1,328 research outputs found
Chemotherapy for advanced gastric cancer.
Gastric cancer is the fifth most common cancer worldwide. In "Western" countries, most people are either diagnosed at an advanced stage, or develop a relapse after surgery with curative intent. In people with advanced disease, significant benefits from targeted therapies are currently limited to HER-2 positive disease treated with trastuzumab, in combination with chemotherapy, in first-line. In second-line, ramucirumab, alone or in combination with paclitaxel, demonstrated significant survival benefits. Thus, systemic chemotherapy remains the mainstay of treatment for advanced gastric cancer. Uncertainty remains regarding the choice of the regimen.
To assess the efficacy of chemotherapy versus best supportive care (BSC), combination versus single-agent chemotherapy and different chemotherapy combinations in advanced gastric cancer.
We searched the Cochrane Central Register of Controlled Trials, MEDLINE and Embase up to June 2016, reference lists of studies, and contacted pharmaceutical companies and experts to identify randomised controlled trials (RCTs).
We considered only RCTs on systemic, intravenous or oral chemotherapy versus BSC, combination versus single-agent chemotherapy and different chemotherapy regimens in advanced gastric cancer.
Two review authors independently identified studies and extracted data. A third investigator was consulted in case of disagreements. We contacted study authors to obtain missing information.
We included 64 RCTs, of which 60 RCTs (11,698 participants) provided data for the meta-analysis of overall survival. We found chemotherapy extends overall survival (OS) by approximately 6.7 months more than BSC (hazard ratio (HR) 0.3, 95% confidence intervals (CI) 0.24 to 0.55, 184 participants, three studies, moderate-quality evidence). Combination chemotherapy extends OS slightly (by an additional month) versus single-agent chemotherapy (HR 0.84, 95% CI 0.79 to 0.89, 4447 participants, 23 studies, moderate-quality evidence), which is partly counterbalanced by increased toxicity. The benefit of epirubicin in three-drug combinations, in which cisplatin is replaced by oxaliplatin and 5-FU is replaced by capecitabine is unknown.Irinotecan extends OS slightly (by an additional 1.6 months) versus non-irinotecan-containing regimens (HR 0.87, 95% CI 0.80 to 0.95, 2135 participants, 10 studies, high-quality evidence).Docetaxel extends OS slightly (just over one month) compared to non-docetaxel-containing regimens (HR 0.86, 95% CI 0.78 to 0.95, 2001 participants, eight studies, high-quality evidence). However, due to subgroup analyses, we are uncertain whether docetaxel-containing combinations (docetaxel added to a single-agent or two-drug combination) extends OS due to moderate-quality evidence (HR 0.80, 95% CI 0.71 to 0.91, 1466 participants, four studies, moderate-quality evidence). When another chemotherapy was replaced by docetaxel, there is probably little or no difference in OS (HR 1.05; 0.87 to 1.27, 479 participants, three studies, moderate-quality evidence). We found there is probably little or no difference in OS when comparing capecitabine versus 5-FU-containing regimens (HR 0.94, 95% CI 0.79 to 1.11, 732 participants, five studies, moderate-quality evidence) .Oxaliplatin may extend (by less than one month) OS versus cisplatin-containing regimens (HR 0.81, 95% CI 0.67 to 0.98, 1105 participants, five studies, low-quality evidence). We are uncertain whether taxane-platinum combinations with (versus without) fluoropyrimidines extend OS due to very low-quality evidence (HR 0.86, 95% CI 0.71 to 1.06, 482 participants, three studies, very low-quality evidence). S-1 regimens improve OS slightly (by less than an additional month) versus 5-FU-containing regimens (HR 0.91, 95% CI 0.83 to 1.00, 1793 participants, four studies, high-quality evidence), however since S-1 is used in different doses and schedules between Asian and non-Asian population, the applicability of this finding to individual populations is uncertain.
