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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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All sourcesNASA NTRSDOE OSTI
DOE OSTI2015

Impact on Patient Safety and Satisfaction of Implementation of an Outpatient Clinic in Interventional Radiology (IPSIPOLI-Study): A Quasi-Experimental Prospective Study

PurposeInterventional radiology (IR) procedures are associated with high rates of preparation and planning errors. In many centers, pre-procedural consultation and screening of patients is performed by referring physicians. Interventional radiologists have better knowledge about procedure details and risks, but often only get acquainted with the patient in the procedure room. We hypothesized that patient safety (PS) and patient satisfaction (PSAT) in elective IR procedures would improve by implementation of a pre-procedural visit to an outpatient IR clinic.Material and MethodsIRB approval was obtained and informed consent was waived. PS and PSAT were measured in patients undergoing elective IR procedures before (control group; n = 110) and after (experimental group; n = 110) implementation of an outpatient IR clinic. PS was measured as the number of process deviations. PSAT was assessed using a questionnaire measuring Likert scores of three dimensions: interpersonal care aspects, information/communication, and patient participation. Differences in PS and PSAT between the two groups were compared using an independent t test.ResultsThe average number of process deviations per patient was 0.39 in the control group compared to 0.06 in the experimental group (p < 0.001). In 9.1 % patients in the control group, no legal informed consent was obtained compared to 0 % in the experimental group. The mean overall Likert score was significantly higher in the experimental group compared to the control group: 2.68 (SD 0.314) versus 2.48 (SD 0.381) (p < 0.001).ConclusionPS and PSAT improve significantly if patients receive consultation and screening in an IR outpatient clinic prior to elective IR procedures.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2022

The association between vaginal microbiota disorders and early missed abortion: A prospective study

Abstract Introduction The objective of this study was to explore the association between disordered vaginal microbiota and missed abortion to ascertain potential causes of missed abortion related to vaginal microbiology. Material and methods This study was a prospective cohort study with a comparison group (reference group). Vaginal secretions from the posterior fornix of women in the early stages of pregnancy were collected in the Xiangya Third Hospital of Central South University in Changsha, Hunan, China, from November 2018 to November 2019. A total of 54 cases of missed abortion (case group) and 50 cases of normal pregnancy requiring induced abortion (reference group) were analyzed. Bacterial DNA was extracted, hybridized with gene‐specific primers, and then detected using a bacterial chip. The composition and relative abundance of vaginal microbiota in the two groups were compared using α‐diversity analysis, β‐diversity analysis, and the linear discriminant analysis effect size method. Results The α‐diversity analysis showed that the Simpson index of the case group was lower than that of the reference group, whereas the Shannon index in the case group was higher. The relative abundance of Firmicutes in the case group (42.52%) was lower than in the reference group (51.03%, p < 0.05), as was the relative abundance of Lactobacillus (case group 16.51%, reference group 23.00%; p < 0.05). Interestingly, levels of Mycoplasma genitalium and Ureaplasma were lower in the case group ( p < 0.05). The relative abundance of Lactobacillus crispatus , Lactobacillus jensenii , and Lactobacillus gasseri was also significantly lower in the case group than in the reference group ( p < 0.05). The pathways enriched in the case group were predominantly related to metabolism, whereas the genetics‐related pathways were predominantly enriched in the reference group. Conclusions Bacteria are more diverse and unevenly distributed in patients with missed abortion. Decreases in the proportion of vaginal Lactobacillus and changes in Lactobacillus species in these patients may increase the chance of genital tract pathogenic bacterial infection. To our knowledge, our study was the first to observe that a decrease of Firmicutes levels in the vaginal microbiota might impair energy metabolism and have an association with missed abortion.

Sun, Dan↗
DOE OSTI2013

A Prospective Study of the Utility of Magnetic Resonance Imaging in Determining Candidacy for Partial Breast Irradiation

