Neutrophil-to-lymphocyte ratio as a bladder cancer biomarker: assessing prognostic and predictive value in SWOG 8710

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The prognostic value of derived neutrophil to lymphocyte ratio in oesophageal cancer treated with definitive chemoradiotherapy

Background and purpose The derived neutrophil–lymphocyte ratio (dNLR) is a validated prognostic biomarker for cancer survival but has not been extensively studied in locally-advanced oesophageal cancer treated with definitive chemoradiotherapy (dCRT). We aimed to identify the prognostic value of dNLR in patients recruited to the SCOPE1 trial. Materials and methods 258 patients were randomised to receive dCRT ± cetuximab. Kaplan–Meier’s curves and both univariable and multivariable Cox regression models were calculated for overall survival (OS), progression free survival (PFS), local PFS inside the radiation volume (LPFSi), local PFS outside the radiation volume (LPFSo), and distant PFS (DPFS). Results An elevated pre-treatment dNLR ≥ 2 was significantly associated with decreased OS in univariable (HR 1.74 [95% CI 1.29–2.35], p < 0.001) and multivariable analyses (HR 1.64 [1.17–2.29], p = 0.004). Median OS was 36 months (95% CI 27.8–42.4) if dNLR < 2 and 18.4 months (95% CI 14.1–24.9) if dNLR ≥ 2. All measures of PFS were also significantly reduced with an elevated dNLR. dNLR was prognostic for OS in cases of squamous cell carcinoma with a non-significant trend for adenocarcinoma/undifferentiated tumours. Conclusions An elevated pre-treatment dNLR may be an independent prognostic biomarker for OS and PFS in oesophageal cancer patients treated with definitive CRT. dNLR is a simple, inexpensive and readily available tool for risk-stratification and should be considered for use in future oesophageal cancer clinical trials

Derived neutrophil to lymphocyte ratio as a prognostic factor in patients with advanced colorectal cancer according to RAS and BRAF status: a post-hoc analysis of the MRC COIN study.

The phase III Continuous or Intermittent (COIN) trial failed to show a benefit in overall survival (OS) of cetuximab in combination with chemotherapy for patients with metastatic colorectal cancer. High derived neutrophil to lymphocyte ratio (dNLR) has been shown to be prognostic in patients with metastatic colorectal cancer. The aim of this analysis is to evaluate dNLR as a predictive biomarker of the survival according to RAS and BRAF mutations status within the COIN trial. A post-hoc exploratory analysis of the COIN trial arms A and B was carried out. All patients with available white blood cell and neutrophil data were analysed. The dNLR was calculated using a formula that has previously shown predictive power in cancer patients: dNLR=ANC/(WBC-ANC). A high dNLR was defined as a value of 2.2 or more. dNLR was correlated with clinical outcomes using Kaplan-Meier and Cox regression analysis. A total of 1603 patients were assigned to the oxaliplatin-based chemotherapy (arm A, N=815) or oxaliplatin-based chemotherapy plus cetuximab (arm B, N=815) arms. There was a strong association between dNLR level and overall survival (OS) using Kaplan-Meier analysis. In all mutation groups, dNLR less than 2.2 was associated with better OS compared to dNLR of 2.2 or more. The median OS in patients with wild-type disease (dNLR<2.2 vs. dNLR≥2.2) was 22.8 versus 13.1 months [hazard ratio (HR)=1.33]; 16.9 versus 11.8 months (HR=1.36) in patients with RAS mutant tumours; and 12.6 versus 6.8 months (HR=1.67) in patients with BRAF mutant tumours. In patients with dNLR less than 2.2, the median OS was 19.2 months in arm A compared to 18.0 months in arm B (HR=1.11). Among patients with dNLR greater than or equal to 2.2, the median OS was 13.0 months in arm A compared with 13.1 months in arm B (HR=0.96). dNLR is strongly prognostic for survival in all mutation groups. dNLR does not predict for benefit from the addition of cetuximab

Evolution and progressive geomorphic manifestation of surface faulting: A comparison of the Wairau and Awatere faults, South Island, New Zealand

