Plasma cfDNA Fragmentomics for Early pNET Detection and Differential Diagnosis of Solid Pancreatic Tumors

NCT ID: NCT05847855

Last Updated: 2026-01-13

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 1000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-02-27
• Study Completion Date: 2026-06-30

Brief Summary

This prospective study aims to evaluate the sensitivity and specificity of an integrated model using fragmentomic profiles of plasma cell-free DNA for early detection of pancreatic neuroendocrine tumors and differential diagnosis of solid pancreatic tumors.

Detailed Description

Pancreatic neuroendocrine tumors (pNETs) are insidious and difficult to diagnose early. Approximately 36.8% of pNET patients have lymph node metastasis[1], and 20% -64% of patients have liver metastasis at the time of diagnosis[2]. The prognosis of pNETs is closely related to tumor grade and the American Joint Committee on Cancer (AJCC) staging. Among patients with known pathological grades in the United States, well-differentiated NETs had the highest median overall survival (OS, 16.2 years), moderately differentiated NETs had the worse OS (8.3 years), and poorly differentiated or undifferentiated NETs had the worst OS (10 months)[3]. The 5-year overall survival rates of localized, locally advanced, and metastatic pNETs were 93%, 77%, and 27%, respectively[4]. Given that the prognosis of early-stage pNETs is significantly better than that of advanced pNETs, early detection of pNETs can provide a cure opportunity and significantly improve survival.

In the past few decades, the application of 68Ga-DOTANOC PET/CT, magnetic resonance imaging (MRI), computed tomography (CT), and endoscopic ultrasound (EUS) has improved the detection rate of pNETs. But their application is limited by high costs, lack of sufficient sensitivity or specificity, and radiation exposure. Therefore, there is an urgent need for accurate and less invasive approaches to use in clinical practice for the early detection of pNETs.

Recently, the study of cell-free DNA (cfDNA) has provided a noninvasive approach for the diagnosis of solid malignancies. cfDNAs represent extracellular DNA fragments released from cell apoptosis and necrosis into human body fluids like plasma, thus carrying the genetic and epigenetic information from the cell and tissue of origin[5]. Among them, circulating tumor DNA (ctDNA), as a part of the total cfDNA, is released into the blood by tumor cells[6]. cfDNA fragmentomics depends on whole genome sequencing, and its characteristics mainly include copy number variation (CNV), nucleosome footprint, fragment length and motif[5, 7, 8], with targets covering the entire genome level. cfDNA fragmentomics has shown excellent predictive performance in multiple studies[5, 9-11]. Therefore, this prospective study aims to evaluate the sensitivity and specificity of an integrated model using fragmentomic profiles of plasma cell-free DNA (cfDNA) for early detection of pancreatic neuroendocrine tumors.

Additionally, once a pancreatic lesion is detected, accurate discrimination between pancreatic ductal adenocarcinoma (PDAC), pNETs and solid pseudopapillary tumor (SPT) is essential. This study therefore has two co-primary objectives: (1) to develop a fragmentomic assay that flags asymptomatic individuals likely to harbor a pNET; (2) to build a differential model that distinguishes PDAC vs pNETs vs SPT in patients with confirmed solid pancreatic neoplasms."

Conditions

Pancreatic Neuroendocrine Tumor; Solid Pancreatic Neoplasms

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

pNETs

Patients with pancreatic neuroendocrine tumors (pNETs).

Blood collection

Intervention Type: DIAGNOSTIC_TEST

Blood collection for fragmentomic profiles of plasma cell-free DNA

Healthy

Healthy volunteers.

Blood collection

Intervention Type: DIAGNOSTIC_TEST

Blood collection for fragmentomic profiles of plasma cell-free DNA

PDAC

Patients with pancreatic ductal adenocarcinoma (PDAC) .

Blood collection

Intervention Type: DIAGNOSTIC_TEST

Blood collection for fragmentomic profiles of plasma cell-free DNA

SPT

Patients with solid pseudopapillary tumor (SPT) of pancreas.

Blood collection

Intervention Type: DIAGNOSTIC_TEST

Blood collection for fragmentomic profiles of plasma cell-free DNA

Interventions

Blood collection

Blood collection for fragmentomic profiles of plasma cell-free DNA

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• Age 18 and above, regardless of gender;
• Histopathological diagnosis with non-functional pancreatic neuroendocrine tumor, pancreatic ductal adenocarcinoma or solid pseudopapillary tumor;
• Not receiving any anti-tumor treatment before surgery, including chemotherapy, embolization, ablation, radiotherapy, and molecular targeted therapy;
• No obvious surgical contraindications;
• Able to comply with research plans, follow-up plans, and other protocol requirements;
• Voluntary participation and signed informed consent.

