Relationship Between ROS1 Gene Status And Chemotherapy Efficacy In Patients With Advanced Lung Adenocarcinoma

Background and objectiveLung cancer is one of the most common malignant tumors in the contemporary world,and also the main cause of death in human.It is becoming an epidemic disease in the world,which is divided into non-small cell lung cancer(NSCLC)(about 85%)and small cell lung cancer(SCLC about 15%)according to the tissue type and prognosis.Currently,the standard treatment of lung cancer mainly includes surgical resection,chemotherapy,radiotherapy and targeted therapy,etc.However,these treatments methods are difficult to achieve ideal results.The 5-year survival rate of lung cancer is only 15%-17%,and 5-year survival rate of small cell lung cancer is lower,only 6%.The lung adenocarcinoma is the most common subtype of non-small cell lung cancer and the incidence is increasing year by year,especially among women,young and non-smokers.The next-generation sequencing(NGS)is used for multi-gene detection and high-throughput genomic mapping analysis.More and more are used in molecular diagnostics.Lung adenocarcinoma is mostly driven by a single oncogene.With the discovery of driving gene,the research of molecular targeted therapy is more and more in-depth,among which tyrosine kinase and monoclonal antibody are widely used,which provides more choice for tumor treatment.ROS1 encodes a special receptor tyrosine kinase,which is a member of the insulin receptor family.ROS1 gene fusion is one of the driver genes of NSCLC,and occurs in 1-2% of lung adenocarcinoma patients.This study collected 304 patients admitted from the First Affiliated Hospital of Zhengzhou University from January 1,2016 to April 12,2018,The relationship between ROS1 gene status and pemetrexed-based chemotherapy efficacy and progressive free survival(PFS)in state Ⅲ/Ⅳ lung adenocarcinoma was retrospectively analyzed.The purpose of this study was to explore the predictive significance of ROS1 gene status in patients with advanced lung adenocarcinoma for pemetrexed chemotherapy.MethodsThe clinical data of 304 patients with advanced lung adenocarcinoma whose epidermal growth factor receptor(EGFR),anaplastic lymphoma kinase(ALK)and rodent sarcoma virus oncogene(KRAS)were negative were retrospectively analyzed.All patients were performed ROS1 gene detection,and according to ROS1 gene status,the patients were divided into two groups.Both groups were treated with pemetrexide combined with platinum chemotherapy.All patients were reviewed chest and abdomen CT every two cycles of chemotherapy,according to response evaluation criteria in solid tumors(RECIST)1.1.The curative effect was evaluated as complete response,partial response,stable disease and progressive disease,and calculate the patients disease control rates(DCR),objective response rate(ORR),progression-free survival(PFS).Telephone follow-up and outpatient follow-up were conducted to compare the efficacy and prognosis of ROS1 positive group and negative group,and to analyze the relationship between ROS1 gene status and chemotherapy efficiency and disease-free survival.The relationship between ROS1 gene status and the response rate of chemotherapy in patients with lung adenocarcinoma was analyzed by chi-square test or Fisher’s exact probability method.The survival curve of Kaplan-Meier was used to analyze the survival rate.The difference between the two groups was observed by Log-rank test.Cox regression was used for multifactor analysis of PFS.P<0.05 was considered statistically significant.Results1.ROS1 gene was detected in all 304 patients.There were 28 cases with positive ROS1 gene and 276 cases with negative ROS1 gene.ROS1 gene fusion was not related to age,clinical stage and PS score,but related to gender and smoking history.The P values were 0.007 and 0.007,respectively2.304 patients had an objective response rate(ORR)of 23.7% and a disease control rate(DCR)of 78.0%.The ORR and DCR of ROS1 positive patients with lung adenocarcinoma were both higher than those of ROS1 negative patients(39.3% vs 22.1%,P=0.042;92.9% VS 76.4%,P=0.031),the difference was statistically significant.ORR was independent of gender,age,clinical stage,smoking status,PS score and platinum used in chemotherapy.DCR of patients aged <60 years old was higher than that of patients aged ≥60 years old(85.3% vs 70.2%,P=0.020).DCR was not related to gender,clinical stage,smoking status,PS score and platinum.3.The median PFS of 304 patients receiving pemetrexed combined with platinum-based chemotherapy was 7.9 months.ROS1 positive patients had longer PFS than ROS1 negative patients(13.7 months vs 7.8 months,P=0.013),and non-smoking patients had longer PFS than smoking patients(8.2 months vs 7.6 months,P=0.029).4.Cox regression multivariate analysis showed that ROS1 gene fragmentation and fusion was an independent factor affecting PFS(HR=0.412,95%CI: 0.190-0.891,P=0.024).Conclusion1.ROS1 gene fusion is more common in women and non-smoking patients with lung adenocarcinoma.2.Compared with wild-type patients,ROS1 gene fusion patients have a higher response rate to pemetrexed combined with platinum chemotherapy and longer PFS.