Field mapping and lidar analysis of surface faulting patterns expressed in flights of geologically similar fluvial terraces at the well-known Branch River and Saxton River sites along the Wairau (Alpine) and Awatere strike-slip faults, South Island, New Zealand, reveal that fault-related deformation patterns expressed in the topography at these sites are markedly less structurally complex along the higher-displacement (hundreds of kilometers), structurally mature Wairau fault than along the Awatere fault (∼13–20 km total slip). These differences, which are generally representative of the surface traces of these faults, provide direct evidence that surface faulting becomes structurally simpler with increasing cumulative fault offset. We also examine the degree to which off-fault deformation (OFD) is expressed in the landscape at the Saxton River site along the less structurally mature Awatere fault. Significantly greater amounts of OFD are discernible as a wide damage zone (∼460 m fault-perpendicular width) in older (ca. 15 ka), more-displaced (64–74 m) fluvial terraces than in younger (ca. 1–7 ka), less-displaced (<55 m) terraces; no OFD is discernible in the lidar data on the least-displaced (<35 m) terraces. From this, we infer that OFD becomes progressively more geomorphically apparent with accumulating displacement. These observations imply that (1) the processes that accommodate OFD are active during each earthquake, but may not be evident in deposits that have experienced relatively small displacements; (2) structures accommodating OFD will become progressively geomorphically clearer with increasing displacement; (3) geomorphic measurements of overall fault zone width taken in deposits that have experienced small displacements will be underestimates; and (4) fault slip rates based on geomorphic surface offsets will be underestimates for immature faults if based solely on measurements along the high-strain fault core

Multiple human tracking in RGB-depth data: A survey

© The Institution of Engineering and Technology. Multiple human tracking (MHT) is a fundamental task in many computer vision applications. Appearance-based approaches, primarily formulated on RGB data, are constrained and affected by problems arising from occlusions and/or illumination variations. In recent years, the arrival of cheap RGB-depth devices has led to many new approaches to MHT, and many of these integrate colour and depth cues to improve each and every stage of the process. In this survey, the authors present the common processing pipeline of these methods and review their methodology based (a) on how they implement this pipeline and (b) on what role depth plays within each stage of it. They identify and introduce existing, publicly available, benchmark datasets and software resources that fuse colour and depth data for MHT. Finally, they present a brief comparative evaluation of the performance of those works that have applied their methods to these datasets

Derived neutrophil lymphocyte ratio is predictive of survival from intermittent therapy in advanced colorectal cancer: a post hoc analysis of the MRC COIN study

BACKGROUND: The phase III COntinuous or INtermittent (COIN) trial failed to show non-inferiority of intermittent compared with continuous chemotherapy for advanced colorectal cancer in overall survival (OS). The present analysis evaluated whether the derived neutrophil to lymphocyte ratio (dNLR) could predict the effect of intermittent vs continuous chemotherapy on OS in patients with advanced colorectal cancer. METHODS: A post hoc exploratory analysis of COIN arms A and C was performed. Landmark analysis was conducted on all patients with available WBC and neutrophils data. The dNLR was calculated using a formula which has previously demonstrated predictive power in cancer patients: dNLR=ANC/(WBC−ANC). A high dNLR was defined using a cut-off value of ⩾2.22. Derived neutrophil to lymphocyte ratio was then correlated with clinical outcomes. Survival curves were generated based on dNLR using the Kaplan–Meier method. Comparison between groups was performed using Cox regression. RESULTS: A total of 1630 patients were assigned to the continuous (N=815) or intermittent (N=815) arms. There was a strong association between dNLR level and OS. The median survival times in the ITT population were 18.6 months and 12.5 months for patients with low and high dNLR, respectively (HR=1.70; 95% CI=1.52–1.90; P<0.001). The estimate of the hazard ratio did not alter substantially (HR=1.54) after adjusting for treatment, tumour status, number of metastatic sites, alkaline phosphate and platelet count. CONCLUSIONS: Derived neutrophil to lymphocyte ratio is strongly prognostic for survival in the COIN intermittent vs continuous treatment arms. Derived neutrophil to lymphocyte ratio does not predict for detrimental survival in patients treated with intermittent therapy

