Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “TOXICITY”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,531 records · Page 85
All sourcesNASA NTRSDOE OSTI
DOE OSTI2015

Anthroposophic lifestyle influences the concentration of metals in placenta and cord blood

Allergic diseases develop in genetically susceptible individuals in a complex interplay with the environment, usually early in life. We have previously shown that the anthroposophic lifestyle is associated with reduced risk of allergic disease in children, but details on the influencing environmental factors are largely unknown. This study aims to elucidate if anthroposophic lifestyle influences fetal exposure to selected toxic and essential elements. Randomly selected non-smoking mothers with (n=40) and without (n=40) anthroposophic lifestyle from the prospective birth cohort ALADDIN were included. Concentrations of 12 toxic and essential elements were analyzed in full term placentas and in the erythrocyte fractions of maternal peripheral blood and of umbilical cord blood, using inductively coupled plasma mass spectrometry. Cadmium concentrations in maternal blood and placenta were significantly higher in mothers with an anthroposophic lifestyle (p<0.001), while concentrations in cord blood were generally low, irrespective of lifestyle. Cobalt concentrations were higher in both maternal blood, placenta and cord blood in the anthroposophic group. Lead concentrations were higher in maternal blood and cord blood, but not placenta, of mothers with anthroposophic lifestyle. Analysis of covariance, including lifestyle, parity, maternal age, gestational age, vegetarian diet, use of herbal medicine and occupation in the model, showed that mainly the anthroposophic lifestyle was significantly associated with cadmium concentrations. In conclusion, women with an anthroposophic lifestyle had higher concentrations of cadmium, cobalt and lead concentrations. Cadmium concentrations might have been influenced by a diet rich in vegetables and/or low iron status of the mothers. - Highlights: • Toxic elements in mother–newborn pairs in relation to anthroposophic lifestyle. • Anthroposophic lifestyle was associated with higher levels of cadmium, cobalt and lead. • A diet rich in vegetables and/or low iron status may explain observed findings. • Nine other elements showed no differences by lifestyle.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2014

Cytotoxicity of TiO{sub 2} nanoparticles towards freshwater sediment microorganisms at low exposure concentrations

There is a persistent need to assess the effects of TiO{sub 2} nanoparticles on the aquatic ecosystem owing to their increasing usage in consumer products and risk of environmental release. The current study is focused on TiO{sub 2} nanoparticle-induced acute toxicity at sub-ppm level (≤1 ppm) on the three different freshwater sediment bacterial isolates and their consortium under two different irradiation (visible light and dark) conditions. The consortium of the bacterial isolates was found to be less affected by the exposure to the nanoparticles compared to the individual cells. The oxidative stress contributed considerably towards the cytotoxicity under both light and dark conditions. A statistically significant increase in membrane permeability was noted under the dark conditions as compared to the light conditions. The optical and fluorescence microscopic images showed aggregation and chain formation of the bacterial cells, when exposed to the nanoparticles. The electron microscopic (SEM, TEM) observations suggested considerable damage of cells and bio-uptake of nanoparticles. The exopolysaccrides (EPS) production and biofilm formation were noted to increase in the presence of the nanoparticles, and expression of the key genes involved in biofilm formation was studied by RT-PCR. - Highlights: • Toxicity of NPs towards freshwater sediment bacteria at sub-ppm concentrations. • Decreased toxicity of the nanoparticles in the consortium of microorganisms. • Enhanced bacterial resistance through EPS and biofilm formation in the presence of NPs. • Considerable surface damage of cells and internalization of NPs. • Gene expression analyses related to biofilm formation in the presence of NPs.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2015

Photocatalytic treatment of pharmaceutical wastewater using new multiwall-carbon nanotubes/TiO{sub 2}/SiO{sub 2} nanocomposites

