Biomedicine & Pharmacotherapy 68 (2014) 213–217
Available online at
ScienceDirect www.sciencedirect.com
Original article
Pre-adjuvant chemotherapy leukocyte count may predict the outcome for advanced gastric cancer after radical resection Dong Pei, Fang Zhu, Xiaofeng Chen, Jing Qian, Shaohua He, Yingying Qian, Hua Shen, Yiqian Liu, Jiali Xu, Yongqian Shu * Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, Guangzhou Road 300#, Nanjing 210029, China
A R T I C L E I N F O
A B S T R A C T
Article history: Received 26 December 2013 Accepted 20 January 2014
Gastric cancer (GC) has a high morbidity worldwide each year especially in China and advanced GC is well known with poor prognosis, for which surgical resection combine adjuvant chemotherapy is the optimal choice for therapy. Leukocyte is an important index during the treatment for its influence on drugs’ dosage and tolerance. Therefore, peripheral blood leukocyte and its subsets during adjuvant chemotherapy may have great clinical value for predicting prognostic. In this retrospective study, we showed the distribution of white blood cell and its subsets in the baseline period before adjuvant chemotherapy in 399 patients who underwent radical resection for advanced GC from January 1, 2008 to August 31, 2012. We investigated the relationship between leukocyte count and overall survival (OS) as well as disease-free survival (DFS). In these patients, females were more likely to have less white blood cells after operation (P = 0.016). Patients with pre-chemotherapy leukocyte count less than 4 109/L got worse DFS (P = 0.028) and OS (P = 0.016). In multivariate analysis, tumor size 6 cm (P = 0.033), TNM stage IV (P = 0.024), vascular or nerval invasion (P = 0.005) and leukocyte count less than 4.0 109/L (P = 0.019) was associated with poor DFS. TNM stage IV (P = 0.008), vascular or nerval invasion (P = 0.001) and lower leukocyte count (P = 0.045) were independent risk factors for poor OS. Taken together, our findings suggest that pre-adjuvant chemotherapy peripheral blood leukocyte count correlates with clinical outcome of patients with advanced GC after radical resection. ß 2014 Elsevier Masson SAS. All rights reserved.
Keywords: Gastric cancer Leukocyte count Prognosis Chemotherapy Operation
1. Introduction Gastric cancer (GC) is the one of the most common cancers in the world. Its incidence is fourth in all cancers and it is the second leading death cause only to lung cancer [1]. Gastric cancer has a higher morbidity in East Asia and nearly half of the world’s total cases occur in China each year [2]. Recent studies have shown that surgical resection followed with adjuvant chemotherapy can achieve long-term survival in patients with early GC. The prognosis for these patients is associated with a 5-year survival rate over 70% [3,4]. On the other hand, despite the improvement in treatment, prognosis for advanced GC still remains low with a 5-year survival rate of less than 20 % [5,6]. Therefore, assessment of prognostic predictors is important for the management of patients with advanced GC. Leukocyte count is a major clinical index for chemotherapy because it may influence dosage of the reagent, tolerance of the therapy and completeness of the entire treatment [7–9]. Recent
* Corresponding author. Tel.: +86 025 68136043; fax: +86 025 68136172. E-mail addresses: [email protected], [email protected] (Y. Shu). 0753-3322/$ – see front matter ß 2014 Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.biopha.2014.01.008
studies reported that leukopenia experienced during chemotherapy is associated with improved survival in patients with advanced GC that could not be resected [10,11]. Also, several investigators reported that higher postoperative lymphocyte count or lower neutrophil-to-lymphocyte ratio (NLR) are related to better outcome in patients with cancer [12–14]. Therefore, we hypothesized that, in advanced GC that could be radical resected, pre-adjuvant chemotherapy peripheral blood leukocyte count and its subsets such as lymphocyte count might be related to prognosis. In our study, we retrospectively analyzed the leukocyte count in the baseline period before adjuvant chemotherapy in patients with advanced GC after gastrectomy. We aimed to evaluate the relationship between leukocyte count and patients’ prognosis including disease-free survival (DFS) and overall survival (OS). 2. Patients and methods 2.1. Patients There were 399 patients in our study. They each underwent radical gastrectomy for GC in Jiangsu Province Hospital, Nanjing, China from January 1, 2008 to August 31, 2012 and the diagnosis of GC was confirmed by pathology. Disease was staged according to
