A Clinical Study on the Efficacy and Safety of Paclitaxel Polymeric Micelles and Cisplatin Combined With Cadonilimab as a Neoadjuvant Therapy for Locally Advanced Esophageal Squamous Cell Carcinoma

Inclusion Criteria:

1. Age ≥18 years, ≤75 years, gender is not limited;
2. Squamous esophageal cancer of thoracic segment confirmed by pathology;
3. Locally advanced patients with no distant metastasis by imaging, resectable or potentially resectable after discussion among oncology, esophageal surgery, and imaging, and clinical stage cT2-4aN+ or cT3-4aN0, M0, stage II, III, or IVA (AJCC 8th edition cTNM staging);
4. ECOG PS score of 0-1;
5. No previous antitumor treatment such as radiotherapy, chemotherapy and immunotherapy;
6. Expected survival \> 6 months;
7. Adequate baseline organ function: (i) WBC ≥3×10\^9/L, ANC ≥1.5×10\^9/L, PLT ≥100×10\^9/L, Hb ≥9g/dL; (ii) Liver function: TBIL ≤2ULN, AST ≤2.5ULN, ALT ≤2.5ULN; (iii) Renal function: cCr\>40 ml/min, Cr≤1.5 ULN; (iv) Cardiac function: no cardiac disease or coronary artery disease. Cardiac function: no heart disease or coronary heart disease, patients with cardiac function grade 1-2;
8. Hypertensive patients applying antihypertensive drugs to control blood pressure within the normal range;
9. Diabetic patients with fasting blood glucose controlled at ≤8mmol/L by hypoglycemic drug treatment;
10. No other serious diseases (such as autoimmune diseases, immunodeficiency, organ transplantation, or other diseases that require continuous hormone therapy) that conflict with this protocol;
11. No history of other malignant tumors;
12. The patient agrees to participate in this clinical study and signs the Informed Consent Form.

Exclusion Criteria:

1. Patients who have previously received anti-tumor therapy (including chemotherapy, radiotherapy, surgery or immunotherapy, etc.);
2. Combination of other incurable malignant tumors (except cured non-malignant skin tumors, cervical cancer in situ, and prostate cancer);
3. Patient has or anticipates a significant risk of esophageal perforation, fistula, and hemorrhage;
4. Active autoimmune or immunodeficiency disease, use of immunosuppressants prior to enrollment, and use of immunosuppressant dosage ≥10 mg/day of oral prednisone for more than 2 weeks;
5. Clinically significant cardiovascular disease including, but not limited to, severe acute myocardial infarction, unstable or severe angina pectoris, coronary artery bypass grafting surgery, congestive heart failure, ventricular arrhythmia requiring medical intervention, left ventricular ejection fraction \<50%, or other anticipated inability to tolerate chemoradiotherapy in the 6 months prior to enrollment;
6. Severe allergies;
7. Pregnant or lactating women;
8. Severe mental disorders;
9. Presence of CTC grade ≥3 peripheral nerve disease;
10. Abnormal coagulation function (PT \> 16s, APTT \> 53s, TT \> 21s, Fib \< 1.5g/L), bleeding tendency or undergoing thrombolytic or anticoagulant therapy;
11. Presence of severe pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, severe impairment of lung function, or active tuberculosis within 1 year;
12. Presence of active hepatitis B or C;
13. Any other condition that the investigator evaluates to be ineligible for enrollment.