Periodic Reporting for period 3 - LEGACy (CeLac and European consortium for a personalized medicine approach to Gastric Cancer)
Reporting period: 2022-01-01 to 2023-06-30
Publications related to LEGACY project are aligned with overall objectives of the project. Particularly, the article published in American Journal of Gastroenterology, establish the link between mucocutaneous manifestations of patients with autoimmune gastritis (Gonzalez A et al., Manifestations in autoimmune gastritis: A prospective case-control study. American Journal of Gastroenterology 2021: 116(12): 2374-2384. DOI: 10.14309/AJG0000000000001501) in order to increase the awareness of clinicians for early detection of gastric atrophy as a premalignant condition, to stratify risk of patients with endoscopic surveillance. On the other hand, the article published by Latorre et al., (Latorre G et al, Implementation of the updated Sydney System biopsy protocol improves the diagnostic yield of gastric preneoplastic conditions: Results from a Real-World Study.Gastroenterologia y Hepatologia 2023. DOI: 10.1016/J.GASTROHEP.2023.08.005) and research letter recently published in Gut journal (Latorre G et al, Comparison of OLGA and OLGIM as predictors of gastric cancer in a latinamerican population: The ECHOS study. Gut 2023.DOI: Gut 2023 Dec 26:Gutjnl-2023-331059) stratify risk of gastric cancer based on gastric atrophy (OLGA staging) and gastric intestinal metaplasia (OLGIM staging). Both articles explains the utility of endoscopic surveillance for early detection of gastric cancer with impact on patients survival. Finally, for primary prevention strategies, LEGACY project included the impact of Helicobacter pylori eradication, including efficacy of eradication schemes in Latin American countries and Europe (Submitted and under review in UEG journal) demonstrating that quadruple therapies are superior to standard triple therapies in both continents.
Our approaches are listed in Table 1.
CS 1.
Final numbers of the recruitment are presented in Table 2.
See Deliverables 2.4 and 2.5.
CS 2.
Final numbers of recruitment are presented in Table 3.
See Deliverables 1.4 and 3.3.
CS 3A.
Final numbers of recruitment are presented in Figure 1.
See Deliverable 4.5.
CS 3B.
Final numbers of recruitment are presented in Table 4.
See Deliverable 2.6.
Almost 95 % of achievements on recruitment, reached the study expectations of recruitment, and allowed us to proceed with the analysis and integration of the results.
During this period, the sample characterization and analysis were performed, and publications are under preparation. One abstract was accepted at ESMO World GI Congress in July 2023, and two abstracts were accepted and will be presented at the poster session at ESMO, Madrid in October 2023.
Summary of the clinical study conclusions.
- Legacy clinical study 1: Significant differences were found regarding lifestyles, diet, and clinical characteristics comparing patients and controls, and comparing EU and LATAM regions. Deliverables 2.4 and 2.5.
- Legacy clinical study 2: After a deep analysis of the LECACy samples, integrating clinical, pathological, and molecular data, we can conclude that gastric cancer subtypes with the highest clinical and biological value are based on validated markers (HER2, MSI/dMMR and EBV) in addition to histopathology (intestinal or diffuse). Regional differences were found in the clinical, pathological, immune, and molecular characteristics. Deliverables 1.4 and 3.3.
- Legacy clinical study 3, Part A: Educational Intervention. The results showed that the intervention improved the knowledge of GC risk factors and symptoms for a short period, but after 3 months, the participants forgot it. Deliverable 4.5.
Therefore, we propose the performance of recurring campaigns focused on gastric cancer awareness, to ensure a higher rate of alphabetization regarding gastric cancer risks and symptoms.
- Legacy clinical study 3, Part B: H. pylori Registry. Overall, we see that quadruple therapies (both, with and without bismuth) are superior to OCA treatment for H. Pylori eradication in the overall recruited cohort, belonging to five different countries and two continents, in line with previously published data. We consider this type of study useful to show which are better treatment options and let the clinical sites of the consortia to adapt to these tested therapeutic approaches. Deliverable 2.6.
The LEGACy clinical studies met the specific endpoints providing new data with a holistic overview of gastric cancer epidemiological, clinical, protein, molecular, immune, and microbiome characteristics of EU and CELAC cohorts, which have been presented to the scientific community and the civic population through different channels. Moreover, our interventional study showed positive results, as a strategy for gastric cancer prevention, that could be easily applied worldwide.
The educational program, including the training and knowledge exchange of the protocols that will be applied for each GC sample, performed during this reporting period:
- Six online educational sessions on relevant topics in GC (17 during the overall project), including international experts lecturing these sessions. The fellowship program is still ongoing.
- At least one exchange session per sub-WP after the first batch of samples was analyzed at the different laboratories.
Finally, the dissemination activities have been carried out in accordance with the project communication plan. During this period the main objective has been raising awareness of the project and preparing the future dissemination and exploitation of the results.
CS 1.
Final numbers of the recruitment are presented in Table 2.
See Deliverables 2.4 and 2.5.
