Feasibility of Circulating Tumor DNA Based Minimal Residual Disease-Guided Adjuvant Therapy in Locally Advanced Gastric Cancer With Neoadjuvant Treatment

Inclusion criteria

• Able to provide written informed consent (ICF) and capable of understanding and agreeing to comply with the study requirements and assessment schedule;
• Male or female aged ≥ 18 years;
• Histologically confirmed gastric adenocarcinoma or gastroesophageal junction adenocarcinoma, with clinical TNM stage (according to the 8th edition of the AJCC/UICC clinical TNM staging system for gastric cancer; see Appendix 1) of cIIB-IVA, and the primary gastric tumor assessed as amenable to radical resection;
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (see Appendix 2), fit to undergo surgical treatment with no contraindications to surgery;
• Capable of providing adequate tumor tissue obtained via gastroscopy (or other means) prior to neoadjuvant treatment for whole-exome sequencing;
• Females of childbearing potential must have a negative pregnancy test within 7 days before initiation of neoadjuvant treatment. Males and females of childbearing potential must agree to use adequate contraception during the study period and for 24 months after the last dose of study treatment (see Appendix 3);
• Hematologic and biochemical parameters meeting the following criteria prior to neoadjuvant treatment:

• Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L
• Platelet count (PLT) ≥ 75 × 10⁹/L
• Hemoglobin (Hb) ≥ 80 g/L
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN)
• Serum creatinine (Cr) ≤ 1.5 × ULN or estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m²
• Serum albumin (ALB) ≥ 30 g/L
• For subjects not receiving anticoagulant therapy: international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN, and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN; for subjects receiving anticoagulant therapy: PT within the expected therapeutic range for the anticoagulant;
• No prior anticancer therapy for the current study-related tumor prior to initiation of neoadjuvant treatment.

Exclusion criteria

• Patients deemed by the investigator to have significant contraindications to or intolerance of neoadjuvant/adjuvant therapy;
• Female patients of childbearing potential who have not undergone surgical sterilization or are not using adequate contraceptive measures, pregnant or lactating women, or male patients planning to father a child within a short period;
• Any severe or uncontrolled systemic disease, including but not limited to uncontrolled hypertension, active hemorrhage, diabetes mellitus, etc.;
• Severe chronic or active infections requiring systemic antibacterial, antifungal, or antiviral therapy, including tuberculosis, human immunodeficiency virus (HIV) infection, etc.;
• Prior history of malignancy or current presence of another malignancy, except for completely resected basal cell or squamous cell skin cancer, superficial bladder cancer, or in situ carcinoma of the prostate, cervix, or breast with at least 5 years without recurrence;
• Other conditions deemed by the investigator to render the patient unsuitable for study participation.