Clinical Efficacy Of Bevacizumab Combined With Chemotherapy For Brain Metastases Of Lung Adenocarcinoma

BackgroundLung cancer is one of the most common cancers in the world and the main cause of cancer-related death.More than 80% of them are nonsmall cell lung cancer(NSCLC),and lung adenocarcinoma is the major subtype of NSCLC.One of the most common and serious complications of lung cancer is brain metastasis,which is estimated to occur in 10 to 30 percent of lung cancer patients.In the past,the survival rate of brain metastases was low and treatment was often considered futile.In recent years,with the advent of molecular targeted therapy and immunotherapy,the survival rate of lung cancer has been increasing.As a result,patients are at greater risk of developing brain metastases,and this trend,combined with the widespread availability of magnetic resonance imaging,suggests that more and more patients will be diagnosed with brain metastases in the coming years.In the event of brain metastases and treatment options are limited,including radiotherapy and surgery,although can prolong the life span of 2 to 5 months,have associated neurotoxic side effects,and the recurrence rate is high,the median survival time(mOS)after brain metastasis is still less than 1 year.At present,most scholars believe that high expression of vascular endothelial growth factor(VEGF)can be detected in brain tumor lesions,and a number of clinical trials have observed that bevacizumab,an anti-VEGF drug,is safe and effective in the treatment of primary brain tumors.VEGF is an over-expressed biomarker in brain metastasis of lung adenocarcinoma,therefore,VEGF can be used as a key therapeutic target for lung adenocarcinoma with brain metastasis.Bevacizumab is mainly used to block the combination of VEGF and VEGFR,thereby reducing the formation of new blood vessels.In addition,bevacizumab seems to normalize abnormal blood vessels and enhance the concentration of anti-tumor drugs in tumor tissues by increasing the permeability of blood vessels.Bevacizumab has been approved by the Chinese FDA for using in a variety of tumor types,including colon cancer,non-squamous non-small cell lung cancer.ObjectivePatients with lung adenocarcinoma with asymptomatic brain metastases who received bevacizumab combined with chemotherapy.Imaging evaluation was conducted by nuclear magnetic resonance(MRI)and CT scan,and the efficacy and safety of bevacizumab were observed by retrospective study.MethodsRetrospective analysis the clinical data of lung adenocarcinoma with asymptomatic brain metastases patients who were treated at the First Affiliated Hospital of Zhengzhou University from July 2016 to August 2018,the enrolled patients should meet the following criteria:(1)Data from patients who were confirmed by histopathology and recurrent,metastatic lung adenocarcinoma;(2)Molecular pathological examination their EGFR gene and ALK gene were wild-type;(3)Examined by MRI,and discovered the patient's has brain metastasis that without the accompanying symptoms of clinical treatment.Bevacizumab was administered at the dose 7.5mg/kg,once every 3 weeks,combined with platinum-containing dual-drug chemotherapy.The intracranial was according to MRI and extracranial according to CT morphological changes every 4 cycles,the efficacy was evaluated by modified Response Evaluation Criteria in Solid Tumors(mRECIST),and the toxicity was evaluated by NCI-CTC 3.0 Standard every cycle.Gender,age,smoking history,treatment regimen before this study,number of treatment lines,number of treatment cycles,adverse reactions,changes of intracranial MRI and extracranial enhanced CT before and after treatments were collected.Among them,intracranial MRI and extracranial CT imaging as main observation indexes.All data were statistically analyzed using SPSS 21.0 software.The frequency data were expressed as percentage(%),the survival analysis was analyzed by the Kaplan-Meier method,and log-rank method was used for comparison between survival groups.P < 0.05 was considered statistically significant.ResultsOur collected 23 lung adenocarcinoma patients who with asymptomatic brain metastasis were treated at the First Affiliated Hospital of Zhengzhou University from July 2016 to August 2018.The intracranial and extracranial findings of 23 patients were evaluated,and intracranial and extracranial with 0 case had complete response.The intracranial with 10 cases had partial response,11 cases had stable disease and 2 cases had progressive disease.The objective response rate Was 43.5%(10/23).The disease control rate was 91.3%(21/23).The extracranial with 9 cases had partial response,9 cases had stable disease and 5 cases had progressive disease.The objective response rate Was 39.1%(9/23).The disease control rate was 78.3%(18/23).Adverse reactions were mainly I and II degrees.The adverse reactions associated with bevacizumab,5 patients(21.7%)had bleeding,2 had proteinuria(8.7%),and 2 patients had hypertension(8.7%),which were relieved after symptomatic treatment.There were no venous thrombosis,allergies,central nervous system hemorrhage,and bronchopleural fistula and other complications.Conclusion1.Bevacizumab combined with chemotherapy is effective and safe for the treatment of lung adenocarcinoma with brain metastases,indicating that this regimen can be used as one of the treatment modes for patients with lung adenocarcinoma with asymptomatic brain metastasis who do not accept or tolerate whole-brain radiotherapy.It is especially suitable for patients with brain metastases who without obvious clinical symptoms and drive gene negative.2.The indications and related adverse reactions of bevacizumab treatment should be strictly mastered.Large,multi-center and randomized controlled trials(RCTS)are needed to further study the short-term and long-term efficacy of bevacizumab in asymptomatic brain metastases.