Exploring the Efficacy of Ferrous Sulfate/Ferrous Succinate Combined With Serplulimab and SOX Regimen in Neoadjuvant Therapy for Gastric Cancer: A Prospective Cohort Study

Patients with locally advanced gastric cancer have a high risk of postoperative recurrence. Neoadjuvant chemotherapy can improve the R0 resection rate, but some patients gain limited benefit from conventional chemotherapy. The PD-1 monoclonal antibody serplulimab combined with chemotherapy has shown potential in improving response rate and survival for advanced gastric cancer. Regulation of tumor metabolism and immune microenvironment may further enhance the efficacy of immunotherapy. Ferrous sulfate supplementation improves anemia and immune cell metabolism; succinate, as a key metabolic signaling molecule, participates in inflammation and immune regulation. This study intends to explore the synergistic effect and safety of oral ferrous sulfate/ferrous succinate in serplulimab plus SOX neoadjuvant therapy.

Inclusion Criteria: * Histologically confirmed gastric adenocarcinoma * Clinically diagnosed as locally advanced gastric cancer (cT2-4aNanyM0) * Age 18-75 years, male or female * Eastern Cooperative Oncology Group (ECOG) performance status 0-1 * Adequate organ and hematologic function: * Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L * Platelets ≥ 100 × 10\^9/L * Hemoglobin ≥ 90 g/L * Total bilirubin ≤ 1.5 × upper limit of normal (ULN) * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN * Creatinine ≤ 1.5 × ULN or estimated creatinine clearance ≥ 50 mL/min * Measurable lesion according to RECIST version 1.1 * No prior anti-cancer therapy for the current gastric cancer * Willing and able to provide written informed consent Exclusion Criteria: * Histologically confirmed gastric squamous cell carcinoma, adenosquamous carcinoma, or neuroendocrine carcinoma * Distant metastasis (M1) or unresectable disease * History of other malignancies within the past 5 years (except adequately treated non-melanoma skin cancer or in situ cervical cancer) * Prior treatment with PD-1/PD-L1 inhibitors, iron supplementation, or chemotherapy for gastric cancer * Known hypersensitivity to any study drug components * Active or uncontrolled autoimmune disease * Severe cardiovascular disease (New York Heart Association class III-IV) or myocardial infarction within 6 months * Active infection requiring systemic anti-infective therapy * Pregnancy or breastfeeding women * Inability to comply with study procedures or follow-up