Efficacy and safety of neoadjuvant FLOT treatment for resectable gastric/gastroesophageal junction adenocarcinoma in Turkish and German patients; a real-world data.

backgroundPerioperative FLOT is the current standard of treatment in resectable gastric adenocarcinoma(GC) and adenocarcinoma of gastroesophageal junction(GEJC). However, many ethnicities remain underrepresented in clinical trials or are not differentiated in subgroup analyses, making it unclear whether outcomes, especially major pathological response (mPR), vary across different populations.

methodsTurkish(Tp) and German(Gp) patients with resectable GC/GEJC who received perioperative FLOT were evaluated retrospectively. The primary endpoint was mPR which was defined as pathological complete response or near-complete response. The secondary endpoints were disease-free survival(DFS), overall survival(OS), and safety.

resultsForty-seven Tp and 55 Gp were included. While Tp had more GC(63.8% vs. 36.2%), GEJC was higher in Gp(41.8% vs. 58.2%)(p = 0.027). Tp had more node-positive diseases(91.5% vs. 63.6%, p = 0.005), and received more cycles of neoadjuvant FLOT(p < 0.001). The most commonly seen side effects were anemia in Tp, and neutropenia and neuropathy in Gp. R0 resection ratio was 87.2% in Tp and 92.7% in Gp. The ratio of mPR was higher in Gp (36% vs. 18.5%, p = 0.04) While German ethnicity and clinical node negativity was associated with better mPR in the univariate analysis, only clinical node negativity was associated with better mPR in the multivariate analysis [OR:3.951, 95% CI (1.168-13.365), p = 0.027]. There was no relation between mPR and other clinical factors including tumor location, histology and intensified neoadjuvant treatment (> 4 cycles of FLOT). Gp had longer DFS(53.22 vs. 21.42 months, p = 0.03) and OS(57.99 vs. 29.37 months, p = 0.05). However, mPR did not show any association with OS and DFS. Turkish ethnicity was related with worse OS and DFS in univariate analysis but not multivariate analysis. Multivariate analysis showed that intensified neoadjuvant treatment(> 4 cycles), signet-cell carcinoma, and higher pathological N-stage were independent risk factors for decreased OS. After adjusting for clinical node positivity and tumor location; intensified neoadjuvant treatment(> 4 cycles), and higher pathological N stage remained associated with worse OS. DISCUSSION: This bicentric study reveals that although ethnicity had limited prognostic impact, lymph node status remained the strongest determinant of outcome in perioperatively treated patients with GC/GEJC. Intensified treatment did not improve mPR and was associated with worse OS, while mPR itself was not independently linked to OS. Pathological nodal positivity and signet-ring cell carcinoma were the key predictors of poor survival. These findings highlight the importance of nodal risk stratification and tailored follow-up over therapy intensification.