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Nutrition and Cancer Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/hnuc20
Prognostic Value of Scores Based on Malnutrition or Systemic Inflammatory Response in Patients With Metastatic or Recurrent Gastric Cancer a
b
Milana Sachlova , Ondrej Majek & Stepan Tucek a
a
Department of Gastroenterology, Masaryk Memorial Cancer Institute, Brno, Czech Republic
b
Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno, Czech Republic Published online: 30 Oct 2014.
Click for updates To cite this article: Milana Sachlova, Ondrej Majek & Stepan Tucek (2014) Prognostic Value of Scores Based on Malnutrition or Systemic Inflammatory Response in Patients With Metastatic or Recurrent Gastric Cancer, Nutrition and Cancer, 66:8, 1362-1370, DOI: 10.1080/01635581.2014.956261 To link to this article: http://dx.doi.org/10.1080/01635581.2014.956261
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions
Nutrition and Cancer, 66(8), 1362–1370 Copyright Ó 2014, Taylor & Francis Group, LLC ISSN: 0163-5581 print / 1532-7914 online DOI: 10.1080/01635581.2014.956261
Prognostic Value of Scores Based on Malnutrition or Systemic Inflammatory Response in Patients With Metastatic or Recurrent Gastric Cancer Milana Sachlova Department of Gastroenterology, Masaryk Memorial Cancer Institute, Brno, Czech Republic
Ondrej Majek Downloaded by [Florida International University] at 11:47 20 December 2014
Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno, Czech Republic
Stepan Tucek Department of Gastroenterology, Masaryk Memorial Cancer Institute, Brno, Czech Republic
Cancer patients are frequently affected by malnutrition and weight loss, which affects their prognosis, length of hospital stay, health care costs, quality of life and survival. Our aim was to assess the prognostic value of different scores based on malnutrition or systemic inflammatory response in 91 metastatic or recurrent gastric cancer patients considered for palliative chemotherapy at the Masaryk Memorial Cancer Institute. We investigated their overall survival according to the following measures: Onodera’s Prognostic Nutritional Index (OPNI), Glasgow Prognostic Score (GPS), nutritional risk indicator (NRI), Cancer Cachexia Study Group (CCSG), as previously defined, and a simple preadmission weight loss. The OPNI, GPS, and CCSG provided very significant prognostic values for survival (log-rank test P value < 0.001). For example, the median survival for patients with GPS 0 was 12.3 mo [95% confidence interval (CI): 7.7–16.7], whereas the median survival for patients with GPS 2 was only 2.9 mo (95% CI: 1.9–4.8). A significantly worse survival of malnourished patients was also suggested by a multivariate model. The values of GPS, OPNI, and CCSG represent useful tools for the evaluation of patients’ prognosis and should be part of a routine evaluation of patients to provide a timely nutrition support.
INTRODUCTION Malnutrition and weight loss is a frequent problem in cancer patients. It affects their prognosis, length of the hospital stay, health care costs, quality of life, and survival (1–4). More than two thirds of patients with advanced cancer suffer from cachexia and/or anorexia; this syndrome is called the cancerrelated anorexia-cachexia syndrome (CACS) and is defined as a weight loss of more than 5% of the patient’s precancer body
weight. It is known that as little as 5% weight loss can significantly decrease the patient’s response to cancer treatment (5). Cachexia and unintended weight loss are mainly consequences of metabolic changes in a cancer patient’s body (4). Observational studies suggest that low levels of serum albumin are associated with higher mortality rates from cancer. Serum albumin has also been described as an independent prognostic factor of survival in various cancers (6,7), such as lung cancer (8), pancreatic cancer (9), gastric cancer (10), colorectal cancer (11), and breast cancer (12). Several studies of prognostic indicators of survival for patients with advanced cancer have been reported over the last 20 years (13). The concentration of serum C-reactive protein (CRP) has positively correlated with weight loss (14), presence of hypermetabolism and anorexia (15), disease recurrence (16), poor prognostic indicators in patients undergoing radiotherapy (17), and worse survival (18,19). Previously, different markers of malnutrition or systemic inflammatory response were combined in prognostic scores for the prediction of outcomes in cancer patients. However, no study has yet compared the prognostic ability of different scores in gastric cancer patients in particular. Therefore, we evaluated the importance of different prognostic scores in patients with advanced gastric adenocarcinoma. We studied several prognostic scores based on serum albumin markers or weight loss and correlated these measures with the overall survival (OS) of patients, focusing particularly on subgroups of patients according to received chemotherapy.
