Total Neoadjuvant Therapy With Induction Immunochemotherapy and Chemoradiotherapy Followed by Surgery for Locally Advanced Esophageal Squamous Cell Carcinoma
Effective systemic therapy such as nivolumab as an adjuvant therapy has been demonstrated to improve the outcomes of patients receiving neoadjuvant chemoradiotherapy (CRT) for locoregional esophageal cancer. A more effective systemic therapy with anti-PD-1 or anti-PD-L1 immune checkpoint inhibitors (ICIs) plus cisplatin-based doublet chemotherapy, which has shown with high tumor response rate and improved survivals in patients with late-stage ESCC, may provide crucial benefit to patients with locally advanced disease by improving the systemic control, downstaging the locoregional tumor burden and reducing recurrence and metastasis. Collectively, the investigators hypothesize that total neoadjuvant therapy (TNT) approach-consisting of induction immunochemotherapy followed by CRT-is a promising strategy to enhance the outcomes for participants with locally advanced esophageal squamous cell carcinoma.
• Pathologically proven squamous cell carcinoma of the intrathoracic esophagus.
• Locally advanced disease, which is defined by the TNM system of the American Joint Committee on Cancer (AJCC) Cancer Staging System (8th edition), fulfilling one of the following criteria as determined by staging procedures (including but not limited to endoscopic ultrasound, computed tomography, bronchoscopy or positron emission tomography):
∙ cT3/4a, N0, M0;
• Tumor length longitudinal ≤ 10cm and radial ≤ 5cm.
• The tumor must not extend more than 2cm into the stomach.
• No invasion of the tracheobronchial tree or presence of tracheoesophageal fistula.
• Age ≥ 18 and ≤ 75 years old.
• Performance status ECOG 0\
• Adequate bone marrow reserves, defined as:
∙ white blood cells (WBC) ≥ 3,000/µl or neutrophil count (ANC) ≥ 1,500/µl;
‣ platelets ≥ 100,000/µl.
• Adequate liver function reserves, defined as:
∙ hepatic transaminases ≤ 2.5 x upper limit of normal (ULN);
‣ serum total bilirubin ≤ 2.0 x upper limit of normal (ULN).
⁃ Adequate renal function: Creatinine ≤1.5 x upper normal limit or estimated creatinine clearance ≥ 50 ml/min (estimated by Cockcroft-Gault formulation)
⁃ Written informed consent.
⁃ Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be mandatory.
⁃ Female subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in Section - Contraception, for the course of the study through 120 days after the last dose of study medication.
⁃ Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
⁃ Male subjects of childbearing potential must agree to use an adequate method of contraception as outlined in Section - Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy.
• Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.