| Objective:About 34%to 79%of patients with esophageal squamous cell carcinoma will have a recurrence after operation.At present,there is no standard chemotherapy regimen for patients with local recurrence and metastasis of advanced esophageal cancer.NCCN guidelines recommend platinum-based systematic chemotherapy for patients with good PS scores,but the response rate is only 35%45%.In this study,retrospective analysis was used to collect the situation of patients in our hospital to analyze and compare the clinical benefits of targeted therapy and immunotherapy compared with platinum as chemotherapy regimen under the guidance of gene sequencing results.to explore the effectiveness of targeting and immunotherapy under the guidance of gene sequencing results,and to carry out survival analysis to explore the effects of various clinical factors on its prognosis.To analyze the possible molecular function,cellular environment and biological process of mutant gene products in patients with advanced esophageal cancer,and to explore the effect of individual significant genes on progression-free survival in patients with advanced recurrent and metastatic esophageal cancer.Methods:1.The ORR of the patients in the group was statistically analyzed,and the short-term curative effect of the patients was described.Survival analysis Kaplan-meier method and Log-rank test were used to analyze the clinical prognosis of 34 patients with unresectable locally advanced or postoperative recurrent and metastatic esophageal cancer.According to the results,the clinical factors with low Pvalue or clinically considered to have influence were selected for COX multivariate regression analysis.To explore the independent risk factors affecting progression-free survival.2.The whole genome sequencing results of patients with unresectable locally advanced or postoperative recurrent and metastatic esophageal cancer were statistically analyzed,and the high frequency variant genes and their correlation with the clinical prognosis of the patients were described.gene function analysis and pathway enrichment analysis were carried out to describe the possible molecular functions of mutant gene products in patients with unresectable locally advanced or postoperative recurrent and metastatic esophageal cancer.And the cellular environment and the biological processes involved.3.To explore the similarities and differences of gene changes in patients with different clinical characteristics:1)to explore the similarities and differences of gene changes in patients who had received postoperative adjuvant radiotherapy and radical radiotherapy;2)to explore the similarities and differences of gene changes in patients with different smoking history;3)to explore the similarities and differences of gene changes in patients with different times of progression before detection.Results:1.The objective remission rate of patients who died with gene sequencing recommended drugs was 30.8%,and the disease control rate DCR reached 76.9%,while the ORR and DCR of patients who refused to use gene sequencing recommended drugs were 12.5%and 50%,respectively.COX multivariate analysis showed that gene sequencing recommended therapy(HR=0.311,P=0.043)and treatment timing(HR=3.856,P=0.009)were independent factors affecting the prognosis of patients with unresectable locally advanced or postoperative recurrent or metastatic esophageal cancer.2.By sequencing the whole genome of 36 patients with unresectable locally advanced or postoperative recurrent and metastatic esophageal cancer,we found 182 tumor-specific gene variants,including TP53,CCND1 amplification and FGF19 amplification.Subgroup analysis showed that radiotherapy could inhibit tumor growth by affecting gene mutation and copy number change,inhibit mRNA transcription and cell proliferation,reduce peripheral microangiogenesis,and inhibit tumor growth,and that there may be a certain correlation between smoking history and FAT1 mutation in patients with advanced esophageal cancer.With the increase of the number of disease progression,most of the significant gene mutations in patients with locally advanced or postoperative recurrent or metastatic esophageal cancer were consistent.Conclusions:Targeted immunotherapy guided by gene detection has clinical benefits for patients with unresectable locally advanced or postoperative recurrent and metastatic esophageal cancer.Radiotherapy can inhibit the transcription and proliferation of mRNA in tumor cells and reduce the formation of peripheral microvessels by affecting gene mutation and copy number changes;the history of smoking in patients with advanced esophageal cancer may be related to the mutation of FAT 1;with the increase of the number of disease progression,the direction of most significant gene variation in patients with locally advanced or postoperative recurrent or metastatic esophageal cancer is consistent. |
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