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At least 199 records · Page 11

Novel Single-Nucleotide Polymorphism Markers Predictive of Pathologic Response to Preoperative Chemoradiation Therapy in Rectal Cancer Patients

Purpose: Studies aimed at predicting individual responsiveness to preoperative chemoradiation therapy (CRT) are urgently needed, especially considering the risks associated with poorly responsive patients. Methods and Materials: A 3-step strategy for the determination of CRT sensitivity is proposed based on (1) the screening of a human genome-wide single-nucleotide polymorphism (SNP) array in correlation with histopathologic tumor regression grade (TRG); (2) clinical association analysis of 113 patients treated with preoperative CRT; and (3) a cell-based functional assay for biological validation. Results: Genome-wide screening identified 9 SNPs associated with preoperative CRT responses. Positive responses (TRG 1-3) were obtained more frequently in patients carrying the reference allele (C) of the SNP CORO2A rs1985859 than in those with the substitution allele (T) (P=.01). Downregulation of CORO2A was significantly associated with reduced early apoptosis by 27% (P=.048) and 39% (P=.023) in RKO and COLO320DM colorectal cancer cells, respectively, as determined by flow cytometry. Reduced radiosensitivity was confirmed by colony-forming assays in the 2 colorectal cancer cells (P=.034 and .015, respectively). The SNP FAM101A rs7955740 was not associated with radiosensitivity in the clinical association analysis. However, downregulation of FAM101A significantly reduced early apoptosis by 29% in RKO cells (P=.047), and it enhanced colony formation in RKO cells (P=.001) and COLO320DM cells (P=.002). Conclusion: CRT-sensitive SNP markers were identified using a novel 3-step process. The candidate marker CORO2A rs1985859 and the putative marker FAM101A rs7955740 may be of value for the prediction of radiosensitivity to preoperative CRT, although further validation is needed in large cohorts.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Grain boundary softening from stress assisted helium cavity coalescence in ultrafine-grained tungsten

The formation of helium cavities in coarse-grained materials produces hardening proportional to the number density and size of the cavities and due to the interaction of dislocations with intragranular helium defects. In nanostructured metals containing a high density of interfacial sinks, preferential cavity formation in the grain boundaries instead produces softening that is often attributed to enhanced interfacial plasticity. Here, employing two grades of ultrafine-grained tungsten, we explore this effect using targeted implantation studies to map cavity evolution as a function of the irradiation conditions and quantify its impact on the mechanical response through nanoindentation. Softening is reported at implantation temperatures above the threshold for preferential grain boundary cavity formation but at a sufficiently low fluence prior to the growth of intragranular cavities. Collective changes in the mean cavity size, density, and morphology beneath a residual impression on an implanted surface indicate that cavity coalescence accompanied the reduction in hardness. Complementary atomistic simulations demonstrate that, in tungsten grain structures exhibiting softening, grain boundary bubble coalescence is driven by stress concentrations that further act to localize strain in the grain boundaries through cooperative deformation processes involving local atomic shuffling and sliding, dislocation emission, and even the nucleation of unstable twinning events.

36 MATERIALS SCIENCE↗

Tailoring broadband light trapping of GaAs and Si substrates by self-organised nanopatterning

We report on the formation of high aspect ratio anisotropic nanopatterns on crystalline GaAs (100) and Si (100) substrates exploiting defocused Ion Beam Sputtering assisted by a sacrificial self-organised Au stencil mask. The tailored optical properties of the substrates are characterised in terms of total reflectivity and haze by means of integrating sphere measurements as a function of the morphological modification at increasing ion fluence. Refractive index grading from sub-wavelength surface features induces polarisation dependent anti-reflection behaviour in the visible-near infrared (VIS-NIR) range, while light scattering at off-specular angles from larger structures leads to very high values of the haze functions in reflection. The results, obtained for an important class of technologically relevant materials, are appealing in view of photovoltaic and photonic applications aiming at photon harvesting in ultrathin crystalline solar cells.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Investigation of static and dynamic behavior of functionally graded piezoelectric actuated Poly-Si micro cantilever probe