Male breast cancer

Male breast cancer (MBC) is a rare disease representing less than 1% of all breast cancers (BC) and less than 1% of cancers in men. Age at presentation is mostly in the late 60s. MBC is recognized as an estrogen-driven disease, specifically related to hyperestrogenism. About 20% of MBC patients have family history for BC. Mutations in BRCA1 and, predominantly, BRCA2, account for approximately 10% of MBC cases. Because of its rarity, MBC is often compared with female BC (FBC). Based on age-frequency distribution, age-specific incidence rate patterns and prognostic factors profiles, MBC is considered similar to late-onset, postmenopausal estrogen/progesterone receptor positive (ER+/PR+) FBC. However, clinical and pathological characteristics of MBC do not exactly overlap FBC. Compared with FBC, MBC has been reported to occur later in life, present at a higher stage, and display lower histologic grade, with a higher proportion of ER+ and PR+ tumors. Although rare, MBC remains a substantial cause for morbidity and mortality in men, probably because of its occurrence in advanced age and delayed diagnosis. Diagnosis and treatment of MBC generally is similar to that of FBC. Men tend to be treated with mastectomy rather than breast-conserving surgery. The backbone of adjuvant therapy or palliative treatment for advanced disease is endocrine, mostly tamoxifen. Use of FBC-based therapy led to the observation that treatment outcomes for MBC are worse and that survival rates for MBC do not improve like FBC. These different outcomes may suggest a non-appropriate utilization of treatments and that different underlying pathogenetic mechanisms may exist between male and female BC

The dopamine D1 receptor is expressed and induces CREB phosphorylation and MUC5AC expression in human airway epithelium

Background Dopamine receptors comprise two subgroups, Gs protein-coupled “D1-like” receptors (D1, D5) and Gi-coupled “D2-like” receptors (D2, D3, D4). In airways, both dopamine D1 and D2 receptors are expressed on airway smooth muscle and regulate airway smooth muscle force. However, functional expression of the dopamine D1 receptor has never been identified on airway epithelium. Activation of Gs-coupled receptors stimulate adenylyl cyclase leading to cyclic AMP (cAMP) production, which is known to induce mucus overproduction through the cAMP response element binding protein (CREB) in airway epithelial cells. We questioned whether the dopamine D1 receptor is expressed on airway epithelium, and whether it promotes CREB phosphorylation and MUC5AC expression. Methods We evaluated the protein expression of the dopamine D1 receptor on native human airway epithelium and three sources of cultured human airway epithelial cells including primary cultured airway epithelial cells, the bronchial epithelial cell line (16HBE14o-), and the pulmonary mucoepidermoid carcinoma cell line (NCI-H292) using immunohistochemistry and immunoblotting. To characterize the stimulation of cAMP through the dopamine D1 receptor, 16HBE14o- cells and NCI-H292 cells were treated with dopamine or the dopamine D1 receptor agonists (SKF38393 or A68930) before cAMP measurements. The phosphorylation of CREB by A68930 in both 16HBE14o- and NCI-H292 cells was measured by immunoblot. The effect of dopamine or A68930 on the expression of MUC5AC mRNA and protein in NCI-H292 cells was evaluated by real-time PCR and immunofluorescence staining, respectively. Results The dopamine D1 receptor protein was detected in native human airway epithelium and three sources of cultured human airway epithelial cells. Dopamine or the dopamine D1-like receptor agonists stimulated cAMP production in 16HBE14o- cells and NCI-H292 cells, which was reversed by the selective dopamine D1-like receptor antagonists (SCH23390 or SCH39166). A68930 significantly increased phosphorylation of CREB in both 16HBE14o- and NCI-H292 cells, which was attenuated by the inhibitors of PKA (H89) and MEK (U0126). Expression of MUC5AC mRNA and protein were also increased by either dopamine or A68930 in NCI-H292 cells. Conclusions These results suggest that the activation of the dopamine D1 receptor on human airway epithelium could induce mucus overproduction, which could worsen airway obstructive symptoms

Testicular Abscess an Unusual Cause for Febrile Neutropenia

Patients with good-risk disseminated testicular cancer are effectively managed with platinum-based chemotherapy. Febrile neutropenia is a dose-limiting event for many chemotherapy regimens. The risk of developing febrile neutropenia is related both to the chemotherapy dose and schedule, and to patient-related factors. Among patients who require ongoing chemotherapy for metastatic disease, it is very unusual for surgical complications to delay the initiation of chemotherapy. We describe a patient who developed febrile neutropenia with testicular abscess when treated with BEP 2 weeks following inguinal orchiectomy