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At least 919 records · Page 51
All sourcesNASA NTRSDOE OSTI
DOE OSTI2013

Association between thyroid profile and perfluoroalkyl acids: Data from NHNAES 2007–2008

The effect of six perfluoroalkyl acids (PFAAs), namely, perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorodecanoic acid (PFDE), perfluorohexane sulfonic acid (PFHxS), 2-(N-methyl-perfluorooctane sulfonamide) acetic acid (MPAH), and perfluorononanoic acid (PFNA) on the levels of six thyroid function variables, namely, thyroid stimulating hormone (TSH), free and total thyroxine (FT4, TT4), free and total triiodothyronine (FT3, TT3), and thyroglobulin (TGN) was evaluated. Data from National Health and Nutrition Examination Survey for the years 2007–2008 were used for this evaluation. TSH levels increased with increase in levels of PFOA (p<0.01). There were no statistically significant associations between the levels of FT3, and FT4 with the levels of any of the six PFAAs. Levels of TT3 were found to increase with the levels of PFOA (p=0.01) and TT4 levels were found to increase with increase in PFHxS levels (p<0.01). Males had statistically significantly higher levels of FT3 than females and females had statistically significantly higher levels of TT4 than males. As compared to non-Hispanics whites and Hispanics, non-Hispanic blacks had lower levels of TSH, FT3, TT3, and TT4 but Hispanics had the lowest levels of TGN. Age was negatively associated with FT3 and TT3 but positively associated with FT4 and TT4. Non-smokers had higher levels of TSH and TT4 than smokers and smokers had higher levels of FT3 and TGN than non-smokers. Iodine deficiency was associated with increased levels of TSH, TT3, TT4, and TGN. -- Highlights: • Levels of total triiodothyronine were found to increase with the levels of PFOA. • Total thyroxine increased with increase in levels of perfluorohexane sulfonic acid. • There was a positive association between the levels of PFOA and TSH. • Iodine deficiency was associated with elevated levels of TSH, total T3 and T4. • Iodine deficiency was associated with elevated levels of thyroglobulin.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Exposure determinants of cadmium in European mothers and their children

The metal cadmium (Cd) is a widespread environmental pollutant with documented adverse effects on the kidneys and bones from long-term environmental exposure, but with insufficiently elucidated public health consequences such as risk of cardiovascular disease, hormone-related cancer in adults and developmental effects in children. This study is the first pan-European human biomonitoring project that succeeded in performing harmonized measurements of Cd in urine in a comparable way in mother–child couples from 16 European countries. The aim of the study was to evaluate the overall Cd exposure and significant determinants of Cd exposure. A study population of 1632 women (24–52 years of age), and 1689 children (5–12 years of age), from 32 rural and urban areas, was examined within a core period of 6 months in 2011–2012. Women were stratified as smokers and non-smokers. As expected, smoking mothers had higher geometric mean (gm) urinary cadmium (UCd; 0.24 µg/g crea; n=360) than non-smoking mothers (gm 0.18 µg/g crea; n=1272; p<0.0001), and children had lower UCd (gm 0.065 µg/g crea; n=1689) than their mothers at the country level. Non-smoking women exposed to environmental tobacco smoke (ETS) at home had 14% (95% CI 1–28%) higher UCd than those who were not exposed to ETS at home (p=0.04). No influence of ETS at home or other places on UCd levels was detected in children. Smoking women with primary education as the highest educational level of the household had 48% (95% CI 18–86%) higher UCd than those with tertiary education (p=0.0008). The same observation was seen in non-smoking women and in children; however they were not statistically significant. In children, living in a rural area was associated with 7% (95% CI 1–13%) higher UCd (p=0.03) compared to living in an urban area. Children, 9–12 years had 7% (95% CI 1–13%) higher UCd (p=0.04) than children 5–8 years. About 1% of the mothers, and 0.06% of the children, exceeded the tolerable weekly intake (TWI) appointed by EFSA, corresponding to 1.0 µg Cd/g crea in urine. Poland had the highest UCd in comparison between the 16 countries, while Denmark had the lowest. Whether the differences between countries are related to differences in the degree of environmental Cd contamination or to differences in lifestyle, socioeconomic status or dietary patterns is not clear. - Highlights: • Comparable measures of urinary Cd for mother–child couples in 16 countries were achieved. • Main urinary Cd predictors were age, smoking, educational level and rural residence. • Mean urinary Cd in children differed by a factor of 7 between countries. • Among non-smoking and smoking women the difference was 3-fold between countries. • The margin between current exposure levels and suspected health effect levels is narrow.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2015

