Systematic Review Of The Efficacy And Safety Of Immunotherapy Combined With Chemotherapy In The First-line Treatment Of Advanced Esophageal Squamous Cell Carcinoma

Objectives:Esophageal carcinoma is one of the most common malignant tumors of digestive system with poor prognosis.In Asia,esophageal squamous cell carcinoma（ESCC）accounts for more than 90%of esophageal carcinoma.Because of the concealment of onset,most of the patients are in advanced stage at the time of diagnosis,and chemotherapy is the main treatment.At present,immunotherapy aimed at immune checkpoints has opened up a new way for the treatment of malignant tumors.Combined chemotherapy can further improve the curative effect and the prognosis of patients with esophageal carcinoma.This study first evaluated the efficacy and safety of immunotherapy combined with chemotherapy in the real world,and then conducted a systematic review of the efficacy and safety of immunotherapy combined with different regimens of chemotherapy in the first-line treatment of advanced esophageal squamous cell carcinoma to explore the efficacy of immunotherapy combined with chemotherapy for patients with esophageal squamous cell carcinoma.Methods:1.A total of 18 patients with advanced esophageal squamous cell carcinoma who received first-line immunotherapy combined with chemotherapy in the Affiliated Hospital of Yangzhou University from January 2020 to March 2022 were included.We collected the general clinical data of these patients,and evaluated the short-term efficacy and adverse reactions of immunotherapy combined with chemotherapy through the imaging and hematological results before and after treatment.2.The literatures related to immunotherapy combined with chemotherapy for esophageal squamous cell carcinoma were searched from Embase,Medline,Web of science and Cochrane databases until February 8,2022.According to the different chemotherapy regimens,the patients were divided into Fluoropyrimidine combined with Platinum（FP）and Taxane combined with Platinum（TP）.We used R studio to combine the effect-quantity and compared the objective response rate（ORR）,disease control rate（DCR）,progression-free survival（PFS）,overall survival（OS）,and the incidence of various adverse reactions between FP group and TP group.Results:1.All 18 patients with advanced esophageal squamous cell carcinoma received first-line immunotherapy combined with chemotherapy.There were 11 males and 8 females.The median age of the patients was 68.5 years old,ranging from 53 to 91 years old.The location of tumor was 6 cases of middle thoracic esophageal cancer and 12 cases of lower thoracic esophageal cancer.10 patients received TP regimen combined with immunotherapy,5 patients received S-1 combined with immunotherapy,1 patient received platinum combined with immunotherapy,1 patient received S-1+docetaxel combined with immunotherapy,and 1 patient received FP regimen combined with immunotherapy.All the patients could evaluate the curative effect.After treatment,there were 2（11.1%）patients achieved CR,9（50.0%）patients achieved PR,4（22.2%）patients achieved SD,and 3（16.7%）patients achieved PD.The ORR rate was 61.1%and the DCR rate was 88.8%.The main adverse event was myelosuppression.Among the grade 3 or higher adverse events,there were 1 cases of leukopenia,3 cases of neutropenia,1 case of thrombocytopenia and 3 case of liver function damage.All the adverse events were improved after symptomatic treatment.2.A total of 10 literatures and 1688 patients with esophageal squamous cell carcinoma were included in this study.Considering that a total of 327 patients with advanced esophageal carcinoma were included in one literature,only 30 of them received combined FP chemotherapy,so they were included in the TP group.One other articles were unable to obtain specific patient groups,so they were not included in the subgroup analysis.Therefore,647 patients were included in the FP group and 980 patients in the TP group finally.The results of analysis were as follows:The ORR rate was 71.4%and the DCR rate was 94.8%in TP group.The ORR rate was 53.3%and the DCR rate was 88.0%in FP group.The ORR rate in TP group was significantly higher than that in FP group（P<0.05）,and there was no significant difference in DCR rate（P>0.05）.In terms of safety,the incidence of grade 3 or higher gastrointestinal adverse events in TP group was lower than that in FP group,the incidences of grade 3 or higher hematological toxicity and treatment-related mortality in TP group was higher than that in FP group.Conclusions:1.The short-term efficacy of immunotherapy combined with chemotherapy in patients with advanced esophageal squamous cell carcinoma is definite and the safety is tolerable.2.In patients with advanced esophageal squamous cell carcinoma,the PFS and OS of immunotherapy combined with TP regimen were superior to those combined with FP regimen.However,the incidences of hematological toxicity and treatment-related mortality of immunotherapy combined with TP regimen were higher than those combined with FP regimen.Further prospective studies are needed for comparison.