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At least 361 records · Page 20

Modeling toxicodynamic effects of trichloroethylene on liver in mouse model of autoimmune hepatitis

Chronic exposure to industrial solvent and water pollutant trichloroethylene (TCE) in female MRL +/+ mice generates disease similar to human autoimmune hepatitis. The current study was initiated to investigate why TCE-induced autoimmunity targeted the liver. Compared to other tissues the liver has an unusually robust capacity for repair and regeneration. This investigation examined both time-dependent and dose-dependent effects of TCE on hepatoprotective and pro-inflammatory events in liver and macrophages from female MRL +/+ mice. After a 12-week exposure to TCE in drinking water a dose-dependent decrease in macrophage production of IL-6 at both the transcriptional and protein level was observed. A longitudinal study similarly showed that TCE inhibited macrophage IL-6 production. In terms of the liver, TCE had little effect on expression of pro-inflammatory genes (Tnfa, Saa2 or Cscl1) until the end of the 40-week exposure. Instead, TCE suppressed hepatic expression of genes involved in IL-6 signaling (Il6r, gp130, and Egr1). Linear regression analysis confirmed liver histopathology in the TCE-treated mice correlated with decreased expression of Il6r. A toxicodynamic model was developed to estimate the effects of TCE on IL-6 signaling and liver pathology under different levels of exposure and rates of repair. This study underlined the importance of longitudinal studies in mechanistic evaluations of immuntoxicants. It showed that later-occurring liver pathology caused by TCE was associated with early suppression of hepatoprotection rather than an increase in conventional pro-inflammatory events. This information was used to create a novel toxicodynamic model of IL-6-mediated TCE-induced liver inflammation. - Highlights: • We developed a toxicodynamic model to study effects of trichloroethylene on liver. • We examined protective as well as pro-inflammatory events in the liver. • Trichloroethylene inhibits IL-6 production by macrophages. • Trichloroethylene inhibits components of the IL-6R in the liver. • Trichloroethylene inhibits events associated with IL-6-mediated hepatoprotection.

60 APPLIED LIFE SCIENCES↗

The Relationship Between Neutrophil–Lymphocyte Ratio and Primary Patency of Percutaneous Transluminal Angioplasty in Hemodialysis Arteriovenous Fistula Stenosis When Using Conventional and Drug-Eluting Balloons

ObjectiveThe aim of this study is to investigate the potential association of neutrophil–lymphocyte ratio (NLR) between primary patency of percutaneous transluminal angioplasty (PTA) in hemodialysis arteriovenous fistula stenosis and type (Conventional and Drug-Eluting) of balloons used in PTA.Material-MethodThis retrospective study consists of 78 patients with significant arteriovenous fistulas stenosis who were treated with PTA by using Drug-Eluting Balloon (DEB) (n = 29) or Conventional Balloon (CB) (n = 49). NLR was calculated from preinterventional blood samples. All patients were classified into two groups. Group A; primary patency <12 months (43/78), Group B; primary patency ≥12 months (35/78). Cox regression analysis and Kaplan–Meier method were used to determine respectively independent factors affecting the primary patency and to compare the primary patency for the two balloon types.ResultsNLR ratio and balloon type of the two groups were significantly different (p = 0.002, p = 0.010). The cut-off value of NLR was 3.18 for determination of primary patency, with sensitivity of 81.4 % and specificity of 51.4 %. Primary patency rates between PTA with DEB and CB displayed statistically significant differences (p < 0.05). The cut-off value was 3.28 for determination of 12-month primary patency with the conventional balloon group; sensitivity was 81.8 % and specificity was 81.3 %. There was no statistical relation between NLR levels and the drug-eluting balloon group in 12-month primary patency (p = 0.927).ConclusionIncreased level of NLR may be a risk factor in the development of early AVF restenosis after successful PTA. Preferring Drug-Eluting Balloon at an increased level of NLR can be beneficial to prolong patency.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Effects of blood lead levels on airflow limitations in Korean adults: Findings from the 5th KNHNES 2011