Insights from an international stakeholder consultation to identify informational needs related to seafood safety

Food safety assessment and communication have a strong importance in reducing human health risks related to food consumption. The research carried out within the ECsafeSEAFOOD project aims to assess seafood safety issues, mainly related to non-regulated priority environmental contaminants, and to evaluate their impact on public health. In order to make the research results accessible and exploitable, and to respond to actual stakeholders' demands, a consultation with international stakeholders was performed by means of a survey. The focus was on policy and decision makers, food producers and processors, and agencies (i.e. EU and National or Regional agencies related to Food Safety or Public Health) and consumer organisations. The survey considered questions related to: seafood safety assessment and mitigation strategies, availability of data, such as the level of information on different contaminants, and communication among different stakeholder groups. Furthermore, stakeholders were asked to give their opinion on how they believe consumers perceive risks associated with environmental contaminants. The survey was distributed to 531 key stakeholders and 91 responses were received from stakeholders from 30 EU and non-EU countries. The main results show that communication between different groups of stakeholders needs to be improved and that there is a deficit of information and data in the field of seafood safety. This pertains mainly to the transfer of contaminants between the environment and seafood, and to the diversity of environmental contaminants such as plastic additives, algal toxins and hormones. On-line tools were perceived to be the most useful communication channel. - Highlights: • We consulted stakeholders to identify their needs about seafood safety. • An on-line survey was prepared and sent to gather stakeholders' opinions. • Communication among stakeholders needs to be improved. • There is a deficit of information and data in the field of seafood safety. • On-line tools are perceived to be the most useful communication channel.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2015

Bisphenol A, bisphenol F and bisphenol S affect differently 5α-reductase expression and dopamine–serotonin systems in the prefrontal cortex of juvenile female rats

Background: Early-life exposure to the endocrine disruptor bisphenol A (BPA) affects brain function and behavior, which might be attributed to its interference with hormonal steroid signaling and/or neurotransmitter systems. Alternatively, the use of structural analogs of BPA, mainly bisphenol F (BPF) and bisphenol S (BPS), has increased recently. However, limited in vivo toxicity data exist. Objectives: We investigated the effects of BPA, BPF and BPS on 5α-reductase (5α-R), a key enzyme involved in neurosteroidogenesis, as well as on dopamine (DA)- and serotonin (5-HT)-related genes, in the prefrontal cortex (PFC) of juvenile female rats. Methods: Gestating Wistar rats were treated with either vehicle or 10 μg/kg/day of BPA, BPF or BPS from gestational day 12 to parturition. Then, female pups were exposed from postnatal day 1 through day 21 (PND21), when they were euthanized and RT-PCR, western blot and quantitative PCR-array experiments were performed. Results: BPA decreased 5α-R2 and 5α-R3 mRNA and protein levels, while both BPF and BPS decreased 5α-R3 mRNA levels in PFC at PND21. Further, BPA, BPF and BPS significantly altered, respectively, the transcription of 25, 56 and 24 genes out of the 84 DA and 5-HT-related genes assayed. Of particular interest was the strong induction by all these bisphenols of Cyp2d4, implicated in corticosteroids synthesis. Conclusions: Our results demonstrate for the first time that BPA, BPF and BPS differentially affect 5α-R and genes related to DA/5-HT systems in the female PFC. In vivo evidence of the potential adverse effects of BPF and BPS in the brain of mammals is provided in this work, raising questions about the safety of these chemicals as substitutes for BPA. - Highlights: • Juvenile prefrontal cortex of female rats exposed to bisphenol A, F or S was analyzed. • We provide the first in vivo data of BPF and BPS effects in mammal brain. • BPA, BPF and BPS differently affected dopamine and serotonin-related genes. • 5α-reductase was found as a potential target for BPA action in juvenile female brain.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

CO-occurring exposure to perchlorate, nitrate and thiocyanate alters thyroid function in healthy pregnant women