Purpose: Retrospective data have demonstrated that breast magnetic resonance imaging (MRI) may change a patient's eligibility for partial breast irradiation (PBI) by identifying multicentric, multifocal, or contralateral disease. The objective of the current study was to prospectively determine the frequency with which MRI identifies occult disease and to establish clinical factors associated with a higher likelihood of MRI prompting changes in PBI eligibility. Methods and Materials: At The University of Chicago, women with breast cancer uniformly undergo MRI in addition to mammography and ultrasonography. From June 2009 through May 2011, all patients were screened prospectively in a multidisciplinary conference for PBI eligibility based on standard imaging, and the impact of MRI on PBI eligibility according to National Surgical Adjuvant Breast and Bowel Project protocol B-39/Radiation Therapy Oncology Group protocol 0413 entry criteria was recorded. Univariable analysis was performed using clinical characteristics in both the prospective cohort and in a separate cohort of retrospectively identified patients. Pooled analysis was used to derive a scoring index predictive of the risk that MRI would identify additional disease. Results: A total of 521 patients were screened for PBI eligibility, and 124 (23.8%) patients were deemed eligible for PBI based on standard imaging. MRI findings changed PBI eligibility in 12.9% of patients. In the pooled univariable analysis, tumor size ≥2 cm on mammography or ultrasonography (P=.02), age <50 years (P=.01), invasive lobular histology (P=.01), and HER-2/neu amplification (P=.01) were associated with a higher likelihood of MRI changing PBI eligibility. A predictive score was generated by summing the number of significant risk factors. Patients with a score of 0, 1, 2, and 3 had changes to eligibility based on MRI findings in 2.8%, 13.2%, 38.1%, and 100%, respectively (P<.0001). Conclusions: MRI identified additional disease in a significant number of patients eligible for PBI, based on standard imaging. Clinical characteristics may be useful in directing implementation of MRI in the staging of PBI candidates.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

Prospective Study of Hippocampal-Sparing Prophylactic Cranial Irradiation in Limited-Stage Small Cell Lung Cancer

Purpose: To prospectively evaluate cognitive function and intracranial failure patterns after hippocampal-sparing prophylactic cranial irradiation (PCI) for limited-stage small cell lung cancer (SCLC). Methods and Materials: Adults with limited-stage SCLC, achieving a complete response to chemoradiotherapy and no brain metastases, were eligible. Patients received PCI 25 Gy/10 fractions, with a mean hippocampal dose limited to <8 Gy and ≥90% of the brain receiving 90% of the prescription. A diverse battery of neuropsychological testing was performed at baseline and 6 and 12 months after PCI. Brain MRI scans were performed at baseline and 6, 12, 18, and 24 months. The primary endpoint was memory measured by the Hopkins Verbal Learning Test-Revised Delayed Recall at 6 months after PCI. The 25-Gy arm of Radiation Therapy Oncology Group protocol 0212 was used as a reference of potential efficacy. Development of intracranial metastases was recorded. Overall survival and progression-free survival were estimated using the Kaplan-Meier method. Results: Eight men and 12 women with a median age of 61 years enrolled. Two-year overall survival was 88% (95% confidence interval 68%-100%). There was no significant decline in performance between baseline and 6 or 12 months for any of the tests. The association between baseline intelligence quotient and change in performance on testing was not significant. Magnetic resonance imaging revealed asymptomatic brain metastases at a cumulative rate of 20%, with no concurrent extracranial progression. Two patients developed a metastasis in the under-dosed region. Neither involved the dentate gyrus, but 1 involved the avoidance region. Both patients concurrently developed additional metastasis in fully treated brain regions. There were 2 neurologic deaths. Conclusions: This prospective study suggests a potential benefit of hippocampal sparing in limiting the neuropsychological sequelae of brain radiation, but with a risk of failures in the spared region. These data strongly support continued enrollment on ongoing cooperative group randomized trials. Clinical Trials registration number: (NCT01797159).

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Clinical Outcomes With Dose-Escalated Adaptive Radiation Therapy for Urinary Bladder Cancer: A Prospective Study