For the photocatalytic removal of bisphenol A (BPA) and carbamazepine (CBZ) from water solution a new multiwall-carbon nanotubes and TiO{sub 2}/SiO{sub 2} nanocomposites (MWCNT–TiO{sub 2}–SiO{sub 2}) were applied. Nanocomposites with the addition of 0.15–17.8 wt% MWCNT show high potential for the removal of both pollutants. The starting concentration of each contaminant was halved during 20 min of UVA irradiation. The decomposition process of CBZ over investigated nanocomposites proceeded differently than it was observed for the classical photocatalyst P25. The kinetics of the removal followed as a pseudo-first order regime with the k{sub 1} in range 0.0827–0.1751 min{sup −1} for BPA and 0.0131–0.0743 min{sup −1} for CBZ. Toxicity to Vibrio fischeri and Daphnia magna was significantly reduced indicating formation of non-toxic products of photooxidation of tested contaminants. - Highlights: • MWCNT enhanced TiO{sub 2} activity in UVA and the removal of BPA and CBZ. • At least 50% PPCPs removal during 30 min of photocatalytic treatment was observed. • MWCNT changed the mechanism of CBZ decomposition but not BPA. • Decomposition products of both BPA and CBZ possessed low toxicity. • Photocatalysis may be recommended for the initial treatment of pharmaceutical wastewater.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2015

Environmental contaminants of emerging concern in seafood – European database on contaminant levels

Marine pollution gives rise to concern not only about the environment itself but also about the impact on food safety and consequently on public health. European authorities and consumers have therefore become increasingly worried about the transfer of contaminants from the marine environment to seafood. So-called “contaminants of emerging concern” are chemical substances for which no maximum levels have been laid down in EU legislation, or substances for which maximum levels have been provided but which require revision. Adequate information on their presence in seafood is often lacking and thus potential risks cannot be excluded. Assessment of food safety issues related to these contaminants has thus become urgent and imperative. A database ( (www.ecsafeseafooddbase.eu)), containing available information on the levels of contaminants of emerging concern in seafood and providing the most recent data to scientists and regulatory authorities, was developed. The present paper reviews a selection of contaminants of emerging concern in seafood including toxic elements, endocrine disruptors, brominated flame retardants, pharmaceuticals and personal care products, polycyclic aromatic hydrocarbons and derivatives, microplastics and marine toxins. Current status on the knowledge of human exposure, toxicity and legislation are briefly presented and the outcome from scientific publications reporting on the levels of these compounds in seafood is presented and discussed. - Highlights: • Development of a European database regarding contaminants of emerging concern. • Current status on knowledge of human exposure, toxicity and legislation. • Review on the occurrence of contaminants of emerging concern in seafood.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2015

POPs in free-ranging pilot whales, sperm whales and fin whales from the Mediterranean Sea: Influence of biological and ecological factors

The pilot whale Globicephala melas, the sperm whale Physeter macrocephalus, and the fin whale Balaenoptera physalus are large cetaceans permanently inhabiting the Mediterranean Sea. These species are subjected to numerous anthropogenic threats such as exposure to high levels of contaminants. Therefore, selected persistent organic pollutants POPs (29 PCBs, 15 organochlorine compounds, 9 PBDEs and 17 PCDD/Fs) were analysed in blubber biopsies of 49 long-finned pilot whales, 61 sperm whales and 70 fin whales sampled in the North Western Mediterranean Sea (NWMS) from 2006 to 2013. Contamination profile and species feeding ecology were then combined through the use of stable isotopes. δ{sup 13}C, δ{sup 15}N values and POPs levels were assessed through IR-MS and GC–MS respectively. To assess the toxic potency of the dioxin-like compounds, the TEQ approach was applied. δ{sup 15}N values were 12.2±1.3‰ for sperm whales, 10.5±0.7‰ for pilot whales and 7.7±0.8‰ in fin whales, positioning sperm whales at higher trophic levels. δ{sup 13}C of the two odontocetes was similar and amounted to −17.3±0.4‰ for sperm whales and −17.8±0.3‰ for pilot whales; whilst fin whales were more depleted (−18.7±0.4‰). This indicates a partial overlap in toothed-whales feeding habitats, while confirms the differences in feeding behaviour of the mysticete. Pilot whales presented higher concentrations than sperm whales for ΣPCBs (38,666±25,731 ng g{sup −1} lw and 22,849±15,566 ng g{sup −1} lw respectively), ΣPBDEs (712±412 ng g{sup −1} lw and 347±173 ng g{sup −1} lw respectively) and ΣDDTs (46,081±37,506 ng g{sup −1} lw and 37,647±38,518 ng g{sup −1} lw respectively). Fin whales presented the lowest values, in accordance with its trophic position (ΣPCBs: 5721±5180 ng g{sup −1} lw, ΣPBDEs: 177±208 ng g{sup −1} lw and ΣDDTs: 6643±5549 ng g{sup −1} lw). Each species was characterized by large inter-individual variations that are more related to sex than trophic level, with males presenting higher contaminant burden than females. The discriminant analysis (DA) confirmed how DDTs and highly chlorinated PCBs were influential in differentiating the three species. Pollutant concentrations of our species were significantly higher than both their Southern Hemisphere and North Atlantic counterparts, possibly due to the particular Mediterranean geomorphology, which influences pollutants distribution and recycle. Dioxin-like PCBs accounted for over 80% of the total TEQ. This study demonstrated (1) an important exposure to pollutants of Mediterranean cetaceans, often surpassing the estimated threshold toxicity value of 17,000 ng g{sup −1} lw for blubber in marine mammals; and (2) how the final pollutant burden in these animals is strongly influenced not only by the trophic position but also by numerous other factors such as sex, age, body size and geographical distribution. - Highlights: • We analysed POPs concentrations in cetaceans from North-western Mediterranean Sea. • We integrated δ{sup 13}C and δ{sup 15}N values to combine trophic position and contamination. • Odontocetes show PCBs level higher than the toxicity threshold of 17 μg g{sup −1} lw. • Trophic position, sex, body size and distribution affect interspecies diversity.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2016

