Dynamic programmed death-ligand 1 and multimodal biomarkers in gastric cancer immunotherapy

Table 1 Proposed dynamic biomarker monitoring in gastric cancer immunotherapy¹

Ref.	Timepoint	Assessments	Evidence-based rationale
Jiang et al[38], 2024; Li et al[59], 2025; Jiang et al[60], 2023	Baseline (pre-treatment)	PD-L1 CPS, MSI status (MMR), EBV status, ctDNA (tumor-informed if possible), CEA/CA19-9/CA72-4	(1) PD-L1 CPS, MSI-H/dMMR, and EBV positivity are validated predictive biomarkers for ICI benefit in advanced GC; (2) Baseline ctDNA reflects tumor burden and genomic landscape; tumor-informed assays may offer improved sensitivity compared with tumor-naïve panels; and (3) CEA/CA19-9/CA72-4 are prognostic but not validated predictive markers for ICI response
Jiang et al[38], 2024; Jin et al[45], 2020	After 2 cycles (approximately 6-8 weeks)	ctDNA kinetics, CEA/CA19-9/CA72-4	Early decline or clearance of ctDNA correlates with objective response and improved survival in GC treated with ICIs ± chemotherapy; CEA/CA19-9/CA72-4 decline may reflect treatment response but lacks immunotherapy-specific validation
Jiang et al[61], 2023	First radiographic evaluation (approximately 8-12 weeks)	CT imaging (RECIST/iRECIST), tumor markers (CEA, CA19-9, CA72-4)	Standard efficacy assessment; follow-up every 8-12 weeks is recommended per iRECIST guidelines
Nguyen et al[62], 2025	Every 12 weeks thereafter	ctDNA monitoring (if available), imaging as per protocol	Serial ctDNA kinetics may detect molecular progression earlier than imaging; timing, thresholds, and clinical algorithms remain unstandardized in GC
Fan et al[32], 2019; Ayala-Mar et al[33], 2021	Exploratory (research setting only)	Exo-PD-L1	Preliminary GC studies suggest a potential association with disease progression; currently investigational with no standardized clinical application

¹Proposed monitoring intervals are derived from current literature and clinical practice patterns but are not yet standardized in gastric cancer immunotherapy.

GC: Gastric cancer; PD-L1: Programmed death-ligand 1; iRECIST: Immune response evaluation criteria in solid tumors; CPS: Combined positive score; MSI: Microsatellite instability; MMR: Mismatch repair; EBV: Epstein-Barr virus; ctDNA: Circulating tumor DNA; CEA: Carcinoembryonic antigen; CA19-9: Carbohydrate antigen 19-9; CA72-4: Carbohydrate antigen 72-4; dMMR: Deficient mismatch repair; ICI: Immune checkpoint inhibitor; CT: Computed tomography; Exo-PD-L1: Exosome-programmed death-ligand 1.