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At least 523 records · Page 29
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Vibrational Studies of Saccharide-Induced Lipid Film Reorganization at Aqueous/Air Interfaces

Vibrational sum frequency generation (VSFG) and surface tension experiments were used to examine the effects of aqueous phase soluble saccharides on the structure and organization of insoluble lipid monolayers adsorbed to aqueous-air interfaces. Changes in dipalmitoylphosphocholine (DPPC) chain structure as a function of aqueous phase saccharide concentration and pH are reported. Complementary differential scanning calorimetry (DSC) measurements performed on solutions containing soluble saccharides and DPPC vesicles measured the effects of the saccharides on the lipid membrane phase behavior. Here, data show that the saccharides glucosamine and glucuronic acid induce a higher degree of organization in compressed DPPC monolayers regardless of the saccharide’s charge.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2015

Evaluation of the effect of divalent metal transporter 1 gene polymorphism on blood iron, lead and cadmium levels

Divalent metal transporter 1 (DMT1), a member of the proton-coupled metal ion transporter family, mediates transport of ferrous iron from the lumen of the intestine into the enterocyte and export of iron from endocytic vesicles. It has an affinity not only for iron but also for other divalent cations including manganese, cobalt, nickel, cadmium, lead, copper, and zinc. DMT1 is encoded by the SLC11a2 gene that is located on chromosome 12q13 in humans and express four major mammalian isoforms (1A/+IRE, 1A/-IRE, 2/+IRE and 2/-IRE). Mutations or polymorphisms of DMT1 gene may have an impact on human health by disturbing metal trafficking. To study the possible association of DMT1 gene with the blood levels of some divalent cations such as iron, lead and cadmium, a single nucleotide polymorphism (SNP) (IVS4+44C/A) in DMT1 gene was investigated in 486 unrelated and healthy individuals in a Turkish population by method of polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). The genotype frequencies were found as 49.8% homozygote typical (CC), 38.3% heterozygote (CA) and 11.9% homozygote atypical (AA). Metal levels were analyzed by dual atomic absorption spectrometer system and the average levels of iron, lead and cadmium in the blood samples were 446.01±81.87 ppm, 35.59±17.72 ppb and 1.25±0.87 ppb, respectively. Individuals with the CC genotype had higher blood iron, lead and cadmium levels than those with AA and CA genotypes. Highly statistically significant associations were detected between IVS4+44 C/A polymorphism in the DMT1 gene and iron and lead levels (p=0.001 and p=0.036, respectively), but no association was found with cadmium level (p=0.344). This study suggested that DMT1 IVS4+44 C/A polymorphism is associated with inter-individual variations in blood iron, lead and cadmium levels. - Highlights: • DMT1 IVS4+44 C/A polymorphism is associated with inter-individual variations in blood iron, cadmium and lead levels. • Individuals with the DMT1 IVS4+44 CC genotype had higher blood iron, lead and cadmium levels. • Individuals with DMT1 IVS4+44 CC genotype may be more susceptible for metal toxicity.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Cerium dioxide (CeO2) nanoparticles decrease arsenite (As(III)) cytotoxicity to 16HBE14o- human bronchial epithelial cells

Highlights: • CeO{sub 2} NPs display a high adsorption capacity for As(III). • As(III) is highly toxic to lung 16HBE14o- cells (81% inhibition at 0.5 mg As/L). • As(III) adsorption onto CeO{sub 2} NPs decreased As(III) cytotoxicity on 16HBE14o- cells. • Cell uptake of As(III)-loaded CeO{sub 2} NPs did not lead to enhanced cytotoxicity. The production and application of engineered nanoparticles (NPs) are increasing in demand with the rapid development of nanotechnology. However, there are concerns that some of these novel materials could lead to emerging environmental and health problems. Some NPs are able to facilitate the transport of contaminants into cells/organisms via a “Trojan Horse” effect which enhances the toxicity of the adsorbed materials. In this work, we evaluated the toxicity of arsenite (As(III)) adsorbed onto cerium dioxide (CeO{sub 2}) NPs to human bronchial epithelial cells (16HBE14o-) using the xCELLigence real time cell analyzing system (RTCA). Application of 0.5 mg/L As(III) resulted in 81.3% reduction of cell index (CI, an RTCA measure of cell toxicity) over 48 h when compared to control cells exposed to medium lacking As(III). However, when the cells were exposed to 0.5 mg/L As(III) in the presence of CeO{sub 2} NPs (250 mg/L), the CI was only reduced by 12.9% compared to the control. The CeO{sub 2} NPs had a high capacity for As(III) adsorption (20.2 mg/g CeO{sub 2}) in the bioassay medium, effectively reducing dissolved As(III) in the aqueous solution and resulting in reduced toxicity. Transmission electron microscopy was used to study the transport of CeO{sub 2} NPs into 16HBE14o- cells. NP uptake via engulfment was observed and the internalized NPs accumulated in vesicles. The results demonstrate that dissolved As(III) in the aqueous solution was the decisive factor controlling As(III) toxicity of 16HBE14o- cells, and that CeO{sub 2} NPs effectively reduced available As(III) through adsorption. These data emphasize the evaluation of mixtures when assaying toxicity.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2014

