Potential of 18F-FDG PET toward personalized radiotherapy or chemoradiotherapy in lung cancer

Purpose We investigated the metabolic response of lung cancer to radiotherapy or chemoradiotherapy by 18F-FDG PET and its utility in guiding timely supplementary therapy. Methods: Glucose metabolic rate (MRglc) was measured in primary lung cancers during the 3 weeks before, and 10–12 days (S2), 3 months (S3), 6 months (S4), and 12 months (S5) after radiotherapy or chemoradiotherapy. The association between the lowest residual MRglc representing the maximum metabolic response (MRglc-MMR) and tumor control probability (TCP) at 12 months was modeled using logistic regression. Results: We accrued 106 patients, of whom 61 completed the serial 18F-FDG PET scans. The median values of MRglc at S2, S3 and S4 determined using a simplified kinetic method (SKM) were, respectively, 0.05, 0.06 and 0.07 μmol/min/g for tumors with local control and 0.12, 0.16 and 0.19 μmol/min/g for tumors with local failure, and the maximum standard uptake values (SUVmax) were 1.16, 1.33 and 1.45 for tumors with local control and 2.74, 2.74 and 4.07 for tumors with local failure (p < 0.0001). MRglc-MMR was realized at S2 (MRglc-S2) and the values corresponding to TCP 95 %, 90 % and 50 % were 0.036, 0.050 and 0.134 μmol/min/g using the SKM and 0.70, 0.91 and 1.95 using SUVmax, respectively. Probability cut-off values were generated for a given level of MRglc-S2 based on its predicted TCP, sensitivity and specificity, and MRglc ≤0.071 μmol/min/g and SUVmax ≤1.45 were determined as the optimum cut-off values for predicted TCP 80 %, sensitivity 100 % and specificity 63 %. Conclusion: The cut-off values (MRglc ≤0.071 μmol/min/g using the SKM and SUVmax ≤1.45) need to be tested for their utility in identifying patients with a high risk of residual cancer after standard dose radiotherapy or chemoradiotherapy and in guiding a timely supplementary dose of radiation or other means of salvage therapy. Electronic supplementary material The online version of this article (doi:10.1007/s00259-013-2348-4) contains supplementary material, which is available to authorized users

A single-nucleotide polymorphism in the methylene tetrahydrofolate reductase (MTHFR) gene is associated with risk of radiation pneumonitis in lung cancer patients treated with thoracic radiation therapy

Background: To study the association between functional single nucleotide polymorphisms (SNPs) in candidate genes from oxidative stress pathways, and risk of radiation pneumonitis (RP) in patients treated with thoracic radiation therapy (RT) for locally advanced lung cancer (LC). Methods: We reviewed 136 patients treated with RT for LC between 2001 and 2007, and had prior genotyping of functional SNPs in oxidative stress genes including superoxide dismutase 2 (SOD2; rs4880) and methylenetetrahydrofolate reductase (MTHFR; rs1801131, rs1801133). RP events were retrospectively scored using the Common Terminology Criteria for Adverse Events, version 4.0. Cox proportional hazard regression was performed to identify clinical variables and genotypes associated with risk of grade ≥2 and grade ≥3 RP on univariate and multivariate analysis. P-values were corrected for multiple hypothesis testing. Results: With a median follow-up of 21.4 months, the incidence of ≥grade 2 RP was 29% and ≥grade 3 RP was 14%. On multivariate analysis, after adjusting for clinical factors such as concurrent chemotherapy, and consolidation docetaxel, and lung dosimetric parameters such as V20 and mean lung dose, MTHFR genotype (rs1801131; AA versus AC/CC) was significantly associated with risk of ≥grade 2 RP (Hazard ratio [HR]: 0.37; 95% confidence interval [CI]: 0.18-0.76; p=0.006, corrected p=0.018) and ≥grade 3 RP (HR: 0.21; 95% CI: 0.06-0.70; p=0.01; corrected p=0.03). SOD2 genotype was not associated with RP. Conclusions: Our study showed an association between MTHFR genotype and risk of clinically significant RP. Further study of MTHFR-related pathways may provide insight into the mechanisms behind RP

