Publications

Publications

PANCAID publications

• Plasma cell-free DNA markers predict occult metastases in patients with resectable pancreatic ductal adenocarcinoma

  Jacob E. Till, Ofer Gal-Rosenberg, Sophia G. Giliberto, Nicholas J. Seewald, Dominique G. Ballinger, Heather E. Samberg, Melinda R. Yin, Qiao-Li Wang, Samuele Cannas, Kristine N. Kim, Kyle Tien, Mohammed Sawi, Vidya Madineedi, C. Sloane Furniss, Vasilena Gocheva, Jonathan Nowak, Lauren K. Brais, Chen Yuan, Michael H. Rosenthal, Robert Roses, Ronald DeMatteo, Major Kenneth Lee, Charles Vollmer, Hersh Sagreiya, Mark H. O'Hara, Ruth Shemer, Brian Wolpin, Yuval Dor, Erica L. Carpenter
  
  Published: January 2026
  
  Dear Editor,
  Detecting pancreatic ductal adenocarcinoma (PDAC) early can yield dramatic improvements in overall survival (OS). Curative intent resection is typically indicated when the disease is localised to the pancreas. However, standard of care imaging lacks sensitivity to detect smaller occult metastases, often resulting in patients undergoing an unnecessary and morbid surgery, followed by early recurrence.1, 2 While we have previously demonstrated detection of early-stage PDAC using exocrine pancreas methylation markers in cfDNA,3 here we show that methylation markers, when combined with circulating tumour KRAS mutation detection and imaging measurements, can predict the presence of occult metastatic disease before curative intent surgery. [...]
  https://onlinelibrary.wiley.com/doi/10.1002/ctm2.70573

• Time is encoded by methylation changes at clustered CpG sites

  Bracha-Lea Ochana, Daniel Nudelman, Daniel Cohen, Ayelet Peretz, Sheina Piyanzin, Ofer Gal Rosenberg, Amit Horn, Netanel Loyfer, Miri Varshavsky, Ron Raisch, Ilona Shapiro, Yechiel Friedlander, Hagit Hochner, Benjamin Glaser, Yuval Dor, Tommy Kaplan, Ruth Shemer
  
  Published: July 2025
  
  Highlights:
  • Deep bisulfite sequencing of >40 age-related loci in >300 human blood samples
  • Single-molecule methylation patterns analyzed using deep neural networks
  • Age-related CpGs show stochastic or block-like regional methylation changes
  • 1.36-year accuracy in chronological age prediction from blood using just two loci
  https://www.cell.com/cell-reports/fulltext/s2211-1247(25)00729-6

• Economic evaluations of early detection strategies for pancreatic cancer: a systematic review

  Robert Wittram, Léon Kreis, Hans-Helmut König, Christian Brettschneider
  
  Published: 5 June 2025
  
  Abstract
  Objectives
  The early detection of pancreatic cancer is an important step in reducing mortality by offering patients curative treatment. The aim of this study was to synthesize available evidence on the costs and cost-effectiveness of strategies for early pancreatic cancer detection.
  
  Methods
  The electronic databases PubMed, Web of Science, and EconLit were searched for peer-reviewed and published papers in English until April 2024 with no date or contextual restrictions. Economic evaluations of early pancreatic cancer detection strategies compared to alternative or no detection strategies were criteria for inclusion.
  
  Results
  Thirty-one articles were included, 22 were full and nine were partial economic evaluations. Fifteen studies screened target populations with pancreatic cancer-associated risk factors and 16 conducted surveillance of patients with precancerous lesions. Six studies found early detection strategies to be cost-effective, one did not, and thirteen reported partially cost-effective results. In all studies, populations of interest had an elevated pancreatic cancer risk compared to the general population. Endoscopic ultrasound, magnetic resonance imaging, and computed tomography were the most frequently evaluated imaging modalities. Patient engagement, valuation of outcomes and choice of discount rates were among incomplete reporting categories, and narrow evaluation perspectives may have biased the results.
  