CS 2.
Final numbers of recruitment are presented in Table 3.
See Deliverables 1.4 and 3.3.
CS 3A.
Final numbers of recruitment are presented in Figure 1.
See Deliverable 4.5.
CS 3B.
Final numbers of recruitment are presented in Table 4.
See Deliverable 2.6.
Almost 95 % of achievements on recruitment, reached the study expectations of recruitment, and allowed us to proceed with the analysis and integration of the results.
During this period, the sample characterization and analysis were performed, and publications are under preparation. One abstract was accepted at ESMO World GI Congress in July 2023, and two abstracts were accepted and will be presented at the poster session at ESMO, Madrid in October 2023.
Summary of the clinical study conclusions.
- Legacy clinical study 1: Significant differences were found regarding lifestyles, diet, and clinical characteristics comparing patients and controls, and comparing EU and LATAM regions. Deliverables 2.4 and 2.5.
- Legacy clinical study 2: After a deep analysis of the LECACy samples, integrating clinical, pathological, and molecular data, we can conclude that gastric cancer subtypes with the highest clinical and biological value are based on validated markers (HER2, MSI/dMMR and EBV) in addition to histopathology (intestinal or diffuse). Regional differences were found in the clinical, pathological, immune, and molecular characteristics. Deliverables 1.4 and 3.3.
- Legacy clinical study 3, Part A: Educational Intervention. The results showed that the intervention improved the knowledge of GC risk factors and symptoms for a short period, but after 3 months, the participants forgot it. Deliverable 4.5.
Therefore, we propose the performance of recurring campaigns focused on gastric cancer awareness, to ensure a higher rate of alphabetization regarding gastric cancer risks and symptoms.
- Legacy clinical study 3, Part B: H. pylori Registry. Overall, we see that quadruple therapies (both, with and without bismuth) are superior to OCA treatment for H. Pylori eradication in the overall recruited cohort, belonging to five different countries and two continents, in line with previously published data. We consider this type of study useful to show which are better treatment options and let the clinical sites of the consortia to adapt to these tested therapeutic approaches. Deliverable 2.6.
The LEGACy clinical studies met the specific endpoints providing new data with a holistic overview of gastric cancer epidemiological, clinical, protein, molecular, immune, and microbiome characteristics of EU and CELAC cohorts, which have been presented to the scientific community and the civic population through different channels. Moreover, our interventional study showed positive results, as a strategy for gastric cancer prevention, that could be easily applied worldwide.
The educational program, including the training and knowledge exchange of the protocols that will be applied for each GC sample, performed during this reporting period:
- Six online educational sessions on relevant topics in GC (17 during the overall project), including international experts lecturing these sessions. The fellowship program is still ongoing.
- At least one exchange session per sub-WP after the first batch of samples was analyzed at the different laboratories.
Finally, the dissemination activities have been carried out in accordance with the project communication plan. During this period the main objective has been raising awareness of the project and preparing the future dissemination and exploitation of the results.
The LEGACy consortium was consolidated during this last reporting period. The multidisciplinary teamwork pushed the project to move forward in the different tasks. The consortium worked committed to finish all the tasks linked to the respective WPs successfully.
Beyond the expected impact, our project identified three main areas to proceed:
• The Educational program: We completed the program as planned.
• The network of biobanks in EU and CELAC countries has been already established. Samples are currently centralized in a Central Biobank located at FISABIO- VALENCIA (Spain), to facilitate further characterizations aligned with the project scope.
• The data management beyond the project: data generated from each sample determination is under preparation to be deposited in EU and CELAC genomic data repositories. Such data will be available to the entire scientific community at Zenodo repository.
In terms of economic impact, we believe that the proposed algorithm based on immunohistochemistry is a cost-effective method that could select patients who really could benefit from the different therapies. A personalized approach allows the reduction of economic costs and side effects for patients who do not benefit from them. On the other hand, a solid Consortium was built for further collaborations, focused on continuing research development, but also to support patient access to therapies, improve the hospital registries and improve the diagnosis circuits. All these actions will result in a better cost-effective use of the resources.
Beyond the expected impact, our project identified three main areas to proceed:
• The Educational program: We completed the program as planned.
• The network of biobanks in EU and CELAC countries has been already established. Samples are currently centralized in a Central Biobank located at FISABIO- VALENCIA (Spain), to facilitate further characterizations aligned with the project scope.
• The data management beyond the project: data generated from each sample determination is under preparation to be deposited in EU and CELAC genomic data repositories. Such data will be available to the entire scientific community at Zenodo repository.
In terms of economic impact, we believe that the proposed algorithm based on immunohistochemistry is a cost-effective method that could select patients who really could benefit from the different therapies. A personalized approach allows the reduction of economic costs and side effects for patients who do not benefit from them. On the other hand, a solid Consortium was built for further collaborations, focused on continuing research development, but also to support patient access to therapies, improve the hospital registries and improve the diagnosis circuits. All these actions will result in a better cost-effective use of the resources.