Environmental exposure to arsenic and chromium in children is associated with kidney injury molecule-1

Environmental hazards from natural or anthropological sources are widespread, especially in the north-central region of Mexico. Children represent a susceptible population due to their unique routes of exposure and special vulnerabilities. In this study we evaluated the association of exposure to environmental kidney toxicants with kidney injury biomarkers in children living in San Luis Potosi (SLP), Mexico. A cross-sectional study was conducted with 83 children (5–12 years of age) residents of Villa de Reyes, SLP. Exposure to arsenic, cadmium, chromium, fluoride and lead was assessed in urine, blood and drinking water samples. Almost all tap and well water samples had levels of arsenic (81.5%) and fluoride (100%) above the permissible levels recommended by the World Health Organization. Mean urine arsenic (45.6 ppb) and chromium (61.7 ppb) were higher than the biological exposure index, a reference value in occupational settings. Using multivariate adjusted models, we found a dose-dependent association between kidney injury molecule-1 (KIM-1) across chromium exposure tertiles [(T1: reference, T2: 467 pg/mL; T3: 615 pg/mL) (p-trend=0.001)]. Chromium upper tertile was also associated with higher urinary miR-200c (500 copies/μl) and miR-423 (189 copies/μL). Arsenic upper tertile was also associated with higher urinary KIM-1 (372 pg/mL). Other kidney injury/functional biomarkers such as serum creatinine, glomerular filtration rate, albuminuria, neutrophil gelatinase-associated lipocalin and miR-21 did not show any association with arsenic, chromium or any of the other toxicants evaluated. We conclude that KIM-1 might serve as a sensitive biomarker to screen children for kidney damage induced by environmental toxic agents. - Highlights: • Children living in Mexico had exceedingly high arsenic and chromium exposure. • Arsenic and chromium exposure was significantly associated with urinary KIM-1. • KIM-1 might serve as a sensitive biomarker to evaluate kidney injury in children.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Macro and trace elements in Paracentrotus lividus gonads from South West Atlantic areas

Highlights: • High levels of Pb and Hg in sea urchin gonads collected in open areas. • Studied areas seem to be suitable for the sustainable exploitation of sea urchin. • Levels of toxic elements in gonads were below MLs, not constituting a health risk. Sea urchin represents one of the most valuable seafood product being harvested and explored for their edible part, the gonads or roe. This species is generally considered a sentinel organism for ecotoxicological studies being widely used in monitoring programs to assess coastal aquatic environments quality, because is directly exposed to anthropogenic contaminants in their habitat. In this context, the aim of this study is to evaluate the concentrations of macro (Cl, K, P, Ca, S) and trace (Zn, Br, Fe, Sr, I, Se, Rb, Cu, Cr, Ni, As, iAs, Cd, Pb, Hg) elements in Paracentrotus lividus gonads from three South West Atlantic production areas subjected to distinct environmental and anthropogenic pressures. In all studied areas, the elements profile in sea urchin gonads was Cl > K > P > Ca > S > Zn > Br > Fe > Sr > I > Rb > Cu > Se > Cr > Ni, suggesting an element guide profile with special interest for sea urchin farming development. Concerning toxic elements, the profile was the following: As > Cd > Pb > Hg > iAs. The results evidenced higher levels of Pb and Hg in open areas. Distinct area characteristics and anthropogenic pressures of production areas evidence the importance of biomonitoring contaminants, particularly toxic elements. In general, the levels of these elements were below maximum levels in foodstuffs (MLs) which pose a minimal health risk to consumers.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

