A Liquid Biopsy for Pancreatic Cancer Early-detection and Disease Monitoring

Официальное название

An Exosome-based and Machine-learning-powered Liquid Biopsy for Pancreatic Cancer Early-detection and Disease Monitoring

Обзор

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy characterized by an asymptomatic early phase, late diagnosis, and poor survival, particularly in individuals who develop disease outside the context of early-stage detection. Early detection strategies are currently limited to imaging-based surveillance (MRI and endoscopic ultrasound) in selected high-risk populations, but these approaches are invasive, costly, and suboptimal in sensitivity. The aim of this study is to evaluate circulating cell-free and exosome-bound microRNAs as non-invasive biomarkers of PDAC risk and disease biology

Подробное описание

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy characterized by an asymptomatic early phase, late diagnosis, and poor survival, particularly in individuals who develop disease outside the context of early-stage detection. Early detection strategies are currently limited to imaging-based surveillance (MRI and endoscopic ultrasound) in selected high-risk populations-including individuals with hereditary or familial pancreatic cancer and those with mucinous pancreatic cystic lesions-but these approaches are invasive, costly, and suboptimal in sensitivity.

The aim of this study is to evaluate circulating cell-free and exosome-bound microRNAs as non-invasive biomarkers of PDAC risk and disease biology, with the hypothesis that combined microRNA profiling can improve molecular risk stratification and potentially anticipate disease progression compared with standard imaging-based surveillance alone. The study population will include adult men and women (≥18 years) at increased risk for PDAC due to familial or hereditary predisposition or mucinous pancreatic cysts, with generally stable health status and existing clinical follow-up; no vulnerable populations are specifically targeted.

No medicinal products or medical devices are administered in this study. The procedure under investigation consists exclusively of laboratory-based measurement of microRNA expression from previously collected plasma samples, using validated exosome isolation and quantification techniques, with no impact on clinical management. Available preliminary and published data demonstrate that combined cell-free and exosomal microRNA signatures can detect early-stage PDAC with high accuracy and show dynamic behavior during disease progression and treatment, supporting their relevance for risk stratification and disease monitoring. Clinical, demographic, and laboratory data will be retrieved.

Вмешательства

• Диагностический тест PANXEON
  A panel of circulating microRNA, whose expression level is tested in cell-free and exosome-derived samples

Первичные конечные точки

• Sensitivity [Срок оценки: Through study completion, an average of 1 year]

Вторичные конечные точки (2)

• Specificity [Срок оценки: Through study completion, an average of 1 year]
• Proportion of correct predictions (true positives and true negatives) among the total number of cases (i.e., accuracy) [Срок оценки: Through study completion, an average of 1 year]

Критерии участия

Критерии включения

• Adult men or women aged ≥18 years at the time of plasma sample collection.
• Classification as at increased risk for pancreatic ductal adenocarcinoma (PDAC) due to familial pancreatic cancer or hereditary pancreatic cancer syndrome
• Classification as at increased risk for pancreatic ductal adenocarcinoma (PDAC) due to the presence of one (or more) mucinous pancreatic cystic lesion(s).
• Availability of stored plasma samples collected as part of routine clinical care or surveillance and archived in the institutional biobank.
• Availability of relevant clinical and demographic data in institutional medical records sufficient to address study objectives.
• Prior provision of informed consent for biobanking and research use of biological samples and data

Критерии исключения

• Absence or insufficient quality/quantity of stored plasma samples for laboratory analysis.
• Lack of clinical data required for cohort classification and/or outcome assessment.
• History of pancreatic surgery or interventional procedures prior to plasma sample collection.
• Concurrent active malignancy at the time of sample collection, other than non-melanoma skin cancer.
• Samples collected outside routine clinical care or not compliant with institutional biobanking and data protection policies.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Италия · 1 центр

• IRCCS San Raffaele Hospital — Milan

Публикации

• Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May-Jun;74(3):229-263. doi: 10.3322/caac.21834. Epub 2024 Apr 4. PMID 38572751
• Henrikson NB, Aiello Bowles EJ, Blasi PR, Morrison CC, Nguyen M, Pillarisetty VG, Lin JS. Screening for Pancreatic Cancer: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2019 Aug 6;322(5):445-454. doi: 10.1001/jama.2019.6190. PMID 31386140
• Rahib L, Wehner MR, Matrisian LM, Nead KT. Estimated Projection of US Cancer Incidence and Death to 2040. JAMA Netw Open. 2021 Apr 1;4(4):e214708. doi: 10.1001/jamanetworkopen.2021.4708. PMID 33825840
• Singhi AD, Koay EJ, Chari ST, Maitra A. Early Detection of Pancreatic Cancer: Opportunities and Challenges. Gastroenterology. 2019 May;156(7):2024-2040. doi: 10.1053/j.gastro.2019.01.259. Epub 2019 Feb 2. PMID 30721664
• Zhao B, Zhao B, Chen F. Diagnostic value of serum carbohydrate antigen 19-9 in pancreatic cancer: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol. 2022 Sep 1;34(9):891-904. doi: 10.1097/MEG.0000000000002415. Epub 2022 Jul 27. PMID 35913776
• Majumder S, Taylor WR, Foote PH, Berger CK, Wu CW, Mahoney DW, Bamlet WR, Burger KN, Postier N, de la Fuente J, Doering KA, Lidgard GP, Allawi HT, Petersen GM, Chari ST, Ahlquist DA, Kisiel JB. High Detection Rates of Pancreatic Cancer Across Stages by Plasma Assay of Novel Methylated DNA Markers and CA19-9. Clin Cancer Res. 2021 May 1;27(9):2523-2532. doi: 10.1158/1078-0432.CCR-20-0235. Epub 2021 PMID 33593879
• Mannucci A, Hernandez G, Uetake H, Yamada Y, Balaguer F, Baba H, Chen T, Chen J, Boland CR, Cavestro GM, Quintero E, Goel A. Prediction of long-term recurrence-free and overall survival in early-onset colorectal cancer: the ENCORE multi-centre study. NPJ Precis Oncol. 2025 Jun 21;9(1):202. doi: 10.1038/s41698-025-00978-7. PMID 40544180
• Miyoshi J, Mannucci A, Scarpa M, Gao F, Toden S, Whitsett T, Inge LJ, Bremner RM, Takayama T, Cheng Y, Bottiglieri T, Nagtegaal ID, Shrubsole MJ, Zaidi AH, Wang X, Coleman HG, Anderson LA, Meltzer SJ, Goel A; FINBAR-EMERALD collaborative group. Liquid biopsy to identify Barrett's oesophagus, dysplasia and oesophageal adenocarcinoma: the EMERALD multicentre study. Gut. 2025 Jan 17;74(2):169-181. do PMID 39562048

Идентификаторы

NCT: NCT07700992 · PANXEON/2026

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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