Adjuvant Chemotherapy for Muscle-invasive Bladder Cancer : A Systematic Review and Meta-analysis of Individual Participant Data from Randomised Controlled Trials

Context Our prior systematic review and meta-analysis of individual participant data (IPD) suggesting a benefit of adjuvant chemotherapy for muscle-invasive bladder cancer was limited by the number and size of included randomised trials. We have updated results to include additional trials, providing the most up-to-date and reliable evidence of the effects of this treatment. Objective To investigate the role of adjuvant cisplatin-based chemotherapy in the treatment of muscle-invasive bladder cancer. Evidence acquisition Published and unpublished trials were sought via searches of bibliographic databases, trials registers, conference proceedings, and hand searching. Updated IPD were centrally collected, checked, and analysed. Results from individual randomised controlled trials (RCTs) were combined using a two-stage fixed-effect model. Prespecified analyses explored any variation in effect by trial and participant characteristics. Evidence synthesis Analyses of ten RCTs (1183 participants) demonstrated a benefit of cisplatin-based adjuvant chemotherapy on overall survival (hazard ratio [HR] = 0.82, 95% confidence interval [CI] = 0.70–0.96, p = 0.02). This represents an absolute improvement in survival of 6% at 5 yr, from 50% to 56%, and a 9% absolute benefit when adjusted for age, sex, pT stage, and pN category (HR = 0.77, 95% CI = 0.65–0.92, p = 0.004). There was no clear evidence that the effect varied by trial or participant characteristics. Adjuvant chemotherapy was also shown to improve recurrence-free survival (HR = 0.71, 95% CI = 0.60–0.83, p < 0.001), locoregional recurrence-free survival (HR = 0.68, 95% CI = 0.55–0.85, p < 0.001), and metastasis-free survival (HR = 0.79, 95% CI = 0.65–0.95, p = 0.01), with absolute benefits of 11%, 11%, and 8%, respectively. Conclusions This systematic review and meta-analysis demonstrates that cisplatin-based adjuvant chemotherapy is a valid option for improving outcomes for muscle-invasive bladder cancer. Patient summary We looked at the effect of cisplatin-based chemotherapy on outcomes in participants with muscle-invasive bladder cancer. We gathered this information from eligible randomised controlled trials. We demonstrated that cisplatin-based chemotherapy is a valid option for improving outcomes of muscle-invasive bladder cancer

Numerosity Estimation in Visual Stimuli in the Absence of Luminance-Based Cues

Numerosity estimation is a basic preverbal ability that humans share with many animal species and that is believed to be foundational of numeracy skills. It is notoriously difficult, however, to establish whether numerosity estimation is based on numerosity itself, or on one or more non-numerical cues like-in visual stimuli-spatial extent and density. Frequently, different non-numerical cues are held constant on different trials. This strategy, however, still allows numerosity estimation to be based on a combination of non-numerical cues rather than on any particular one by itself.Here we introduce a novel method, based on second-order (contrast-based) visual motion, to create stimuli that exclude all first-order (luminance-based) cues to numerosity. We show that numerosities can be estimated almost as well in second-order motion as in first-order motion.The results show that numerosity estimation need not be based on first-order spatial filtering, first-order density perception, or any other processing of luminance-based cues to numerosity. Our method can be used as an effective tool to control non-numerical variables in studies of numerosity estimation

The Gaia mission

Gaia is a cornerstone mission in the science programme of the EuropeanSpace Agency (ESA). The spacecraft construction was approved in 2006, following a study in which the original interferometric concept was changed to a direct-imaging approach. Both the spacecraft and the payload were built by European industry. The involvement of the scientific community focusses on data processing for which the international Gaia Data Processing and Analysis Consortium (DPAC) was selected in 2007. Gaia was launched on 19 December 2013 and arrived at its operating point, the second Lagrange point of the Sun-Earth-Moon system, a few weeks later. The commissioning of the spacecraft and payload was completed on 19 July 2014. The nominal five-year mission started with four weeks of special, ecliptic-pole scanning and subsequently transferred into full-sky scanning mode. We recall the scientific goals of Gaia and give a description of the as-built spacecraft that is currently (mid-2016) being operated to achieve these goals. We pay special attention to the payload module, the performance of which is closely related to the scientific performance of the mission. We provide a summary of the commissioning activities and findings, followed by a description of the routine operational mode. We summarise scientific performance estimates on the basis of in-orbit operations. Several intermediate Gaia data releases are planned and the data can be retrieved from the Gaia Archive, which is available through the Gaia home page. http://www.cosmos.esa.int/gai

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

The side effects of Bacillus Calmette-Guerin in the treatment of Ta T1 bladder cancer do not predict its efficacy: Results from a European organisation for research and treatment of cancer genito-urinary group phase III trial

Objectives: Previous publications have suggested that patients developing local and/or systemic side effects to Bacillus Calmette-Guerin (BCG) have a better clinical result, however it is necessary to determine if toxicity is responsible for improved efficacy. Methods: After transurethral resection, intravesical instillations of BCG were given during a 6-week induction course followed by 3-weekly maintenance courses at 3, 6, 12, 18, 24, 30 and 36 months. The prognostic importance of delaying or stopping BCG due to local and/or systemic side effects was assessed in 487 patients. Results: Patients with local BCG side effects had a significantly longer time to first recurrence, suggesting that side effects are related to efficacy. However patients with a better outcome remain on study for a longer period of time and receive more BCG, thus increasing their risk to develop side effects. To prove whether toxicity is responsible for improved efficacy, the prognostic importance of toxicity occurring prior to the 6 month instillations was assessed using the landmark method. Neither local nor systemic BCG toxicity prior to 6 months was related to subsequent recurrence. Conclusions: While a correlation between BCG toxicity and efficacy exists, this study does not confirm that BCG toxicity is actually responsible for an improved outcome. (C) 2003 Elsevier B.V. All rights reserved

Somatostatin receptor subtypes in hormone-refractory (castration-resistant) prostatic carcinoma

The aim of this study was to examine the tissue expression and localisation of the somatostatin receptors (SSTRs) in hormone-refractory (HR) prostate cancer (PCa). Five SSTRs were evaluated immunohistochemically in 20 radical prostatectomies (RPs) with Gleason score (GS) 3+3=6 PCa, in 20 RPs with GS 4+4=8 and 4+5=9 PCa, and 20 transurethral resection of the prostate specimens with HR PCa. The mean values in the cytoplasm (all five SSTRs were expressed), membrane (only SSTR3 and SSTR4 were expressed) and nuclei (only SSTR4 and SSTR5 were expressed) of the glands in HR PCa were 20-70% lower than in the other two groups, the differences being statistically significant. All five SSTRs were expressed in the smooth muscle and endothelial cells of HR PCa, the mean values being lower than in the other two groups. In conclusion, this study expands our knowledge on the expression and localisation of five SSTRs in the various tissue components in the HR PCa compared with hormone-sensitive PCa. Asian Journal of Andrology (2011) 13, 242-247; doi:10.1038/aja.2010.100; published online 13 December 201