Purpose: The purpose of this study was to assess feasibility, clinical outcomes, and toxicity in patients with bladder cancer treated with adaptive, image guided radiation therapy (IGRT) for bladder preservation as a part of trimodality treatment. The role of dose escalation was also studied. Methods and Materials: Forty-four patients with localized bladder cancer were enrolled in a prospective study. They underwent maximal safe resection of bladder tumor and concurrent platinum-based chemotherapy. Patients with large tumors were offered induction chemotherapy. Radiation therapy planning was done using either 3 (n=34) or 6 (n=10) concentrically grown planning target volumes (PTV). Patients received 64 Gy in 32 fractions to the whole bladder and 55 Gy to the pelvic nodes and, if appropriate, a simultaneous integrated boost to the tumor bed to 68 Gy (equivalent dose for 2-Gy fractions assuming α/β of 10 [EQD2]{sub 10} = 68.7 Gy). Daily megavoltage (MV) imaging helped to choose the most appropriate PTV encompassing bladder for the particular day (using plan-of-the-day approach). Results: Most patients (88%) had T2 disease. Sixteen patients (36%) received neoadjuvant chemotherapy. A majority of the patients (73%) received prophylactic nodal irradiation, whereas 55% of the patients received escalated dose to the tumor bed. With a median follow-up of 30 months, the 3-year locoregional control (LRC), disease-free survival, and overall survival (OS) were 78%, 66%, and 67%, respectively. The bladder preservation rate was 83%. LRC (87% vs 68%, respectively, P=.748) and OS (74% vs 60%, respectively, P=.36) rates were better in patients receiving dose escalation. Instances of acute and late Radiation Therapy Oncology Group (RTOG) grade 3 genitourinary toxicity was seen in 5 (11%) and 2 (4%) patients, respectively. There was no acute or late RTOG grade 3 or higher gastrointestinal toxicity. Conclusions: Adaptive IGRT using plan-of-the-day approach for bladder preservation is clinically feasible, with good oncological outcomes and low rates of acute and late toxicities. Dose escalation is safe and possibly improves outcomes in bladder preservation.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

WE-AB-207B-12: Prospective Study of the Relationship Between Dose-Volume Clinical Toxicity and Patient Reported Outcomes in Lung Cancer Patients Treated with SBRT

Purpose: To determine in a prospective study, the correlation between radiation dose/volume, clinical toxicities and patient-reported, quality of life (QOL) resulting from lung SBRT. Methods: For 106 non-small cell lung cancer (NSCLC) patients receiving SBRT (12 Gy × 4), symptoms including cough, dyspnea, fatigue and pneumonitis were measured at baseline (before treatment), after treatment and 3, 6, and 12 months post-treatment. Toxicity was graded from zero to five. Dosimetric parameters such as the MLD, D10%, D20%, and lung subvolumes (V10 and V20) were obtained from the treatment plan. Dosimetric parameters and number of patients demonstrating toxicity ≥ grade 2 were tabulated. Linear regression analysis was used to calculate correlations between MLD and D10, D20, V10 and V20. Results: The percentages of patients with > grade 2 pneumonitis, fatigue, cough, and dyspnea over 3 to 12 months increased from 0.0% to 3.5%, 3.2% to 10.5%, 4.3% to 8.3%, and 10.8% to 18.8%, respectively. Computed dose indices D10%, D20% were 7.9±4.8 Gy and 3.0±2.3 Gy, respectively. MLD ranged from 0.34 Gy up to 9.9 Gy with overall average 3.0±1.7 Gy. The averages of the subvolumes V10 and V20 were respectively 8.9±5.3% and 3.0±2.4%. The linear regression analysis showed that V10 and D10 demonstrated the strongest correlation to MLD; R2= 0.92 and 0.87, respectively. V20, and D20 were also strongly correlated with MLD; R2 = 0.81 and 0.84 respectively. A correlation was also found to exist between MLD > 2 Gy and ≥ grade 2 cough and dyspnea. Subvolume values for 2Gy MLD were 5.3% for V10 and 2% for V20. Conclusion: Dosimetric indices: MLD ≥ 2Gy, D10 ≥ 5Gy and V10 ≥ 5% of the total lung volume were predictive of > grade 2 cough and dyspnea QOL data. The QOL results are a novel component of this work. acknowledgement of the Varian grant support.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Smoking, Alcohol, and Biliary Tract Cancer Risk: A Pooling Project of 26 Prospective Studies

Abstract Background Tobacco and alcohol are well-established risk factors for numerous cancers, yet their relationship to biliary tract cancers remains unclear. Methods We pooled data from 26 prospective studies to evaluate associations of cigarette smoking and alcohol consumption with biliary tract cancer risk. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with smoking and alcohol consumption were calculated. Random-effects meta-analysis produced summary estimates. All statistical tests were two-sided. Results Over a period of 38 369 156 person-years of follow-up, 1391 gallbladder, 758 intrahepatic bile duct, 1208 extrahepatic bile duct, and 623 ampulla of Vater cancer cases were identified. Ever, former, and current smoking were associated with increased extrahepatic bile duct and ampulla of Vater cancers risk (eg, current vs never smokers HR = 1.69, 95% CI = 1.34 to 2.13 and 2.22, 95% CI = 1.69 to 2.92, respectively), with dose-response effects for smoking pack-years, duration, and intensity (all Ptrend < .01). Current smoking and smoking intensity were also associated with intrahepatic bile duct cancer (eg, >40 cigarettes per day vs never smokers HR = 2.15, 95 % CI = 1.15 to 4.00; Ptrend = .001). No convincing association was observed between smoking and gallbladder cancer. Alcohol consumption was only associated with intrahepatic bile duct cancer, with increased risk for individuals consuming five or more vs zero drinks per day (HR = 2.35, 95%CI = 1.46 to 3.78; Ptrend = .04). There was evidence of statistical heterogeneity among several cancer sites, particularly between gallbladder cancer and the other biliary tract cancers. Conclusions Smoking appears to increase the risk of developing all biliary tract cancers except gallbladder cancer. Alcohol may increase the risk of intrahepatic bile duct cancer. Findings highlight etiologic heterogeneity across the biliary tract.