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Effects of Interfractional Anatomical Changes on Water-Equivalent Pathlength in Charged-Particle Radiotherapy of Lung Cancer

Intrafractional motion and interfractional changes affect the accuracy of the delivered dose in radiotherapy, particularly in charged-particle radiotherapy. Most recent studies are focused on intrafractional motion (respiratory motion). Here, we report a quantitative simulation analysis of the effects of interfractional changes on water-equivalent pathlength (WEL) in charged-particle lung therapy. Serial four-dimensional (4D) CT scans were performed under free breathing conditions; the time span between the first and second 4DCT scans was five weeks. We quantified WEL changes between the first and second CT scans due to interfractional changes (tumor shrinkage and tissue density changes) and compared the particle-beam-stopping point between the serial 4DCT scans with use of the same initial bolus. Both tumor-shrinkage and lung-density changes were observed in a single patient over the course of therapy. The lung density decreased by approximately 0.1 g/cm3 between the first and second-CT scans, resulting in a 1.5 cm WEL changes. Tumor shrinkage resulted in approximately 3 cm WEL changes. If the same initial bolus and plan were used through the treatment course, an unexpected significant beam overshoot would occur by interfractional changes due to tumor shrinkage and lung density variation

Two years after pandemic influenza A/2009/H1N1: What have we learned?

The world had been anticipating another influenza pandemic since the last one in 1968. The pandemic influenza A H1N1 2009 virus (A/2009/H1N1) finally arrived, causing the first pandemic influenza of the new millennium, which has affected over 214 countries and caused over 18,449 deaths. Because of the persistent threat from the A/H5N1 virus since 1997 and the outbreak of the severe acute respiratory syndrome (SARS) coronavirus in 2003, medical and scientific communities have been more prepared in mindset and infrastructure. This preparedness has allowed for rapid and effective research on the epidemiological, clinical, pathological, immunological, virological, and other basic scientific aspects of the disease, with impacts on its control. A PubMed search using the keywords "pandemic influenza virus H1N1 2009" yielded over 2,500 publications, which markedly exceeded the number published on previous pandemics. Only representative works with relevance to clinical microbiology and infectious diseases are reviewed in this article. A significant increase in the understanding of this virus and the disease within such a short amount of time has allowed for the timely development of diagnostic tests, treatments, and preventive measures. These findings could prove useful for future randomized controlled clinical trials and the epidemiological control of future pandemics. © 2012, American Society for Microbiology. All Rights Reserved.link_to_subscribed_fulltex

Dark Energy Survey Year 3 results: galaxy sample for BAO measurement

In this paper, we present and validate the galaxy sample used for the analysis of the baryon acoustic oscillation (BAO) signal in the Dark Energy Survey (DES) Y3 data. The definition is based on a colour and redshift-dependent magnitude cut optimized to select galaxies at redshifts higher than 0.5, while ensuring a high-quality determination. The sample covers ∼4100 deg2to a depth of i = 22.3 (AB) at 10σ. It contains 7031 993 galaxies in the redshift range from z = 0.6 to 1.1, with a mean effective redshift of 0.835. Redshifts are estimated with the machine learning algorithm dnf, and are validated using the VIPERS PDR2 sample. We find a mean redshift bias of zbias∼0.01 and a mean uncertainty, in units of 1 + z⁠, of σ68∼0.03⁠. We evaluate the galaxy population of the sample, showing it is mostly built upon Elliptical to Sbc types. Furthermore, we find a low level of stellar contamination of ≲4 per cent⁠. We present the method used to mitigate the effect of spurious clustering coming from observing conditions and other large-scale systematics. We apply it to the BAO sample and calculate weights that are used to get a robust estimate of the galaxy clustering signal. This paper is one of a series dedicated to the analysis of the BAO signal in DES Y3. In the companion papers, we present the galaxy mock catalogues used to calibrate the analysis and the angular diameter distance constraints obtained through the fitting to the BAO scale