Trends in the full blood count blood test and colorectal cancer detection: a longitudinal, case-control study of UK primary care patient data [version 2; peer review: 2 approved, 1 not approved]

Background: The full blood count (FBC) is a common blood test performed in general practice. It consists of many individual parameters that may change over time due to colorectal cancer. Such changes are likely missed in practice. We identified trends in these FBC parameters to facilitate early detection of colorectal cancer. Methods: We performed a retrospective, case-control, longitudinal analysis of UK primary care patient data. LOWESS smoothing and mixed effects models were derived to compare trends in each FBC parameter between patients diagnosed and not diagnosed over a prior 10-year period. Results: There were 399,405 males (2.3%, n = 9,255 diagnosed) and 540,544 females (1.5%, n = 8,153 diagnosed) in the study. There was no difference between cases and controls in FBC trends between 10 and four years before diagnosis. Within four years of diagnosis, trends in many FBC levels statistically significantly differed between cases and controls, including red blood cell count, haemoglobin, white blood cell count, and platelets (interaction between time and colorectal cancer presence: p <0.05). FBC trends were similar between Duke’s Stage A and D colorectal tumours, but started around one year earlier in Stage D diagnoses. Conclusions: Trends in FBC parameters are different between patients with and without colorectal cancer for up to four years prior to diagnosis. Such trends could help earlier identification

Study protocol: a multi-centre randomised study of induction chemotherapy followed by capecitabine +/- nelfinavir with high- or standard-dose radiotherapy for locally advanced pancreatic cancer (SCALOP-2)

Background Induction chemotherapy followed by chemoradiation is a treatment option for patients with locally advanced pancreatic cancer (LAPC). However, overall survival is comparable to chemotherapy alone and local progression occurs in nearly half of all patients, suggesting chemoradiation strategies should be optimised. SCALOP-2 is a randomised phase II trial testing the role of radiotherapy dose escalation and/or the addition of the radiosensitiser nelfinavir, following induction chemotherapy of gemcitabine and nab-paclitaxel (GEMABX). A safety run-in phase (stage 1) established the nelfinavir dose to administer with chemoradiation in the randomised phase (stage 2). Methods Patients with locally advanced, inoperable, non-metastatic pancreatic adenocarcinoma receive three cycles of induction GEMABX chemotherapy prior to radiological assessment. Those with stable/responding disease are eligible for further trial treatment. In Stage 1, participants received one further cycle of GEMABX followed by capecitabine-chemoradiation with escalating doses of nelfinavir in a rolling-six design. Stage 2 aims to register 262 and randomise 170 patients with responding/stable disease to one of five arms: capecitabine with high- (arms C + D) or standard-dose (arms A + B) radiotherapy with (arms A + C) or without (arms B + D) nelfinavir, or three more cycles of GEMABX (arm E). Participants allocated to the chemoradiation arms receive another cycle of GEMABX before chemoradiation begins. Co-primary outcomes are 12-month overall survival (radiotherapy dose-escalation question) and progression-free survival (nelfinavir question). Secondary outcomes include toxicity, quality of life, disease response rate, resection rate, treatment compliance, and CA19–9 response. SCALOP-2 incorporates a detailed radiotherapy quality assurance programme. Discussion SCALOP-2 aims to optimise chemoradiation in LAPC and incorporates a modern induction regimen

Search for heavy neutral leptons in final states with electrons, muons, and hadronically decaying tau leptons in proton-proton collisions at s \sqrt{s} = 13 TeV

A search for heavy neutral leptons (HNLs) of Majorana or Dirac type using proton-proton collision data at = 13 TeV is presented. The data were collected by the CMS experiment at the CERN LHC and correspond to an integrated luminosity of 138 fb−1. Events with three charged leptons (electrons, muons, and hadronically decaying tau leptons) are selected, corresponding to HNL production in association with a charged lepton and decay of the HNL to two charged leptons and a standard model (SM) neutrino. The search is performed for HNL masses between 10 GeV and 1.5 TeV. No evidence for an HNL signal is observed in data. Upper limits at 95% confidence level are found for the squared coupling strength of the HNL to SM neutrinos, considering exclusive coupling of the HNL to a single SM neutrino generation, for both Majorana and Dirac HNLs. The limits exceed previously achieved experimental constraints for a wide range of HNL masses, and the limits on tau neutrino coupling scenarios with HNL masses above the W boson mass are presented for the first time

Measurement of the polarizations of prompt and non-prompt J/ψ and ψ (2S) mesons produced in pp collisions at s\sqrt{s} = 13 TeV

The polarizations of prompt and non-prompt J∕ψ and ψ(2S) mesons are measured in proton-proton collisions at √ = 13 TeV, using data samples collected by the CMS experiment in 2017 and 2018, corresponding to a total integrated luminosity of 103.3 fb$^{−1}$. Based on the analysis of the dimuon decay angular distributions in the helicity frame, the polar anisotropy, , is measured as a function of the transverse momentum, $_T$, of the charmonium states, in the 25–120 and 20–100 GeV ranges for the J∕ψ and ψ(2S), respectively. The non-prompt polarizations agree with predictions based on the hypothesis that, for T ≳ 25 GeV, the non-prompt J∕ψ and ψ(2S) are predominantly produced in two-body B meson decays. The prompt results clearly exclude strong transverse polarizations, even for $_T$ exceeding 30 times the J∕ψ mass, where tends to an asymptotic value around 0.3. Taken together with previous measurements, by CMS and LHCb at √ = 7 TeV, the prompt polarizations show a significant variation with $_T$, at low $_T$