McGee, Emma E.↗
DOE OSTI2016

Hemorrhagic Complications of Percutaneous Cryoablation for Renal Tumors: Results from a 7-year Prospective Study

PurposeCryoablation of renal tumors is assumed to have a higher risk of hemorrhagic complications compared to other ablative modalities. Our purpose was to establish the exact risk and to identify hemorrhagic risk factors.Materials and MethodsThis IRB approved, 7-year prospective study included 261 renal cryoablations. Procedures were under conscious sedation and CT guidance. Pre- and postablation CT was obtained, and hemorrhagic complications were CTCAE tabulated. Age, gender, tumor size, histology, and probes number were tested based on averages or proportions using their exact permutation distribution. “High-risk” subgroups (those exceeding the thresholds of all variables) were tested for each variable alone, and for all combinations of variable threshold values. We compared the subgroup with the best PPV using one variable, with the subgroup with the best PPV using all variables (McNemmar test).ResultsThe hemorrhagic complication rate was 3.5 %. Four patients required transfusions, two required emergent angiograms, one required both a transfusion and angiogram, and two required bladder irrigation for outlet obstruction. Perirenal space hemorrhage was more clinically significant than elsewhere. Univariate risks were tumor size >2 cm, number of probes >2, and malignant histology (P = 0.005, 0.002, and 0.033, respectively). Multivariate analysis showed that patients >55 years with malignant tumors >2 cm requiring 2 or more probes yielded the highest PPV (7.5 %).ConclusionsAlthough older patients (>55 years old) with larger (>2 cm), malignant tumors have an increased risk of hemorrhagic complications, the low PPV does not support the routine use of embolization. Percutaneous cryoablation has a 3.5 % risk of significant hemorrhage, similar to that reported for other types of renal ablative modalities.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

Radiation Therapy for Hypersalivation: A Prospective Study in 50 Amyotrophic Lateral Sclerosis Patients

Purpose: This study aimed to evaluate the efficiency and the tolerance of radiation therapy (RT) on salivary glands in a large series of amyotrophic lateral sclerosis (ALS) patients with hypersalivation. Methods and Materials: Fifty ALS patients that had medically failure pretreatment were included in this prospective study. RT was delivered through a conventional linear accelerator with 6-MV photons and 2 opposed beams fields including both submandibular glands and two-thirds of both parotid glands. Total RT dose was 10 Gy in 2 fractions (n=30) or 20 Gy in 4 fractions (n=20). RT efficacy was assessed with the 9-grade Sialorrhea Scoring Scale (SSS), recently prospectively validated as the most effective and sensitive tool to measure sialorrhea in ALS patients. Results: At the end of RT, all patients had improved: 46 had a complete response (92% CR, SSS 1-3) and 4 had a partial response (8% PR, SSS 4-5). A significant lasting salivary reduction was observed 6 months after RT completion: there was 71% CR and 26% PR, and there was a significant SSS reduction versus baseline (P<10{sup −6}). There was no grade 3 to 4 toxicity, and most side effects (34%) occurred during RT. Nine patients (18%) underwent a second salivary gland RT course, with a 3-months mean delay from the first RT, resulting in a SSS decrease (−77%). Both RT dose regimens induced a significant SSS decrease with no significant toxicity. There were, however, more patients with CR/PR in the 20-Gy protocol (P=.02), and 8 of 9 patients (89%) receiving a second RT course had previously been treated within the 10-Gy protocol. Conclusion: Radiation therapy of 20 Gy in 4 fractions is an efficient and safe treatment for ALS patients with sialorrhea. A shorter RT course (10 Gy in 2 fractions) may be proposed in patients in poor medical condition.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Prospective Study of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors Concurrent With Individualized Radiotherapy for Patients With Locally Advanced or Metastatic Non-Small-Cell Lung Cancer