A Prospective Quasi-Randomized Comparison of Intraoperatively Built Custom-Linked Seeds Versus Loose Seeds for Prostate Brachytherapy

Purpose: To compare dosimetric parameters, seed migration rates, operation times, and acute toxicities of intraoperatively built custom-linked (IBCL) seeds with those of loose seeds for prostate brachytherapy. Methods and Materials: Participants were 140 patients with low or intermediate prostate cancer prospectively allocated to an IBCL seed group (n=74) or a loose seed group (n=66), using quasirandomization (allocated by week of the month). All patients underwent prostate brachytherapy using an interactive plan technique. Computed tomography and plain radiography were performed the next day and 1 month after brachytherapy. The primary endpoint was detection of a 5% difference in dose to 90% of prostate volume on postimplant computed tomography 1 month after treatment. Seed migration was defined as a seed position >1 cm from the cluster of other seeds on radiography. A seed dropped into the seminal vesicle was also defined as a migrated seed. Results: Dosimetric parameters including the primary endpoint did not differ significantly between groups, but seed migration rate was significantly lower in the IBCL seed group (0%) than in the loose seed group (55%; P<.001). Mean operation time was slightly but significantly longer in the IBCL seed group (57 min) than in the loose seed group (50 min; P<.001). No significant differences in acute toxicities were seen between groups (median follow-up, 9 months). Conclusions: This prospective quasirandomized control trial showed no dosimetric differences between IBCL seed and loose seed groups. However, a strong trend toward decreased postimplant seed migration was shown in the IBCL seed group.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Evaluation of Online/Offline Image Guidance/Adaptation Approaches for Prostate Cancer Radiation Therapy

Purpose: To evaluate online/offline image-guided/adaptive treatment techniques for prostate cancer radiation therapy with daily cone-beam CT (CBCT) imaging. Methods and Materials: Three treatment techniques were evaluated retrospectively using daily pre- and posttreatment CBCT images on 22 prostate cancer patients. Prostate, seminal vesicles (SV), rectal wall, and bladder were delineated on all CBCT images. For each patient, a pretreatment intensity modulated radiation therapy plan with clinical target volume (CTV) = prostate + SV and planning target volume (PTV) = CTV + 3 mm was created. The 3 treatment techniques were as follows: (1) Daily Correction: The pretreatment intensity modulated radiation therapy plan was delivered after online CBCT imaging, and position correction; (2) Online Planning: Daily online inverse plans with 3-mm CTV-to-PTV margin were created using online CBCT images, and delivered; and (3) Hybrid Adaption: Daily Correction plus an offline adaptive inverse planning performed after the first week of treatment. The adaptive plan was delivered for all remaining 15 fractions. Treatment dose for each technique was constructed using the daily posttreatment CBCT images via deformable image registration. Evaluation was performed using treatment dose distribution in target and critical organs. Results: Treatment equivalent uniform dose (EUD) for the CTV was within [85.6%, 100.8%] of the pretreatment planned target EUD for Daily Correction; [98.7%, 103.0%] for Online Planning; and [99.2%, 103.4%] for Hybrid Adaptation. Eighteen percent of the 22 patients in Daily Correction had a target dose deficiency >5%. For rectal wall, the mean ± SD of the normalized EUD was 102.6% ± 2.7% for Daily Correction, 99.9% ± 2.5% for Online Planning, and 100.6% ± 2.1% for Hybrid Adaptation. The mean ± SD of the normalized bladder EUD was 108.7% ± 8.2% for Daily Correction, 92.7% ± 8.6% for Online Planning, and 89.4% ± 10.8% for Hybrid Adaptation. Conclusions: Both Online Planning and Hybrid Adaptation can achieve comparable target coverage and normal tissue sparing and are superior to the Daily Correction technique. The Daily Correction technique using a 3-mm target margin in the pretreatment plan is not appropriate to compensate for residual variations in CBCT image-guided prostate cancer radiation therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Nodal Clearance Rate and Long-Term Efficacy of Individualized Sentinel Node–Based Pelvic Intensity Modulated Radiation Therapy for High-Risk Prostate Cancer

