Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate: an analysis of the NETTER-1 study

Purpose: To assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate. Methods: In the phase 3 NETTER-1 trial, patients with advanced, progressive midgut neuroendocrine tumours (NET) were randomised to 177Lu-Dotatate (every 8 weeks, four cycles) plus octreotide long-acting release (LAR) or to octreotide LAR 60 mg. Primary endpoint was progression-free survival (PFS). Analyses of PFS by baseline factors, including liver tumour burden, ALP elevation, and target lesion size, were performed using Kaplan-Meier estimates; hazard ratios (HRs) with corresponding 95% CIs were estimated using Cox regression. Results: Significantly prolonged median PFS occurred with 177Lu-Dotatate versus octreotide LAR 60 mg in patients with low ( 50%) liver tumour burden (HR 0.187, 0.216, 0.145), and normal or elevated ALP (HR 0.153, 0.177), and in the presence or absence of a large target lesion (diameter > 30 mm; HR, 0.213, 0.063). Within the 177Lu-Dotatate arm, no significant difference in PFS was observed amongst patients with low/moderate/high liver tumour burden (P = 0.7225) or with normal/elevated baseline ALP (P = 0.3532), but absence of a large target lesion was associated with improved PFS (P = 0.0222). Grade 3 and 4 liver function abnormalities were rare and did not appear to be associated with high baseline liver tumour burden. Conclusions: 177Lu-Dotatate demonstrated significant prolongation in PFS versus high-dose octreotide LAR in patients with advanced, progressive midgut NET, regardless of baseline liver tumour burden, elevated ALP, or the presence of a large target lesion. Clinicaltrials.gov : NCT01578239, EudraCT: 2011-005049-11

Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate: an analysis of the NETTER-1 study

Purpose: To assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate. Methods: In the phase 3 NETTER-1 trial, patients with advanced, progressive midgut neuroendocrine tumours (NET) were randomised to 177Lu-Dotatate (every 8 weeks, four cycles) plus octreotide long-acting release (LAR) or to octreotide LAR 60 mg. Primary endpoint was progression-free survival (PFS). Analyses of PFS by baseline factors, including liver tumour burden, ALP elevation, and target lesion size, were performed using Kaplan-Meier estimates; hazard ratios (HRs) with corresponding 95% CIs were estimated using Cox regression. Results: Significantly prolonged median PFS occurred with 177Lu-Dotatate versus octreotide LAR 60 mg in patients with low ( 50%) liver tumour burden (HR 0.187, 0.216, 0.145), and normal or elevated ALP (HR 0.153, 0.177), and in the presence or absence of a large target lesion (diameter > 30 mm; HR, 0.213, 0.063). Within the 177Lu-Dotatate arm, no significant difference in PFS was observed amongst patients with low/moderate/high liver tumour burden (P = 0.7225) or with normal/elevated baseline ALP (P = 0.3532), but absence of a large target lesion was associated with improved PFS (P = 0.0222). Grade 3 and 4 liver function abnormalities were rare and did not appear to be associated with high baseline liver tumour burden. Conclusions: 177Lu-Dotatate demonstrated significant prolongation in PFS versus high-dose octreotide LAR in patients with advanced, progressive midgut NET, regardless of baseline liver tumour burden, elevated ALP, or the presence of a large target lesion. Clinicaltrials.gov: NCT01578239, EudraCT: 2011-005049-11

Measurement of nuclear modification factors of gamma(1S)), gamma(2S), and gamma(3S) mesons in PbPb collisions at root s(NN)=5.02 TeV

The cross sections for ϒ(1S), ϒ(2S), and ϒ(3S) production in lead-lead (PbPb) and proton-proton (pp) collisions at √sNN = 5.02 TeV have been measured using the CMS detector at the LHC. The nuclear modification factors, RAA, derived from the PbPb-to-pp ratio of yields for each state, are studied as functions of meson rapidity and transverse momentum, as well as PbPb collision centrality. The yields of all three states are found to be significantly suppressed, and compatible with a sequential ordering of the suppression, RAA(ϒ(1S)) > RAA(ϒ(2S)) > RAA(ϒ(3S)). The suppression of ϒ(1S) is larger than that seen at √sNN = 2.76 TeV, although the two are compatible within uncertainties. The upper limit on the RAA of ϒ(3S) integrated over pT, rapidity and centrality is 0.096 at 95% confidence level, which is the strongest suppression observed for a quarkonium state in heavy ion collisions to date. © 2019 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Funded by SCOAP3.Peer reviewe

Electroweak production of two jets in association with a Z boson in proton-proton collisions root s =13 TeV