Purpose: To establish the safety profile and efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) concurrent with individualized radiotherapy (RT) in patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC). Patients and Methods: Between June 2007 and January 2010, 26 patients with Stage III/IV NSCLC were enrolled in this prospective study. These patients were treated with EGFR-TKIs (gefitinib 250 mg or erlotinib 150 mg, oral daily) concurrent with individualized RT with curative intent. The thoracic RT plans were individually designed on the basis of tumor size and normal tissue volume constraints. All patients were assessed for toxicity, and 25 patients were available for efficacy. The primary endpoints were acute toxicity, overall survival, and median survival time. The secondary endpoints included local control rate, time to tumor progression, and progression-free survival (PFS). Results: Median gross tumor volume, mean lung dose, and lung V20 were 56 cm{sup 3}, 8.6 Gy, and 14%, respectively. Median thoracic radiation dose was 70 Gy at a margin of gross tumor volume (range, 42-82 Gy), and median biological equivalent dose was 105 Gy (range, 60-119 Gy). Acute skin, hematologic, esophageal, and pulmonary toxicities were acceptable and manageable. Severe adverse events included neutropenia (Grade 4, 4%) and thrombocytopenia (Grade 4, 8%), esophagitis (Grade 3, 4%), and pneumonitis (Grade 3, 4%). With a median follow-up of 10.2 months, a local control rate of 96% was achieved for thoracic tumor. Median time to progression, median PFS, and median survival time were 6.3, 10.2, and 21.8 months, respectively. The 1- and 2-year PFS rates were both 42%, and 1-, 2-, and 3-year overall survival rates were 57%, 45%, and 30%, respectively. Conclusion: Concurrent EGFR-TKIs with individualized RT shows a favorable safety profile and promising outcome, therefore serving as a therapeutic option for patients with locally advanced or metastatic NSCLC.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

SU-F-R-34: Quantitative Perfusion Measurement in Rectal Cancer Using Three Different Pharmacokinetic Models: Implications for Prospective Study Design

Purpose: To compare three different pharmacokinetic models for analysis of dynamic-contrast-enhanced (DCE)-CT data with respect to different acquisition times and location of region of interest. Methods: Eight rectal cancer patients with pre-treatment DCE-CTs were included. The dynamic sequence started 4–10seconds(s) after the injection of contrast agent. The scan included a 110s acquisition with intervals of 40×1s+15×3s+4×6s. An experienced oncologist outlined the tumor region. Hotspots with top-5%-enhancement were also identified. Pharmacokinetic analysis was performed using three different models: deconvolution method, Patlak model, and modified Toft’s model. Perfusion parameters as blood flow (BF), blood volume (BV), mean transit time (MTT), permeability-surface-area-product (PS), volume transfer constant (Ktrans), and flux rate constant (Kep), were compared with respect to different acquisition times of 45s, 65s, 85s and 105s. Both hotspot and whole-volume variances were also assessed. The differences were compared using the Wilcoxon matched-pairs test and Bland-Altman plots. Results: Moderate correlation was observed for various perfusion parameters (r=0.56–0.72, p<0.0001) but the Wilcoxon test revealed a significant difference among the three models (P < .001). Significant differences in PS were noted between acquisitions of 45s versus longer time of 85s or 105s (p<0.05) using Patlak but not with the deconvolution method. In addition, measurements varied substantially between whole-volume vs. hotspot analysis. Conclusion: The radiation dose of DCE-CT was on average 1.5 times of an abdomen/pelvic CT, which is not insubstantial. To take the DCE-CT forward as a biomarker in oncology, prospective studies should be carefully designed with the optimal image acquisition and analysis technique. Our study suggested that: (1) different kinetic models are not interchangeable; (2) a 45s acquisition might not be sufficient for reliable permeability measurement in rectal cancer using Patlak model, but might be achievable using deconvolution method; and (3) local variations existed inside the tumor, and both whole-volume-averaged and local-heterogeneity analysis is recommended for future quantitative studies. This work is supported by the National High-tech R&D program for Young Scientists by the Ministry of Science and Technology of China (Grant No. 2015AA020917), Natural Science Foundation of China (NSFC Grant No. 81201091).

