RESUMEN
We present treatment planning methods based on four-dimensional computed tomography (4D-CT) to incorporate tumour motion using (1) a static field and (2) a dynamic field. Static 4D fields are determined to include the target in all breathing phases, whereas dynamic 4D fields are determined to follow the shape of the tumour assessed from 4D-CT images with a dynamic weighting factor. The weighting factor selection depends on the reliability of patient breathing and limitations of the delivery system. The static 4D method is compared with our standard protocol for gross tumour volume (GTV) coverage, mean lung dose and V20. It was found that the GTV delineated on helical CT without incorporating breathing motion does not adequately represent the target compared to the GTV delineated from 4D-CT. Dosimetric analysis indicates that the static 4D-CT based technique results in a reduction of the mean lung dose compared with the standard protocol. Measurements on a moving phantom and simulations indicated that 4D radiotherapy (4D-RT) synchronized with respiration-induced motion further reduces mean lung dose and V20, and may allow safe application of dose escalation and CRT/IMRT. The motions of the chest cavity, tumour and thoracic structures of 24 lung cancer patients are also analysed.
Asunto(s)
Imagenología Tridimensional/métodos , Neoplasias Pulmonares/radioterapia , Movimiento , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia Conformacional/métodos , Tomografía Computarizada por Rayos X/métodos , Artefactos , Carga Corporal (Radioterapia) , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Fantasmas de Imagen , Radiometría/métodos , Dosificación Radioterapéutica , Radioterapia Asistida por Computador/métodos , Tomografía Computarizada por Rayos X/instrumentaciónRESUMEN
BACKGROUND: Environmental imperatives to eliminate the use of chlorofluorocarbon (CFC) propellants in metered-dose inhalers have led to the development of metered-dose inhalers with the hydrofluoroalkane (HFA-134a) propellants. OBJECTIVES: To evaluate the clinical effect of switching from Ventolin CFC to Ventolin HFA and to compare the efficacy and safety of Ventolin CFC, Ventolin HFA, and placebo in patients with asthma. METHODS: Multicenter, double-blind, randomized safety and efficacy trial comparing regular use of Ventolin CFC versus Ventolin HFA versus placebo for 12 weeks in 313 patients with asthma aged 12 years and older who received Ventolin CFC during a 3-week run-in period. RESULTS: Patients who were switched from Ventolin CFC to Ventolin HFA maintained pulmonary function and other measures of asthma control at levels comparable with run-in baseline. Serial pulmonary function testing demonstrated that both Ventolin treatments had significantly greater mean improvement in FEV1 over baseline than the placebo group at treatment day 1 and weeks 6 and 12 (P < .001). Both Ventolin groups had comparable pulmonary function at every visit. Predose FEV1 values were maintained or improved over time with all treatments. Treatments were well-tolerated. The adverse event profile for both Ventolin treatments was comparable with placebo. No clinically relevant effects on ECG, vital signs, or clinical laboratory tests were noted. Asthma exacerbation rates were 4% to 5% in the Ventolin groups and slightly higher (8%) in the placebo group. CONCLUSIONS: Patients who were switched from Ventolin CFC to Ventolin HFA maintained comparable asthma control with a similar safety profile.
Asunto(s)
Agonistas Adrenérgicos beta/administración & dosificación , Albuterol/administración & dosificación , Asma/tratamiento farmacológico , Broncodilatadores/administración & dosificación , Clorofluorocarburos/administración & dosificación , Hidrocarburos Fluorados/administración & dosificación , Adolescente , Agonistas Adrenérgicos beta/efectos adversos , Adulto , Propelentes de Aerosoles/administración & dosificación , Propelentes de Aerosoles/efectos adversos , Albuterol/efectos adversos , Asma/fisiopatología , Broncodilatadores/efectos adversos , Clorofluorocarburos/efectos adversos , Método Doble Ciego , Femenino , Volumen Espiratorio Forzado , Humanos , Hidrocarburos Fluorados/efectos adversos , Masculino , Cooperación del PacienteRESUMEN
BACKGROUND: Administration of inhaled medications to very young children is sometimes difficult. Administration of inhaled medications via metered dose inhalers (MDIs) to pediatric patients younger than 4 years of age requires use of a holding chamber/spacer with an attached facemask. OBJECTIVE: This in vitro study was conducted to determine the particle size distribution and overall dose of salmeterol delivered in conjunction with the use of various US-marketed valved holding chambers (VHCs) in comparison to the dose-delivered via MDI without VHCs. METHODS: Cascade impaction methodology with high-performance liquid chromatography was used to evaluate the fine particle mass (FPM) of salmeterol administered without and with the use of the following VHCs: Optichamber, medium and large Aerochambers, adult Aerochamber, and medium Aerochamber Plus. RESULTS: Particle size distributions for the Optichamber, various sizes of Aerochamber, and the Aerochamber Plus were very similar and the particle size distributions for all VHCs were similar to the distribution of the control. The FPM for particles ranging from 0.7 to <3.3 microm in diameter (in the range shown to provide the greatest lung dose to negotiate the small airways of infants) was similar across the various VHCs tested. Statistical comparison of the fine particle fraction for these stages shows a very similar profile when differences from the salmeterol MDI control were evaluated. CONCLUSIONS: In vitro results obtained under these test conditions demonstrate that all FPM values for the VHCs tested were within 15% of the control range, a difference that is unlikely to be clinically meaningful. These results indicate that the difference in FPM does not warrant a change in the recommended dosage of salmeterol administered when using the VHCs tested. Our results demonstrate that the use of an MDI and VHC provides a reasonable therapeutic approach for administration of salmeterol MDI to young children and other patients who have difficulties administering the MDI alone.
Asunto(s)
Albuterol/análogos & derivados , Albuterol/administración & dosificación , Broncodilatadores/administración & dosificación , Nebulizadores y Vaporizadores , Administración por Inhalación , Asma/tratamiento farmacológico , Preescolar , Cromatografía Líquida de Alta Presión , Diseño de Equipo , Humanos , Lactante , Máscaras , Nebulizadores y Vaporizadores/normas , Tamaño de la Partícula , Xinafoato de SalmeterolRESUMEN
BACKGROUND: Aerosolized asthma medications with chlorofluorocarbon (CFC) propellants are being phased out because of environmental concerns about the ozone layer. Medications are being reformulated with non-ozone-depleting propellants. OBJECTIVE: To evaluate the clinical comparability of albuterol sulfate formulated in a new hydrofluoroalkane-134a (HFA) propellant (Ventolin HFA Inhalation Aerosol), and conventional CFC-containing albuterol (Ventolin Inhalation Aerosol) in children with asthma. DESIGN: Randomized, double-blind, placebo-controlled 2-week clinical trial with a 1- to 2-week run-in period. During the run-in, patients took Ventolin CFC as needed. Patients (n = 135) aged 4 to 11 years with asthma then were assigned randomly to treatment with Ventolin HFA, Ventolin CFC, or placebo administered 4 times daily via metered-dose inhaler for 2 weeks. All patients were allowed rescue albuterol use in matching propellant as needed for relief of breakthrough symptoms. The main outcome measure was the mean percentage of predicted peak expiratory flow (PEF) after the morning dose of study drug on day 1 and after 2 weeks as assessed by results of 6-hour serial tests. RESULTS: At day 1, the mean (+/- SE) percentage of predicted PEF increased postdose by 14% (+/- 1%) in the Ventolin HFA group and 13% (+/- 1%) in the Ventolin CFC group compared with 6% (+/- 2%) in the placebo group (P