Measurement of the Systemic Inflammatory Response Predicts Cancer-Specific and Non-Cancer Survival in Patients With Cancer Donald C. McMillan, Maqsood M. Elahi, Naveed Sattar, Wilson J. Angerson, Jennie Johnstone, and Colin S. McArdle Abstract and Introduction Abstract The assessment of prognosis in patients with advanced cancer remains problematical. The value of C-reactive protein concentration in this context has not been clearly defined. Patients with a diagnosis of colorectal (n = 182), gastric (n = 87), breast (n = 99), or bronchogenic (n = 404) cancer and who had measurements of C-reactive protein and albumin were identified. Median survival, from the time of sampling, ranged from 478 days in the colorectal cancer patients to 60 days in patients with bronchogenic cancer. On univariate analysis, there was, in each tumor type, a significant relationship between the duration of survival and both log10 C-reactive protein and albumin concentrations (P When all four groups of cancer patients were analyzed (n = 772), the hazard ratio for a 10-fold increase in C-reactive protein concentration in cancer-specific survival was 2.21 (95% confidence interval = 1.92-2.56, P < 0.0001) and the corresponding hazard ratio for non-cancer survival was 5.48 (95% confidence interval = 3.55-8.46, P < 0.0001). The results of the present study indicate that in advanced cancer patients the presence of a systemic inflammatory response and the magnitude of that response predict the duration of cancer-specific and non-cancer survival. Introduction There is increasing evidence that the presence of a systemic inflammatory response is associated with reduced survival in patients with a variety of solid tumors. For example, it has been reported that the presence of an inflammatory response, as evidenced by C-reactive protein concentration, is associated with tumor progression in colorectal cancer[1,2] and is an important predictor of survival, independent of stage, in pancreatic,[3] colorectal,[4,5] gastric,[6] and lung cancer.[7] In the above studies, the role of C-reactive protein was evaluated at or around the time of diagnosis and initial treatment. However, at the time of diagnosis, C-reactive protein is only one of many prognostic factors. In contrast, the assessment of patients with advanced disease is more problematical, since few established prognostic factors are available.[8,9] The potential value of C-reactive protein has only recently been assessed in this context in gastrointestinal cancer patients.[10]The aim of the present study was to assess the value of the incidental measurement of C-reactive protein concentration as a prognostic factor in a large cohort of patients with a variety of common solid tumors. Discussion This study has a number of limitations. The patients were selected on the basis that measurements of C-reactive protein and albumin had been performed and were, therefore, not necessarily representative of all cancer patients treated in this hospital. Furthermore, sampling was incidental and not performed at a standard time during the course of the disease. However, given that the median survival from the time of sampling was ~1 yr or less in each of the tumors examined, it is likely that the majority of patients had locally advanced or metastatic cancer at this time. Analysis was limited to the following variables: age, sex, C-reactive protein, albumin, and tumor type. Since sampling was performed at variable times during the course of the disease, clinicopathological stage at diagnosis and subsequent treatment were not included in the analysis. Nevertheless, despite the lack of information on clinicopathological stage and treatment and the variable time of sampling, C-reactive protein was an independent predictor of cancer-specific survival within each tumor type and across different tumors. Moreover, in the present study, there was no relationship between the time elapsed from diagnosis to sampling and C-reactive protein concentrations. Overall, the hazard ratio for a 10-fold increase in C-reactive protein concentration was 3.1 in colorectal cancer, which is similar to that previously reported, with clinicopathological stage at diagnosis taken into account.[5]It was also of interest that there was a negative correlation between C-reactive protein and albumin concentrations. Because in the present study the relationship between C-reactive protein and albumin was essentially independent of tumor type, this relationship suggests a prototypical response in patients with advanced solid tumors. Indeed, C-reactive protein is the prototypical acute-phase protein, the concentrations of which are sensitive to inflammatory stimuli such as trauma, surgery, infection, and cancer. Clinically, it is the most useful measurement in differentiating inflammatory from noninflammatory conditions.[12] The mechanism by which a systemic inflammatory response might impact on cancer-specific survival is not clear. However, it is known that as part of the systemic inflammatory response to the tumor there is a release of proinflammatory cytokines and growth factors,[13,14] which have profound catabolic effects on host metabolism.[15,16] For example, interleukin-6, produced by the tumor or surrounding cells,[17] stimulates liver production of acute-phase proteins (such as C-reactive protein and fibrinogen) in the fasted and fed state.