Early Response-guided Sequential Radiotherapy After Chemoimmunotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma

Korábbi kezelés

• Previous or concurrent malignancy, except adequately treated basal cell carcinoma of skin or cervical carcinoma in situ.
• Previous thoracic radiotherapy.
• Previous treatment with PD-1, PD-L1, or CTLA-4 inhibitors, or known hypersensitivity to PD-1 inhibitors or macromolecular protein products.
• Current use of immunosuppressive therapy or systemic corticosteroids exceeding the equivalent of prednisone 10 mg/day within 2 weeks before enrollment.
• Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks before study treatment.
• Participation in another clinical trial within 1 month before enrollment or concurrent systemic anticancer therapy.
• Receipt of live vaccines within 4 weeks before treatment or planned live vaccination during study treatment.

Más betegség

• Active autoimmune disease or history of clinically significant autoimmune disease requiring systemic treatment.
• Uncontrolled cardiovascular disease, including:
• NYHA class II or higher heart failure;
• Unstable angina;
• Myocardial infarction within 1 year;
• Clinically significant arrhythmias requiring treatment.
• Significant coagulation abnormalities, bleeding tendency, or ongoing thrombolytic/anticoagulant therapy.
• Active gastrointestinal disorders associated with bleeding or perforation risk, including esophageal varices, active gastric/duodenal ulcer, ulcerative colitis, portal hypertension, or active tumor bleeding.
• History of severe bleeding, clinically significant hemoptysis, or thromboembolic events within specified periods.
• Active infection or unexplained fever >38.5°C before treatment initiation.
• History or evidence of interstitial lung disease, pulmonary fibrosis, radiation pneumonitis, drug-induced pneumonitis, pneumoconiosis, or severe pulmonary impairment.
• Known immunodeficiency, including HIV infection, or active hepatitis infection requiring exclusion according to protocol criteria.
• Known history of substance abuse, alcoholism, or drug abuse.
• Any other medical, psychological, social, or safety-related condition judged by the investigator to make the participant unsuitable for study participation.

Egyéb

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• Participants will be excluded if any of the following criteria apply:
• Evidence of distant metastasis.
• Clinically significant ascites or pleural effusion requiring therapeutic drainage.
• Inability or unwillingness to comply with study-related procedures, examinations, or required costs.

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• Participants must meet all of the following criteria:
• Provide written informed consent before enrollment.
• Age >18 years, male or female.
• Histologically confirmed thoracic esophageal squamous cell carcinoma (ESCC).
• Locally advanced, resectable disease according to AJCC/UICC 8th edition TNM staging system, defined as:
• cT3-4aN0-2M0 or cT1-2N1-2M0;
• No evidence of distant metastasis;
• Considered initially resectable by a multidisciplinary surgical team.
• Patients who have received neoadjuvant chemoimmunotherapy and have measurable disease response assessment according to RECIST v1.1, including complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD).
• At least one measurable lesion according to RECIST version 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Expected survival time >6 months.
• Adequate organ function meeting the following criteria:
• Bone marrow function:
• Absolute neutrophil count ≥1,500/mm³;
• Platelet count ≥100,000/mm³;
• Hemoglobin ≥9 g/dL.
• 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.
• Participants of childbearing potential must agree to use medically approved contraception during study treatment and for 3 months after completion of treatment. Female participants of childbearing potential must have a negative serum or urine pregnancy test within 7 days before enrollment and must not be breastfeeding.
• Willingness and ability to comply with study procedures, safety assessments, and survival follow-up.