  Conclusions
  Early detection strategies for pancreatic cancer may be cost-effective for certain high-risk patient groups. However, evaluations so far have applied heterogeneous methods, used different modalities, had various target groups and screened at different frequencies. Further evaluations will be required to systematically synthesize economic evidence regarding specific early detection strategies.
  https://link.springer.com/article/10.1007/s10198-025-01793-4

• Exploring the psychological burden in a pancreatic cancer surveillance programme based on high-risk individuals: a Swedish cross-sectional study

  Anna Vesterberg, Ebba Asplund, Giulia Marras, Miroslav Vujasinovic, Cecilia Haddad Ringborg, Yvonne Wengström, Matthias Löhr
  
  Published: 30 April 2025
  
  Abstract:
  Introduction
  Pancreatic cancer, an aggressive cancer that presents with few or unspecific symptoms, has a poor prognosis. Thus, diagnosis at an early stage is vital for survival and a chance for curative treatment. Therefore, surveillance programmes for high-risk individuals are of the utmost importance. However, data on the psychological burden among participants in these programmes are limited.
  
  Aims
  This study aimed to investigate the psychological burden for participants in a pancreatic cancer surveillance programme and explore whether the psychological burden was related to the individual’s risk level for pancreatic cancer.
  
  Methods
  This single-centre cross-sectional study investigated cancer worry, anxiety, coping and perceived physical and mental health using a digital questionnaire, including the following instruments: Cancer Worry Scale (CWS), State–Trait Anxiety Inventory (STAI), 13-Item Sense of Coherence and 12-Item Short-Form Survey. The invited participants (n=413) were healthy individuals with an increased risk of pancreatic cancer enrolled in a pancreatic cancer surveillance programme.
  
  Results
  The results indicated high cancer worry among respondents (n=78) with high scores on CWS (mean, 16.45). The majority (69.3%) had scores indicating high cancer worry (≥14). Anxiety was not equally high among respondents (mean STAI-T, 35.13; STAI-S, 35.9). Female sex and younger age were significantly correlated with higher cancer worry and anxiety (p < 0.001). Outcomes in coping and perceived health were similar to those of the normal population.
  
  Conclusions
  Cancer worry is particularly high among participants. No correlation was found between the risk level and psychological burden.
  https://bmjopen.bmj.com/content/15/4/e097814

• Differences in the Fecal Metabolome of AutoimmunePancreatitis Patients

  Vladyslav Dovhalyuk, Fan Yang, Sara Nikolic, Miroslav Vujasinovic, Matthias Löhr, Daniel Globisch
  
  Published: 17 April 2025
  
  Abstract
  Background
  Chronic pancreatitis is a risk factor for pancreatic cancer. Autoimmune pancreatitis is a unique form of chronic pancreatitis that is primarily characterized by its immune mediate etiology, clinically resembling pancreatic cancer, yet uniquely responsive to steroid treatment.
  
  Objective
  Early and accurate diagnosis of autoimmune pancreatitis is vital for effective treatment and patient prognosis, for which new diagnostic tools are urgently required. Gut microbiota dysbiosis has been identified to correlate with the development of pancreatic diseases, which provides new opportunities for the discovery of disease biomarkers.
  
  Methods
  We utilized a mass spectrometric global metabolomics investigation of patient autoimmune pancreatitis and chronic pancreatitis fecal samples, investigating microbiome, dietary and human metabolism.
  
  Results
  We discovered a series of newly identified metabolic signatures between both patient groups including enterolactone, 4-guanidinobutanoic acid, and methylthioadenosine sulfoxide. Additionally, the analysis revealed significant differences in several metabolic pathways such as fatty acids, alkaloids, amino acids and peptides.
  
  Conclusion
  Our observations provide novel insights into important metabolic human pathways and microbiome-derived metabolites to distinguish autoimmune pancreatitis from chronic pancreatitis. These findings reveal systemic metabolic responses and the identified metabolites may be developed into potential biomarkers for future diagnosis to distinguish between autoimmune pancreatitis and chronic pancreatitis.
  https://onlinelibrary.wiley.com/doi/full/10.1002/ueg2.70025

• Early Detection of Sporadic Pancreatic Cancer

  Hans Scherübl; Roland Andersson; Daniel Ansari; Irene Esposito; Thilo Hackert; J.-Matthias Löhr
  
