The Research Of Clinical Characteristic And Prognosis Among Young Patients With Non-small-cell Lung Cancer

BackgroundLung cancer is the most common incident cancer and the leading cause of cancer death in China,It is a major public health problem.Most patients with lung cancer are more than 50 years old.With increasing incidence of lung cancer,it has shown trends of increasing incidence rates of lung cancer among young patients.It is important to study young patients with lung cancer.Previous reports have recognized the unique clinical features of young patients,including a high proportion of female patients,non-smokers,advanced stages,and an increased likelihood of gene mutations.However,the survival benefits for young patients receiving first-line molecular target agentsare poorly understood.The aims of this study were to document the clinical features,gene mutations,and survival of young patients with non-small-cell lung cancer(NSCLC).Method According to previous documents,young patients with NSCLC are more than 40 years in our study.From February 2001 to October 2016,7,494 patients with lung cancer at the Jinling Hospital were eligible for this study.After excluding cases without proven pathology or cytology,or cases combined with another type of malignant disease,the cohort of young patients with lung cancer comprised 270 patients aged<40 years.Two hundred and fifty-two(93%)were diagnosed withNSCLC and eighteen(7%)patients were diagnosed as small cell lung cancer(SCLC).Of these,42(15%)had squamous histologic findings,and 210(78%)had confirmed non-squamous cell carcinoma.To further investigate the characteristics of patients with NSCLC,we divided the participants according to their histologic types into the non-squamous cell carcinoma and squamous cell carcinoma groups.We analyzed tumor biopsy samples obtained by bronchoscope,percutaneous lung puncture biopsy guided by computed tomography,tumor resection,or pleural effusion.Specific targetable genomic alteration assessment methods included amplification-refractory mutation system assays for EGFR mutations,immunohistochemical assays for ALK alterations,and fluorescence in situ hybridization for ROS1 fusions.Patients with late-stage lung adenocarcinoma who received first-line molecular target agentsharbored either EGFR mutations or ALK rearrangements.Progression-free survival(PFS)was defined as the duration from the date of initial treatment to the date of disease progression,death,or the patient's last visit.Overall survival(OS)was measured from the day of diagnosis until the time of death or the patient's last visit.Data of PFS and OS were obtained by telephone.The patients participated in follow-up sessions until April 4,2017.We performed the chi-square test to identify associations among the categorical variables.PFS and OS were calculated using the Kaplan-Meier method and log-rank test.Statistical significance was defined as P<0.05.Results Of 270 young patients,252(93%)showed NSCLC and 18(7%)showed SCLC.Young patients with NSCLC were consisted of 210(78%)patients with non-squamous cell carcinoma,and 42(15%)patients with squamous cell carcinoma.The median ages of the non-squamous cell carcinoma and squamous cell carcinoma groups were 35 years and 38 years,respectively.Among patients with non-squamous cell carcinoma,194 patients(72%)had histologically confirmed adenocarcinoma,11 patients(4%)were adenosquamous cell carcinoma,and 5 patients(2%)had large cell carcinoma.In the non-squamous cell carcinoma group(n = 210),there were 28(13%)patients in stage I,8(4%)patients in stage II,22(10%)patients in stage ?a,10(5%)patients in stage ?b,136(65%)patients in stage ?,and 6(3%)patientsnot in detail;103(49%)patients were female,and 171(81%)patients had no history of smoking.In the squamous cell carcinoma group(n = 42),there were 3(7%)patients in stage ?,1(2%)patients in stage ?,8(19%)patients in stage ?a,4(10%)patients in stage ?b,23(55%)patients in stage ?,and 3(7%)patients not in detail;14(33%)patients were female;and 25(60%)had never smoked.Overall,the four most common metastases,in descending order,were bone(69/159,43%),intrapulmonary lesions(59/159,37%),pleura(47/159,30%),and brain(33/159,21%).In the squamous cell carcinoma group,those were intrapulmonary lesions(11/23,48%),pleura(6/23,26%),bone(11/23,48%),and liver(5/23,22%)metastases.In the non-squamous cell carcinoma group,those were intrapulmonary lesions(48/136,35%),pleura(41/136,30%),bone(58/136,43%),and brain(32/136,24%)metastases.Among patients with adenocarcinoma,29(40%,n=73)harbored epidermal growth factor receptor(EGFR)mutations,25(34%,n = 74)harbored anaplastic lymphoma kinase(ALK)translations,and 1(14%,n= 7)harbored ROS proto-oncogene 1 receptor tyrosine kinase(ROS1)translations.In the 29 cases with EGFR mutations,19(66%)patients had exon 19 deletions,9(31%)had L858R,2(7%)harbored T790M point mutations,and a patient had both 19 deletions and T790M.The median progression-free survival(PFS)and overall survival(OS)were 3.3 months and 27.6 months for patients receiving chemotherapy(n = 65),and 12.1 months and 33.6 months for patients receiving EGFR tyrosine kinase inhibitors(TKIs)(n = 13),respectively.Patients receiving crizotinib had a median PFS time of 21.9 months(n = 8).ConclusionsYoung patients are associated with an increased likelihood of gene mutations,especially ALK fusions.Young patients harboring driver oncogenes can derive a better survival benefit from receiving molecular target agents.