Chemotherapy improves survival (by an additional 6.7 months) in comparison to BSC, and combination chemotherapy improves survival (by an additional month) compared to single-agent 5-FU. Testing all patients for HER-2 status may help to identify patients with HER-2-positive tumours, for whom, in the absence of contraindications, trastuzumab in combination with capecitabine or 5-FU in combination with cisplatin has been shown to be beneficial. For HER-2 negative people, all different two-and three-drug combinations including irinotecan, docetaxel, oxaliplatin or oral 5-FU prodrugs are valid treatment options for advanced gastric cancer, and consideration of the side effects of each regimen is essential in the treatment decision. Irinotecan-containing combinations and docetaxel-containing combinations (in which docetaxel was added to a single-agent or two-drug (platinum/5-FUcombination) show significant survival benefits in the comparisons studied above. Furthermore, docetaxel-containing three-drug regimens have increased response rates, but the advantages of the docetaxel-containing three-drug combinations (DCF, FLO-T) are counterbalanced by increased toxicity. Additionally, oxaliplatin-containing regimens demonstrated a benefit in OS as compared to the same regimen containing cisplatin, and there is a modest survival improvement of S-1 compared to 5-FU-containing regimens.Whether the survival benefit for three-drug combinations including cisplatin, 5-FU, and epirubicin as compared to the same regimen without epirubicin is still valid when second-line therapy is routinely administered and when cisplatin is replaced by oxaliplatin and 5-FU by capecitabine is questionable. Furthermore, the magnitude of the observed survival benefits for the three-drug regimens is not large enough to be clinically meaningful as defined recently by the American Society for Clinical Oncology (Ellis 2014). In contrast to the comparisons in which a survival benefit was observed by adding a third drug to a two-drug regimen at the cost of increased toxicity, the comparison of regimens in which another chemotherapy was replaced by irinotecan was associated with a survival benefit (of borderline statistical significance), but without increased toxicity. For this reason irinotecan/5-FU-containing combinations are an attractive option for first-line treatment. Although they need to be interpreted with caution, subgroup analyses of one study suggest that elderly people have a greater benefit form oxaliplatin, as compared to cisplatin-based regimens, and that people with locally advanced disease or younger than 65 years might benefit more from a three-drug regimen including 5-FU, docetaxel, and oxaliplatin as compared to a two-drug combination of 5-FU and oxaliplatin, a hypothesis that needs further confirmation. For people with good performance status, the benefit of second-line chemotherapy has been established in several RCTs
Phenomenology of the nMSSM from colliders to cosmology
Low energy supersymmetric models provide a solution to the hierarchy problem
and also have the necessary ingredients to solve two of the most outstanding
issues in cosmology: the origin of dark matter and baryonic matter. One of the
most attractive features of this framework is that the relevant physical
processes are related to interactions at the weak scale and therefore may be
tested in collider experiments in the near future. This is true for the Minimal
Supersymmetric Standard Model (MSSM) as well as for its extension with the
addition of one singlet chiral superfield, the so-called nMSSM. It has been
recently shown that within the nMSSM an elegant solution to both the problem of
baryogenesis and dark matter may be found, that relies mostly on the mixing of
the singlet sector with the Higgs sector of the theory. In this work we review
the nMSSM model constraints from cosmology and present the associated collider
phenomenology at the LHC and the ILC. We show that the ILC will efficiently
probe the neutralino, chargino and Higgs sectors, allowing to confront
cosmological observations with computations based on collider measurements. We
also investigate the prospects for a direct detection of dark matter and the
constraints imposed by the current bounds of the electron electric dipole
moment in this model.Comment: 44 pp, 10 figures; Fig.9 replaced; discussion on CP violation
extended and references added; few minor additions in text about details of
the cut
How Many CMEs Have Flux Ropes? Deciphering the Signatures of Shocks, Flux Ropes, and Prominences in Coronagraph Observations of CMEs
We intend to provide a comprehensive answer to the question on whether all
Coronal Mass Ejections (CMEs) have flux rope structure. To achieve this, we
present a synthesis of the LASCO CME observations over the last sixteen years,
assisted by 3D MHD simulations of the breakout model, EUV and coronagraphic
observations from STEREO and SDO, and statistics from a revised LASCO CME
database. We argue that the bright loop often seen as the CME leading edge is
the result of pileup at the boundary of the erupting flux rope irrespective of
whether a cavity or, more generally, a 3-part CME can be identified. Based on
our previous work on white light shock detection and supported by the MHD
simulations, we identify a new type of morphology, the `two-front' morphology.