Search for new physics in high-mass diphoton events from proton-proton collisions at √s = 13 TeV

Results are presented from a search for new physics in high-mass diphoton events from proton-proton collisions at sqrt(s) = 13 TeV. The data set was collected in 2016–2018 with the CMS detector at the LHC and corresponds to an integrated luminosity of 138 fb−1 . Events with a diphoton invariant mass greater than 500 GeV are considered. Two diferent techniques are used to predict the standard model backgrounds: parametric fts to the smoothly-falling background and a frst-principles calculation of the standard model diphoton spectrum at next-to-next-to-leading order in perturbative quantum chromodynamics calculations. The frst technique is sensitive to resonant excesses while the second technique can identify broad diferences in the invariant mass shape. The data are used to constrain the production of heavy Higgs bosons, Randall-Sundrum gravitons, the large extra dimensions model of Arkani-Hamed, Dimopoulos, and Dvali (ADD), and the continuum clockwork mechanism. No statistically signifcant excess is observed. The present results are the strongest limits to date on ADD extra dimensions and RS gravitons with a coupling parameter greater than 0.1

Patterns in haemoglobin levels over 10 years to predict diagnosis of colorectal cancer by Duke’s staging: preliminary findings using UK primary care routine blood test data

Stage at diagnosis of colorectal cancer influences 5-year survival: 94% at the earliest stage, but 7% at the latest. Tumour growth causes subtle changes in levels of blood components, such as haemoglobin, which may go unnoticed. Such changes have not been explored. We report patterns in haemoglobin levels up to 10 years before a diagnosis of colorectal cancer, by Duke’s tumour staging

Study protocol: a multi-centre randomised study of induction chemotherapy followed by capecitabine ± nelfinavir with high- or standard-dose radiotherapy for locally advanced pancreatic cancer (SCALOP-2)

Background: induction chemotherapy followed by chemoradiation is a treatment option for patients with locally advanced pancreatic cancer (LAPC). However, overall survival is comparable to chemotherapy alone and local progression occurs in nearly half of all patients, suggesting chemoradiation strategies should be optimised. SCALOP-2 is a randomised phase II trial testing the role of radiotherapy dose escalation and/or the addition of the radiosensitiser nelfinavir, following induction chemotherapy of gemcitabine and nab-paclitaxel (GEMABX). A safety run-in phase (stage 1) established the nelfinavir dose to administer with chemoradiation in the randomised phase (stage 2).Methods: patients with locally advanced, inoperable, non-metastatic pancreatic adenocarcinoma receive three cycles of induction GEMABX chemotherapy prior to radiological assessment. Those with stable/responding disease are eligible for further trial treatment. In Stage 1, participants received one further cycle of GEMABX followed by capecitabine-chemoradiation with escalating doses of nelfinavir in a rolling-six design. Stage 2 aims to register 262 and randomise 170 patients with responding/stable disease to one of five arms: capecitabine with high- (arms C + D) or standard-dose (arms A + B) radiotherapy with (arms A + C) or without (arms B + D) nelfinavir, or three more cycles of GEMABX (arm E). Participants allocated to the chemoradiation arms receive another cycle of GEMABX before chemoradiation begins. Co-primary outcomes are 12-month overall survival (radiotherapy dose-escalation question) and progression-free survival (nelfinavir question). Secondary outcomes include toxicity, quality of life, disease response rate, resection rate, treatment compliance, and CA19–9 response. SCALOP-2 incorporates a detailed radiotherapy quality assurance programme.Discussion: SCALOP-2 aims to optimise chemoradiation in LAPC and incorporates a modern induction regimen

Early detection of colorectal cancer using symptoms and the ColonFlag: case-control and cohort studies

Background: Early detection of colorectal cancer confers substantial prognostic benefit. Most symptoms are non-specific and easily missed. The ColonFlag algorithm identifies risk of undiagnosed colorectal cancer using age, sex and changes in full blood count (FBC) indices. The aim of this study was to investigate whether the ColonFlag detects undiagnosed colorectal cancer prior to the recording of symptoms in general practice. Methods: We conducted case-control and cohort studies by linking primary care data from the Clinical Practice Research Datalink with colorectal cancer diagnoses from the National Cancer Registry. A ColonFlag score was derived for each FBC. We assessed the prevalence of symptoms at six-monthly intervals prior to index date (diagnosis date for cases, randomly selected date for controls). We then derived odds ratios (ORs) and area under the receiver operating characteristic (AUROC) curve for the ColonFlag, and for symptoms using logistic regression at each interval (primary outcome 18-24 months). Results: We included 1,893,641 patients, 10,875,556 FBCs and 8,918,037 ColonFlag scores. ColonFlag scores began to increase in cases compared with controls around 3-4 years before diagnosis. The AUROC for a diagnosis 18-24 months following the ColonFlag score was 0.736 (95% CI 0.715-0.759), falling to 0.536 (95% CI 0.523-0.548) with adjustment for age. ORs for individual symptoms became non-significant prior to 12 months before index date, except for abdominal pain (females OR=1.29, p<0.0001 at 12-18 months) and rectal bleeding (females OR=2.09, males OR=1.92, p<0.0001 at 18-24 months). Conclusions: Symptoms appear relatively late in the colorectal cancer process and are limited for supporting early stage detection. The ColonFlag can discriminate usefully at 18-24 months before diagnosis, suggesting a role for this algorithm in primary care, although some of its discriminatory ability comes from the age variable