Background: Neoadjuvant chemotherapy is frequently applied to improve the prognosis of patients with locally advanced gastric cancer. However, only a major histopathological response will provide a survival benefit in these patients. Recent studies suggest that [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) significantly correlates with histopathological response and survival in patients with gastroesophageal adenocarcinomas undergoing neoadjuvant chemotherapy followed by surgical resection. Therefore, we evaluated the potential of FDG-PET) for the assessment of histopathologic response and prognosis in the multimodality treatment of patients with gastric cancer.Methods: Study patients were recruited from a prospective clinical observation trial on neoadjuvant chemotherapy for gastric cancer between 1997 and 2007. Forty-two patients with locally advanced gastric cancer (cT3-4, Nx, M0) were included (33 men, 9 women; median age 57 years). All patients received neoadjuvant chemotherapy according to the PLF-protocol (cisplatin, leucovorin, 5-FU; 2 cycles over 6 weeks) and subsequently 40 patients underwent standardized total gastrectomy while 2 patients received definitive chemotherapy because of tumor progression. Histomorphologic regression was defined as major histopathological response when resected specimens contained less than 10 % vital residual tumor cells. FDG-PET was performed before and 2 weeks after the end of neoadjuvant chemotherapy with assessment of the intratumoral FDG-uptake [pre-treatment standardized uptake value (SUV1); post-treatment standardized uptake value (SUV2); percentage change (SUVΔ%)]. These variables were correlated with histopathological response and survival.Results: Neoadjuvant chemoradiation led to a significant reduction of intratumoral FDG-uptake (p=0.0006). However, no significant correlations between SUV1, SUV2 or SUVΔ% and histopathological response or prognosis were found. Histomorphological tumor regression was confirmed as an important prognostic factor (p=0.04; log-rank test).Conclusion: Our study does not support recent reports that the metabolic response by FDG-PET is associated with histomorphological response or survival in patients with gastric cancer following neoadjuvant therapy and gastrectomy.