Background: Adequate maternal thyroid function during pregnancy is necessary for normal fetal brain development, making pregnancy a critical window of vulnerability to thyroid disrupting insults. Sodium/iodide symporter (NIS) inhibitors, namely perchlorate, nitrate, and thiocyanate, have been shown individually to competitively inhibit uptake of iodine by the thyroid. Several epidemiologic studies examined the association between these individual exposures and thyroid function. Few studies have examined the effect of this chemical mixture on thyroid function during pregnancy Objectives: We examined the cross sectional association between urinary perchlorate, thiocyanate and nitrate concentrations and thyroid function among healthy pregnant women living in New York City using weighted quantile sum (WQS) regression. Methods: We measured thyroid stimulating hormone (TSH) and free thyroxine (FreeT4) in blood samples; perchlorate, thiocyanate, nitrate and iodide in urine samples collected from 284 pregnant women at 12 (±2.8) weeks gestation. We examined associations between urinary analyte concentrations and TSH or FreeT4 using linear regression or WQS adjusting for gestational age, urinary iodide and creatinine. Results: Individual analyte concentrations in urine were significantly correlated (Spearman's r 0.4–0.5, p<0.001). Linear regression analyses did not suggest associations between individual concentrations and thyroid function. The WQS revealed a significant positive association between the weighted sum of urinary concentrations of the three analytes and increased TSH. Perchlorate had the largest weight in the index, indicating the largest contribution to the WQS. Conclusions: Co-exposure to perchlorate, nitrate and thiocyanate may alter maternal thyroid function, specifically TSH, during pregnancy. - Highlights: • Perchlorate, nitrate, thiocyanate and iodide measured in maternal urine. • Thyroid function (TSH and Free T4) measured in maternal blood. • Weighted quantile sum (WQS) regression examined complex mixture effect. • WQS identified an inverse association between the exposure mixture and maternal TSH. • Perchlorate indicated as the ‘bad actor’ of the mixture.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2016

Exposure to lithium through drinking water and calcium homeostasis during pregnancy: A longitudinal study

There is increasing evidence of adverse health effects due to elevated lithium exposure through drinking water but the impact on calcium homeostasis is unknown. This study aimed at elucidating if lithium exposure through drinking water during pregnancy may impair the maternal calcium homeostasis. In a population-based mother-child cohort in the Argentinean Andes (n=178), with elevated lithium concentrations in the drinking water (5–1660 μg/L), blood lithium concentrations (correlating significantly with lithium in water, urine and plasma) were measured repeatedly during pregnancy by inductively coupled plasma mass spectrometry and used as exposure biomarker. Markers of calcium homeostasis included: plasma 25-hydroxyvitamin D{sub 3}, serum parathyroid hormone (PTH), and calcium, phosphorus and magnesium concentrations in serum and urine. The median maternal blood lithium concentration was 25 μg/L (range 1.9–145). In multivariable-adjusted mixed-effects linear regression models, blood lithium was inversely associated with 25-hydroxyvitamin D{sub 3} (−6.1 nmol/L [95%CI −9.5; −2.6] for a 25 μg/L increment in blood lithium). The estimate increased markedly with increasing percentiles of 25-hydroxyvitamin D{sub 3}. In multivariable-adjusted mixed-effects logistic regression models, the odds ratio of having 25-hydroxyvitamin D3<30 nmol/L (19% of the women) was 4.6 (95%CI 1.1; 19.3) for a 25 μg/L increment in blood lithium. Blood lithium was also positively associated with serum magnesium, but not with serum calcium and PTH, and inversely associated with urinary calcium and magnesium. In conclusion, our study suggests that lithium exposure through drinking water during pregnancy may impair the calcium homeostasis, particularly vitamin D. The results reinforce the need for better control of lithium in drinking water, including bottled water. - Highlights: • Elevated drinking water lithium (Li) concentrations are increasingly reported. • We studied a Li-exposed population-based mother-child cohort in northern Argentina. • Li exposure during pregnancy affected maternal calcium homeostasis. • Blood Li was consistently inversely associated with maternal plasma vitamin D{sub 3}. • Associations were independent of season of sampling and lifestyle.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2017

Effects of environmental pollutants on signaling pathways in rat pituitary GH3 adenoma cells