METHODS Submitted 16 December 2013; accepted in final form 12 August 2014. Address correspondence to Milana Sachlova, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, 65653, Czech Republic. E-mail: [email protected]
1362
Patients We reviewed 91 medical records of patients with metastatic or locoregionally advanced gastric adenocarcinoma (all Stage
Downloaded by [Florida International University] at 11:47 20 December 2014
PROGNOSTIC VALUE OF MALNUTRITION-BASED SCORES
III and IV disease) considered for palliative chemotherapy at the Masaryk Memorial Cancer Institute in Brno, Czech Republic between January 2010 and October 2012. The inclusion criteria were as follows: a histologically confirmed gastric adenocarcinoma, a metastatic or locoregionally advanced or recurrent disease, and the availability of clinical data at the initiation of therapy. Patients with the affection of distal esophagus and/or gastroesophageal junction were excluded from the study. We evaluated only patients with gastric cancer before palliative treatment who had no other serious medical problems (such as renal failure or infection). Relevant clinical characteristics (age, sex, body weight, and height) and performance status (PS) according to the World Health Organization were recorded. Patients were weighed without shoes. Blood samples were analyzed in the biochemical laboratory at the Masaryk Memorial Cancer Institute for albumin, CRP, serum proteins, total lymphocyte counts, and tumor markers such as CEA, ca 19-9, ca 72-4. All patients were followed up at the Department of Comprehensive Cancer Care. The nutritional assessments were performed by a trained dietitian. The food consumptions were entered to medical records.
Utilized Prognostic Scores Several composite scores of the nutritional status (usually including biochemical and anthropometric parameters) showed a correlation with prognosis (20). We followed previously published reports in the choice of prognostic scores (16,21,21,23,30,). Consequently, we have chosen Glasgow Prognostic Score (GPS), Onodera’s Prognostic Nutritional Index (OPNI), Cancer Cachexia Study Group (CCSG), and nutritional risk indicator (NRI) prognostic scores. OPNI is an assessment tool for the nutritional status and potentially predicts the patients’ prognosis (21–23). OPNI is calculated from the serum albumin concentration, and the peripheral blood lymphocyte count has been used to assess the immunological and nutritional condition of patients with a digestive disease. OPNI is calculated as 10 £ serum albumin (g/dl) C 0.005 £ total lymphocyte count. High-risk values are 40. GPS is defined as follows: patients with either elevated CRP (10 mg/L) and hypoalbuminaemia (35 g/L) are assigned a score of 2. The patients with only one of these biochemical abnormalities are assigned a score of 1. The patients with neither of these are assigned a score of 0 (24). NRI is a simple score using the serum albumin and a recent weight loss (25). NRI is calculated as [1.519 £ serum albumin (g/L)] C 0.417 £ (present weight/usual weight £ 100). An NRI score higher than 97.5 indicates that the patient is not malnourished, a score of 97.5–83.5 indicates a moderate malnutrition, and a score lower than 83.5 indicates a severe malnutrition. CCSG suggested that 3 diagnostic criteria for cancer cachexia should be used: a weight loss 10%, an intake
1363
1500 kcal/day, and CRP 10 mg/L. Scores 2 and 3 are indicators for cachexia (4).
Statistical Methods We evaluated the survival of cancer patients in relation with the listed prognostic scores or a simple recent weight loss. In the multivariate modelling analysis, we adjusted their prognostic value using their age, sex, PS and disease (new/recurrent). The overall survival (OS) was defined as the time period between the diagnosis of a new or recurrent gastric cancer considered for palliative chemotherapy, and death (or censoring date at last visit before April 2013). The cumulative survival was visualized using the Kaplan-Meier estimator, and differences between survival functions were tested using the logrank test. The Cox proportional hazards model was used for the multivariate modelling of OS. The proportional hazards assumption was checked with the Schoenfeld residuals based test. The influence diagnostics (the so-called dfbetas) was used to detect the overly influential observations. The Harrell’s C statistic (26) was used to compare the prognostic ability of considered statistical models. Subgroups of patients according to whether they underwent chemotherapy were also compared as regards their survival; for this comparison, we used the logrank test and the Cox model with interaction between the nutritional status and chemotherapy. Statistical analyses were performed using the Stata/IC 10.1 software (College Station, TX: StataCorp LP).