This study aimed to examine whether blood levels of heavy metals, such as lead, mercury and cadmium, are related with pulmonary function in Korean adults. This investigation included 870 Korean adults (≥40 years) who received pulmonary function testing in the Korea National Health and Nutrition Examination Survey (KNHANES) V-2, 2011. Data of blood levels of heavy metals, pulmonary function tests and anthropometric measurements were acquired. Blood lead levels showed inverse correlations with the FEV{sub 1}/FVC ratio before (r=−0.276, p<0.001) and after adjustment of multiple compounding factors (r=−0.115, p=0.001). A logistic multiple regression analysis revealed that blood lead levels were a significant influencing factor for the FEV{sub 1}/FVC ratio (β=−0.017, p=0.001, adjusted R{sup 2}=0.267). The odds ratios (ORs) for the FEV{sub 1}/FVC ratio were significantly lower in the highest tertile group of the blood lead levels than in the lowest tertile group in Model 1 (OR=0.007, 95% CI=0.000−0.329) and Model 2 (OR=0.006, 95% CI=0.000−0.286). These findings imply that environmental exposure to lead might be an important factor that may cause airflow limitations in Korean adults. - Highlights: • Blood lead levels showed inverse correlations with the FEV{sub 1}/FVC ratio. • Blood lead level was a significant influencing factor for the FEV{sub 1}/FVC ratio. • ORs for FEV{sub 1}/FVC were lower in the highest blood lead group than in the lowest group. • Environmental exposure to lead might be an important factor for airflow limitations.

54 ENVIRONMENTAL SCIENCES↗

Clinical Validation of 4-Dimensional Computed Tomography Ventilation With Pulmonary Function Test Data

Purpose: A new form of functional imaging has been proposed in the form of 4-dimensional computed tomography (4DCT) ventilation. Because 4DCTs are acquired as part of routine care for lung cancer patients, calculating ventilation maps from 4DCTs provides spatial lung function information without added dosimetric or monetary cost to the patient. Before 4DCT-ventilation is implemented it needs to be clinically validated. Pulmonary function tests (PFTs) provide a clinically established way of evaluating lung function. The purpose of our work was to perform a clinical validation by comparing 4DCT-ventilation metrics with PFT data. Methods and Materials: Ninety-eight lung cancer patients with pretreatment 4DCT and PFT data were included in the study. Pulmonary function test metrics used to diagnose obstructive lung disease were recorded: forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity. Four-dimensional CT data sets and spatial registration were used to compute 4DCT-ventilation images using a density change–based and a Jacobian-based model. The ventilation maps were reduced to single metrics intended to reflect the degree of ventilation obstruction. Specifically, we computed the coefficient of variation (SD/mean), ventilation V20 (volume of lung ≤20% ventilation), and correlated the ventilation metrics with PFT data. Regression analysis was used to determine whether 4DCT ventilation data could predict for normal versus abnormal lung function using PFT thresholds. Results: Correlation coefficients comparing 4DCT-ventilation with PFT data ranged from 0.63 to 0.72, with the best agreement between FEV1 and coefficient of variation. Four-dimensional CT ventilation metrics were able to significantly delineate between clinically normal versus abnormal PFT results. Conclusions: Validation of 4DCT ventilation with clinically relevant metrics is essential. We demonstrate good global agreement between PFTs and 4DCT-ventilation, indicating that 4DCT-ventilation provides a reliable assessment of lung function. Four-dimensional CT ventilation enables exciting opportunities to assess lung function and create functional avoidance radiation therapy plans. The present work provides supporting evidence for the integration of 4DCT-ventilation into clinical trials.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Margin Size is an Independent Predictor of Local Tumor Progression After Ablation of Colon Cancer Liver Metastases

