Periodic Reporting for period 1 - ENDEAVOR (Endoscopic brush cytology and single cell clinal dynamics of early easophageal adenocarcinoma for detecting cost effective surveillance strategies and prediction of cancer recurrence)
Reporting period: 2024-01-01 to 2025-06-30
In many European countries, the incidence of esophageal adenocarcinoma (EAC) is increasing. EAC is strongly associated with Barrett’s esophagus, which can progress via dysplasia to early and invasive adenocarcinoma. Endoscopic treatment is the mainstay for early mucosal cancer (T1a/b stage) but requires intense post-treatment surveillance. This results in overtreatment in most, and undertreatment in only a subset of patients. There is a need for accurate risk stratification in Barrett’s esophagus patients with early EAC to tailor treatment and follow-up, thereby enhancing cost-effectiveness and patient quality of life.
The ENDEAVOR consortium, consisting of more than 10 partners from 7 European countries, will execute a 5-year project to develop a risk stratification model guiding treatment and surveillance, alongside a cost-effectiveness analysis, health-economic modeling and health-related quality of life (HR-QoL) investigation. The project will recruit patients with Barrett’s esophagus and early mucosal adenocarcinoma (T1a/b) from 10 European clinical sites. Patient and stakeholder groups will be involved. The first study comprises a pilot cohort study of 60 patients, involving tissue biopsies, cytology, blood samples and QoL questionnaires (EQ-5D-5L and Cancer Worry Scale). Outcomes include optimizing a biomarker-based risk stratification model, validation of Cancer Worry Scale questionnaire and e-clinical tools. These results will inform a second randomized controlled trial (RCT). Extensive reviews based on Barrett’s esophagus progression and QoL will be performed. Findings will be disseminated and guide future surveillance protocols in Barrett’s esophagus patients.
Thus, this project seeks to address key challenges in Barrett’s esophagus patients with early adenocarcinoma by validating a biomarker-based risk model, conducting health-economic modeling, assessing HR-QoL and engaging stakeholders to enhance patient care.
The ENDEAVOR consortium, consisting of more than 10 partners from 7 European countries, will execute a 5-year project to develop a risk stratification model guiding treatment and surveillance, alongside a cost-effectiveness analysis, health-economic modeling and health-related quality of life (HR-QoL) investigation. The project will recruit patients with Barrett’s esophagus and early mucosal adenocarcinoma (T1a/b) from 10 European clinical sites. Patient and stakeholder groups will be involved. The first study comprises a pilot cohort study of 60 patients, involving tissue biopsies, cytology, blood samples and QoL questionnaires (EQ-5D-5L and Cancer Worry Scale). Outcomes include optimizing a biomarker-based risk stratification model, validation of Cancer Worry Scale questionnaire and e-clinical tools. These results will inform a second randomized controlled trial (RCT). Extensive reviews based on Barrett’s esophagus progression and QoL will be performed. Findings will be disseminated and guide future surveillance protocols in Barrett’s esophagus patients.
Thus, this project seeks to address key challenges in Barrett’s esophagus patients with early adenocarcinoma by validating a biomarker-based risk model, conducting health-economic modeling, assessing HR-QoL and engaging stakeholders to enhance patient care.
At this stage of the project, the Endeavor consortium has reached consensus on the design of the study. In collaboration with different stakeholders, such as physicians, epidemiologists, patient representatives, biologists, local and national protocols governing the treatment and surveillance of early-stage Barrett's esophagus cancers were scrutinized. A consensus on a unified study protocol was forged for patient tailored treatment based on the biomarker outcomes versus standard surveillance in the control arm of the RCT study.
