Gastric cancer has a high incidence and mortality rate worldwide. Epidemiological, clinical, and molecular features significantly impact patient outcomes. In regions lacking a national gastric cancer registry, hospital-based registries can provide crucial data that may aid in planning therapeutic strategies for the disease. A retrospective observational cohort design was carried out in European Union (EU) and Latin American (LATAM) countries participating in the LEGACy project. Survival estimates were determined using actuarial Kaplan–Meier curves. Comparison was carried out with the log-rank test, and differences were considered statistically significant for P values ≤0.05. A total of 689 patients diagnosed with gastric cancer from November 2018 to November 2019 were included. Both cohorts had the body as the most common site reported (34.4% for EU and 51% for LATAM). The most used method for staging was computed tomography for both cohorts, although 6.9% of the LATAM population had positron emission tomography/computed tomography instead. Intestinal histological subtype was the most common (41.9% and 46.3% reported by EU and LATAM), while diffuse subtype was 44.9% for the LATAM and 21.3% for the EU population. Among patients tested for human epidermal growth factor receptor 2 (HER2), 12.5% were positive in the EU cohort and 13.8% in the LATAM cohort. For both cohorts, the most common site of human epidermal growth factor receptor 2 positivity was the gastroesophageal junction. Systemic treatment with curative intention was indicated in 50.7% in the EU cohort and 46.4% of the LATAM cohort. The most frequent scheme indicated for both the localized and the advanced setting was platinum-based (42.6% and 84.8% for EU and LATAM). Considering both cohorts, only 14.4% of the patients received second-line treatment, and 3% received a third-line treatment. After using Cox regression analysis, no difference in overall survival was reported, with a median of 10.9 months. Despite the limitations of hospital-based registry analysis, our study has provided valuable insights into clinical characteristics and treatment approaches of EU and LATAM populations.

Background: Gastric cancer (GC) patients from European (EU) and especially Latin American (LATAM) countries are underrepresented in previous large-scale multi-omic studies that have identified clinically relevant subgroups. The LEGACY study aimed to profile the molecular and immunological features of GCs from EU and LATAM countries. Methods: Tumor biopsies from 95 EU and 56 LATAM GCs were profiled with immunohistochemistry (CD3, CD8, FOXP3, PD-L1, MSI and HER2), Nanostring mRNA expression analyses, and microbiome sequencing. Results: Immune profiling identified four distinct immune clusters: a T cell dominant cluster with enriched activation pathways, a macrophage dominant cluster and an immune excluded microenvironment which were equally distributed among the countries. A fourth cluster of mostly Mexican patients consisted of excessive T cell numbers accompanied by enhanced cytokine signaling in absence of enhanced antigen presentation and cytotoxicity signatures and a strong association with H. pylori infection. Discussion: Both EU and LATAM countries have GCs with a T cell inflamed microenvironment that might benefit from checkpoint inhibition. We identified a highly inflamed GC subgroup that lacked antigen presentation and cytotoxicity associated with H. pylori CagA-positive strains, suggesting their contribution to tumor immune tolerance. Future studies are needed to unravel whether these cancers benefit from immunotherapy as well.