Effect Of Bevacizumab Combined With Chemotherapy On Brain Metastasis Of Non-small Cell Lung Cancer

Background: Lung cancer is one of tumors with the highest incidence in the world. Non-small cell lung cancer (NSCLC) is the most important pathological type and accounts for 80% of the total lung cancer, of which 30%-65% develop brain metastases in the progression of the disease.Brain metastases seriously affect the patient’s cognitive function, survival time and quality of life. Natural course of brain metastases is only 1-3 months. Although CV plus radiotherapy can reduce the incidence of extracranial metastases in patients with advanced NSCLC, it cannot reduce theincidence of brain metastases..Due to the existence of blood-brain barrier, the traditional chemotherapy drugs is difficult to enter the brain tissue, for the treatment and prevention of brain metastases are very limited. Vascular endothelial growth factor (VEGF) is a very important regulator of tumor angiogenesis and plays an important role in the development and progression of tumor. CA9 is related to tumour cell proliferation,cell adhesion and tumour progression. As a monoclonal antibody to VEGF, a number of clinical trials have observed that bevacizumab combined with chemotherapy has a significant efficacy on brain metastases, but previous studies were conducted in patients who developed brain metastases, but rarely in patients with no primary brain metastases. In this study, we aim to determine the efficacy of bevacizumab combined with chemotherapy in NSCLC patients with no primary brain metastases. and to explore the relationship between VEGF、CA9 status and the efficacy of bev acizumab combined with chemotherapy on brain metastasesObjective: 1、To determine the effects of bevacizumab plus chemotherapy and chemotherapy on the incidence of brain metastases in advanced non-small cell lung cancer (NSCLC) by a retrospective study. 2、To explore the relationship between VEGF status and the efficacy of bevacizumab combined with chemotherapy on brain metastases, 3、To explore the relationship between different carbonic anhydrase IX (CA9) status and efficacy of ofbevacizumab combined with chemotherapy on brain metastases.Methods: Part A: we used retrospective research methods to collect and analyze the clinical data of patients, the primary indicators was the cumulative incidence of brain metastases, and the secondary indicators is the overall survival(OS). Log-rank test of Kaplan-Meier was used for survival analysis and COX regression model was used for analysis of related factors influencing brain metastasis. Part B: VEGF of patients were detected by Immunohistochemical method, and the relationship between different VEGF status, bevacizumab combined with chemotherapy and brain metastases was observed. Part C: Serum CA9 concentration was measured by ELISA before and after treatment for 6 cycles. The relationship between CA9 status and bevacizumab combined with chemotherapy and brain metastases was observed.Results: A total of 159 patients from January 2009 to December 2010 were included for two groups based on the different treatment: 110 for Bevacizumab +chemotherapy group (BV + CT) and 49 for chemotherapy (CT). Treatment grouping, age, sex, smoking history, PS score, pathological type, TNM stage,previous treatment history and VEGF expression status were collected. To the end of the follow-up, 110 received BV+CT and 49 received CT. Both groups had 15 patients with brain metastases (14% vs 31%, P□<□0.05). 40 patients (36%)survived after BV+CT treatment, whereas only 11 patients (22%) survived after CT treatment. The outcome of the BV+CT group was significantly better than the CT group. Compared to CT alone, BV+CT reduced the risk of brain metastasis and prolonged overall patient survivalbut for VEGF positive patients. The CA9 concentrations in patients with high CA9 expression decreased significantly after BVtreatment. The risk of brain metastasis was significantly reduced in patients with high CA9 expression in the BV+CT group. There was no significant difference in the risk of brain metastasis between the two groups in patients with low expression of serum CA9 concentration. By multivariate analysis, only the use of BV was an independent factor for determining the risk of brain metastasesConclusion:1. Bevacizumab combined with chemotherapy can reduce the incidence of brain metastases in advanced non-small lung cancer patients for better survival;2. Vascular endothelial growth factor-positive patients may benefit more from BV treatment;3. Bevacizumab combined with chemotherapy significantly decreased the incidence of brain metastases in patients with high expression of serum CA9 concentration ; the efficacy of Bevacizumab may be related to CA9 expression.