An increased rate of acromegaly was reported in industrialized areas, suggesting an involvement of environmental pollutants in the pathogenesis and behavior of GH-secreting pituitary adenomas. Based on these premises, the aim of the study was to evaluate the effects of some widely diffused pollutants (i.e. benzene, BZ; bis(2-ethylhexyl) phthalate, DEHP and polychlorinated biphenyls, PCB) on growth hormone secretion, the somatostatin and estrogenic pathways, viability and proliferation of rat GH-producing pituitary adenoma (GH3) cells. All the pollutants induced a statistically significant increase in GH secretion and interfered with cell signaling. They all modulated the expression of SSTR2 and ZAC1, involved in the somatostatin signaling, and the expression of the transcription factor FOXA1, involved in the estrogen receptor signaling. Moreover, all the pollutants increased the expression of the CYP1A1, suggesting AHR pathway activation. None of the pollutants impacted on cell proliferation or viability. Present data demonstrate that exposure to different pollutants, used at in vivo relevant concentrations, plays an important role in the behavior of GH3 pituitary adenoma cells, by increasing GH secretion and modulating several cellular signaling pathways. These observations support a possible influence of different pollutants in vivo on the GH-adenoma aggressiveness and biological behavior. - Highlights: • A link between pollutants and biological behavior of pituitary adenomas is proposed. • Different pollutants are able to induce GH secretion in GH3 cells. • Somatostatin receptor 2 and ZAC1 are downregulated. • Transcriptor factor FOXA1, involved in the estrogen receptor signaling, is induced. • AHR pathway is activated.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Exposure to bisphenols and parabens during pregnancy and relations to steroid changes

Highlights: • BPA, BPA alternatives, and parabens were detected in maternal and cord plasma. • BPA was significantly higher in mixed cord than in maternal plasma (p=0.0455). • Parabens were negatively associated with testosterone in mixed cord plasma. • Main hormonal steroids and selected neurosteroids were determined in both fluids. The harmful effects of endocrine disrupting compounds (EDCs) on human health are generally well-known, and exposure during fetal development may have lasting effects. Fetal exposure to bisphenol A (BPA) has been recently relatively well-studied; however, less is known about alternatives such as bisphenol S (BPS), bisphenol F (BPF) and bisphenol AF (BPAF), which have started to appear in consumer products. Parabens are another widespread group of EDCs, with confirmed transplacental passage. The usage of many cosmetic, pharmaceutical and consumer products during the pregnancy that may contain parabens and bisphenols has led to the need for investigation.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Wi-Fi is an important threat to human health

Highlights: • 7 effects have each been repeatedly reported following Wi-Fi & other EMF exposures. • Established Wi-Fi effects, include apoptosis, oxidat. stress &: • testis/sperm dysfunct; Neuropsych; DNA impact; hormone change; Ca2+ rise. • Wi-Fi is thought to act via voltage-gated calcium channel activation. • One claim of no Wi-Fi effects was found to be deeply flawed. Repeated Wi-Fi studies show that Wi-Fi causes oxidative stress, sperm/testicular damage, neuropsychiatric effects including EEG changes, apoptosis, cellular DNA damage, endocrine changes, and calcium overload. Each of these effects are also caused by exposures to other microwave frequency EMFs, with each such effect being documented in from 10 to 16 reviews. Therefore, each of these seven EMF effects are established effects of Wi-Fi and of other microwave frequency EMFs. Each of these seven is also produced by downstream effects of the main action of such EMFs, voltage-gated calcium channel (VGCC) activation. While VGCC activation via EMF interaction with the VGCC voltage sensor seems to be the predominant mechanism of action of EMFs, other mechanisms appear to have minor roles. Minor roles include activation of other voltage-gated ion channels, calcium cyclotron resonance and the geomagnetic magnetoreception mechanism. Five properties of non-thermal EMF effects are discussed. These are that pulsed EMFs are, in most cases, more active than are non-pulsed EMFs; artificial EMFs are polarized and such polarized EMFs are much more active than non-polarized EMFs; dose-response curves are non-linear and non-monotone; EMF effects are often cumulative; and EMFs may impact young people more than adults. These general findings and data presented earlier on Wi-Fi effects were used to assess the Foster and Moulder (F&M) review of Wi-Fi. The F&M study claimed that there were seven important studies of Wi-Fi that each showed no effect. However, none of these were Wi-Fi studies, with each differing from genuine Wi-Fi in three distinct ways. F&M could, at most conclude that there was no statistically significant evidence of an effect. The tiny numbers studied in each of these seven F&M-linked studies show that each of them lack power to make any substantive conclusions. In conclusion, there are seven repeatedly found Wi-Fi effects which have also been shown to be caused by other similar EMF exposures. Each of the seven should be considered, therefore, as established effects of Wi-Fi.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Persistent organic pollutants as predictors of increased FSH:LH ratio in naturally cycling, reproductive age women

