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

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At least 289 records · Page 16
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

Flow structures of the cross-flow over a five-layer helically coiled steam generator geometry

The helically-coiled heat exchanger (HCSG) offers advantages over straight tubes such as compactness in geometry, increased heat transfer coefficients, and capability to absorb thermal expansion. In this study, the time-resolved velocity field data of shell-side crossflow over a five-layer helically coiled steam generator geometry was obtained using Particle Image Velocimetry (PIV) between adjacent rods in four regions with up to 5000 frames per second (5 kHz) at approximately Re u = 3600. The slant rod bundle created different flow patterns in different regions. Proper Orthogonal Decomposition (POD) revealed high-energy-mode flow structures. Due to the confined flow channel geometry, the large flow structures were not advected resulting in no strong POD mode paring. Continuous Wavelet Transform (CWT) visualized the characteristics of flow fluctuation in time and frequency domain simultaneously, which ranged in Strouhal number, S u , between 0.03 and 1.17. In the wake regions of the rods, flows changed in both pattern and magnitude over time. Once a pattern formed, it continued for relatively shorter than straight tube arrays, before changing the pattern again. The histograms of the POD time coefficients presented this multimodal flow characteristics. The current study focuses more on whole flow field analyses in the selected regions rather than local point-wise analyses. Finally, this study revealed that various Strouhal numbers can exist in the helically coiled heat exchanger geometry, which was not observed in straight tube arrays. In particular, Strouhal numbers smaller than 0.1 do not seem to be caused by vortex shedding but seem to be the result of the combination of complex geometry and possible multimodal trends. Based on the current observation, further works would involve intensive instantaneous point-wise analyses on the interactions between important locations such as separation points, stagnation points, shear layers, etc.

42 ENGINEERING↗
DOE OSTI2018

Towards a greater understanding of serrated flows in an Al-containing high-entropy-based alloy

A serrated flow, which occurs in a material undergoing mechanical deformation, is a complex process of great engineering significance. Here statistical, dynamical, and multifractal modeling and analyses were performed on the stress-time series to characterize and model the stress-drop behavior of an Al 0.5 CoCrCuFeNi high-entropy alloy (HEA). Results indicate that the spatiotemporal dynamics of the serrated flow is affected by changes in the strain rate and test temperature. The sample entropy, in general, was found to be the highest in the samples tested at 500°C. The higher complexity in the serrated flow at this temperature appeared to be associated with the stress-drop behavior that had intermediate values in terms of the maximum stress drop, the multifractality of the data set, and the histogram distributions. Moreover, the sample entropy was the lowest for the samples tested at 600 °C. The lower complexity values were associated with a wider multifractal spectrum and a less uniform and sparser distribution of the stress-drop magnitudes. In terms of the serration types, Type-C serrations were related to the lowest complexity values, widest multifractal spectra, and higher probability of exhibiting larger stress drops. Conversely, Type-A and B serrations were associated with the higher complexity, narrower spectra, and lower probability of higher stress drops. In conclusion, the body-centered-cubic (BCC) structure and the fully-ordered L1 2 nano-particles were found to emerge in the samples at 600°C and are thought to be linked to the decreased spatiotemporal correlations in the stressdrop behavior.

36 MATERIALS SCIENCE↗
DOE OSTI2013

A Knowledge-Based Approach to Improving and Homogenizing Intensity Modulated Radiation Therapy Planning Quality Among Treatment Centers: An Example Application to Prostate Cancer Planning