Beside preparing the RCT study protocol, all the necessary processes were conducted to successfully conduct the prospective pilot cohort study. A general protocol and informed consent form for the pilot study were made, subsequently adapted to national regulations by each recruiting site and submitted to the local ethical committees. Besides ethical documents, legal documentation such as clinical trial agreements and material transfer agreements were drafted and signed by the partners. On a technical level, the consortium developed an electronic case report form to correctly capture all study data and guarantee secure data storage and quality. In addition, e-clinical tools were developed for the assessment of health related patient quality of life and cancer-related anxiety. Parallel to the technical developments, the consortium members investigated how to establish the best methods regarding tissue and blood sampling procedures, and sample analysis procedures. A detailed sample flow was set up, as well as infrastructure to guarantee secure storage of the study samples in the central biobank and timely shipment of the samples for analysis in several laboratories. Lastly, logistical preparations were performed to ensure a smooth execution of the clinical trial: preparation and finalization of standard operating procedures and an extensive study manual, testing sample shipments, finalizing courier arrangements, ordering materials and assembling study lab kits at the central biobank. The first site initiation visits for the pilot study have been performed, paving the way for a successful execution of the pilot study.
Beside preparing the RCT study protocol, all the necessary processes were conducted to successfully conduct the prospective pilot cohort study. A general protocol and informed consent form for the pilot study were made, subsequently adapted to national regulations by each recruiting site and submitted to the local ethical committees. Besides ethical documents, legal documentation such as clinical trial agreements and material transfer agreements were drafted and signed by the partners. On a technical level, the consortium developed an electronic case report form to correctly capture all study data and guarantee secure data storage and quality. In addition, e-clinical tools were developed for the assessment of health related patient quality of life and cancer-related anxiety. Parallel to the technical developments, the consortium members investigated how to establish the best methods regarding tissue and blood sampling procedures, and sample analysis procedures. A detailed sample flow was set up, as well as infrastructure to guarantee secure storage of the study samples in the central biobank and timely shipment of the samples for analysis in several laboratories. Lastly, logistical preparations were performed to ensure a smooth execution of the clinical trial: preparation and finalization of standard operating procedures and an extensive study manual, testing sample shipments, finalizing courier arrangements, ordering materials and assembling study lab kits at the central biobank. The first site initiation visits for the pilot study have been performed, paving the way for a successful execution of the pilot study.
A consensus on a unified protocol was forged for patient tailored treatment and the study design. In alignment with the protocol, a detailed sample flow, data flow, standard operating procedures and an extensive study manual were created based on preparatory scientific and logistical work to enable a smooth execution of the clinical study. Also, preparations for working with a central biobank and electronic case report form were finalized to ensure secure storage of patient biological samples and data. Questionnaires to assess health related patient quality of life and patient anxiety levels were selected and translated for incorporation in the ENDEAVOR e-clinical tools.
The efforts described above pave the way for the prospective pilot cohort study, aiming to optimize the risk model and rectify gender biases in anticipation of the RCT. This initiative will also serve as a platform for evaluating novel High-Throughput methods for assessing clonal diversity, with an eye toward future applications of biomarkers.
The overarching aim is to maximize the societal and scientific impact of the ENDEAVOR project. This will be achieved through timely and targeted dissemination of key messages and engagement of groups including regulatory bodies, the general public, patients and patient advocacy groups, the scientific and medical community, investors and industry stakeholders. To this end, the ENDEAVOR consortium has set up a website, social media accounts and an agreement with the International Society for Diseases of the Esophagus has been made for publication and additional reporting on their website, social media and e-Newsletter.
The efforts described above pave the way for the prospective pilot cohort study, aiming to optimize the risk model and rectify gender biases in anticipation of the RCT. This initiative will also serve as a platform for evaluating novel High-Throughput methods for assessing clonal diversity, with an eye toward future applications of biomarkers.
The overarching aim is to maximize the societal and scientific impact of the ENDEAVOR project. This will be achieved through timely and targeted dissemination of key messages and engagement of groups including regulatory bodies, the general public, patients and patient advocacy groups, the scientific and medical community, investors and industry stakeholders. To this end, the ENDEAVOR consortium has set up a website, social media accounts and an agreement with the International Society for Diseases of the Esophagus has been made for publication and additional reporting on their website, social media and e-Newsletter.