RESULTS Tables 1A and 1B show the baseline characteristics of 91 gastric cancer patients. Most patients were newly diagnosed with Stage IV cancer (78%); however, patients with inoperable (5%) and recurring (16%) disease were also included. Most patients received palliative chemotherapy (71%). Table 1A also reviews the distributions of patients with respect to different prognostic scores (OPNI, GPS, NRI, CCSG, and weight loss). Quantitative characteristics are shown in Table 1B. Table 2 summarizes the median OS for patients with different values of nutritional prognostic scores (visualization of survival functions according to values of different prognostic indices is provided in Fig. 1). Three of these indicators (OPNI, GPS, and CCSG) provided very significant prognostic values for OS (P value < 0.001). For example, the median OS for patients with GPS 0 was 12.3 months [95% confidence interval [CI]: 7.7–16.7), while the median OS for patients with GPS 2 was only 2.9 months (95% CI: 1.9–4.8). Survival rates differed substantially between subgroups of patients with and without chemotherapy even after the stratification using prognostic scores (Table 3). However, the absolute difference in the median OS for patients with and without chemotherapy was considerably lower in malnourished patients (e.g., the difference was approximately 9 mo
1364
M. SACHLOVA ET AL.
TABLE 1A Baseline patients characteristics (N D 91)
Downloaded by [Florida International University] at 11:47 20 December 2014
Characteristics Age 40 40 GPS 0 1 2 NRI >97.5 83.5–97.5 40 40 GPS 0 1 2 NRI >97.5 83.5–97.5
Nutrition and Cancer Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/hnuc20
Prognostic Value of Scores Based on Malnutrition or Systemic Inflammatory Response in Patients With Metastatic or Recurrent Gastric Cancer a
b
Milana Sachlova , Ondrej Majek & Stepan Tucek a
a
Department of Gastroenterology, Masaryk Memorial Cancer Institute, Brno, Czech Republic
b
Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno, Czech Republic Published online: 30 Oct 2014.
Click for updates To cite this article: Milana Sachlova, Ondrej Majek & Stepan Tucek (2014) Prognostic Value of Scores Based on Malnutrition or Systemic Inflammatory Response in Patients With Metastatic or Recurrent Gastric Cancer, Nutrition and Cancer, 66:8, 1362-1370, DOI: 10.1080/01635581.2014.956261 To link to this article: http://dx.doi.org/10.1080/01635581.2014.956261
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions
Nutrition and Cancer, 66(8), 1362–1370 Copyright Ó 2014, Taylor & Francis Group, LLC ISSN: 0163-5581 print / 1532-7914 online DOI: 10.1080/01635581.2014.956261
Prognostic Value of Scores Based on Malnutrition or Systemic Inflammatory Response in Patients With Metastatic or Recurrent Gastric Cancer Milana Sachlova Department of Gastroenterology, Masaryk Memorial Cancer Institute, Brno, Czech Republic
Ondrej Majek Downloaded by [Florida International University] at 11:47 20 December 2014
Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno, Czech Republic
Stepan Tucek Department of Gastroenterology, Masaryk Memorial Cancer Institute, Brno, Czech Republic
Cancer patients are frequently affected by malnutrition and weight loss, which affects their prognosis, length of hospital stay, health care costs, quality of life and survival. Our aim was to assess the prognostic value of different scores based on malnutrition or systemic inflammatory response in 91 metastatic or recurrent gastric cancer patients considered for palliative chemotherapy at the Masaryk Memorial Cancer Institute. We investigated their overall survival according to the following measures: Onodera’s Prognostic Nutritional Index (OPNI), Glasgow Prognostic Score (GPS), nutritional risk indicator (NRI), Cancer Cachexia Study Group (CCSG), as previously defined, and a simple preadmission weight loss. The OPNI, GPS, and CCSG provided very significant prognostic values for survival (log-rank test P value < 0.001). For example, the median survival for patients with GPS 0 was 12.3 mo [95% confidence interval (CI): 7.7–16.7], whereas the median survival for patients with GPS 2 was only 2.9 mo (95% CI: 1.9–4.8). A significantly worse survival of malnourished patients was also suggested by a multivariate model. The values of GPS, OPNI, and CCSG represent useful tools for the evaluation of patients’ prognosis and should be part of a routine evaluation of patients to provide a timely nutrition support.
