Abstract Background：Gastroesophageal junction (G/GEJ) cancer is a global health burden with poor prognosis, especially for locally advanced or metastatic cases. While perioperative chemotherapy improves outcomes, survival remains limited. Immunotherapy combined with chemotherapy has shown promise in advanced disease, prompting investigations into neoadjuvant settings. This study evaluates a novel regimen of low-dose interval radiotherapy, tislelizumab (a PD-1 inhibitor), and SOX chemotherapy (oxaliplatin + S-1) for locally advanced G/GEJ adenocarcinoma. Methods and analysis：This is a prospective, single-center, single-arm clinical trial enrolling 32 patients with cT4N+M0 G/GEJ adenocarcinoma. The neoadjuvant regimen includes 5×3Gy radiotherapy in cycles 1 and 3, tislelizumab (200 mg IV D6), oxaliplatin (130 mg/m² IV D6), and S-1 (40 mg/m²oral BID D6–19), with 4 cycles of SOX adjuvant chemotherapy post-surgery. Primary endpoints are pathological complete response (pCR), major pathological response (MPR), and objective response rate (ORR). Secondary endpoints include R0 resection rate, safety, complications, event-free survival (EFS), and overall survival (OS). Discussion: This study explores a novel neoadjuvant regimen combining low-dose interval radiotherapy with immunotherapy and chemotherapy for locally advanced GC/GEJ. The combination is expected to significantly increase the pCR rate and improve other therapeutic outcomes while maintaining safety. Ethics and dissemination: The study was approved by the Ethical Committee of the Shandong Provincial Hospital Affiliated to Shandong First Medical University and registered with ClinicalTrials.gov (NCT06766578). Trial registration：ClinicalTrials.gov (NCT06766578)
Shang et al. (Fri,) studied this question.