A Single-center, Prospective Cohort Study of Neoadjuvant Anti-PD-1 Plus Chemotherapy in Locally Advanced Resectable Esophageal Squamous Cell Carcinoma
The purpose of this study is to evaluate the outcomes and identify predictors of neoadjuvant anti-PD-1 plus chemotherapy in locally advanced resectable esophageal squamous cell carcinoma (ESCC). In this single-center cohort study, we are aiming to (1) evaluate the therapeutic efficacy and survival benefits on patients with locally advanced resectable ESCC (cT3-4aN0-1M0); (2) evaluate the value of genomic indicators including MMR alternation status in predicting therapeutic responses and prognosis; (3) evaluate the value of transcriptomic indicators including B cell lineage features in predicting therapeutic responses and prognosis; (4) evaluate the value of microbial and metabolite indicators in predicting therapeutic responses and prognosis. Whole exome sequencing, RNA sequencing, 16S rRNA sequencing and Liquid Chromatography with tandem mass spectrometry (LC-MS-MS) of samples of patients to neoadjuvant chemoimmunotherapy before and after treatment are performed to explore the mechanisms of drug resistance and identification of predictive and prognosis biomarkers.
• Histologically-confirmed squamous cell carcinoma of the esophagus;
• Tumors of the esophagus are located in the thoracic cavity;
• Pre-treatment stage as cT3-4aN0-1M0 (AJCC/UICC 7th Edition) (In case of stage cT4a, curative resectability has to be explicitly verified by the local surgical investigator prior to randomization).
• Age is between 18 years and 75 years,
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
• Adequate cardiac function. All patients should perform ECG, and those with a cardiac history or ECG abnormality should perform echocardiography with the left ventricular ejection fraction \> 50 %;
• Adequate respiratory function with FEV1≥1.2L, FEV1%≥50% and DLCO≥50% shown in pulmonary function tests;
• Adequate bone marrow function (White Blood Cells \>4x10\^9 /L; Neutrophil \>2.0×10\^9 /L; Hemoglobin \> 90 g/L; platelets\>100x10\^9 /L);
• Adequate liver function (Total bilirubin \<1.5x Upper Level of Normal (ULN); Aspartate transaminase(AST) and Alanine transaminase (ALT)\<1.5x ULN);
⁃ Adequate renal function (Glomerular filtration rate (CCr) \>60 ml/min; serum creatinine (SCr) ≤120 µmol/L);
⁃ The patient has provided written informed consent and is able to understand and comply with the study;