Purpose: Intensity modulated radiation therapy (IMRT) treatment planning can have wide variation among different treatment centers. We propose a system to leverage the IMRT planning experience of larger institutions to automatically create high-quality plans for outside clinics. We explore feasibility by generating plans for patient datasets from an outside institution by adapting plans from our institution. Methods and Materials: A knowledge database was created from 132 IMRT treatment plans for prostate cancer at our institution. The outside institution, a community hospital, provided the datasets for 55 prostate cancer cases, including their original treatment plans. For each “query” case from the outside institution, a similar “match” case was identified in the knowledge database, and the match case’s plan parameters were then adapted and optimized to the query case by use of a semiautomated approach that required no expert planning knowledge. The plans generated with this knowledge-based approach were compared with the original treatment plans at several dose cutpoints. Results: Compared with the original plan, the knowledge-based plan had a significantly more homogeneous dose to the planning target volume and a significantly lower maximum dose. The volumes of the rectum, bladder, and femoral heads above all cutpoints were nominally lower for the knowledge-based plan; the reductions were significantly lower for the rectum. In 40% of cases, the knowledge-based plan had overall superior (lower) dose–volume histograms for rectum and bladder; in 54% of cases, the comparison was equivocal; in 6% of cases, the knowledge-based plan was inferior for both bladder and rectum. Conclusions: Knowledge-based planning was superior or equivalent to the original plan in 95% of cases. The knowledge-based approach shows promise for homogenizing plan quality by transferring planning expertise from more experienced to less experienced institutions.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

A Fully Automated Method for CT-on-Rails-Guided Online Adaptive Planning for Prostate Cancer Intensity Modulated Radiation Therapy

Purpose: This study was designed to validate a fully automated adaptive planning (AAP) method which integrates automated recontouring and automated replanning to account for interfractional anatomical changes in prostate cancer patients receiving adaptive intensity modulated radiation therapy (IMRT) based on daily repeated computed tomography (CT)-on-rails images. Methods and Materials: Nine prostate cancer patients treated at our institution were randomly selected. For the AAP method, contours on each repeat CT image were automatically generated by mapping the contours from the simulation CT image using deformable image registration. An in-house automated planning tool incorporated into the Pinnacle treatment planning system was used to generate the original and the adapted IMRT plans. The cumulative dose–volume histograms (DVHs) of the target and critical structures were calculated based on the manual contours for all plans and compared with those of plans generated by the conventional method, that is, shifting the isocenters by aligning the images based on the center of the volume (COV) of prostate (prostate COV-aligned). Results: The target coverage from our AAP method for every patient was acceptable, while 1 of the 9 patients showed target underdosing from prostate COV-aligned plans. The normalized volume receiving at least 70 Gy (V{sub 70}), and the mean dose of the rectum and bladder were reduced by 8.9%, 6.4 Gy and 4.3%, 5.3 Gy, respectively, for the AAP method compared with the values obtained from prostate COV-aligned plans. Conclusions: The AAP method, which is fully automated, is effective for online replanning to compensate for target dose deficits and critical organ overdosing caused by interfractional anatomical changes in prostate cancer.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

Novel Parameter Predicting Grade 2 Rectal Bleeding After Iodine-125 Prostate Brachytherapy Combined With External Beam Radiation Therapy

Purpose: To propose a novel parameter predicting rectal bleeding on the basis of generalized equivalent uniform doses (gEUD) after {sup 125}I prostate brachytherapy combined with external beam radiation therapy and to assess the predictive value of this parameter. Methods and Materials: To account for differences among radiation treatment modalities and fractionation schedules, rectal dose–volume histograms (DVHs) of 369 patients with localized prostate cancer undergoing combined therapy retrieved from corresponding treatment planning systems were converted to equivalent dose-based DVHs. The gEUDs for the rectum were calculated from these converted DVHs. The total gEUD (gEUD{sub sum}) was determined by a summation of the brachytherapy and external-beam radiation therapy components. Results: Thirty-eight patients (10.3%) developed grade 2+ rectal bleeding. The grade 2+ rectal bleeding rate increased as the gEUD{sub sum} increased: 2.0% (2 of 102 patients) for <70 Gy, 10.3% (15 of 145 patients) for 70-80 Gy, 15.8% (12 of 76 patients) for 80-90 Gy, and 19.6% (9 of 46 patients) for >90 Gy (P=.002). Multivariate analysis identified age (P=.024) and gEUD{sub sum} (P=.000) as risk factors for grade 2+ rectal bleeding. Conclusions: Our results demonstrate gEUD to be a potential predictive factor for grade 2+ late rectal bleeding after combined therapy for prostate cancer.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

