Staging the tumour and staging the host: Pre-treatment combined Neutrophil Lymphocyte Ratio and modified Glasgow Prognostic Score is associated with overall survival in patients with oesophagogastric cancers undergoing treatment with curative intent

Background: This study examined whether an innate systemic inflammatory response (SIR) measured by combination neutrophil to lymphocyte ratio (NLR) and modified Glasgow Prognostic Score (mGPS) was associated with overall survival (OS) in patients with esophagogastric cancer (EC) undergoing neoadjuvant chemotherapy (NAC) followed by surgery. Methods: Patients diagnosed with EC, managed with NAC prior to surgery at a regional referral center, between January 2010 and December 2015, were included. The mGPS and NLR were calculated within 12 weeks before NAC. Patients were grouped by combined NLR/mGPS score into three groups of increasing SIR: NLR ≤ 3 (n = 152), NLR > 3 + mGPS = 0 (n = 55), and NLR > 3 + mGPS > 0 (n = 32). Univariable and multivariable Cox regression was used to analyse OS. Results: Overall, 337 NAC patients were included, with 301 (89%) proceeding to surgery and 215 (64%) having R0 resection. There were 203 deaths, with a median follow-up of those alive at censor of 69 months (range 44–114). Higher combined NLR/mGPS score (n = 239) was associated with poorer OS independent of clinical stage and performance status (hazard ratio 1.28, 95% confidence interval 1.02–1.61; p = 0.032), higher rate of progression on NAC (7% vs. 7% vs. 19%; p = 0.003), and lower proportion of eventual resection (80% vs. 84% vs. 53%; p = 0.003). Conclusions: The combined NLR/mGPS score was associated with OS and initial treatment outcomes in patients undergoing NAC prior to surgery for EC, stratifying survival in addition to clinical staging and performance status. The host SIR may be a useful adjunct to multidisciplinary decision making

Cachexia index for prognostication in surgical patients with locally advanced oesophageal or gastric cancer: multicentre cohort study

Background Features of cancer cachexia adversely influence patient outcomes, yet few currently inform clinical decision-making. This study assessed the value of the cachexia index (CXI), a novel prognostic marker, in patients for whom neoadjuvant chemotherapy and surgery for oesophagogastric cancer is planned. Methods Consecutive patients newly diagnosed with locally advanced (T3–4 or at least N1) oesophagogastric cancer between 1 January 2010 and 31 December 2015 were identified through the West of Scotland and South-East Scotland Cancer Networks. CXI was calculated as (L3 skeletal muscle index) × (serum albumin)/(neutrophil lymphocyte ratio). Sex-stratified cut-off values were determined based on the area under the curve (AUC), and patients were divided into groups with low or normal CXI. Primary outcomes were disease progression during neoadjuvant chemotherapy and overall survival (at least 5 years of follow-up). Results Overall, 385 patients (72% men, median age 66 years) were treated with neoadjuvant chemotherapy for oesophageal (274) or gastric (111) cancer across the study interval. Although patients with a low CXI (men: CXI below 52 (AUC 0.707); women: CXI below 41 (AUC 0.759)) were older with more co-morbidity, disease characteristics were comparable to those in patients with a normal CXI. Rates of disease progression during neoadjuvant chemotherapy, leading to inoperability, were higher in patients with a low CXI (28 versus 12%; adjusted OR 3.07, 95% c.i. 1.67 to 5.64; P < 0.001). Low CXI was associated with worsened postoperative mortality (P = 0.019) and decreased overall survival (median 14.9 versus 56.9 months; adjusted HR 1.85, 1.42 to 2.42; P < 0.001). Conclusion CXI is associated with disease progression, worse postoperative mortality, and overall survival, and could improve prognostication and decision-making in patients with locally advanced oesophagogastric cancer

The relationship between computed tomography-derived sarcopenia, cardiopulmonary exercise testing performance, systemic inflammation, and survival in good performance status patients with oesophago-gastric cancer undergoing neoadjuvant treatment