The role of B7 costimulation in benzene immunotoxicity and its potential association with cancer risk

Highlights: • Benzene occupational exposure decreases the B7.1 and B7.2 gene and protein expressions. • Benzene occupational exposure decreases the p53 gene expression. • B7.1, B7.2 and p53 gene expressions were associated among each other. Benzene is a recognized human carcinogen; however, there are still some gaps in the knowledge regarding the mechanism of toxicity of this organic solvent and potential early biomarkers for the damage caused by it. In a previous study, our research group demonstrated that the adhesion molecules of the immune system (B7.1 and B7.2) could be potential biomarkers in the early detection of immunotoxicity caused by benzene exposure. Therefore, this study was developed to deepen the understanding regarding this important topic, aiming to contribute to the comprehension of the benzene toxicity mechanism mediated by B7.1 and B7.2 and its potential association with the risk of carcinogenicity. B7.1 and B7.2 protein expression in blood monocytes and B7.1 and B7.2 gene expression in PBMCs were evaluated. Additionally, complement C3 and C4 levels in serum were measured, as well as p53 gene expression in PBMCs. Seventy-four gas station workers (GSW group) and 71 non-occupationally exposed subjects (NEG) were evaluated. Our results demonstrated decreased levels of B7.1 and B7.2 protein and gene expression in the GSW group compared to the NEG (n = 71) (p < 0.01). Along the same lines, decreased levels of the complement system were observed in the GSW group (p < 0.01), demonstrating the impairment of this immune system pathway as well. Additionally, a reduction was observed in p53 gene expression in the GSA group (p < 0.01). These alterations were associated with both the benzene exposure biomarker evaluated, urinary trans, trans-muconic acid, and with exposure time (p < 0.05). Moreover, strong correlations were observed between the gene expression of p53 vs. B7.1 (r = 0.830; p < 0.001), p53 vs. B7.2 (r = 0.685; p < 0.001), and B7.1 vs. B7.2 (r = 0.702; p < 0.001). Taken together, these results demonstrate that the immune system co-stimulatory molecule pathway is affected by benzene exposure. Also, the decrease in p53 gene expression, even at low exposure levels, reinforces the carcinogenicity effect of benzene in this pathway. Therefore, our results suggest that the promotion of immune evasion together with a decrease in p53 gene expression may play an important role in the benzene toxicity mechanism. However, further and targeted studies are needed to confirm this proposition.

02 PETROLEUM↗
DOE OSTI2018

Stress axis variability is associated with differential ozone-induced lung inflammatory signaling and injury biomarker response

