| Lung cancer is one of the most malignant tumors and the leading cause of cancer-related deaths in China. Although the treatment strategies such as surgical techniques, targeted therapy, chemotherapy and radiotherapy were greatly improved, the survival of patients with lung cancer was still unsatisfying, with the 1-year survival rate less than 30%, and 5-year survival rate about 16%. According to the American National Comprehensive Cancer Network guidelines, patients with stage Ⅰ non-small cell lung cancer were not suggested to receive adjuvant radiotherapy and/or chemotherapy following the complete surgical resection, whereas the 5-years survival rate of patients with stage Ⅰ NSCLC was about 61.3%, indicating that some patients with stage Ⅰ NSCLC suffered from cancer recurrence and/or distant metastasis and then died within 5 years after complete surgical resection. Therefore, it is critical to search for useful, convenient and accurate predictors of patients’ survival with complete resected early-stage NSCLC in order to seek out what kind of patients would benefit most from the complete resection and discriminate the group of patients with the high risk of cancer recurrence and deaths, which would benefit from further adjuvant therapies. Identifying patients who benefit from complete surgical resection will positively contribute to determining the optimal treatment strategies and improve the patients’5-year survival rate with early-stage NSCLC.It is demonstrated that the prognosis of the tumor patients was not only determined by tumor itself such as pathological staging, but also associated with the patients’ own characteristics. Hence, there are more and more studies carried out on the predictive values of the patient’s own characteristics, such as smoking index, body mass index, underlying health problems and systemic inflammatory responses, on which much focuses were put.In 1863, Rudolf Virchow suggested the existence of inflammatory cells in tumor tissue, indicating the possible association between inflammation and tumor. Tumor associated inflammation plays a critical role in modulation of tumor microenvironment, which is one of the ten hallmarks of cancer. It was also demonstrated that tumor associated inflammation had a role in tumor initiation, development, invasion and metastasis. In addition, epidemological evidences showed that inflammation was a definite carcinogenic factor for various cancers, such as Helicobacter pylori infection and gastric cancer, HPV infection and cervical cancer, chronic B/C hepatitis and hepatocellular cancer etc. Furthermore, the risk of lung cancer was increased significantly for patients with chronic obstructive pulmonary disease (COPD), which indicated that chronic inflammation of the lung played an important role in the initiation and development of lung cancerRecently, the novel parameters of systemic inflammation and immune, such as the ratio of neutrophils and lymphocytes (NLR), the ratio of platelets and lymphocyte (PLR), had attracted more and more attention of researchers, because NLR and PLR can be calculated by cheap and easily acquired blood routine tests, and they were stable and reproducible, which may be the reason why more and more studies focused on NLR, PLR as prognostic factors. NLR is defined as the ratio of blood neutrophils count to lymphocytes count, which is economic, simple, fast, less invasive, and has higher specificity and sensitivity as prognostic markers. NLR represented the balance between inflammatory and host immunity, while higher NLR indicated an imbalance between tumor associated inflammation and host immunities. Numerous studies have demonstrated increased NLR associated with poor prognosis of patients with a variety of cancers, including lung cancer, breast cancer, gastric cancer, colorectal cancer, bladder cancer, and pancreatic cancer. PLR is indexed as the ratio of blood platelet count to lymphocyte count, recent reports predicted that the role of PLR in predicting the prognosis of cancer patients was similar with NLR. Studies have shown that in patients with epithelial ovarian cancer, the overall survival and progression-free survival in patents with PLR≥200 significantly reduced compared with patients with PLR <200. Moreover, in patients with advanced NSCLC who accepted paclitaxel and cisplatin regimen, NLR and PLR are related with hypoalbuminemia and weight loss caused by chemotherapy toxicity.However, there is no study which confirmed whether PLR is correlated with prognosis of patients with lymph node metastasis negative NSCLC. The purpose of this study is to determine whether the preoperative PLR level correlated