Purpose: To assess the efficacy of individual sentinel node (SN)-guided pelvic intensity modulated radiation therapy (IMRT) by determining nodal clearance rate [(n expected nodal involvement − n observed regional recurrences)/n expected nodal involvement] in comparison with surgically staged patients. Methods and Materials: Data on 475 high-risk prostate cancer patients were examined. Sixty-one consecutive patients received pelvic SN-based IMRT (5 × 1.8 Gy/wk to 50.4 Gy [pelvic nodes + individual SN] and an integrated boost with 5 × 2.0 Gy/wk to 70.0 Gy to prostate + [base of] seminal vesicles) and neo-/adjuvant long-term androgen deprivation therapy; 414 patients after SN–pelvic lymph node dissection were used to calculate the expected nodal involvement rate for the radiation therapy sample. Biochemical control and overall survival were estimated for the SN-IMRT patients using the Kaplan-Meier method. The expected frequency of nodal involvement in the radiation therapy group was estimated by imputing frequencies of node-positive patients in the surgical sample to the pattern of Gleason, prostate-specific antigen, and T category in the radiation therapy sample. Results: After a median follow-up of 61 months, 5-year OS after SN-guided IMRT reached 84.4%. Biochemical control according to the Phoenix definition was 73.8%. The nodal clearance rate of SN-IMRT reached 94%. Retrospective follow-up evaluation is the main limitation. Conclusions: Radiation treatment of pelvic nodes individualized by inclusion of SNs is an effective regional treatment modality in high-risk prostate cancer patients. The pattern of relapse indicates that the SN-based target volume concept correctly covers individual pelvic nodes. Thus, this SN-based approach justifies further evaluation, including current dose-escalation strategies to the prostate in a larger prospective series.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Moderate Hypofractionated Protracted Radiation Therapy and Dose Escalation for Prostate Cancer: Do Dose and Overall Treatment Time Matter?

Purpose: This was a retrospective study of 2 sequential dose escalation regimens of twice-weekly 4 Gy/fractions hypofractionated intensity modulated radiation therapy (IMRT): 56 Gy and 60 Gy delivered within a protracted overall treatment time (OTT) of 6.5 and 7 weeks, respectively. Methods and Materials: 163 prostate cancer patients with cT1c-T3a disease and nodal involvement risk ≤20% (Roach index) were treated twice weekly to the prostate ± seminal vesicles with 2 sequential dose-escalated IMRT schedules: 56 Gy (14 × 4 Gy, n=81) from 2003 to 2007 and 60 Gy (15 × 4 Gy, n=82) from 2006 to 2010. Patient repositioning was made with bone matching on portal images. Gastrointestinal (GI) and genitourinary (GU) toxicities were scored according to the Common Terminology Criteria for Adverse Events version 3.0 grading scale. Results: There were no significant differences regarding the acute GU and GI toxicities in the 2 dose groups. The median follow-up times were 80.2 months (range, 4.5-121 months) and 56.5 months (range, 1.4-91.2 months) for patients treated to 56 and 60 Gy, respectively. The 5-year grade ≥2 late GU toxicity-free survivals with 56 Gy and 60 Gy were 96 ± 2.3% and 78.2 ± 5.1% (P=.001), respectively. The 5-year grade ≥2 late GI toxicity-free survivals with 56 Gy and 60 Gy were 98.6 ± 1.3% and 85.1 ± 4.5% (P=.005), respectively. Patients treated with 56 Gy showed a 5-year biochemical progression-free survival (bPFS) of 80.8 ± 4.7%, worse than patients treated with 60 Gy (93.2 ± 3.9%, P=.007). A trend for a better 5-year distant metastasis-free survival was observed among patients treated in the high-dose group (95.3 ± 2.7% vs 100%, P=.073, respectively). On multivariate analysis, only the 60-Gy group predicted for a better bPFS (P=.016, hazard ratio = 4.58). Conclusions: A single 4-Gy additional fraction in patients treated with a hypofractionated protracted IMRT schedule of 14 × 4 Gy resulted in a similar and minimal acute toxicity, in worse moderate to severe urinary and GI late effects, but a significantly better biochemical control.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Predictive Parameters of Symptomatic Hematochezia Following 5-Fraction Gantry-Based SABR in Prostate Cancer

