Summary Since the initial work, a decade ago that the combination of C-reactive protein and albumin, the Glasgow Prognostic Score (GPS), had independent prognostic value in patients with cancer, ...there have been more than 60 studies (>30,000 patients) that have examined and validated the use of the GPS or the modified GPS (mGPS) in a variety of cancer scenarios. The present review provides a concise overview of these studies and comments on the current and future clinical utility of this simple objective systemic inflammation-based score. The GPS/mGPS had independent prognostic value in (a) unselected cohorts (4 studies, >19,400 patients) (b) operable disease (28 studies, >8,000 patients) (c) chemo/radiotherapy (11 studies, >1500 patients) (d) inoperable disease (11 studies, >2,000 patients). Association studies (15 studies, >2,000 patients) pointed to an increased GPS/mGPS being associated with increased weight and muscle loss, poor performance status, increased comorbidity, increased pro-inflammatory and angiogenic cytokines and complications on treatment. These studies have originated from 13 different countries, in particular the UK and Japan. A chronic systemic inflammatory response, as evidenced by the GPS/mGPS, is clearly implicated in the prognosis of patients with cancer in a variety of clinical scenarios. The GPS/mGPS is the most extensively validated of the systemic inflammation-based prognostic scores and therefore may be used in the routine clinical assessment of patients with cancer. It not only identifies patients at risk but also provides a well defined therapeutic target for future clinical trials. It remains to be determined whether the GPS has prognostic value in other disease states.
Summary Inflammation is a recognised hallmark of cancer that substantially contributes to the development and progression of malignancies. In established cancers, there is increasing evidence for the ...roles that local immune response and systemic inflammation have in progression of tumours and survival of patients with cancer. This knowledge provides an opportunity to target these inflammatory responses to improve patient outcomes. In this Review, we examine the complex interplay between local immune responses and systemic inflammation, and their influence on clinical outcomes, and propose potential anti-inflammatory interventions for patients with cancer.
There is now good evidence in humans that a chronic systemic inflammatory response results in the cardinal features of cancer cachexia, principally the progressive loss of weight (in particular lean ...tissue). This review examines the role of recent simple objective systemic inflammation-based scores in predicting reduction of nutritional status and survival.
The most common measure of the systemic inflammatory response in cancer patients has been an elevated C-reactive protein concentration. This has now been included in recent definitions of cancer cachexia. There are also recent systemic inflammation-based scores, the Glasgow Prognostic Score, Neutrophil Lymphocyte Ratio and the Platelet Lymphocyte Ratio that have been shown to have prognostic value in cancer patients. These scores, in particular the Glasgow Prognostic Score, enable identification of patients who are, or likely, to develop cachexia, have a poor response to treatment and who are likely to have poor survival.
A chronic systemic inflammatory response is clearly implicated in the progressive nutritional and functional decline in the cancer patients and their subsequent poor outcome. Systemic inflammation-based prognostic scores not only identify patients at risk but also provide well defined therapeutic targets for future clinical trials targeting nutritional decline.
Abstract Progress in the treatment of progressive involuntary weight loss in patients with cancer (cancer cachexia) remains dismally slow. Cancer cachexia and its associated clinical symptoms, ...including weight loss, altered body composition, poor functional status, poor food intake, and poorer quality of life, have long been recognised as indicators of poorer prognosis in the patient with cancer. In order to make some progress a starting point is to have general agreement on what constitutes cancer cachexia. In recent years a plethora of different definitions and consensus statements have been proposed as a framework for investigation and treatment of this debilitating and terminal condition. However, there are significant differences in the criteria used in these and all include poorly defined or subjective criteria and their prognostic value has not been established. The aim of the present review was to examine the hypothesis that a systemic inflammatory response accounts for most of the effect of cancer cachexia and its associated clinical symptoms on poor outcome in patients with cancer. Furthermore, to put forward the case for the Glasgow Prognostic Score to act a simple objective framework for the investigation and treatment of cancer cachexia.
Background Operative injury to the body from all procedures causes a stereotypical cascade of neuroendocrine, cytokine, myeloid, and acute phase responses. This response has been examined commonly by ...the use of cortisol, interleukin-6 (IL-6), white cell count, and C-reactive protein (CRP). We aimed to determine which markers of the systemic inflammatory response were useful in determining the magnitude of injury after elective operations. Methods A systematic review of the literature was performed using surgery, endocrine response, systemic inflammatory response, cortisol, IL-6, white cell count, and CRP. For each analyte the studies were grouped according to whether the operative injury was considered to be minor, moderate, or major and then by the operative procedure. Results A total of 164 studies were included involving 14,362 patients. The IL-6 and CRP responses clearly were associated with the magnitude of operative injury and the invasiveness of the operative procedure. For example, the peak CRP response increased from 52 mg/L with cholecystectomy to 123 mg/L with colorectal cancer resection, 145 mg/L with hip replacement, 163 mg/L after abdominal aortic aneurysm repair, and 189 mg/L after open cardiac surgery. There also appeared to be a difference between minimally invasive/laparoscopic and open procedures such as cholecystectomy (27 vs 80 mg/L), colorectal cancer resection (97 vs 133 mg/L), and aortic aneurysm repair (132 vs 180 mg/L). Conclusion Peak IL-6 and CRP concentrations consistently were associated with the magnitude of operative injury and operative procedure. These markers may be useful in the objective assessment of which components of Enhanced Recovery after Surgery are likely to improve patient outcome and to assess the possible impact of operative injury on immune function.