In the present paper a novel functionally graded piezoelectric (FGP) actuated Poly-Si micro cantilever probe is proposed for atomic force microscope. The shear piezoelectric coefficient d{sub 15} has much higher value than coupling coefficients d{sub 31} and d{sub 33}, hence in the present work the micro cantilever beam actuated by d{sub 15} effect is utilized. The material properties are graded in the thickness direction of actuator by a simple power law. A three dimensional finite element analysis has been performed using COMSOL Multiphysics® (version 4.2) software. Tip deflection and free vibration analysis for the micro cantilever probe has been done. The results presented in the paper shall be useful in the design of micro cantilever probe and their subsequent utilization in atomic force microscopes.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Stereotactic Body Radiation Therapy for Non-Small Cell Lung Cancer Tumors Greater Than 5 cm: Safety and Efficacy

Purpose: The purpose of this study was to determine outcomes of patients with node-negative medically inoperable non-small cell lung cancer (NSCLC) whose primary tumors exceeded 5 cm and were treated with stereotactic body radiation therapy (SBRT). Methods and Materials: We surveyed our institutional prospective lung SBRT registry to identify treated patients with tumors >5 cm. Treatment outcomes for local control (LC), locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) were assessed by Kaplan-Meier estimates. Toxicities were graded according to Common Terminology Criteria for Adverse Events version 4. Mean pretreatment pulmonary function test values were compared to mean posttreatment values. Results: From December 2003 to July 2014, 40 patients met study criteria. Median follow-up was 10.8 months (range: 0.4-70.3 months). Median age was 76 years (range: 56-90 years), median body mass index was 24.3 (range: 17.7-37.2), median Karnofsky performance score was 80 (range: 60-90), and median Charlson comorbidity index score was 2 (range: 0-5). Median forced expiratory volume in 1 second (FEV1) was 1.41 L (range: 0.47-3.67 L), and median diffusion capacity (DLCO) was 47% of predicted (range: 29%-80%). All patients were staged by fluorodeoxyglucose-positron emission tomography/computed tomography staging, and 47.5% underwent mediastinal staging by endobronchial ultrasonography. Median tumor size was 5.6 cm (range: 5.1-10 cm), median SBRT dose was 50 Gy (range: 30-60 Gy) in 5 fractions (range: 3-10 fractions). Eighteen-month LC, LRC, DFS, and OS rates were 91.2%, 64.4%, 34.6%, and 59.7%, respectively. Distant failure was the predominant pattern of failure (32.5%). Three patients (7.5%) experienced grade 3 or higher toxicity. Mean posttreatment FEV1 was not significantly reduced (P=.51), but a statistically significant absolute 6.5% (P=.03) reduction in DLCO was observed. Conclusions: Lung SBRT for medically inoperable node-negative NSCLC with primary tumors larger than 5 cm is safe and provides excellent local control with limited toxicity. The predominant pattern of failure in this population was distant failure.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

