Induction Immuno-chemotherapy and Concurrent Chemoradiotherapy With or Without Apatinib in Unresectable, Locally Advanced Esophageal Squamous Cell Carcinoma

Inclusion Criteria:

* Diagnosed with esophageal squamous cell carcinoma through pathological examination or cytological examination;
* Evaluated as locally advanced esophageal cancer that is unresectable through endoscopic ultrasound, imaging studies including barium swallow, CT scans of the neck, chest, and upper abdomen, MR imaging of the neck and chest, whole-body bone scan, or PET/CT, with staging ranging from T2-4, N0-3, M0-1 (M1 only includes patients with supraclavicular lymph node metastasis);
* Male or female aged between 18 and 80 years old;
* No prior chemotherapy, radiotherapy, surgery, targeted therapy, or immunotherapy;
* Expected survival of ≥12 weeks;
* ECOG performance status score of 0 or 1;
* Organ and bone marrow function meeting the following criteria: forced expiratory volume in 1 second (FEV1) ≥800 ml; absolute neutrophil count ≥1.5×109/L; platelet count ≥100×109/L; hemoglobin ≥90 g/L; serum creatinine clearance calculated according to the Cockcroft-Gault formula ≥50 mL/min (Cockcroft and Gault 1976); serum bilirubin ≤1.5 times the upper limit of normal (ULN); aspartate aminotransferase and alanine aminotransferase ≤2.5 times ULN;
* Signed and dated informed consent form is required before any study procedures are performed.

Exclusion Criteria:

* Participating in another clinical study concurrently, unless it is an observational (non-interventional) clinical study;
* Prior use of any targeted therapy or immunotherapy;
* Underwent major surgery (excluding vascular access) within 4 weeks before entering the study;
* Uncontrolled complications, including but not limited to persistent or active infections, symptomatic congestive heart failure, poorly controlled hypertension, unstable angina, arrhythmias, active peptic ulcer disease or gastritis, intestinal perforation, intestinal obstruction, active bleeding disorders, or psychiatric illness/social situations that would limit compliance with study requirements or impair the ability to provide written informed consent;
* Performance status score of 2-4;
* Any of the following organ and bone marrow dysfunctions: forced expiratory volume in 1 second (FEV1) \<1000ml; absolute neutrophil count \<1.5×109/L; platelet count \<100×109/L; hemoglobin \<90 g/L; serum creatinine clearance calculated according to the Cockcroft-Gault formula \<50 mL/min (Cockcroft and Gault 1976); serum bilirubin \>1.5 times the upper limit of normal (ULN); aspartate aminotransferase and alanine aminotransferase \>2.5 times ULN;
* Conditions that may interfere with the assessment of the efficacy or safety of apatinib;
* Use of immunosuppressive drugs within 28 days before the first infusion of trastuzumab, excluding physiologic doses of inhaled corticosteroids; or systemic corticosteroids ≤10 mg/d of prednisone or equivalent;
* History of autoimmune diseases within the past 2 years;
* History of active or inflammatory bowel disease (such as Crohn's disease, ulcerative colitis);
* History of organ transplantation requiring immunosuppressive therapy;
* Receipt of attenuated live vaccines within 30 days before the study initiation or within 30 days after receiving trastuzumab;
* History of another primary malignancy within 5 years before starting trastuzumab, except adequately treated basal or squamous cell skin cancer or in situ cervical cancer;
* Pregnant or lactating females; or sexually active males or females of reproductive potential not using effective contraception methods.