with prognosis of patients with lymph node metastasis negative NSCLC, and to evaluate value of NLR as a predictor in patients with lymph node metastasis negative NSCLC. According to the predictors of prognosis of patients with lymph node metastasis negative NSCLC, we attempted to establish a new clinical risk model, and to make a preliminary evaluation of the patient’s condition, and to help to the clinicians select the most appropriate treatment strategies, which will reduce the risk of recurrence and death, and increase the overall survival of patients with lung cancer.OBJECTIVE:The aims of this study were to investigate whether the preoperative hematologic markers, WBC, NEU, LYM, PLT, the neutrophil -lymphocyte ratio (NLR) or the platelet-lymphocyte ratio (PLR) were prognostic indicators and to develop a novel risk stratification model in pN0 non-small cell lung cancer (NSCLC).METHODS:We performed a retrospective analysis of 400 consecutive pNO NSCLC patients who underwent surgical resection in Provincial Hospital Affiliated to Shandong University between January 2006 and December 2009. Patients’ basal characteristics, postoperative pathological information, blood routine tests and follow up were recorded. Patients’basal characteristics include sex, age and history of smoking.The postoperative pathological information consisted of TNM stage, histology, tumor size and so on. The blood routine tests included the WBC, NEU, LYM and PLT counts. NLR and PLR were calculated according to the blood routine results. NLR was calculated as neutrophil count divided by lymphocyte count and PLR was defined as the platelet counts to lymphocyte ratio. The optimum cut-off values of the preoperative WBC, NEU、LYM、PLT、NLR and PLR were identified through receiver operator characteristic (ROC) curve analysis according to the patients’overall survival, and the patients were then classified into two groups:low and high group. Prognostic factors were evaluated by univariate and multivariate Cox proportional hazard model analyses. Patients were divided into different risk groups according to relative risks for patients’survival. Survival curves according to risk groups were constructed using the Kaplan-Meier method and compared using the log-rank test. Statistical analysis was performed with SPSS 18.0 software. Significance was set at P of less than 0.05.RESULTS:Of the 400 patients, 272(68.0%) were male, 128(32.0%) were female. The mean age was 60.8±9.2 years (range from 27 to 84 years). 220 patients had smoking history. Lobectomies (including sleeve, bronchoplastic lobectomies) were performed in 369 patients, and 31 patients underwent wedge resection. Mediastinal dissection was added in all patients. In the recruited cases, there were 161 (40.3%) SCCs, and 239 (59.7%) ADCs. There were 310 and 90 patients staged as pathologically stage Ⅰand Ⅱrespectively. The median follow-up duration was 46 months (range from 1 to 78 months). During this period, 117 patients had cancer recurrence, and 86 patients died. Significant correlation between WB、NEU and gender, smoke status, histology, tumor size and TNM stage were observed. There were no significant correlation between LYM and patients’basal characteristics. Significant correlation between PLT and gender, tumor size and TNM stage were observed. Significant correlation between NLR and age, gender, smoke status, histology, tumor size and TNM stage were observed. In terms of PLR, only TNM stage correlated with PLR. In univariate analysis, age, gender, smoke status and tumor size as well as WBC, NEU, LYM, PLR and NLR were significantly associated with patients’prognosis. In multivariate analysis, age, tumor size and NLR were independent predictors for patients’disease free survival (P=0.016,0.001,and 0.007 respectively) and overall survival (P= 0.024,0.001, and 0.002 respectively). PLR didn’t associated with patients’ survival in multivariate analysis. Patients were stratified into 3 risk groups:low risk group, intermediate risk group and high risk group. From the curves, we could see that clear distinctions between the three groups were observed according to DFS. Distinctions between the three groups were also observed according to OS, however no clear distinction was seen between low and intermediate risk group according to patients’OS.CONCLUSION: We confirmed that NLR other than PLR was an independent prognostic factor for patients’disease free and overall survival. Combination of NLR, age and tumor size could stratify pNO NSCLC patients into 3 risk groups and enabled us to develop a novel risk stratification model. |
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