214
D. Pei et al. / Biomedicine & Pharmacotherapy 68 (2014) 213–217
the International Union Against Cancer classification for GC [15]. All these cases were TNM stage III or TNM stage IV (with resectable liver metastasis). Our cohort consisted of only patients who received primary gastrectomy and then adjuvant chemotherapy in at most 2 months. Each patient had at least two cycles of chemotherapy and the regimens were mostly 5-fluorouracil or it derivates (capecitabine or gimeracil and oteracil porassium capsules) combined with platinums and/or taxanes. Patients with stomach operation history, neo-adjuvant treatments or those who had hematological system diseases were excluded from our study. This study was approved by the ethnics committee of the First Affiliated Hospital of Nanjing Medical University. 2.2. Laboratory test results and other clinical data collection Absolute pre-adjuvant chemotherapy leukocyte count, lymphocyte and neutrophil count were routinely determined in peripheral venous samples usually one or two days before the first cycle of adjuvant chemotherapy. Blood test results of each patient were obtained from the laboratory information system of Jiangsu Province Hospital. Detailed clinicopathologic information was obtained from the medical records system. OS was the main endpoint of this analysis and DFS was the second. Recurrence of GC was defined as newly detected abdominal or extra-abdominal tumors by computed tomography or magnetic resonance image. OS was calculated from the date of surgery to the date of death or to the last follow-up. DFS was defined as the time from surgery to radiologic recurrence, death or last follow-up. Date of death or recurrence was acquired from clinical documents or their families by follow-up telephone calls. The last follow-up date was September 31, 2013. 2.3. Statistical analysis All statistics were analyzed using the SPSS 18.0 software (SPSS Statistics, China). Clinicopathological continuous variables were classified into two groups for the Fisher exact test and then the Cox proportional hazard regression model as follows: age
Available online at
ScienceDirect www.sciencedirect.com
Original article
Pre-adjuvant chemotherapy leukocyte count may predict the outcome for advanced gastric cancer after radical resection Dong Pei, Fang Zhu, Xiaofeng Chen, Jing Qian, Shaohua He, Yingying Qian, Hua Shen, Yiqian Liu, Jiali Xu, Yongqian Shu * Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, Guangzhou Road 300#, Nanjing 210029, China
A R T I C L E I N F O
A B S T R A C T
Article history: Received 26 December 2013 Accepted 20 January 2014
Gastric cancer (GC) has a high morbidity worldwide each year especially in China and advanced GC is well known with poor prognosis, for which surgical resection combine adjuvant chemotherapy is the optimal choice for therapy. Leukocyte is an important index during the treatment for its influence on drugs’ dosage and tolerance. Therefore, peripheral blood leukocyte and its subsets during adjuvant chemotherapy may have great clinical value for predicting prognostic. In this retrospective study, we showed the distribution of white blood cell and its subsets in the baseline period before adjuvant chemotherapy in 399 patients who underwent radical resection for advanced GC from January 1, 2008 to August 31, 2012. We investigated the relationship between leukocyte count and overall survival (OS) as well as disease-free survival (DFS). In these patients, females were more likely to have less white blood cells after operation (P = 0.016). Patients with pre-chemotherapy leukocyte count less than 4 109/L got worse DFS (P = 0.028) and OS (P = 0.016). In multivariate analysis, tumor size 6 cm (P = 0.033), TNM stage IV (P = 0.024), vascular or nerval invasion (P = 0.005) and leukocyte count less than 4.0 109/L (P = 0.019) was associated with poor DFS. TNM stage IV (P = 0.008), vascular or nerval invasion (P = 0.001) and lower leukocyte count (P = 0.045) were independent risk factors for poor OS. Taken together, our findings suggest that pre-adjuvant chemotherapy peripheral blood leukocyte count correlates with clinical outcome of patients with advanced GC after radical resection. ß 2014 Elsevier Masson SAS. All rights reserved.
