RESUMEN
This work describes the dosimetric commissioning of the treatment planning system (TPS) RayStation v6.1 from RaySearch Laboratories (Stockholm, Sweden) for a synchrotron-based scanned proton beam delivery with isocentric and non-isocentric setups at MedAustron. Focus was on the comparison of the pencil beam (PBv4.1) and Monte Carlo (MCv4.0) calculation algorithms. Commissioning of dose calculations was done first for 1D/2D dose delivery where the performance of the beam model in reproducing dosimetric properties for the delivery of single static pencil beams and mono-energetic layers with multiple spots was evaluated. The commissioning for 3D beam delivery employed test cases with increasing complexity: from box-shaped fields in homogeneous phantoms to the introduction of oblique incidences and inhomogeneities. Dose calculations were compared to the measured data for different air gaps and using beams with and without range shifter (RaShi). Depth-dose curves and spot shape comparisons showed good agreement of the results obtained with PBv4.1 and MCv4.0 algorithms at isocentric setup for open beam configurations (without RaShi). Comparison of transverse dose profiles for lateral heterogeneities at different depths showed better performance of the MCv4.0 algorithm in comparison to the PBv4.1 algorithm. In the case of 3D delivery comparisons of measured and TPS-calculated dose with MCv4.0 algorithm in box-shaped fields in water showed an average agreement within 2%. The results for dose calculations with the PBv4.1 algorithm showed larger deviations for beams with RaShi at all evaluated air gaps (from 64.8 cm to 14.8 cm). Our results suggest that the MCv4.0 algorithm shall be used in clinics for final dose calculation when beams with RaShi are used especially in the presence of large air gaps, inclined patient surface and lateral inhomogeneities. The detailed stepwise methodology implemented for the RayStation commissioning in this work could serve as further guidance for other facilities introducing a new TPS for proton beam therapy.
Asunto(s)
Terapia de Protones/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Algoritmos , Humanos , Método de Montecarlo , Fantasmas de Imagen , Dosificación RadioterapéuticaRESUMEN
This paper describes end-to-end test procedures as the last fundamental step of medical commissioning before starting clinical operation of the MedAustron synchrotron-based pencil beam scanning (PBS) therapy facility with protons. One in-house homogeneous phantom and two anthropomorphic heterogeneous (head and pelvis) phantoms were used for end-to-end tests at MedAustron. The phantoms were equipped with alanine detectors, radiochromic films and ionization chambers. The correction for the 'quenching' effect of alanine pellets was implemented in the Monte Carlo platform of the evaluation version of RayStation TPS. During the end-to-end tests, the phantoms were transferred through the workflow like real patients to simulate the entire clinical workflow: immobilization, imaging, treatment planning and dose delivery. Different clinical scenarios of increasing complexity were simulated: delivery of a single beam, two oblique beams without and with range shifter. In addition to the dose comparison in the plastic phantoms the dose obtained from alanine pellet readings was compared with the dose determined with the Farmer ionization chamber in water. A consistent systematic deviation of about 2% was found between alanine dosimetry and the ionization chamber dosimetry in water and plastic materials. Acceptable agreement of planned and delivered doses was observed together with consistent and reproducible results of the end-to-end testing performed with different dosimetric techniques (alanine detectors, ionization chambers and EBT3 radiochromic films). The results confirmed the adequate implementation and integration of the new PBS technology at MedAustron. This work demonstrates that alanine pellets are suitable detectors for end-to-end tests in proton beam therapy and the developed procedures with customized anthropomorphic phantoms can be used to support implementation of PBS technology in clinical practice.
