EPID-based in vivo dosimetry using Dosimetry Check™: Overview and clinical experience in a 5-yr study including breast, lung, prostate, and head and neck cancer patients.

BACKGROUND: Independent verification of the dose delivered by complex radiotherapy can be performed by electronic portal imaging device (EPID) dosimetry. This paper presents 5-yr EPID in vivo dosimetry (IVD) data obtained using the Dosimetry Check (DC) software on a large cohort including breast, lung, prostate, and head and neck (H&N) cancer patients. MATERIAL AND METHODS: The difference between in vivo dose measurements obtained by DC and point doses calculated by the Eclipse treatment planning system was obtained on 3795 radiotherapy patients treated with volumetric modulated arc therapy (VMAT) (n = 842) and three-dimensional conformal radiotherapy (3DCRT) (n = 2953) at 6, 10, and 15 MV. In cases where the dose difference exceeded ±10% further inspection and additional phantom measurements were performed. RESULTS: The mean and standard deviation ( µ ± σ ) of the percentage difference in dose obtained by DC and calculated by Eclipse in VMAT was: 0.19 ± 3.89 % in brain, 1.54 ± 4.87 % in H&N, and 1.23 ± 4.61 % in prostate cancer. In 3DCRT, this was 1.79 ± 3.51 % in brain, - 2.95 ± 5.67 % in breast, - 1.43 ± 4.38 % in bladder, 1.66 ± 4.77 % in H&N, 2.60 ± 5.35% in lung and - 3.62 ± 4.00 % in prostate cancer. A total of 153 plans exceeded the ±10% alert criteria, which included: 88 breast plans accounting for 7.9% of all breast treatments; 28 H&N plans accounting for 4.4% of all H&N treatments; and 12 prostate plans accounting for 3.5% of all prostate treatments. All deviations were found to be as a result of patient-related anatomical deviations and not from procedural errors. CONCLUSIONS: This preliminary data shows that EPID-based IVD with DC may not only be useful in detecting errors but has the potential to be used to establish site-specific dose action levels. The approach is straightforward and has been implemented as a radiographer-led service with no disruption to the patient and no impact on treatment time.

Perfluorinated alkyl substances in Spanish adults: Geographical distribution and determinants of exposure.

Per- and polyfluoroalkyl substances (PFAS) are widely found in humans and the environment. Their persistence, bioaccumulation and toxicity make them a source of increasing public health concern. In this study, we analyzed the concentrations and geographical distribution of six PFAS in the serum of 755 Spanish adults aged 18-65. The geometric mean concentrations (and P95 values) for PFOS (perfluoroctane sulfonate), PFOA (perfluorooctanoic acid), PFHxS (perfluorohexane sulfonate), PFNA (perfluorononanoic acid) and PFDA (perfluorodecanoic acid) were 7.67 (19.3), 1.99 (5.48), 0.91 (2.84), 0.96 (2.44) and 0.42 (0.99) µg/L, respectively. N-Methylperfluorooctane sulfonamide (N-MeFOSAA) was detected in only 3.3% of samples. Residents in northeast (Catalonia) and northwest of Spain (Galicia) were found to have the highest serum values, whereas residents in the Canary Islands had the lowest values for almost all PFAS. Men presented higher levels than women, and we confirm that lactation (breastfeeding) contributes to a reduced body burden for all PFAS in women. Our data provide new information on exposure to PFAS in a national cross section sample of Spanish adults, thus providing a proxy for reference values for the Spanish population and forming the base for following temporal trends in the future.

Cadmium levels in a representative sample of the Spanish adult population: The BIOAMBIENT.ES project.

Urinary cadmium levels (U-Cd) were measured in 1770 adults (aged 18-65 years) as a representative sample of the Spanish workforce. The geometric mean (GM) was 0.28 µg/l with 95% CI: 0.27-0.32 µg/l (GM: 0.20 µg/g 95% CI: 0.18-022 µg/g creatinine). The 95% percentile was 1.03 µg/l. U-Cd increased with age, with women showing higher U-Cd than men (p<0.001; 0.24 µg/g vs 0.17 µg/g). A multivariate analysis confirmed that sex, age and smoking habit significantly influence U-Cd. Smoking habit increases U-Cd by ∼90% per 10 years of age, almost twice the increase observed for non-smoking. Female smokers had 85% higher U-Cd than non-smokers, whereas the corresponding value for male smokers and non-smokers was 45%. No regional differences were observed with respect to the national reference level. The Spanish population studied here exhibits similar urinary cadmium levels to its European counterparts in Germany and slightly lower levels than in France, the Czech Republic, Italy and the United Kingdom. This paper provides the first baseline information concerning cadmium exposure in the Spanish adult population on a national scale. As such, these findings will help us to establish reference levels, follow temporal trends and identify high-exposure groups, thereby enabling comparisons with other countries and contributing to the improvement of public health and environmental quality.