This study was designed to evaluate the relationship between the minimal margin size and local tumor progression (LTP) following CT-guided radiofrequency ablation (RFA) of colorectal cancer liver metastases (CLM). An institutional review board-approved, HIPPA-compliant review identified 73 patients with 94 previously untreated CLM that underwent RFA between March 2003 and May 2010, resulting in an ablation zone completely covering the tumor 4-8 weeks after RFA dynamic CT. Comparing the pre- with the post-RFA CT, the minimal margin size was categorized to 0, 1-5, 6-10, and 11-15 mm. Follow-up included CT every 2-4 months. Kaplan-Meier methodology and Cox regression analysis were used to evaluate the effect of the minimal margin size, tumor location, size, and proximity to a vessel on LTP. Forty-five of 94 (47.9 %) CLM progressed locally. Median LTP-free survival (LPFS) was 16 months. Two-year LPFS rates for ablated CLM with minimal margin of 0, 1-5 mm, 6-10 mm, 11-15 mm were 26, 46, 74, and 80 % (p < 0.011). Minimal margin (p = 0.002) and tumor size (p = 0.028) were independent risk factors for LTP. The risk for LTP decreased by 46 % for each 5-mm increase in minimal margin size, whereas each additional 5-mm increase in tumor size increased the risk of LTP by 22 %. An ablation zone with a minimal margin uniformly larger than 5 mm 4-8 weeks postablation CT is associated with the best local tumor control.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Treatment Outcomes of Locally Advanced Oropharyngeal Cancer: A Comparison Between Combined Modality Radio-Chemotherapy and Two Variants of Single Modality Altered Fractionation Radiotherapy

Purpose: To compare outcomes in patients with locally advanced oropharyngeal cancer treated with radio-chemotherapy (RT-CT), accelerated fractionation radiotherapy (AccRT), or hypofractionated radiotherapy (HypoRT). Methods and Materials: Subjects were 321 consecutive patients with newly diagnosed oropharyngeal cancer, Stage III or IVA/B, treated between January 2001 and December 2005 at the BC Cancer Agency with RT-CT (n = 157), AccRT (n = 57), or HypoRT (n = 107). Outcomes examined were disease-specific survival (DSS), locoregional control (LRC), overall survival (OS), rate of G-tube use, and rate of hospitalization for acute complications. Results: Median follow-up was 3.4 years. Three-year Kaplan-Meier DSS with RT-CT, AccRT, and HypoRT were 80%, 81%, and 74%, respectively (p = 0.219). Cox regression analysis identified treatment modality as a significant factor affecting DSS (p = 0.038). Compared with RT-CT, the hazard ratio (HR) for DSS was 1.0 with AccRT and 2.0 with HypoRT (p = 0.021). Kaplan-Meier pairwise comparisons found no significant difference in LRC and OS between RT-CT and AccRT. HypoRT was associated with significantly lower LRC (p = 0.005) and OS (p = 0.008) compared with RT-CT. There were significant differences in the rates of G-tube use (p < 0.001) and of hospitalization (p = 0.036) among the three treatment groups, with the most frequent rates observed in the RT-CT group. Conclusions: In patients with locally advanced oropharyngeal cancer, AccRT conferred DSS, LRC, and OS comparable to that of RT-CT. Patients treated with RT-CT experienced higher rates of treatment-related acute toxicities. HypoRT was associated with the least favorable outcomes.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Rise Kinetics of Up-Conversion Luminescence of the LiY{sub 0.8}Yb{sub 0.2}F{sub 4}:Tm{sup 3+} (0.2 at %) Crystal with Pulsed Excitation

The regression analysis of the rise kinetics of up-conversion luminescence of the LiY{sub 0.8}Yb{sub 0.2}F{sub 4}:Tm{sup 3+} (0.2 at %) crystal is performed. The kinetics curve is obtained with rectangular pulsed excitation by radiation from a laser diode (IR LD) with a wavelength of λ{sub p} = 933 nm. The most important—in these experimental conditions—mechanisms of the energy transfer from Yb{sup 3+} ions to Tm{sup 3+} ions are established, which are responsible for the transitions between the ground {sup 3}H{sub 6} and excited {sup 3}F{sub 4}, {sup 3}H{sub 4}, {sup 1}G{sub 4}, {sup 1}D{sub 2}, and {sup 1}I{sub 6} terms of the Tm{sup 3+} ions. The durations of the relevant energy transfer processes are determined. It is shown that the energy transfer between rare earth ions in the LiY{sub 0.8}Yb{sub 0.2}F{sub 4}:Tm{sup 3+} (0.2 at %) crystal occurs through the dipole–dipole interactions.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Quenching or Bursting: Star Formation Acceleration—A New Methodology for Tracing Galaxy Evolution

