Prognostic Biomarkers and Targeted Therapy in Gastric Cancer: Reply Gennaro Galizia Æ Eva Lieto Æ Michele Orditura Æ Paolo Castellano Æ Anna La Mura Æ Vincenzo Imperatore Æ Margherita Pinto Æ Anna Zamboli Æ Ferdinando De Vita Æ Francesca Ferraraccio Published online: 15 January 2008 Ó Socie ´te ´ Internationale de Chirurgie 2008 We very much appreciate the interest in our article, ‘‘Epi- dermalGrowth FactorReceptor(EGFR) Expression Is Associated with aWorsePrognosisin GastricCancer Patients Undergoing Curative Surgery’’ (World Journal of Surgery, 2007; 31:1458–1468) expressed by Liakakos et al. (DOI:10.1007/s00268-9434-3), from the well-known and distinguished oncological team of the Ioannina University School of Medicine, Greece. Gastric cancer is the fourth most common cancer world- wide, with an estimated 934,000 new cases per year, and it is the second most common cause of cancer deaths worldwide, with an estimated 700,000 deaths annually [ 1]. Complete tumor removal by surgery, so called R0 resection, is the only available treatment to provide cure in localized, nonmeta- static gastric cancer [2]. However, even after a R0 resection, locoregional recurrence and metastatic spread frequently occur, accounting for the still modest 5-year survival rates (35%–45% in Westerncountries)[3, 4]. Integrated treatments have been advocated to reduce postoperative relapse rates. In the USA,adjuvant 5-fluorouracil (5-FU)- based chemoradiotherapy after limited D1 gastrectomy is established as standard treatment [5]; and in the UK, sinc perioperative ECF (epirubicin, cisplatin, 5-FU) chemother- apy significantly improved survival after D2 gastrectomy [6],it was proposed as the standard treatment for gastric cancer patients undergoing potentially curative surgery [ 7 Despite tremendous efforts to improve the clinical out- comesof resectedpatients,no definitiveconclusions concerning the efficacy of adjuvant chemotherapy were reached until the recent reportof a Japanese ACTS-GC trial thatis the firststudy showing, in II and III TNM stages, a significantly better long-term survival in gastric cancer patients treated with radical surgery plus oral S-1 (tegafur, gimeracil, and oteracil) than in patients under- going surgery alone (3-year survival rates were 80.5% and 70.1%,respectively; hazard ratio 0.68 [95% confidence interval 0.52–0.87], p = 0.0024) [8]. These combined-modality treatments have been highly questioned, however, because of eligibility criteria, very tr benefits, and,limited to the single Japanese trial, doubts about the use of S-1 in Western patients who seem to tole this drug very poorly because of the genetic polymorphism the tegafur-converting enzyme, CYP2A6 [ 9–12]. Moreover, different clinical outcomes among patients in the same TN stage receiving the same integrated treatments suggest, on the one hand, biological and clinical heterogeneity of gast cancer, and, on the other hand, an urgent need to investig new prognostic factors capable of selecting patients with a high risk of recurrence [13]. Thus, controversy still exists about the best managemen of gastric cancer [14]. Recently, it has been suggested that molecularly based approaches may be critical in predicting clinical outcome G. Galizia (&) E. Lieto P. Castellano V. Imperatore M. Pinto A. Zamboli Division of Surgical Oncology, ‘‘F. Magrassi - A. Lanzara’’ Department of Clinical and Experimental Medicine and Surgery, Second University of Naples School of Medicine, c/o II Policlinico,Edificio 17, Via Pansini, 5, 80131 Naples, Italy e-mail: gennaro.galizia@unina2.it M. Orditura F.De Vita Division of Medical Oncology, ‘‘F. Magrassi - A. Lanzara’’ Department of Clinical and Experimental Medicine and Surgery, Second University of Naples School of Medicine, c/o II Policlinico,Edificio 17, Via Pansini, 5, 80131 Naples, Italy A. L. Mura F. Ferraraccio Division of Pathology, ‘‘F. Magrassi - A. Lanzara’’ Department of Clinical and Experimental Medicine and Surgery, Second University of Naples School of Medicine, c/o II Policlinico, Edificio 17, Via Pansini, 5, 80131 Naples, Italy 123 World J Surg (2008) 32:1227–1229 DOI 10.1007/s00268-007-9335-5