407 research outputs found
Adjuvant chemotherapy with or without bevacizumab in patients with resected non-small-cell lung cancer (E1505): an open-label, multicentre, randomised, phase 3 trial.
BackgroundAdjuvant chemotherapy for resected early-stage non-small-cell lung cancer (NSCLC) provides a modest survival benefit. Bevacizumab, a monoclonal antibody directed against VEGF, improves outcomes when added to platinum-based chemotherapy in advanced-stage non-squamous NSCLC. We aimed to evaluate the addition of bevacizumab to adjuvant chemotherapy in early-stage resected NSCLC.MethodsWe did an open-label, randomised, phase 3 trial of adult patients (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1 and who had completely resected stage IB (≥4 cm) to IIIA (defined by the American Joint Committee on Cancer 6th edition) NSCLC. We enrolled patients from across the US National Clinical Trials Network, including patients from the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) affiliates in Europe and from the Canadian Cancer Trials Group, within 6-12 weeks of surgery. The chemotherapy regimen for each patient was selected before randomisation and administered intravenously; it consisted of four 21-day cycles of cisplatin (75 mg/m2 on day 1 in all regimens) in combination with investigator's choice of vinorelbine (30 mg/m2 on days 1 and 8), docetaxel (75 mg/m2 on day 1), gemcitabine (1200 mg/m2 on days 1 and 8), or pemetrexed (500 mg/m2 on day 1). Patients in the bevacizumab group received bevacizumab 15 mg/kg intravenously every 21 days starting with cycle 1 of chemotherapy and continuing for 1 year. We randomly allocated patients (1:1) to group A (chemotherapy alone) or group B (chemotherapy plus bevacizumab), centrally, using permuted blocks sizes and stratified by chemotherapy regimen, stage of disease, histology, and sex. No one was masked to treatment assignment, except the Data Safety and Monitoring Committee. The primary endpoint was overall survival, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00324805.FindingsBetween June 1, 2007, and Sept 20, 2013, 1501 patients were enrolled and randomly assigned to the two treatment groups: 749 to group A (chemotherapy alone) and 752 to group B (chemotherapy plus bevacizumab). 383 (26%) of 1458 patients (with complete staging information) had stage IB, 636 (44%) had stage II, and 439 (30%) had stage IIIA disease (stage of disease data were missing for 43 patients). Squamous cell histology was reported for 422 (28%) of 1501 patients. All four cisplatin-based chemotherapy regimens were used: 377 (25%) patients received vinorelbine, 343 (23%) received docetaxel, 283 (19%) received gemcitabine, and 497 (33%) received pemetrexed. At a median follow-up of 50·3 months (IQR 32·9-68·0), the estimated median overall survival in group A has not been reached, and in group B was 85·8 months (95% CI 74·9 to not reached); hazard ratio (group B vs group A) 0·99 (95% CI 0·82-1·19; p=0·90). Grade 3-5 toxicities of note (all attributions) that were reported more frequently in group B (the bevacizumab group) than in group A (chemotherapy alone) were overall worst grade (ie, all grade 3-5 toxicities; 496 [67%] of 738 in group A vs 610 [83%] of 735 in group B), hypertension (60 [8%] vs 219 [30%]), and neutropenia (241 [33%] vs 275 [37%]). The number of deaths on treatment did not differ between the groups (15 deaths in group A vs 19 in group B). Of these deaths, three in group A and ten in group B were considered at least possibly related to treatment.InterpretationAddition of bevacizumab to adjuvant chemotherapy did not improve overall survival for patients with surgically resected early-stage NSCLC. Bevacizumab does not have a role in this setting and should not be considered as an adjuvant therapy for patients with resected early-stage NSCLC.FundingNational Cancer Institute of the National Institutes of Health
Observation of resonances consistent with pentaquark states in decays
Observations of exotic structures in the channel, that we refer to
as pentaquark-charmonium states, in decays are
presented. The data sample corresponds to an integrated luminosity of 3/fb
acquired with the LHCb detector from 7 and 8 TeV pp collisions. An amplitude
analysis is performed on the three-body final-state that reproduces the
two-body mass and angular distributions. To obtain a satisfactory fit of the
structures seen in the mass spectrum, it is necessary to include two
Breit-Wigner amplitudes that each describe a resonant state. The significance
of each of these resonances is more than 9 standard deviations. One has a mass
of MeV and a width of MeV, while the second
is narrower, with a mass of MeV and a width of MeV. The preferred assignments are of opposite parity, with one
state having spin 3/2 and the other 5/2.Comment: 48 pages, 18 figures including the supplementary material, v2 after
referee's comments, now 19 figure
Observation of the decay
The decay is observed in collision
data corresponding to an integrated luminosity of 3 fb recorded by the
LHCb detector at centre-of-mass energies of 7 TeV and 8 TeV. This is the first
observation of this decay channel, with a statistical significance of 15
standard deviations. The mass of the meson is measured to be
MeV/c. The branching fraction ratio
is measured to be 0.0115\,\pm\, 0.0012\, ^{+0.0005}_{-0.0009}.
In both cases, the first uncertainty is statistical and the second is
systematic. No evidence for non-resonant or decays is found.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-033.htm
Measurement of the CKM angle γ from a combination of B±→Dh± analyses
A combination of three LHCb measurements of the CKM angle γ is presented. The decays B±→D K± and
B±→Dπ± are used, where D denotes an admixture of D0 and D0 mesons, decaying into K+K−, π+π−, K±π∓, K±π∓π±π∓, K0Sπ+π−, or K0S K+K− final states. All measurements use a dataset corresponding to 1.0 fb−1 of integrated luminosity. Combining results from B±→D K± decays alone a best-fit value of
γ =72.0◦ is found, and confidence intervals are set
γ ∈ [56.4,86.7]◦ at 68% CL,
γ ∈ [42.6,99.6]◦ at 95% CL.
