Positron emission tomography-based assessment of metabolic gradient and other prognostic features in sarcoma

Intratumoral heterogeneity biomarkers derived from positron emission tomography (PET) imaging with fluorodeoxyglucose (FDG) are of interest for a number of cancers, including sarcoma. A range of radiomic texture variables, adapted from general methodologies for image analysis, has shown promise in the setting. In the context of sarcoma, our group introduced an alternative model-based approach to the measurement of heterogeneity. In this approach, the heterogeneity of a tumor is characterized by the extent to which the 3-D FDG uptake pattern deviates from a simple elliptically contoured structure. By using a nonparametric analysis of the uptake profile obtained from this spatial model, a variable assessing the metabolic gradient of the tumor is developed. The work explores the prognostic potential of this new variable in the context of FDG-PET imaging of sarcoma. A mature clinical series involving 197 patients, 88 of whom have complete time-to-death information, is used. Texture variables based on the imaging data are also evaluated in this series and a range of appropriate machine learning methodologies are then used to explore the complementary prognostic roles for structure and texture variables. We conclude that both texture-based and model-based variables can be combined to achieve enhanced prognostic assessments of outcome for patients with sarcoma based on FDG-PET imaging information

Statistical assessment of treatment response in a cancer patient based on pre-therapy and post-therapy FDG-PET scans

This work arises from consideration of sarcoma patients in which fluorodeoxyglucose positron emission tomography (FDG-PET) imaging pre-therapy and post-chemotherapy is used to assess treatment response. Our focus is on methods for evaluation of the statistical uncertainty in the measured response for an individual patient. The gamma distribution is often used to describe data with constant coefficient of variation, but it can be adapted to describe the pseudo-Poisson character of PET measurements. We propose co-registering the pre-therapy and post- therapy images and modeling the approximately paired voxel-level data using the gamma statistics. Expressions for the estimation of the treatment effect and its variability are provided. Simulation studies explore the performance in the context of testing for a treatment effect. The impact of misregistration errors and how test power is affected by estimation of variability using simplified sampling assumptions, as might be produced by direct bootstrapping, is also clarified. The results illustrate a marked benefit in using a properly constructed paired approach. Remarkably, the power of the paired analysis is maintained even if the pre-image and post- image data are poorly registered. A theoretical explanation for this is indicated. The methodology is further illustrated in the context of a series of fluorodeoxyglucose-PET sarcoma patient studies. These data demonstrate the additional prognostic value of the proposed treatment effect test statistic

Assessment of the prognostic value of radiomic features in 18F-FMISO PET imaging of hypoxia in postsurgery brain cancer patients: secondary analysis of imaging data from a single-center study and the multicenter ACRIN 6684 trial

Hypoxia is associated with resistance to radiotherapy and chemotherapy in malignant gliomas, and it can be imaged by positron emission tomography with 18F-fluoromisonidazole (18F-FMISO). Previous results for patients with brain cancer imaged with 18F-FMISO at a single center before conventional chemoradiotherapy showed that tumor uptake via T/Bmax (tissue SUVmax/blood SUV) and hypoxic volume (HV) was associated with poor survival. However, in a multicenter clinical trial (ACRIN 6684), traditional uptake parameters were not found to be prognostically significant, but tumor SUVpeak did predict survival at 1 year. The present analysis considered both study cohorts to reconcile key differences and examine the potential utility of adding radiomic features as prognostic variables for outcome prediction on the combined cohort of 72 patients with brain cancer (30 University of Washington and 42 ACRIN 6684). We used both 18F-FMISO intensity metrics (T/Bmax, HV, SUV, SUVmax, SUVpeak) and assessed radiomic measures that determined first-order (histogram), second-order, and higher-order radiomic features of 18F-FMISO uptake distributions. A multivariate model was developed that included age, HV, and the intensity of 18F-FMISO uptake. HV and SUVpeak were both independent predictors of outcome for the combined data set (P < .001) and were also found significant in multivariate prognostic models (P < .002 and P < .001, respectively). Further model selection that included radiomic features showed the additional prognostic value for overall survival of specific higher order texture features, leading to an increase in relative risk prediction performance by a further 5%, when added to the multivariate clinical model

Cultural Value: The Story of Lidice and Stoke-on-Trent: Towards Deeper Understanding of the Role of Arts and Culture

This report details the research activities, findings and outputs from our six month Research Development Award exploring the value of arts and culture in relation to empathy, compassion and understanding. Our research focused on storytelling approaches in the context of exhibitions and community and participatory arts projects. We use as a case study the relationship between Stoke-on-Trent and the village of Lidice in the Czech Republic. Following the destruction of Lidice by the Nazis in 1942, Stoke-on-Trent Doctor and Councillor Barnett Stross launched the ‘Lidice Shall Live’ campaign, rallying local working people to contribute to a fund that eventually contributed to re-building the village after the war. Many people demonstrated tremendous empathy and compassion by donating up to a week’s wages despite the hardships of the time. In recent years, the links between Stoke-on-Trent and Lidice have been refreshed and are explored, expressed and celebrated almost exclusively through arts and culture. Our main research question is therefore why we would choose the medium of arts and culture to link distant geographical communities in ways that foster empathy, compassion and understanding. We held interviews and focus groups with a multi-disciplinary group of academics and with a wide range of artists and creative practitioners to discuss issues of empathy, compassion and understanding, and the value of arts and culture. A working group of participants was formed to explore new ways of identifying and expressing such value. In June 2014, some of the working group travelled to the Czech Republic and took part in a research visit that included participation in arts and cultural activities and events. A range of resources to support the design and evaluation of arts activities was developed, including a series of short films to disseminate the findings and to encourage on-going reflection and debate