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↗
DOE OSTI2013

Linear Energy Transfer-Guided Optimization in Intensity Modulated Proton Therapy: Feasibility Study and Clinical Potential

Purpose: To investigate the feasibility and potential clinical benefit of linear energy transfer (LET) guided plan optimization in intensity modulated proton therapy (IMPT). Methods and Materials: A multicriteria optimization (MCO) module was used to generate a series of Pareto-optimal IMPT base plans (BPs), corresponding to defined objectives, for 5 patients with head-and-neck cancer and 2 with pancreatic cancer. A Monte Carlo platform was used to calculate dose and LET distributions for each BP. A custom-designed MCO navigation module allowed the user to interpolate between BPs to produce deliverable Pareto-optimal solutions. Differences among the BPs were evaluated for each patient, based on dose–volume and LET–volume histograms and 3-dimensional distributions. An LET-based relative biological effectiveness (RBE) model was used to evaluate the potential clinical benefit when navigating the space of Pareto-optimal BPs. Results: The mean LET values for the target varied up to 30% among the BPs for the head-and-neck patients and up to 14% for the pancreatic cancer patients. Variations were more prominent in organs at risk (OARs), where mean LET values differed by a factor of up to 2 among the BPs for the same patient. An inverse relation between dose and LET distributions for the OARs was typically observed. Accounting for LET-dependent variable RBE values, a potential improvement on RBE-weighted dose of up to 40%, averaged over several structures under study, was noticed during MCO navigation. Conclusions: We present a novel strategy for optimizing proton therapy to maximize dose-averaged LET in tumor targets while simultaneously minimizing dose-averaged LET in normal tissue structures. MCO BPs show substantial LET variations, leading to potentially significant differences in RBE-weighted doses. Pareto-surface navigation, using both dose and LET distributions for guidance, provides the means for evaluating a large variety of deliverable plans and aids in identifying the clinically optimal solution.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

Safety of {sup 90}Y Radioembolization in Patients Who Have Undergone Previous External Beam Radiation Therapy

Purpose: Previous external beam radiation therapy (EBRT) is theoretically contraindicated for yttrium-90 ({sup 90}Y) radioembolization (RE) because the liver has a lifetime tolerance to radiation before becoming vulnerable to radiation-induced liver disease. We analyzed the safety of RE as salvage treatment in patients who had previously undergone EBRT. Methods and Materials: Between June 2004 and December 2010, a total of 31 patients who had previously undergone EBRT were treated with RE. Three-dimensional treatment planning with dose–volume histogram (DVH) analysis of the liver was used to calculate the EBRT liver dose. Liver-related toxicities including RE-induced liver disease (REILD) were reviewed and classified according to Common Terminology Criteria for Adverse Events version 4.02. Results: The mean EBRT and RE liver doses were 4.40 Gy (range, 0-23.13 Gy) and 57.9 Gy (range, 27.0-125.9 Gy), respectively. Patients who experienced hepatotoxicity (≥grade2; n=12) had higher EBRT mean liver doses (7.96 ± 8.55 Gy vs 1.62 ± 3.39 Gy; P=.037), the only independent predictor in multivariate analysis. DVH analysis showed that the fraction of liver exposed to ≥30 Gy (V30) was the strongest predictor of hepatotoxicity (10.14% ± 12.75% vs 0.84% ± 3.24%; P=.006). All patients with V30 >13% experienced hepatotoxicity. Fatal REILD (n=2) occurred at the 2 highest EBRT mean liver doses (20.9 Gy and 23.1 Gy) but also at the highest cumulative liver doses (91.8 Gy and 149 Gy). Conclusions: Prior exposure of the liver to EBRT may lead to increased liver toxicity after RE treatment, depending on fractional liver exposure and dose level. The V30 was the strongest predictor of toxicity. RE appears to be safe for the treatment of hepatic malignancies only in patients who have had limited hepatic exposure to prior EBRT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

Use of EORTC Target Definition Guidelines for Dose-Intensified Salvage Radiation Therapy for Recurrent Prostate Cancer: Results of the Quality Assurance Program of the Randomized Trial SAKK 09/10