HIGH-STRENGTH LIGHTWEIGHT ENGINES FOR HEAVY-DUTY DIESEL TRUCKS

This project with Cummins supports the development of next generation heavy duty diesel engines that can achieve a 50% or better Break Thermal Efficiency (BTE). The fuel efficiency roadmap for the 50% BTE engine considers six main areas for efficiency improvement in the baseline engine, several of which involve making more efficient use of thermal energy (heat) in the engine. Increased operating temperatures and improved thermal management are expected to enable significant increases in $power$ $density$, thus resulting in greater power output for the same sized engine or engine downsizing (or light weighting) for the same power output. However, it has become apparent that several key components will be exposed to temperatures beyond the capabilities of current engine and exhaust materials, requiring the availability of the next generation of high temperature materials to allow the engine to reach the targeted efficiencies, commercially viable durability, and emission targets. The objective of this project was to identify and/or develop key materials, and evaluate their critical properties to enable the design and development of a lightweight, higher efficiency engine, with enhanced temperature capability and reduced heat-loss to the atmosphere in order to facilitate waste heat recovery and improved efficiency. An increase in the temperature capability of exhaust manifold materials, and piston materials were identified as having a positive influence on the efficiency of the next generation diesel engines. Since the current materials (High SiMo cast irons used in exhaust manifolds, and 4140 steel in pistons) are already operating near their limits of their temperature and strength capabilities, it was determined that new materials with the right combination of properties are required for these components. Oxidation and constrained thermal fatigue tests were used to down-select CF8C plus (CF8CP), a cast austenitic stainless steel, for exhaust manifolds capable of operating at higher temperatures. A prototype exhaust manifold was fabricated using CF8CP and successfully tested in a marine engine. A functionally graded multiple-layer thermal barrier coating system was designed with four layers of mixed bondcoat alloy (NiCoCrAlYHfSi) and yttria stabilized zirconia (YSZ) and was shown to reduce the effective thermal conductivity of the coating-substrate (steel and Ti-6Al-4V) system. The graded alloy and YSZ mixture were intended to achieve better match of thermal expansion coefficient (CTE) and minimize thermal stresses. Such coatings can increase the temperature capability of pistons fabricated from steel and Ti-alloys. Effect of oil additives and friction conformal contact friction tests showed there was a 15-30% reduction in friction by the polymer-graphite composite coating compared to the uncoated steel piston. Standalone Mn-P coating had little beneficial impact. Changing the oil from CJ-4 to PC-11 had little impact on the friction behavior in boundary lubrication. Wear behavior was tested under a point contact configuration with a high contact pressure. The candidate CK-4 oil showed similar or slightly better lubricity compared to the CJ-4 oil while the candidate FA-4 oil decisively increased the piston skirt wear. Although both coatings prevented scuffing failure observed for the uncoated steel skirt in a base oil without an additive package, they surprisingly caused a higher piston wear rate when tested in any of the fully formulated engine oil. The detrimental impact was attributed to the Mn-P film, either as a standalone coating, or a coating interlayer. The porous and brittle Mn-P film was broken during the wear test and the released hard Mn-P grains are suspected to cause third-body abrasion to accelerate the wear process. This work also evaluated the feasibility of developing an improved high temperature, low mass, cost-neutral turbocharger compressor wheel for heavy-duty engine applications from TiAl using additive manufacturing, utilizing its unique ability to fabricate high strength, low weight structures. This work has shown that the phase transforming nature of the TiAl alloys enable obtaining equiaxed microstructures in the as-built state without the need for tedious beam parameter manipulations. The HIPed structures have good RT tensile properties that will enable them to be surface machined to the required tolerance that can 2 then be heat treated to obtain the desired microstructures. Additionally, the negligible residual stresses stemming from the high build chamber temperatures ensure the parts are formed without cracks (one of the major issues in traditional manufacturing of these intermetallics).

33 ADVANCED PROPULSION SYSTEMS↗

Phase 2 Study of Temozolomide-Based Chemoradiation Therapy for High-Risk Low-Grade Gliomas: Preliminary Results of Radiation Therapy Oncology Group 0424

Purpose: Radiation Therapy Oncology Group (RTOG) 0424 was a phase 2 study of a high-risk low-grade glioma (LGG) population who were treated with temozolomide (TMZ) and radiation therapy (RT), and outcomes were compared to those of historical controls. This study was designed to detect a 43% increase in median survival time (MST) from 40.5 to 57.9 months and a 20% improvement in 3-year overall survival (OS) rate from 54% to 65% at a 10% significance level (1-sided) and 96% power. Methods and Materials: Patients with LGGs with 3 or more risk factors for recurrence (age ≥40 years, astrocytoma histology, bihemispherical tumor, preoperative tumor diameter of ≥6 cm, or a preoperative neurological function status of >1) were treated with RT (54 Gy in 30 fractions) and concurrent and adjuvant TMZ. Results: From 2005 to 2009, 129 evaluable patients (75 males and 54 females) were accrued. Median age was 49 years; 91% had a Zubrod score of 0 or 1; and 69%, 25%, and 6% of patients had 3, 4, and 5 risk factors, respectively. Patients had median and minimum follow-up examinations of 4.1 years and 3 years, respectively. The 3-year OS rate was 73.1% (95% confidence interval: 65.3%-80.8%), which was significantly improved compared to that of prespecified historical control values (P<.001). Median survival time has not yet been reached. Three-year progression-free survival was 59.2%. Grades 3 and 4 adverse events occurred in 43% and 10% of patients, respectively. One patient died of herpes encephalitis. Conclusions: The 3-year OS rate of 73.1% for RTOG 0424 high-risk LGG patients is higher than that reported for historical controls (P<.001) and the study-hypothesized rate of 65%.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Mica filled polyetherketoneketones for material extrusion 3D printing

