University of São Paulo

About: University of São Paulo is a education organization based out in São Paulo, Brazil. It is known for research contribution in the topics: Population & Context (language use). The organization has 136513 authors who have published 272320 publications receiving 5127869 citations. The organization is also known as: USP & Universidade de São Paulo.

Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial

Abstract: Summary Background Olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, has previously shown efficacy in a phase 2 study when given in capsule formulation to all-comer patients with platinum-sensitive, relapsed high-grade serous ovarian cancer. We aimed to confirm these findings in patients with a BRCA1 or BRCA2 (BRCA1/2 ) mutation using a tablet formulation of olaparib. Methods This international, multicentre, double-blind, randomised, placebo-controlled, phase 3 trial evaluated olaparib tablet maintenance treatment in platinum-sensitive, relapsed ovarian cancer patients with a BRCA1/2 mutation who had received at least two lines of previous chemotherapy. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status at baseline of 0–1 and histologically confirmed, relapsed, high-grade serous ovarian cancer or high-grade endometrioid cancer, including primary peritoneal or fallopian tube cancer. Patients were randomly assigned 2:1 to olaparib (300 mg in two 150 mg tablets, twice daily) or matching placebo tablets using an interactive voice and web response system. Randomisation was stratified by response to previous platinum chemotherapy (complete vs partial) and length of platinum-free interval (6–12 months vs ≥12 months) and treatment assignment was masked for patients, those giving the interventions, data collectors, and data analysers. The primary endpoint was investigator-assessed progression-free survival and we report the primary analysis from this ongoing study. The efficacy analyses were done on the intention-to-treat population; safety analyses included patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01874353, and is ongoing and no longer recruiting patients. Findings Between Sept 3, 2013, and Nov 21, 2014, we enrolled 295 eligible patients who were randomly assigned to receive olaparib (n=196) or placebo (n=99). One patient in the olaparib group was randomised in error and did not receive study treatment. Investigator-assessed median progression-free survival was significantly longer with olaparib (19·1 months [95% CI 16·3–25·7]) than with placebo (5·5 months [5·2–5·8]; hazard ratio [HR] 0·30 [95% CI 0·22–0·41], p vs two [2%] of 99 patients in the placebo group), fatigue or asthenia (eight [4%] vs two [2%]), and neutropenia (ten [5%] vs four [4%]). Serious adverse events were experienced by 35 (18%) patients in the olaparib group and eight (8%) patients in the placebo group. The most common in the olaparib group were anaemia (seven [4%] patients), abdominal pain (three [2%] patients), and intestinal obstruction (three [2%] patients). The most common in the placebo group were constipation (two [2%] patients) and intestinal obstruction (two [2%] patients). One (1%) patient in the olaparib group had a treatment-related adverse event (acute myeloid leukaemia) with an outcome of death. Interpretation Olaparib tablet maintenance treatment provided a significant progression-free survival improvement with no detrimental effect on quality of life in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation. Apart from anaemia, toxicities with olaparib were low grade and manageable. Funding AstraZeneca.

International Society of Geriatric Oncology Consensus on Geriatric Assessment in Older Patients With Cancer

Abstract: Purpose To update the International Society of Geriatric Oncology (SIOG) 2005 recommendations on geriatric assessment (GA) in older patients with cancer. Methods SIOG composed a panel with expertise in geriatric oncology to develop consensus statements after literature review of key evidence on the following topics: rationale for performing GA; findings from a GA performed in geriatric oncology patients; ability of GA to predict oncology treatment–related complications; association between GA findings and overall survival (OS); impact of GA findings on oncology treatment decisions; composition of a GA, including domains and tools; and methods for implementing GA in clinical care. Results GA can be valuable in oncology practice for following reasons: detection of impairment not identified in routine history or physical examination, ability to predict severe treatment-related toxicity, ability to predict OS in a variety of tumors and treatment settings, and ability to influence treatment choice and intensit...

Semi‐empirical analysis of Sloan Digital Sky Survey galaxies – I. Spectral synthesis method

Abstract: The study of stellar populations in galaxies is entering a new era with the availability of large and high-quality data bases of both observed galactic spectra and state-of-the-art evolutionary synthesis models. In this paper we investigate the power of spectral synthesis as a means to estimate the physical properties of galaxies. Spectral synthesis is nothing more than the decomposition of an observed spectrum in terms of a superposition of a base of simple stellar populations of various ages and metallicities, producing as output the star formation and chemical histories of a galaxy, its extinction and velocity dispersion. Our implementation of this method uses the recent models of Bruzual & Charlot and observed spectra in the 3650–8000 A range. The reliability of this approach is studied by three different means: (1) simulations, (2) comparison with previous work based on a different technique, and (3) analysis of the consistency of results obtained for a sample of galaxies from the Sloan Digital Sky Survey (SDSS). We find that spectral synthesis provides reliable physical parameters as long as one does not attempt a very detailed description of the star formation and chemical histories. Robust and physically interesting parameters are obtained by combining the (individually uncertain) strengths of each simple stellar population in the base. In particular, we show that, besides providing excellent fits to observed galaxy spectra, this method is able to recover useful information on the distributions of stellar ages and, more importantly, stellar metallicities. Stellar masses, velocity dispersion and extinction are also found to be accurately retrieved for realistic signal-to-noise ratios. We apply this synthesis method to a volume-limited sample of 50 362 galaxies from the SDSS Data Release 2, producing a catalogue of stellar population properties. Emission lines are also studied, their measurement being performed after subtracting the computed starlight spectrum from the observed one. A comparison with recent estimates of both observed and physical properties of these galaxies obtained by other groups shows good qualitative and quantitative agreement, despite substantial differences in the methods of analysis. The confidence in the present method is further strengthened by several empirical and astrophysically reasonable correlations between synthesis results and independent quantities. For instance, we report the existence of strong correlations between stellar and nebular metallicities, stellar and nebular extinctions, mean stellar age and equivalent width of Hα and 4000-A break, and between stellar mass and velocity dispersion.