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At least 721 records · Page 40

Saddle point sampling using scaled normal coordinates

The sampling of saddle points (SPs) on a potential energy surface (PES) is critical for describing the dynamics and transport properties of materials. In this paper we propose a saddle point search (SPS) method that enables efficient sampling of practically meaningful SPs around a local minimum by converting the PES to the scaled normal coordinates (SNCs), together with the dimer method. We find that the pathway leading to a SP using SNCs is highly efficient and is independent of the system size. This results in the significantly increased SPS efficiency and the enhanced possibility of a complete catalog of the SPs. In addition, we perform SPSs using the SNCs for the diffusion of a vacancy and a dumbbell in body-centered cubic Fe and demonstrate (1) the required number of system force evaluations for a SPS decreases by at least an order of magnitude, (2) the effects of the system size on the number of force evaluations are greatly decreased, and (3) the effects of the number of atoms involved in the SPS on the probability of finding practically meaningful SPs is mostly eliminated. We also discuss the computational cost of introducing the SNCs. It should be highlighted that the SNCs could also be applied to other minimum-mode following methods, demonstrating the general versatility of the proposed method.

36 MATERIALS SCIENCE↗

A novel means to flexibly operate a hybrid concentrated solar power plant and improve operation during non-ideal direct normal irradiation conditions

Hybridization of concentrated solar power (CSP) with other energy sources can drastically increase how much solar energy is harnessed and potentially expand the current geographical deployment of CSP installlations. In this study, a novel operation strategy referred to as flexible heat integration (FHI), is proposed and applied to a hybrid CSP-natural gas power plant. The proposed plant, modeled in Simulink, employs a solar central receiver (SCR) and dual-source gas boiler to drive a steam Rankine power cycle. FHI involves collecting and dispatching solar energy at modified temperatures during off-design direct normal irradiance (DNI). During low-grade (<100 W/m 2 ) and medium-grade (100–500 W/m 2 ) levels of DNI, molten salt is used for steam boiling and feedwater preheating, respectively, rather than superheating usually seen in SCR steam plants. Hybrid gas-firing supplies energy to bypassed systems. FHI is applied to a hybrid plant over the course of a day from each season for a plant located in Salt Lake City, Utah, an unconventional location due to off-design DNI variability. A spring day exhibiting variable DNI is used as the main case study to demonstrate the dynamics and robust operation under the FHI framework. The operation of the plant over the winter day shows the largest improvement in solar-to-electric (STE) efficiency whereas the summer day exhibits the smallest improvement. Monthly results follow a similar trend with FHI improving STE from 15.3% and 16.3% to 17.0% and 16.7% in January and July, respectively. Yearly results show FHI improving STE efficiency from 16.1% to 17.1% relative to standard hybrid operation. Altogether, the proposed concept expands the current understanding of energy management in hybrid SCR-natural power plants under non-ideal DNI conditions and locations that have lower DNI by applying FHI.

14 SOLAR ENERGY↗

Regulation of the central safety factor and normalized beta under low NBI torque in DIII-D

An algorithm has been designed to simultaneously control the central safety factor (q 0 ) and normalized beta (β N ) while ensuring near-zero torque from the neutral beam injection in DIII-D. Feedback control of q 0 and β N in tokamaks can be beneficial due to the close relationship that these variables have with plasma performance and magneto-hydrodynamic stability. In addition, low neutral-beam-torque conditions are of special interest in present devices because future burning-plasma tokamaks such as ITER will most likely operate at very low plasma rotation. The control synthesis of the algorithm presented in this work is based on a linearized, one-dimensional (1D) model of the current-profile dynamics coupled with a zero-dimensional (0D) plasma-energy balance. The actuators considered are neutral beam injection and electron-cyclotron heating and current drive, and discrete logic determines the neutral-beam injection powers that deliver near-zero torque. Here, the algorithm has been tested in nonlinear, 1D simulations using COTSIM (Control-Oriented Transport SIMulator) and in DIII-D experiments, demonstrating satisfactory performance.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Energetic electrons driven in the polarization direction of an intense laser beam incident normal to a solid target