Highlights: • Endocrine disrupting chemicals pose a threat to female fecundity and reproduction. • Examined organochlorines and a marker of ovarian responsivity, FSH:LH ratio. • Increasing concentrations of estrogenic PCBs predict FSH:LH ratio > 2. • PCB congeners related to airborne exposure are associated with FSH:LH ratio > 2. Although several recent studies suggest endocrine disrupting compounds, such as polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (p,p′, DDE), and hexachlorobenzene (HCB), target different organs and systems in the body, their impact on female reproductive function in humans is not well characterized. We seek to determine the relationship between several known endocrine disrupting compounds and a marker of ovarian responsivity, the FSH:LH ratio (higher ratio indicates less ovarian responsivity). For this analysis, 169 naturally cycling women between 21 and 38 years of age completed interviews and had their blood drawn on day 3 of their menstrual cycle for analyses of toxicants, gonadal sex hormones (E{sub 2} and P{sub 4}), and gonadotropins (FSH and LH). PCB congeners were classified into five groups based on their environmental persistence, distribution in human tissue, and toxicological action, reflecting the structure, mechanism, and known biological activity of individual PCB congeners. For every unit (ppb) increase in the level of the estrogenic PCB group, there was a 5-fold greater risk of a FSH:LH ratio ≥ 2, controlling for individual differences in age, percent body fat, cycle day 3 estradiol levels, parity, alcohol use and cigarette smoking in the past year (exp[ß] = 5; p = ≤0.01). PCB congeners identified as estrogenic were analyzed individually, and, of the 19 potentially estrogenic congeners, five were significantly, and positively related to an increased FSH:LH ratio. Four of these congeners are non-persistent, easily volatilize in the environment, and are easily metabolized, and hence, are indicative of very recent or current exposure. p,p′-DDE and HCB were not associated with FSH:LH ratio. We find a clinical indicator of ovarian responsivity, FSH:LH ratio, is associated with a specific group of estrogenic PCBs. These congeners may become airborne when they volatilize from dredged PCB-contaminated soil or from indoor PCB-containing window caulk and sealants in older buildings leading to inhalation exposure. PCB exposure, particularly to non-persistent, estrogenic congeners, may pose an unrecognized threat to female fecundity within the general population.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Exposure to environment chemicals and its possible role in endocrine disruption of children from a rural area

Highlights: • Rural children had elevated blood and hair Mn and Cr levels. • Disruption on thyroid function can be related to metals exposure in rural areas. • Dyslipidemia is associated to thyroid dysfunction in children exposed to metals. • Cholinesterase inhibitors insecticides affect the glucose homeostasis of children. • Children exposed to high levels of Mn can be evaluated through the prolactin. Endocrine disrupting chemicals (EDCs), including pesticides and metals, are present in rural areas, endangering the health of exposed populations. This work aimed to investigate the possible association between the exposure to these xenobiotics and thyroid dysfunction in children living in a rural community of Southern Brazil. Fifty-four children aged 5–16 years participated in this study. Peripheral biomarker evaluations were performed in periods of low and high exposure to pesticides. Thyroid ultrasonography was evaluated in the high exposure period. Blood levels of chromium (Cr), manganese (Mn), mercury (Hg), and lead (Pb), as well as hair Pb levels were positively correlated with thyroid stimulating hormone (TSH) concentrations and negatively associated with free thyroxine (fT4) levels in the low exposure period. Prolactin was positively associated with hair Mn in both periods. In the ultrasound tests, the majority of children presented a normal echogenicity of thyroid. Glucose was inversely associated with the biomarker of exposure to cholinesterase inhibitor insecticides, butyrylcholinesterase (BuChE). Lipid profile was above the recommended levels in both periods. In summary, our results show that children environmentally exposed to a mixture of xenobiotics in an agricultural community may have health impairments, especially on thyroid function, dyslipidemia, and glucose homeostasis disruption.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2010