Polyetherketoneketone (PEKK) has superior physical properties to most available thermoplastics compatible with material extrusion-based 3D printing, including analogs in the polyaryletherketone (PAEK) family. To date, the performance of fused filament fabrication (FFF) compatible PEKK has been detailed primarily as a function of varying the isomer ratios composing the co-polymer structure. The strategy to form blends or composites with PEKK for FFF is attractive for further tailoring of performance in application, yet has received limited attention. Here, we report the integration of three grades of mica platelets into PEKK at 10% and 30% mass loadings to generate an array of filament feedstocks that were then used to print objects with a simple FFF machine. The effects of mica coating chemistry and surface treatment on the compatibility with PEKK and resulting properties are described. Mica fillers at both loadings have only subtle influence on the FFF relevant melt rheological properties inherent to PEKK. Pigment micas at high loadings can lower the melting temperature of PEKK (up to 19 ºC) without shifting its glass transition temperature and inhibit much of the undesirable crystallization occurring during processing with unfilled PEKK. The printed composites were effectively cold crystallized post-printing, affording crystalline fractions up to 90% relative to unfilled PEKK with increased dimensional stabilities. All micas, when used as fillers in low and high relative PEKK crystallinities, significantly increased the tensile modulus (as high as 126% or to 7.31 GPa) of parts in correlation to the loading. Furthermore, the underlying microstructural features of a printed composite were compared to unfilled PEKK by use of a high-resolution helical micro-computed tomography instrument. Practically, pigment micas can confer a wide range of rich colors to 3D-printed PEKK.

36 MATERIALS SCIENCE↗

The effect of pore structure in ethane-selective metal-organic frameworks for ethylene purification

Separation of ethylene from ethane is of great importance in petrochemical industry. Adsorptive separation making use of porous materials such as metal-organic frameworks (MOFs) is an energy efficient technology compared to the conventional cryogenic distillation. However, preferential adsorption of ethylene over ethane represents the major current challenge. Here we demonstrate how pore structure can significantly alter the adsorption selectivity in two isoreticular Zr-MOFs. A simple ligand functionalization in UiO-66 yields smaller/better matching pore for ethane, and weaker interaction with ethylene, greatly enhancing ethane/ethylene selectivity in MOF-801. Ab initio calculations combined with in situ infrared spectroscopic analysis unveil the nature of host-guest interactions and differences in the overall binding energies. Polymer-grade ethylene (99.9%) can be produced directly from ethane/ethylene mixture in a single step. Having well-balanced adsorption capacity and selectivity, low-cost synthesis and easy scalability MOF-801 stands out as a promising ethane-selective adsorbent for one-step ethylene purification under ambient conditions.

36 MATERIALS SCIENCE↗

Functional Promoter Variant rs2868371 of HSPB1 Is Associated With Risk of Radiation Pneumonitis After Chemoradiation for Non-Small Cell Lung Cancer

Purpose: To date, no biomarkers have been found to predict, before treatment, which patients will develop radiation pneumonitis (RP), a potentially fatal toxicity, after chemoradiation for lung cancer. We investigated potential associations between single nucleotide polymorphisms (SNPs) in HSPB1 and risk of RP after chemoradiation for non-small cell lung cancer (NSCLC). Methods and Materials: Subjects were patients with NSCLC treated with chemoradiation at 1 institution. The training data set comprised 146 patients treated from 1999 to July 2004; the validation data set was 125 patients treated from August 2004 to March 2010. We genotyped 2 functional SNPs of HSPB1 (rs2868370 and rs2868371) from all patients. We used Kaplan-Meier analysis to assess the risk of grade ≥2 or ≥3 RP in both data sets and a parametric log-logistic survival model to evaluate the association of HSPB1 genotypes with that risk. Results: Grade ≥3 RP was experienced by 13% of those with CG/GG and 29% of those with CC genotype of HSPB1 rs2868371 in the training data set (P=.028); corresponding rates in the validation data set were 2% CG/GG and 14% CC (P=.02). Univariate and multivariate analysis confirmed the association of CC of HSPB1 rs2868371 with higher risk of grade ≥3 RP than CG/GG after adjustment for sex, age, performance status, and lung mean dose. This association was validated both in the validation data set and with Harrell's C statistic. Conclusions: The CC genotype of HSPB1 rs2868371 was associated with severe RP after chemoradiation for NSCLC.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Use of 4-Dimensional Computed Tomography-Based Ventilation Imaging to Correlate Lung Dose and Function With Clinical Outcomes

