Despite improvements in adjuvant therapies for gastric cancer in recent years, the disease is characterized by high recurrence rates and a dismal prognosis. The major improvement in the treatment of recurrent or metastatic gastric cancer in recent years has been the incorporation of trastuzumab, a monoclonal antibody that inhibits human epidermal growth factor receptor 2 (HER2) heterodimerization, after the demonstrated predictive value of the overexpression and/or amplification of this receptor. Beyond HER2, other genetic abnormalities have been identified, and these mutations may be targetable by tyrosine kinase inhibitors or monoclonal antibodies. The demonstration of four distinct molecular subtypes of gastric cancer by the Cancer Genome Atlas study highlight the enormous heterogeneity of the disease and its complex interplay between genetic and epigenetic alterations and provide a roadmap to implement genome-guided personalized therapy in gastric cancer. In the present review, we aim to discuss, from a clinical point of view, the genomic landscape of gastric cancer described in recent studies, the therapeutic insights derived from these findings, and the clinical trials that have been conducted and those in progress that take into account tailored therapies for gastric cancer.

The cure fraction models are usually used to model lifetime time data with long-term survivors. In the present article, we introduce a Bayesian analysis of the four-parameter generalized modified Weibull (GMW) distribution in presence of cure fraction, censored data and covariates. In order to include the proportion of "cured" patients, mixture and non-mixture formulation models are considered. To demonstrate the ability of using this model in the analysis of real data, we consider an application to data from patients with gastric adenocarcinoma. Inferences are obtained by using MCMC (Markov Chain Monte Carlo) methods.

BackgroundThere is no consensus about the prognostic role of HER2 expression and that of other members of the EGFR family in gastric cancer patients. The aim of this study was to evaluate the prognostic value of the EGFR family in gastric cancer.MethodsThis retrospective study included 201 patients with gastric and esophagogastric junction adenocarcinoma stages 0–IV (AJCC 6th edition) who underwent primary tumor resection. Tissues from primary tumors were analyzed by tissue microarray technology and immunohistochemistry. Correlations between receptor expression and clinicopathological characteristics were performed according to the chi-square test. Survival analysis was calculated according to the Weibull model with a mixture model incorporating long-term survivors. Multivariate analysis of prognostic factors was performed by a regression model incorporating long-term survivors with the Weibull distribution.ResultsMembrane expression of HER1, HER2, and HER4 were 9, 17, and 15 %, respectively. No membrane expression of HER3 was observed. Cytoplasmic expression of HER1, HER3, and HER4 were 45, 62, and 24 %, respectively. HER2 and HER3 expression were correlated (p < 0.001) and associated with intestinal-type histology (p = 0.001 and p < 0.001, respectively) and advanced age (p = 0.011 and p = 0.008, respectively). According to a regression model adjusted for age, surgical radicality, surgical modality, Laurén histology, adjuvant therapy, TNM stage, and receptor expressions, only TNM stage showed prognostic influence.ConclusionsAccording to analysis by a parametric model, the EGFR family did not have prognostic influence in the gastric cancer population studied. The data presented showed a correlation between HER2 and HER3 expression, which might suggest a potential role for HER2–HER3 heterodimerization inhibitors.

BackgroundAdjuvant chemoradiotherapy (CRT) is the standard treatment in Western countries for gastric cancer patients submitted to curative resection. However, the role of adjuvant CRT in gastric cancer treated with D2 lymphadenectomy has not been well defined.MethodsWe conducted a retrospective study in patients with stage II to IV gastric adenocarcinoma with no distant metastases, who underwent curative resection with D2 lymphadenectomy between January 2002 and December 2007. The present study compared the 3-year overall survival of two treatments (adjuvant CRT according to the INT 0116 trial versus resection alone). Survival curves were estimated by the Kaplan–Meier method and compared with a log-rank test. Multivariate analysis of prognostic factors was performed by the Cox proportional hazards model.ResultsA total of 185 patients were included, 104 patients (56 %) received adjuvant CRT and 81 received resection alone. The 3-year overall survival was 64.4 % in the CRT group and 61.7 % in the resection-alone group (p: 0.415). However, according to the Cox proportional hazards model, adjuvant CRT was a prognostic factor for 3-year overall survival (hazard ratio [HR] 0.46, 95 % confidence interval [CI] 0.26–0.82, p: 0.008).ConclusionsIn the present study, adjuvant CRT was associated with a lower risk of death over a 3-year period in gastric cancer patients treated with D2 lymphadenectomy.

Gastric cancer is one of the main cancer-related causes of death worldwide. The curative treatment of gastric cancer consists of tumor resection and lymphadenectomy. However, surgical treatment alone is associated with high recurrence rates. Adjuvant treatment strategies have been studied over the last decades, but there have been controversial results from the initial studies. The pivotal INT0116 study demonstrated that the use of adjuvant chemoradiotherapy with 5-fluorouracil increases relapse-free and overall survival, and it has been adopted across the Western world. The high toxicity of radiochemotherapy and suboptimal surgical treatment employed, with fewer than 10% of the patients submitted to D2 lymphadenectomy, were the main study limitations. Since its publication, other adjuvant treatment modalities have been studied, and radiochemotherapy is being refined to improve its efficacy and safety. A multimodal approach has been demonstrated to significantly increase relapse-free and overall survival, and it can be offered in the form of perioperative chemotherapy, adjuvant chemoradiotherapy or adjuvant chemotherapy, regardless of the extent of lymphadenectomy. The objective of the present review is to report the major advances obtained in the last decades in the adjuvant treatment of gastric cancer as well as the perspectives of treatment based on recent knowledge of the molecular biology of the disease.