Purpose: This study identified predictors of high-grade late hematochezia (HH) following 5-fraction gantry-based stereotactic ablative radiation therapy (SABR). Methods and Materials: Hematochezia data for 258 patients who received 35 to 40 Gy SABR in 5-fractions as part of sequential phase 2 prospective trials was retrieved. Grade 2 or higher late rectal bleeding was labeled HH. Hematochezia needing steroid suppositories, 4% formalin, or 1 to 2 sessions of argon plasma coagulation (APC) was labeled grade 2. More than 2 sessions of APC, blood transfusion, or a course of hyperbaric oxygen was grade 3 and development of visceral fistula, grade 4. Various dosimetric and clinical factors were analyzed using univariate and multivariate analyses. Receiver operating characteristic (ROC) curve analysis and recursive partitioning analysis were used to determine clinically valid cut-off points and identify risk groups, respectively. Results: HH was observed in 19.4%, grade ≥3 toxicity in 3.1%. Median follow-up was 29.7 months (interquartile range [IQR]: 20.6-61.7) Median time to develop HH was 11.7 months (IQR: 9.0-15.2) from the start of radiation. At 2 years, cumulative HH was 4.9%, 27.2%, and 42.1% in patients who received 35 Gy to prostate (4-mm planning target volume [PTV] margin), 40 Gy to prostate (5-mm PTV margin), and 40 Gy to prostate/seminal vesicles (5-mm PTV margin), respectively (P<.0001). In the ROC analysis, volume of rectum receiving radiation dose of 38 Gy (V38) was a strong predictor of HH with an area under the curve of 0.65. In multivariate analysis, rectal V38 (≥2.0 cm{sup 3}; odds ratio [OR]: 4.7); use of anticoagulants in the follow-up period (OR: 6.5) and presence of hemorrhoids (OR: 2.7) were the strongest predictors. Recursive partitioning analysis showed rectal V38 < 2.0 cm{sup 3}, and use of anticoagulants or rectal V38 ≥ 2.0 cm{sup 3} plus 1 other risk factor resulted in an HH risk of >30%. Conclusions: Rectal V38 and 2 clinical factors were strong predictors of HH following 5-fraction SABR. Planning constraints should keep rectal V38 below 2.0 cm{sup 3}.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

A Prospective Comparison of the Effects of Interfractional Variations on Proton Therapy and Intensity Modulated Radiation Therapy for Prostate Cancer

Purpose: To quantify and compare the impact of interfractional setup and anatomic variations on proton therapy (PT) and intensity modulated radiation therapy (IMRT) for prostate cancer. Methods and Materials: Twenty patients with low-risk or intermediate-risk prostate cancer randomized to receive passive-scattering PT (n=10) and IMRT (n=10) were selected. For both modalities, clinical treatment plans included 50.4 Gy(RBE) to prostate and proximal seminal vesicles, and prostate-only boost to 79.2 Gy(RBE) in 1.8 Gy(RBE) per fraction. Implanted fiducials were used for prostate localization and endorectal balloons were used for immobilization. Patients in PT and IMRT arms received weekly computed tomography (CT) and cone beam CT (CBCT) scans, respectively. The planned dose was recalculated on each weekly image, scaled, and mapped onto the planning CT using deformable registration. The resulting accumulated dose distribution over the entire treatment course was compared with the planned dose using dose-volume histogram (DVH) and γ analysis. Results: The target conformity index remained acceptable after accumulation. The largest decrease in the average prostate D{sub 98} was 2.2 and 0.7 Gy for PT and IMRT, respectively. On average, the mean dose to bladder increased by 3.26 ± 7.51 Gy and 1.97 ± 6.84 Gy for PT and IMRT, respectively. These values were 0.74 ± 2.37 and 0.56 ± 1.90 for rectum. Differences between changes in DVH indices were not statistically significant between modalities. All volume indices remained within the protocol tolerances after accumulation. The average pass rate for the γ analysis, assuming tolerances of 3 mm and 3%, for clinical target volume, bladder, rectum, and whole patient for PT/IMRT were 100/100, 92.6/99, 99.2/100, and 97.2/99.4, respectively. Conclusion: The differences in target coverage and organs at risk dose deviations for PT and IMRT were not statistically significant under the guidelines of this protocol.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Dose-Escalated Stereotactic Body Radiation Therapy for Patients With Intermediate- and High-Risk Prostate Cancer: Initial Dosimetry Analysis and Patient Outcomes

