Is systemic inflammation the result of insufficient cortisol production in patients with colorectal cancer?

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14092-e14092
Author(s):  
Michelle Leana Ramanathan ◽  
Campbell SD Roxburgh ◽  
Paul G Horgan ◽  
Donald C. Mcmillan

e14092 Background: Patients with colorectal cancer who have a raised systemic inflammatory response have been shown to have poorer outcomes, independent of their tumour stage. In particular, the combination of C-reactive protein (CRP) and albumin, the modified Glasgow Prognostic Score (mGPS) has been shown to have consistent and superior prognostic value. However, the basis of a systemic inflammatory response in these patients is not clear. One hypothesis is that the presence of a systemic inflammatory response in patients with colorectal cancer may be due to impaired cortisol production, a potent anti-inflammatory agent. Therefore, the aim of the present study was to examine the relationship between preoperative systemic inflammatory response and endogenous cortisol production. Methods: A prospective study was performed to incorporate the assessment of adrenocortical function using synthetic ACTH, a short Synacthen test, as part of the preoperative assessment of patients undergoing potentially curative resection for colorectal cancer. Preoperative systemic inflammatory response was assessed using mGPS. Results: A total of 80 patients underwent short Synacthen testing. The majority of patients were under 75 years old (79%), were male (59%), had colon cancer (75%) and had TNM stage I/II disease (54%). Approximately 50% received adjuvant treatment. Using standard criteria (peak cortisol <450 nmol/L = inadequate) impaired cortisol response was seen in 3 (4%) patients. There were no significant associations between the baseline, 30 minute, or change in cortisol (both relative and absolute) and age (p=0.814, p=0.443, p=0.730, p=0.929), sex (p=0.714, p=0.440, p=0.324, p=0.953), site (p=0.519, p=0.255, p=0.145, p=0.222), TNM stage (p=0.115, p=0.591, p=0.492, p=0.289), mGPS (p=0.280, p=0.202, p=0.800, p=0.818), or white cell count (p=0.787, p=0.316, p=0.462, p=0.567). Conclusions: The results of the present study show that impaired cortisol production, as evidenced by the short Synacthen test, was uncommon in patients with potentially curable colorectal cancer. Moreover, they indicate that the presence of a systemic inflammatory response is not associated with impaired cortisol production.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 130-130
Author(s):  
Tanvir Abbass ◽  
Ross Dolan ◽  
Stephen Thomas McSorley ◽  
Paul G. Horgan ◽  
Donald C. McMillan

130 Background: There is now good evidence that sarcopenia and myosteatosis, measured as low skeletal muscle index (SMI) and low skeletal muscle density (SMD) from CT scans, are associated with poor survival in patients undergoing surgery for CRC. However, this is not clear whether this is as a result of tumour burden or chronic inflammation. Methods: The relationship between tumour stage, systemic inflammatory response using modified Glasgow prognostic score (mGPS), neutrophil lymphocyte ratio (NLR) and sarcopenia and myosteatosis using defined SMI/SMD was examined in 840 patients undergoing CRC resection from a prospectively maintained database. Results: The majority of patients were > 65 years of age (64.5%), male (55%) and did not have sarcopenia (51%) but had myosteatosis (65%). In those patients with a mGPS = 0 (n = 617), mGPS = 1 (n = 99), mGPS = 2 (n = 124), TNM stage of 0-I, II and III was not associated with sarcopenia (p = 0.260, p = 0.869 and p = 0.458 respectively) or myosteatosis (p = 0.136, p = 0.879 and p = 0.06 respectively). In those patients with TNM stage of 0-I (n = 202), stage II (n = 346) and stage III (n = 292), mGPS (0,1,2) was significantly associated with sarcopenia (p = 0.329, p = 0.001 and p = 0.002 respectively) and myosteatosis (p = 0.329, p < 0.001 and p = 0.001 respectively). In patients with TNM stage of 0-I, stage II and stage III, NLR was significantly associated with sarcopenia (p = 0.492, p = 0.299 and 0.027 respectively) and myosteatosis (p = 0.870, p = 0.012 and p = 0.019 respectively). Conclusions: Compared with tumour burden, the systemic inflammatory response (particularly mGPS) appears to have a greater influence on the development of sarcopenia and myosteatosis. These results have implications for the treatment of sarcopenia and myosteatosis in patients undergoing surgery for CRC.


2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 456-456 ◽  
Author(s):  
K. A. Kwon ◽  
S. Oh ◽  
S. Kim ◽  
S. Lee ◽  
J. Han ◽  
...  