Experiments were performed at the LLNL Titan laser to measure the propagation direction of the energetic electrons that were generated during the interaction of the polarized laser beam with solid targets in the case of normal incidence. The energetic electrons propagated through vacuum to spectator metal wires in the polarization direction and in the perpendicular direction, and the K shell spectra from the different wire materials were recorded as functions of the distance from the laser focal spot. It was found that the fluence of the energetic electrons driven into the spectator wires in the polarization direction compared to the perpendicular direction was larger and increased with the distance from the focal spot. Finally, this indicates that energetic electrons are preferentially driven in the direction of the intense oscillating electric field of the incident laser beam in agreement with the multiphoton inverse Bremsstrahlung absorption process.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Application of laser-driven capacitor-coil to target normal sheath acceleration

A laser-driven accelerator generates protons with tens of MeV in energy by a compact, strong, and transient accelerating electric field produced as a result of laser–plasma interactions at relativistic intensities. In previous studies, two- and three-dimensional particle-in-cell simulations revealed that the application of a kT-level axial magnetic field results in an enhancement of proton acceleration via the target normal sheath acceleration mechanism due to reduced lateral electron divergence and improved electron heating efficiency. An experimental investigation of this scheme on the GEKKO-XII and the LFEX facilities found that the number and maximum energy of the accelerated protons decreased with increasing the temporal delay between the pulse driving the external magnetic-field and the pulse accelerating the protons, contrary to the theoretical and numerical expectations. Finally, we identify sources responsible for the degradation of the proton beam performance and we propose an alternative experimental setup to mitigate the degradation in future experiments.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Validation of Normal Tissue Complication Probability Predictions in Individual Patient: Late Rectal Toxicity

Purpose: To perform validation of risk predictions for late rectal toxicity (LRT) in prostate cancer obtained using a new approach to synthesize published normal tissue complication data. Methods and Materials: A published study survey was performed to identify the dose-response relationships for LRT derived from nonoverlapping patient populations. To avoid mixing models based on different symptoms, the emphasis was placed on rectal bleeding. The selected models were used to compute the risk estimates of grade 2+ and grade 3+ LRT for an independent validation cohort composed of 269 prostate cancer patients with known toxicity outcomes. Risk estimates from single studies were combined to produce consolidated risk estimates. An agreement between the actuarial toxicity incidence 3 years after radiation therapy completion and single-study or consolidated risk estimates was evaluated using the concordance correlation coefficient. Goodness of fit for the consolidated risk estimates was assessed using the Hosmer-Lemeshow test. Results: A total of 16 studies of grade 2+ and 5 studies of grade 3+ LRT met the inclusion criteria. The consolidated risk estimates of grade 2+ and 3+ LRT were constructed using 3 studies each. For grade 2+ LRT, the concordance correlation coefficient for the consolidated risk estimates was 0.537 compared with 0.431 for the best-fit single study. For grade 3+ LRT, the concordance correlation coefficient for the consolidated risk estimates was 0.477 compared with 0.448 for the best-fit single study. No evidence was found for a lack of fit for the consolidated risk estimates using the Hosmer-Lemeshow test (P=.531 and P=.397 for grade 2+ and 3+ LRT, respectively). Conclusions: In a large cohort of prostate cancer patients, selected sets of consolidated risk estimates were found to be more accurate predictors of LRT than risk estimates derived from any single study.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Effect of Normal Lung Definition on Lung Dosimetry and Lung Toxicity Prediction in Radiation Therapy Treatment Planning