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Alanina/química , Cabeza/diagnóstico por imagen , Pelvis/diagnóstico por imagen , Fantasmas de Imagen , Protones , Radiometría/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Humanos , Método de Montecarlo , Dosis de Radiación , SincrotronesRESUMEN
INTRODUCTION: Vertebral fracture is a strong risk factor for future spine and hip fractures; yet recent data suggest that only 5-20% of subjects with a spine fracture are identified in primary care. We aimed to develop easily applicable algorithms predicting a high risk of future spine fracture in men and women over 50 years of age. METHODS: Data was analysed from 5,561 men and women aged 50+ years participating in the European Prospective Osteoporosis Study (EPOS). Lateral thoracic and lumbar spine radiographs were taken at baseline and at an average of 3.8 years later. These were evaluated by an experienced radiologist. The risk of a new (incident) vertebral fracture was modelled as a function of age, number of prevalent vertebral fractures, height loss, sex and other fracture history reported by the subject, including limb fractures occurring between X-rays. Receiver Operating Characteristic (ROC) curves were used to compare the predictive ability of models. RESULTS: In a negative binomial regression model without baseline X-ray data, the risk of incident vertebral fracture significantly increased with age [RR 1.74, 95% CI (1.44, 2.10) per decade], height loss [1.08 (1.04, 1.12) per cm decrease], female sex [1.48 (1.05, 2.09)], and recalled fracture history; [1.65 (1.15, 2.38) to 3.03 (1.66, 5.54)] according to fracture site. Baseline radiological assessment of prevalent vertebral fracture significantly improved the areas subtended by ROC curves from 0.71 (0.67, 0.74) to 0.74 (0.70, 0.77) P=0.013 for predicting 1+ incident fracture; and from 0.74 (0.67, 0.81) to 0.83 (0.76, 0.90) P=0.001 for 2+ incident fractures. Age, sex and height loss remained independently predictive. The relative risk of a new vertebral fracture increased with the number of prevalent vertebral fractures present from 3.08 (2.10, 4.52) for 1 fracture to 9.36 (5.72, 15.32) for 3+. At a specificity of 90%, the model including X-ray data improved the sensitivity for predicting 2+ and 1+ incident fractures by 6 and 4 fold respectively compared with random guessing. At 75% specificity the improvements were 3.2 and 2.4 fold respectively. With the modelling restricted to the subjects who had BMD measurements (n=2,409), the AUC for predicting 1+ vs. 0 incident vertebral fractures improved from 0.72 (0.66, 0.79) to 0.76 (0.71, 0.82) upon adding femoral neck BMD (P=0.010). CONCLUSION: We conclude that for those with existing vertebral fractures, an accurately read spine X-ray will form a central component in future algorithms for targeting treatment, especially to the most vulnerable. The sensitivity of this approach to identifying vertebral fracture cases requiring anti-osteoporosis treatment, even when X-rays are ordered highly selectively, exceeds by a large margin the current standard of practice as recorded anywhere in the world.
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Algoritmos , Osteoporosis/complicaciones , Osteoporosis/diagnóstico por imagen , Fracturas de la Columna Vertebral/etiología , Columna Vertebral/diagnóstico por imagen , Factores de Edad , Anciano , Antropometría/métodos , Estatura , Densidad Ósea , Métodos Epidemiológicos , Europa (Continente)/epidemiología , Femenino , Fémur/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Modelos Biológicos , Osteoporosis/epidemiología , Osteoporosis/fisiopatología , Radiografía , Fracturas de la Columna Vertebral/epidemiología , Fracturas de la Columna Vertebral/fisiopatología , Columna Vertebral/fisiopatologíaRESUMEN
Vertebral fractures are associated with back pain and disability. There are, however, few prospective data looking at back pain and disability following identification of radiographic vertebral fracture. The aim of this analysis was to determine the impact of radiographically identified vertebral fracture on the subsequent occurrence of back pain and disability. Women aged 50 years and over were recruited from population registers in 18 European centers for participation in the European Prospective Osteoporosis Study. Participants completed an interviewer-administered questionnaire which included questions about back pain in the past year and various activities of daily living, and they had lateral spine radiographs performed. Participants in these centers were followed prospectively and had repeat spine radiographs performed a mean of 3.7 years later. In addition they completed a questionnaire with the same baseline questions concerning back pain and activities of daily living. The presence of prevalent and incident vertebral fracture was defined using established morphometric criteria. The data were analyzed using logistic regression with back pain or disability (present or absent) at follow-up as the outcome variable with adjustment made for the baseline value of the variable. The study included 2,260 women, mean age 62.2 years. The mean time between baseline and follow-up survey was 5.0 years. Two hundred and forty participants had prevalent fractures at the baseline survey, and 85 developed incident fractures during follow-up. After adjustment for age, center, and the baseline level of disability, compared with those without baseline prevalent fracture, those with a prevalent fracture (odds ratio [OR] = 1.4; 95% confidence interval [CI] 1.0 to 2.0) or an incident fracture (OR = 1.7; 95% CI, 0.9 to 3.2) were more likely to report disability at follow-up, though the confidence intervals embraced unity. Those with both a prevalent and incident fracture, however, were significantly more likely to report disability at follow-up (OR = 3.1; 95% CI, 1.4 to 7.0). After adjustment for age, center, and frequency of back pain at baseline, compared with those without baseline vertebral fracture, those with a prevalent fracture were no more likely to report back pain at follow-up (OR = 1.2; 95% CI, 0.8 to 1.7). There was a small increased risk among those with a preexisting fracture who had sustained an incident fracture during follow-up (OR = 1.6; 95% CI, 0.6 to 4.1) though the confidence intervals embraced unity. In conclusion, although there was no significant increase in the level of back pain an average of 5 years following identification of radiographic vertebral fracture, women who suffered a further fracture during follow-up experienced substantial levels of disability with impairment in key physical functions of independent living.