Background: Thought to capture the nutritional and functional reserve of the cancer patient, whether the computed tomography (CT)-derived sarcopenia score (CT-SS) has complimentary prognostic value to commonly utilized pre-treatment host assessments in patients with oesophago-gastric (OG) cancer is unknown. The aim of the present study was to examine if the CT-SS can stratify survival in OG cancer patients with good performance status [Eastern Cooperative Oncology Group Performance Status (ECOG-PS) 0/1]. Furthermore, if the CT-SS had complimentary prognostic value to cardiopulmonary exercise testing (CPET) performance and systemic inflammation. Methods: Consecutive patients with confirmed OG cancer and good performance status, who received neoadjuvant chemotherapy (NAC) with a view to surgical resection with curative intent, between 1 January 2010 and 31 December 2015, within NHS Greater Glasgow and Clyde (NHSGGC) and NHS Forth Valley (NHSFV), were identified from a prospectively maintained database. CT-SSs were grouped as 0/1/2. CPET variables recorded included VO2 anaerobic threshold (AT) and peak. Systemic inflammatory response was determined by modified Glasgow prognostic score (mGPS) and neutrophil/lymphocyte ratio (NLR). Associations between categorical variables were examined using χ2 test and binary logistics regression analysis. Results: A total of 232 patients met the inclusion criteria. 75% (n = 174) of patients were male, 54% (n = 126) were 65 years or older, and 60% (n = 139) were overweight [body mass index (BMI) ≥25 kg/m2]; 33% (n = 77) of patients had CT-SS ≥ 1, 36% (n = 83) had a low VO2 AT (≤11 ml/kg/min), and 57% (n = 132) had a low VO2 peak (≤19 ml/kg/min). Of the 200 patients who had pre-NAC bloods facilitating calculation of the mGPS, 28% (n = 55) had mGPS ≥ 1. Of the 211 patients who had pre-NAC bloods facilitating calculation of NLR, 38% (n = 80) had an NLR ≥ 3; 82% (n = 190) and 53% (n = 122) were alive at 1 and 3 years post-NAC, respectively. On univariate analysis, CT-SS was significantly associated with sex (P < 0.05), histological cell type (P < 0.05), low VO2 AT (P < 0.05), low VO2 peak (P < 0.05), BMI (P < 0.05), mGPS (P < 0.05), and 3-year survival (P < 0.05). On multivariate analysis, tumour, node, and metastasis (TNM) stage (P < 0.05) and CT-SS (P < 0.05) remained significantly associated with 3-year survival. CT-SS was significantly associated with 3-year survival in patients who had mGPS 0 (P < 0.05), but not low VO2 AT (P = 0.066) or peak (P = 0.065). Conclusion: The CT-SS would appear to capture the nutritional and functional reserve of the patient and is a useful objective measure for stratifying long-term survival in patients with good performance status undergoing potentially curative treatment for OG cancer

Skagit River Interim Agreement Studies, Vol. I, Vol. II + appen.: Instream flow fish habitat analysis

City of Seattl

Development of the echinoderm sperm bioassay for testing toxic substances

EP

Prespawning mortality and the reproductive efficiency of Cedar River sockeye salmon

WS Water Research Cente

Sand dollar sperm and embryo bioassay of Puget Sound receiving water samples

WD

The effects of hydroelectric discharge fluctuations on salmon and steelhead survival in the Skagit River, Washington

City of Seattl

BEK, a Receptor for Multiple Members of the Fibroblast Growth Factor (FGF) Family, Maps to Human Chromosome 10q25.3----q26

The gene for the fibroblast growth factor receptor BEK was assigned to human chromosome 10 by applying polymerase chain reaction techniques to DNAs from a panel of human x rodent somatic cell hybrids. The gene was further localized to 10q25.3----q26 by in situ hybridization

Effects of hydroelectric discharge fluctuation on salmon and steelhead in the Skagit River, WA

City of Seattl