Young Men Have Equivalent Biochemical Outcomes Compared With Older Men After Treatment With Brachytherapy for Prostate Cancer

Purpose: To evaluate retrospectively the biochemical outcomes of young men treated with low-dose-rate brachytherapy for prostate cancer. Methods and Materials: From 1990 to 2005, 1,665 men with clinically localized prostate cancer were treated with low-dose-rate brachytherapy {+-} hormone therapy (HT) {+-} external beam radiotherapy and underwent {>=}2 years of follow-up. Patients were stratified on the basis of age: {<=}60 (n = 378) and >60 years (n = 1,287). Biochemical failure was defined as a prostate-specific antigen (PSA) nadir plus 2 ng/mL. Univariate and multivariate analyses were used to determine the association of variables with freedom from biochemical failure (FFbF). Results: Median follow-up was 68 months (range, 24-180) for men {<=}60 years and 66 months (range, 24-200) for men >60. For the entire group, the actuarial 5- and 8-year FFbF rates were 94% and 88%, respectively. Men {<=}60 demonstrated similar 5- and 8-year FFbF (95% and 92%) compared with men >60 (93% and 87%; p = 0.071). A larger percent of young patients presented with low-risk disease; lower clinical stage, Gleason score (GS), and pretreatment PSA values; were treated after 1997; did not receive any HT; and had a high biologic effective dose (BED) of radiation (all ps <0.001). On multivariate analysis, PSA (p = 0.001), GS (p = 0.005), and BED (p < 0.001) were significantly associated with FFbF, but age was not (p = 0.665). Conclusion: Young men achieve excellent 5- and 8-year biochemical control rates that are comparable to those of older men after prostate brachytherapy. Young age should not be a deterrent when considering brachytherapy as a primary treatment option for clinically localized prostate cancer.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2010

The Impact of Acute Urinary Retention After Iodine-125 Prostate Brachytherapy on Health-Related Quality of Life

Purpose: To evaluate the impact of acute urinary retention (AUR) in patients treated with {sup 125}I prostate brachytherapy on short- and long-term health-related quality of life (HRQOL); and to assess whether pretreatment HRQOL has additional value in the prediction of AUR. Methods and Materials: For 127 patients treated with {sup 125}I brachytherapy for localized prostate cancer between December 2000 and June 2003, toxicity and HRQOL data were prospectively collected. Patients received a HRQOL questionnaire at five time points: before and 1 month, 6 months, 1 year, and 6 years after treatment. The questionnaire included the RAND-36 generic health survey, the cancer-specific European Organization for Research and Treatment of Cancer core questionnaire (EORTC QLQ-C30), the tumor-specific EORTC prostate cancer module (EORTC QLQ-PR25), and the American Urological Association (AUA) symptom index. Results: Of 127 patients, 13 (10.2%) developed AUR. Patients with AUR had a significantly worse urinary QOL at all time points compared with patients without AUR. The mean difference over time (6 years) between both groups for the EORTC QLQ-PR25 urinary symptom score was 13.0 points (p < 0.001) and for the AUA urinary symptom score was 15.7 points (p = 0.001). Global QOL scores (EORTC QLQ-C30) over time for patients who developed AUR were significantly worse compared with patients without AUR (mean difference 6.7 points; p = 0.043). In multivariate logistic regression analysis, pretreatment International Prostate Symptom Score (p = 0.004) and neoadjuvant hormonal treatment (p = 0.034) were predictors of AUR. Quality of life did not have added predictive value. Conclusion: Acute urinary retention after prostate brachytherapy has a significant negative impact on patient's HRQOL up to 6 years after treatment, in terms of both global QOL measures and urinary symptom scores. Furthermore, our results suggest limited value of pretreatment HRQOL measures for the prediction of AUR.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2010

A Phase I/II Trial of Gefitinib Given Concurrently With Radiotherapy in Patients With Nonmetastatic Prostate Cancer