  Published: March 2025
  
  Scherübl/Hackert: Who Are the High-Risk Individuals That Should Be Offered Surveillance for Pancreatic Cancer?
  Andersson and Ansari
  Currently, surveillance is recommended for those with a strong family history of pancreatic cancer (PC) or those with germline mutations in PC susceptibility genes, such as ATM, BRCA1, BRCA2, CDKN2A, PALB2, or STK11. In the future, with the availability of accurate early detection tests, additional high-risk individuals may be included in surveillance programs, such as those with new-onset diabetes >50 years, those with early symptoms suggestive of PC, or those with premalignant cystic lesions. [...]
  https://karger.com/vis/article/41/5/294/924541/Early-Detection-of-Sporadic-Pancreatic-Cancer

• Pancreatic incidentaloma: incidental f indings from history towards the era of liquid biopsy

  Matthias Löhr, Miroslav Vujasinovic, Nikolaos Kartalis, Philipp Osten
  
  Published: 9 September 2024
  
  Abstract
  This report provides an overview of the most common diagnostic methodss that bring to light incidental findings of pancreatic cancer. It reviews the impact of medical imaging and genetic assessment on the definitions of incidental findings and incidentaloma of the pancreas. For different diagnostic approaches (eg, MRI and CT) and for different affections (cysts/intraductal papillary mucinous neoplasia, solid lesions), specific guidelines have been proposed and some are established. Based on this, we summarise the differences between the traditional methods with those applied in the PANCAID project. Biomarkers, genetic predispositions, mutations and circulating tumour cells give rise to different levels of concern. The final part of the report discusses the risks and the opportunities associated with further diagnostic procedures and surgical interventions. From the ethical perspective, the most urging question is, can a screening based on liquid biopsy and blood samples open a gateway for the prevention of pancreatic cancer - even if morbidity and lethality of today’s surgical interventions is still very high?
  https://egastroenterology.bmj.com/content/2/3/e100082

• Multibiomarker panels in liquid biopsy for early detection of pancreatic cancer – a comprehensive review

  Kim‑Lea Reese, Klaus Pantel and Daniel J. Smit
  
  Published: 2 September 2024
  
  Abstract
  Pancreatic ductal adenocarcinoma (PDAC) is frequently detected in late stages, which leads to limited therapeutic options and a dismal overall survival rate. To date, no robust method for the detection of early-stage PDAC that can be used for targeted screening approaches is available. Liquid biopsy allows the minimally invasive collection of body fluids (typically peripheral blood) and the subsequent analysis of circulating tumor cells or tumor-associated molecules such as nucleic acids, proteins, or metabolites that may be useful for the early diagnosis of PDAC. Single biomarkers may lack sensitivity and/or specificity to reliably detect PDAC, while combinations of these circulating biomarkers in multimarker panels may improve the sensitivity and specificity of blood test-based diagnosis. In this narrative review, we present an overview of different liquid biopsy biomarkers for the early diagnosis of PDAC and discuss the validity of multimarker panels.
  https://jeccr.biomedcentral.com/articles/10.1186/s13046-024-03166-w

• Economic evaluations of pancreatic cancer screening: a systematic review protocol

  Robert Wittram, Hans-Helmut König, Christian Brettschneider
  
  Published: 17 August 2024
  
  Abstract
  Introduction: The early detection of pancreatic cancer is an important step in reducing mortality by offering patients curative treatment. Screening strategies in risk populations and by means of different detection methods have been economically evaluated. However, a synthesis of screening studies to inform resource allocation towards early detection within the disease area has not been done. Therefore, studies evaluating the cost-effectiveness and costs of screening for pancreatic cancer should be systematically reviewed.
  
  Methods and analysis: A systematic review of economic evaluations reporting the cost-effectiveness or costs of pancreatic cancer screening will be conducted. The electronic databases Medline, Web of Science and EconLit will be searched without geographical or time restrictions. Two independent reviewers will select eligible studies based on predefined criteria. The study quality will be assessed using the Consolidated Health Economic Evaluation Reporting Standards statement and the Bias in Economic Evaluation checklist. One reviewer will extract relevant data and a second reviewer will cross-check compliance with the extraction sheet. Key items will include characteristics of screened individuals, the screening strategies used, and costs, health effects and cost-effectiveness as study outputs. Differences of opinion between the reviewers will be solved by consulting a third reviewer.
  
