The Correlation Between Genetic Mutations And Prognosis In Extensive-stage Small-cell Lung Cancer

Purpose:With the application of Next-generation Sequencing(NGS),genetic researches are widely conducted in non-small-cell lung cancer(NSCLC).However,NGS related study in small-cell lung cancer(SCLC)is limited.It remains unclear whether genetic mutations in SCLC have effects on the survival.Our retrospective study aimed to identify the correlation between genetic mutations and progression-free survival(PFS)in extensive-stage SCLC after first-line chemotherapy.Methods:A total of 75 patients with extensive-stage SCLCconfirmed by histopathology from February 2018 to February 2019 were retrospectively analyzed.The biopsy specimens of all patients were analyzed by NGS.All patients received first-line chemotherapy and follow-up at Shanghai Chest Hospital.Results:Eleven genes were mutated in at least 10% of the 75 patients,including TP53(96%),RB1(77%),SMAD4(32%),NOTCH1(21%),PTEN(16%),FGFR1(16%),KDR(15%),PIK3CA(15%),ROS1(15%),BRCA2(13%),ERBB4(10%).The median number of mutated genes among all patients was 5.Univariate analysis showed patients with more than 5 mutated genes(PFS=6.7months,P=0.004),mutant TP53(PFS=5.0 months,P=0.011),and mutant BRCA2(PFS=6.7months,P=0.046)had better PFS after first-line chemotherapy.Multivariate Cox regression analysis showed that patients who achieved PR(HR 3.729,95%CI 2.038-6.822),had more than 5 mutated genes(HR1.929,95%CI 1.096-3.396),with mutant BRCA2(HR 4.581,95%CI 1.721-12.195),and without liver metastasis(HR 0.415,95%CI 0.181-0.951)obtained PFS benefit after first-line chemotherapy.Conclusions:Our retrospective study showed the number of mutated genes and BRCA2 mutation status in extensive-stage SCLC were significantly related to PFS after first-line chemotherapy.