Keywords: Gastric cancer Leukocyte count Prognosis Chemotherapy Operation
1. Introduction Gastric cancer (GC) is the one of the most common cancers in the world. Its incidence is fourth in all cancers and it is the second leading death cause only to lung cancer [1]. Gastric cancer has a higher morbidity in East Asia and nearly half of the world’s total cases occur in China each year [2]. Recent studies have shown that surgical resection followed with adjuvant chemotherapy can achieve long-term survival in patients with early GC. The prognosis for these patients is associated with a 5-year survival rate over 70% [3,4]. On the other hand, despite the improvement in treatment, prognosis for advanced GC still remains low with a 5-year survival rate of less than 20 % [5,6]. Therefore, assessment of prognostic predictors is important for the management of patients with advanced GC. Leukocyte count is a major clinical index for chemotherapy because it may influence dosage of the reagent, tolerance of the therapy and completeness of the entire treatment [7–9]. Recent
* Corresponding author. Tel.: +86 025 68136043; fax: +86 025 68136172. E-mail addresses: [email protected], [email protected] (Y. Shu). 0753-3322/$ – see front matter ß 2014 Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.biopha.2014.01.008
studies reported that leukopenia experienced during chemotherapy is associated with improved survival in patients with advanced GC that could not be resected [10,11]. Also, several investigators reported that higher postoperative lymphocyte count or lower neutrophil-to-lymphocyte ratio (NLR) are related to better outcome in patients with cancer [12–14]. Therefore, we hypothesized that, in advanced GC that could be radical resected, pre-adjuvant chemotherapy peripheral blood leukocyte count and its subsets such as lymphocyte count might be related to prognosis. In our study, we retrospectively analyzed the leukocyte count in the baseline period before adjuvant chemotherapy in patients with advanced GC after gastrectomy. We aimed to evaluate the relationship between leukocyte count and patients’ prognosis including disease-free survival (DFS) and overall survival (OS). 2. Patients and methods 2.1. Patients There were 399 patients in our study. They each underwent radical gastrectomy for GC in Jiangsu Province Hospital, Nanjing, China from January 1, 2008 to August 31, 2012 and the diagnosis of GC was confirmed by pathology. Disease was staged according to
214
D. Pei et al. / Biomedicine & Pharmacotherapy 68 (2014) 213–217
the International Union Against Cancer classification for GC [15]. All these cases were TNM stage III or TNM stage IV (with resectable liver metastasis). Our cohort consisted of only patients who received primary gastrectomy and then adjuvant chemotherapy in at most 2 months. Each patient had at least two cycles of chemotherapy and the regimens were mostly 5-fluorouracil or it derivates (capecitabine or gimeracil and oteracil porassium capsules) combined with platinums and/or taxanes. Patients with stomach operation history, neo-adjuvant treatments or those who had hematological system diseases were excluded from our study. This study was approved by the ethnics committee of the First Affiliated Hospital of Nanjing Medical University. 2.2. Laboratory test results and other clinical data collection Absolute pre-adjuvant chemotherapy leukocyte count, lymphocyte and neutrophil count were routinely determined in peripheral venous samples usually one or two days before the first cycle of adjuvant chemotherapy. Blood test results of each patient were obtained from the laboratory information system of Jiangsu Province Hospital. Detailed clinicopathologic information was obtained from the medical records system. OS was the main endpoint of this analysis and DFS was the second. Recurrence of GC was defined as newly detected abdominal or extra-abdominal tumors by computed tomography or magnetic resonance image. OS was calculated from the date of surgery to the date of death or to the last follow-up. DFS was defined as the time from surgery to radiologic recurrence, death or last follow-up. Date of death or recurrence was acquired from clinical documents or their families by follow-up telephone calls. The last follow-up date was September 31, 2013. 2.3. Statistical analysis All statistics were analyzed using the SPSS 18.0 software (SPSS Statistics, China). Clinicopathological continuous variables were classified into two groups for the Fisher exact test and then the Cox proportional hazard regression model as follows: age
