BENCHMARKING AND IMPLEMENTATION OF A NEW INDEPENDENT MONTE CARLO DOSE CALCULATION QUALITY ASSURANCE AUDIT TOOL FOR CLINICAL TRIALS

Introduction Commercial treatment planning systems employ a variety of dose calculation algorithms to plan and predict the dose distributions a patient receives during external beam radiation therapy. Traditionally, the Radiological Physics Center has relied on measurements to assure that institutions participating in the National Cancer Institute sponsored clinical trials administer radiation in doses that are clinically comparable to those of other participating institutions. To complement the effort of the RPC, an independent dose calculation tool needs to be developed that will enable a generic method to determine patient dose distributions in three dimensions and to perform retrospective analysis of radiation delivered to patients who enrolled in past clinical trials. Methods A multi-source model representing output for Varian 6 MV and 10 MV photon beams was developed and evaluated. The Monte Carlo algorithm, know as the Dose Planning Method (DPM), was used to perform the dose calculations. The dose calculations were compared to measurements made in a water phantom and in anthropomorphic phantoms. Intensity modulated radiation therapy and stereotactic body radiation therapy techniques were used with the anthropomorphic phantoms. Finally, past patient treatment plans were selected and recalculated using DPM and contrasted against a commercial dose calculation algorithm. Results The multi-source model was validated for the Varian 6 MV and 10 MV photon beams. The benchmark evaluations demonstrated the ability of the model to accurately calculate dose for the Varian 6 MV and the Varian 10 MV source models. The patient calculations proved that the model was reproducible in determining dose under similar conditions described by the benchmark tests. Conclusions The dose calculation tool that relied on a multi-source model approach and used the DPM code to calculate dose was developed, validated, and benchmarked for the Varian 6 MV and 10 MV photon beams. Several patient dose distributions were contrasted against a commercial algorithm to provide a proof of principal to use as an application in monitoring clinical trial activity.

Genes in glucose metabolism and association with spina bifida.

The authors test single nucleotide polymorphisms (SNPs) in coding sequences of 12 candidate genes involved in glucose metabolism and obesity for associations with spina bifida. Genotyping was performed on 507 children with spina bifida and their parents plus anonymous control DNAs from Hispanic and Caucasian individuals. The transmission disequilibrium test was performed to test for genetic associations between transmission of alleles and spina bifida in the offspring (P < .05). A statistically significant association between Lys481 of HK1 (G allele), Arg109Lys of LEPR (G allele), and Pro196 of GLUT1 (A allele) was found ( P = .019, .039, and .040, respectively). Three SNPs on 3 genes involved with glucose metabolism and obesity may be associated with increased susceptibility to spina bifida.

The local safety net, health insurance, preventable hospitalizations and costs: Harris County (Houston), Texas

The aim of this study was to examine the association between determinants of access to healthcare and preventable hospitalizations, based on Davidson et al.'s framework for evaluating the effects of individual and community determinants on access to healthcare. The study population consisted of the low income, non-elderly, hospitalized adults residing in Harris County, Texas in 2004. The objectives of this study were to examine the proportion of the variance in preventable hospitalizations at the ZIP-code level, to analyze the association between the proximity to the nearest safety net clinic and preventable hospitalizations, to examine how the safety net capacity relates to preventable hospitalizations, to compare the relative strength of the associations of health insurance and the proximity to the nearest safety net clinic with preventable hospitalizations, and to estimate and compare the costs of preventable hospitalizations in Harris County with the average cost in the literature. The data were collected from Texas Health Care Information Collection (2004), Census 2000, and Project Safety Net (2004). A total of 61,841 eligible individuals were included in the final data analysis. A random-intercept multi-level model was constructed with two different levels of data: the individual level and the ZIP-code level. The results of this study suggest that ZIP-code characteristics explain about two percent of the variance in preventable hospitalizations and safety net capacity was marginally significantly associated with preventable hospitalizations (p= 0.062). Proximity to the nearest safety net clinic was not related to preventable hospitalizations; however, health insurance was significantly associated with a decreased risk of preventable hospitalization. The average direct cost was $6,466 per preventable hospitalization, which is significantly different from reports in the literature. ^

Association between cardiorespiratory fitness and Alzheimer's mortality: A prospective cohort study

Context. Alzheimer’s disease is a major source of morbidity and mortality in aging societies. Preventive measures, such as increasing cardiorespiratory fitness, to reduce the risk of Alzheimer’s disease mortality have not been sufficiently examined.^ Objective. To examine the association between levels of cardiorespiratory fitness and Alzheimer’s disease mortality.^ Design, Setting, and Patients. A prospective cohort study of 53,911 men and 18,876 women (mean age, 51.4 [SD, 10.0] years; range 20-88) enrolled in the Cooper Center Longitudinal Study who completed a baseline health examination during 1970-2006. The primary exposure, cardiorespiratory fitness, was assessed via a maximal exercise test. Fitness was categorized according to age- and sex-specific tertiles based on the participants’ distribution of maximal treadmill exercise test duration, in metabolic equivalent tasks (METs). The main outcome measure was Alzheimer’s disease mortality, defined as the underlying or contributing cause of death using the National Death Index and death certificates through December 31, 2006.^ Results. There were 175 Alzheimer’s disease deaths during a mean follow up of 37 years and 1,309,170 person-years of exposure. Women in the high fitness category had a 70% reduction in risk of Alzheimer’s mortality compared to women in the low fitness category (HR=0.3; 95% CI, 0.1-0.8; P=.02), while adjusting for potential confounders. Similarly, women in the moderate fitness category had a 70% reduction in risk for AD mortality compared to women in the low fit category (HR=0.3; 95% CI, 0.1-0.7; P=.005). Among men, the relationship between fitness level and AD mortality risk was examined but none were of statistical significance. The adjusted comparison of men in the high fitness category to low fit men yielded an HR of 0.9 (95% CI, 0.6-1.5; P=.79), while moderately fit men compared to low fit men yielded an HR of 1.3 (95% CI, 0.9-1.9; P=.21).^ Conclusions. Higher levels of cardiorespiratory fitness were associated with decreased risk of AD mortality, in women. No statistically significant association was found among men. Physical fitness may be an important protective factor against Alzheimer’s disease death in women, further supporting its clinical and public health values.^