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Dolor de Espalda/etiología , Evaluación de la Discapacidad , Fracturas de la Columna Vertebral/diagnóstico por imagen , Actividades Cotidianas , Anciano , Dolor de Espalda/diagnóstico por imagen , Dolor de Espalda/epidemiología , Europa (Continente)/epidemiología , Femenino , Humanos , Incidencia , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Radiografía , Autoevaluación (Psicología) , Fracturas de la Columna Vertebral/complicaciones , Fracturas de la Columna Vertebral/epidemiología , Factores de TiempoRESUMEN
The aim of this analysis was to determine the influence of lifestyle, anthropometric and reproductive factors on the subsequent risk of incident vertebral fracture in men and women aged 50-79 years. Subjects were recruited from population registers from 28 centers across Europe. At baseline, they completed an interviewer-administered questionnaire and had lateral thoraco-lumbar spine radiographs performed. Repeat spinal radiographs were performed a mean of 3.8 years later. Incident vertebral fractures were defined morphometrically and also qualitatively by an experienced radiologist. Poisson regression was used to determine the influence of the baseline risk factor variables on the occurrence of incident vertebral fracture. A total of 3173 men (mean age 63.1 years) and 3402 women (mean age 62.2 years) contributed data to the analysis. In total there were 193 incident morphometric and 224 qualitative fractures. In women, an age at menarche 16 years or older was associated with an increased risk of vertebral fracture (RR = 1.80; 95%CI 1.24, 2.63), whilst use of hormonal replacement was protective (RR = 0.58; 95%CI 0.34, 0.99). None of the lifestyle factors studied including smoking, alcohol intake, physical activity or milk consumption showed any consistent associations with incident vertebral fracture. In men and women, increasing body weight and body mass index were associated with a reduced risk of vertebral fracture though, apart from body mass index in men, the confidence intervals embraced unity. For most variables the strengths of the associations observed were similar using the qualitative and morphometric approaches to fracture definition. In conclusion our data suggest that modification of other lifestyle risk factors is unlikely to have a major impact on the population occurrence of vertebral fractures. The important biological mechanisms underlying vertebral fracture risk need to be explored using new investigational strategies.
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Osteoporosis/complicaciones , Fracturas de la Columna Vertebral/etiología , Distribución por Edad , Anciano , Antropometría/métodos , Índice de Masa Corporal , Europa (Continente)/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Estilo de Vida , Masculino , Persona de Mediana Edad , Osteoporosis Posmenopáusica/complicaciones , Osteoporosis Posmenopáusica/epidemiología , Estudios Prospectivos , Historia Reproductiva , Factores de Riesgo , Distribución por Sexo , Fracturas de la Columna Vertebral/epidemiologíaRESUMEN
The aim of this population-based prospective study was to determine the incidence of limb fracture by site and gender in different regions of Europe. Men and women aged 50-79 years were recruited from population registers in 31 European centers. Subjects were invited to attend for an interviewer-administered questionnaire and lateral spinal radiographs. Subjects were subsequently followed up using an annual postal questionnaire which included questions concerning the occurrence of new fractures. Self-reported fractures were confirmed where possible by radiograph, attending physician or subject interview. There were 6451 men and 6936 women followed for a median of 3.0 years. During this time there were 140 incident limb fractures in men and 391 in women. The age-adjusted incidence of any limb fracture was 7.3/1000 person-years [pyrs] in men and 19 per 1000 pyrs in women, equivalent to a 2.5 times excess in women. Among women, the incidence of hip, humerus and distal forearm fracture, though not 'other' limb fracture, increased with age, while in men only the incidence of hip and humerus fracture increased with age. Among women, there was evidence of significant variation in the occurrence of hip, distal forearm and humerus fractures across Europe, with incidence rates higher in Scandinavia than in other European regions, though for distal forearm fracture the incidence in east Europe was similar to that observed in Scandinavia. Among men, there was no evidence of significant geographic variation in the occurrence of these fractures. This is the first large population-based study to characterize the incidence of limb fracture in men and women over 50 years of age across Europe. There are substantial differences in the descriptive epidemiology of limb fracture by region and gender.