We introduce a new methodology for the direct extraction of galaxy physical parameters from multiwavelength photometry and spectroscopy. We use semianalytic models that describe galaxy evolution in the context of large-scale cosmological simulation to provide a catalog of galaxies, star formation histories, and physical parameters. We then apply models of stellar population synthesis and a simple extinction model to calculate the observable broadband fluxes and spectral indices for these galaxies. We use a linear regression analysis to relate physical parameters to observed colors and spectral indices. The result is a set of coefficients that can be used to translate observed colors and indices into stellar mass, star formation rate, and many other parameters, including the instantaneous time derivative of the star formation rate, which we denote the Star Formation Acceleration (SFA), We apply the method to a test sample of galaxies with GALEX photometry and SDSS spectroscopy, deriving relationships between stellar mass, specific star formation rate, and SFA. We find evidence for a mass-dependent SFA in the green valley, with low-mass galaxies showing greater quenching and higher-mass galaxies greater bursting. We also find evidence for an increase in average quenching in galaxies hosting an active galactic nucleus. A simple scenario in which lower-mass galaxies accrete and become satellite galaxies, having their star-forming gas tidally and/or ram-pressure stripped, while higher-mass galaxies receive this gas and react with new star formation, can qualitatively explain our results.

79 ASTRONOMY AND ASTROPHYSICS↗

SU-C-207-07: Quantification of Coronary Artery Cross-Sectional Area in CT Angiography Using Integrated Density: A Phantom Study

Purpose: To investigate the feasibility of quantifying the cross-sectional area (CSA) of coronary arteries using integrated density in a physics-based model with a phantom study. Methods: In this technique the total integrated density of the object as compared with its local background is measured so it is possible to account for the partial volume effect. The proposed method was compared to manual segmentation using CT scans of a 10 cm diameter Lucite cylinder placed inside a chest phantom. Holes with cross-sectional areas from 1.4 to 12.3 mm{sup 2} were drilled into the Lucite and filled with iodine solution, producing a contrast-to-noise ratio of approximately 26. Lucite rods 1.6 mm in diameter were used to simulate plaques. The phantom was imaged with and without the Lucite rods placed in the holes to simulate diseased and normal arteries, respectively. Linear regression analysis was used, and the root-mean-square deviations (RMSD) and errors (RMSE) were computed to assess the precision and accuracy of the measurements. In the case of manual segmentation, two readers independently delineated the lumen in order to quantify the inter-reader variability. Results: The precision and accuracy for the normal vessels using the integrated density technique were 0.32 mm{sup 2} and 0.32 mm{sup 2}, respectively. The corresponding results for the manual segmentation were 0.51 mm{sup 2} and 0.56 mm{sup 2}. In the case of diseased vessels, the precision and accuracy of the integrated density technique were 0.46 mm{sup 2} and 0.55 mm{sup 2}, respectively. The corresponding results for the manual segmentation were 0.75 mm{sup 2} and 0.98 mm{sup 2}. The mean percent difference for the two readers was found to be 8.4%. Conclusion: The CSA based on integrated density had improved precision and accuracy as compared with manual segmentation in a Lucite phantom. The results indicate the potential for using integrated density to improve CSA measurements in CT angiography.

60 APPLIED LIFE SCIENCES↗

Can magnetic resonance imaging differentiate among transurethral bulking agent, urethral diverticulum, and periurethral cyst?