Purpose: To report the short-term clinical outcomes and acute and late treatment-related genitourinary (GU) and gastrointestinal (GI) toxicities in patients with intermediate- and high-risk prostate cancer treated with dose-escalated stereotactic body radiation therapy (SBRT). Methods and Materials: Between 2011 and 2014, 24 patients with prostate cancer were treated with SBRT to the prostate gland and proximal seminal vesicles. A high-dose avoidance zone (HDAZ) was created by a 3-mm expansion around the rectum, urethra, and bladder. Patients were treated to a minimum dose of 36.25 Gy in 5 fractions, with a simultaneous dose escalation to a dose of 50 Gy to the target volume away from the HDAZ. Acute and late GU and GI toxicity outcomes were measured according to the National Cancer Institute Common Terminology Criteria for Adverse Events toxicity scale, version 4. Results: The median follow-up was 25 months (range, 18-45 months). Nine patients (38%) experienced an acute grade 2 GU toxicity, which was medically managed, and no patients experienced an acute grade 2 GI toxicity. Two patients (8%) experienced late grade 2 GU toxicity, and 2 patients (8%) experienced late grade 2 GI toxicity. No acute or late grade ≥3 GU or GI toxicities were observed. The 24-month prostate-specific antigen relapse-free survival outcome for all patients was 95.8% (95% confidence interval 75.6%-99.4%), and both biochemical failures occurred in patients with high-risk disease. All patients are currently alive at the time of this analysis and continue to be followed. Conclusions: A heterogeneous prostate SBRT planning technique with differential treatment volumes (low dose: 36.25 Gy; and high dose: 50 Gy) with an HDAZ provides a safe method of dose escalation. Favorable rates of biochemical control and acceptably low rates of acute and long-term GU and GI toxicity can be achieved in patients with intermediate- and high-risk prostate cancer treated with SBRT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Image Guided Planning for Prostate Carcinomas With Incorporation of Anti-3-[18F]FACBC (Fluciclovine) Positron Emission Tomography: Workflow and Initial Findings From a Randomized Trial

Purpose: {sup 18}F-Fluciclovine (anti-1-amino-3-[{sup 18}F]fluorocyclobutane-1-carboxylic acid) is a novel positron emission tomography (PET)/computed tomography (CT) radiotracer that has demonstrated utility for detection of prostate cancer. Our goal is to report the initial results from a randomized controlled trial of the integration of {sup 18}F-fluciclovine PET-CT into treatment planning for defining prostate bed and lymph node target volumes. Methods and Materials: We report our initial findings from a cohort of 41 patients, of the first enrolled on a randomized controlled trial, who were randomized to the {sup 18}F-fluciclovine arm. All patients underwent {sup 18}F-fluciclovine PET-CT for the detection of metabolic abnormalities and high-resolution CT for treatment planning. The 2 datasets were registered first by use of a rigid registration. If soft tissue displacement was observable, the rigid registration was improved with a deformable registration. Each {sup 18}F-fluciclovine abnormality was segmented as a percentage of the maximum standard uptake value (SUV) within a small region of interest around the lesion. The percentage best describing the SUV falloff was integrated in planning by expanding standard target volumes with the PET abnormality. Results: In 21 of 55 abnormalities, a deformable registration was needed to map the {sup 18}F-fluciclovine activity into the simulation CT. The most selected percentage was 50% of maximum SUV, although values ranging from 15% to 70% were used for specific patients, illustrating the need for a per-patient selection of a threshold SUV value. The inclusion of {sup 18}F-fluciclovine changed the planning volumes for 46 abnormalities (83%) of the total 55, with 28 (51%) located in the lymph nodes, 11 (20%) in the prostate bed, 10 (18%) in the prostate, and 6 (11%) in the seminal vesicles. Only 9 PET abnormalities were fully contained in the standard target volumes based on the CT-based segmentations and did not necessitate expansion. Conclusions: The use of {sup 18}F-fluciclovine in postprostatectomy radiation therapy planning was feasible and led to augmentation of the target volumes in the majority (30 of 41) of the patients studied.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Macroscopic Hematuria After Conventional or Hypofractionated Radiation Therapy: Results From a Prospective Phase 3 Study

