Relationship Between EGFR Mutations And Clinicopathological Features In NSCLC And Prognostic Analysis Of TKI Treatment

Background and purposeLung cancer is one of the most frequently diagnosed cancers.An estimated 1.8 million new lung cancer cases has been diagnosed worldwide, accounting for about 13% of total cancer diagnoses.Lung cancer is the most common cause of cancer-related mortality globally, accounting for more than 1.4 million deaths per year.Outcomes remain poor, despite advances in diagnostics and therapeutics, with a five-year survival rate of 15% worldwide while it is only less than 10% in China.Prognosis is determined by stage at presentation with surgical resection of early stage disease offering patients the higher probability of cure; unfortunately the majority of patients were diagnosed at an advanced stage of their disease, leading to poor outcomes.Traditional treatment options for advanced patients is platinum-based chemotherapy, the popular programs include gemcitabine and cisplatin, docetaxel and cisplatin, carboplatin and paclitaxel and cisplatin and paclitaxel, with which median overall survival was 8-10 months.In the past few years, much investigation has focused on targets including EGFR, K-RAS and VEGF in the field of molecular targeting therapy; and a good number of molecular targeting agents against these targets have emerged.Epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs) has high selectivity for populations.Multiple clinical studies suggested female Asian patients who had never smoked had superior efficacy with it, particularly those with adecarcinoma.The median overall survival of EGFR mutation-positive patients is more than 2 years.This therapy is targeted, high efficiency, long progression free survival and mild side effects, has become the main method of treatment of advanced non small cell lung cancer.Based on 758 cases in our hospital patients detected EGFR were analyzed retrospectively, investigate the relationship between mutations status of epidermal growth factor receptor gene and the clinicopathological features and progression free survival time of those patients harboring common mutation treated with tyrosine kinase inhibitors.Data and MethodsThe patients who had the EGFR test from September 3rd 2013 to September 13 th 2014 in the First Affiliated Hospital of Zhengzhou University were enrolled.The overall 758 cases were tested EGFR mutation used ARMS-PCR,to investigate the association of mutation state and clinicopathological features.Select the eligible non small cell lung cancer patients and evaluate the progression free survival according to RECIST(Response evaluation criteria in solid tumor,RECIST) standard to find out the difference between different common mutations.Methods1.EGFR test Firstly, estimate the number and proportion cancer cells of testedsamples to meet detection requirements.Then extract DNA fromparaffin-embedded tissues used OMEGA(USA) E.Z.N.A.FFPE DNA KIT, anddetect the mutation states of about 29 sites in exon 18、19、20 and 21 of epidermalgrowth factor receptor gene.2.Inclusion criteria(1)Inpatients who had the EGFR test from September 3rd 2013 to September 13 th 2014 in the First Affiliated Hospital of Zhengzhou University were enrolled, and the results turned out to be 19 or 21 mutation positive;(2)TNM staging is IV stage, and patients should be treated with oral tyrosine kinase inhibitors(Gefitinib 250 mg QD, Erlotinib 150 mg QD or Icotinib 125 mg TID) until disease progression;(3)Unsynchronized receiving other anti-tumor chemotherapy or other treatment during taking oral targeted drug;(4)Never received radiation therapy before(including internal or external radiation and so on);(5)Complete clinical information, at least one clinically evaluable lesion and regularly CT scans to evaluate the efficacy in our hospital.3 Evaluation Method According to RECIST criteria to define progression free survival as the period from the first application of molecular targeted drugs to definite disease progression or death.4 Statistical MethodApply IBM SPSS 20.0 software for data analysis, use c2 test to analyze the correlation between EGFR mutations and clinicopathological features, if P value was less than 0.05 was considered to be statistically significant.The difference of progression free survival between the two subgroups were analyzed using the Kaplan-Meier survival analysis, and survival distribution were tested by Log rank test, P value less than 0.05 was statistically significant as well.Results1.Of the 758 cases of non small cell lung cancer, with an average age is 59.6, 377(49.7%) are found to have EGFR mutation while 381(50.3%) are not founded EGFR mutation.Of all, five patients has exon 18 mutation, accounting for 0.7%.One hundred and ninety-six patients has exon 19 mutation, accounting for 25.9%.Twelve patients has exon 20 mutation, accounting for 1.6%.One hundred and fifty-six patients has exon 21 mutation, accounting for 20.6%.Eight patients has composite mutation(two or more kinds of mutations), accounting for 1.1%.2.Epidermal growth factor receptor mutation status is associated with gender, history of smoking and pathological type whose P value is all less than 0.05, but regardless of age whose P value is more than 0.05.3.EGFR mutation status and clinicopathological features were evaluated by multivariate logistic regression analysis.Women and adenocarcinoma are independent risk factors, but history of smoking is not independent risk factor.4.Patients who are eligible for inclusion criteria are 79, include 45 cases harboring exon 19 mutation and 34 cases harboring exon 21 mutation.The progression free survival were evaluated by response evaluation criteria in solid tumor(RECIST).The minimum is zero while the maximum is 14.8 months((95%CI: 6.344~7.656).The median progression free survival is 7.0 months.The minimum of exon 21 is zero while the maximum is 15.0 months and the median progression free survival is 7.7 months(95%CI: 5.986~9.414).The median progression free survival of exon 19 is shorter than exon 21, but there is no statistical difference(c2=1.194, P=0.274).CONCLUSIONFemale, non-smokers and adenocarcinoma have a higher EGFR mutation rate, Female and adenocarcinoma were independent risk factors, but EGFR test for squamous cell carcinoma and patients with a history of smoking should not be ignored in our routine clinical work.There is no difference between the PFS of exon 19 and exon 21.