INTRODUCTION Malnutrition and weight loss is a frequent problem in cancer patients. It affects their prognosis, length of the hospital stay, health care costs, quality of life, and survival (1–4). More than two thirds of patients with advanced cancer suffer from cachexia and/or anorexia; this syndrome is called the cancerrelated anorexia-cachexia syndrome (CACS) and is defined as a weight loss of more than 5% of the patient’s precancer body
weight. It is known that as little as 5% weight loss can significantly decrease the patient’s response to cancer treatment (5). Cachexia and unintended weight loss are mainly consequences of metabolic changes in a cancer patient’s body (4). Observational studies suggest that low levels of serum albumin are associated with higher mortality rates from cancer. Serum albumin has also been described as an independent prognostic factor of survival in various cancers (6,7), such as lung cancer (8), pancreatic cancer (9), gastric cancer (10), colorectal cancer (11), and breast cancer (12). Several studies of prognostic indicators of survival for patients with advanced cancer have been reported over the last 20 years (13). The concentration of serum C-reactive protein (CRP) has positively correlated with weight loss (14), presence of hypermetabolism and anorexia (15), disease recurrence (16), poor prognostic indicators in patients undergoing radiotherapy (17), and worse survival (18,19). Previously, different markers of malnutrition or systemic inflammatory response were combined in prognostic scores for the prediction of outcomes in cancer patients. However, no study has yet compared the prognostic ability of different scores in gastric cancer patients in particular. Therefore, we evaluated the importance of different prognostic scores in patients with advanced gastric adenocarcinoma. We studied several prognostic scores based on serum albumin markers or weight loss and correlated these measures with the overall survival (OS) of patients, focusing particularly on subgroups of patients according to received chemotherapy.
METHODS Submitted 16 December 2013; accepted in final form 12 August 2014. Address correspondence to Milana Sachlova, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, 65653, Czech Republic. E-mail: [email protected]
1362
Patients We reviewed 91 medical records of patients with metastatic or locoregionally advanced gastric adenocarcinoma (all Stage
Downloaded by [Florida International University] at 11:47 20 December 2014
PROGNOSTIC VALUE OF MALNUTRITION-BASED SCORES
III and IV disease) considered for palliative chemotherapy at the Masaryk Memorial Cancer Institute in Brno, Czech Republic between January 2010 and October 2012. The inclusion criteria were as follows: a histologically confirmed gastric adenocarcinoma, a metastatic or locoregionally advanced or recurrent disease, and the availability of clinical data at the initiation of therapy. Patients with the affection of distal esophagus and/or gastroesophageal junction were excluded from the study. We evaluated only patients with gastric cancer before palliative treatment who had no other serious medical problems (such as renal failure or infection). Relevant clinical characteristics (age, sex, body weight, and height) and performance status (PS) according to the World Health Organization were recorded. Patients were weighed without shoes. Blood samples were analyzed in the biochemical laboratory at the Masaryk Memorial Cancer Institute for albumin, CRP, serum proteins, total lymphocyte counts, and tumor markers such as CEA, ca 19-9, ca 72-4. All patients were followed up at the Department of Comprehensive Cancer Care. The nutritional assessments were performed by a trained dietitian. The food consumptions were entered to medical records.