Purpose: To assess the macroscopic hematuria rates within a single-institution randomized phase 3 trial comparing dose-escalated, conventionally fractionated radiation therapy (CFRT) and moderately hypofractionated radiation therapy (MHRT) for localized prostate cancer. Methods and Materials: Patients with intermediate- to high-risk localized prostate cancer were treated with conformal RT and short-course androgen deprivation. Both the prostate and the entire seminal vesicles were treated to 80 Gy in 40 fractions over 8 weeks (CFRT) or 62 Gy in 20 fractions over 5 weeks (MHRT). The endpoint of the present study was the development of any episode or grade of macroscopic hematuria. The median follow-up period was 93 months (range 6-143). Results: Macroscopic hematuria was reported by 25 of 168 patients (14.9%). The actuarial estimate of hematuria at 8 years was 17.0% (95% confidence interval [CI] 10.7%-23.3%). The number of patients with hematuria was 6 and 19 in the CFRT and MHRT arms, respectively, for an actuarial 8-year estimate of 9.7% and 24.3%, respectively (hazard ratio 3.468, 95% CI 1.385-8.684; P=.008). Overall, 8 of 25 patients were found to have biopsy-proven urothelial carcinoma (3 in the CFRT arm and 5 in the MHRT arm; P=.27). Thus, the 8-year actuarial incidence of macroscopic hematuria (after censoring urothelial cancer–related episodes) was 4.1% and 18.2% after CFRT and MHRT, respectively (hazard ratio 4.961, 95% CI 1.426-17.263; P=.012). The results were confirmed by multivariate analysis after accounting for several patient-, treatment-, and tumor-related covariates. Conclusions: MHRT was associated with a statistically significant increased risk of macroscopic hematuria compared with CFRT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Salvage Radiation Therapy Dose Response for Biochemical Failure of Prostate Cancer After Prostatectomy—A Multi-Institutional Observational Study

Purpose: To determine whether a dose-response relationship exists for salvage radiation therapy (RT) of biochemical failure after prostatectomy for prostate cancer. Methods and Materials: Individual data from 1108 patients who underwent salvage RT at 10 academic centers were pooled. The cohort was enriched for selection criteria more likely associated with tumor recurrence in the prostate bed (margin positive and pre-RT prostate-specific antigen [PSA] level of ≤2.0 ng/mL) and without the confounding of planned androgen suppression. The cumulative incidence of biochemical failure and distant metastasis over time was computed, and competing risks hazard regression models were used to investigate the association between potential predictors and these outcomes. The association of radiation dose with outcomes was the primary focus. Results: With a 65.2-month follow-up duration, the 5- and 10-year estimates of freedom from post-RT biochemical failure (PSA level >0.2 ng/mL and rising) was 63.5% and 49.8%, respectively, and the cumulative incidence of distant metastasis was 12.4% by 10 years. A Gleason score of ≥7, higher pre-RT PSA level, extraprostatic tumor extension, and seminal vesicle invasion were associated with worse biochemical failure and distant metastasis outcomes. A salvage radiation dose of ≥66.0 Gy was associated with a reduced cumulative incidence of biochemical failure, but not of distant metastasis. Conclusions: The use of salvage radiation doses of ≥66.0 Gy are supported by evidence presented in the present multicenter pooled analysis of individual patient data. The observational reporting method, limited sample size, few distant metastasis events, modest follow-up duration, and elective use of salvage therapy might have diminished the opportunity to identify an association between the radiation dose and this endpoint.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

Continued Benefit to Rectal Separation for Prostate Radiation Therapy: Final Results of a Phase III Trial