Purpose: Different international target volume delineation guidelines exist and different treatment techniques are available for salvage radiation therapy (RT) for recurrent prostate cancer, but less is known regarding their respective applicability in clinical practice. Methods and Materials: A randomized phase III trial testing 64 Gy vs 70 Gy salvage RT was accompanied by an intense quality assurance program including a site-specific and study-specific questionnaire and a dummy run (DR). Target volume delineation was performed according to the European Organisation for the Research and Treatment of Cancer guidelines, and a DR-based treatment plan was established for 70 Gy. Major and minor protocol deviations were noted, interobserver agreement of delineated target contours was assessed, and dose-volume histogram (DVH) parameters of different treatment techniques were compared. Results: Thirty European centers participated, 43% of which were using 3-dimensional conformal RT (3D-CRT), with the remaining centers using intensity modulated RT (IMRT) or volumetric modulated arc technique (VMAT). The first submitted version of the DR contained major deviations in 21 of 30 (70%) centers, mostly caused by inappropriately defined or lack of prostate bed (PB). All but 5 centers completed the DR successfully with their second submitted version. The interobserver agreement of the PB was moderate and was improved by the DR review, as indicated by an increased κ value (0.59 vs 0.55), mean sensitivity (0.64 vs 0.58), volume of total agreement (3.9 vs 3.3 cm{sup 3}), and decrease in the union volume (79.3 vs 84.2 cm{sup 3}). Rectal and bladder wall DVH parameters of IMRT and VMAT vs 3D-CRT plans were not significantly different. Conclusions: The interobserver agreement of PB delineation was moderate but was improved by the DR. Major deviations could be identified for the majority of centers. The DR has improved the acquaintance of the participating centers with the trial protocol.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

Dosimetric and Radiobiological Consequences of Computed Tomography–Guided Adaptive Strategies for Intensity Modulated Radiation Therapy of the Prostate

Purpose: To examine a range of scenarios for image-guided adaptive radiation therapy of prostate cancer, including different schedules for megavoltage CT imaging, patient repositioning, and dose replanning. Methods and Materials: We simulated multifraction dose distributions with deformable registration using 35 sets of megavoltage CT scans of 13 patients. We computed cumulative dose–volume histograms, from which tumor control probabilities and normal tissue complication probabilities (NTCPs) for rectum were calculated. Five-field intensity modulated radiation therapy (IMRT) with 18-MV x-rays was planned to achieve an isocentric dose of 76 Gy to the clinical target volume (CTV). The differences between D{sub 95}, tumor control probability, V{sub 70Gy}, and NTCP for rectum, for accumulated versus planned dose distributions, were compared for different target volume sizes, margins, and adaptive strategies. Results: The CTV D{sub 95} for IMRT treatment plans, averaged over 13 patients, was 75.2 Gy. Using the largest CTV margins (10/7 mm), the D{sub 95} values accumulated over 35 fractions were within 2% of the planned value, regardless of the adaptive strategy used. For tighter margins (5 mm), the average D{sub 95} values dropped to approximately 73.0 Gy even with frequent repositioning, and daily replanning was necessary to correct this deficit. When personalized margins were applied to an adaptive CTV derived from the first 6 treatment fractions using the STAPLE (Simultaneous Truth and Performance Level Estimation) algorithm, target coverage could be maintained using a single replan 1 week into therapy. For all approaches, normal tissue parameters (rectum V{sub 70Gy} and NTCP) remained within acceptable limits. Conclusions: The frequency of adaptive interventions depends on the size of the CTV combined with target margins used during IMRT optimization. The application of adaptive target margins (<5 mm) to an adaptive CTV determined 1 week into therapy minimizes the need for subsequent dose replanning.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

Symptomatic Pericardial Effusion After Chemoradiation Therapy in Esophageal Cancer Patients