Purpose: To evaluate magnetic resonance imaging findings that differentiate among periurethral bulking agents (primarily collagen), urethral diverticulum, and periurethral cyst. Methods: We searched our radiologic database retrospectively from 2001 to 2017 for periurethral cystic lesions, identifying a total of 50 patients with 68 lesions. Final diagnoses in 68 lesions were bulking agents (27), urethral diverticula (29), and periurethral cysts (12). Two abdominal radiologists, blinded to clinical history, independently evaluated T1, T2, and post-contrast images. The readers assessed number, morphological features, location, connection to urethra and mass effect, signal intensity, and enhancement for each lesion. Fisher exact test and logistic regression analysis were performed for each univariate significant feature. The operative and pathologic reports were the reference standard. Results: Magnetic resonance imaging features found more often in bulking agents versus urethral diverticulum were multiple lesions (P = 0.011), upper or upper-mid-urethral location (P ≤ 0.0001), lack of internal fluid/fluid level (P = 0.002), no urethral connection (P = 0.005), T1 isointensity, and T2 mild hyperintensity compared to muscles but lower T2 signal than urine (P < 0.0001). Most cases of urethral diverticula and periurethral cysts were detected at mid- and lower urethra. Urethral diverticula were larger than bulking agents and periurethral cysts (P = 0.005 and P = 0.023) (mean diameter = 24, 16, 15 mm, respectively). Most bulking agents (93%) and urethral diverticula (90%) showed mass effect on urethra, while periurethral cysts (75%) did not (P < 0.0001). Conclusion: Signal intensity and lesion characterization on magnetic resonance imaging can significantly differentiate bulking agent from urethral diverticulum and periurethral cyst. Radiologists should consider differential diagnosis of a bulking agent, especially when distinguishing characteristics described here are present to prevent incorrect diagnosis and ultimately unnecessary surgical intervention.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Cycle length dependence of stellar magnetic activity and solar cycle 23

Solar cycle (SC) 23 was extraordinarily long with remarkably low magnetic activity. We have investigated whether this is a common behavior of solar-type stars. From the Ca ii H and K line intensities of 111 stars observed at Mount Wilson Observatory from 1966 to 1991, we have retrieved data of all 23 G-type stars and recalculated their cycle lengths using the damped least-squares method for the chromospheric activity index S as a function of time. A regression analysis was performed to find relations between the derived cycle length, P{sub avg}, and the index for excess chromospheric emission, R{sub HK}{sup ′}. As a noteworthy result, we found a segregation between young and old solar-type stars in the cycle length-activity correlation. We incorporated the relation for the solar-type stars into the previously known rule for stellar chromospheric activity and brightness to estimate the variation of solar brightness from SC 22 to SC 23 as (0.12 ± 0.06)%, much higher than the actual variation of total solar irradiance (TSI) ≤0.02%. We have then examined solar spectral irradiance (SSI) to find a good phase correlation with a sunspot number in the wavelength range of 170–260 nm, which is close to the spectral range effective in heating the Earth’s atmosphere. Therefore, it appears that SSI rather than TSI is a good indicator of the chromospheric activity, and its cycle length dependent variation would be more relevant to the possible role of the Sun in the cyclic variation of the Earth’s atmosphere.

79 ASTRONOMY AND ASTROPHYSICS↗

Transarterial Chemoembolization for Hepatocellular Carcinomas with Central Bile Duct Invasion: Safety, Prognosis, and Predictive Factors