Purpose: SpaceOAR, a Food and Drug Administration–approved hydrogel intended to create a rectal–prostate space, was evaluated in a single-blind phase III trial of image guided intensity modulated radiation therapy. A total of 222 men were randomized 2:1 to the spacer or control group and received 79.2 Gy in 1.8-Gy fractions to the prostate with or without the seminal vesicles. The present study reports the final results with a median follow-up period of 3 years. Methods and Materials: Cumulative (Common Terminology Criteria for Adverse Events, version 4.0) toxicity was evaluated using the log-rank test. Quality of life (QOL) was examined using the Expanded Prostate Cancer Index Composite (EPIC), and the mean changes from baseline in the EPIC domains were tested using repeated measures models. The proportions of men with minimally important differences (MIDs) in each domain were tested using repeated measures logistic models with prespecified thresholds. Results: The 3-year incidence of grade ≥1 (9.2% vs 2.0%; P=.028) and grade ≥2 (5.7% vs 0%; P=.012) rectal toxicity favored the spacer arm. Grade ≥1 urinary incontinence was also lower in the spacer arm (15% vs 4%; P=.046), with no difference in grade ≥2 urinary toxicity (7% vs 7%; P=0.7). From 6 months onward, bowel QOL consistently favored the spacer group (P=.002), with the difference at 3 years (5.8 points; P<.05) meeting the threshold for a MID. The control group had a 3.9-point greater decline in urinary QOL compared with the spacer group at 3 years (P<.05), but the difference did not meet the MID threshold. At 3 years, more men in the control group than in the spacer group had experienced a MID decline in bowel QOL (41% vs 14%; P=.002) and urinary QOL (30% vs 17%; P=.04). Furthermore, the control group were also more likely to have experienced large declines (twice the MID) in bowel QOL (21% vs 5%; P=.02) and urinary QOL (23% vs 8%; P=.02). Conclusions: The benefit of a hydrogel spacer in reducing the rectal dose, toxicity, and QOL declines after image guided intensity modulated radiation therapy for prostate cancer was maintained or increased with a longer follow-up period, providing stronger evidence for the benefit of hydrogel spacer use in prostate radiation therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

Exosomes and Exosomal MicroRNAs in Prostate Cancer Radiation Therapy

Despite current risk stratification systems using traditional clinicopathologic factors, many localized and locally advanced prostate cancers fail radical treatment (ie, radical prostatectomy, radiation therapy with or without androgen deprivation therapy). Therefore, a pressing need exists for enhanced methods of disease stratification through novel prognostic and predictive tools that can reliably be applied in clinical practice. Exosomes are 50- to 150-nm small vesicles released by cancer cells that reflect the genetic and nongenetic materials of parent cancer cells. Cancer cells can contain distinct sets of microRNA profiles, the expression of which can change owing to stress such as radiation therapy. These alterations or distinctions in contents allow exosomes to be used as prognostic and/or predictive biomarkers and to monitor the treatment response. Additionally, microRNAs have been shown to influence multiple processes in prostate tumorigenesis, including cell proliferation, induction of apoptosis, migration, oncogene inhibition, and radioresistance. Thus, comparative exosomal microRNA profiling at different levels could help portray tumor aggressiveness and response to radiation therapy. Although technical challenges persist in exosome isolation and characterization, recent improvements in microRNA profiling have evolved toward in-depth analyses of the exosomal cargo and its functions. We have reviewed the role of exosomes and exosomal microRNAs in biologic processes of prostate cancer progression and radiation therapy response, with a particular focus on the development of clinical assays for treatment personalization.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Smoothed dissipative particle dynamics with angular momentum conservation

Smoothed dissipative particle dynamics (SDPD) combines two popular mesoscopic techniques, the smoothed particle hydrodynamics and dissipative particle dynamics (DPD) methods, and can be considered as an improved dissipative particle dynamics approach. Despite several advantages of the SDPD method over the conventional DPD model, the original formulation of SDPD by Español and Revenga (2003) [9], lacks angular momentum conservation, leading to unphysical results for problems where the conservation of angular momentum is essential. To overcome this limitation, we extend the SDPD method by introducing a particle spin variable such that local and global angular momentum conservation is restored. The new SDPD formulation (SDPD+a) is directly derived from the Navier–Stokes equation for fluids with spin, while thermal fluctuations are incorporated similarly to the DPD method. We test the new SDPD method and demonstrate that it properly reproduces fluid transport coefficients. Also, SDPD with angular momentum conservation is validated using two problems: (i) the Taylor–Couette flow with two immiscible fluids and (ii) a tank-treading vesicle in shear flow with a viscosity contrast between inner and outer fluids. For both problems, the new SDPD method leads to simulation predictions in agreement with the corresponding analytical theories, while the original SDPD method fails to capture properly physical characteristics of the systems due to violation of angular momentum conservation. In conclusion, the extended SDPD method with angular momentum conservation provides a new approach to tackle fluid problems such as multiphase flows and vesicle/cell suspensions, where the conservation of angular momentum is essential.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