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Stereotactic Body Radiation Therapy Can Be Used Safely to Boost Residual Disease in Locally Advanced Non-Small Cell Lung Cancer: A Prospective Study

Purpose: To report the results of a prospective, single-institution study evaluating the feasibility of conventional chemoradiation (CRT) followed by stereotactic body radiation therapy (SBRT) as a means of dose escalation for patients with stage II-III non-small cell lung cancer (NSCLC) with residual disease. Methods and Materials: Patients without metastatic disease and with radiologic evidence of limited residual disease (≤5 cm) within the site of the primary tumor and good or complete nodal responses after standard CRT to a target dose of 60 Gy were considered eligible. The SBRT boost was done to achieve a total combined dose biological equivalent dose >100 Gy to the residual primary tumor, consisting of 10 Gy × 2 fractions (20 Gy total) for peripheral tumors, and 6.5 Gy × 3 fractions (19.5 Gy total) for medial tumors using the Radiation Therapy Oncology Group protocol 0813 definitions. The primary endpoint was the development of grade ≥3 radiation pneumonitis (RP). Results: After a median follow-up of 13 months, 4 patients developed acute grade 3 RP, and 1 (2.9%) developed late and persistent grade 3 RP. No patients developed grade 4 or 5 RP. Mean lung dose, V2.5, V5, V10, and V20 values were calculated for the SBRT boost, and none were found to significantly predict for RP. Only advancing age (P=.0147), previous smoking status (P=.0505), and high CRT mean lung dose (P=.0295) were significantly associated with RP development. At the time of analysis, the actuarial local control rate at the primary tumor site was 82.9%, with only 6 patients demonstrating recurrence. Conclusions: Linear accelerator-based SBRT for dose escalation of limited residual NSCLC after definitive CRT was feasible and did not increase the risk for toxicity above that for standard radiation therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Multicenter prospective study validating the efficacy of a quantitative assessment tool for frailty in patients with urological cancers

We prospectively validate the efficacy of the frailty discriminant score (FDS) in individuals with urological cancers, as there has been growing importance in evaluating frailty in clinical practice. A prospective, multicenter study was conducted from February 2017 to April 2019. We enrolled 258 patients with urological cancers and 301 community-dwelling participants who were assessed for frailty. Frailty was assessed using FDS that includes ten items, such as physical, mental, and blood biochemical tests. The primary outcome was the non-inferiority (margin 5%) of FDS in discriminating patients with urological cancers from controls (Ctrl). The sensitivity, specificity, and area under the receiver operating characteristic (AUROC) curve for each predictive test were calculated. The secondary endpoints included the prediction of overall survival between patients with urological cancer who have high and low FDS. FDS was significantly higher in patients with urological cancers than that in the Ctrl. The AUROC curves for individuals with non-prostate cancers (such as bladder cancer, upper tract urothelial carcinoma, and renal cell carcinoma; 0.942) and those with prostate cancer (0.943) were within the non-inferior margin. The overall survival values were significantly lower in patients with higher FDS score than in those with lower FDS score. The study met its primary and secondary endpoints. The FDS is a reliable and valid tool for assessing frailty and prognosis in patients with urological cancers.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

A prospective study of the incidence of myocarditis/pericarditis and new onset cardiac symptoms following smallpox and influenza vaccination

Although myocarditis/pericarditis (MP) has been identified as an adverse event following smallpox vaccine (SPX), the prospective incidence of this reaction and new onset cardiac symptoms, including possible subclinical injury, has not been prospectively defined. The study's primary objective was to determine the prospective incidence of new onset cardiac symptoms, clinical and possible subclinical MP in temporal association with immunization. New onset cardiac symptoms, clinical MP and cardiac specific troponin T (cTnT) elevations following SPX (above individual baseline values) were measured in a multi-center prospective, active surveillance cohort study of healthy subjects receiving either smallpox vaccine or trivalent influenza vaccine (TIV). Results New onset chest pain, dyspnea, and/or palpitations occurred in 10.6% of SPX-vaccinees and 2.6% of TIV-vaccinees within 30 days of immunization (relative risk (RR) 4.0, 95% CI: 1.7-9.3). Among the 1081 SPX-vaccinees with complete follow-up, 4 Caucasian males were diagnosed with probable myocarditis and 1 female with suspected pericarditis. This indicates a post-SPX incidence rate more than 200-times higher than the pre-SPX background population surveillance rate of myocarditis/pericarditis (RR 214, 95% CI 65-558). Additionally, 31 SPX-vaccinees without specific cardiac symptoms were found to have over 2-fold increases in cTnT (>99th percentile) from baseline (pre-SPX) during the window of risk for clinical myocarditis/pericarditis and meeting a proposed case definition for possible subclinical myocarditis. This rate is 60-times higher than the incidence rate of overt clinical cases. No clinical or possible subclinical myocarditis cases were identified in the TIV-vaccinated group. In conclusion, passive surveillance significantly underestimates the true incidence of myocarditis/pericarditis after smallpox immunization. Evidence of subclinical transient cardiac muscle injury post-vaccinia immunization is a finding that requires further study to include long-term outcomes surveillance. Active safety surveillance is needed to identify adverse events that are not well understood or previously recognized.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

