For patients with unresectable locally advanced or metastatic gastric cancer, systemic anti-tumor therapy remains the mainstay of treatment. Combining chemotherapy with immune checkpoint inhibitors has gradually become the standard first-line treatment for advanced gastric cancer. Radiotherapy can enhance the release of tumor-associated antigens, thereby improving the responsiveness of MSS/pMMR tumors to PD-1 inhibitors. Tumor-draining lymph nodes (TDLNs) are key sites for the anti-tumor activity of PD-1 blockade; however, radiation-induced damage and fibrosis may impair lymphatic drainage and local immune responses. Previous studies have suggested that irradiation of the primary tumor combined with immune checkpoint blockade can produce an abscopal effect, mediating regression of distant metastases. This study aims to evaluate whether node-sparing modified short-course radiotherapy followed by chemotherapy and PD-1 blockade can improve 2-year progression-free survival (PFS) in patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma.
Voluntarily signs a written informed consent form.
Aged between 18 and 75 years at the time of enrollment.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Expected survival of more than 3 months.
• Radiotherapy within 4 weeks prior to enrollment or radionuclide therapy within 8 weeks, except for palliative radiotherapy to bone metastases.
History of other malignancies within 5 years prior to enrollment, except for those considered cured by local therapy, such as basal cell carcinoma, squamous cell carcinoma of the skin, superficial bladder cancer, or ductal carcinoma in situ of the breast.
Gastrointestinal perforation and/or fistula within 6 months prior to enrollment.
Clinically significant bowel obstruction.