PurposeTo assess the safety and effectiveness of transarterial chemoembolization (TACE) of patients who have hepatocellular carcinomas (HCCs) with central bile duct invasion.Materials and MethodsThe institutional review board approved this retrospective study and waived informed consent. Fifty-three patients, initially treated with TACE for HCCs with central bile duct invasion from January 1999 to September 2012, were included. Clinical, laboratory, and survival data were reviewed. Complications and hospitalization length were evaluated using the χ{sup 2} test, Fisher’s exact test, and logistic regression analysis. Survival was analyzed using the Kaplan–Meier method with log-rank test and Cox proportional hazard model.ResultsSeven patients experienced TACE-related major complications (severe post-embolization syndrome in 3, non-fatal sepsis in 3, and secondary bacterial peritonitis in 1). The overall major complication rate was 13.2 %, but there were no permanent adverse sequelae or deaths within 30 days. Serum total bilirubin ≥3.0 mg/dL was the only significant risk factor for long hospitalization [hazard ratio (HR) = 4.341, p = .022]. The median survival was 12.2 months. Extrahepatic metastasis (HR = 6.145, p < .001), international normalized ratio (PT-INR) ≥1.20 (HR = 4.564, p < .001), vascular invasion (HR = 3.484, p = .001), and intermediate tumor enhancement (HR = 2.417, p = .019) were significantly associated with shorter survival.ConclusionTACE can be a safe and effective treatment for patients who have HCCs with central bile duct invasion. In particular, long-term survival can be expected if patients have strongly enhancing tumors without poor prognostic factors such as extrahepatic metastasis, PT-INR prolongation, and vascular invasion.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Type 2 diabetes mellitus correlates with systolic function during myocardial stress perfusion scanning with Nitrogen-13 ammonia PET

Background: The influence of type 2 diabetes mellitus (DM2) on systolic function is partially determined by the coronary vasodilator function, nevertheless, an independent effect is suspected. We evaluated the relationship between DM2 and systolic function considering PET quantitative myocardial perfusion. Methods: We analyzed 585 patients without a previous myocardial infarction referred to a rest and adenosine stress Nitrogen-13 ammonia PET. A bootstrapped multiple linear regression analysis was performed using DM2, stress myocardial blood flow (sMBF), myocardial perfusion reserve (MPR), and clinical risk factors as predictors and LVEF as the outcome variable; an interaction term was additionally investigated. Results: Two hundred and ninety male and 295 female patients (mean age 65.3 ± 9.9 and 67.4 ± 10 years, respectively) were included. 57.1% presented hypertension, 16% smoking, 37.6% hypercholesterolemia, 33.8% family history for CAD, and 15.2% DM2. The mean MPR was 2.13 ± 0.48 and 2.21 ± 0.60, mean sMBF was 2.01 ± 0.51 and 2.15 ± 0.54, and mean LVEF was 63% ± 10.4 and 67% ± 10.1 for diabetics and non-diabetics, respectively. A significant relation was detected for sMBF (B = 5.830 95% CI [3.505, 9.549], P = .001) and DM2 (B = −2.599 95% CI [−5.125, −0.119], P = .03) with LVEF. The interaction (DM2 × sMBF) yielded no significance (P = .512). Conclusion: DM2 influences PET-measured systolic function in patients without previous myocardial infarction independently from myocardial perfusion parameters. Our study supports the importance of DM2 as an independent risk factor for deteriorating systolic function.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Acute Esophagus Toxicity in Lung Cancer Patients After Intensity Modulated Radiation Therapy and Concurrent Chemotherapy

Purpose: The purpose of this study was to investigate the dose-effect relation between acute esophageal toxicity (AET) and the dose-volume parameters of the esophagus after intensity modulated radiation therapy (IMRT) and concurrent chemotherapy for patients with non-small cell lung cancer (NSCLC). Patients and Methods: One hundred thirty-nine patients with inoperable NSCLC treated with IMRT and concurrent chemotherapy were prospectively analyzed. The fractionation scheme was 66 Gy in 24 fractions. All patients received concurrently a daily dose of cisplatin (6 mg/m Superscript-Two ). Maximum AET was scored according to Common Toxicity Criteria 3.0. Dose-volume parameters V5 to V70, D{sub mean} and D{sub max} of the esophagus were calculated. A logistic regression analysis was performed to analyze the dose-effect relation between these parameters and grade {>=}2 and grade {>=}3 AET. The outcome was compared with the clinically used esophagus V35 prediction model for grade {>=}2 after radical 3-dimensional conformal radiation therapy (3DCRT) treatment. Results: In our patient group, 9% did not experience AET, and 31% experienced grade 1 AET, 38% grade 2 AET, and 22% grade 3 AET. The incidence of grade 2 and grade 3 AET was not different from that in patients treated with CCRT using 3DCRT. The V50 turned out to be the most significant dosimetric predictor for grade {>=}3 AET (P=.012). The derived V50 model was shown to predict grade {>=}2 AET significantly better than the clinical V35 model (P<.001). Conclusions: For NSCLC patients treated with IMRT and concurrent chemotherapy, the V50 was identified as most accurate predictor of grade {>=}3 AET. There was no difference in the incidence of grade {>=}2 AET between 3DCRT and IMRT in patients treated with concurrent chemoradiation therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Very High-Risk Localized Prostate Cancer: Outcomes Following Definitive Radiation