The best-fit value of γ found from a combination of results from B±→Dπ± decays alone, is γ =18.9◦,
and the confidence intervals
γ ∈ [7.4,99.2]◦ ∪ [167.9,176.4]◦ at 68% CL
are set, without constraint at 95% CL. The combination of results from B± → D K± and B± → Dπ±
decays gives a best-fit value of γ =72.6◦ and the confidence intervals
γ ∈ [55.4,82.3]◦ at 68% CL,
γ ∈ [40.2,92.7]◦ at 95% CL
are set. All values are expressed modulo 180◦, and are obtained taking into account the effect of D0–D0
mixing
Study of decays to the final state and evidence for the decay
A study of decays is performed for the first time
using data corresponding to an integrated luminosity of 3.0
collected by the LHCb experiment in collisions at centre-of-mass energies
of and TeV. Evidence for the decay
is reported with a significance of 4.0 standard deviations, resulting in the
measurement of
to
be .
Here denotes a branching fraction while and
are the production cross-sections for and mesons.
An indication of weak annihilation is found for the region
, with a significance of
2.4 standard deviations.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-022.html,
link to supplemental material inserted in the reference
Measurement of the ratio of branching fractions BR(B0 -> K*0 gamma)/BR(Bs0 -> phi gamma)
The ratio of branching fractions of the radiative B decays B0 -> K*0 gamma
and Bs0 -> phi gamma has been measured using 0.37 fb-1 of pp collisions at a
centre of mass energy of sqrt(s) = 7 TeV, collected by the LHCb experiment. The
value obtained is BR(B0 -> K*0 gamma)/BR(Bs0 -> phi gamma) = 1.12 +/- 0.08
^{+0.06}_{-0.04} ^{+0.09}_{-0.08}, where the first uncertainty is statistical,
the second systematic and the third is associated to the ratio of fragmentation
fractions fs/fd. Using the world average for BR(B0 -> K*0 gamma) = (4.33 +/-
0.15) x 10^{-5}, the branching fraction BR(Bs0 -> phi gamma) is measured to be
(3.9 +/- 0.5) x 10^{-5}, which is the most precise measurement to date.Comment: 15 pages, 1 figure, 2 table
Precise measurements of the properties of the B-1(5721)(0,+) and B-2*(5747)(0,+) states and observation of B-+,B-0 pi(-,+) mass structures
Invariant mass distributions of B+π− and B0π+ combinations are investigated in order to study excited B mesons. The analysis is based on a data sample corresponding to 3.0 fb−1 of pp collision data, recorded by the LHCb detector at centre-of-mass energies of 7 and 8 TeV. Precise measurements of the masses and widths of the B1(5721)0,+ and B2(5747)0,+ states are reported. Clear enhancements, particularly prominent at high pion transverse momentum, are seen over background in the mass range 5850-6000 MeV in both B+π− and B0π+ combinations. The structures are consistent with the presence of four excited B mesons, labelled BJ (5840)0,+ and BJ (5960)0,+, whose masses and widths are obtained under different hypotheses for their quantum numbers
Amplitude analysis of decays
The first full amplitude analysis of with
, decays is performed with a data sample
of 3 fb of collision data collected at and TeV
with the LHCb detector. The data cannot be described by a model that contains
only excited kaon states decaying into , and four
structures are observed, each with significance over standard deviations.
The quantum numbers of these structures are determined with significance of at
least standard deviations. The lightest has mass consistent with, but width
much larger than, previous measurements of the claimed state. The
model includes significant contributions from a number of expected kaon
excitations, including the first observation of the
transition.Comment: 62 pages 26 figure
Emerging ethnic differences in lung cancer therapy
Although global clinical trials for lung cancer can enable the development of new agents efficiently, whether the results of clinical trials performed in one population can be fully extrapolated to another population remains questionable. A comparison of phase III trials for the same drug combinations against lung cancer in different countries shows a great diversity in haematological toxicity. One possible reason for this diversity may be that different ethnic populations may have different physiological capacities for white blood cell production and maturation. In addition, polymorphisms in the promoter and coding regions of drug-metabolising enzymes (e.g., CYP3A4 and UGT1A1) or in transporters (e.g., ABCB1) may vary among different ethnic populations. For example, epidermal growth factor receptor (EGFR) inhibitors are more effective in Asian patients than in patients of other ethnicities, a characteristic that parallels the incidence of EGFR-activating mutations. Interstitial lung disease associated with the administration of gefitinib is also more common among Japanese patients than among patients of other ethnicities. Although research into these differences has just begun, these studies suggest that possible pharmacogenomic and tumour genetic differences associated with individual responses to anticancer agents should be carefully considered when conducting global clinical trials
Differential branching fractions and isospin asymmetries of B -> K ((*)) μ(+) μ(-) decays
The isospin asymmetries of B -> K μ(+) μ(-) and B -> K (*) μ(+) μ(-) decays and the partial branching fractions of the B (0) -> K (0) μ(+) μ(-), B (+) -> K (+) μ(+) μ(-) and B (+) -> K (*+) μ(+) μ(-) decays are measured as functions of the dimuon mass squared, q (2). The data used correspond to an integrated luminosity of 3 fb(-1) from proton-proton collisions collected with the LHCb detector at centre-of-mass energies of 7 TeV and 8 TeV in 2011 and 2012, respectively. The isospin asymmetries are both consistent with the Standard Model expectations. The three measured branching fractions favour lower values than their respective theoretical predictions, however they are all individually consistent with the Standard Model
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