AI-Driven Digital Twin and Drug Simulation for Esophageal Cancer

Prior treatment

• Unstable angina within 3 months or myocardial infarction within 6 months prior to enrollment.
• Known or concurrent hemorrhagic disorders.
• Patients with pre-existing or concurrent pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, or other severe pulmonary impairment.

Other illness

• Presence of multiple primary malignancies (synchronous or metachronous).
• Active infections requiring systemic treatment.
• Requirement for continuous systemic corticosteroid therapy (\>10 mg/day prednisone or equivalent) for comorbid conditions.
• Psychiatric disorders that may affect study compliance.
• Autoimmune diseases, immunodeficiency states, or history of organ transplantation.
• Known hypersensitivity to the study drugs (toripalimab, paclitaxel, cisplatin) or their excipients.
• Active hepatitis B (HBV) or hepatitis C (HCV) infection. (Patients who are HBsAg positive or HBcAb positive may be eligible if HBV DNA is below the lower limit of detection/quantification; patients who are HCV antibody positive may be eligible if HCV RNA is below the lower limit of detection/quantification.)
• Human immunodeficiency virus (HIV) positivity.
• Any other condition that, in the investigator's judgment, may compromise patient safety, interfere with study compliance, or preclude successful completion of the study.

Lab values

• Abnormal coagulation function (PT \> 16s, APTT \> 53s, TT \> 21s, Fib \< 1.5 g/L), bleeding tendency, or patients receiving thrombolytic or anticoagulant therapy.

Other

• Patients not meeting the inclusion criteria.
• Female patients who are pregnant or breastfeeding.
• Bronchial asthma requiring intermittent use of bronchodilators or medical intervention.

• Treatment-naïve patients with clinical stage locally advanced (T1N1-3M0 or T2-3N0-3M0) thoracic esophageal squamous cell carcinoma, according to the 8th UICC-TNM staging system.
• Cervical color Doppler ultrasound shows no suspicious metastatic lymph nodes, or patients with suspected lymph node metastasis on ultrasound who are eligible for three-field lymphadenectomy.
• No prior antitumor therapy for esophageal cancer (including chemotherapy, radiotherapy, or immunotherapy).
• Preoperative evaluation of organ function indicates no surgical contraindications.
• Adequate bone marrow, liver, and renal function, confirmed by the following laboratory tests performed within 7 days prior to enrollment:
  • Hemoglobin ≥ 90 g/L;
  • White blood cell count ≥ 4.0 × 10\^9/L;
  • Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L;
  • Platelet count ≥ 100 × 10\^9/L;
  • Total bilirubin ≤ 1.5 × upper limit of normal (ULN);
  • ALT and AST ≤ 2.5 × ULN;
  • International normalized ratio (INR) of prothrombin time ≤ 1.5 × ULN, with activated partial thromboplastin time (APTT) within normal range;
  • Serum creatinine ≤ 1.5 × ULN.
• No prior chemotherapy, radiotherapy, or hormone therapy for malignant tumors; no history of other malignancies, except for prostate cancer patients who received hormone therapy and have achieved disease-free survival (DFS) \> 5 years.
• Expected to achieve R0 resection.
• Eastern Cooperative Oncology Group (ECOG) performance status score 0 to 1.
• Life expectancy ≥ 3 months.
• Women of childbearing potential must agree to use effective contraceptive measures (e.g., intrauterine device, oral contraceptives, or condoms) during the study and for 6 months after study completion. Serum or urine pregnancy test must be negative within 7 days prior to enrollment, and patients must not be breastfeeding. Male patients must agree to use contraceptive measures during the study and for 6 months after study completion.
• Patients must voluntarily participate in the study, provide written informed consent, demonstrate good compliance, and agree to follow-up.