Purpose: Four-dimensional computed tomography (4DCT)-based ventilation is an emerging imaging modality that can be used in the thoracic treatment planning process. The clinical benefit of using ventilation images in radiation treatment plans remains to be tested. The purpose of the current work was to test the potential benefit of using ventilation in treatment planning by evaluating whether dose to highly ventilated regions of the lung resulted in increased incidence of clinical toxicity. Methods and Materials: Pretreatment 4DCT data were used to compute pretreatment ventilation images for 96 lung cancer patients. Ventilation images were calculated using 4DCT data, deformable image registration, and a density-change based algorithm. Dose–volume and ventilation-based dose function metrics were computed for each patient. The ability of the dose–volume and ventilation-based dose–function metrics to predict for severe (grade 3+) radiation pneumonitis was assessed using logistic regression analysis, area under the curve (AUC) metrics, and bootstrap methods. Results: A specific patient example is presented that demonstrates how incorporating ventilation-based functional information can help separate patients with and without toxicity. The logistic regression significance values were all lower for the dose–function metrics (range P=.093-.250) than for their dose–volume equivalents (range, P=.331-.580). The AUC values were all greater for the dose–function metrics (range, 0.569-0.620) than for their dose–volume equivalents (range, 0.500-0.544). Bootstrap results revealed an improvement in model fit using dose–function metrics compared to dose–volume metrics that approached significance (range, P=.118-.155). Conclusions: To our knowledge, this is the first study that attempts to correlate lung dose and 4DCT ventilation-based function to thoracic toxicity after radiation therapy. Although the results were not significant at the .05 level, our data suggests that incorporating ventilation-based functional imaging can improve prediction for radiation pneumonitis. We present an important first step toward validating the use of 4DCT-based ventilation imaging in thoracic treatment planning.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Physical and thermal property changes under uniform oxidation in nuclear graphite

Material property changes of fine- and medium-grain nuclear graphite grades were measured after subjection to uniform oxidation. The cores of high temperature reactors are composed of large nuclear graphite block components. Here, these large core components are designed to provide neutron moderation and reflection, create a large thermal sink to assist in operational control, and form the solid core structure containing the nuclear fuel, coolant channels, and the safety critical channels for control rod insertion. Oxidation is a principle degradation mechanism affecting all aspects of the nuclear graphite component functions. This study addresses the underlying physical property changes of nuclear-graphite components for oxidized mass loss ranges beyond the current recommended ASME code rule limits to ensure structural integrity within the graphite components (a maximum mass loss = 10%).

11 - NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

Review of Graphite Properties Relevant to Micro-Reactor Design

Microreactors are advanced reactors that are designed to be small, scalable, and portable with up to 20 MW power. These reactors could operate independently, or as part of a microgrid, without need of a frequent refueling. Micro-reactors are designed to be deployable to provide electric power in remote locations, therefore providing greater flexibility. Several micro-reactors are under development in the US. These reactors are based on advanced gas-cooled or heat-pipe concepts. While Graphite can be found in various applications, some high-temperature reactors plan to employ Graphite in their core components due to its role as a moderator and its ability to maintain its structural integrity when subjected to elevated temperatures and high neutron fluence. Although there is significant experience with use of Graphite in nuclear applications, there are still unknowns that should be addressed. Graphite properties depend on the graphite type and affected by the fabrication procedures. Material properties are functions of the temperature and irradiation dose. The fundamental properties also affected by the oxidation environment. Therefore, in-depth understanding of graphite properties, including the effect of irradiation, oxidation and other influencing parameters are required to evaluate the design accurately. This draft aims to provide a comprehensive review of material properties for Graphite relevant to micro reactor design. For this work, two distinct grades of graphite were considered, namely IG-110 and Mersen-2114. Physical, thermal, and mechanical properties for these grades were comparatively evaluated. The properties that are discussed in this draft aim to serve as a basis for design and safety analysis.