Highlights: • Fischer and Lewis rats exhibited distinct stress axis responses to ozone inhalation. • Hypo-stress responsive Lewis rats had a greater lung inflammatory response. • Hyper-stress responsive Fischer rats had a greater lung injury response. • Innate stress axis differences may play a role in ozone-induced lung toxicity. Ozone (O{sub 3}), a ubiquitous urban air pollutant, causes adverse pulmonary and extrapulmonary effects. A large variability in acute O{sub 3}-induced effects has been observed; however, the basis for interindividual differences in susceptibility is unclear. We previously demonstrated a role for the hypothalamic-pituitary-adrenal (HPA) stress axis and glucocorticoid response in acute O{sub 3} toxicity. Glucocorticoids have important anti-inflammatory actions, and have been shown to regulate lung inflammatory responses. We hypothesised that a hyporesponsive HPA axis would be associated with greater O{sub 3}-dependent lung inflammatory signaling. Two genetically-related rat strains with known differences in stress axis reactivity, highly-stress responsive Fischer (F344) and less responsive Lewis (LEW), were exposed for 4 h by nose-only inhalation to clean air or 0.8 ppm O{sub 3}, and euthanized immediately after exposure. As expected, baseline (air-exposed) plasma corticosterone was significantly lower in the hypo-stress responsive LEW. Although O{sub 3} exposure increased plasma corticosterone in both strains, corticosterone remained significantly lower in LEW when compared to F334. LEW exhibited greater O{sub 3}-induced inflammatory cytokine/chemokine signaling compared to F344, consistent with the lower corticosterone levels. Since we observed strain-specific differences in inflammatory signaling, we further investigated injury biomarkers (total protein, albumin and lactate dehydrogenase). Although the hyper-responsive F344 exhibited lower inflammatory signaling in response to O{sub 3} compared with LEW, they had greater levels of lung injury biomarkers. Our results indicate that stress axis variability is associated with differential O{sub 3}-induced lung toxicity. Given the large variability in stress axis reactivity among humans, stress axis regulation could potentially be a determining factor underlying O{sub 3} sensitivity.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2011

Preoperative Chemoradiation for Rectal Cancer Using Capecitabine and Celecoxib Correlated With Posttreatment Assessment of Thymidylate Synthase and Thymidine Phosphorylase Expression

Purpose: Thymidylate synthase (TS) and thymidine phosphorylase (TP) expression have been shown to be predictors of response to therapy. The toxicity, efficacy, surgical morbidity, and immunohistochemical TS and TP expression were assessed in surgical resection specimens after preoperative chemoradiation. Methods and Materials: Twenty patients with clinical stage I to III rectal adenocarcinoma received preoperative chemoradiation and underwent surgical resection 6 weeks later. Results: Posttreatment tumor stages were T1 to T2 and N0 in 30% of patients; T3 to T4 and N0 in 30% of patients; and T1 to T3 and N1 to N2 in 15% of patients. Pathologic complete response (pCR) was evident in 25% and tumor regression occurred in a total of 80% of patients. Anal sphincter-sparing surgery was performed in 80% of cases. Acute and perioperative complications were minimal, with no grade 3/4 toxicity or treatment breaks. Pelvic control was obtained in 90% of patients. With a median follow-up of 65.5 months (range, 8-80 months), the 6-year actuarial survival rate was 75%. Local failure was significantly associated with nonresponse to therapy and with high TS and low TP expression (p = 0.008 and p = 0.04, respectively). Conclusions: The combination of capecitabine, celecoxib, and x-radiation therapy yields excellent response: a 25% pathologic pCR, no acute grade 3/4 toxicity, and minimal surgical morbidity. Nonresponders expressed significantly increased TS levels and decreased TP levels in posttreatment resection specimens compared to responders.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Conformal Radiotherapy in the Treatment of Advanced Juvenile Nasopharyngeal Angiofibroma With Intracranial Extension: An Institutional Experience

Purpose: To describe the results of conformal radiotherapy in advanced juvenile nasopharyngeal angiofibroma in a tertiary care institution. Methods and Materials: Retrospective chart review was conducted for 8 patients treated with conformal radiotherapy between 2006 and 2009. The median follow-up was 17 months. All patients had Stage IIIB disease with intracranial extension. Radiotherapy was considered as treatment because patients were deemed inoperable owing to extensive intracranial/intraorbital extension or proximity to optic nerve. All but 1 patient were treated with intensity-modulated radiotherapy using seven coplanar fields. Median (range) dose prescribed was 39.6 (30-46) Gy. Actuarial analysis of local control and descriptive analysis of toxicity profile was conducted. Results: Despite the large and complex target volume (median planning target volume, 292 cm{sup 3}), intensity-modulated radiotherapy achieved conformal dose distributions (median van't Reit index, 0.66). Significant sparing of the surrounding organs at risk was obtained. No significant Grade 3/4 toxicities were experienced during or after treatment. Actual local control at 2 years was 87.5%. One patient died 1 month after radiotherapy secondary to massive epistaxis. The remaining 7 patients had progressive resolution of disease and were symptom-free at last follow-up. Persistent rhinitis was the only significant toxicity, seen in 1 patient. Conclusions: Conformal radiotherapy results in good local control with minimal acute and late side effects in juvenile nasopharyngeal angiofibromas, even in the presence of advanced disease.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Does the Addition of Involved Field Radiotherapy to High-Dose Chemotherapy and Stem Cell Transplantation Improve Outcomes for Patients With Relapsed/Refractory Hodgkin Lymphoma?