Purpose: We investigated clinical and treatment-related factors as predictors of symptomatic pericardial effusion in esophageal cancer patients after concurrent chemoradiation therapy. Methods and Materials: We reviewed 214 consecutive primary esophageal cancer patients treated with concurrent chemoradiation therapy between 2001 and 2010 in our institute. Pericardial effusion was detected on follow-up computed tomography. Symptomatic effusion was defined as effusion ≥grade 3 according to Common Terminology Criteria for Adverse Events v4.0 criteria. Percent volume irradiated with 5 to 65 Gy (V5-V65) and mean dose to the pericardium were evaluated employing dose-volume histograms. To evaluate dosimetry for patients treated with two-dimensional planning in the earlier period (2001-2005), computed tomography data at diagnosis were transferred to a treatment planning system to reconstruct three-dimensional plans without modification. Optimal dosimetric thresholds for symptomatic pericardial effusion were calculated by receiver operating characteristic curves. Associating clinical and treatment-related risk factors for symptomatic pericardial effusion were detected by univariate and multivariate analyses. Results: The median follow-up was 29 (range, 6-121) months for eligible 167 patients. Symptomatic pericardial effusion was observed in 14 (8.4%) patients. Dosimetric analyses revealed average values of V30 to V45 for the pericardium and mean pericardial doses were significantly higher in patients with symptomatic pericardial effusion than in those with asymptomatic pericardial effusion (P<.05). Pericardial V5 to V55 and mean pericardial doses were significantly higher in patients with symptomatic pericardial effusion than in those without pericardial effusion (P<.001). Mean pericardial doses of 36.5 Gy and V45 of 58% were selected as optimal cutoff values for predicting symptomatic pericardial effusion. Multivariate analysis identified mean pericardial dose as the strongest risk factor for symptomatic pericardial effusion. Conclusions: Dose-volume thresholds for the pericardium facilitate predicting symptomatic pericardial effusion. Mean pericardial dose was selected based not only on the optimal dose-volume threshold but also on the most significant risk factor for symptomatic pericardial effusion.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

Peripheral Dose Heterogeneity Due to the Thread Effect in Total Marrow Irradiation With Helical Tomotherapy

Purpose: To report potential dose heterogeneity leading to underdosing at different skeletal sites in total marrow irradiation (TMI) with helical tomotherapy due to the thread effect and provide possible solutions to reduce this effect. Methods and Materials: Nine cases were divided into 2 groups based on patient size, defined as maximum left-to-right arm distance (mLRD): small mLRD (≤47 cm) and large mLRD (>47 cm). TMI treatment planning was conducted by varying the pitch and modulation factor while a jaw size (5 cm) was kept fixed. Ripple amplitude, defined as the peak-to-trough dose relative to the average dose due to the thread effect, and the dose–volume histogram (DVH) parameters for 9 cases with various mLRD was analyzed in different skeletal regions at off-axis (eg, bones of the arm or femur), at the central axis (eg, vertebrae), and planning target volume (PTV), defined as the entire skeleton plus 1-cm margin. Results: Average ripple amplitude for a pitch of 0.430, known as one of the magic pitches that reduce thread effect, was 9.2% at 20 cm off-axis. No significant differences in DVH parameters of PTV, vertebrae, or femur were observed between small and large mLRD groups for a pitch of ≤0.287. Conversely, in the bones of the arm, average differences in the volume receiving 95% and 107% dose (V95 and V107, respectively) between large and small mLRD groups were 4.2% (P=.016) and 16% (P=.016), respectively. Strong correlations were found between mLRD and ripple amplitude (rs=.965), mLRD and V95 (rs=−.742), and mLRD and V107 (rs=.870) of bones of the arm. Conclusions: Thread effect significantly influences DVH parameters in the bones of the arm for large mLRD patients. By implementing a favorable pitch value and adjusting arm position, peripheral dose heterogeneity could be reduced.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

Preliminary Toxicity Analysis of 3-Dimensional Conformal Radiation Therapy Versus Intensity Modulated Radiation Therapy on the High-Dose Arm of the Radiation Therapy Oncology Group 0126 Prostate Cancer Trial

