Planificación radioterápica de intensidad modulada basada en un modelo de simulación explícita del transporte de partículas mediante optimización por imágen médica

Falta resumen y palabras claveIntroducción: La planificación radioterápica más precisa es la basada en un cálculo del transporte explícito del haz de partículas, desde su generación en la cabeza del acelerador lineal, y en su interacción con los modificadores y colimadores, hasta la deposición de su energía en los tejidos del paciente con densidades heterogéneas. No obstante, este cálculo exige un tiempo de computación inviable para la práctica clínica diaria. En este trabajo se presenta un modelo de optimización de abertura directa que está exclusivamente basado en los datos de la imagen del paciente, y que se implementa en un sistema propio de planificación de tratamientos Monte Carlo (MCTPS), con objeto de resolver tratamientos de radioterapia complejos con resultados óptimos y en tiempos eficientes para ser adaptado a la práctica clínica. Método: El sistema de planificación es un sistema full Monte Carlo (fMC), controlado mediante una interfaz de Matlab®, que está basado en la generación de matrices, que conforman un mapa denominado biofísico, el cual es generado a partir de los datos de la imagen del paciente para conseguir un juego de segmentos realizable óptimo. En orden a reducir los tiempos de computación necesarios, el mapa de fluencia convencional ha sido sustituido por el conjunto de mapas biofísicos, el cual es secuenciado para proporcionar las aberturas que posteriormente serán pesadas mediante un algoritmo de optimización basado en un modelo de programación lineal, que permite optimizar la distribución de dosis al nivel del vóxel. Un algoritmo de ray-casting extrae del CT del paciente la información de las estructuras de interés, el espesor atravesado, así como los valores PET, si los hay. Los datos son guardados para generar los mapas biofísicos en cada incidencia. Estos mapas son los ficheros inputs de un secuenciador propio desarrollado para este fin. Se simularon espacios de fase para distintos aceleradores (Primus de Siemens y Axesse de Elekta) para varias energías (6, 9, 12, 15 MeVy 6 MV). Los espacios de fase fueron simulados con el código EGSnrc/BEAMnrc. El cálculo de dosis en el paciente fue simulado con el código BEAMDOSE. Este código es una versión modificada de EGSnrc/DOSXYZnrc capaz de calcular la dosis sobre cada vóxel debido a cada segmento, y así estar en disposición de combinarlos con diferentes pesos durante el proceso de optimización. Resultados: Se han estudiado casos complejos con distintas características, para chequear el algoritmo de planificación en situaciones en las que el cálculo MC ofrece un valor añadido: Un caso de cabeza y cuello (Caso I) con tres blancos delineados a partir de la imagen PET/CT y con un escalado de dosis exigente; un caso de mama parcial (Caso II) para ser resuelto con haces de electrones modulados (IMRT+MERT); y un caso de lecho prostático (Caso III) con una geometría cóncava acusada. En estos tres casos, las dosis de prescripción y límites en los órganos de riesgo fueron satisfactorias en un tiempo lo suficientemente corto como para permitir implementarlo en la rutina clínica. Estas soluciones teóricas fueron verificadas experimentalmente con éxito. Conclusiones: Se ha desarrollado un modelo de planificación de tratamiento Monte Carlo basado exclusivamente en mapas diseñados a partir de la imagen del paciente. La secuenciación de estos mapas permite obtener aberturas realizables las cuales son moduladas mediante una formulación de programación lineal, permitiendo una optimización de la dosis al nivel del vóxel. El modelo es capaz de resolver casos complejos de radioterapia con una gran precisión y empleando tiempos de computación asumibles para la aplicación clínica

Accurate,robust and harmonized implementation of morpho-functional imaging in treatment planning for personalized radiotherapy

In this work we present a methodology able to use harmonized PET/CT imaging in dose painting by number (DPBN) approach by means of a robust and accurate treatment planning system. Image processing and treatment planning were performed by using a Matlab-based platform, called CARMEN, in which a full Monte Carlo simulation is included. Linear programming formulation was developed for a voxel-by-voxel robust optimization and a specific direct aperture optimization was designed for an efficient adaptive radiotherapy implementation. DPBN approach with our methodology was tested to reduce the uncertainties associated with both, the absolute value and the relative value of the information in the functional image. For the same H&N case, a single robust treatment was planned for dose prescription maps corresponding to standardized uptake value distributions from two different image reconstruction protocols: One to fulfill EARL accreditation for harmonization of [18F]FDG PET/CT image, and the other one to use the highest available spatial resolution. Also, a robust treatment was planned to fulfill dose prescription maps corresponding to both approaches, the dose painting by contour based on volumes and our voxel-by-voxel DPBN. Adaptive planning was also carried out to check the suitability of our proposal. Different plans showed robustness to cover a range of scenarios for implementation of harmonizing strategies by using the highest available resolution. Also, robustness associated to discretization level of dose prescription according to the use of contours or numbers was achieved. All plans showed excellent quality index histogram and quality factors below 2%. Efficient solution for adaptive radiotherapy based directly on changes in functional image was obtained. We proved that by using voxel-by-voxel DPBN approach it is possible to overcome typical drawbacks linked to PET/CT images, providing to the clinical specialist confidence enough for routinely implementation of functional imaging for personalized radiotherapy.Junta de Andalucía (FISEVI, reference project CTS 2482)European Regional Development Fund (FEDER

Biological control of strawberry soil-borne pathogens Macrophomina phaseolina and Fusarium solani, using Trichoderma asperellum and Bacillus spp.