Purpose: To evaluate the value of adding involved field radiotherapy (IFRT) to patients with relapsed/refractory Hodgkin lymphoma (HL) undergoing high-dose chemotherapy (HDCT) and stem cell transplantation (SCT). Methods and Materials: Ninety-two patients with relapsed/refractory HL undergoing HDCT and SCT from 1995 to 2008 were analyzed in a case-control design. Forty-six HL patients treated with IFRT within 2 months of SCT were matched to 46 HL patients who did not receive IFRT based on age, stage at relapse, timing of relapse, histology, and year of SCT. All were evaluated for response, survival, and toxicity with a median followup of 63.5 months. Results: There was a trend for better disease control in patients receiving IFRT. Specifically, 10/46 IFRT patients (22%) relapsed/progressed after SCT compared with 17/46 control patients (37%). Of the failures after IFRT, 70% were inside the radiation field, all in sites of bulky disease. In patients with nonbulky disease, IFRT also resulted in significantly improved outcomes (failure rate 6% vs. 33%, respectively). When stratified by disease bulk, the use of IFRT was found to significantly improve DFS (p = 0.032), but did not affect OS. In addition, IFRT and nonbulky disease were found to be positive prognostic indicators for DFS with hazard ratios of 0.357 (p = 0.032) and 0.383 (p = 0.034), respectively. Grade IV/V toxicities were significantly higher in the IFRT vs. non-IFRT group (28% vs. 2%; p < 0.001), observed only in patients receiving a busulfan-based conditioning regimen. Conclusion: Patients with refractory or relapsed HL undergoing HDCT and SCT have a high risk of relapse in sites of prior disease involvement, especially in sites of bulky disease. The use of IFRT is associated with a lower risk of disease progression in these sites; however bulky disease sites are still difficult to control. Toxicity risk is significant, particularly when busulfan-based conditioning is combined with IFRT, and alternative chemotherapy conditioning regimens should be considered.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

CHOD/BVAM Chemotherapy and Whole-Brain Radiotherapy for Newly Diagnosed Primary Central Nervous System Lymphoma

Purpose: To assess the efficacy and toxicity of chemotherapy consisting of cyclophosphamide, doxorubicin (Adriamycin), vincristine, and dexamethasone (CHOD) plus bis-chloronitrosourea (BCNU), cytosine arabinoside, and methotrexate (BVAM) followed by whole-brain irradiation (WBRT) for patients with primary central nervous system lymphoma (PCNSL). Methods and Materials: Patients 70 years old and younger with newly diagnosed, biopsy-proven PCNSL received one cycle of CHOD followed by two cycles of BVAM. Patients then received WBRT, 30.6 Gy, if a complete response was evoked, or 50.4 Gy if the response was less than complete; both doses were given in 1.8-Gy daily fractions. The primary efficacy endpoint was 1-year survival. Results: Thirty-six patients (19 men, 17 women) enrolled between 1995 and 2000. Median age was 60.5 years (range, 34 to 69 years). Thirty (83%) patients had baseline Eastern Cooperative Oncology Group performance scores of 0 to 1. All 36 patients were eligible for survival and response evaluations. Median time to progression was 12.3 months, and median survival was 18.5 months. The percentages of patients alive at 1, 2, and 3 years were 64%, 36%, and 33%, respectively. The best response was complete response in 10 patients and immediate progression in 7 patients. Ten (28%) patients had at least one grade 3 or higher neurologic toxicity. Conclusions: This regimen did improve the survival of PCNSL patients but also caused substantial toxicity. The improvement in survival is less than that reported with high-dose methotrexate-based therapies.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Proton Beam Therapy of Stage II and III Non-Small-Cell Lung Cancer