Purpose: To give a preliminary report of clinical and treatment factors associated with toxicity in men receiving high-dose radiation therapy (RT) on a phase 3 dose-escalation trial. Methods and Materials: The trial was initiated with 3-dimensional conformal RT (3D-CRT) and amended after 1 year to allow intensity modulated RT (IMRT). Patients treated with 3D-CRT received 55.8 Gy to a planning target volume that included the prostate and seminal vesicles, then 23.4 Gy to prostate only. The IMRT patients were treated to the prostate and proximal seminal vesicles to 79.2 Gy. Common Toxicity Criteria, version 2.0, and Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late morbidity scores were used for acute and late effects. Results: Of 763 patients randomized to the 79.2-Gy arm of Radiation Therapy Oncology Group 0126 protocol, 748 were eligible and evaluable: 491 and 257 were treated with 3D-CRT and IMRT, respectively. For both bladder and rectum, the volumes receiving 65, 70, and 75 Gy were significantly lower with IMRT (all P<.0001). For grade (G) 2+ acute gastrointestinal/genitourinary (GI/GU) toxicity, both univariate and multivariate analyses showed a statistically significant decrease in G2+ acute collective GI/GU toxicity for IMRT. There were no significant differences with 3D-CRT or IMRT for acute or late G2+ or 3+ GU toxicities. Univariate analysis showed a statistically significant decrease in late G2+ GI toxicity for IMRT (P=.039). On multivariate analysis, IMRT showed a 26% reduction in G2+ late GI toxicity (P=.099). Acute G2+ toxicity was associated with late G3+ toxicity (P=.005). With dose–volume histogram data in the multivariate analysis, RT modality was not significant, whereas white race (P=.001) and rectal V70 ≥15% were associated with G2+ rectal toxicity (P=.034). Conclusions: Intensity modulated RT is associated with a significant reduction in acute G2+ GI/GU toxicity. There is a trend for a clinically meaningful reduction in late G2+ GI toxicity with IMRT. The occurrence of acute GI toxicity and large (>15%) volumes of rectum >70 Gy are associated with late rectal toxicity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

Implications of Intercellular Signaling for Radiation Therapy: A Theoretical Dose-Planning Study

Purpose: Recent in vitro results have shown significant contributions to cell killing from signaling effects at doses that are typically used in radiation therapy. This study investigates whether these in vitro observations can be reconciled with in vivo knowledge and how signaling may have an impact on future developments in radiation therapy. Methods and Materials: Prostate cancer treatment plans were generated for a series of 10 patients using 3-dimensional conformal therapy, intensity modulated radiation therapy (IMRT), and volumetric modulated arc therapy techniques. These plans were evaluated using mathematical models of survival following modulated radiation exposures that were developed from in vitro observations and incorporate the effects of intercellular signaling. The impact on dose–volume histograms and mean doses were evaluated by converting these survival levels into “signaling-adjusted doses” for comparison. Results: Inclusion of intercellular communication leads to significant differences between the signalling-adjusted and physical doses across a large volume. Organs in low-dose regions near target volumes see the largest increases, with mean signaling-adjusted bladder doses increasing from 23 to 33 Gy in IMRT plans. By contrast, in high-dose regions, there is a small decrease in signaling-adjusted dose due to reduced contributions from neighboring cells, with planning target volume mean doses falling from 74 to 71 Gy in IMRT. Overall, however, the dose distributions remain broadly similar, and comparisons between the treatment modalities are largely unchanged whether physical or signaling-adjusted dose is compared. Conclusions: Although incorporating cellular signaling significantly affects cell killing in low-dose regions and suggests a different interpretation for many phenomena, their effect in high-dose regions for typical planning techniques is comparatively small. This indicates that the significant signaling effects observed in vitro are not contradicted by comparison with clinical observations. Future investigations are needed to validate these effects in vivo and to quantify their ranges and potential impact on more advanced radiation therapy techniques.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

Intensity Modulated Proton Beam Radiation for Brachytherapy in Patients With Cervical Carcinoma

