...NLR contributed more prognostic value in patients without weight loss compared with the prognostic value of weight loss in patients who were not systemically inflamed. Furthermore, we are ...consistent with the concept that cachexia may be more aptly considered disease-related inflammation with weight loss in the GLIM paradigm. 3 Since the recognition of the importance of weight loss as a prognostic factor in ancient times, it has been a constant reference point in clinical diagnosis, prognosis and the treatment of cancer. ...although clinically routinely measured, compared with mGPS, the NLR is less sensitive to the presence of systemic inflammation, and the thresholds are not well defined. 4 Given the limitations of the NLR and in the context of cancer immunotherapy, mGPS has been increasingly adopted for routine monitoring of the systemic inflammatory response. 5,6 Therefore, it would be of considerable interest to compare the relative prognostic value of NLR and mGPS in the WLAIGS.
Background
Computed tomography (CT) analysis of body composition has garnered interest as a potential prognostic tool in those with cancer. A range of pre‐defined thresholds currently exist within ...the literature to define low skeletal muscle mass and density. The aim of the present systematic review was to assess the prevalence of low skeletal muscle index (SMI) and density (SMD) within the literature, across a range of common solid tumours.
Methods
A systematic search of PubMed was carried out to identify studies reporting CT analysis of SMI and SMD in patients with colorectal, oesophageal, gastric, hepatobiliary, pancreatic, breast, and lung cancer. The type of cancer, whether curative or non‐curative disease, the anthropomorphic parameter studied, threshold used to define low SMI and SMD, and the prevalence of these anthropomorphic measurements within the population were recorded.
Results
Of the 160 studies included, 156 reported an assessment of SMI and 35 reported assessment of SMD. The median prevalence of low SMI was 43% (30.1–57.1) and low SMD 49.4% (31.7–58.5) across the entire cohort. There was little variation in the prevalence of low SMI and SMD when studies were divided into curative and non‐curative cohorts—40.7% (27.5–51.3) vs. 48.4% (30.9–60.1) and 37.8% (32.2–52.2) vs. 55.3% (38.5–64.7) respectively. When divided into colorectal, oesophageal, gastric, hepatobiliary, pancreatic, breast and lung cancers, similar prevalence of low SMI (46.0% %, 49.8%, 35.7%, 41.1%, 32.3%, 34%, and 49.5%) and low SMD were also observed (52.1%, 54.3%, 71.2%, 56.8%, 55.3%, and 52.6%). This was maintained when studies were stratified into cohorts by threshold used—low SMI (Martin 48.9%, Prado 49.9%, and Others 36.0%) and low SMD (Martin 52.4% and Others 48.6%).
Conclusions
Low SMI and SMD are endemic across a range of cancer types and disease stage, challenging pre‐existing dogma of the determinants of prevalence.
Low skeletal muscle mass and density, as assessed by CT-body composition (CT-BC), are recognised to have prognostic value in non-cancer and cancer patients. The aim of the present study was to ...compare CT-BC parameters between non-cancer (abdominal aortic aneurysm, AAA) and cancer (colorectal cancer, CRC) patients.
Two retrospective multicentre cohorts were compared. Thresholds of visceral fat area (VFA, Doyle), skeletal fat index (SFI, Ebadi), skeletal muscle index (SMI, Martin), and skeletal muscle density (SMD, Martin) were applied to these cohorts and compared. The systemic inflammatory response (SIR) was measured by the systemic inflammatory grade (SIG).
1695 patients were included; 759 patients with AAA and 936 patients with CRC. Low SMD (33% vs. 66%, p <0.001) was more prevalent in the CRC cohort. Low SMI prevalence was similar in both cohorts (51% vs. 51%, p = 0.80). Compared with the AAA cohort, the CRC cohort had a higher prevalence of raised SIG (p <0.001). Increasing age (OR 1.54, 95% CI 1.38-1.72, p < 0.001) and elevated SIG (OR 1.23, 95% CI 1.09-1.40, p = 0.001) were independently associated with increased odds of low SMI. Increasing age (OR 1.90, 95% CI 1.66-2.17, p < 0.001) CRC diagnosis (OR 5.89, 95% CI 4.55-7.62, p < 0.001), ASA > 2 (OR 1.37, 95% CI 1.08-1.73, p = 0.01), and elevated SIG (OR 1.19, 95% CI 1.03-1.37, p = 0.02) were independently associated with increased odds of low SMD.
