Dynamic variations in peripheral blood indices and their association with efficacy and adverse reactions of pd- 1 inhibitor combined chemotherapy in patients with advanced gastric cancer.

[BACKGROUND] Gastric cancer (GC) continues to pose a significant global health challenge, particularly in advanced stages where treatment options are severely constrained. Immunotherapy represents a groundbreaking advancement in cancer treatment, exhibiting promising therapeutic effects in patients diagnosed with gastric cancer. However, the efficacy of immunotherapy is not universally applicable to all individuals. Revealing precise biomarkers for tumor immunotherapy as targets or indicators for detection and evaluation can facilitate the resolution of this predicament. This study aims to identify serum tumor markers and blood cell ratios as predictive biomarkers to aid in the selection of gastric cancer patients who may benefit from PD-1 inhibitors therapy.

[METHODS] A retrospective analysis was conducted on the medical records and hematological data of 98 patients with HER2-negative and microsatellite-stable (MSS) metastatic gastric cancer who received first-line treatment with PD-1 inhibitors in combination with chemotherapy at our institution. We investigated peripheral blood parameters, including Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), C-Reactive Protein-to-Albumin Ratio (CAR), AFP, Carcinoembryonic Antigen (CEA), and Sugar antigens 199 (CA199). Logistic regression and Cox regression analyses were employed to assess the correlation of these parameters with treatment response and survival duration. The relationship between these indicators and overall survival was assessed by employing Kaplan-Meier survival curves, in conjunction with an analysis of Overall Response Rate (ORR), Disease Control Rate (DCR), Progression-Free Survival (PFS), Overall Survival (OS), and safety profiles..

[RESULTS] Higher pre-treatment levels of NLR, CAR, AFP, and CA199, along with subsequent reductions in NLR, CAR, and CA199 at 12 weeks post-treatment, were significantly associated with extended PFS and OS. Multivariate Cox analysis suggested that pre-treatment levels of AFP, as well as the reduction in NLR and CA199 at 12 weeks post-treatment, were strongly correlated with PFS and OS in patients with gastric cancer undergoing immunotherapy. Additionally, the reduction in NLR, CAR, and CA199 observed at 12 weeks after treatment showed a significant positive correlation with improved DCR and ORR. Multivariate logistic regression analysis indicated that the decline in NLR and CA199 levels at 12 weeks post-treatment might be associated with DCR, while pre-treatment CAR levels and the decrease in CAR after 12 weeks could potentially predict ORR in immunotherapy for gastric cancer. Notably, patients with normal AFP levels exhibited significantly prolonged median progression-free survival (mPFS) of 6.8 months and median overall survival (mOS) of 13.2 months compared to those with elevated AFP levels (mPFS: 5.2 months; mOS: 9.4 months), and this difference was statistically significant (P < 0.05).