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Extremidades/lesiones , Fracturas Óseas/epidemiología , Osteoporosis/complicaciones , Distribución por Edad , Anciano , Europa (Continente)/epidemiología , Femenino , Fracturas Óseas/etiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Distribución por Sexo , Encuestas y CuestionariosRESUMEN
Vertebral fracture is one of the major adverse clinical consequences of osteoporosis; however, there are few data concerning the incidence of vertebral fracture in population samples of men and women. The aim of this study was to determine the incidence of vertebral fracture in European men and women. A total of 14,011 men and women aged 50 years and over were recruited from population-based registers in 29 European centers and had an interviewer-administered questionnaire and lateral spinal radiographs performed. The response rate for participation in the study was approximately 50%. Repeat spinal radiographs were performed a mean of 3.8 years following the baseline film. All films were evaluated morphometrically. The definition of a morphometric fracture was a vertebra in which there was evidence of a 20% (+4 mm) or more reduction in anterior, middle, or posterior vertebral height between films--plus the additional requirement that a vertebra satisfy criteria for a prevalent deformity (using the McCloskey-Kanis method) in the follow-up film. There were 3174 men, mean age 63.1 years, and 3,614 women, mean age 62.2 years, with paired duplicate spinal radiographs (48% of those originally recruited to the baseline survey). The age standardized incidence of morphometric fracture was 10.7/1,000 person years (pyr) in women and 5.7/1,000 pyr in men. The age-standardized incidence of vertebral fracture as assessed qualitatively by the radiologist was broadly similar-12.1/1,000 pyr and 6.8/1,000 pyr, respectively. The incidence increased markedly with age in both men and women. There was some evidence of geographic variation in fracture occurrence; rates were higher in Sweden than elsewhere in Europe. This is the first large population-based study to ascertain the incidence of vertebral fracture in men and women over 50 years of age across Europe. The data confirm the frequent occurrence of the disorder in men as well as in women and the rise in incidence with age.
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Osteoporosis/epidemiología , Fracturas de la Columna Vertebral/epidemiología , Distribución por Edad , Anciano , Comorbilidad , Europa (Continente)/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Distribución por SexoRESUMEN
There is important geographic variation in the occurrence of the major osteoporotic fractures across Europe. The aim of this study was to determine whether between-center variation in limb fracture rates across Europe could be explained by variation in the incidence of falls. Men and women, aged 50-79 years, were recruited from population-based registers in 30 European centers. Subjects were followed by postal questionnaire to ascertain the occurrence of incident fractures, and were also asked about the occurrence and number of recent falls. Self-reported fractures were confirmed, where possible, by review of the radiographs, medical record, or subject interview. The age- and gender-adjusted incidence of falls was calculated by center using Poisson regression. Poisson regression was also used to assess the extent to which between-center differences in the incidence of limb fractures could be explained by differences in the age- and gender-adjusted incidence of falls at those centers. In all, 6302 men (mean age 63.9 years) and 6761 women (mean age 63.1 years) completed at least one questionnaire concerning fractures and falls. During a median follow-up time of 3 years, 3647 falls were reported by men and 4783 by women. After adjusting for age and gender, there was evidence of significant between-center differences in the occurrence of falls. There was also between-center variation in the occurrence of upper limb, lower limb, and distal forearm fractures. Variation in the age- and gender-adjusted center-specific fall rates explained 24%, 14%, and 6% of the between-center variation in incidence of distal forearm and upper and lower limb fractures, respectively. Given the constraints inherent in such an analysis, in men and women aged 50-79 years, variation in fall rates could explain a significant proportion of the between-center variation in the incidence of limb fracture across Europe.