Analysis Of Genetic Mutations And The Efficacy Of Potential Molecular Targets In Pulmonary Sarcomatoid Carcinoma

Introduction:Pulmonary sarcomatoid carcinoma(PSC)is a rare and highly heterogeneous disease.Targeted molecular therapy is considered one of the most efficient strategies,whereas genetic profiles and the efficacy of targeted therapy remain largely uncertain.Materials and methods:We performed a systematic literature search of the Pub Med,Embase,and Web of Science databases from January 2016 to December 2020,pooled PSC patient clinical characteristics and gene mutation data in the studies that met the inclusion and exclusion criteria for deeper analysis.PSC patients were divided into Chinese PSC group and non-Chinese PSC group for comparative analysis to understand the differences in gene mutation levels between domestic and foreign PSC patients.PSC patient detailed mutation data were compared to conventional non-small-cell lung cancer(NSCLC)genetic mutations from The Cancer Genome Atlas(TCGA).Furthermore,28 PSC patients underwent genetic testing in our hospital,7 PSCs of them treated with first-line Epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)who harbored EGFR mutations were included for analysis.PSC clinical characteristics and gene mutation expression levels were compared using Pearson’s chi-square test and Kaplan-Meier curves were employed for survival analysis.Results:We identified 10 eligible publications,and 476 patients were enrolled.The majority of PSCs were men(246/376,65%)with smoking history(195/251,78%).Among 271 patients with reported TNM stage at the time of diagnosis,150(55%)patients had advanced stage IIIA-IVB disease.The most common pathology subtype was PLC(148/214,69%).TP53(69%)was the most frequently mutated gene.Other common mutations included the EGFR(8%),MET(11%),MET 14 exon skipping(6%),KRAS(30%),BRAF(6%),and PIK3CA(5%)genes.In the Chinese PSC group and the non-Chinese PSC group,with 100 and 376 PSC patients,respectively,significantly higher EGFR(21% vs.5%,P<0.001)and MET 14 exon skipping(12%vs.5%,P=0.008)mutation rates the results indicated that the Chinese PSCs than in non-Chinese PSCs.Although MET and MET 14 exon skipping mutations were much higher in PSC,most gene mutations rate including EGFR were intermediate between LUAC and LUSC.The frequency of EGFR mutation was 25%(7/28)in our hospital,among the 7 PSCs treated with EGFR-TKIs as first-line therapy,6 patients(86%)achieved PR or CR,the median PFS and OS were 13 months(95% CI: 3.56-22.4months)and 18.6 months(95% CI: 6.25-30.94 months),respectively.Conclusion:Ethnic differences were detected for PSCs with EGFR or MET mutations.Chinese PSC patients have a higher rate of EGFR or MET mutations than non-Chinese and are expected to benefit from treatment with TKIs.The efficacy of EGFR-TKIs for Chinese PSC is promising.