Sintilimab Combined With Chemoradiotherapy as Neoadjuvant Therapy for Locally Advanced Gastroesophageal Junction Cancer

Prior treatment

• Patients considered unsuitable by the multidisciplinary team for neoadjuvant chemoradiotherapy, immunotherapy, or subsequent radical surgery.
  • Definite distant metastasis, peritoneal dissemination, or other M1 disease. Previous surgery, radiotherapy, chemotherapy, targeted therapy, or immunotherapy for the current gastroesophageal junction tumor.
  • Previous radiotherapy to the mediastinum, upper abdomen, or gastroesophageal junction region that may affect radiotherapy administration or safety assessment.
  • Severe hypersensitivity to sintilimab, oxaliplatin, capecitabine, or related components.
  • Unhealed gastrointestinal perforation, gastrointestinal fistula, active gastrointestinal bleeding, complete obstruction, or other severe gastrointestinal disease that may substantially increase treatment risk.
  • Active autoimmune disease or a history of autoimmune disease requiring systemic immunosuppressive treatment that may increase the risk of immunotherapy.
  • Grade ≥2 peripheral sensory neuropathy at baseline. Uncontrolled serious infection, including active hepatitis B, hepatitis C, HIV infection, or other infection considered clinically significant by the investigator.
  • Serious cardiovascular or cerebrovascular events within 6 months before enrollment, uncontrolled arrhythmia, or NYHA class III-IV heart failure.
  • Uncontrolled hypertension, severe hepatic or renal dysfunction, severe pulmonary disease, active interstitial lung disease, or other serious underlying disease that may affect treatment or surgical safety.
  • Pregnant or breastfeeding women, or individuals of childbearing potential unwilling to use effective contraception during study treatment and for the protocol-specified period after the last dose.
  • Other malignancy within the previous 5 years, except specified low-risk malignancies.
  • Psychiatric disorders, substance abuse, or other conditions that may interfere with informed consent, treatment adherence, or follow-up.
  • Participation in another interventional clinical study or any other condition considered inappropriate for study participation by the investigator.

• Age 18 to 75 years, regardless of sex, willing to participate in the study and able to provide written informed consent.
  • Histologically confirmed gastroesophageal junction adenocarcinoma. Tumor classification meeting the definition of Siewert type I, II, or III gastroesophageal junction adenocarcinoma.
  • Locally advanced, resectable or potentially resectable disease based on baseline imaging, with clinical stage cT2-4aN0-3M0 or cT1N+M0.
  • No previous surgery, radiotherapy, chemotherapy, targeted therapy, or immunotherapy for the current gastroesophageal junction tumor.
  • Measurable/evaluable primary tumor and/or regional lymph node lesions on baseline imaging.
  • Considered suitable by a multidisciplinary team for sintilimab plus XELOX induction therapy, sintilimab plus capecitabine concurrent chemoradiotherapy, and optional sintilimab plus XELOX consolidation therapy, with the potential to undergo radical surgery.
  • ECOG performance status of 0-1. Adequate major organ function to receive study treatment and subsequent surgery.
  • Able to understand and comply with the study treatment, assessments, surgery, and follow-up procedures and provide written informed consent.