External Beam Radiation Therapy or Brachytherapy With or Without Short-course Neoadjuvant Androgen Deprivation Therapy: Results of a Multicenter, Prospective Study of Quality of Life

Purpose: The long-term effects of neoadjuvant androgen deprivation therapy (NADT) with radiation therapy on participant-reported health-related quality of life (HRQOL) have not been characterized in prospective multicenter studies. We evaluated HRQOL for 2 years among participants undergoing radiation therapy (RT) with or without NADT for newly diagnosed, early-stage prostate cancer. Methods and Materials: We analyzed longitudinal cohort data from the Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment Consortium to ascertain the HRQOL trajectory of men receiving NADT with external beam RT (EBRT) or brachytherapy. HRQOL was measured using the expanded prostate cancer index composite 26-item questionnaire at 2, 6, 12, and 24 months after the initiation of NADT. We used the χ{sup 2} or Fisher exact test to compare the shift in percentages between groups that did or did not receive NADT. Analyses were conducted at the 2-sided 5% significance level. Results: For subjects receiving EBRT, questions regarding the ability to have an erection, ability to reach an orgasm, quality of erections, frequency of erections, ability to function sexually, and lack of energy were in a significantly worse dichotomized category for the patients receiving NADT. Comparing the baseline versus 24-month outcomes, 24%, 23%, and 30% of participants receiving EBRT plus NADT shifted to the worse dichotomized category for the ability to reach an orgasm, quality of erections, and ability to function sexually compared with 14%, 13%, and 16% in the EBRT group, respectively. Conclusions: Compared with baseline, at 2 years, participants receiving NADT plus EBRT compared with EBRT alone had worse HRQOL, as measured by the ability to reach orgasm, quality of erections, and ability to function sexually. However, no difference was found in the ability to have an erection, frequency of erections, overall sexual function, hot flashes, breast tenderness/enlargement, depression, lack of energy, or change in body weight. The improved survival in intermediate- and high-risk patients receiving NADT and EBRT necessitates pretreatment counseling of the HRQOL effect of NADT and EBRT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

Toxicities Affecting Quality of Life After Chemo-IMRT of Oropharyngeal Cancer: Prospective Study of Patient-Reported, Observer-Rated, and Objective Outcomes

Purpose: To test the hypothesis that intensity modulated radiation therapy (IMRT) aiming to spare the salivary glands and swallowing structures would reduce or eliminate the effects of xerostomia and dysphagia on quality of life (QOL). Methods and Materials: In this prospective, longitudinal study, 72 patients with stage III-IV oropharyngeal cancer were treated uniformly with definitive chemo-IMRT sparing the salivary glands and swallowing structures. Overall QOL was assessed by summary scores of the Head Neck QOL (HNQOL) and University of Washington QOL (UWQOL) questionnaires, as well as the HNQOL “Overall Bother” question. Quality of life, observer-rated toxicities (Common Toxicity Criteria Adverse Effects scale, version 2), and objective evaluations (videofluoroscopy assessing dysphagia and saliva flow rates assessing xerostomia) were recorded from before therapy through 2 years after therapy. Correlations between toxicities/objective evaluations and overall QOL were assessed using longitudinal repeated measures of analysis and Pearson correlations. Results: All observer-rated toxicities and QOL scores worsened 1-3 months after therapy and improved through 12 months, with minor further improvements through 24 months. At 12 months, dysphagia grades 0-1, 2, and 3, were observed in 95%, 4%, and 1% of patients, respectively. Using all posttherapy observations, observer-rated dysphagia was highly correlated with all overall QOL measures (P<.0001), whereas xerostomia and mucosal and voice toxicities were significantly correlated with some, but not all, overall QOL measures, with lower correlation coefficients than dysphagia. Late overall QOL (≥6 or ≥12 months after therapy) was primarily associated with observer-rated dysphagia, and to a lesser extent with xerostomia. Videofluoroscopy scores, but not salivary flows, were significantly correlated with some of the overall QOL measures. Conclusion: After chemo-IMRT, although late dysphagia was on average mild, it was still the major correlate of QOL. Further efforts to reduce swallowing dysfunction are likely to yield additional gains in QOL.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