In south-western Spain, Macrophomina phaseolina and Fusarium solani were found to be associated in strawberry plants with, respectively, charcoal rot, and crown and root rot symptoms. For management of both fungal diseases, the antagonistic effects of two commercial formulations, one based on Trichoderma asperellum T18 strain (Prodigy®) and the other on Bacillus megaterium and B. laterosporus (Fusbact®), were evaluated in vitro and under controlled environment and field conditions. Two inoculation methods (root-dipping and soil application) and two application times (pre- and post-pathogen inoculation, as preventive and curative treatments, respectively) were assessed. Dual plate confrontation experiments demonstrated the antagonistic effects of T. asperellum and Bacillus spp. by inhibiting radial growth of M. phaseolina and F. solani by more than 36%. Preventive application of T. asperellum by root-dipping reduced the incidence of charcoal rot (up to 44% in a growth chamber and up to 65% under field conditions) and also reduced disease progression, the percentage of crown necrosis, as well as the level of infection measured as ng of pathogen DNA g-1 plant by quantitative real-time PCR. This treatment was also the most effective for reduction of crown and root rot caused by F. solani (up to 100% in a greenhouse and up to 81% under field conditions). These results were nearly comparable with the control achieved using chemical fungicides. The Bacillus spp.-based formulation was also effective for control of charcoal rot and showed variable results for control of F. solani, depending on the growth conditions

3D VMAT Verification Based on Monte Carlo Log File Simulation with Experimental Feedback from Film Dosimetry.

A model based on a specific phantom, called QuAArC, has been designed for the evaluation of planning and verification systems of complex radiotherapy treatments, such as volumetric modulated arc therapy (VMAT). This model uses the high accuracy provided by the Monte Carlo (MC) simulation of log files and allows the experimental feedback from the high spatial resolution of films hosted in QuAArC. This cylindrical phantom was specifically designed to host films rolled at different radial distances able to take into account the entrance fluence and the 3D dose distribution. Ionization chamber measurements are also included in the feedback process for absolute dose considerations. In this way, automated MC simulation of treatment log files is implemented to calculate the actual delivery geometries, while the monitor units are experimentally adjusted to reconstruct the dose-volume histogram (DVH) on the patient CT. Prostate and head and neck clinical cases, previously planned with Monaco and Pinnacle treatment planning systems and verified with two different commercial systems (Delta4 and COMPASS), were selected in order to test operational feasibility of the proposed model. The proper operation of the feedback procedure was proved through the achieved high agreement between reconstructed dose distributions and the film measure- ments (global gamma passing rates > 90% for the 2%/2 mm criteria). The necessary discre- tization level of the log file for dose calculation and the potential mismatching between calculated control points and detection grid in the verification process were discussed. Besides the effect of dose calculation accuracy of the analytic algorithm implemented in treatment planning systems for a dynamic technique, it was discussed the importance of the detection density level and its location in VMAT specific phantom to obtain a more reliable DVH in the patient CT. The proposed model also showed enough robustness and efficiency to be considered as a pre-treatment VMAT verification system.Ministerio de Ciencia y Tecnología SAF2011- 27116; IPT-2011-1480-900000

Impact of SBRT fractionation in hypoxia dose painting - Accounting for heterogeneous and dynamic tumor oxygenation

Purpose Tumor hypoxia, often found in nonsmall cell lung cancer (NSCLC), implies an increased resistance to radiotherapy. Pretreatment assessment of tumor oxygenation is, therefore, warranted in these patients, as functional imaging of hypoxia could be used as a basis for dose painting. This study aimed at investigating the feasibility of using a method for calculating the dose required in hypoxic subvolumes segmented on F-18-HX4 positron emission tomography (PET) imaging of NSCLC. Methods Positron emission tomography imaging data based on the hypoxia tracer F-18-HX4 of 19 NSCLC patients were included in the study. Normalized tracer uptake was converted to oxygen partial pressure (pO(2)) and hypoxic target volumes (HTVs) were segmented using a threshold of 10 mmHg. Uniform doses required to overcome the hypoxic resistance in the target volumes were calculated based on a previously proposed method taking into account the effect of interfraction reoxygenation, for fractionation schedules ranging from extremely hypofractionated stereotactic body radiotherapy (SBRT) to conventionally fractionated radiotherapy. Results Gross target volumes ranged between 6.2 and 859.6 cm(3), and the hypoxic fraction <10 mmHg between 1.2% and 72.4%. The calculated doses for overcoming the resistance of cells in the HTVs were comparable to those currently prescribed in clinical practice as well as those previously tested in feasibility studies on dose escalation in NSCLC. Depending on the size of the HTV and the distribution of pO(2), HTV doses were calculated as 43.6-48.4 Gy for a three-fraction schedule, 51.7-57.6 Gy for five fractions, and 59.5-66.4 Gy for eight fractions. For patients in whom the HTV pO(2) distribution was more favorable, a lower dose was required despite a bigger volume. Tumor control probability was lower for single-fraction schedules, while higher levels of tumor control probability were found for schedules employing several fractions. Conclusions The method to account for heterogeneous and dynamic hypoxia in target volume segmentation and dose prescription based on F-18-HX4-PET imaging appears feasible in NSCLC patients. The distribution of oxygen partial pressure within HTV could impact the required prescribed dose more than the size of the volume

Organic amendments conditions on the control of Fusarium crown and root rot of asparagus caused by three Fusarium spp.