Purpose: Existing definitions of high-risk prostate cancer consist of men who experience significant heterogeneity in outcomes. As such, criteria that identify a subpopulation of National Comprehensive Cancer Network (NCCN) high-risk prostate cancer patients who are at very high risk (VHR) for poor survival outcomes following prostatectomy were recently developed at our institution and include the presence of any of the following disease characteristics: multiple NCCN high-risk factors, primary Gleason pattern 5 disease and/or ≥5 biopsy cores with Gleason sums of 8 to 10. Whether these criteria also apply to men undergoing definitive radiation is unclear, as is the optimal treatment regimen in these patients. Methods and Materials: All men consecutively treated with definitive radiation by a single provider from 1993 to 2006 and who fulfilled criteria for NCCN high-risk disease were identified (n=288), including 99 patients (34%) with VHR disease. Multivariate-adjusted competing risk regression models were constructed to assess associations between the VHR definition and biochemical failure (BF), distant metastasis (DM), and prostate cancer–specific mortality (PCSM). Multivariate-adjusted Cox regression analysis assessed the association of the VHR definition with overall mortality (OM). Cumulative incidences of failure endpoints were compared between VHR men and other NCCN high-risk men. Results: Men with VHR disease compared to other NCCN high-risk men experienced a higher 10-year incidence of BF (54.0% vs 35.4%, respectively, P<.001), DM (34.9% vs 13.4%, respectively, P<.001), PCSM (18.5% vs 5.9%, respectively, P<.001), and OM (36.4% vs 27.0%, respectively, P=.04). VHR men with a detectable prostate-specific antigen (PSA) concentration at the end of radiation (EOR) remained at high risk of 10-year PCSM compared to VHR men with an undetectable EOR PSA (31.0% vs 13.7%, respectively, P=.05). Conclusions: NCCN high-risk prostate cancer patients who meet VHR criteria experience distinctly worse outcomes following definitive radiation and long-term androgen deprivation therapy, particularly if an EOR PSA is detectable. Optimal use of local therapies for VHR patients should be explored further, as should novel agents.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Type of Diabetes Mellitus and the Odds of Gleason Score 8 to 10 Prostate Cancer

Purpose: It has been recently shown that diabetes mellitus (DM) is significantly associated with the likelihood of presenting with high-grade prostate cancer (PCa) or Gleason score (GS) 8 to 10; however, whether this association holds for both Type 1 and 2 DM is unknown. In this study we evaluated whether DM Type 1, 2, or both are associated with high-grade PCa after adjusting for known predictors of high-grade disease. Methods and Materials: Between 1991 and 2010, a total of 15,330 men diagnosed with PCa and treated with radiation therapy were analyzed. A polychotomous logistic regression analysis was performed to evaluate whether Type 1 or 2 DM was associated with odds of GS 7 or GS 8 to 10 compared with 6 or lower PCa, adjusting for African American race, age, prostate-specific antigen (PSA) level, and digital rectal examination findings. Results: Men with Type 1 DM (adjusted odds ratio [AOR], 2.05; 95% confidence interval [CI], 1.28-3.27; p = 0.003) or Type 2 DM (AOR, 1.58; 95% CI, 1.26-1.99; p < 0.001) were significantly more likely to be diagnosed with GS 8 to 10 PCa compared with nondiabetic men. However this was not true for GS 7, for which these respective results were AOR, 1.30; 95% CI, 0.93-1.82; p = 0.12 and AOR, 1.13; 95% CI, 0.98-1.32; p = 0.10. Conclusion: Type 1 and 2 DM were associated with a higher odds of being diagnosed with Gleason score 8 to 10 but not 7 PCa. Pending validation, men who are diagnosed with Type I DM with GS 7 or lower should be considered for additional workup to rule out occult high-grade disease.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Respiration Induced Heart Motion and Indications of Gated Delivery for Left-Sided Breast Irradiation