Purpose: To evaluate intensity modulated proton therapy (IMPT) in patients with cervical cancer in terms of coverage, conformity, and dose–volume histogram (DVH) parameters correlated with recommendations from magnetic resonance imaging (MRI)-guided brachytherapy. Methods and Materials: Eleven patients with histologically proven cervical cancer underwent primary chemoradiation for the pelvic lymph nodes, the uterus, the cervix, and the parametric region, with a symmetric margin of 1 cm. The prescription was for 50.4 Gy, with 1.8 Gy per fraction. The prescribed dose to the parametria was 2.12 Gy up to 59.36 Gy in 28 fractions as a simultaneous boost. For several reasons, the patients were unable to undergo brachytherapy. As an alternative, IMPT was planned with 5 fractions of 6 Gy to the cervix, including the macroscopic tumor with an MRI-guided target definition, with an isotropic margin of 5 mm for planning target volume (PTV) definition. Groupe-Europeen de Curietherapie and European society for Radiotherapy and Oncology (GEC-ESTRO) criteria were used for DVH evaluation. Reference comparison plans were optimized for volumetric modulated rapid arc (VMAT) therapy with the RapidArc (RA). Results: The dose to the high-risk volume was calculated with α/β = 10 with 89.6 Gy. For IMPT, the clinical target volume showed a mean dose of 38.2 ± 5.0 Gy (35.0 ±1.8 Gy for RA). The D{sub 98%} was 31.9 ± 2.6 Gy (RA: 30.8 ± 1.0 Gy). With regard to the organs at risk, the 2Gy Equivalent Dose (EQD2) (α/β = 3) to 2 cm{sup 3} of the rectal wall, sigmoid wall, and bladder wall was 62.2 ± 6.4 Gy, 57.8 ± 6.1 Gy, and 80.6 ± 8.7 Gy (for RA: 75.3 ± 6.1 Gy, 66.9 ± 6.9 Gy, and 89.0 ± 7.2 Gy, respectively). For the IMPT boost plans in combination with external beam radiation therapy, all DVH parameters correlated with <5% risk for grades 2 to 4 late gastrointestinal and genitourinary toxicity. Conclusion: In patients who are not eligible for brachytherapy, IMPT as a boost technique additionally to external beam radiation therapy provides good target coverage and conformity and superior DVH parameters, compared with recommendations to MRI-guided brachytherapy. For selected patients, IMPT might be a valid alternative to brachytherapy and also superior to reference VMAT plans.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

Dosimetric Implications of an Injection of Hyaluronic Acid for Preserving the Rectal Wall in Prostate Stereotactic Body Radiation Therapy

Purpose: This study assessed the contribution of ahyaluronic acid (HA) injection between the rectum and the prostate to reducing the dose to the rectal wall in stereotactic body radiation therapy (SBRT). Methods and Materials: As part of a phase 2 study of hypofractionated radiation therapy (62 Gy in 20 fractions), the patients received a transperineal injection of 10 cc HA between the rectum and the prostate. A dosimetric computed tomographic (CT) scan was systematically performed before (CT1) and after (CT2) the injection. Two 9-beam intensity modulated radiation therapy-SBRT plans were optimized for the first 10 patients on both CTs according to 2 dosage levels: 5 × 6.5 Gy (PlanA) and 5 × 8.5 Gy (PlanB). Rectal wall parameters were compared with a dose–volume histogram, and the prostate–rectum separation was measured at 7 levels of the prostate on the center line of the organ. Results: For both plans, the average volume of the rectal wall receiving the 90% isodose line (V90%) was reduced up to 90% after injection. There was no significant difference (P=.32) between doses received by the rectal wall on CT1 and CT2 at the base of the prostate. This variation became significant from the median plane to the apex of the prostate (P=.002). No significant differences were found between PlanA without HA and PlanB with HA for each level of the prostate (P=.77, at the isocenter of the prostate). Conclusions: HA injection significantly reduced the dose to the rectal wall and allowed a dose escalation from 6.5 Gy to 8.5 Gy without increasing the dose to the rectum. A phase 2 study is under way in our department to assess the rate of acute and late rectal toxicities when SBRT (5 × 8.5 Gy) is combined with an injection of HA.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

