Prognostic Factors To Efficacy Of Bevacizumab In Nonsqua-Mous Non-Small-Cell Lung Cancer Patients

BackgroundNon-small-cell lung cancer(NSCLC)is one of the most commonly diagnosed solid tumors and the most common cause of cancer-related deaths in the world.NSCLC is mostly diagnosed at advanced stages(?B or ?)of the disease,making curable surgery rarely attainable,and leading to a poor prognosis.Recently,the discovery of epidermal growth factor receptor tyrosine kinase inhibitor,anaplastic lymphoma kinase tyrosine kinase inhibitor and antivascular endothelial growth factor(VEGF)monoclonal antibody opened a new chapter for clinical treantment of advanced NSCLC.However,only part of patient habor oncogenic driver mutations such as EGFR mutations and ALK rearrangment,and platinum-doublet chemotherapy is still the standard treatment for these patients.ECOG 4599 have demonstrated the benefits of adding the vascular endothelial growth factor(VEGF)-targeted monoclonal antibody Bevacizumab to the standard regimen of paclitaxel and carboplatin(PC)in nonsquamous NSCLC.However,the ORR was only 35%,which meant that not all the patients could benefit from the Bevacizumab.The surrogate markers of Bevacizumab efficacy have been analyzed before,including imaging,circulating VEGF before treatment and so on,with the negative results.There were some factors demonstrated to be related to the efficacy of bevacizumab,including P53 mutation;circulating ICAM-1,however none of them were validated in clinical.In summary,screening which part of the advanced nonsquamous NSCLC patients could get the maximum benefit from Beibacizumab has become an urgent problem.ObjectivesAccording to the analysis of clinical features,pathological features,elementary data including tumor biomarkers,serum biochemical levels of our patients,to explore prognostic factors which could predict the effect of Bevacizumab in advanced nonsquamous NSCLC.On the basis of clinical accessible data,to identify patients who may benefit most from receiving Bevacizumab therapy,which guide the clinical application of bevacizumab and bring accurate therapy for advanced nonsquamous NSCLC patients.Materials and MethodsWe retrospectively collected and analyzed total of 112 patients who had recepted Bevacizumab from June 2011 to January 2017 in Shandong Cancer Hospital and Institute.The clinical features,pathological featuresn laboratory index?treatment and survival were analyzed in those patients.PFS was evaluated using the Kaplan-Meier method univariate Cox and a comparison between survival curves was done with log-rank test.Multivariate Cox regression analysis with a backward-forward stepwise method assessed prognostic factors for OS.In the multivariate Cox regression model,all variables with P values<0.10 in the univariate analysis were included.All statistical tests were 2-tailed,and P<0.05 was considered significant.ResultsUntil January 2017,the range of follow up duration was 2-36 months,median follow up time was 11 months.Median PFS of all the patients was 11 months.From the short-term effects of the application of bevacizumab,the ORR was higher in patients who were female patients(ORR 37%,?2 =0.364,p=0.024)?local can-cer(ORR 40%,?2 =8.370,p=0.04)?before the application of bevacizumab without bone metastasis(ORR 35.5%,?2=0.483,p=0.028)?lung metastasis(ORR 37.1%,?2=9.455,p=0.002).number of metastatic sites ?2(ORR 41.2%,?2 =5.216,p=0.022)?Neutrophil lymphocyte ratio ?2.29(ORR 37.0%,?2=5.099,p=0.024)?Platelet lymphocyte ratio<150(ORR 43.5%,?2=10.468,p=0.001)?Median platelet volume ?9.9fL(ORR 36.7%,?2=5.873,p=0.015)?Lactate dehydrogenase<179.5 U/L(ORR 43.8%,?2=18.223,p=0.000)and with statically significant?From the short-term effects of the application of bevacizumab,age(?2=3.557,p=0.059),lobe location of tumor(?2=34.987,p=0.000)and anatomical classifica-tion(?2=12.853,p=0.000)of tumor,synchronous chemotherapy regimen(?2=14.602,p=0.000),application time(?2=14.577,p=0.001)T stage(?2=4.389,p=0.000),N stage(?2=3.149,p=0.0076),number of metastatic sites(?2=3.141,p=0.076),hepatic metastases(?2=7.758,p=0.005)or not,bone metastases or not(?2=4.34,p=0 037),the level of HGB(?2=3.288,p=0.07-),LDH(?2=4.266,p=0.039),ALB(?2=7.324,p=0.007),D-dimer(?2=7.403,p=0.007),were demonstrated related to the efficacy of Bevacizumab.Age(HR=4.133,p=0.007),lobe location of tumor(HR=37.206,p=0.000),T stage of tumor(HR=0.114,p=0.000),bone metastasis(HR=2.685,p=0.044),the level of ALB(HR=7.670,p=0.001),LDH(HR=0.245,p=0.012)were demonstrated to be the independent prognostic factor of the applyment of Bevacizumab.ConclusionsOf all nonsquamous NSCLC patients with Bevacizumab,patients with age>60 year old,lower lobe tumor,T1-T2 stage tumor,without bone metastasis,the level of ALB>42.1g/L,LDH<179.5U/L were demonstrated to be the independent prognostic fator of the applyment of Bevacizumab.