It consists of a faint front followed by diffuse emission and the bright
loop-like CME leading edge. We show that the faint front is caused by density
compression at a wave (or possibly shock) front driven by the CME. We also
present high-detailed multi-wavelength EUV observations that clarify the
relative positioning of the prominence at the bottom of a coronal cavity with
clear flux rope structure. Finally, we visually check the full LASCO CME
database for flux rope structures. In the process, we classify the events into
two clear flux rope classes (`3-part', `Loop'), jets and outflows (no clear
structure). We find that at least 40% of the observed CMEs have clear flux rope
structures. We propose a new definition for flux rope CMEs (FR-CMEs) as a
coherent magnetic, twist-carrying coronal structure with angular width of at
least 40 deg and able to reach beyond 10 Rsun which erupts on a time scale of a
few minutes to several hours. We conclude that flux ropes are a common
occurrence in CMEs and pose a challenge for future studies to identify CMEs
that are clearly not FR-CMEs.Comment: 26 pages, 9 figs, to be published in Solar Physics Topical Issue
"Flux Rope Structure of CMEs
Production of Lambda and Sigma^0 hyperons in proton-proton collisions
This paper reports results on simultaneous measurements of the reaction
channels pp -> pK+\Lambda and pp -> pK+\Sigma^0 at excess energies of 204, 239,
and 284 MeV (\Lambda) and 127, 162, and 207 MeV (\Sigma^0). Total and
differential cross sections are given for both reactions. It is concluded from
the measured total cross sections that the high energy limit of the cross
section ratio is almost reached at an excess energy of only about 200 MeV. From
the differential distributions observed in the overall CMS as well as in the
Jackson and helicity frames, a significant contribution of interfering nucleon
resonances to the \Lambda production mechanism is concluded while resonant
\Sigma^0-production seems to be of lesser importance and takes place only
through specific partial waves of the entrance channel. The data also indicate
that kaon exchange plays a minor role in the case of \Lambda- but an important
role for \Sigma^0-production. Thus the peculiar energy dependence of the
\Lambda-to-\Sigma^0 cross section ratio appears in a new light as its
explanation requires more than mere differences between the p\Lambda and the
p\Sigma^0 final state interaction. The data provide a benchmark for theoretical
models already available or yet to come.Comment: 18 pages, 10 figures; accepted by The European Physical Journal A
(EPJ A
Discovery of the Binary Pulsar PSR B1259-63 in Very-High-Energy Gamma Rays around Periastron with H.E.S.S
We report the discovery of very-high-energy (VHE) gamma-ray emission of the
binary system PSR B1259-63/SS 2883 of a radio pulsar orbiting a massive,
luminous Be star in a highly eccentric orbit. The observations around the 2004
periastron passage of the pulsar were performed with the four 13 m Cherenkov
telescopes of the H.E.S.S. experiment, recently installed in Namibia and in
full operation since December 2003. Between February and June 2004, a gamma-ray
signal from the binary system was detected with a total significance above 13
sigma. The flux was found to vary significantly on timescales of days which
makes PSR B1259-63 the first variable galactic source of VHE gamma-rays
observed so far. Strong emission signals were observed in pre- and
post-periastron phases with a flux minimum around periastron, followed by a
gradual flux decrease in the months after. The measured time-averaged energy
spectrum above a mean threshold energy of 380 GeV can be fitted by a simple
power law F_0(E/1 TeV)^-Gamma with a photon index Gamma =
2.7+-0.2_stat+-0.2_sys and flux normalisation F_0 = (1.3+-0.1_stat+-0.3_sys)
10^-12 TeV^-1 cm^-2 s^-1. This detection of VHE gamma-rays provides unambiguous
evidence for particle acceleration to multi-TeV energies in the binary system.
In combination with coeval observations of the X-ray synchrotron emission by
the RXTE and INTEGRAL instruments, and assuming the VHE gamma-ray emission to
be produced by the inverse Compton mechanism, the magnetic field strength can
be directly estimated to be of the order of 1 G.Comment: 10 pages, 8 figures, accepted in Astronomy and Astrophysics on 2 June
2005, replace: document unchanged, replaced author field in astro-ph entry -
authors are all members of the H.E.S.S. collaboration and three additional
authors (99+3, see document
Time-integrated luminosity recorded by the BABAR detector at the PEP-II e+e- collider