Increasing age and systemic inflammation appear to be important determinants of loss of skeletal muscle mass and quality irrespective of disease.
Frailty, determined by the Canadian Study of Health and Aging-Clinical Frailty Scale (CFS), is strongly associated with clinical outcomes including mortality in patients with COVID-19. However, the ...relationship between frailty and other recognised prognostic factors including age, nutritional status, obesity, sarcopenia and systemic inflammation is poorly understood. Therefore, the aim of this study was to examine the relationship between frailty and other prognostic domains, in patients admitted with COVID-19.
Patients who presented to our institutions between 1st April 2020-6th July 2020 with confirmed COVID-19 were assessed for inclusion. Data collected included general demographic details, clinicopathological variables, CFS admission assessment, Malnutrition Universal Screening Tool (MUST), CT-BC measurements and markers of systemic inflammation.
106 patients met the study inclusion criteria. The majority of patients were aged ≥ 70 years (67%), male (53%) and frail (scoring > 3 on the CFS, 72%). The majority of patients were not malnourished (MUST 0, 58%), had ≥ 1 co-morbidity (87%), were sarcopenic (low SMI, 80%) and had systemic inflammation (mGPS ≥ 1, 81%, NLR > 5, 55%). On multivariate binary logistics regression analysis, age (p < 0.01), COPD (p < 0.05) and NLR (p < 0.05) remained independently associated with frailty. On univariate binary logistics regression, NLR (p < 0.05) was significantly associated with 30-day mortality.
Frailty was independently associated with age, co-morbidity, and systemic inflammation. The basis of the relationship between frailty and clinical outcomes in COVID-19 requires further study. Trial registration Registered with clinicaltrials.gov (NCT04484545).
While the current literature suggests an association with frailty and clinical outcomes in patients undergoing surgery for colorectal cancer (CRC), the basis of this relationship is unclear.
Examine ...the relationship between frailty, malnutrition, body composition, systemic inflammation and short-term clinical outcomes in patients undergoing surgery for colorectal cancer.
Consecutive patients who underwent potentially curative resection for colorectal cancer, between April 2008 and April 2018, were identified from a prospectively maintained database. Frailty was defined using the modified five-item frailty index (mFI-5). Body composition measures included CT-derived skeletal muscle index (SMI) and density (SMD). Systemic inflammatory status was determined using Systemic Inflammatory Grade (SIG). Outcomes of interest were the incidence of post-operative complications and thirty-day mortality. Associations between categorical variables were examined using χ
test and binary logistics regression analysis.
1002 patients met the inclusion criteria. 28% (n = 221) scored 2 or more on the mFI-5. 39% (n = 388) of patients had a post-operative complication (Clavien-Dindo I-IV) and 1% (n = 11) died within thirty days of surgery. On univariate analysis, mFI-5 frailty score, was significantly associated with advanced age (p < 0.001), colonic tumours (p < 0.001), reduced use of neo-adjuvant chemotherapy (p < 0.05), higher BMI (p < 0.05), low SMD (p < 0.001), elevated NLR (p < 0.05), elevated mGPS (p < 0.05), elevated SIG (p < 0.05), incidence of post-operative complications (p < 0.001) and thirty-day mortality (p < 0.05). On multivariate analysis, male sex (p < 0.05), elevated SIG (p < 0.05) and mFI-5 score (p < 0.01) remained significantly associated with the incidence of post-operative complications. mFI-5 frailty was found to remain significantly associated with the incidence post-operative complications in patients who were SIG 0 (p < 0.05).
mFI-5 frailty score was found to be significantly associated with age, systemic inflammation and post-operative outcomes in patients undergoing potentially curative resections for CRC. Incorporation of an assessment of systemic inflammatory status in future frailty screening tools may improve their prognostic value.