Purpose: The present retrospective study assessed the role of proton beam therapy (PBT) in the treatment of patients with Stage II or III non-small-cell lung cancer who were inoperable or ineligible for chemotherapy because of co-existing disease or refusal. Patients and Methods: Between November 2001 and July 2008, PBT was given to 35 patients (5 patients with Stage II, 12 with Stage IIIA, and 18 with Stage IIIB) whose median age was 70.3 years (range, 47.4-85.4). The median proton dose given was 78.3 Gy (range, 67.1-91.3) (relative biologic effectiveness). Results: Local progression-free survival for Stage II-III patients was 93.3% at 1 year and 65.9% at 2 years during a median observation period of 16.9 months. Four patients (11.4%) developed local recurrence, 13 (37.1%) developed regional recurrence, and 7 (20.0%) developed distant metastases. The progression-free survival rate for Stage II-III patients was 59.6% at 1 year and 29.2% at 2 years. The overall survival rate of Stage II-III patients was 81.8% at 1 year and 58.9% at 2 years. Grade 3 or greater toxicity was not observed. A total of 15 patients (42.9%) developed Grade 1 and 6 (17.1%) Grade 2 toxicity. Conclusion: PBT for Stage II-III non-small-cell lung cancer without chemotherapy resulted in good local control and low toxicity. PBT has a definite role in the treatment of patients with Stage II-III non-small-cell lung cancer who are unsuitable for surgery or chemotherapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Early Side Effects of Three-Dimensional Conformal External Beam Accelerated Partial Breast Irradiation to a Total Dose of 40 Gy in One Week (A Phase II Trial)

Purpose: Several accelerated partial breast irradiation (APBI) techniques are described in the literature, and apparently, the three-dimensional (3D)-conformal technique is being used increasingly. Nonetheless, the optimal radiation dose is not yet known. Here, we report feasibility and early toxicities of APBI delivering 40 Gy over 5 days, in a phase II trial. Methods and Materials: From October 2007 to September 2008, 25 patients with pT1N0 cancer received 3D-conformal APBI. The prescribed radiation dose was 40 Gy in 4-Gy fractions given twice daily. This technique used two minitangents and an 'en face' electron field. Toxicities were systematically assessed at 1, 2, and 6 months and then once every 6 months. Results: The planning tumor volume for evaluation (PTV{sub E}VAL) coverage was adequate: the mean dose to the PTV{sub E}VAL was 41.8 Gy (range, 41-42.4 Gy). Mean doses to the ipsilateral lung and heart were 1.6 Gy (range, 1.0-2.3 Gy) and 1.2 Gy (range, 1.0-1.6 Gy), respectively. One and two months after completion of APBI, most patients had no or mild erythema (n = 16 patients at 1 month; n = 25 patients at 2 months); none of these patients developed moist desquamation. After a median follow-up of 12 months, only 1 patient had a significant moderate field contracture (grade 2). Other reported late toxicities were grade 1. Conclusions: 3D-conformal APBI (with two minitangents and an 'en face' electron field) using a total dose of 40 Gy in 10 fractions twice daily over 5 days achieved appropriate PTV{sub E}VAL coverage and offered significant sparing of normal tissue. Early tolerance was excellent.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Hypofractionated Versus Conventionally Fractionated Radiotherapy for Prostate Carcinoma: Final Results of Phase III Randomized Trial

Purpose: To evaluate the long-term efficacy and toxicity of a hypofractionated (55 Gy in 20 fractions within 4 weeks) vs. a conventionally fractionated (64 Gy in 32 fractions within 6.5 weeks) dose schedule for radiotherapy (RT) for localized carcinoma of the prostate. Methods and Materials: A total of 217 patients were randomized to either the hypofractionated (n = 108) or the conventional (n = 109) dose schedule. Most patients (n = 156) underwent RT planning and RT using a two-dimensional computed tomography method. Efficacy using the clinical, radiologic, and prostate-specific antigen data in each patient was evaluated before RT and at predetermined intervals after RT until death. Gastrointestinal and genitourinary toxicity using the modified Late Effect in Normal Tissue - Subjective Objective Management Analytic (LENT-SOMA) scales was also evaluated before and at intervals after RT to 60 months. Results: The whole group has now been followed for a median of 90 months (range, 3-138). Of the 217 patients, 85 developed biochemical relapse (nadir prostate-specific antigen level + 2 {mu}g/L), 36 in the hypofractionated and 49 in the conventional group. The biochemical relapse-free, but not overall, survival at 90 months was significantly better with the hypofractionated (53%) than with the conventional (34%) schedule. Gastrointestinal and genitourinary toxicity persisted 60 months after RT and did not differ between the two dose schedules. Multivariate analyses revealed that the conventional schedule was of independent prognostic significance, not only for biochemical failure, but also for an increased risk of worse genitourinary symptoms at 4 years. Conclusions: A therapeutic advantage of the hypofractionated compared with the conventional dose schedule for RT of prostate cancer was evident at 90 months in the present study.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Proton Beam Therapy for Unresectable Malignancies of the Nasal Cavity and Paranasal Sinuses