Fish consumption patterns and hair mercury levels in children and their mothers in 17 EU countries.

The toxicity of methylmercury (MeHg) in humans is well established and the main source of exposure is via the consumption of large marine fish and mammals. Of particular concern are the potential neurodevelopmental effects of early life exposure to low-levels of MeHg. Therefore, it is important that pregnant women, children and women of childbearing age are, as far as possible, protected from MeHg exposure. Within the European project DEMOCOPHES, we have analyzed mercury (Hg) in hair in 1799 mother-child pairs from 17 European countries using a strictly harmonized protocol for mercury analysis. Parallel, harmonized questionnaires on dietary habits provided information on consumption patterns of fish and marine products. After hierarchical cluster analysis of consumption habits of the mother-child pairs, the DEMOCOPHES cohort can be classified into two branches of approximately similar size: one with high fish consumption (H) and another with low consumption (L). All countries have representatives in both branches, but Belgium, Denmark, Spain, Portugal and Sweden have twice as many or more mother-child pairs in H than in L. For Switzerland, Czech Republic, Hungary, Poland, Romania, Slovenia and Slovakia the situation is the opposite, with more representatives in L than H. There is a strong correlation (r=0.72) in hair mercury concentration between the mother and child in the same family, which indicates that they have a similar exposure situation. The clustering of mother-child pairs on basis of their fish consumption revealed some interesting patterns. One is that for the same sea fish consumption, other food items of marine origin, like seafood products or shellfish, contribute significantly to the mercury levels in hair. We conclude that additional studies are needed to assess and quantify exposure to mercury from seafood products, in particular. The cluster analysis also showed that 95% of mothers who consume once per week fish only, and no other marine products, have mercury levels 0.55 µg/g. Thus, the 95th percentile of the distribution in this group is only around half the US-EPA recommended threshold of 1 µg/g mercury in hair. Consumption of freshwater fish played a minor role in contributing to mercury exposure in the studied cohort. The DEMOCOPHES data shows that there are significant differences in MeHg exposure across the EU and that exposure is highly correlated with consumption of fish and marine products. Fish and marine products are key components of a healthy human diet and are important both traditionally and culturally in many parts of Europe. Therefore, the communication of the potential risks of mercury exposure needs to be carefully balanced to take into account traditional and cultural values as well as the potential health benefits from fish consumption. European harmonized human biomonitoring programs provide an additional dimension to national HMB programs and can assist national authorities to tailor mitigation and adaptation strategies (dietary advice, risk communication, etc.) to their country's specific requirements.

Urinary polycyclic aromatic hydrocarbon metabolites levels in a representative sample of the Spanish adult population: The BIOAMBIENT.ES project.

In 2009, the Spanish Ministry of Agriculture, Food and Environment promoted the BIOAMBIENT.ES project, a Human Biomonitoring program on the national scale to estimate reference levels of environmental pollutants on a representative sample of the Spanish adults. The present study focuses on polycyclic aromatic hydrocarbons (PAHs). The urinary metabolites 1-hydroxypyrene, 1-,2-,3-,4- and 9-hydroxyphenanthrene and 3-hydroxybenzo[a]pyrene were selected as indicators of PAH exposure. Urine samples from 957 subjects (16-65 years old) were collected during year 2009-2010. Geometric mean and 95th percentile for 1-hydroxypyrene in µg g(-1) creatinine were 0.117 (non-smoker: 0.079, smokers: 0.184) and 0.67 µg g(-1) creatinine (non-smokers: 0.31, smokers: 0.69) respectively. GM and 95th percentile for sum of hydroxyphenanthrenes in µg g(-1) creatinine were 0.130 (non-smokers: 0.089, smokers: 0.317) and 1.29 (non-smokers: 0.71, smokers: 1.51) respectively. 3-Hydroxybenzo[a]pyrene was below the limit of quantitation (0.05 µg L(-1)) in all cases. Significant differences (p<0.05) regarding smokers and non-smokers, coal and wood heating, body mass index and second hand smoke were found, while other variables like gender, age, or diet showed no significant association. The geographical distribution of the metabolites showed higher levels in people who lived in the north and northwest of Spain. The PAH metabolites levels found were in the same range or lower than those reported from other European countries and they were higher than those found in the U.S. This study represents the first nationwide survey of exposure to PAHs in Spain and provides a background reference range for exposure to PAHs in the Spanish adult occupied population.

