Neoadjuvant Sintilimab Plus Chemotherapy For Locally Advanced Esophageal Squamous Cell Carcinoma: A Pilot Study

Background:Esophageal cancer（EC）is the sixth leading cause of cancer-related death worldwide,with nearly 510,000 deaths per year from EC.In China,EC ranks respectively sixth and fifth in morbidity and mortality,of which more than 90%are esophageal squamous cell carcinoma（ESCC）.In recent years,there have been continuous optimization and breakthroughs in EC treatment methods,but the overall survival benefit of patients is still unsatisfactory.Currently,neoadjuvant chemoradiotherapy（n CRT）combined with radical esophagectomy is recommended as the standard neoadjuvant therapy for resectable esophageal squamous cell carcinoma.However,nearly half of the patients still have tumor recurrence after surgical treatment,and distant metastasis is the most common.n CRT has not effectively suppressed the main cause of treatment failure in locally advanced esophageal cancer.In recent years,immunotherapy targeting immune checkpoints has made breakthroughs in the treatment of solid tumors,bringing revolutionary changes to the treatment of various tumors including esophageal squamous cell carcinoma.The role of standard first-line therapy in neoadjuvant therapy is still a hot research topic.Therefore,this study aimed to investigate the safety and efficacy of neoadjuvant immunochemotherapy（sintilimab combined with platinum-based chemotherapy）in the treatment of locally advanced esophageal squamous cell carcinoma.Methods:The clinical data of locally advanced ESCC patients who received neoadjuvant immunochemotherapy（n ICT）in Lanzhou University Second Hospital from September 2020 to February 2022 were summarized.Neoadjuvant regimen:sintilimab（200 mg,administered by intravenous infusion on first day of each cycle）,paclitaxel（135 mg/m~2,administered by intravenous infusion on second day of each cycle）,and cisplatin（80 mg/m~2,administered by intravenous infusion on second day of each cycle）,every 3 weeks is a cycle,and 4 to 6 weeks after the completion of 2 cycles of treatment,the patient undergoes radical resection（Mc Keown procedure）.Adverse events（AEs）,immunotherapy-related adverse events（ir AEs）,and completion rates of neoadjuvant therapy were recorded;objective response rate（ORR）,disease control rate（DCR）,complete pathological response rate（p CR）,major Pathological response rate（MPR）,R0 resection rate and perioperative complication rate.Results:A total of 38 patients with locally advanced ESCC were recruited during the period,and 37 patients（97.4%）completed at least 2 cycles of neoadjuvant therapy.There were 34 males and 3 females,ranging in age from 42 to 79 years old（64.5±8.5）.The main AEs were alopecia（20/37,54.1%）,nausea（17/37,45.9%）,fatigue（14/37,37.8%）,anemia（11/37,29.7%）,vomiting（8/37,21.6%）.Grade 3 AEs occurred in 2.7%（1/37）,with no grade 4 or higher AEs.Ir AEs included 2 cases of hypothyroidism（2/37,5.4%）,and no grade 4～5 ir AEs occurred.According to the Response Evaluation Criteria in Solid Tumors（RECIST version 1.1）,2 patients（2/37,5.4%）had a complete response（CR）,18 patients（18/37,48.6%）had a partial response（PR）,and 15 patients had a partial response（PR）.（15/37,40.5%）had stable disease（SD）,2 patients（2/37,5.4%）had progressive disease（PD）,the objective response rate（ORR）was 54.1%（20/37）,disease control Rate（DCR）was 94.6%（35/37）.According to Stooler criteria,19patients（19/37,51.4%）had significant improvement in dysphagia after treatment.17patients underwent Mc Keown radical resection for esophageal cancer,16 males and 1female,aged 42-76 years（62.3±8.7）,all achieved R0 resection,tumor regression response（TRG）:TRG1（p CR）patients in 4 cases（4/17,23.5%）,5 TRG2（MPR）patients（5/17,29.4%）,3 TRG3 patients（3/17,17.6%）,5 TRG4 patients（5/17,29.4%）,new After adjuvant therapy,52.9%（9/17）patients achieved TRG1/TRG2.20 patients did not undergo surgery,6 patients（6/20,30.0%）were PR patients,and 12 patients（12/20,60.0%）were SD patients;2 patients with PD（2/20,10.0%）;5 patients with endoscopic complete remission（Endoscopic CR）（5/20,25.0%）.There were 3 cases（3/17,17.6%）of perioperative complications,including 2 cases of pulmonary infection and 1 case of anastomotic leakage,and there was no death case within 30 days after operation.Conclusion:Sintilimab combined with platinum-based chemotherapy is safe and effective in neoadjuvant treatment of locally advanced ESCC,and the long-term survival benefit still needs to be followed up and verified.A multicenter,randomized,phaseⅢclinical study is necessary to confirm these results.