Coronary CTA and Quantitative Cardiac CT Perfusion (CCTP) in Coronary Artery Disease

We assessed the benefit of combining stress cardiac CT perfusion (CCTP) myocardial blood flow (MBF) with coronary CT angiography (CCTA) using our innovative CCTP software. By combining CCTA and CCTP, one can uniquely identify a flow limiting stenosis (obstructive-lesion + low-MBF) versus MVD (no-obstructive-lesion + low-MBF. We retrospectively evaluated 104 patients with suspected CAD, including 18 with diabetes, who underwent CCTA+CCTP. Whole heart and territorial MBF was assessed using our automated pipeline for CCTP analysis that included beam hardening correction; temporal scan registration; automated segmentation; fast, accurate, robust MBF estimation; and visualization. Stenosis severity was scored using the CCTA coronary-artery-disease-reporting-and-data-system (CAD-RADS), with obstructive stenosis deemed as CAD-RADS>=3. We established a threshold MBF (MBF=199-mL/min-100g) for normal perfusion. In patients with CAD-RADS>=3, 28/37(76%) patients showed ischemia in the corresponding territory. Two patients with obstructive disease had normal perfusion, suggesting collaterals and/or a hemodynamically insignificant stenosis. Among diabetics, 10 of 18 (56%) demonstrated diffuse ischemia consistent with MVD. Among non-diabetics, only 6% had MVD. Sex-specific prevalence of MVD was 21%/24% (M/F). On a per-vessel basis (n=256), MBF showed a significant difference between territories with and without obstructive stenosis (165 +/- 61 mL/min-100g vs. 274 +/- 62 mL/min-100g, p <0.05). A significant and negative rank correlation (rho=-0.53, p<0.05) between territory MBF and CAD-RADS was seen. CCTA in conjunction with a new automated quantitative CCTP approach can augment the interpretation of CAD, enabling the distinction of ischemia due to obstructive lesions and MVD

Cardiac CT perfusion imaging of pericoronary adipose tissue (PCAT) highlights potential confounds in coronary CTA

Features of pericoronary adipose tissue (PCAT) assessed from coronary computed tomography angiography (CCTA) are associated with inflammation and cardiovascular risk. As PCAT is vascularly connected with coronary vasculature, the presence of iodine is a potential confounding factor on PCAT HU and textures that has not been adequately investigated. Use dynamic cardiac CT perfusion (CCTP) to inform contrast determinants of PCAT assessment. From CCTP, we analyzed HU dynamics of territory-specific PCAT, myocardium, and other adipose depots in patients with coronary artery disease. HU, blood flow, and radiomics were assessed over time. Changes from peak aorta time, Pa, chosen to model the time of CCTA, were obtained. HU in PCAT increased more than in other adipose depots. The estimated blood flow in PCAT was ~23% of that in the contiguous myocardium. Comparing PCAT distal and proximal to a significant stenosis, we found less enhancement and longer time-to-peak distally. Two-second offsets [before, after] Pa resulted in [ 4-HU, 3-HU] differences in PCAT. Due to changes in HU, the apparent PCAT volume reduced ~15% from the first scan (P1) to Pa using a conventional fat window. Comparing radiomic features over time, 78% of features changed >10% relative to P1. CCTP elucidates blood flow in PCAT and enables analysis of PCAT features over time. PCAT assessments (HU, apparent volume, and radiomics) are sensitive to acquisition timing and the presence of obstructive stenosis, which may confound the interpretation of PCAT in CCTA images. Data normalization may be in order.Comment: 13 pages, 8 figure

REQUITE: A prospective multicentre cohort study of patients undergoing radiotherapy for breast, lung or prostate cancer

Purpose: REQUITE aimed to establish a resource for multi-national validation of models and biomarkers that predict risk of late toxicity following radiotherapy. The purpose of this article is to provide summary descriptive data. Methods: An international, prospective cohort study recruited cancer patients in 26 hospitals in eight countries between April 2014 and March 2017. Target recruitment was 5300 patients. Eligible patients had breast, prostate or lung cancer and planned potentially curable radiotherapy. Radiotherapy was prescribed according to local regimens, but centres used standardised data collection forms. Pre-treatment blood samples were collected. Patients were followed for a minimum of 12 (lung) or 24 (breast/prostate) months and summary descriptive statistics were generated. Results: The study recruited 2069 breast (99% of target), 1808 prostate (86%) and 561 lung (51%) cancer patients. The centralised, accessible database includes: physician-(47,025 forms) and patient-(54,901) reported outcomes; 11,563 breast photos; 17,107 DICOMs and 12,684 DVHs. Imputed genotype data are available for 4223 patients with European ancestry (1948 breast, 1728 prostate, 547 lung). Radiation-induced lymphocyte apoptosis (RILA) assay data are available for 1319 patients. DNA (n = 4409) and PAXgene tubes (n = 3039) are stored in the centralised biobank. Example prevalences of 2-year (1-year for lung) grade >= 2 CTCAE toxicities are 13% atrophy (breast), 3% rectal bleeding (prostate) and 27% dyspnoea (lung). Conclusion: The comprehensive centralised database and linked biobank is a valuable resource for the radiotherapy community for validating predictive models and biomarkers. Patient summary: Up to half of cancer patients undergo radiation therapy and irradiation of surrounding healthy tissue is unavoidable. Damage to healthy tissue can affect short-and long-term quality-of-life. Not all patients are equally sensitive to radiation "damage" but it is not possible at the moment to identify those who are. REQUITE was established with the aim of trying to understand more about how we could predict radiation sensitivity. The purpose of this paper is to provide an overview and summary of the data and material available. In the REQUITE study 4400 breast, prostate and lung cancer patients filled out questionnaires and donated blood. A large amount of data was collected in the same way. With all these data and samples a database and biobank were created that showed it is possible to collect this kind of information in a standardised way across countries. In the future, our database and linked biobank will be a resource for research and validation of clinical predictors and models of radiation sensitivity. REQUITE will also enable a better understanding of how many people suffer with radiotherapy toxicity