Purpose: The cure rate for unresectable malignancies of the nasal cavity and paranasal sinuses is low. Because irradiation with proton beams, which are characterized by their rapid fall-off at the distal end of the Bragg peak and sharp lateral penumbra, depending on energy, depth, and delivery, provide better dose distribution than X-ray irradiation, proton beam therapy (PBT) might improve treatment outcomes for conditions located in proximity to risk organs. We retrospectively analyzed the clinical profile of PBT for unresectable malignancies of the nasal cavity and paranasal sinuses. Methods and Materials: We reviewed 39 patients in our database fulfilling the following criteria: unresectable malignant tumors of the nasal cavity, paranasal sinuses or skull base; N0M0 disease; and treatment with PBT (>60 GyE) from January 1999 to December 2006. Results: Median patient age was 57 years (range, 22-84 years); 22 of the patients were men and 17 were women. The most frequent primary site was the nasal cavity (n = 26, 67%). The local control rates at 6 months and 1 year were 84.6% and 77.0%, respectively. With a median active follow-up of 45.4 months, 3-year progression-free and overall survival were 49.1% and 59.3%, respectively. The most common acute toxicities were mild dermatitis (Grade 2, 33.3%), but no severe toxicity was observed (Grade 3 or greater, 0%). Five patients (12.8%) experienced Grade 3 to 5 late toxicities, and one treatment-related death was reported, caused by cerebrospinal fluid leakage Grade 5 (2.6%). Conclusion: These findings suggest that the clinical profile of PBT for unresectable malignancies of the nasal cavity and paranasal sinuses make it is a promising treatment option.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Elevation in Exhaled Nitric Oxide Predicts for Radiation Pneumonitis

Purpose: Radiation pneumonitis is a major toxicity after thoracic radiotherapy (RT), with no method available to accurately predict the individual risk. This was a prospective study to evaluate exhaled nitric oxide as a predictive biomarker for radiation pneumonitis in esophageal cancer patients. Patients and Methods: A total of 34 patients prescribed neoadjuvant chemoradiotherapy for esophageal cancer were enrolled in the present trial. Each patient underwent respiratory surveys and exhaled nitric oxide (NO) measurements before, at the end of, and 1 to 2 months after completing RT. Pneumonitis toxicity was scored using the Common Terminology Criteria for Adverse Events, version 4.0. The demographics, dosimetric factors, and exhaled NO levels were evaluated for correlation with symptomatic patients (scores {>=}2). Results: Of the 34 patients, 28 were evaluable. All had received 50.4 Gy RT with concurrent chemotherapy. The pneumonitis toxicity score was Grade 3 for 1, Grade 2 for 3, Grade 1 for 7, and Grade 0 for 17. The dosimetric factors were not predictive of symptoms. The mean exhaled NO level measured before, at completion, and at restaging was 17.3 {+-} 8.5 (range, 5.5-36.7), 16.0 {+-} 14.2 (range, 5.8-67.7), and 14.7 {+-} 6.2 (range, 5.5-28.0) parts per billion, respectively. The ratio of exhaled NO at the end of RT vs. before treatment was 3.4 (range, 1.7-6.7) for the symptomatic and 0.8 (range, 0.3-1.3) for the asymptomatic (p = .0017) patients. The elevation in exhaled NO preceded the peak symptoms by 33 days (range, 21-50). The interval to peak symptoms was inversely related to the exhaled NO elevation. Conclusions: Elevations in exhaled NO at the end of RT was found to predict for radiation pneumonitis symptoms.

62 RADIOLOGY AND NUCLEAR MEDICINE↗