Periodic Reporting for period 1 - PANCAID (PANcreatic CAncer Initial Detection via liquid biopsy)
Reporting period: 2023-01-01 to 2024-06-30
Pancreatic cancer (PDAC) is usually detected at late stages and most patients die within one year after diagnosis. In PANCAID we will therefore develop a blood test for early detection of PDAC and its precursor lesions as well as individuals at risk to develop PDAC.
The main objectives of PANCAID include:
1. Establishment of a unique resource of blood samples of early PDAC and risk groups
2. Establishment of a breakthrough blood test for early diagnosis of PDAC
3. Identification of the best composite biomarker panel by integrating multimodal features in an AI-assisted computational analysis
4. Analysis of the socio-economic impact of early PDAC diagnosis
5. Definition of the ethics parameters relevant to early PDAC detection
A robust multi-biomarker panel will be determined during the training period (year 1-3) and subsequently validated on bio-banked blood samples. PANCAID will provide the design of a future prospective study for validation of the developed composite blood test in an international multi-center setting required to introduce blood-based tests (referred to as liquid biopsies) into screening programs for high-risk individuals. This action is part of the Cancer Mission cluster of projects on ‘Prevention, including Screening’.
The main objectives of PANCAID include:
1. Establishment of a unique resource of blood samples of early PDAC and risk groups
2. Establishment of a breakthrough blood test for early diagnosis of PDAC
3. Identification of the best composite biomarker panel by integrating multimodal features in an AI-assisted computational analysis
4. Analysis of the socio-economic impact of early PDAC diagnosis
5. Definition of the ethics parameters relevant to early PDAC detection
A robust multi-biomarker panel will be determined during the training period (year 1-3) and subsequently validated on bio-banked blood samples. PANCAID will provide the design of a future prospective study for validation of the developed composite blood test in an international multi-center setting required to introduce blood-based tests (referred to as liquid biopsies) into screening programs for high-risk individuals. This action is part of the Cancer Mission cluster of projects on ‘Prevention, including Screening’.
1. Establishment of a unique resource of blood samples of early PDAC and risk groups
All previously bio-banked samples which were made available from our contributing partners have been compiled and grouped according to their pre-malignant classification or tumour stage. Moreover, data containing information on patients as well as samples, have been summarized in a common database which is required for tracking of shipments, and subsequent statistical analyses of the liquid biopsy assays. To further increase the sample size of our cohort, we aim at receiving further bio-banked samples from additional institutions while we have also prepared a prospective study which will support us in analysing a multitude of complementary measurements from the same patient. Clinical data will be added over the course of the project.
2. Establishment of a breakthrough blood test for early diagnosis of PDAC
Preparatory measures have been undertaken to ensure a rapid processing once samples from the biobanks are delivered to the analysing partners. These include establishment and improvement of research protocols, training of personnel, and the establishment of legal documents and corresponding logistics. The liquid biopsy analytes which will be investigated in PANCAID include circulating tumour DNA (ctDNA), extracellular vesicles (EVs), circulating tumour cells (CTCs), proteins, circulating immune cells, and metabolites. A pilot study has been initiated to verify the quality of the bio-banked samples and has already underscored the feasibility of the analysis of ctDNA and proteins in the samples. Further analysis will follow during the project.
3. Identification of the best composite biomarker panel by integrating multimodal features in an AI-assisted computational analysis
A data repository has been established and all samples and aliquots have been assigned to PANCAID IDs which will be the prerequisite for the following statistical analysis. Moreover, the statistical analysis plan was established to improve the statistical and AI-based methodologies for data analysis as well as a data management plan. The legal framework for data safety was further developed to ensure the protection of sensitive data. As soon as the results from the analysis are obtained, the integration of the data will begin.
4. Analysis of the socio-economic impact of early PDAC diagnosis
In PANCAID, we also lay a special emphasis on the economic aspects of early detection of PDAC, particularly with regards to its costs and benefits within the Swedish and German health care systems. The work is foreseen later in the project. During the first phase of the project, two literature reviews have been prepared on the topics of “Economic evaluations of pancreatic cancer screening”, and “Loss in life expectancy following pancreatic cancer in Sweden”, to prepare for the implementation of the results from the PANCAID liquid biopsy analyses.
5. Definition of the ethics parameters relevant to early PDAC detection
To establish the PANCAID project's ethical foundation and justification and to determine how the results from a highly sensitive liquid biopsy test should be handled, several ethical aspects of early pancreas cancer surveillance are under investigation. Literature research on the topics of PDAC surveillance have been conducted and a report on incidental findings has already been finalised for publication. To assess the psychological burden of surveillance a survey has been prepared on the topic of “the right to know in pancreatic cancer surveillance” and will be conducted in the near future.