Evaluation of a Longitudinal Institutional Advanced Pharmacy Practice Model

&nbsp; Objective: To evaluate a longitudinal experiential training model for advanced pharmacy practice experiences (APPEs). Innovation: A six-month longitudinal pilot program named the Focused Institutional Longitudinal Experience (FILE) program was developed at two academic medical centers to maximize active participation of the student and minimize the time spent orienting and onboarding students to each APPE experience.&nbsp; A unique component of the FILE program is the longitudinal service project, which involved a medication use evaluation, including a review of published literature and drug policy recommendations to medical center quality committees. Analysis: Student ratings regarding the quality and value of the FILE student experience was compared to the traditional APPE model.&nbsp; Nine quality measures were compared (e.g. amount of opportunity for direct patient care experience, learning, integration into healthcare team, and accountability for patient outcomes) between students from the FILE program to peers completing similar APPEs outside the FILE program. FILE students and APPE preceptors also completed surveys regarding the value of several program aspects. Key Findings: There was no difference between FILE and non-FILE student self-rated measures of APPE quality, and thus the decision to participate in a longitudinal APPE program should be based on the personal preference of the student.&nbsp; Students in the FILE program agreed or strongly agreed (mean score 4.3) that they felt prepared for post-graduate training at the completion of the program. The potential value that students in a longitudinal program might bring to the site is reinforced by the general agreement by preceptors in the end of year survey&nbsp; that FILE students take less of their time to orient to their service and the trend toward perception that FILE students are more likely to independently participate in patient care activities.&nbsp; Next Steps: To address feedback on preceptor-mentor role and the desire for more interaction with pharmacy residents, students are now paired with a pharmacy resident, and the student and resident work together on the service project with a clinical pharmacist as an advisor.&nbsp; Updated standards of practice clearly delineate the roles and responsibilities of students, residents, and the clinical pharmacist preceptor.&nbsp; Annual surveys of FILE students and preceptors provide necessary feedback to continuously improve the quality of the program.&nbsp;&nbsp; &nbsp; Article Type:&nbsp; Not

Assessment of a statistical AIF extraction method for dynamic PET studies with 15O water and 18F fluorodeoxyglucose in locally advanced breast cancer patients

Blood flow-metabolism mismatch from dynamic positron emission tomography (PET) studies with O-15-labeled water (H2O) and F-18-labeled fluorodeoxyglucose (FDG) has been shown to be a promising diagnostic for locally advanced breast cancer (LABCa) patients. The mismatch measurement involves kinetic analysis with the arterial blood time course (AIF) as an input function. We evaluate the use of a statistical method for AIF extraction (SAIF) in these studies. Fifty three LABCa patients had dynamic PET studies with H2O and FDG. For each PET study, two AIFs were recovered, an SAIF extraction and also a manual extraction based on a region of interest placed over the left ventricle (LV-ROI). Blood flow-metabolism mismatch was obtained with each AIF, and kinetic and prognostic reliability comparisons were made. Strong correlations were found between kinetic assessments produced by both AIFs. SAIF AIFs retained the full prognostic value, for pathologic response and overall survival, of LV-ROI AIFs. (c) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI

StereoTactic radiotherapy for wet Age-Related macular degeneration (STAR):Study protocol for a randomized controlled clinical trial

BACKGROUND: The standard of care for neovascular age-related macular degeneration (nAMD) involves ongoing intravitreal injections of anti-angiogenic drugs targeting vascular endothelial growth factor (VEGF). The most commonly used anti-VEGF drugs are ranibizumab, bevacizumab and aflibercept. The main objective of the STAR trial is to determine if stereotactic radiotherapy can reduce the number of anti-VEGF injections that patients with nAMD require. METHODS/DESIGN: STAR is a multicentre, double-masked, randomised, sham-controlled clinical trial. It evaluates a new device (manufactured by Oraya, Newark, CA, USA) designed to deliver stereotactic radiotherapy (SRT) to nAMD lesions. The trial enrols participants with chronic, active nAMD. Participants receive a single SRT treatment (16 Gy or sham) with a concomitant baseline intravitreal injection of 0.5 mg ranibizumab. Thereafter, they attend every month for 24 months, and ranibizumab is administered at the visit if retreatment criteria are met. The primary outcome is the number of pro re nata ranibizumab injections during the first 24 months. Secondary outcomes include visual acuity, lesion morphology, quality of life and safety. Additional visits occur at 36 and 48 months to inspect for radiation retinopathy. The target sample size of 411 participants (randomised 2:1 in favour of radiation) is designed to detect a reduction of 2.5 injections against ranibizumab monotherapy, at 90% power, and a significance level (alpha) of 0.025 (one-sided two-sample t test). This gives 97% power to detect non-inferiority of visual acuity at a five-letter margin. The primary analyses will be by intention to treat. DISCUSSION: The safety and efficacy outcomes will help determine the role of SRT in the management of chronic, active nAMD. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number: ISRCTN12884465. Registered on 28 November 2014. ClinicalTrials.gov: NCT02243878. Registered on 17 September 2014

Extent and consistency of linkage disequilibrium and identification of DNA markers for production and egg quality traits in commercial layer chicken populations

A 3,072 single nucleotide polymorphism (SNP) panel was used to identify genetic markers linked to quantitative trait loci (QTL). Two association methods were used to search for QTL, SNP-wise and genome-wise models. The QTL associated with SNPs, found using both of these methods, can be applied to breeding programs in marker assisted selection (MAS). The extent and consistency of linkage disequilibrium (LD) was measured in two lines of commercial egg laying chickens by analysis of SNPs. Correlations were drawn between measurements of two consecutive years to determine consistency. At short distances, LD is retained which allows for markers at high LD with a trait to be effectively applied in MAS