Efficacy Observations Of Bevacizumab In Brain Metastases Of Lung Cancer Patients With Serious Cerebral Edema

Background Lung cancer is currently the world’s highest incidence of cancer,with the highest incidence rate and mortality rate of cancer at present.Nealy 50% of lung cancer patients in course of brain metastasis happens in the progression of the disease,the average survival time is less than 3 months,directly impact on patients’ prognosis,and is common cause of death of advanced lung cancer.Especially peritumoral brain edema accompanied by90% brain metastasis,which is one of urgency troubles in advanced tumor,usually suddenly exacerbate,then develop cerebral hernia in a short time,causing cardiac and respiratory arrest,and lead to death.It’s so serious that usually need emergency treatment to quickly relieve symptoms.Now radiotherapy,chemotherapy,targeted therapy and surgical resection has been recognized as the main methods of treatment of brain metastasis,but how to deal with peritumoral brain edema more effectively is still a puzzle.Surgery for tumors of peritumoral brain edema has certain taboos.The conventional methods combining glucocorticoid with mannitol can’t solve the fundamental problem,and come out low effective rate and short eddective duration.General chemotherapy,targeted drugs cannot get into the intracranial enough due to the presence of the blood-brain barrier,so the effect of treatment of brain metastases is limited,and the effect of reducing peritumoral brain edema is more poor.Radiation therapy often damages brain tissue and makes peritumoral brain edema worse else.At present,a number of scholars consider that encephalopathy in the brain such as brain tumor and brain edema can be detected high expression of vascular endothelial growth factor VEGF,a number of clinical trials have observed that bevacizumab for the treatment of primary cerebroma is safe and effective.Bevacizumab plays its effects through neutralizing VEGF,blocking combination of VEGF and VEGFR of vascular endothelial cells,impacting on the VEGF signal pathway.Besides,bevacizumab can make the vascular of tumor degenerate,make the structure of the tumor vessels from disorderly to orderly,lower the vascular permeability,reduce the interstitial hydraulic pressure,reduce intravascular substance seeping outward,so ease edema.It also can improve tumor cells content of oxygen,increase the drug infusing to the tumor,so that the effect can enhance.Currently bevacizumab has established its first-line treatment status in NSCLC(non-squamous),and based on these above mechanism,we use bevacizumab to treat brain metastases of lung cancer patients with serious cerebral edem,and observe its effects of combining with radiation and chemotherapyor using alone.Objective Use bevacizumab to treat brain metastases of NSCLC patients with serious cerebral edema,evaluate the distinction of their MRI appearances before or after treatment,and observe its effects and adverse reactions through retrospective study.Methods Collect the clinical data of brain metastasis patients of NSCLC with serious cerebral edema in our hospital,a retrospective study was performed on patients who met the following criteria:(1)Data from patients in our department during October 2013 to June 2016 and were definitely diagnosed as NSCLC(non-squamous cell)through pathological methods,and their EGFR gene and ALK gene were wild-type.(2)Examined by MRI,and discovered he or she has brain metastasis and accompanied with serious peritumoral brain edema.Patients used bevacizuma were studied as observation group.Sign the informed consent before using bevacizuma.Patients were treated with bevacizuma at the dose 5mg/kg,every 2to 3 weeks,according to the patient’s condition.Patients without bevacizuma treatmens were studied as control group,dealed with hormone and mannitol as normal processing,and can accept radiotherapy or chemotherapy at the same time.Record details include: the patient’s name,gender,age,weight,treatments before this study,clinical symptoms before and after treatments,imaging displays,the adverse reaction and so on.Use EI(edema index)as main observation indexes,KPS and so on were secondary indicators.Use the sofeware SAS 9.3 to compare the data of KPS and EI(edema index),before and after treatment.The paired t-test was used to fit the normal distribution,otherwise use the rank-sum test.The difference was statistically significant with(P﹤0.05).Results From October 2013 to June 2016,our department had recepted 68NSCLC(non-squamous cell)patients who with brain metastasis,patients who do not conform to the conditions were eliminated,there were 49 patients were studied.In observation group 24 cases were studied.18 patients’ symptoms were significantly relieved after bevacizumab treatment,the other 6 cases were not obvious.Their KPS all rised after treated with bevacizumab((63.75±12.45)vs(76.7±10.5),P<0.005);MRI indicated that the edema volumes after treatment were significantly reduced,and the EI reduced((12.09±10.75)vs(4.45±4.28),P < 0.05).Adverse reactions associated with bevacizumab included nose-bleed in 4 patients,a little blood-stained sputum in 2 patient,stomach upset in 2patient,hematochezia in 1 patient,hypertension in 1 patient,above can be easily controlled.There is no hemoptysis,bronchopleural fistula,proteinuria,gastrointestinal perforation,gastrointestinal bleeding,artery thrombosis,weak,abdominal pain,diarrhea and other complications.In control group 25 cases were studied.6 patients’ symptoms were relieved after treatment,5 cases were not obvious,the other 14 cases’ symptom were aggravated,disease progressed.The KPS decreased after treatment((61.2±13.64)vs(58.4±16.5),P<0.05);andEI rised(8.42±6.74)vs(11.03±10.47),P<0.05).Conclusion1 Bevacizumab has more significant efficacy,faster effect time than treated withoutbevacizumab for serious cerebral edema of brain metastases of NSCLC(non-squamous cell),no matter single use or combined with chemotherapy orradiotherapy,patients can benefit from a certain extent with small side and goodtolerance.It can be a better choise for patients with wild-type EGFR and ALKgenes.2 When use bevacizumab we need to strictly grasp the indications,and pay attention toits adverse reactions at the same time.We still need more large sample,multi-centerclinical research to further study its effect in near or long term.3 MRI can show more objective and precise scope and severity of peritumoral brainedema,so that it can be a good evaluation index for peritumoral brain edema.