normally to transferrin. Their number is modulated by the intracellular iron level, but is independent of exogenous interleukin 2. They also exhibit immunological and biochemical abnormalities, in that: (a) they react preferentially with monoclonal antibodies (MAb) that recognize ligand-binding domains of TrfR (42/6 and 43/31), as compared to MAbs (B3/25, OKT9) that interact with the nonligand binding domains; (b) they have a reduced molecular weight, as compared to TrfR on normal thymocytes and activated T-lymphocytes: this phenomenon is apparently related to a defective glycosylation. It is noteworthy that expression of TrfR was not observed in a large series of other types of acute leukemias, i.e., pre-B, B, and myeloid leukemias, excluding erythroleukemias. The constitutive, high level expression of TrfRs on T-ALL blasts may play a key role in the stepwise progression of this malignancy and particularly provide a proliferative advantage to T-ALL blasts as compared to normal T-lymphocytes. Furthermore, indirect evidence suggests that the glycosylation defect of TrfR on T-ALL blasts contributes to their tumorigenic capacity.
Assuntos
Leucemia-Linfoma de Células T do Adulto/metabolismo , Receptores da Transferrina/metabolismo , Linfócitos T/metabolismo , Anticorpos Monoclonais/imunologia , Northern Blotting , Eletroforese em Gel de Poliacrilamida , Glicosilação , Humanos , Ferro/farmacologia , Quelantes de Ferro/farmacologia , RNA Mensageiro/análise , Receptores da Transferrina/efeitos dos fármacos , Receptores da Transferrina/genética , Receptores da Transferrina/imunologiaRESUMO
There is interest in the particle therapy community in using prompt gammas (PGs), a natural byproduct of particle treatment, for range verification and eventually dose control. However, PG production is a rare process and therefore estimation of PGs exiting a patient during a proton treatment plan executed by a Monte Carlo (MC) simulation converges slowly. Recently, different approaches to accelerating the estimation of PG yield have been presented. Sterpin et al (2015 Phys. Med. Biol. 60 4915-46) described a fast analytic method, which is still sensitive to heterogeneities. El Kanawati et al (2015 Phys. Med. Biol. 60 8067-86) described a variance reduction method (pgTLE) that accelerates the PG estimation by precomputing PG production probabilities as a function of energy and target materials, but has as a drawback that the proposed method is limited to analytical phantoms. We present a two-stage variance reduction method, named voxelized pgTLE (vpgTLE), that extends pgTLE to voxelized volumes. As a preliminary step, PG production probabilities are precomputed once and stored in a database. In stage 1, we simulate the interactions between the treatment plan and the patient CT with low statistic MC to obtain the spatial and spectral distribution of the PGs. As primary particles are propagated throughout the patient CT, the PG yields are computed in each voxel from the initial database, as a function of the current energy of the primary, the material in the voxel and the step length. The result is a voxelized image of PG yield, normalized to a single primary. The second stage uses this intermediate PG image as a source to generate and propagate the number of PGs throughout the rest of the scene geometry, e.g. into a detection device, corresponding to the number of primaries desired. We achieved a gain of around 103 for both a geometrical heterogeneous phantom and a complete patient CT treatment plan with respect to analog MC, at a convergence level of 2% relative uncertainty in the 90% yield region. The method agrees with reference analog MC simulations to within 10-4, with negligible bias. Gains per voxel range from 102 to 104. The presented generic PG yield estimator is drop-in usable with any geometry and beam configuration. We showed a gain of three orders of magnitude compared to analog MC. With a large number of voxels and materials, memory consumption may be a concern and we discuss the consequences and possible tradeoffs. The method is available as part of Gate 7.2.
Assuntos
Simulação por Computador , Raios gama , Método de Monte Carlo , Imagens de Fantasmas , Terapia com Prótons , Radiometria/instrumentação , Humanos , Prótons , Radiometria/métodos , Radioterapia Assistida por ComputadorRESUMO
PURPOSE: A multiinstitutional trial was performed to confirm the clinical activity, in terms of response rate and toxicity (primary objectives) and duration of responses and survival (secondary objectives), of an intensive weekly regimen in advanced gastric cancer. PATIENTS AND METHODS: Patients with measurable unresectable and/or metastatic gastric carcinoma received 1-day per week administration of cisplatin (CDDP) 40 mg/m2, fluorouracil (5FU) 500 mg/m2, epi-doxorubicin (epi-ADR) 35 mg/m2, 6S-stereoisomer of leucovorin 250 mg/m2, and glutathione 1.5 g/m2. On the other days, filgrastim was administered by subcutaneous injection at a dose of 5 mg/kg. One cycle of therapy consisted of eight 1-week treatments. Patients who showed a response or stable disease received a further 6 weeks of therapy. RESULTS: Of 105 enrolled patients, 11 had locally advanced unresectable disease only; 33 had primary nonresected and metastatic disease; 48 had metastatic disease and primary tumor resected; 10 had locoregional recurrence and metastatic disease; and three had locoregional recurrence only. After one cycle, 18 complete responses (CRs) and 47 partial responses (PRs) were achieved, for an overall response rate of 62% (95% confidence interval [CI], 53% to 71%). Twenty patients had stable disease and 20 progressed on therapy. The median survival duration of all 105 patients was 11 months, with 1- and 2-year survival rates of 42% and 5%, respectively. World Health Organization (WHO) grade III to IV toxicity, in terms of anemia, neutropenia, thrombocytopenia, and mucositis, was experienced by 40 patients (38%). There were no treatment-related deaths. CONCLUSION: These data support the results of the pilot study and confirmed the high activity of the regimen, with acceptable toxicity. This schedule deserves evaluation in the adjuvant setting.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Análise de SobrevidaRESUMO
BACKGROUND: Screening for oesophageal varices represents an important part of the diagnostic work-up of cirrhotic patients. We have previously shown that the platelet count/spleen diameter ratio is a parameter that can rule out the presence of oesophageal varices safely and in a cost-effective fashion. AIM: To evaluate the prognostic and diagnostic accuracy of the platelet count/spleen diameter ratio for ruling out the presence of oesophageal varices in the follow-up of a cohort of cirrhotic patients without oesophageal varices at inclusion. METHODS: After initial endoscopy, the 106 cirrhotic patients without oesophageal varices who participated in our previous study were followed-up with annual or biannual surveillance endoscopy. Patients were censored at the time of diagnosis of oesophageal varices or at their last visit, and at that time platelet count and spleen diameter were recorded. Sixty-eight patients made up the study cohort after excluding patients who were lost to follow-up or died before undergoing control endoscopy. RESULTS: During the follow-up, 27 patients (40%) developed oesophageal varices. Patients with higher baseline platelet count/spleen diameter ratios (p<0.0001) as well as a ratio above 909 were less likely to develop oesophageal varices (p<0.0005). At follow-up, a platelet count/spleen diameter ratio < or = 909 had 100% negative predictive value and 84% efficiency in identifying the presence of oesophageal varices. CONCLUSIONS: The use of the platelet count/spleen diameter ratio proved to be an effective means for ruling out the presence of oesophageal varices even in the longitudinal follow-up of patients.