  Ethics and dissemination: Ethics approval is not required for this study since no original data will be collected. The results will be disseminated through presentations at conferences and publication in a peer-reviewed journal. The results of the systematic review will inform future economic evaluations of pancreatic screening, which provide guidance for decision-making in healthcare resource prioritisation.
  https://bmjopen.bmj.com/content/14/8/e087003

• Can our experience with surveillance for inherited pancreatic cancer help to identify early pancreatic cancer in the general population?

  J.-Matthias Löhr, Daniel Öhlund, Emma Söreskog, Emil Andersson, Miroslav Vujasinovic, Niklas Zethraeus, Malin Sund
  
  Published: 5 March 2024
  
  Abstract
  Screening of the general population for cancer is a matter of primary prevention reducing the burden of disease. Whilst this is successful for several cancers including breast, colon and prostate, the situation to screen and hence prevent pancreatic cancer is different. The organ is not as accessible to simple physical exam or biological samples (fecal or blood
  test). Neither exists a blood test such as PSA that is cost-effective. Reviewing the evidence from screening risk groups for pancreatic cancer, one must conclude that there is no rational at present to screen the general population, for a lack of appropriate tests.
  https://doi.org/10.1007/s10689-024-00363-6

Background Literature

• UEG position paper on pancreatic cancer. Bringing pancreatic cancer to the 21st century: Prevent, detect, and treat the disease earlier and better

  Patrick Michl, Matthias Löhr, John P. Neoptolemos, et al. (2021)
  
  Research on pancreatic cancer has being receiving little or minimal funds
  from European funding bodies. UEG is calling for public‐private partnerships that
  would effectively fund research on pancreatic cancer.
  Conclusion: This would increase our understanding of this disease and better
  treatment, through pan‐European efforts that take advantage of the strong academic European research
  https://doi.org/10.1002/ueg2.12123

• Liquid Biopsy: From Discovery to Clinical Application

  Catherine Alix-Panabières and, Klaus Pantel (2021)
  
  Over the past 10 years, circulating tumor cells (CTC) and circulating tumor DNA (ctDNA) have received enormous attention as new biomarkers and subjects of translational research. Although both biomarkers are already used in numerous clinical trials, their clinical utility is still under investigation with promising first results. Clinical applications include early cancer detection, improved cancer staging, early detection of relapse, real-time monitoring of therapeutic efficacy, and detection of therapeutic targets and resistance mechanisms. Here, we propose a conceptual framework of CTC and ctDNA assays and point out current challenges of CTC and ctDNA research, which might structure this dynamic field of translational cancer research. SIGNIFICANCE: The analysis of blood for CTCs or cell-free nucleic acids called "liquid biopsy" has opened new avenues for cancer diagnostics, including early detection of tumors, improved risk assessment and staging, as well as early detection of relapse and monitoring of tumor evolution in the context of cancer therapies.
  https://pubmed.ncbi.nlm.nih.gov/33811121/

• Pancreatic Cancer: A Review of Current Treatment and Novel Therapies

  Hordur Mar Kolbeinsson, Sreenivasa Chandana, G. Paul Wright & Mathew Chung (2023)
  
  The paper provides information on the current treatment and novel therapies for pancreatic cancer, including the use of surgery, systemic chemotherapy, genomic testing, and targeted therapies. It does not specifically mention what is known about pancreatic cancer in general.
  https://www.doi.org/10.1080/08941939.2022.2129884

• A comprehensive review of pancreatic cancer and its therapeutic challenges

  Shan Jiang, Johan Bourghardt Fagman, Yunyun Ma, et al. (2022)
  
  The paper provides information on the molecular mechanisms of pancreatic cancer, drug resistance, immune escaping mechanisms, and potential therapeutic approaches. It also mentions that surgery is currently the only potentially curative treatment for pancreatic cancer patients.
  https://www.doi.org/10.18632/aging.204310

• Pancreatic Cancer: A Review of Risk Factors, Diagnosis, and Treatment

  ZhiYu Zhao and Wei Liu (2020)
  
  Pancreatic cancer is a highly invasive malignant tumor that mainly affects men and older adults. It is also increasingly observed in young patients.
  https://www.doi.org/10.1177/1533033820962117