Urinary levels of eight phthalate metabolites and bisphenol A in mother-child pairs from two Spanish locations.

Exposure to some phthalate diesters and bisphenol A in the general population is a cause of increasing concern because of their potential adverse effects on the reproductive and endocrine systems and their broad presence in foodstuff and consumer products. The aims of this work are to assess patterns of exposure to phthalates and bisphenol A in a pilot sample of Spanish mothers and their children, and to provide basic information to address priorities in future Spanish surveys/research. Urinary levels of eight phthalate metabolites and bisphenol A have been measured in samples from 120 mother-child pairs in one rural and one urban location in central Spain, recruited as part of the European project DEMOCOPHES. More than 96% of the participants were exposed to all the compounds studied here with generally higher levels in children than their mothers. The sum of secondary DEHP metabolites gave a GM of 33.3µg/g creatinine (95% CI 30.2-36.6) for mothers and 63.0µg/g creatinine (95% CI 56.8-69.8) for children. Mono-ethyl phthalate (MEP) was the metabolite with the highest levels, with geometric means (GM) of 150.8µg/g creatinine (95% CI 124.0-183.5) for mothers and 198.9µg/g creatinine (95% CI 165.2-239.6) for children. Bisphenol A urinary levels were relatively low with geometric means of 2.0µg/g (95% CI 1.6-2.4) for mothers and 2.01µg/g (95% CI 1.7-2.4) for children. Personal care products like body lotions and fragrances showed associations with MEHP, MEP, MnBP and cx-MiNP and canteen food with MBzP and bisphenol A. Exposure of mothers and their children are correlated, except for MEP. As phthalates and bisphenol A are non-persistent chemicals, a daily, intermittent exposure of the population is taking place.

Urinary BPA measurements in children and mothers from six European member states: Overall results and determinants of exposure.

For the first time in Europe, both European-wide and country-specific levels of urinary Bisphenol A (BPA) were obtained through a harmonized protocol for participant recruitment, sampling and quality controlled biomarker analysis in the frame of the twin projects COPHES and DEMOCOPHES. 674 child-mother pairs were recruited through schools or population registers from six European member states (Belgium, Denmark, Luxembourg, Slovenia, Spain and Sweden). Children (5-12 y) and mothers donated a urine sample. Information on socio-demographic characteristics, life style, dietary habits, and educational level of the parents was provided by mothers. After exclusion of urine samples with creatinine values below 300 mg/L or above 3000 mg/L, 653 children and 639 mothers remained for which BPA was measured. The geometric mean (with 95% confidence intervals) and 90th percentile were calculated for BPA separately in children and in mothers and were named "European reference values". After adjustment for confounders (age and creatinine), average exposure values in each country were compared with the mean of the "European reference values" by means of a weighted analysis of variance. Overall geometric means of all countries (95% CI) adjusted for urinary creatinine, age and gender were 2.04 (1.87-2.24) µg/L and 1.88 (1.71-2.07) µg/L for children (n=653) and mothers (n=639), respectively. Multiple regression analysis was used to identify significant environmental, geographical, personal or life style related determinants. Consumption of canned food and social class (represented by the highest educational level of the family) were the most important predictors for the urinary levels of BPA in mothers and children. The individual BPA levels in children were significantly correlated with the levels in their mothers (r=0.265, p<0.001), which may suggest a possible common environmental/dietary factor that influences the biomarker level in each pair. Exposure of the general European population was well below the current health-based guidance values and no participant had BPA values higher than the health-based guidance values.