Purpose: This study aimed to compare lung dose–volume histogram (DVH) parameters such as mean lung dose (MLD) and the lung volume receiving ≥20 Gy (V20) of commonly used definitions of normal lung in terms of tumor/target subtraction and to determine to what extent they differ in predicting radiation pneumonitis (RP). Methods and Materials: One hundred lung cancer patients treated with definitive radiation therapy were assessed. The gross tumor volume (GTV) and clinical planning target volume (PTV{sub c}) were defined by the treating physician and dosimetrist. For this study, the clinical target volume (CTV) was defined as GTV with 8-mm uniform expansion, and the PTV was defined as CTV with an 8-mm uniform expansion. Lung DVHs were generated with exclusion of targets: (1) GTV (DVH{sub G}); (2) CTV (DVH{sub C}); (3) PTV (DVH{sub P}); and (4) PTV{sub c} (DVH{sub Pc}). The lung DVHs, V20s, and MLDs from each of the 4 methods were compared, as was their significance in predicting radiation pneumonitis of grade 2 or greater (RP2). Results: There are significant differences in dosimetric parameters among the various definition methods (all Ps<.05). The mean and maximum differences in V20 are 4.4% and 12.6% (95% confidence interval 3.6%-5.1%), respectively. The mean and maximum differences in MLD are 3.3 Gy and 7.5 Gy (95% confidence interval, 1.7-4.8 Gy), respectively. MLDs of all methods are highly correlated with each other and significantly correlated with clinical RP2, although V20s are not. For RP2 prediction, on the receiver operating characteristic curve, MLD from DVH{sub G} (MLD{sub G}) has a greater area under curve of than MLD from DVH{sub C} (MLD{sub C}) or DVH{sub P} (MLD{sub P}). Limiting RP2 to 30%, the threshold is 22.4, 20.6, and 18.8 Gy, for MLD{sub G}, MLD{sub C}, and MLD{sub P}, respectively. Conclusions: The differences in MLD and V20 from various lung definitions are significant. MLD from the GTV exclusion method may be more accurate in predicting clinical significant radiation pneumonitis.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Multivariate Normal Tissue Complication Probability Modeling of Heart Valve Dysfunction in Hodgkin Lymphoma Survivors

Purpose: To establish a multivariate normal tissue complication probability (NTCP) model for radiation-induced asymptomatic heart valvular defects (RVD). Methods and Materials: Fifty-six patients treated with sequential chemoradiation therapy for Hodgkin lymphoma (HL) were retrospectively reviewed for RVD events. Clinical information along with whole heart, cardiac chambers, and lung dose distribution parameters was collected, and the correlations to RVD were analyzed by means of Spearman's rank correlation coefficient (Rs). For the selection of the model order and parameters for NTCP modeling, a multivariate logistic regression method using resampling techniques (bootstrapping) was applied. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). Results: When we analyzed the whole heart, a 3-variable NTCP model including the maximum dose, whole heart volume, and lung volume was shown to be the optimal predictive model for RVD (Rs = 0.573, P<.001, AUC = 0.83). When we analyzed the cardiac chambers individually, for the left atrium and for the left ventricle, an NTCP model based on 3 variables including the percentage volume exceeding 30 Gy (V30), cardiac chamber volume, and lung volume was selected as the most predictive model (Rs = 0.539, P<.001, AUC = 0.83; and Rs = 0.557, P<.001, AUC = 0.82, respectively). The NTCP values increase as heart maximum dose or cardiac chambers V30 increase. They also increase with larger volumes of the heart or cardiac chambers and decrease when lung volume is larger. Conclusions: We propose logistic NTCP models for RVD considering not only heart irradiation dose but also the combined effects of lung and heart volumes. Our study establishes the statistical evidence of the indirect effect of lung size on radio-induced heart toxicity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Reduced Activity of Double-Strand Break Repair Genes in Prostate Cancer Patients With Late Normal Tissue Radiation Toxicity