All previously bio-banked samples which were made available from our contributing partners have been compiled and grouped according to their pre-malignant classification or tumour stage. Moreover, data containing information on patients as well as samples, have been summarized in a common database which is required for tracking of shipments, and subsequent statistical analyses of the liquid biopsy assays. To further increase the sample size of our cohort, we aim at receiving further bio-banked samples from additional institutions while we have also prepared a prospective study which will support us in analysing a multitude of complementary measurements from the same patient. Clinical data will be added over the course of the project.
2. Establishment of a breakthrough blood test for early diagnosis of PDAC
Preparatory measures have been undertaken to ensure a rapid processing once samples from the biobanks are delivered to the analysing partners. These include establishment and improvement of research protocols, training of personnel, and the establishment of legal documents and corresponding logistics. The liquid biopsy analytes which will be investigated in PANCAID include circulating tumour DNA (ctDNA), extracellular vesicles (EVs), circulating tumour cells (CTCs), proteins, circulating immune cells, and metabolites. A pilot study has been initiated to verify the quality of the bio-banked samples and has already underscored the feasibility of the analysis of ctDNA and proteins in the samples. Further analysis will follow during the project.
3. Identification of the best composite biomarker panel by integrating multimodal features in an AI-assisted computational analysis
A data repository has been established and all samples and aliquots have been assigned to PANCAID IDs which will be the prerequisite for the following statistical analysis. Moreover, the statistical analysis plan was established to improve the statistical and AI-based methodologies for data analysis as well as a data management plan. The legal framework for data safety was further developed to ensure the protection of sensitive data. As soon as the results from the analysis are obtained, the integration of the data will begin.
4. Analysis of the socio-economic impact of early PDAC diagnosis
In PANCAID, we also lay a special emphasis on the economic aspects of early detection of PDAC, particularly with regards to its costs and benefits within the Swedish and German health care systems. The work is foreseen later in the project. During the first phase of the project, two literature reviews have been prepared on the topics of “Economic evaluations of pancreatic cancer screening”, and “Loss in life expectancy following pancreatic cancer in Sweden”, to prepare for the implementation of the results from the PANCAID liquid biopsy analyses.
5. Definition of the ethics parameters relevant to early PDAC detection
To establish the PANCAID project's ethical foundation and justification and to determine how the results from a highly sensitive liquid biopsy test should be handled, several ethical aspects of early pancreas cancer surveillance are under investigation. Literature research on the topics of PDAC surveillance have been conducted and a report on incidental findings has already been finalised for publication. To assess the psychological burden of surveillance a survey has been prepared on the topic of “the right to know in pancreatic cancer surveillance” and will be conducted in the near future.
With PDAC being the cancer entity with the lowest survival in Europe, the lack of suitable detection methods remains the biggest hurdle in its diagnosis. More specifically, the main challenges for diagnosis include the lack of a blood-based test for both pre-malignant and advanced stages, the inability to predict the malignant conversion from pre-cancerous lesions to PDAC, and moreover, the need for an early diagnosis of PDAC as most patients present with advanced stage disease that is associated with impaired outcome. The PANCAID project is addressing those shortcomings in PDAC diagnosis by developing a blood-based test using a multitude of different liquid biopsy biomarkers.
In PANCAID, we have collected samples and associated clinical data from multiple biobanks from leading hospitals in Europe for PDAC samples, which will be required to establish a blood-based signature for early PDAC detection. We have performed all preparatory measures to use our state-of-the-art technologies for the examination of a multitude of analytes from this unique cohort and will combine our expertise.
With the results from the liquid biopsy analyses, at the end of the project a protocol for a randomized prospective study will be available in order to confirm whether the previously determined choice of a combinatory liquid biomarker assay can be fully integrated into clinical decision making and how the findings can help medical practitioners select the most appropriate multimodal therapy, ultimately leading to better patient care.
Furthermore, we have undertaken preparations to simulate costs and health effects associated with different early detection strategies, to ultimately empower policy makers, stakeholders, and health care providers that will lead to reduced economic burden and will thus serve the patients in terms of health and optimised allocation of health care resources.
In PANCAID, we have collected samples and associated clinical data from multiple biobanks from leading hospitals in Europe for PDAC samples, which will be required to establish a blood-based signature for early PDAC detection. We have performed all preparatory measures to use our state-of-the-art technologies for the examination of a multitude of analytes from this unique cohort and will combine our expertise.
With the results from the liquid biopsy analyses, at the end of the project a protocol for a randomized prospective study will be available in order to confirm whether the previously determined choice of a combinatory liquid biomarker assay can be fully integrated into clinical decision making and how the findings can help medical practitioners select the most appropriate multimodal therapy, ultimately leading to better patient care.
Furthermore, we have undertaken preparations to simulate costs and health effects associated with different early detection strategies, to ultimately empower policy makers, stakeholders, and health care providers that will lead to reduced economic burden and will thus serve the patients in terms of health and optimised allocation of health care resources.