Comparison of efficacy in patients with metastatic melanoma treated with ipilimumab and nivolumab who did or did not discontinue treatment due to immune-related adverse events:A real-world data study

SIMPLE SUMMARY: This retrospective study of real-world patients with metastatic melanoma shows that discontinuing treatment with combination immunotherapy due to adverse events does not result in a poorer outcome compared to patients that did not discontinue due to toxicity. This is important knowledge for clinicians and patients, as discontinuing treatment may cause great anxiety for patients because they believe that it may limit the response. ABSTRACT: Immune-related adverse events (irAEs) are very prevalent when treating patients with ipilimumab and nivolumab in combination, and 30–40% of patients discontinue the treatment for this reason. It is of high clinical relevance to investigate the consequences of discontinuing the treatment early since combination therapy with ipilimumab and nivolumab is the first line of treatment for many patients with metastatic melanoma. In this follow-up study, with real-world data from the nationwide DAMMED database, we investigated whether there was a difference in progression-free survival (PFS) and overall survival (OS) for patients who discontinued or did not discontinue treatment within the first four doses of treatment due to irAEs. In total, 448 patients were treated with ipilimumab and nivolumab. Of these, 133 patients discontinued due to irAEs in the induction phase. Using the Cox proportional hazards model, there was no significant difference in PFS when comparing the group that discontinued with the group that did not discontinue. The group that discontinued had a significantly longer OS than the group that received the full length of treatment. Therefore, we conclude that there is no significant negative impact on efficacy for patients who discontinue due to irAEs in the induction phase of combination immunotherapy for metastatic melanoma

Precision measurement of the mass difference between light nuclei and anti-nuclei

The measurement of the mass differences for systems bound by the strong force has reached a very high precision with protons and anti-protons1,2. The extension of such measurement from (anti-)baryons to (anti-)nuclei allows one to probe any difference in the interactions between nucleons and anti-nucleons encoded in the (anti-)nuclei masses. This force is a remnant of the underlying strong interaction among quarks and gluons and can be described by effective theories3, but cannot yet be directly derived from quantum chromodynamics. Here we report a measurement of the difference between the ratios of the mass and charge of deuterons (d) and anti-deuterons (), and 3He and nuclei carried out with the ALICE (A Large Ion Collider Experiment)4 detector in Pb–Pb collisions at a centre-of-mass energy per nucleon pair of 2.76 TeV. Our direct measurement of the mass-over-charge differences confirms CPT invariance to an unprecedented precision in the sector of light nuclei5,6. This fundamental symmetry of nature, which exchanges particles with anti-particles, implies that all physics laws are the same under the simultaneous reversal of charge(s) (charge conjugation C), reflection of spatial coordinates (parity transformation P) and time inversion (T)

D-S(+) meson production at central rapidity in proton-proton collisions at root s=7 TeV

The P-T-differential inclusive production cross section of the prompt charm-strange meson D-s(+) in the rapidity range vertical bar y vertical bar phi pi(+) with phi -> K-K+, and its charge conjugate, about 480 D-s(+/-) mesons were counted, after selection cuts, in the transverse momentum range 2 < P-T < 12 GeV/c. The results are compared with predictions from models based on perturbative QCD. The ratios of the cross sections of four D meson species (namely D-0, D+, D*+ and D-s(+)) were determined both as a function of p(T) and integrated over p(T)after extrapolating to full p(T) range, together with the strangeness suppression factor in charm fragmentation. The obtained values are found to be compatible within uncertainties with those measured by other experiments in e(+)e(-), ep and pp interactions at various centre-of-mass energies. (C) 2012 CERN. Published by Elsevier By. All rights reserved

Measurement of charm production at central rapidity in proton-proton collisions at root s=7 TeV

The p(t)-differential inclusive production cross sections of the prompt charmed mesons D-0, D+, and D*(+) in the rapidity range vertical bar y vertical bar K-pi(+), D+ -> K-pi(+)pi(+), D*(+) -> D-0 pi(+), and their charge conjugates, about 8,400 D-0, 2,900 D+, and 2,600 D*(+) mesons with 1 < p(t) < 24 GeV/c were counted, after selection cuts, in a data sample of 3.14 x 10(8) events collected with a minimum-bias trigger (integrated luminosity L-int = 5 nb(-1)). The results are described within uncertainties by predictions based on perturbative QCD

D-S(+) meson production at central rapidity in proton-proton collisions at root s=7 TeV