Purpose: To investigate clinical parameters and DNA damage response as possible risk factors for radiation toxicity in the setting of prostate cancer. Methods and Materials: Clinical parameters of 61 prostate cancer patients, 34 with (overresponding, OR) and 27 without (non-responding, NR) severe late radiation toxicity were assembled. In addition, for a matched subset the DNA damage repair kinetics (γ-H2AX assay) and expression profiles of DNA repair genes were determined in ex vivo irradiated lymphocytes. Results: Examination of clinical data indicated none of the considered clinical parameters to be correlated with the susceptibility of patients to develop late radiation toxicity. Although frequencies of γ-H2AX foci induced immediately after irradiation were similar (P=.32), significantly higher numbers of γ-H2AX foci were found 24 hours after irradiation in OR compared with NR patients (P=.03). Patient-specific γ-H2AX foci decay ratios were significantly higher in NR patients than in OR patients (P<.0001). Consequently, NR patients seem to repair DNA double-strand breaks (DSBs) more efficiently than OR patients. Moreover, gene expression analysis indicated several genes of the homologous recombination pathway to be stronger induced in NR compared with OR patients (P<.05). A similar trend was observed in genes of the nonhomologous end-joining repair pathway (P=.09). This is congruent with more proficient repair of DNA DSBs in patients without late radiation toxicity. Conclusions: Both gene expression profiling and DNA DSB repair kinetics data imply that less-efficient repair of radiation-induced DSBs may contribute to the development of late normal tissue damage. Induction levels of DSB repair genes (eg, RAD51) may potentially be used to assess the risk for late radiation toxicity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Clinical Evaluation of Normalized Metal Artifact Reduction in kVCT Using MVCT Prior Images (MVCT-NMAR) for Radiation Therapy Treatment Planning

Purpose: To evaluate the metal artifacts in diagnostic kilovoltage computed tomography (kVCT) images of patients that are corrected by use of a normalized metal artifact reduction (NMAR) method with megavoltage CT (MVCT) prior images: MVCT-NMAR. Methods and Materials: MVCT-NMAR was applied to images from 5 patients: 3 with dual hip prostheses, 1 with a single hip prosthesis, and 1 with dental fillings. The corrected images were evaluated for visualization of tissue structures and their interfaces and for radiation therapy dose calculations. They were compared against the corresponding images corrected by the commercial orthopedic metal artifact reduction algorithm in a Phillips CT scanner. Results: The use of MVCT images for correcting kVCT images in the MVCT-NMAR technique greatly reduces metal artifacts, avoids secondary artifacts, and makes patient images more useful for correct dose calculation in radiation therapy. These improvements are significant, provided the MVCT and kVCT images are correctly registered. The remaining and the secondary artifacts (soft tissue blurring, eroded bones, false bones or air pockets, CT number cupping within the metal) present in orthopedic metal artifact reduction corrected images are removed in the MVCT-NMAR corrected images. A large dose reduction was possible outside the planning target volume (eg, 59.2 Gy to 52.5 Gy in pubic bone) when these MVCT-NMAR corrected images were used in TomoTherapy treatment plans without directional blocks for a prostate cancer patient. Conclusions: The use of MVCT-NMAR corrected images in radiation therapy treatment planning could improve the treatment plan quality for patients with metallic implants.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Quantifying Unnecessary Normal Tissue Complication Risks due to Suboptimal Planning: A Secondary Study of RTOG 0126

Purpose: The purpose of this study was to quantify the frequency and clinical severity of quality deficiencies in intensity modulated radiation therapy (IMRT) planning in the Radiation Therapy Oncology Group 0126 protocol. Methods and Materials: A total of 219 IMRT patients from the high-dose arm (79.2 Gy) of RTOG 0126 were analyzed. To quantify plan quality, we used established knowledge-based methods for patient-specific dose-volume histogram (DVH) prediction of organs at risk and a Lyman-Kutcher-Burman (LKB) model for grade ≥2 rectal complications to convert DVHs into normal tissue complication probabilities (NTCPs). The LKB model was validated by fitting dose-response parameters relative to observed toxicities. The 90th percentile (22 of 219) of plans with the lowest excess risk (difference between clinical and model-predicted NTCP) were used to create a model for the presumed best practices in the protocol (pDVH{sub 0126,top10%}). Applying the resultant model to the entire sample enabled comparisons between DVHs that patients could have received to DVHs they actually received. Excess risk quantified the clinical impact of suboptimal planning. Accuracy of pDVH predictions was validated by replanning 30 of 219 patients (13.7%), including equal numbers of presumed “high-quality,” “low-quality,” and randomly sampled plans. NTCP-predicted toxicities were compared to adverse events on protocol. Results: Existing models showed that bladder-sparing variations were less prevalent than rectum quality variations and that increased rectal sparing was not correlated with target metrics (dose received by 98% and 2% of the PTV, respectively). Observed toxicities were consistent with current LKB parameters. Converting DVH and pDVH{sub 0126,top10%} to rectal NTCPs, we observed 94 of 219 patients (42.9%) with ≥5% excess risk, 20 of 219 patients (9.1%) with ≥10% excess risk, and 2 of 219 patients (0.9%) with ≥15% excess risk. Replanning demonstrated the predicted NTCP reductions while maintaining the volume of the PTV receiving prescription dose. An equivalent sample of high-quality plans showed fewer toxicities than low-quality plans, 6 of 73 versus 10 of 73 respectively, although these differences were not significant (P=.21) due to insufficient statistical power in this retrospective study. Conclusions: Plan quality deficiencies in RTOG 0126 exposed patients to substantial excess risk for rectal complications.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Identification of Patient Benefit From Proton Therapy for Advanced Head and Neck Cancer Patients Based on Individual and Subgroup Normal Tissue Complication Probability Analysis