Utilized Prognostic Scores Several composite scores of the nutritional status (usually including biochemical and anthropometric parameters) showed a correlation with prognosis (20). We followed previously published reports in the choice of prognostic scores (16,21,21,23,30,). Consequently, we have chosen Glasgow Prognostic Score (GPS), Onodera’s Prognostic Nutritional Index (OPNI), Cancer Cachexia Study Group (CCSG), and nutritional risk indicator (NRI) prognostic scores. OPNI is an assessment tool for the nutritional status and potentially predicts the patients’ prognosis (21–23). OPNI is calculated from the serum albumin concentration, and the peripheral blood lymphocyte count has been used to assess the immunological and nutritional condition of patients with a digestive disease. OPNI is calculated as 10 £ serum albumin (g/dl) C 0.005 £ total lymphocyte count. High-risk values are 40. GPS is defined as follows: patients with either elevated CRP (10 mg/L) and hypoalbuminaemia (35 g/L) are assigned a score of 2. The patients with only one of these biochemical abnormalities are assigned a score of 1. The patients with neither of these are assigned a score of 0 (24). NRI is a simple score using the serum albumin and a recent weight loss (25). NRI is calculated as [1.519 £ serum albumin (g/L)] C 0.417 £ (present weight/usual weight £ 100). An NRI score higher than 97.5 indicates that the patient is not malnourished, a score of 97.5–83.5 indicates a moderate malnutrition, and a score lower than 83.5 indicates a severe malnutrition. CCSG suggested that 3 diagnostic criteria for cancer cachexia should be used: a weight loss 10%, an intake
1363
1500 kcal/day, and CRP 10 mg/L. Scores 2 and 3 are indicators for cachexia (4).
Statistical Methods We evaluated the survival of cancer patients in relation with the listed prognostic scores or a simple recent weight loss. In the multivariate modelling analysis, we adjusted their prognostic value using their age, sex, PS and disease (new/recurrent). The overall survival (OS) was defined as the time period between the diagnosis of a new or recurrent gastric cancer considered for palliative chemotherapy, and death (or censoring date at last visit before April 2013). The cumulative survival was visualized using the Kaplan-Meier estimator, and differences between survival functions were tested using the logrank test. The Cox proportional hazards model was used for the multivariate modelling of OS. The proportional hazards assumption was checked with the Schoenfeld residuals based test. The influence diagnostics (the so-called dfbetas) was used to detect the overly influential observations. The Harrell’s C statistic (26) was used to compare the prognostic ability of considered statistical models. Subgroups of patients according to whether they underwent chemotherapy were also compared as regards their survival; for this comparison, we used the logrank test and the Cox model with interaction between the nutritional status and chemotherapy. Statistical analyses were performed using the Stata/IC 10.1 software (College Station, TX: StataCorp LP).
RESULTS Tables 1A and 1B show the baseline characteristics of 91 gastric cancer patients. Most patients were newly diagnosed with Stage IV cancer (78%); however, patients with inoperable (5%) and recurring (16%) disease were also included. Most patients received palliative chemotherapy (71%). Table 1A also reviews the distributions of patients with respect to different prognostic scores (OPNI, GPS, NRI, CCSG, and weight loss). Quantitative characteristics are shown in Table 1B. Table 2 summarizes the median OS for patients with different values of nutritional prognostic scores (visualization of survival functions according to values of different prognostic indices is provided in Fig. 1). Three of these indicators (OPNI, GPS, and CCSG) provided very significant prognostic values for OS (P value < 0.001). For example, the median OS for patients with GPS 0 was 12.3 months [95% confidence interval [CI]: 7.7–16.7), while the median OS for patients with GPS 2 was only 2.9 months (95% CI: 1.9–4.8). Survival rates differed substantially between subgroups of patients with and without chemotherapy even after the stratification using prognostic scores (Table 3). However, the absolute difference in the median OS for patients with and without chemotherapy was considerably lower in malnourished patients (e.g., the difference was approximately 9 mo
1364
M. SACHLOVA ET AL.
TABLE 1A Baseline patients characteristics (N D 91)
Downloaded by [Florida International University] at 11:47 20 December 2014
Characteristics Age 40 40 GPS 0 1 2 NRI >97.5 83.5–97.5 40 40 GPS 0 1 2 NRI >97.5 83.5–97.5