456 Background: Several inflammatory response materials could be biomarkers for prediction of prognosis of cancer patients; elevated C-reactive protein (CRP), increased white cell, neutrophil, platelet, and decreased albumin. The Glasgow Prognostic Score (GPS) combines circulating CRP and albumin level, the neutrophil/lymphocyte ratio (NLR), and the platelet/lymphocyte ratio (PLR) has been introduced for prognostic scoring system in colorectal cancer (CRC). Thus, in this study, we attempted to identify an more adequate prognostic model related with systemic inflammatory response for CRC. Methods: Between Mar 2005 and Dec 2008, 200 patients who underwent curative resection for colorectal cancer were enrolled in this study. Systemic inflammatory parameters (CRP, albumin, neutrophil, lymphocyte, and platelet count) were checked for making 3 scoring systems. Based on clinical survival data, we then compared PFS and OS with GPS, NLR, and PLR. Results: Male to female were 123:77. Median age of the patients was 64 years (range, 26-83 years). Median follow-up duration was 27.2 months (range 7.8-52.7 months). 36 patients were observed disease progression or death. 19 patients were passed away during follow-up duration. 3 year PFS and OS were 72% and 86%, respectively. Numbers of GPS 0,1, and 2 patients were 154 (77%), 44 (22%), and 2 (1%), respectively. Survival analysis according to GPS, PFS and OS could not be able to show the prognostic significance (P=0.313 and P=263). Cut-off value of NLR and PLR were determined 3 and 180 by ROC curve. Both of NLR and PLR were observed as a good prognostic biomarker of PFS and OS (P=0.009 and P<0.001 in PFS, P=0.006 and P=0.001 in OS). Conclusions: Although GPS, NLR, and PLR were introduced as prognostic scoring systems for operable CRC, PLR which is constructed of platelet/lymphocyte count may represent a useful prognostic index for the prediction of PFS and OS in operable CRC. No significant financial relationships to disclose.


Author(s):  
Pedro Marques ◽  
Friso de Vries ◽  
Olaf M Dekkers ◽  
Márta Korbonits ◽  
Nienke R Biermasz ◽  
...  

Abstract Context Serum inflammation-based scores reflect systemic inflammatory response and/or patients’ nutritional status, and may predict clinical outcomes in cancer. While these are well-described and increasingly used in different cancers, their clinical usefulness in the management of patients with endocrine tumors is less known. Evidence acquisition A comprehensive PubMed search was performed using the terms “endocrine tumor”, “inflammation”, “serum inflammation-based score”, “inflammatory-based score”, “inflammatory response-related scoring”, “systemic inflammatory response markers”, “Neutrophil-to-lymphocyte ratio”, “Neutrophil-to-platelet ratio”, “Lymphocyte-to-monocyte ratio”, “Glasgow Prognostic Score”, “Neutrophil-Platelet Score”, “Systemic Immune-Inflammation Index”, and “Prognostic Nutrition Index” in clinical studies. Evidence synthesis The Neutrophil-to-Lymphocyte Ratio and the Platelet-to-Lymphocyte Ratio are the ones most extensively investigated in patients with endocrine tumors. Other scores have also been considered in some studies. Several studies focused in finding whether serum inflammatory biomarkers may stratify the endocrine tumor patients’ risk and detect those at risk for developing more aggressive and/or refractory disease, particularly after endocrine surgery. Conclusions In this review, we summarize the current knowledge on the different serum inflammation-based scores and their usefulness in predicting the phenotype, clinical aggressiveness, disease outcomes and prognosis in patients with endocrine tumors. The value of such serum inflammation-based scores in the management of patients with endocrine tumors has been emerging over the last decade. However, further research is necessary to establish useful markers and their cut-offs for routine clinical practice for individual diseases.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 682-682
Author(s):  
Stephen Thomas McSorley ◽  
Bo Khor ◽  
Paul G. Horgan ◽  
Donald C McMillan