Purpose: The purpose of this study was to determine, by treatment plan comparison along with normal tissue complication probability (NTCP) modeling, whether a subpopulation of patients with head and neck squamous cell carcinoma (HNSCC) could be identified that would gain substantial benefit from proton therapy in terms of NTCP. Methods and Materials: For 45 HNSCC patients, intensity modulated radiation therapy (IMRT) was compared to intensity modulated proton therapy (IMPT). Physical dose distributions were evaluated as well as the resulting NTCP values, using modern models for acute mucositis, xerostomia, aspiration, dysphagia, laryngeal edema, and trismus. Patient subgroups were defined based on primary tumor location. Results: Generally, IMPT reduced the NTCP values while keeping similar target coverage for all patients. Subgroup analyses revealed a higher individual reduction of swallowing-related side effects by IMPT for patients with tumors in the upper head and neck area, whereas the risk reduction of acute mucositis was more pronounced in patients with tumors in the larynx region. More patients with tumors in the upper head and neck area had a reduction in NTCP of more than 10%. Conclusions: Subgrouping can help to identify patients who may benefit more than others from the use of IMPT and, thus, can be a useful tool for a preselection of patients in the clinic where there are limited PT resources. Because the individual benefit differs within a subgroup, the relative merits should additionally be evaluated by individual treatment plan comparisons.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Pitfalls in Prediction Modeling for Normal Tissue Toxicity in Radiation Therapy: An Illustration With the Individual Radiation Sensitivity and Mammary Carcinoma Risk Factor Investigation Cohorts

Purpose: To identify the main causes underlying the failure of prediction models for radiation therapy toxicity to replicate. Methods and Materials: Data were used from two German cohorts, Individual Radiation Sensitivity (ISE) (n=418) and Mammary Carcinoma Risk Factor Investigation (MARIE) (n=409), of breast cancer patients with similar characteristics and radiation therapy treatments. The toxicity endpoint chosen was telangiectasia. The LASSO (least absolute shrinkage and selection operator) logistic regression method was used to build a predictive model for a dichotomized endpoint (Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer score 0, 1, or ≥2). Internal areas under the receiver operating characteristic curve (inAUCs) were calculated by a naïve approach whereby the training data (ISE) were also used for calculating the AUC. Cross-validation was also applied to calculate the AUC within the same cohort, a second type of inAUC. Internal AUCs from cross-validation were calculated within ISE and MARIE separately. Models trained on one dataset (ISE) were applied to a test dataset (MARIE) and AUCs calculated (exAUCs). Results: Internal AUCs from the naïve approach were generally larger than inAUCs from cross-validation owing to overfitting the training data. Internal AUCs from cross-validation were also generally larger than the exAUCs, reflecting heterogeneity in the predictors between cohorts. The best models with largest inAUCs from cross-validation within both cohorts had a number of common predictors: hypertension, normalized total boost, and presence of estrogen receptors. Surprisingly, the effect (coefficient in the prediction model) of hypertension on telangiectasia incidence was positive in ISE and negative in MARIE. Other predictors were also not common between the 2 cohorts, illustrating that overcoming overfitting does not solve the problem of replication failure of prediction models completely. Conclusions: Overfitting and cohort heterogeneity are the 2 main causes of replication failure of prediction models across cohorts. Cross-validation and similar techniques (eg, bootstrapping) cope with overfitting, but the development of validated predictive models for radiation therapy toxicity requires strategies that deal with cohort heterogeneity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Methods for Reducing Normal Tissue Complication Probabilities in Oropharyngeal Cancer: Dose Reduction or Planning Target Volume Elimination