Purpose: To estimate the safety and tolerability of daily administration of 250 mg of gefitinib given concurrently with three-dimensional conformal radiotherapy for patients with nonmetastatic prostate cancer. Methods and Materials: A total of 42 patients with T2-T3N0M0 tumors were treated in a nonrandomized single-center study. A prostate-specific antigen (PSA) level of <20 and a good performance status (WHO, 0-1) were required. Adjuvant or neoadjuvant hormone treatments were not allowed. A daily regimen of 250 mg of gefitinib was started 1 week before radiation therapy began and lasted for the duration of radiation therapy. A dose of 50.4 Gy (1.8 Gy/day) was administered to the tumor, prostate, and seminal vesicles, followed by a 22-Gy booster (2 Gy/day) for a total dose of 72.4 Gy. Correlative studies included analysis of epidermal growth factor receptor (EGFR), EGFRvIII, and phosphorylated EGFR in tumors and tumor necrosis factor, interleukin-1{alpha} (IL-1{alpha}), and IL-6 in serum. Results: Maximum tolerated dose was not reached in phase I (12 patients), and 30 additional patients were treated in phase II. Thirty (71.4%) patients completed trial medication. Dose-limiting toxicities were recorded for 16 (38.1%) patients, the most common of which was a grade 3 to 4 increase in transaminase (6 patients). After a median follow-up of 38 months, there were no deaths due to prostate cancer. The estimated PSA relapse-free survival rate at 4 years (Kaplan-Meier) was 97%, the salvage therapy-free survival rate was 91%, and the overall survival rate was 87%. These figures compared favorably with those of matched patients treated with radiation only at higher doses. Conclusions: The combination of gefitinib and radiation is reasonably well tolerated and has promising activity against nonmetastatic prostate cancer.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2010

Predicting Post-External Beam Radiation Therapy PSA Relapse of Prostate Cancer Using Pretreatment MRI

Purpose: To investigate whether pretreatment endorectal magnetic resonance imaging (MRI) findings can predict biochemical relapse in patients with clinically localized prostate cancer treated with external beam radiation therapy (EBRT). Methods and Materials: Between January 2000 and January 2002, 224 patients (median age, 69 years; age range, 45-82 years) with biopsy-proven prostate cancer underwent endorectal MRI before high-dose ({>=}81Gy) EBRT. The value of multiple clinical and MRI variables in predicting prostate-specific antigen (PSA) relapse at 5 years was determined by use of univariate and multivariate stepwise Cox regression. Clinical variables included pretreatment PSA, clinical T stage, Gleason score, use of neoadjuvant hormonal therapy, and radiation dose. Magnetic resonance imaging variables, derived from retrospective consensus readings by two radiologists, were used to measure intraprostatic and extraprostatic tumor burden. Results: After a median follow-up of 67 months, PSA relapse developed in 37 patients (16.5%). The significant predictors of PSA relapse on univariate analysis were pretreatment PSA, clinical T stage, and multiple MRI variables, including MRI TN stage score; extracapsular extension (ECE) status; number of sextants involved by ECE, all lesions, or index (dominant) lesion; apical involvement; and diameter and volume of index lesion. Pretreatment PSA and ECE status were the only significant independent predictors on multivariate analysis (p < 0.05 for both). Extracapsular extension status was associated with the highest hazard ratio, 3.04; 5-year PSA relapse rates were 7% for no ECE, 20% for unilateral ECE, and 48% for bilateral ECE. Conclusions: Magnetic resonance imaging findings can be used to predict post-EBRT PSA relapse, with ECE status on MRI and pretreatment PSA being significant independent predictors of this endpoint.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Prostate-Specific Antigen Bounce After Permanent Iodine-125 Prostate Brachytherapy-An Australian Analysis

Purpose: To report on prostate-specific antigen (PSA) 'bounces' after {sup 125}I prostate brachytherapy to review the relationship to biochemical control and correlate both clinical and dosimetric variables. Methods and Materials: We analyzed 194 hormone-naive patients with a follow-up of {>=}3 years. Four bounce definitions were applied: an increase of {>=}0.2 ng/mL (definition I), {>=}0.4 ng/mL (definition II), {>=}15% (definition III), and {>=}35% (definition IV) of a previous value with spontaneous return to the prebounce level or lower. Results: Using definition I, II, III, and IV, a bounce was detected in 50%, 34%, 11%, and 9% of patients, respectively. The median time to onset was 14-16 months, the duration was 12-21.5 months, and the magnitude of the increase was 0.5-2 ng/mL. A magnitude of >2 ng/mL, fulfilling the criteria for biochemical failure (BF) according to the American Society for Therapeutic Radiology and Oncology Phoenix definition, was detected in 11.3%, 16.9%, 47.6%, and 50% using definitions I, II, III, and IV, respectively; 11 patients (5.7%) had true BF. The PSA bounces occurred earlier than BF (p < 0.001). The prediction of BF remains controversial and is probably unrelated to biochemical control. The only statistically significant factor predictive of a PSA bounce was younger age (definitions I and II). Conclusion: PSA bounces are common after brachytherapy. All definitions resulted in a high number of false-positive calls for BF during the first 2 years. The definition of an increase of {>=}0.2 ng/mL should be preferred because of the lowest number of false-positive results for BF. Patients experiencing a PSA bounce during the first 2 years after brachytherapy should undergo surveillance every 3-6 months. Additional investigations are recommended for elevated postimplant PSA levels that have not corrected by 3 years of follow-up.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Overall Survival Benefit From Postoperative Radiation Therapy for Organ-Confined, Margin-Positive Prostate Cancer