[16] This increases the demand for certain amino acids, which, if limited in the diet, may be obtained from the breakdown of skeletal muscle.[18,19] In this way, the presence and magnitude of a chronic systemic inflammatory response in advanced cancer patients may produce a progressive nutritional and functional decline, ultimately resulting in reduced survival. Furthermore, in the present study, it was of interest that raised C-reactive protein concentrations were also associated with a higher risk of noncancer deaths. Indeed, the risk was greater than that for cancer death. The basis of the relationship of C-reactive protein and noncancer death is not clear. However, it is well recognized that, in population studies, C-reactive protein is a strong predictor of death from cardiovascular disease.[11] Nevertheless, it would appear that the presence and the magnitude of the systemic inflammatory response are associated with an increased risk of cancer-specific and noncancer death in patients with advanced cancer.The relationship between the systemic inflammatory response and cancer-specific and non-cancer survival may have important implications for the assessment and treatment of patients with advanced cancer. It is well recognized that predicting the life expectancy of patients is difficult, and clinicians often overestimate survival.[9,10] Current methods of assessing the suitability of such patients for treatment are usually based on measures of weight loss, performance status, or albumin concentration. It is of interest that C-reactive protein retains its prognostic significance irrespective of when it is measured during the course of the disease. The results of this and previous studies[7,10] suggest that use of C-reactive protein concentrations may improve the assessment of these patients.In summary, the results of the present study indicate that in advanced cancer patients the presence of a systemic inflammatory response and the magnitude of that response predict the duration of cancer-specific and non-cancer survival. Further prospective studies with serial measurements of C-reactive protein are required to establish the clinical utility of this measurement in predicting survival in patients with different cancers. D. C. McMillan, M. M. Elahi, and W. J. Angerson are affiliated with the University Department of Surgery and N. Slater and J. Johnstone with the University Department of Biochemistry, Royal Infirmary, Glasgow G31 2ER, UK. C. S. McArdle is affiliated with the University Department of Surgery, Royal Infirmary, Edinburgh EH3 9YW, UK. Nutr Cancer 41(1):64-69, 2001. © 2001 Lawrence Erlbaum Associates, Inc. Measurement of the Systemic Inflammatory Response Predicts Cancer-Specific and Non-Cancer Survival in Patients With Cancer from Nutrition and Cancer Posted 07/31/2002 Donald C. McMillan, Maqsood M. Elahi, Naveed Sattar, Wilson J. Angerson, Jennie Johnstone, and Colin S. McArdle Abstract and Introduction Abstract The assessment of prognosis in patients with advanced cancer remains problematical. The value of C-reactive protein concentration in this context has not been clearly defined. Patients with a diagnosis of colorectal (n = 182), gastric (n = 87), breast (n = 99), or bronchogenic (n = 404) cancer and who had measurements of C-reactive protein and albumin were identified. edian survival, from the time of sampling, ranged from 478 days in the colorectal cancer patients to 60 days in patients with bronchogenic cancer. On univariate analysis, there was, in each tumor type, a significant relationship between the duration of survival and both log10 C-reactive protein and albumin concentrations (P When all four groups of cancer patients were analyzed (n = 772), the hazard ratio for a 10-fold increase in C-reactive protein concentration in cancer-specific survival was 2.21 (95% confidence interval = 1.92-2.56, P < 0.0001) and the corresponding hazard ratio for non-cancer survival was 5.48 (95% confidence interval = 3.55-8.46, P < 0.0001). The results of the present study indicate that in advanced cancer patients the presence of a systemic inflammatory response and the magnitude of that response predict the duration of cancer-specific and non-cancer survival. Introduction There is increasing evidence that the presence of a systemic inflammatory response is associated with reduced survival in patients with a variety of solid tumors. For example, it has been reported that the presence of an inflammatory response, as evidenced by C-reactive protein concentration, is associated with tumor progression in colorectal cancer[1,2] and is an important predictor of survival, independent of stage, in pancreatic,[3] colorectal,[4,5] gastric,[6] and lung cancer.[7] In the above studies, the role of C-reactive protein was evaluated at or around the time of diagnosis and initial treatment. However, at the time of diagnosis, C-reactive protein is only one of many prognostic factors. In contrast, the assessment of patients with advanced disease is more problematical, since few established prognostic factors are available.[8,9] The potential value of C-reactive protein has only recently been assessed in this context in gastrointestinal cancer patients.