Purpose: Strategies to reduce the toxicities of head and neck radiation (ie, dysphagia [difficulty swallowing] and xerostomia [dry mouth]) are currently underway. However, the predicted benefit of dose and planning target volume (PTV) reduction strategies is unknown. The purpose of the present study was to compare the normal tissue complication probabilities (NTCP) for swallowing and salivary structures in standard plans (70 Gy [P70]), dose-reduced plans (60 Gy [P60]), and plans eliminating the PTV margin. Methods and Materials: A total of 38 oropharyngeal cancer (OPC) plans were analyzed. Standard organ-sparing volumetric modulated arc therapy plans (P70) were created and then modified by eliminating the PTVs and treating the clinical tumor volumes (CTVs) only (C70) or maintaining the PTV but reducing the dose to 60 Gy (P60). NTCP dose models for the pharyngeal constrictors, glottis/supraglottic larynx, parotid glands (PGs), and submandibular glands (SMGs) were analyzed. The minimal clinically important benefit was defined as a mean change in NTCP of >5%. The P70 NTCP thresholds and overlap percentages of the organs at risk with the PTVs (56-59 Gy, vPTV{sub 56}) were evaluated to identify the predictors for NTCP improvement. Results: With the P60 plans, only the ipsilateral PG (iPG) benefited (23.9% vs 16.2%; P<.01). With the C70 plans, only the iPG (23.9% vs 17.5%; P<.01) and contralateral SMG (cSMG) (NTCP 32.1% vs 22.9%; P<.01) benefited. An iPG NTCP threshold of 20% and 30% predicted NTCP benefits for the P60 and C70 plans, respectively (P<.001). A cSMG NTCP threshold of 30% predicted for an NTCP benefit with the C70 plans (P<.001). Furthermore, for the iPG, a vPTV{sub 56} >13% predicted benefit with P60 (P<.001) and C70 (P=.002). For the cSMG, a vPTV{sub 56} >22% predicted benefit with C70 (P<.01). Conclusions: PTV elimination and dose-reduction lowered the NTCP of the iPG, and PTV elimination lowered the NTCP of the cSMG. NTCP thresholds and the percentage of overlap of the PTV with organs at risk can predict which patients will benefit and inform future clinical trial design.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Normal Tissue Response of Combined Temporal and Spatial Fractionation in Proton Minibeam Radiation Therapy

Proton minibeam radiation therapy, a spatial fractionation concept, widens the therapeutic window. By reducing normal tissue toxicities, it allows a temporally fractionated regime with high daily doses. However, an array shift between daily fractions can affect the tissue-sparing effect by decreasing the total peak-to-valley dose ratio. Therefore, combining temporal fractions with spatial fractionation raises questions about the impact of daily applied dose modulations, reirradiation accuracies, and total dose modulations.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Ultra-high-dose-rate FLASH and Conventional-Dose-Rate Irradiation Differentially Affect Human Acute Lymphoblastic Leukemia and Normal Hematopoiesis

Ultra-high-dose-rate FLASH radiation therapy has been shown to minimize side effects of irradiation in various organs while keeping antitumor efficacy. This property, called the FLASH effect, has caused enthusiasm in the radiation oncology community because it opens opportunities for safe dose escalation and improved radiation therapy outcome. Here, we investigated the impact of ultra-high-dose-rate FLASH versus conventional-dose-rate (CONV) total body irradiation (TBI) on humanized models of T-cell acute lymphoblastic leukemia (T-ALL) and normal human hematopoiesis.

62 RADIOLOGY AND NUCLEAR MEDICINE↗