Fusarium oxysporum (Fo), F. proliferatum (Fp) and F. solani (Fs) are causal agents associated with roots of asparagus affected by crown and root rot, a disease inflicting serious losses worldwide. The propagule viability of Fusarium spp. was determined on substrate artificially infested with Fo5, Fp3or Fs2 isolates,amended with either poultry manure (PM), its pellet (PPM), or olive residue compost (ORC) and, thereafter, incubated at 30 or 35°C for different periods. Inoculum viability was significantly affected by these organic amendments (OAs) in combination with temperature and incubation period. The greatest reduction in viability of Fo5 and Fs2 occurred with PPM and loss of viability achieved was higher at 35°C than at 30ºC, and longer incubation period (45 days). However, the viability of Fp3 did not decrease greatly in most of the treatments, as compared to the infested and un-amended control, when incubated at 30ºC. After incubation, seedlings of asparagus `Grande´ were transplanted into pots containing substrates infested with the different species of Fusarium. After three months in greenhouse, symptoms severity in roots showed highly significant decreases, but Fp3 caused lower severity than Fo5 and Fs2. Severity reduction was particularly high at 30ºC (by 15 days incubation for Fs2 and by 30-45 days for Fo5), after PPM treatment, as well as PM-2% for Fo5and Fs2 incubated during 30 and 45 days at both temperatures, and with ORC (15-30 days incubation). Moreover, assessment of plants fresh weight showed significantly high increases in Fo5 and Fs2, with some rates of the three OAs tested, depending on incubation period and temperature.This research was funded by a JAEPredoc-CSIC grant to AIBB; Ministerio de Agricultura, Alimentación y Medio Ambiente, Spain (project INIA RTA 2006-00045); and Consejería de Economía, Innovación y Ciencia, Junta de Andalucía, Spain (Project P06-AGR-02313).Peer reviewe

Estimation of the risk for radiation-induced liver disease following photon- or proton-beam radiosurgery of liver metastases

Abstract Background Radiotherapy of liver metastases is commonly being performed with photon-beam based stereotactic body radiation therapy (SBRT). The high risk for radiation-induced liver disease (RILD) is a limiting factor in these treatments. The use of proton-beam based SBRT could potentially improve the sparing of the healthy part of the liver. The aim of this study was to use estimations of normal tissue complication probability (NTCP) to identify liver-metastases patients that could benefit from being treated with intensity-modulated proton therapy (IMPT), based on the reduction of the risk for RILD. Methods Ten liver metastases patients, previously treated with photon-beam based SBRT, were retrospectively planned with IMPT. A CTV-based robust optimisation (accounting for setup and range uncertainties), combined with a PTV-based conventional optimisation, was performed. A robustness criterion was defined for the CTV (V95% > 98% for at least 10 of the 12 simulated scenarios). The NTCP was estimated for different endpoints using the Lyman-Kutcher-Burman model. The ΔNTCP (NTCP IMPT  − NTCP SBRT ) for RILD was registered for each patient. The patients for which the NTCP (RILD) < 5% were also identified. A generic relative biological effectiveness of 1.1 was assumed for the proton beams. Results For all patients, the objectives set for the PTV and the robustness criterion set for the CTV were fulfilled with the IMPT plans. An improved sparing of the healthy part of the liver, right kidney, lungs, spinal cord and the skin was achieved with the IMPT plans, compared to the SBRT plans. Mean liver doses larger than the threshold value of 32 Gy led to NTCP values for RILD exceeding 5% (7 patients with SBRT and 3 patients with the IMPT plans). ΔNTCP values (RILD) ranging between − 98% and − 17% (7 patients) and between 0 and 2% (3 patients), were calculated. Conclusions In this study, liver metastases patients that could benefit from being treated with IMPT, based on the NTCP reductions, were identified. The clinical implementation of such a model-based approach to select liver metastases patients to proton therapy needs to be made with caution while considering the uncertainties involved in the NTCP estimations

Estrategias de control químico, físico y biológico para la reducción de la incidencia de Sclerotium cepivorum en el ajo morado de las pedroñeras

Resúmenes del XI Congreso de la Sociedad Española de Fitopatología.Peer reviewe

Efecto del aporte de enmiendas orgánicas al suelo sobre las poblaciones de Fusarium spp. y sobre la podredumbre de rizomas y raíces de espárrago

Resúmenes del XIII Congreso de la Sociedad Española de FitopatologíaPeer reviewe