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Scalable and high throughput photothermal water disinfection with negligible CO2 footprint utilizing nanostructured carbon coatings

Abstract Water heating and disinfection with reduced energy and CO2 footprint demands new and efficient materials for solar-thermal conversion technologies. Here, we demonstrate nanostructured porous hard-carbon florets (NCF) as effective solar absorber coating achieving excellent photon thermalization efficiency (87%). Functional NCF coating on three-dimensionally tapered helical solar receivers generate high surface temperatures (up to 95 °C). Such ‘green-heat’ is channeled to heat water up to 82 °C that simultaneously results in water disinfection through thermal shock. Untreated lake-water with high turbidity (5 NTU), high bacterial load (106 CFU mL−1) and pathogenic fungi is effectively disinfected in a continuous flow process. Translating this, a fully automated SWAP prototype (solar water antimicrobial purifier), delivers bacteria free hot water at an output capacity of 42 L m−2 day−1 with the lowest CO2 footprint (5 kg L−1) in comparison to all other existing approaches (>40 kg L−1)

Exploiting the Synergism of a Carbon–Catalyst Interface to Achieve Magneto-Electrocatalytic Overall Water Splitting at 2.197 V

The desire to electrolyze water at low energy and high kinetics for achieving rapid H2 production forms the holy grail for the paradigm shift to a sustainable H2-driven economy. While alkaline electrolysis is preferred due to the use of earth-abundant catalysts, its sluggish kinetics and high overpotential are the persistent challenges. Addressing this, we demonstrate the coupling of an externally applied magnetic field (Hext) to a synergistically designed interface of nanostructured carbon floret with antiferromagnetic NiO nanoflakes that act in unison to achieve rapid hydrogen generation (6.3 N m3 h–1 W–1) that is comparable with existing technologies. Specifically, the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) overpotentials are simultaneously reduced by 10 and 7%, respectively, under the influence of a weak fridge magnet (Hext = 200 mT). Consequently, ∼11% improvement in the energy efficiency is observed with a 21% reduced cell voltage for overall water splitting. The stability of the system is demonstrated over a prolonged lifetime of ∼95 h. This performance enhancement with Hext for both HER and OER is explained in terms of improved kinetic facility for the reaction and lower resistance of charge transfer pathway. Moreover, the electrocatalyst is seen to retain the improved performance for prolonged usage (∼3 h) even after the removal of the Hext, and hence, it provides an energy-efficient hydrogen and oxygen generation pathway

REQUITE: A prospective multicentre cohort study of patients undergoing radiotherapy for breast, lung or prostate cancer

PURPOSE: REQUITE aimed to establish a resource for multi-national validation of models and biomarkers that predict risk of late toxicity following radiotherapy. The purpose of this article is to provide summary descriptive data. METHODS: An international, prospective cohort study recruited cancer patients in 26 hospitals in eight countries between April 2014 and March 2017. Target recruitment was 5300 patients. Eligible patients had breast, prostate or lung cancer and planned potentially curable radiotherapy. Radiotherapy was prescribed according to local regimens, but centres used standardised data collection forms. Pre-treatment blood samples were collected. Patients were followed for a minimum of 12 (lung) or 24 (breast/prostate) months and summary descriptive statistics were generated. RESULTS: The study recruited 2069 breast (99% of target), 1808 prostate (86%) and 561 lung (51%) cancer patients. The centralised, accessible database includes: physician- (47,025 forms) and patient- (54,901) reported outcomes; 11,563 breast photos; 17,107 DICOMs and 12,684 DVHs. Imputed genotype data are available for 4223 patients with European ancestry (1948 breast, 1728 prostate, 547 lung). Radiation-induced lymphocyte apoptosis (RILA) assay data are available for 1319 patients. DNA (n = 4409) and PAXgene tubes (n = 3039) are stored in the centralised biobank. Example prevalences of 2-year (1-year for lung) grade ≥2 CTCAE toxicities are 13% atrophy (breast), 3% rectal bleeding (prostate) and 27% dyspnoea (lung). CONCLUSION: The comprehensive centralised database and linked biobank is a valuable resource for the radiotherapy community for validating predictive models and biomarkers. PATIENT SUMMARY: Up to half of cancer patients undergo radiation therapy and irradiation of surrounding healthy tissue is unavoidable. Damage to healthy tissue can affect short- and long-term quality-of-life. Not all patients are equally sensitive to radiation "damage" but it is not possible at the moment to identify those who are. REQUITE was established with the aim of trying to understand more about how we could predict radiation sensitivity. The purpose of this paper is to provide an overview and summary of the data and material available. In the REQUITE study 4400 breast, prostate and lung cancer patients filled out questionnaires and donated blood. A large amount of data was collected in the same way. With all these data and samples a database and biobank were created that showed it is possible to collect this kind of information in a standardised way across countries. In the future, our database and linked biobank will be a resource for research and validation of clinical predictors and models of radiation sensitivity. REQUITE will also enable a better understanding of how many people suffer with radiotherapy toxicity.status: publishe