Nutrition and Cancer, 0(0), 1–7 Copyright Ó 2015, Taylor & Francis Group, LLC ISSN: 0163-5581 print / 1532-7914 online DOI: 10.1080/01635581.2015.1032430
Evaluation of Prognostic Nutritional Index in Patients Undergoing Radical Surgery with Nonsmall Cell Lung Cancer Chen Qiu and Xiao Qu Institute of Oncology, Shandong Provincial Hospital, Shandong University, Jinan, P.R. China
Hongchang Shen Department of Oncology, Shandong Provincial Hospital, Shandong University, Jinan, P.R. China
Chunlong Zheng and Linhai Zhu Institute of Oncology, Shandong Provincial Hospital, Shandong University, Jinan, P.R. China
Long Meng and Jiajun Du Department of Thoracic Surgery, Shandong Provincial Hospital, Shandong University, Jinan, P.R. China
The prognostic nutritional index (PNI) has been reported to be a prognostic indicator in some malignant tumors. However, its prognostic value in nonsmall cell lung cancer (NSCLC) has not been fully investigated. A retrospective review of 1416 patients with NSCLC who underwent radical surgery between January 2006 and December 2011 was conducted. To obtain optimal cutoff levels of PNI, running log-rank statistics was applied. Survival was calculated by the Kaplan-Meier method. The prognostic significance of PNI, together with various clinicopathological factors, was evaluated by multivariate analysis. The optimal cutoff point for PNI was 52. The 1-, 3-, and 5-yr survival rates in patients with PNI of less than 52 were 80.0%, 61.3%, and 50.4%, respectively, and were significantly more unfavorable than those in patients with PNI 52 or higher (84.7%, 71.5%, and 60.3%, respectively, P < 0.001). Multivariate analysis suggested that gender (P D 0.026), age (P < 0.001), PNI (P D 0.005), differentiation (P D 0.024), pathology T category (P D 0.003), and pathology N category (P < 0.001) were revealed to be independent prognostic factors. Our results indicate that PNI is an independent predictor of survival for patients undergoing radical surgery with NSCLC.
INTRODUCTION Nonsmall cell lung cancer (NSCLC) remains a major cause of cancer death, and the 5-yr survival rate is still poor despite early detection and therapeutic modalities (1). Although it is recognized that the development of cancer has a genetic basis, there is increasing evidence that the host-related factors play
Submitted 22 May 2014; accepted in final form 19 March 2015. Address correspondence to Jiajun Du, Department of Thoracic Surgery, Shandong Provincial Hospital, Shandong University, #324 Jingwu Road, Jinan 250021, P. R. China. Tel: C86-13001739988. Fax: C86-0531-68777100. E-mail: [email protected]
an important role in the development and progression of cancer (2,3). Hypoalbuminemia is often observed in advanced cancer patients and is usually regarded as an index of malnutrition and cachexia (4). Aside from the conventional use of serum albumin levels as an index of nutritional health, this parameter has received some attention as a reasonable correlate of morbidity and mortality in malignancies patients (5,6). Evidence also suggested that the development of hypoalbuminemia was caused by a reduced albumin synthesis rate, considered a consequence of systemic inflammation (7,8). Therefore, the Onodera’s prognostic nutritional index (PNI), composed of serum albumin and total lymphocyte count, representing the coexistence of ongoing systemic inflammation and host nutrition status, might provide additional prognostic information. Accumulating evidence indicates that the PNI is a reliant and practical tool for outcome prognostication in patients with various malignancies (9–12). However, there is lack of such evidence in surgery for NSCLC. In the present study, we measured the preoperative PNI in 1416 NSCLC patients to determine its clinicopathological relationship and prognostic significance.
MATERIALS AND METHODS Patients Between January 2006 and December 2011, a total of 1448 patients with primary NSCLC who underwent radical surgery at our institution were investigated. We excluded 23 patients with preoperative treatment, and 1 patient whose serum albumin data from preoperative blood tests was unavailable; in addition, to avoid the confounding effect of comorbidities on albumin and total lymphocyte count, 2 patients with 1
2
C. QUI ET AL.
autoimmune disease, 1 patients with renal disorders, and 5 patients with hepatic disorder were excluded. A total of 1416 patients who had complete cancer registry follow up were included in the study. All patients underwent physical examination, computed tomography (CT) or magnetic resonance imaging (MRI) of the brain, chest, and abdomen, emission computed tomography of bone preoperatively to make a definite diagnosis and make sure that there was no metastasis. All medical records were reviewed retrospectively. We collected data from preoperative blood tests, including serum albumin and total lymphocyte count of the peripheral blood. The PNI was calculated by 10 £ Alb. C 0.005 £ Lymph. C., where Alb. is serum albumin level (g/100 ml) and Lymph. C. is total lymphocytes count/mm3 peripheral blood (13).
