Efficacy and Safety of Tislelizumab Plus Chemotherapy as Conversion Therapy in Unresectable Locally Advanced ESCC

Inclusion criteria

• Written informed consent is obtained prior to any study-related procedures.
• Age 18 to 75 years, inclusive; both male and female patients are eligible.
• Histologically and radiologically confirmed thoracic esophageal squamous cell carcinoma (ESCC) with initially unresectable locally advanced disease, defined as:

T4b tumors invading adjacent critical structures, including the heart, great vessels, trachea, or other adjacent organs (including liver, pancreas, lung, or spleen); or Multiple-station or bulky lymph node metastases.

• No evidence of distant metastasis.
• At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Estimated life expectancy of ≥6 months.
• Adequate organ function, as defined below (without transfusion of blood products or use of hematopoietic growth factors within 14 days prior to assessment):

Hematologic function: absolute neutrophil count (ANC) ≥1,500/mm³; platelet count ≥100,000/mm³; hemoglobin ≥9 g/dL (5.6 mmol/L).

Renal function: serum creatinine ≤1.5 mg/dL and/or creatinine clearance ≥60 mL/min.

Hepatic function: total bilirubin ≤1.5 × upper limit of normal (ULN); AST and ALT ≤1.5 × ULN.

• For women of childbearing potential: must have a negative serum or urine pregnancy test within 7 days prior to enrollment, must not be breastfeeding, and must agree to use a medically acceptable method of contraception (e.g., intrauterine device, oral contraceptives, or barrier methods) during the study treatment period and for at least 3 months after the last dose.

For men with partners of childbearing potential: must agree to use a medically acceptable method of contraception during the study treatment period and for at least 3 months after the last dose.

• Willingness to participate in the study, good compliance, and ability to adhere to study procedures, including safety and survival follow-up.

Exclusion criteria

• Prior receipt of radiotherapy, chemotherapy, hormonal therapy, surgery, or molecular targeted therapy for esophageal cancer.
• Evidence of distant metastasis confirmed by imaging.
• History of other malignancies, except for adequately treated basal cell carcinoma of the skin or carcinoma in situ of the cervix.
• Prior treatment with any anti-PD-1 or anti-PD-L1 agents; known hypersensitivity to monoclonal antibodies or any component of tislelizumab.
• Active autoimmune disease or a history of autoimmune disease, including but not limited to autoimmune hepatitis, interstitial lung disease, uveitis, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, or hypothyroidism.
• Patients with vitiligo or a history of childhood asthma that has completely resolved and requires no intervention in adulthood may be eligible.
• Patients with asthma requiring bronchodilator therapy are not eligible.
• Current use of immunosuppressive medications, including systemic corticosteroids or absorbable local steroids for immunosuppressive purposes (dose >10 mg/day prednisone or equivalent) within 2 weeks prior to enrollment.

Clinically significant ascites or pleural effusion requiring therapeutic drainage.

Uncontrolled or clinically significant cardiovascular disease, including but not limited to:

New York Heart Association (NYHA) class II or higher heart failure; Unstable angina; Myocardial infarction within 1 year prior to enrollment; Clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention.

• Coagulation abnormalities, defined as: prothrombin time (PT) >16 seconds, activated partial thromboplastin time (APTT) >43 seconds, thrombin time (TT) >21 seconds, or fibrinogen (Fbg) >2 g/L; or presence of bleeding tendency, or ongoing thrombolytic or anticoagulant therapy.
• Presence of gastrointestinal conditions associated with a high risk of bleeding or perforation within 3 months prior to enrollment, including but not limited to esophageal varices, active gastric or duodenal ulcers, ulcerative colitis, portal hypertension, or unresected tumors with active bleeding; or any other condition judged by the investigator to pose a risk of gastrointestinal bleeding or perforation.