Purpose: Radical prostatectomy for invasive prostate cancer is associated with positive margin rates in 10% to 50% of resected specimens. Postoperative radiation therapy may benefit patients who have organ-confined prostate cancer with positive margins. Methods and Materials: We performed a retrospective analysis to examine whether adjunctive radiation therapy enhanced long-term survival for prostate cancer patients who underwent prostatectomy for localized prostate cancer but with positive margins. We used the Hoag Cancer Center database to identify patients diagnosed with invasive prostate cancer. Relative and overall survival rates were calculated. Results: Among 1,474 patients diagnosed with localized invasive prostate cancer during the years 1990 to 2006 and undergoing prostatectomy, 113 (7.7%) were identified who had positive margins and did not have local extension of disease, positive lymph nodes, or distant metastases. A total of 17 patients received adjunctive radiation therapy (Group A), whereas 96 did not (Group B; 3 received hormonal therapy). Both groups had a median age of 64 years and median follow-up of 7.5 years. In Group A, no patients have died as of last follow-up, but in Group B, 18 have died. Estimated 10-year and 15-year overall survival rates were both 100% for Group A compared with 85% and 57% respectively for Group B (p{sub 2} = 0.050, log rank). Relative 10- and 15 year survival rates were both 100% for Group A compared with 100% and 79% respectively for Group B. Conclusions: This retrospective analysis suggests that prostate cancer patients with localized disease but positive margins do derive a survival benefit from adjuvant radiation therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Accelerated Partial Breast Irradiation: 5-Year Results of the German-Austrian Multicenter Phase II Trial Using Interstitial Multicatheter Brachytherapy Alone After Breast-Conserving Surgery

Purpose: To evaluate the impact of accelerated partial breast irradiation on local control, side effects, and cosmesis using multicatheter interstitial brachytherapy as the sole method for the adjuvant local treatment of patients with low-risk breast cancer. Methods and Materials: 274 patients with low-risk breast cancer were treated on protocol. Patients were eligible for the study if the tumor size was < 3 cm, resection margins were clear by at least 2 mm, no lymph node metastases existed, age was >35 years, hormone receptors were positive, and histologic grades were 1 or 2. Of the 274 patients, 175 (64%) received pulse-dose-rate brachytherapy (D{sub ref} = 50 Gy). and 99 (36%) received high-dose-rate brachytherapy (D{sub ref} = 32.0 Gy). Results: Median follow-up was 63 months (range, 9-103). Only 8 of 274 (2.9%) patients developed an ipsilateral in-breast tumor recurrence at the time of analysis. The 5-year actuarial local recurrence-free survival probability was 98%. The 5- year overall and disease-free survival probabilities of all patients were 97% and 96%, respectively. Contralateral in-breast malignancies were detected in 2 of 274 (0.7%) patients, and distant metastases occurred in 6 of 274 (2.2%). Late side effects {>=}Grade 3 (i.e., breast tissue fibrosis and telangiectasia) occurred in 1 patient (0.4%, 95%CI:0.0-2.0%) and 6 patients (2.2%, 95%CI:0.8-4.7%), respectively. Cosmetic results were good to excellent in 245 of 274 patients (90%). Conclusions: The long-term results of this prospective Phase II trial confirm that the efficacy of accelerated partial breast irradiation using multicatheter brachytherapy is comparable with that of whole breast irradiation and that late side effects are negligible.

62 RADIOLOGY AND NUCLEAR MEDICINE↗