Treatment and Following Up Blood tests routinely performed 1–3 days before operation. Patients who underwent lobectomy, bilobectomy, or pneumonectomy were enrolled in this study. A complete mediastinal lymphadenectomy was routinely performed. Pathologic staging was based on the current 7th edition of the TNM classification (14). The main adjuvant treatment that patients underwent after operation was chemotherapy or radiotherapy. The chemotherapy was routine program for NSCLC according to the National Comprehensive Cancer Network (NCCN)(15). Patients were followed up every 3 mo for 1 yr after operation, every 6 mo for 3 yr, and every year thereafter, with a median follow-up period of 48 (range D 3 to 92) mo. A total of 1416 patients were followed up until death or the last day of follow-up (August 15, 2013). The overall survival (OS) in each patient was defined as the interval between the date of the definitive resection and the date of the last follow-up or death.
Ethics Statement The lung cancer databases used in this study have a general ethic committee admittance from the Ethic Committee of Shandong Provincial Hospital. The data are to be handled and analyzed without possibility to identify individual patients, and no written consents are thus requested.
Statistical Analysis Medical records and survival data were obtained from all patients. Demographic and clinical data at baseline were described by means of percentages. To obtain optimal cutoff levels of PNI, running log-rank statistics was applied (16). Relationships between clinicopathological parameters and PNI were evaluated by means of the x2 test. The Kaplan– Meier method was used to plot the survival curves, and the log-rank test was used to evaluate differences among the subgroups. Multivariate survival analysis and calculation of the
odds ratios with 95% confidence interval was performed using a Cox proportional hazard regression model, including all covariates that were identified as significant by univariate analysis, additional adjustment for smoking at diagnosis (as a proxy for continued smoking after diagnosis) was performed as some studies suggest persistent smoking among lung cancer survivors (17). The result was considered to be significant when the P value was less than 0.05. All statistical analysis was performed using the SPSS Statistics software package v.17.0 (SPSS Inc., Chicago, IL).
RESULTS Baseline Characteristics A total of 1416 patients were eligible for the study. Detailed clinicopathological characteristics of the patients are listed in Table 1. Included in this study were 999 men and 417 women with a median age of 59.7 years (range D 20–84). Most patients’ albumin and lymphocyte concentrations were in the normal range. A total of 164 patients (11.6%) had hypoalbuminemia (
Evaluation of Prognostic Nutritional Index in Patients Undergoing Radical Surgery with Nonsmall Cell Lung Cancer Chen Qiu and Xiao Qu Institute of Oncology, Shandong Provincial Hospital, Shandong University, Jinan, P.R. China
Hongchang Shen Department of Oncology, Shandong Provincial Hospital, Shandong University, Jinan, P.R. China
Chunlong Zheng and Linhai Zhu Institute of Oncology, Shandong Provincial Hospital, Shandong University, Jinan, P.R. China
Long Meng and Jiajun Du Department of Thoracic Surgery, Shandong Provincial Hospital, Shandong University, Jinan, P.R. China
The prognostic nutritional index (PNI) has been reported to be a prognostic indicator in some malignant tumors. However, its prognostic value in nonsmall cell lung cancer (NSCLC) has not been fully investigated. A retrospective review of 1416 patients with NSCLC who underwent radical surgery between January 2006 and December 2011 was conducted. To obtain optimal cutoff levels of PNI, running log-rank statistics was applied. Survival was calculated by the Kaplan-Meier method. The prognostic significance of PNI, together with various clinicopathological factors, was evaluated by multivariate analysis. The optimal cutoff point for PNI was 52. The 1-, 3-, and 5-yr survival rates in patients with PNI of less than 52 were 80.0%, 61.3%, and 50.4%, respectively, and were significantly more unfavorable than those in patients with PNI 52 or higher (84.7%, 71.5%, and 60.3%, respectively, P < 0.001). Multivariate analysis suggested that gender (P D 0.026), age (P < 0.001), PNI (P D 0.005), differentiation (P D 0.024), pathology T category (P D 0.003), and pathology N category (P < 0.001) were revealed to be independent prognostic factors. Our results indicate that PNI is an independent predictor of survival for patients undergoing radical surgery with NSCLC.