Relationship Between Radiation-Induced Apoptosis of T Lymphocytes and Chronic Toxicity in Patients With Prostate Cancer Treated by Radiation Therapy: A Prospective Study

Purpose: To assess the correlation of radiation-induced apoptosis in vitro of CD4 and CD8 T lymphocytes with late toxicity of prostate cancer patients treated with radiation therapy. Methods and Materials: 214 patients were prospectively included in the study. Peripheral blood was drawn from patients before treatment and irradiated with 8 Gy. The percentage of CD4+ and CD8+ T lymphocytes that underwent radiation-induced apoptosis was assessed by flow cytometry. Toxicity and mortality were correlated in 198 cases with pretreatment apoptosis and clinical and biological variables by use of a Cox proportional hazards model. Results: The mean percentage of CD4+ and CD8+ T lymphocyte radiation-induced apoptosis was 28.58% (±14.23) and 50.76% (±18.9), respectively. Genitourinary (GU) toxicity was experienced by 39.9% of patients, while gastrointestinal (GI) toxicity was experienced by 19.7%. The probability of development of GU toxicity was nearly doubled (hazard ratio [HR] 1.99, P=.014) in those patients in whom the percentage of in vitro radiation-induced apoptosis of CD4+ T-lymphocytes was ≤28.58%. It was also almost double in patients who received doses ≥50 Gy in 65% of the bladder volume (V65 ≥50) (HR 1.92, P=.048). No correlation was found between GI toxicity and any of the variables studied. The probability of death during follow-up, after adjustment for different variables, was 2.7 times higher in patients with a percentage of CD8+ T lymphocyte apoptosis ≤50.76% (P=.022). Conclusions: In conclusion, our study shows, in the largest prospective cohort of prostate cancer patients undergoing radiation therapy, that in vitro radiation-induced apoptosis of CD4+ T lymphocytes assessed before radiation therapy was associated with the probability of developing chronic GU toxicity. In addition, the radiation dose received in the urinary bladder (V65 ≥50) affected the occurrence of GU toxicity. Finally, we also demonstrate that radiation-induced apoptosis of CD8+ T lymphocytes was associated with overall survival, although larger series are needed to confirm this finding.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Validating a Local Failure Risk Stratification for Use in Prospective Studies of Adjuvant Radiation Therapy for Bladder Cancer

Purpose: To inform prospective trials of adjuvant radiation therapy (adj-RT) for bladder cancer after radical cystectomy, a locoregional failure (LF) risk stratification was proposed. This stratification was developed and validated using surgical databases that may not reflect the outcomes expected in prospective trials. Our purpose was to assess sources of bias that may affect the stratification model's validity or alter the LF risk estimates for each subgroup: time bias due to evolving surgical techniques; trial accrual bias due to inclusion of patients who would be ineligible for adj-RT trials because of early disease progression, death, or loss to follow-up shortly after cystectomy; bias due to different statistical methods to estimate LF; and subgrouping bias due to different definitions of the LF subgroups. Methods and Materials: The LF risk stratification was developed using a single-institution cohort (n=442, 1990-2008) and the multi-institutional SWOG 8710 cohort (n=264, 1987-1998) treated with radical cystectomy with or without chemotherapy. We evaluated the sensitivity of the stratification to sources of bias using Fine-Gray regression and Kaplan-Meier analyses. Results: Year of radical cystectomy was not associated with LF risk on univariate or multivariate analysis after controlling for risk group. By use of more stringent inclusion criteria, 26 SWOG patients (10%) and 60 patients from the single-institution cohort (14%) were excluded. Analysis of the remaining patients confirmed 3 subgroups with significantly different LF risks with 3-year rates of 7%, 17%, and 36%, respectively (P<.01), nearly identical to the rates without correcting for trial accrual bias. Kaplan-Meier techniques estimated higher subgroup LF rates than competing risk analysis. The subgroup definitions used in the NRG-GU001 adj-RT trial were validated. Conclusions: These sources of bias did not invalidate the LF risk stratification or substantially change the model's LF estimates.

62 RADIOLOGY AND NUCLEAR MEDICINE↗