The P-T-differential inclusive production cross section of the prompt charm-strange meson D-s(+) in the rapidity range vertical bar y vertical bar phi pi(+) with phi -> K-K+, and its charge conjugate, about 480 D-s(+/-) mesons were counted, after selection cuts, in the transverse momentum range 2 < P-T < 12 GeV/c. The results are compared with predictions from models based on perturbative QCD. The ratios of the cross sections of four D meson species (namely D-0, D+, D*+ and D-s(+)) were determined both as a function of p(T) and integrated over p(T)after extrapolating to full p(T) range, together with the strangeness suppression factor in charm fragmentation. The obtained values are found to be compatible within uncertainties with those measured by other experiments in e(+)e(-), ep and pp interactions at various centre-of-mass energies. (C) 2012 CERN. Published by Elsevier By. All rights reserved

Suppression of high transverse momentum D mesons in central Pb-Pb collisions at root s(NN)=2.76 TeV

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)The production of the prompt charm mesons D-0, D+, D*(+), and their antiparticles, was measured with the ALICE detector in Pb-Pb collisions at the LHC, at a centre-of-mass energy root s(NN) = 2.76 TeV per nucleon-nucleon collision. The p(t)-differential production yields in the range 2 < p(t) < 16 GeV/c at central rapidity, vertical bar y vertical bar < 0.5, were used to calculate the nuclear modification factor R-AA with respect to a proton-proton reference obtained from the cross section measured at root s = 7 TeV and scaled to root s = 2.76 TeV. For the three meson species, R-AA shows a suppression by a factor 3-4, for transverse momenta larger than 5 GeV/c in the 20% most central collisions. The suppression is reduced for peripheral collisions.9Calouste Gulbenkian Foundation from Lisbon and Swiss Fonds Kidagan, ArmeniaConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Financiadora de Estudos e Projetos (FINEP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)National Natural Science Foundation of China (NSFC)Chinese Ministry of Education (CMOE)Ministry of Science and Technology of China (MSTC)Ministry of Education and Youth of the Czech RepublicDanish Natural Science Research CouncilCarlsberg FoundationDanish National Research FoundationEuropean Research Council under the European CommunityHelsinki Institute of PhysicsAcademy of FinlandFrench CNRS-IN2P3Region Pays de LoireRegion AlsaceRegion AuvergneCEA, FranceGerman BMBFHelmholtz AssociationGeneral Secretariat for Research and Technology, Ministry of Development, GreeceHungarian OTKANational Office for Research and Technology (NKTH)Department of Atomic Energy and Department of Science and Technology of the Government of IndiaIstituto Nazionale di Fisica Nucleare (INFN) of ItalyMEXTJoint Institute for Nuclear Research, DubnaNational Research Foundation of Korea (NRF)CONACYTDGAPA, MexicoALFA-ECHELEN Program (High-Energy physics Latin-American-European Network)Stichting voor Fundamenteel Onderzoek der Materie (FOM)Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO), NetherlandsResearch Council of Norway (NFR)Polish Ministry of Science and Higher EducationNational Authority for Scientific Research - NASR (Autoritatea Nationala pentru Cercetare Stiintifica - ANCS)Federal Agency of Science of the Ministry of Education and Science of Russian FederationInternational Science and Technology CenterRussian Academy of SciencesRussian Federal Agency of Atomic EnergyRussian Federal Agency for Science and InnovationsCERN-INTASMinistry of Education of SlovakiaDepartment of Science and Technology, South AfricaCIEMATEELAMinisterio de Educacion y Ciencia of SpainXunta de Galicia (Conselleria de Educacion)CEADENCubaenergia, CubaIAEA (International Atomic Energy Agency)Swedish Research Council (VR)Knut & Alice Wallenberg Foundation (KAW)Ukraine Ministry of Education and ScienceUnited Kingdom Science and Technology Facilities Council (STFC)United States Department of EnergyUnited States National Science FoundationState of TexasState of OhioFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Light vector meson production in pp collisions at root s=7 TeV ALICE Collaboration

