Clinico-pathological features and the role of CD4/CD8 lymphocyte ratio in predicting response to neoadjuvant FLOT (5-fluorouracil, leucovorin, oxaliplatin, and docetaxel) chemotherapy in locally advanced gastric cancer

Objectives: Neoadjuvant chemotherapy (NACT) is recommended in resectable, locally advanced gastric cancer (GC) patients, but only about 40% have a pathological response. There is a delay in definitive management for those who don’t respond. Predictive biomarkers will show which group of patients benefits from NACT. The aim was to study clinic-pathological features and CD4/CD8 ratio as a predictive marker for response to NACT in GC patients. Material and Methods: A prospective study of GC patients was conducted at our institute from January 2023 to December 2024. Patients >18y, PS 0/1, gastric or gastroesophageal junction (GEJ) adenocarcinoma, stage ≥ T2 and/or Node positive, non-metastatic patients who underwent curative surgery after NACT: 5-Fluorouracil, leucovorin, oxaliplatin, docetaxel (FLOT) chemotherapy were included. CD4 and CD8 cells were calculated by immunohistochemistry (IHC) on the pre-chemotherapy biopsy. Tumor regression grade (TRG) assessments were done by the modified Ryan criteria. Clinicopathological factors, including the CD4/CD8 ratio, were correlated with TRG. Results: 90 patients were studied. 83% (N=75) of the patients underwent definitive surgery and were included for analysis. Median age was 55 years (35-70). Males were 71%. The most common symptom was abdominal pain (55%). 39% were smokers. The most common site was GEJ (40%). 9% had signet-ring histology. 27% had grade 3/4 neutropenia. All had R0 resection. 8% achieved pathological CR. 60% received adjuvant chemotherapy (21% FOLFOX or 5FU/LCV, 39% FLOT). There was a statistically significant correlation between TRG and smoking history (p value 0.02); site of tumor (Proximal versus distal) (p value 0.03); and CD4/CD8 ratio (p value <0.001). Conclusion: Patients who were nonsmokers, those with proximal GCs, and those with a higher CD4/CD8 ratio showed better response to FLOT NACT. CD4/CD8 ratio can be used as a biomarker that predicts response to FLOT NACT in operable gastric cancer patients.