Progressive involuntary weight loss, in particular the loss of lean tissue, is common in patients with advanced cancer and has long been recognised to result in a deterioration in performance status ...and quality of life, increased morbidity and mortality. The aetiology of such weight loss or cachexia is complex and involves both tumour and host responses. Thus, identification of patients who are or are likely to become cachectic has been problematic. In addition to a reduction in appetite and increased satiety leading to poor dietary intake, there is now increasing clinical evidence that the activation of a chronic ongoing systemic inflammatory response is one of the earliest and most important contributory factors to cachexia. Such findings help to explain the failure of simple nutritional programmes to reverse weight loss adequately in patients with cancer. In the present paper the development of an inflammation-based score is described, which is derived from the acute-phase proteins C-reactive protein and albumin and is termed the Glasgow prognostic score (GPS). Its value as a predictor of survival, independent of tumour stage, performance status and treatment (active or palliative), has been shown in a variety of advanced common solid tumours. The nature of the relationship between the GPS, appetite, body composition, performance status and quality of life of the patient with advanced cancer will be described. Recently, it has become evident that the systemic inflammatory response is also present in a smaller proportion of patients with primary operable cancer and is also predictive of disease progression and poor survival. The role of GPS in clinical decision making will be discussed.
Micronutrients such as trace elements and vitamins are important as enzyme cofactors in the metabolism of all cells in the body and therefore key to determining nutritional status. The present ...systematic review examined the evidence of the impact of the systemic inflammatory response on plasma micronutrient status in acute (surgical) and chronic tissue injury. A literature review using targeted subject headings was carried out. Plasma C-reactive protein was used to classify minor (80 mg/l) inflammation. The literature search produced 2344 publications and plasma vitamin D, zinc and carotenoids were most commonly studied and plasma vitamins K, B2 and B6 were least studied. In acute injury thirteen studies (all prospective) and in chronic injury twenty-four studies (largely retrospective) were included in the review. There was consistent evidence that most common measured micronutrients in the plasma (zinc, selenium, vitamins A, D, E, K, B2, B6, B12, C, lutein, lycopene, α- and β-carotene) were significantly lowered from minor to moderate to major inflammation. The results of the present systematic review indicate that most plasma micronutrients fall as part of the systemic inflammatory response irrespective of acute or chronic injury. Therefore, in the presence of a systemic inflammation, plasma micronutrient concentrations should be interpreted with caution. There are a number of methods applied to adjust plasma micronutrient concentrations to avoid misdiagnosis of deficiency. Alternatively, intracellular measurements appear to obviate the need for such plasma adjustment to assess micronutrient status.
Nuclear factor-κB (NF-κB) has been widely implicated in the development and progression of cancer. In colorectal cancer (CRC), NF-κB has a key role in cancer-related processes such as cell ...proliferation, apoptosis, angiogenesis, and metastasis. The role of NF-κB in CRC is complex, owed to the cross talk with other signaling pathways. Although there is sufficient evidence gained from cell lines and animal models that NF-κB is involved in cancer-related processes, because of a lack of studies in human tissue, the clinical evidence of its importance is limited in patients with CRC. This review summarizes evidence relating to how NF-κB is involved in the development and progression of CRC and comments on future work to be carried out.
Markers of the systemic inflammatory response, including C-reactive protein and albumin (combined to form the modified Glasgow Prognostic Score), as well as neutrophil, lymphocyte and platelet counts ...have been shown to be prognostic of survival in patients with cancer. The aim of the present study was to examine the prognostic relationship between these markers of the systemic inflammatory response and all-cause, cancer, cardiovascular and cerebrovascular mortality in a large incidentally sampled cohort.
Patients (n = 160 481) who had an incidental blood sample taken between 2000 and 2008 were studied for the prognostic value of C-reactive protein (>10mg/l, albumin (>35mg/l), neutrophil (>7.5×109/l) lymphocyte and platelet counts. Also, patients (n = 52 091) sampled following the introduction of high sensitivity C-reactive protein (>3mg/l) measurements were studied. A combination of these markers, to make cumulative inflammation-based scores, were investigated.
In all patients (n = 160 481) C-reactive protein (>10mg/l) (HR 2.71, p<0.001), albumin (>35mg/l) (HR 3.68, p<0.001) and neutrophil counts (HR 2.18, p<0.001) were independently predictive of all-cause mortality. These associations were also observed in cancer, cardiovascular and cerebrovascular mortality before and after the introduction of high sensitivity C-reactive protein measurements (>3mg/l) (n = 52 091). A combination of high sensitivity C-reactive protein (>3mg/l), albumin and neutrophil count predicted all-cause (HR 7.37, p<0.001, AUC 0.723), cancer (HR 9.32, p<0.001, AUC 0.731), cardiovascular (HR 4.03, p<0.001, AUC 0.650) and cerebrovascular (HR 3.10, p<0.001, AUC 0.623) mortality.
The results of the present study showed that an inflammation-based prognostic score, combining high sensitivity C-reactive protein, albumin and neutrophil count is prognostic of all-cause mortality.
Highlights • Provides comprehensive evidence for the prognostic role of the SIR in advanced cancer. • This review will prove to be clinically very useful in guiding evidence based patient care. • ...Including surgical and oncological treatments.
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