Purpose: To investigate respiration-induced heart motion for left-sided breast irradiation using a four-dimensional computed tomography (4DCT) technique and to determine novel indications to assess heart motion and identify breast patients who may benefit from a gated treatment. Methods and Materials: Images of 4DCT acquired during free breathing for 20 left-sided breast cancer patients, who underwent whole breast irradiation with or without regional nodal irradiation, were analyzed retrospectively. Dose distributions were reconstructed in the phases of 0%, 20%, and 50%. The intrafractional heart displacement was measured in three selected transverse CT slices using D{sub LAD} (the distance from left ascending aorta to a fixed line [connecting middle point of sternum and the body] drawn on each slice) and maximum heart depth (MHD, the distance of the forefront of the heart to the line). Linear regression analysis was used to correlate these indices with mean heart dose and heart dose volume at different breathing phases. Results: Respiration-induced heart displacement resulted in observable variations in dose delivered to the heart. During a normal free-breathing cycle, heart-induced motion D{sub LAD} and MHD changed up to 9 and 11 mm respectively, resulting in up to 38% and 39% increases of mean doses and V{sub 25.2} for the heart. MHD and D{sub LAD} were positively correlated with mean heart dose and heart dose volume. Respiratory-adapted gated treatment may better spare heart and ipsilateral-lung compared with the conventional non-gated plan in a subset of patients with large D{sub LAD} or MHD variations. Conclusion: Proposed indices offer novel assessment of heart displacement based on 4DCT images. MHD and D{sub LAD} can be used independently or jointly as selection criteria for respiratory gating procedure before treatment planning. Patients with great intrafractional MHD variations or tumor(s) close to the diaphragm may particularly benefit from the gated treatment.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

SU-E-T-285: Revisiting the Nomogram for Intra-Operative Planning Based Pd-103 Brachytherapy

Purpose: The seed implant technique at our institution involves using a published nomogram for seed ordering based on CT based volume studies of the prostate. Ultrasound volume studies are subsequently used in the operating room for planning a modified peripheral loading with urethra sparing seed implant. The purpose of this study is to determine the appropriate modality for prostate volume measurement and creating an updated nomogram for intra-operative planning specific to our technique for pd-103 brachytherapy for efficient seed ordering. Methods: Prostate volumes based on pre-implant CT (Pre-CT), intra-operative ultrasound (TRUS), and post-implant CT (post-CT) studies as well as the total airkerma strength (AKS) of the implants were analyzed for 135 seed implant cases (69 monotherapy, 66 boost). Regression analysis was performed to derive the relationship between the total AKS and pre-CT and TRUS volumes. The correlation between TRUS and pre-CT volumes and TRUS and post-CT volumes were also studied. Results: Ultrasound based prostate volume exhibited a stronger correlation with total AKS than the pre-implant CT volume (R{sup 2} = 0.97 vs 0.88 for monotherapy and 0.96 vs 0.89 for boost). In general the pre-CT overestimated the prostate volume leading to ordering of a larger number of seeds and thus leading to higher number of unused/wasted seeds. Newly derived TRUS based nomogram was better suited for our technique than the published data. The post-implant CT volume closely followed the ultrasound volume (R{sup 2} = 0.88) as compared to pre-implant CT volumes (R{sup 2} = 0.57). Conclusion: In an era of costconscious health care where waste reduction is of utmost importance, an updated technique-specific nomogram is useful for ordering optimal number of seeds resulting in significant cost savings. In addition, our study shows that ultrasound based prostate volume is a better predictor for seed ordering for intra-operative planning than pre-implant CT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