Efficacy and toxicity outcomes of total neoadjuvant FLOT versus perioperative FLOT in resectable gastric cancer: Results from the Turkish Oncology Gastrointestinal Cancer Working Group.

414 Background: In resectable gastric cancer, most patients are unable to complete the perioperative FLOT regimen (Per-FLOT; 4 cycles of FLOT → surgery → 4 cycles of FLOT) due to treatment intolerance. Consequently, some centers prefer total neoadjuvant FLOT therapy (TNT; 8 cycles of FLOT → surgery). In this study, we aimed to compare the efficacy and toxicity profiles of these two regimens. Methods: Our study included newly diagnosed resectable gastric cancer patients from 18 centers across Turkey between 2018 and 2025. Patients were compared according to their clinical and epidemiological characteristics using appropriate statistical methods, and survival analyses were performed with the Kaplan–Meier method and the log-rank test. Results: A total of 370 patients were included in the Per-FLOT group and 183 in the TNT group. All-grade toxicity was observed in 39 patients (21.3%) in the TNT group and 212 patients (57.3%) in the Per-FLOT group (p < 0.001, OR 5.11, 95% CI 3.38–7.72). In multivariate analyses, treatment type (TNT vs Per-FLOT) remained significantly associated with toxicity (p < 0.001) alongside hemoglobin and albumin levels. Anemia (72% vs 40%, p < 0.001), thrombocytopenia (32% vs 18%, p < 0.001), neutropenia (43% vs 26%, p < 0.001), and elevated liver function tests (33% vs 11%, p < 0.001) were more frequent in the TNT group, whereas nausea (15% vs 35%, p < 0.001), Loss of appetite (13% vs 38%, p < 0.001), fatigue (15% vs 43%, p < 0.001), diarrhea (2% vs 11%, p < 0.001), neuropathy (9% vs 16%, p = 0.054), and myalgia (3% vs 10%, p = 0.004) were more common in the Per-FLOT group. Survival analyses revealed no significant difference in OS (p = 0.77) or PFS (p = 0.22). In the TNT group, 23% of patients achieved a complete pathological response, 48.5% a partial response, and 28.5% a minimal response. In the Per-FLOT group, the rates of complete, partial, and minimal pathological responses were 15.8%, 56.5%, and 27.7%, respectively (p = 0.09). Treatment completion rates were significantly higher in the TNT group (97.3%) compared with the Per-FLOT group (82.2%) (p < 0.001). Conclusions: TNT FLOT showed similar efficacy but was associated with significantly higher treatment completion and a more favorable overall toxicity profile compared with perioperative FLOT. These findings support TNT FLOT as a promising alternative strategy in resectable gastric adenocarcinoma.