Spots Global Cancer Trial Database for Dissecting the Role of MIcrobioMe in gastroEsophageal Tumor: a multIdisCiplinary Longitudinal Study

Study Description

Brief Summary: Gastric cancer (GC) is the second leading cause of cancer mortality and remains the fourth common cancer worldwide. Gastric and esophageal cancers treated with curative intent both have a poor prognosis with five-year survival rate varying between 30% and 40% \[Hagen\]. Therefore, even in the localized or locally advanced (LA) disease, relapse-related death remains a major challenge for curative treatment. Currently, there are several strategies for the curative treatment of GC including perioperative chemotherapy (peri-Op cht), adjuvant chemotherapy and adjuvant chemoradiotherapy. Despite the therapeutic management of localized or LA GC is well established, there is uncertainty about the power of prognostic and predictive factors to tailor anticancer treatments. In addition to that, further investigation is needed to investigate if pre-existing environment factors may act on carcinogenesis and to explore the molecular mechanisms that underlying cancer growth and invasiveness.

Detailed Description: Gastric cancer (GC) is the second leading cause of cancer mortality and remains the fourth common cancer worldwide. Gastric and esophageal cancers treated with curative intent both have a poor prognosis with five-year survival rate varying between 30% and 40%. Therefore, even in the localized or locally advanced (LA) disease, relapse-related death remains a major challenge for curative treatment. Currently, there are several strategies for the curative treatment of GC including perioperative chemotherapy (peri-Op cht), adjuvant chemotherapy and adjuvant chemoradiotherapy. Despite the therapeutic management of localized or LA GC is well established, there is uncertainty about the power of prognostic and predictive factors to tailor anticancer treatments. In addition to that, further investigation is needed to investigate if pre-existing environment factors may act on carcinogenesis and to explore the molecular mechanisms that underlying cancer growth and invasiveness. Gastric carcinogenesis arises as a consequence of a complex interaction between host and environmental factors. It is known that dietary, lifestyle and metabolic factors are implicated in GC. However, although their impact in terms of cancer prevention have been already addressed, we disregard if nutritional disorders and dietary habits may have a potential predictive or prognostic power in LA GC. Therefore, further knowledge is strongly warranted to realize the actual impact of dietary- and lifestyle-factors in GC risk and - conversely - to examine if nutritional disorders are able to negatively impact the outcome of anticancer treatments. H. pylori infection is the major risk factor associated with non-cardia gastric cancer, and data has emerged with regard to the role of H. pylori eradication for primary prevention of gastric cancer. Smoking has also been implicated as a risk factor for non-cardia cancer. Furthermore, host genetic polymorphisms have an impact on host responses to gastric inflammation and acid secretion, thereby interacting with H. pylori infection and other environmental factors in gastric carcinogenesis. In contrast to non-cardia cancer, H. pylori infection does not play an important role in cardia cancer, with obesity and smoking identified as the main risk factors. Although dietary, lifestyle and metabolic risk factors have been identified, and addressing these lifestyle and metabolic risk factors may contribute to health, the actual impact in modulating cancer response and outcomes is still debated. Results from epidemiological studies reported that dietary factors may play an important role in gastric cancer etiology. Malnutrition is an independent predictor of increased morbidity and mortality. Additionally, weight loss and sarcopenia leads to higher chemotherapy-induced toxicity. In addition, neoadjuvant chemotherapy and chemoradiation therapy, which often worsen a patient's nutritional status, have become a standard treatments. In some cases, anti-cancer treatments may induce weight gain; on the other hand, overweight and obesity represent a risk factor for metabolic syndrome and they may foster disease recurrence. Therefore, it is challenging to estimate how anti-cancer treatments affect nutritional status and vice versa. These serious changes in nutritional status are also associated with marked deterioration in quality of life and can affect the ability to resist infection and recover from surgery. Screening for nutritional risk as early as possible allows for the identification of patients at risk of becoming malnourished. Screening should be done as early as possible, and recent literature suggests that it should be done at diagnosis or at hospital admission; screening should be repeated in the course of treatment for referral for evaluation if needed.Another source of investigation concerns the human microbiome, since microbiota is involved in human health and in several disease. Growing interest in microbiome and immune interaction in oncology lead to the awareness that cancer therapies perturb the microbiota and the host immune response, with resulting dysbiosis. On the other hand, existing evidence supports the hypothesis that gut microbiota can modulate the pharmacological effects and the toxicity profile of anticancer treatments. Therefore, it would be addressed if gut microbiota can shape the efficiency of drugs through several key mechanisms: metabolism, immunomodulation, translocation, enzymatic degradation, reduction of diversity, and ecological variability. Accordingly, microbiome is emerged as a novel target to be explored in different cancer settings. The strongest known risk factor for GC is infection with H.pylori, which drives the development of premalignant lesions (such as gastric atrophy, intestinal metaplasia, and dysplasia) that can lead to gastric cancer. However, although H.pylori is the most common bacterial infection worldwide and colonizes greater than 50% of the global population, only 1%-3% of infected individuals ever develop gastric cancer. In conclusion, although great advances have been made in understanding the complex interplay between the gastric microbiota and H.pylori in the development of gastric inflammation and cancer, further studies are still needed in well-defined human populations to compare differences in the microbiota of H.pylori-infected persons with and without neoplastic lesions. Cross-sectional studies can provide initial insights into microbial associations with cancer; however, reverse effects are a concern, as it is difficult to discern whether carcinogenesis leads to changes in the local microenvironment that creates a new niche for microbes or whether alterations in the microbial population or its functions contribute to carcinogenesis.The study aims to create a unique platform to integrate clinical, biological and imaging data regarding patients with resectable gastric and esophageal adenocarcinoma (GEA). This innovative approach looks at either implementing the data source in resectable GEA and mapping the complex interaction among the aforementioned features (nutrition-microbiome-genomics-radiomics), in order to sharpen the actual precision medicine toward a patient-centric model.

Keywords

Eligibility

Minimum Age: 18 Years

Eligible Ages: ADULT, OLDER_ADULT

Sex: ALL

Healthy Volunteers: No

Locations

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