A measurement of the electroweak (EW) production of two jets in association with a Z boson in proton-proton collisions at root s = 13 TeV is presented, based on data recorded in 2016 by the CMS experiment at the LHC corresponding to an integrated luminosity of 35.9 fb(-1). The measurement is performed in the lljj final state with l including electrons and muons, and the jets j corresponding to the quarks produced in the hard interaction. The measured cross section in a kinematic region defined by invariant masses m(ll) > 50 GeV, m(jj) > 120 GeV, and transverse momenta P-Tj > 25 GeV is sigma(EW) (lljj) = 534 +/- 20 (stat) fb (syst) fb, in agreement with leading-order standard model predictions. The final state is also used to perform a search for anomalous trilinear gauge couplings. No evidence is found and limits on anomalous trilinear gauge couplings associated with dimension-six operators are given in the framework of an effective field theory. The corresponding 95% confidence level intervals are -2.6 <cwww/Lambda(2) <2.6 TeV-2 and -8.4 <cw/Lambda(2) <10.1 TeV-2. The additional jet activity of events in a signal-enriched region is also studied, and the measurements are in agreement with predictions.Peer reviewe

Search for new physics in dijet angular distributions using proton-proton collisions at root s=13 TeV and constraints on dark matter and other models

An Erratum to this article was published on 29 April 2022: https://doi.org/10.1140/epjc/s10052-022-10278-0search is presented for physics beyond the standard model, based on measurements of dijet angular distributions in proton-proton collisions at root s = 13 TeV. The data collected with the CMS detector at the LHC correspond to an integrated luminosity of 35.9 fb(-1). The observed distributions, corrected to particle level, are found to be in agreement with predictions from perturbative quantum chromodynamics that include electroweak corrections. Constraints are placed on models containing quark contact interactions, extra spatial dimensions, quantum black holes, or dark matter, using the detector-level distributions. In a benchmark model where only left-handed quarks participate, contact interactions are excluded at the 95% confidence level up to a scale of 12.8 or 17.5 TeV, for destructive or constructive interference, respectively. The most stringent lower limits to date are set on the ultraviolet cutoff in the Arkani-Hamed-Dimopoulos-Dvali model of extra dimensions. In the Giudice-Rattazzi-Wells convention, the cutoff scale is excluded up to 10.1 TeV. The production of quantum black holes is excluded for masses below 5.9 and 8.2 TeV, depending on the model. For the first time, lower limits between 2.0 and 4.6 TeV are set on the mass of a dark matter mediator for (axial-)vector mediators, for the universal quark coupling g(q) = 1.0.Peer reviewe

Measurement of differential cross sections for the production of top quark pairs and of additional jets in lepton+jets events from pp collisions at s=\sqrt{s} = 13 TeV

Differential and double-differential cross sections for the production of top quark pairs in proton-proton collisions at $\sqrt{s} =$ 13 TeV are measured as a function of kinematic variables of the top quarks and the top quark-antiquark ($\mathrm{t}\overline{\mathrm{t}}$) system. In addition, kinematic variables and multiplicities of jets associated with the $\mathrm{t}\overline{\mathrm{t}}$ production are measured. This analysis is based on data collected by the CMS experiment at the LHC in 2016 corresponding to an integrated luminosity of 35.8 fb$^{-1}$. The measurements are performed in the lepton+jets decay channels with a single muon or electron and jets in the final state. The differential cross sections are presented at the particle level, within a phase space close to the experimental acceptance, and at the parton level in the full phase space. The results are compared to several standard model predictions that use different methods and approximations. The kinematic variables of the top quarks and the $\mathrm{t}\overline{\mathrm{t}}$ system are reasonably described in general, though none predict all the measured distributions. In particular, the transverse momentum distribution of the top quarks is more steeply falling than predicted. The kinematic distributions and multiplicities of jets are adequately modeled by certain combinations of next-to-leading-order calculations and parton shower models

Measurement of the top quark mass with lepton+jets final states using pp collisions at s=\sqrt{s}= 13 TeV

The mass of the top quark is measured using a sample of $\mathrm{t\overline{t}}$ events containing one isolated muon or electron and at least four jets in the final state, collected by the CMS detector using proton-proton collisions at $\sqrt{s}=$ 13 TeV at the CERN LHC. The events are selected from data corresponding to an integrated luminosity of 35.9 fb$^{-1}$. For each event the mass is reconstructed from a kinematic fit of the decay products to a \ttbar hypothesis. Using the ideogram method, the top quark mass is determined simultaneously with an overall jet energy scale factor (JSF), constrained by the mass of the W boson in $\mathrm{q\overline{q}'}$ decays. The measurement is calibrated on samples simulated at next-to-leading order matched to a leading-order parton shower. The top quark mass is found to be 172.25$\pm$0.08 (stat+JSF)$\pm$0.62 (syst) GeV. The dependence of this result on the kinematic properties of the event is studied and compared to predictions of different models of $\mathrm{t\overline{t}}$ production, and no indications of a bias in the measurements are observed