42 ENGINEERING↗

Multi-Institutional Experience of Ductal Carcinoma In Situ in Black vs White Patients Treated With Breast-Conserving Surgery and Whole Breast Radiation Therapy

Purpose: Given the paucity of data on racial disparities in ductal carcinoma in situ (DCIS), the data from a multi-institutional cohort of DCIS patients treated with breast-conserving surgery and whole breast radiation therapy (RT) were analyzed to determine whether racial disparities or differences exist. Methods and Materials: A total of 533 white and 76 black DCIS patients from 3 university-based cancer centers were uniformly treated with breast-conserving surgery and RT. All patient data were collected and analyzed as a function of race. Results: The median follow-up was 5.2 years. No significant racial differences were seen in tumor size, age at diagnosis, estrogen receptor status, necrosis, or grade (all P>.05). Of the treatment parameters, the RT dose delivered, boost, positive margin rates, frequency of hormone receptor status assessment, and receipt of hormonal therapy for the 2 cohorts did not significantly differ (all P>.05). The local relapse-free survival was similar at 5 years (96.1% and 98.1%, P=.399) and 10 years (92.8% vs 95.8%, P=.360), with no significant overall survival difference at 10 years (94.0% vs 88.9%, P=.290) between the white and black patients, respectively. On multivariate analysis, race was not an independent predictor of local relapse-free survival or overall survival when accounting for age, grade, and margin status. Conclusion: In our large cohort of DCIS patients uniformly treated at 3 institutions with breast conservation without any apparent differences in treatment delivery parameters, we demonstrated that the clinical and pathologic features and local survival outcomes did not differ as a function of race. Our results suggest that when black patients with DCIS are appropriately selected for breast conservation and receive adjuvant RT without racial disparities in the treatment parameters, differences in the outcomes as a function of race do not exist.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Exact analytical solution of shear-induced flexural vibration of functionally graded piezoelectric beam

The priority of this paper is to obtain the exact analytical solution for free flexural vibration of FGPM beam actuated using the d{sub 15} effect. In piezoelectric actuators, the potential use of d{sub 15} effect has been of particular interest for engineering applications since shear piezoelectric coefficient d15 is much higher than the other piezoelectric coupling constants d{sub 31} and d{sub 33}. The applications of shear actuators are to induce and control the flexural vibrations of beams and plates. In this study, a modified Timoshenko beam theory is used where electric potential is assumed to vary sinusoidaly along the thickness direction. The material properties are assumed to be graded across the thickness in accordance with power law distribution. Hamilton's principle is employed to obtain the equations of motion along with the associated boundary conditions for FGPM beams. Exact analytical solution is derived thus obtained equations of motion. Results for clamped-clamped and clamped-free boundary conditions are presented. The presented result and method shell serve as benchmark for comparing the results obtained from the other approximate methods.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Modeling of Stress and Temperature Effects on Creep of Reduced Activation Ferritic-Martensitic Steel Alloy F82H (Tertiary Creep Modeling of RAFM Steel)

A Bayesian optimization procedure is presented for calibrating a multi-mechanism micromechanical model for creep to experimental data of F82H steel. Reduced activation ferritic martensitic (RAFM) steels based on are the most promising candidates for some fusion reactor structures. Although there are indications that RAFM steel could be viable for fusion applications at temperatures up to 600 °C, the maximum operating temperature will be determined by the creep properties of the structural material and the breeder material compatibility with the structural material. Due to the relative paucity of available creep data on F82H steel compared to other alloys such as Grade 91 steel, micromechanical models are sought for simulating creep based on relevant deformation mechanisms. As a point of departure, this work recalibrates a model form that was previously proposed for Grade 91 steel to match creep curves for F82H steel. Due to the large number of parameters (9) and cost of the nonlinear simulations, an automated approach for tuning the parameters is pursued using a recently developed Bayesian optimization for functional output (BOFO) framework [1]. Incorporating extensions such as batch sequencing and weighted experimental load cases into BOFO, a reasonably small error between experimental and simulated creep curves at two load levels is achieved in a reasonable number of iterations. Validation with an additional creep curve provides confidence in the fitted parameters obtained from the automated calibration procedure to describe the creep behavior of F82H steel at 600 °C. The model is further extended using a temperature dependent scaling law approach to simulate creep response between 550 °C and 650 °C. The efficacy of this extension is compared with the previously used scaling law approach for Grade 91 steel.