Frailty is a complex multifactorial syndrome characterised by a significant increase in vulnerability and worsened health outcomes. Despite a range of proposed frailty screening measures, the ...prevalence and prognostic value of frailty in patients undergoing surgery for colorectal cancer is not clear.
The aim of this present review was to examine the use of commonly employed frailty screening measures in patients undergoing surgery for colorectal cancer.
A systematic search of PubMed and Medline was carried out to identify studies reporting the use of frailty screening tools or measures in patients undergoing surgery for colorectal cancer. The screening measure used and prevalence of frailty within the population were recorded. Outcomes of interest were the incidence of post-operative complications, 30-day mortality and overall survival.
Of the 15 studies included (n = 97, 898 patients), 9 studies were retrospective and included patients aged 70 years or older (n = 96, 120 patients). 5 of 12 studies reported that frailty was independently associated with the incidence of post-operative complications. There was also evidence that frailty was independently associated with 30-day mortality (1 of 4 studies, n = 9, 252 patients) and long-term survival (2 of 3 studies, n = 1, 420 patients).
Frailty was common in patients with colorectal cancer and the assessment of frailty may have prognostic value in patients undergoing surgery. However, the basis of the relationship between frailty and post-operative outcomes is not clear and merits further study.
High vagal nerve activity, reliability measured by HRV, is considered protective in cancer, reducing oxidative stress, inflammation and opposing sympathetic nerve activity. The present monocentric ...study examines the relationship between HRV, TNM stage, co-morbidity, systemic inflammation and survival in patients who underwent potentially curative resections for colorectal cancer (CRC). Time-domain HRV measures, Standard Deviation of NN-intervals (SDNN) and Root Mean Square of Successive Differences (RMSSD), were examined as categorical (median) and continuous variables. Systemic inflammation was determined using systemic inflammatory grade (SIG) and co-morbidity using ASA. The primary end point was overall survival (OS) and was analysed using Cox regression. There were 439 patients included in the study and the median follow-up was 78 months. Forty-nine percent (n = 217) and 48% (n = 213) of patients were categorised as having low SDNN (< 24 ms) and RMSSD (< 29.8 ms), respectively. On univariate analysis, SDNN was not significantly associated with TNM stage (p = 0.830), ASA (p = 0.598) or SIG (p = 0.898). RMSSD was not significantly associated with TNM stage (p = 0.267), ASA (p = 0.294) or SIG (p = 0.951). Neither SDNN or RMSSD, categorical or continuous, were significantly associated with OS. In conclusion, neither SDNN or RMSSD were associated with TNM stage, ASA, SIG or survival in patients undergoing potentially curative surgery for CRC.
Micronutrients have been associated with disease severity and poorer clinical outcomes in patients with COVID-19. However, there is a paucity of studies examining if the relationship with ...micronutrient status and clinical outcomes is independent of recognised prognostic factors, specifically frailty and the systemic inflammatory response (SIR). The aim of the present study was to examine the relationship between micronutrient status, frailty, systemic inflammation, and clinical outcomes in patients admitted with COVID-19.
Retrospective analysis of prospectively collected data was performed on patients with confirmed COVID-19, admitted to hospital between the 1st April 2020-6th July 2020. Clinicopathological characteristics, frailty assessment, biochemical and micronutrient laboratory results were recorded. Frailty status was determined using the Clinical Frailty scale. SIR was determined using serum CRP. Clinical outcomes of interest were oxygen requirement, ITU admission and 30-day mortality. Categorical variables were analysed using chi-square test and binary logistics regression analysis. Continuous variables were analysed using the Mann-Whitney U or Kruskal Wallis tests.