Exclusion Criteria

• Pathological diagnosis was not pancreatic neuroendocrine tumor, pancreatic ductal adenocarcinoma or solid pseudopapillary tumor;
• Currently diagnosed with other types of tumors or any cancer history;
• Diagnosed with familial syndromes;
• Receiving anti-tumor treatment before surgery, including chemotherapy, embolization, ablation, radiotherapy, and molecular targeted therapy;
• Ongoing fever or recipient of anti-inflammation therapy within 14 days prior to study blood draw;
• Recipient of blood transfusion within 30 days prior to study blood draw;
• Recipient of organ transplant or prior non-autologous (allogeneic) bone marrow or stem cell transplant;
• Poor health condition and not suitable for blood draw;
• Any other disease/condition deemed not suitable for study enrollment by researcher.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Xian-Jun Yu

President of Shanghai Pancreatic Cancer Institute

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Xianjun Yu, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Fudan University

Locations

Fudan University shanghai cancer center

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xianjun Yu, MD, PhD

Role: CONTACT

yuxianjun@fudanpci.org

021-64175590-88503

Shunrong Ji, MD, PhD

Role: CONTACT

jishunrong@fudanpci.org

13788993956

Facility Contacts

Shunrong Ji, MD,PhD

Role: primary

13788993956

References

Fischer L, Bergmann F, Schimmack S, Hinz U, Priess S, Muller-Stich BP, Werner J, Hackert T, Buchler MW. Outcome of surgery for pancreatic neuroendocrine neoplasms. Br J Surg. 2014 Oct;101(11):1405-12. doi: 10.1002/bjs.9603. Epub 2014 Aug 13.

Reference Type: BACKGROUND

PMID: 25132004 (View on PubMed)

Dasari A, Shen C, Halperin D, Zhao B, Zhou S, Xu Y, Shih T, Yao JC. Trends in the Incidence, Prevalence, and Survival Outcomes in Patients With Neuroendocrine Tumors in the United States. JAMA Oncol. 2017 Oct 1;3(10):1335-1342. doi: 10.1001/jamaoncol.2017.0589.

Reference Type: BACKGROUND

PMID: 28448665 (View on PubMed)

Zhang X, Wang Z, Tang W, Wang X, Liu R, Bao H, Chen X, Wei Y, Wu S, Bao H, Wu X, Shao Y, Fan J, Zhou J. Ultrasensitive and affordable assay for early detection of primary liver cancer using plasma cell-free DNA fragmentomics. Hepatology. 2022 Aug;76(2):317-329. doi: 10.1002/hep.32308. Epub 2022 Jan 26.

Reference Type: BACKGROUND

PMID: 34954829 (View on PubMed)

Fece de la Cruz F, Corcoran RB. Methylation in cell-free DNA for early cancer detection. Ann Oncol. 2018 Jun 1;29(6):1351-1353. doi: 10.1093/annonc/mdy134. No abstract available.

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PMID: 29668834 (View on PubMed)

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Reference Type: BACKGROUND

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Snyder MW, Kircher M, Hill AJ, Daza RM, Shendure J. Cell-free DNA Comprises an In Vivo Nucleosome Footprint that Informs Its Tissues-Of-Origin. Cell. 2016 Jan 14;164(1-2):57-68. doi: 10.1016/j.cell.2015.11.050.

Reference Type: BACKGROUND

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Guo W, Chen X, Liu R, Liang N, Ma Q, Bao H, Xu X, Wu X, Yang S, Shao Y, Tan F, Xue Q, Gao S, He J. Sensitive detection of stage I lung adenocarcinoma using plasma cell-free DNA breakpoint motif profiling. EBioMedicine. 2022 Jul;81:104131. doi: 10.1016/j.ebiom.2022.104131. Epub 2022 Jun 30.

Reference Type: BACKGROUND

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Bao H, Wang Z, Ma X, Guo W, Zhang X, Tang W, Chen X, Wang X, Chen Y, Mo S, Liang N, Ma Q, Wu S, Xu X, Chang S, Wei Y, Zhang X, Bao H, Liu R, Yang S, Jiang Y, Wu X, Li Y, Zhang L, Tan F, Xue Q, Liu F, Cai S, Gao S, Peng J, Zhou J, Shao Y. Letter to the Editor: An ultra-sensitive assay using cell-free DNA fragmentomics for multi-cancer early detection. Mol Cancer. 2022 Jun 11;21(1):129. doi: 10.1186/s12943-022-01594-w.

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Ma X, Chen Y, Tang W, Bao H, Mo S, Liu R, Wu S, Bao H, Li Y, Zhang L, Wu X, Cai S, Shao Y, Liu F, Peng J. Multi-dimensional fragmentomic assay for ultrasensitive early detection of colorectal advanced adenoma and adenocarcinoma. J Hematol Oncol. 2021 Oct 26;14(1):175. doi: 10.1186/s13045-021-01189-w.

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Other Identifiers

CSPAC-NEN-4

Identifier Type: -

Identifier Source: org_study_id