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)The ALICE experiment has measured low-mass dimuon production in pp collisions at root s = 7 TeV in the dimuon rapidity region 2.5 < y < 4. The observed dimuon mass spectrum is described as a superposition of resonance decays (eta, rho, omega, eta', phi) into muons and semi-leptonic decays of charmed mesons. The measured production cross sections for omega and phi are sigma(omega)(1 < p(t) < 5 GeV/c. 2.5 < y < 4) = 5.28 +/- 0.54(stat) +/- 0.49(syst) mb and sigma(phi)(1 < p(t) < 5 GeV/c. 2.5 < y < 4) = 0.940 +/- 0.084(stat) +/- 0.076(syst) mb. The differential cross sections d(2)sigma/dy dp(t) are extracted as a function of p(t) for omega and phi. The ratio between the rho and omega cross section is obtained. Results for the phi are compared with other measurements at the same energy and with predictions by models. (C) 2012 CERN. Published by Elsevier B.V. All rights reserved.71004/mai557568Department of Science and Technology, South AfricaCalouste Gulbenkian Foundation from LisbonSwiss Fonds Kidagan, ArmeniaConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Financiadora de Estudos e Projetos (FINEP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)National Natural Science Foundation of China (NSFC)Chinese Ministry of Education (CMOE)Ministry of Science and Technology of China (MSTC)Ministry of Education and Youth of the Czech RepublicDanish Natural Science Research CouncilCarlsberg FoundationDanish National Research FoundationEuropean Research Council under the European CommunityHelsinki Institute of PhysicsAcademy of FinlandFrench CNRS-IN2P3Region Pays de LoireRegion AlsaceRegion AuvergneCEA, FranceGerman BMBFHelmholtz AssociationGeneral Secretariat for Research and Technology, Ministry of Development, GreeceHungarian OTKANational Office for Research and Technology (NKTH)Department of Atomic EnergyDepartment of Science and Technology of the Government of IndiaIstituto Nazionale di Fisica Nucleare (INFN) of ItalyMEXT, JapanJoint Institute for Nuclear Research, DubnaNational Research Foundation of Korea (NRF)CONACYTDGAPA, MexicoALFA-ECHELEN (High-Energy physics Latin-American-European Network)Stichting voor Fundamenteel Onderzoek der Materie (FOM)Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO), NetherlandsResearch Council of Norway (NFR)Polish Ministry of Science and Higher EducationNational Authority for Scientific Research - NASR (Autoritatea Nationala pentru Cercetare Stiintifica - ANCS)Federal Agency of Science of the Ministry of Education and Science of Russian FederationInternational Science and Technology CenterRussian Academy of SciencesRussian Federal Agency of Atomic EnergyRussian Federal Agency for Science and InnovationsCERN-INTASMinistry of Education of SlovakiaCIEMATEELAMinisterio de Educacion y Ciencia of SpainXunta de Galicia (Conselleria de Educacion)CEADENCubaenergia, CubaIAEA (International Atomic Energy Agency)Swedish Research Council (VR)Knut & Alice Wallenberg Foundation (KAW)Ukraine Ministry of Education and ScienceUnited Kingdom Science and Technology Facilities Council (STFC)United States Department of EnergyUnited States National Science FoundationState of TexasState of OhioFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Long-range angular correlations of pi, K and p in p-Pb collisions at root s(NN)=5.02 TeV

Angular correlations between unidentified charged trigger particles and various species of charged associated particles (unidentified particles, pions, kaons, protons and antiprotons) are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV in the transverse-momentum range 0.3 < p(T) < 4 GeV/c. The correlations expressed as associated yield per trigger particle are obtained in the pseudorapidity range vertical bar n(lab)vertical bar < 0.8. Fourier coefficients are extracted from the long-range correlations projected onto the azimuthal angle difference and studied as a function of p(T) and in intervals of event multiplicity. In high-multiplicity events, the second-order coefficient for protons, 4, is observed to be smaller than that for pions, v(2)(pi), up to about p(T) = 2 GeV/c. To reduce correlations due to jets, the per-trigger yield measured in low-multiplicity events is subtracted from that in high-multiplicity events. A two-ridge structure is obtained for all particle species. The Fourier decomposition of this structure shows that the second-order coefficients for pions and kaons are similar. The v(2)(p) is found to be smaller at low P-T and larger at higher p(T) than v(2)(pi), with a crossing occurring at about 2 GeV/c. This is qualitatively similar to the elliptic-flow pattern observed in heavy-ion collisions. A mass ordering effect at low transverse momenta is consistent with expectations from hydrodynamic model calculations assuming a collectively expanding system. (C) 2013 CERN. Published by Elsevier B.V. All rights reserved

D Meson Elliptic Flow in Noncentral Pb-Pb Collisions at root(S)(NN)=2.76 TeV

Azimuthally anisotropic distributions of D0, D+, and D*+ mesons were studied in the central rapidity region (|y|&lt;0.8) in Pb-Pb collisions at a center-of-mass energy sNN‾‾‾‾√=2.76  TeV per nucleon-nucleon collision, with the ALICE detector at the LHC. The second Fourier coefficient v2 (commonly denoted elliptic flow) was measured in the centrality class 30%–50% as a function of the D meson transverse momentum pT, in the range 2–16  GeV/c. The measured v2 of D mesons is comparable in magnitude to that of light-flavor hadrons. It is positive in the range 2&lt;6  GeV/c with 5.7σ significance, based on the combination of statistical and systematic uncertainties