Impact of Dose to the Bladder Trigone on Long-Term Urinary Function After High-Dose Intensity Modulated Radiation Therapy for Localized Prostate Cancer

Purpose: To determine the potential association between genitourinary (GU) toxicity and planning dose–volume parameters for GU pelvic structures after high-dose intensity modulated radiation therapy in localized prostate cancer patients. Methods and Materials: A total of 268 patients who underwent intensity modulated radiation therapy to a prescribed dose of 86.4 Gy in 48 fractions during June 2004-December 2008 were evaluated with the International Prostate Symptom Score (IPSS) questionnaire. Dose–volume histograms of the whole bladder, bladder wall, urethra, and bladder trigone were analyzed. The primary endpoint for GU toxicity was an IPSS sum increase ≥10 points over baseline. Univariate and multivariate analyses were done by the Kaplan-Meier method and Cox proportional hazard models, respectively. Results: Median follow-up was 5 years (range, 3-7.7 years). Thirty-nine patients experienced an IPSS sum increase ≥10 during follow-up; 84% remained event free at 5 years. After univariate analysis, lower baseline IPSS sum (P=.006), the V90 of the trigone (P=.006), and the maximal dose to the trigone (P=.003) were significantly associated with an IPSS sum increase ≥10. After multivariate analysis, lower baseline IPSS sum (P=.009) and increased maximal dose to the trigone (P=.005) remained significantly associated. Seventy-two patients had both a lower baseline IPSS sum and a higher maximal dose to the trigone and were defined as high risk, and 68 patients had both a higher baseline IPSS sum and a lower maximal dose to the trigone and were defined as low risk for development of an IPSS sum increase ≥10. Twenty-one of 72 high-risk patients (29%) and 5 of 68 low-risk patients (7%) experienced an IPSS sum increase ≥10 (P=.001; odds ratio 5.19). Conclusions: The application of hot spots to the bladder trigone was significantly associated with relevant changes in IPSS during follow-up. Reduction of radiation dose to the lower bladder and specifically the bladder trigone seems to be associated with a reduction in late GU toxicity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

Threshold Doses for Focal Liver Reaction After Stereotactic Ablative Body Radiation Therapy for Small Hepatocellular Carcinoma Depend on Liver Function: Evaluation on Magnetic Resonance Imaging With Gd-EOB-DTPA

Purpose: Focal liver reaction (FLR) appears on radiographic images after stereotactic ablative body radiation therapy (SABR) in patients with hepatocellular carcinoma (HCC) and chronic liver disease. We investigated the threshold dose (TD) of FLR and possible factors affecting the TD on gadoxetate acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI). Methods and Materials: In 50 patients who were treated with SABR for small HCC and followed up by MRI for >6 months, FLR, seen as a hypointense area, was evaluated on the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI. The follow-up MRI with the largest extent of FLR was fused to the planning computed tomography (CT) image, and patients with good image fusion concordance were eligible. After delineating the border of the FLR manually, a dose–volume histogram was used to identify the TD for the FLR. Clinical and volumetric factors were analyzed for correlation with the TD. Results: A total of 45 patients were eligible for analysis with a median image fusion concordance of 84.9% (range, 71.6-95.4%). The median duration between SABR and subsequent hepatobiliary phase MRI with the largest extent of FLR was 3 months (range, 1-6 months). The median TD for FLR was 28.0 Gy (range, 22.3-36.4 Gy). On univariate analysis, pre-treatment Child-Pugh (CP) score and platelet count were significantly correlated with the TD. On multiple linear regression analysis, CP score was the only parameter that predicted TD. Median TDs were 30.5 Gy (range, 26.2.3-36.4 Gy) and 25.2 Gy (range, 22.3-27.5 Gy) for patients with CP-A and CP-B disease, respectively. Conclusion: The TD was significantly correlated with baseline liver function. We propose 30 Gy for CP-A disease and 25 Gy for CP-B disease in 5 fractions as TDs for FLR after SABR for patients with HCC and chronic liver disease. Use of these TDs will help to predict potential loss of liver tissue after SABR.

62 RADIOLOGY AND NUCLEAR MEDICINE↗