682 Background: The magnitude of the systemic inflammatory response before and after surgery for rectal cancer is increasingly understood to have an impact on clinical outcomes. The aim of the present study was to examine the impact of neoadjuvant chemoradiotherapy (nCRT) on pre- and postoperative systemic inflammation and clinical outcomes in patients undergoing surgery for rectal cancer. Methods: Data was recorded prospectively for patients who underwent elective, potentially curative surgery for rectal cancer, from 2008 to 2015 at a single centre, n = 251. Patients had routine pre- and postoperative blood sampling. Results: Of the 251 patients, the majority were male (62%) and over 65 years old (57%) with node negative disease (66%). 85 patients (33%) were allocated to preoperative nCRT based on probable margin threatening disease at preoperative MRI. nCRT was significantly associated with a higher proportion of patients having neutrophil lymphocyte ratio (NLR) > 5 (39% vs. 12%, p < 0.001), and a modified Glasgow Prognostic Score (mGPS) of 2 (14% vs. 6%, p = 0.035) prior to surgery. There was no significant association between nCRT and the magnitude of the postoperative systemic inflammatory response or complications. Of the 85 patients who underwent nCRT, there was a small but significant reduction in CRP following treatment (3.25 mg/L vs. 4.1 mg/L, p = 0.007). Of the 16 patients who were systemically inflamed prior to nCRT, 9 patients achieved mGPS score 0 after treatment (p = 0.004). There was a significant association between having an mGPS score 1 or 2 both before and after nCRT and breaching established thresholds of CRP on postoperative days 2 (190mg/L, 86% vs. 33%, p = 0.002), 3 (170mg/L, 86% vs. 38%, p = 0.015) and 4 (145mg/L, 71% vs. 36%, p = 0.031). Conclusions: Allocation to nCRT was significantly associated with a systemic inflammatory response prior to surgery for rectal cancer. nCRT was significantly associated with attenuation of existing systemic inflammation. Such attenuation of the systemic inflammatory response may in part explain the efficacy of nCRT in patients with rectal cancer.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3055-3055 ◽  
Author(s):  
Claire Gervais ◽  
Pascaline Boudou-Rouquette ◽  
Anne Jouinot ◽  
Olivier Huillard ◽  
Jerome Alexandre ◽  
...  

3055 Background: Nivolumab is the first checkpoint immunotherapeutic agent approved for NSCLC. By enabling host immune-mediated cytotoxic activity against tumor cells, nivolumab induces a tumor response in 15% of patients (pts). However, host-related parameters to predict nivolumab activity are still missing. We evaluated the predictive and prognostic value of the presence of a systemic inflammatory response. Methods: From July 2015 to December 2016, we measured at nivolumab initiation the Glasgow Prognostic Score (GPS), a cumulative prognostic score based on C-reactive protein and albumin, the neutrophil-lymphocyte ratio (NLR), the Nutrition Risk Index (NRI) and the Prognostic Nutritional Index (PNI). Univariate and multivariate analyses tested the association between initial patient characteristics and clinical outcome. Results: The characteristics of the 57 consecutive pts analyzed are: median age of 66 years (range 41-78), 65% non-squamous cell lung cancer, 61.4% males and 52.6% Performance Status (PS) 0-1. GPS was 0 in 27 (47.4%), 1 in 21 (36.8%) and 2 in 9 (15.8%) pts. In multivariate analysis, parameters associated with disease progression (per RECIST 1.1) were GPS (1-2 vs 0; HR 1.45 [1.11-1.90], p= 0.009) and number of metastatic sites (>2 vs ≤ 2; HR: 0.75 [0.57-0.98], p = 0.04). Overall survival was significantly worse for pts with PS 2-3 vs PS 0-1 (p=0.01) and for pts with GPS 2 vs GPS 0-1 (p=0.01). The GPS was an independent predictive marker of progression and was superior to other inflammation-based prognostic scores in our cohort (Table). Conclusions: The Glasgow Prognostic Score (GPS) allows identifying patients with disease progression and long survivors among metastatic NSCLC patients treated with nivolumab. [Table: see text]


2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Derek Grose ◽  
Graham Devereux ◽  
Louise Brown ◽  
Richard Jones ◽  
Dave Sharma ◽  
...  

Background. Prediction of survival in patients diagnosed with lung cancer remains problematical. The aim of the present study was to examine the clinical utility of an established objective marker of the systemic inflammatory response, the Glasgow Prognostic Score, as the basis of risk stratification in patients with lung cancer. Methods. Between 2005 and 2008 all newly diagnosed lung cancer patients coming through the multidisciplinary meetings (MDTs) of four Scottish centres were included in the study. The details of 882 patients with a confirmed new diagnosis of any subtype or stage of lung cancer were collected prospectively. Results. The median survival was 5.6 months (IQR 4.8–6.5). Survival analysis was undertaken in three separate groups based on mGPS score. In the mGPS 0 group the most highly predictive factors were performance status, weight loss, stage of NSCLC, and palliative treatment offered. In the mGPS 1 group performance status, stage of NSCLC, and radical treatment offered were significant. In the mGPS 2 group only performance status and weight loss were statistically significant. Discussion. This present study confirms previous work supporting the use of mGPS in predicting cancer survival; however, it goes further by showing how it might be used to provide more objective risk stratification in patients diagnosed with lung cancer.


PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0251924
Author(s):  
Donogh Maguire ◽  
Conor Richards ◽  
Marylynne Woods ◽  
Ross Dolan ◽  
Jesse Wilson Veitch ◽  
...  

Background In order to manage the COVID-19 systemic inflammatory response, it is important to identify clinicopathological characteristics across multiple cohorts. Methods The aim of the present study was to compare the 4C mortality score, other measures of the systemic inflammatory response and clinicopathological characteristics in two consecutive cohorts of patients on admission with COVID-19. Electronic patient records for 2 consecutive cohorts of patients admitted to two urban teaching hospitals with COVID-19 during two 7-week periods of the COVID-19 pandemic in Glasgow, U.K. (cohort 1: 17/3/2020–1/5/2020) and (cohort 2: 18/5/2020–6/7/2020) were examined for routine clinical, laboratory and clinical outcome data. Results Compared with cohort 1, cohort 2 were older (p<0.001), more likely to be female (p<0.05) and have less independent living circumstances (p<0.001). More patients in cohort 2 were PCR positive, CXR negative (both p<0.001) and had low serum albumin concentrations (p<0.001). 30-day mortality was similar between both cohorts (23% and 22%). In cohort 2, age >70 (p<0.05), male gender (p<0.05), COPD (p<0.05), cognitive impairment (p<0.05), frailty (p<0.001), delirium (p = 0.001), CRP>150mg/L (p<0.05), albumin <30 g/L (p<0.01), elevated perioperative Glasgow Prognostic Score (p<0.05), elevated neutrophil-lymphocyte ratio (p<0.001), low haematocrit (p<0.01), elevated PT (p<0.05), sodium <133 mmol/L (p<0.01) elevated urea (p<0.001), creatinine (p<0.001), glucose (p<0.05) and lactate (p<0.001) and the 4C score (p<0.001) were associated with 30-day mortality. In multivariate analysis, greater frailty (CFS>3) (OR 11.3, 95% C.I. 2.3–96.7, p<0.05), low albumin (<30g/L) (OR 2.5, 95% C.I. 1.0–6.2, p<0.05), high NLR (≥3) (OR 2.2, 95% C.I. 1.5–4.5, p<0.05) and the 4C score (OR 2.4, 95% C.I. 1.0–5.6, p<0.05) remained independently associated with 30-day mortality. Conclusion In addition to the 4C mortality score, frailty score and a low albumin were strongly independently associated with 30-day mortality in two consecutive cohorts of patients admitted to hospital with COVID-19. Trial registration clinicaltrials.gov: NCT04484545.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3611-3611
Author(s):  
Donald C. Mcmillan ◽  
Campbell SD Roxburgh ◽  
Paul G Horgan

3611 Background: There is now good evidence that, in addition to TNM stage, the pre-operative combination of the standardised measurements of C-reactive protein and albumin, the Glasgow Prognostic Score (mGPS) provides valuable prognostic information. The aim of the present study was to examine the clinical application of the pre-operative mGPS in a large mature cohort of patients undergoing potentially curative resection for colorectal cancer. Methods: From a prospectively maintained database, consecutive patients (n= 797) with histologically proven colorectal cancer who were considered to have undergone potentially curative resection between January 1997 and December 2010 in a single surgical unit at the Royal Infirmary, Glasgow were included in the study. Results: Patients with an elevated mGPS were more likely to be older (p<0.001), female (p<0.05), have colonic tumours (<0.001), present as an emergency (p<0.001), had higher TNM stage (p<0.05) and more likely to die of their disease (p<0.01). The median follow-up was 66 months and using 3 year cancer-specific mortality as an endpoint, the area under the receiver operator curve was 0.652 (95% CI, 0.591–0.714; p<0.001) for the mGPS and 0.668 (95% CI, 0.610–0.727; p<0.001) for TNM stage. The cancer-specific survival, at 3 years, varied between 86% and 64% according to the mGPS and between 88% and 72% according to TNM stage. The cancer-specific survival, at 3 years, in patients with a mGPS 0 was 91% and 81% for TNM stage II and III respectively. The cancer-specific survival, at 3 years, in patients with a mGPS 1 was 89% and 66% for TNM stage II and III respectively. The cancer-specific survival, at 3 years, in patients with a mGPS 2 was 77% and 43% for TNM stage II and III respectively. Conclusions: The results of the present study show the clinical utility of the pre-operative mGPS in predicting cancer specific survival of potentially curative surgery for colorectal cancer.


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