[10]The aim of the present study was to assess the value of the incidental measurement of C-reactive protein concentration as a prognostic factor in a large cohort of patients with a variety of common solid tumors. Discussion This study has a number of limitations. The patients were selected on the basis that measurements of C-reactive protein and albumin had been performed and were, therefore, not necessarily representative of all cancer patients treated in this hospital. Furthermore, sampling was incidental and not performed at a standard time during the course of the disease. However, given that the median survival from the time of sampling was ~1 yr or less in each of the tumors examined, it is likely that the majority of patients had locally advanced or metastatic cancer at this time. Analysis was limited to the following variables: age, sex, C-reactive protein, albumin, and tumor type. Since sampling was performed at variable times during the course of the disease, clinicopathological stage at diagnosis and subsequent treatment were not included in the analysis. Nevertheless, despite the lack of information on clinicopathological stage and treatment and the variable time of sampling, C-reactive protein was an independent predictor of cancer-specific survival within each tumor type and across different tumors. Moreover, in the present study, there was no relationship between the time elapsed from diagnosis to sampling and C-reactive protein concentrations. Overall, the hazard ratio for a 10-fold increase in C-reactive protein concentration was 3.1 in colorectal cancer, which is similar to that previously reported, with clinicopathological stage at diagnosis taken into account.[5]It was also of interest that there was a negative correlation between C-reactive protein and albumin concentrations. Because in the present study the relationship between C-reactive protein and albumin was essentially independent of tumor type, this relationship suggests a prototypical response in patients with advanced solid tumors. Indeed, C-reactive protein is the prototypical acute-phase protein, the concentrations of which are sensitive to inflammatory stimuli such as trauma, surgery, infection, and cancer. Clinically, it is the most useful measurement in differentiating inflammatory from noninflammatory conditions.[12] The mechanism by which a systemic inflammatory response might impact on cancer-specific survival is not clear. However, it is known that as part of the systemic inflammatory response to the tumor there is a release of proinflammatory cytokines and growth factors,[13,14] which have profound catabolic effects on host metabolism.[15,16] For example, interleukin-6, produced by the tumor or surrounding cells,[17] stimulates liver production of acute-phase proteins (such as C-reactive protein and fibrinogen) in the fasted and fed state.[16] This increases the demand for certain amino acids, which, if limited in the diet, may be obtained from the breakdown of skeletal muscle.[18,19] In this way, the presence and magnitude of a chronic systemic inflammatory response in advanced cancer patients may produce a progressive nutritional and functional decline, ultimately resulting in reduced survival. Furthermore, in the present study, it was of interest that raised C-reactive protein concentrations were also associated with a higher risk of noncancer deaths. Indeed, the risk was greater than that for cancer death. The basis of the relationship of C-reactive protein and noncancer death is not clear. However, it is well recognized that, in population studies, C-reactive protein is a strong predictor of death from cardiovascular disease.[11] Nevertheless, it would appear that the presence and the magnitude of the systemic inflammatory response are associated with an increased risk of cancer-specific and noncancer death in patients with advanced cancer.The relationship between the systemic inflammatory response and cancer-specific and non-cancer survival may have important implications for the assessment and treatment of patients with advanced cancer. It is well recognized that predicting the life expectancy of patients is difficult, and clinicians often overestimate survival.[9,10] Current methods of assessing the suitability of such patients for treatment are usually based on measures of weight loss, performance status, or albumin concentration. It is of interest that C-reactive protein retains its prognostic significance irrespective of when it is measured during the course of the disease. The results of this and previous studies[7,10] suggest that use of C-reactive protein concentrations may improve the assessment of these patients.In summary, the results of the present study indicate that in advanced cancer patients the presence of a systemic inflammatory response and the magnitude of that response predict the duration of cancer-specific and non-cancer survival. Further prospective studies with serial measurements of C-reactive protein are required to establish the clinical utility of this measurement in predicting survival in patients with different cancers. D. C. McMillan, M. M. Elahi, and W. J. Angerson are affiliated with the University Department of Surgery and N. Slater and J. Johnstone with the University Department of Biochemistry, Royal Infirmary, Glasgow G31 2ER, UK. C. S. McArdle is affiliated with the University Department of Surgery, Royal Infirmary, Edinburgh EH3 9YW, UK. Nutr Cancer 41(1):64-69, 2001. © 2001 Lawrence Erlbaum Associates, Inc. C Reactive Protein Am J Med, 12/03 Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.