This article is the Preprint version of the final published artcile which can be accessed at the link below.We describe a measurement of the time-integrated luminosity of the data collected by the BABAR experiment at the PEP-II asymmetric-energy e+e- collider at the Ï(4S), Ï(3S), and Ï(2S) resonances and in a continuum region below each resonance. We measure the time-integrated luminosity by counting e+e-âe+e- and (for the Ï(4S) only) e+e-âÎŒ+ÎŒ- candidate events, allowing additional photons in the final state. We use data-corrected simulation to determine the cross-sections and reconstruction efficiencies for these processes, as well as the major backgrounds. Due to the large cross-sections of e+e-âe+e- and e+e-âÎŒ+ÎŒ-, the statistical uncertainties of the measurement are substantially smaller than the systematic uncertainties. The dominant systematic uncertainties are due to observed differences between data and simulation, as well as uncertainties on the cross-sections. For data collected on the Ï(3S) and Ï(2S) resonances, an additional uncertainty arises due to Ïâe+e-X background. For data collected off the Ï resonances, we estimate an additional uncertainty due to time dependent efficiency variations, which can affect the short off-resonance runs. The relative uncertainties on the luminosities of the on-resonance (off-resonance) samples are 0.43% (0.43%) for the Ï(4S), 0.58% (0.72%) for the Ï(3S), and 0.68% (0.88%) for the Ï(2S).This work is supported by the US Department of Energy and National Science Foundation, the Natural Sciences and Engineering Research Council (Canada), the Commissariat Ă lâEnergie Atomique and Institut National de Physique NuclĂ©aire et de Physiquedes Particules (France), the Bundesministerium fĂŒr Bildung und Forschung and Deutsche Forschungsgemeinschaft (Germany), the Istituto Nazionale di Fisica Nucleare (Italy), the Foundation for Fundamental Research on Matter (The Netherlands), the Research Council of Norway, the Ministry of Education and Science of the Russian Federation, Ministerio de Ciencia e InnovaciĂłn (Spain), and the Science and Technology Facilities Council (United Kingdom). Individuals have received support from the Marie-Curie IEF program (European Union) and the A.P. Sloan Foundation (USA)
First Measurement of Z/gamma* Production in Compton Scattering of Quasi-real Photons
We report the first observation of Z/gamma* production in Compton scattering
of quasi-real photons. This is a subprocess of the reaction e+e- to
e+e-Z/gamma*, where one of the final state electrons is undetected.
Approximately 55 pb-1 of data collected in the year 1997 at an e+e-
centre-of-mass energy of 183 GeV with the OPAL detector at LEP have been
analysed. The Z/gamma* from Compton scattering has been detected in the
hadronic decay channel. Within well defined kinematic bounds, we measure the
product of cross-section and Z/gamma* branching ratio to hadrons to be
(0.9+-0.3+-0.1) pb for events with a hadronic mass larger than 60 GeV,
dominated by (e)eZ production. In the hadronic mass region between 5 GeV and 60
GeV, dominated by (e)egamma* production, this product is found to be
(4.1+-1.6+-0.6) pb. Our results agree with the predictions of two Monte Carlo
event generators, grc4f and PYTHIA.Comment: 18 pages, LaTeX, 5 eps figures included, submitted to Physics Letters
Search for Higgs Bosons in e+e- Collisions at 183 GeV
The data collected by the OPAL experiment at sqrts=183 GeV were used to
search for Higgs bosons which are predicted by the Standard Model and various
extensions, such as general models with two Higgs field doublets and the
Minimal Supersymmetric Standard Model (MSSM). The data correspond to an
integrated luminosity of approximately 54pb-1. None of the searches for neutral
and charged Higgs bosons have revealed an excess of events beyond the expected
background. This negative outcome, in combination with similar results from
searches at lower energies, leads to new limits for the Higgs boson masses and
other model parameters. In particular, the 95% confidence level lower limit for
the mass of the Standard Model Higgs boson is 88.3 GeV. Charged Higgs bosons
can be excluded for masses up to 59.5 GeV. In the MSSM, mh > 70.5 GeV and mA >
72.0 GeV are obtained for tan{beta}>1, no and maximal scalar top mixing and
soft SUSY-breaking masses of 1 TeV. The range 0.8 < tanb < 1.9 is excluded for
minimal scalar top mixing and m{top} < 175 GeV. More general scans of the MSSM
parameter space are also considered.Comment: 49 pages. LaTeX, including 33 eps figures, submitted to European
Physical Journal
A Measurement of the Product Branching Ratio f(b->Lambda_b).BR(Lambda_b->Lambda X) in Z0 Decays
The product branching ratio, f(b->Lambda_b).BR(Lambda_b->Lambda X), where
Lambda_b denotes any weakly-decaying b-baryon, has been measured using the OPAL
detector at LEP. Lambda_b are selected by the presence of energetic Lambda
particles in bottom events tagged by the presence of displaced secondary
vertices. A fit to the momenta of the Lambda particles separates signal from B
meson and fragmentation backgrounds. The measured product branching ratio is
f(b->Lambda_b).BR(Lambda_b->Lambda X) = (2.67+-0.38(stat)+0.67-0.60(sys))%
Combined with a previous OPAL measurement, one obtains
f(b->Lambda_b).BR(Lambda_b->Lambda X) = (3.50+-0.32(stat)+-0.35(sys))%.Comment: 16 pages, LaTeX, 3 eps figs included, submitted to the European
Physical Journal
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