281 patients were included. 55% (n = 155) were aged ≥ 70 years and 39% (n = 109) were male. 49% (n = 138) of patients were frail (CFS > 3). 86% (n = 242) of patients had a serum CRP > 10 mg/L. On univariate analysis, frailty was significantly associated with thirty-day mortality (p < 0.001). On univariate analysis, serum CRP was found to be significantly associated with an oxygen requirement on admission in non-frail patients (p = 0.004). Over a third (36%) of non-frail patients had a low vitamin B1, despite having normal reference range values of red cell B2, B6 and selenium. Furthermore, serum CRP was found to be significantly associated with a lower median red cell vitamin B1 (p = 0.029).
Vitamin B1 stores may be depleted in COVID-19 patients experiencing a significant SIR and providing rationale for thiamine supplementation. Further longitudinal studies are warranted to delineate the trend in thiamine status following COVID-19.
Background
Second‐line immunotherapy is currently recognized to help only a subset of patients with advanced forms of non‐small cell lung cancer (NSCLC). The current study analyzes the connection ...between prior treatment host/tumor characteristics and survival in advanced NSCLC patients receiving nivolumab as a second‐line therapy.
Methods
A retrospective cohort analysis was carried out on individuals with advanced NSCLC receiving second‐line Nivolumab with palliative intent between February 2016 and May 2019 across three health boards in NHS Greater Glasgow and Clyde, Lanarkshire, Ayrshire, and Arran in Scotland to examine the association between systemic inflammation, body composition, and survival were determined using computed tomography (CT).
Results
The current study investigates the connection between prior treatment host/tumor characteristics and survival in advanced NSCLC patients receiving nivolumab as a second‐line therapy. The majority were 65 years of age or older (51%), female (53%), had adenocarcinoma (53%), and had good performance status (ECOG 0/1) (86%). Most patients had high SFI (70%) or VFA (54%). The median overall survival after starting Nivolumab was 15 months. ECOG‐PS and hypoalbuminemia were significant predictors of 12‐month survival in patients with advanced NSCLC following Nivolumab treatment, according to Cox regression (p‐value = 0.047 and 0.014, respectively).
Conclusion
In patients with advanced NSCLC receiving Nivolumab as a second‐line therapy, ECOG‐PS and hypoalbuminemia were strongly associated with survival. Systemic inflammation and hypoalbuminemia measurements may enhance the ECOG‐PS stratification of expected outcomes.
The relationship between pre‐treatment clinicopathological variables, systemic inflammation, CT‐body composition, and 12 months survival in patients with NSCLC receiving Nivolumab as a second line treatment.
The present study examined the relationships between CT-derived muscle measurements, systemic inflammation, and survival in advanced cancer patients with good performance status (ECOG-PS 0/1). Data ...was collected prospectively from patients with advanced cancer undergoing anti-cancer therapy with palliative intent. The CT Sarcopenia score (CT-SS) was calculated by combining the CT-derived skeletal muscle index (SMI) and density (SMD). The systemic inflammatory status was determined using the modified Glasgow Prognostic Score (mGPS). The primary outcome of interest was overall survival (OS). Univariate and multivariate Cox regressions were used for survival analysis. Three hundred and seven patients met the inclusion criteria, out of which 62% (n = 109) were male and 47% (n = 144) were ≥65 years of age, while 38% (n = 118) were CT-SS ≥ 1 and 47% (n = 112) of patients with pre-study blood were inflamed (mGPS ≥ 1). The median survival from entry to the study was 11.1 months (1-68.1). On univariate analysis, cancer type (
< 0.05) and mGPS (
< 0.001) were significantly associated with OS. On multivariate analysis, only mGPS (
< 0.001) remained significantly associated with OS. In patients who were ECOG-PS 0, mGPS was significantly associated with CT-SS (
< 0.05). mGPS may dominate the prognostic value of CT-derived sarcopenia in good-performance-status patients with advanced cancer.