INTRODUCTION Nonsmall cell lung cancer (NSCLC) remains a major cause of cancer death, and the 5-yr survival rate is still poor despite early detection and therapeutic modalities (1). Although it is recognized that the development of cancer has a genetic basis, there is increasing evidence that the host-related factors play
Submitted 22 May 2014; accepted in final form 19 March 2015. Address correspondence to Jiajun Du, Department of Thoracic Surgery, Shandong Provincial Hospital, Shandong University, #324 Jingwu Road, Jinan 250021, P. R. China. Tel: C86-13001739988. Fax: C86-0531-68777100. E-mail: [email protected]
an important role in the development and progression of cancer (2,3). Hypoalbuminemia is often observed in advanced cancer patients and is usually regarded as an index of malnutrition and cachexia (4). Aside from the conventional use of serum albumin levels as an index of nutritional health, this parameter has received some attention as a reasonable correlate of morbidity and mortality in malignancies patients (5,6). Evidence also suggested that the development of hypoalbuminemia was caused by a reduced albumin synthesis rate, considered a consequence of systemic inflammation (7,8). Therefore, the Onodera’s prognostic nutritional index (PNI), composed of serum albumin and total lymphocyte count, representing the coexistence of ongoing systemic inflammation and host nutrition status, might provide additional prognostic information. Accumulating evidence indicates that the PNI is a reliant and practical tool for outcome prognostication in patients with various malignancies (9–12). However, there is lack of such evidence in surgery for NSCLC. In the present study, we measured the preoperative PNI in 1416 NSCLC patients to determine its clinicopathological relationship and prognostic significance.
MATERIALS AND METHODS Patients Between January 2006 and December 2011, a total of 1448 patients with primary NSCLC who underwent radical surgery at our institution were investigated. We excluded 23 patients with preoperative treatment, and 1 patient whose serum albumin data from preoperative blood tests was unavailable; in addition, to avoid the confounding effect of comorbidities on albumin and total lymphocyte count, 2 patients with 1
2
C. QUI ET AL.
autoimmune disease, 1 patients with renal disorders, and 5 patients with hepatic disorder were excluded. A total of 1416 patients who had complete cancer registry follow up were included in the study. All patients underwent physical examination, computed tomography (CT) or magnetic resonance imaging (MRI) of the brain, chest, and abdomen, emission computed tomography of bone preoperatively to make a definite diagnosis and make sure that there was no metastasis. All medical records were reviewed retrospectively. We collected data from preoperative blood tests, including serum albumin and total lymphocyte count of the peripheral blood. The PNI was calculated by 10 £ Alb. C 0.005 £ Lymph. C., where Alb. is serum albumin level (g/100 ml) and Lymph. C. is total lymphocytes count/mm3 peripheral blood (13).
Treatment and Following Up Blood tests routinely performed 1–3 days before operation. Patients who underwent lobectomy, bilobectomy, or pneumonectomy were enrolled in this study. A complete mediastinal lymphadenectomy was routinely performed. Pathologic staging was based on the current 7th edition of the TNM classification (14). The main adjuvant treatment that patients underwent after operation was chemotherapy or radiotherapy. The chemotherapy was routine program for NSCLC according to the National Comprehensive Cancer Network (NCCN)(15). Patients were followed up every 3 mo for 1 yr after operation, every 6 mo for 3 yr, and every year thereafter, with a median follow-up period of 48 (range D 3 to 92) mo. A total of 1416 patients were followed up until death or the last day of follow-up (August 15, 2013). The overall survival (OS) in each patient was defined as the interval between the date of the definitive resection and the date of the last follow-up or death.
Ethics Statement The lung cancer databases used in this study have a general ethic committee admittance from the Ethic Committee of Shandong Provincial Hospital. The data are to be handled and analyzed without possibility to identify individual patients, and no written consents are thus requested.
Statistical Analysis Medical records and survival data were obtained from all patients. Demographic and clinical data at baseline were described by means of percentages. To obtain optimal cutoff levels of PNI, running log-rank statistics was applied (16). Relationships between clinicopathological parameters and PNI were evaluated by means of the x2 test. The Kaplan– Meier method was used to plot the survival curves, and the log-rank test was used to evaluate differences among the subgroups. Multivariate survival analysis and calculation of the
odds ratios with 95% confidence interval was performed using a Cox proportional hazard regression model, including all covariates that were identified as significant by univariate analysis, additional adjustment for smoking at diagnosis (as a proxy for continued smoking after diagnosis) was performed as some studies suggest persistent smoking among lung cancer survivors (17). The result was considered to be significant when the P value was less than 0.05. All statistical analysis was performed using the SPSS Statistics software package v.17.0 (SPSS Inc., Chicago, IL).
RESULTS Baseline Characteristics A total of 1416 patients were eligible for the study. Detailed clinicopathological characteristics of the patients are listed in Table 1. Included in this study were 999 men and 417 women with a median age of 59.7 years (range D 20–84). Most patients’ albumin and lymphocyte concentrations were in the normal range. A total of 164 patients (11.6%) had hypoalbuminemia (