36 MATERIALS SCIENCE↗

Genetic Variants of NPAT-ATM and AURKA are Associated With an Early Adverse Reaction in the Gastrointestinal Tract of Patients With Cervical Cancer Treated With Pelvic Radiation Therapy

Purpose: This study sought to associate polymorphisms in genes related to cell cycle regulation or genome maintenance with radiotherapy (RT)-induced an early adverse reaction (EAR) in patients with cervical cancer. Methods and Materials: This study enrolled 243 cervical cancer patients who were treated with pelvic RT. An early gastrointestinal reaction was graded using the National Cancer Institute Common Toxicity Criteria, version 2. Clinical factors of the enrolled patients were analyzed, and 208 patients were grouped for genetic analysis according to their EAR (Grade {<=}1, n = 150; Grade {>=}2, n = 58). Genomic DNA was genotyped, and association with the risk of EAR for 44 functional single-nucleotide polymorphisms (SNPs) of 19 candidate genes was assessed by single-locus, haplotype, and multilocus analyses. Results: Our analysis revealed two haplotypes to be associated with an increased risk of EAR. The first, comprising rs625120C, rs189037T, rs228589A, and rs183460G, is located between the 5' ends of NPAT and ATM (OR = 1.86; 95% CI, 1.21-2.87), whereas the second is located in the AURKA gene and comprises rs2273535A and rs1047972G (OR = 1.75; 95% CI, 1.10-2.78). A third haplotype, rs2273535T and rs1047972A in AURKA, was associated with a reduced EAR risk (OR = 0.42; 95% CI, 0.20-0.89). The risk of EAR was significantly higher among patients with both risk diplotypes than in those possessing the other diplotypes (OR = 3.24; 95% CI, 1.52-6.92). Conclusions: Individual radiosensitivity of intestine may be determined by haplotypes in the NPAT-ATM and AURKA genes. These variants should be explored in larger association studies in cervical cancer patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Carbon Ion Irradiation of the Rat Spinal Cord: Dependence of the Relative Biological Effectiveness on Linear Energy Transfer

Purpose: To measure the relative biological effectiveness (RBE) of carbon ions in the rat spinal cord as a function of linear energy transfer (LET). Methods and Materials: As an extension of a previous study, the cervical spinal cord of rats was irradiated with single doses of carbon ions at 6 positions of a 6-cm spread-out Bragg peak (16-99 keV/μm). The TD{sub 50} values (dose at 50% complication probability) were determined according to dose-response curves for the development of paresis grade 2 within an observation time of 300 days. The RBEs were calculated using TD{sub 50} for photons of our previous study. Results: Minimum latency time was found to be dose-dependent, but not significantly LET-dependent. The TD{sub 50} values for the onset of paresis grade 2 within 300 days were 19.5 ± 0.4 Gy (16 keV/μm), 18.4 ± 0.4 Gy (21 keV/μm), 17.7 ± 0.3 Gy (36 keV/μm), 16.1 ± 1.2 Gy (45 keV/μm), 14.6 ± 0.5 Gy (66 keV/μm), and 14.8 ± 0.5 Gy (99 keV/μm). The corresponding RBEs increased from 1.26 ± 0.05 (16 keV/μm) up to 1.68 ± 0.08 at 66 keV/μm. Unexpectedly, the RBE at 99 keV/μm was comparable to that at 66 keV/μm. Conclusions: The data suggest a linear relation between RBE and LET at high doses for late effects in the spinal cord. Together with additional data from ongoing fractionated irradiation experiments, these data will provide an extended database to systematically benchmark RBE models for further improvements of carbon ion treatment planning.

62 RADIOLOGY AND NUCLEAR MEDICINE↗