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

March 23, 2026 updated by: Xian-Jun Yu, Fudan University

A Prospective Study of Plasma Cell-free DNA Fragmentomics for Early Detection of Pancreatic Neuroendocrine Tumors and Differential Diagnosis of Solid Pancreatic Tumors

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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."

Study Type

Observational

Enrollment (Estimated)

1000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China, 200032
        • Recruiting
        • Fudan University Shanghai Cancer Center
        • Principal Investigator:
          • Xianjun Yu
        • Contact:
          • Shunrong Ji, MD,PhD
          • Phone Number: 13788993956
        • Sub-Investigator:
          • Shunrong Ji
    • Sichuan
      • Chengdu, Sichuan, China, 610041
        • Recruiting
        • West China Hospital, Sichuan University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

The study population enrolled by the main center and the sub-center is uniformly divided into four groups with the same enrollment criteria for all.

  1. pNET Group: Not receiving anti-tumor treatment before surgery, and were histopathologically confirmed pancreatic neuroendocrine tumors.
  2. PDAC group: Patients with histopathologically confirmed pancreatic ductal adenocarcinoma (PDAC) who have not received any anti-tumor treatment before surgery.
  3. SPT group: Patients with histopathologically confirmed solid pseudopapillary tumor (SPT) of the pancreas who have not received any anti-tumor treatment before surgery.
  4. Healthy group: Healthy volunteers without a history of tumors and no pancreatic organic diseases.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
pNETs
Patients with pancreatic neuroendocrine tumors (pNETs). The prospective cases enrolled by the sub-center shall strictly comply with the study's inclusion/exclusion criteria, consistent with the main center, and no independent adjustment of the enrollment criteria is allowed.
Diagnostic test: Blood collection
Blood collection for fragmentomic profiles of plasma cell-free DNA. The sub-center shall use the same blood collection consumables (EDTA anticoagulant vacutainer tubes) and blood collection volume (10ml) as the main center; plasma separation shall be completed within 2 hours after blood collection, and all operations shall comply with the study's unified SOP.
Healthy
Healthy volunteers. The prospective cases enrolled by the sub-center shall strictly comply with the study's inclusion/exclusion criteria, consistent with the main center, and no independent adjustment of the enrollment criteria is allowed.
Diagnostic test: Blood collection
Blood collection for fragmentomic profiles of plasma cell-free DNA. The sub-center shall use the same blood collection consumables (EDTA anticoagulant vacutainer tubes) and blood collection volume (10ml) as the main center; plasma separation shall be completed within 2 hours after blood collection, and all operations shall comply with the study's unified SOP.
PDAC
Patients with pancreatic ductal adenocarcinoma (PDAC) . The prospective cases enrolled by the sub-center shall strictly comply with the study's inclusion/exclusion criteria, consistent with the main center, and no independent adjustment of the enrollment criteria is allowed.
Diagnostic test: Blood collection
Blood collection for fragmentomic profiles of plasma cell-free DNA. The sub-center shall use the same blood collection consumables (EDTA anticoagulant vacutainer tubes) and blood collection volume (10ml) as the main center; plasma separation shall be completed within 2 hours after blood collection, and all operations shall comply with the study's unified SOP.
SPT
Patients with solid pseudopapillary tumor (SPT) of pancreas. The prospective cases enrolled by the sub-center shall strictly comply with the study's inclusion/exclusion criteria, consistent with the main center, and no independent adjustment of the enrollment criteria is allowed.
Diagnostic test: Blood collection
Blood collection for fragmentomic profiles of plasma cell-free DNA. The sub-center shall use the same blood collection consumables (EDTA anticoagulant vacutainer tubes) and blood collection volume (10ml) as the main center; plasma separation shall be completed within 2 hours after blood collection, and all operations shall comply with the study's unified SOP.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sensitivity and specificity of the model for differential diagnosis among solid pancreatic tumors
Time Frame: From first blood draw until histopathological diagnosis, up to 3 years
Sensitivity and specificity of the model for differential diagnosis among PDAC, pNET and SPT.
From first blood draw until histopathological diagnosis, up to 3 years
Sensitivity and specificity of the integrated fragmentomic model for detecting pNETs
Time Frame: From date of first blood draw until first documented pNETs diagnosis, assessed up to 3 years.
Sensitivity and specificity of the integrated model using fragmentomic profiles of plasma cfDNA for early detection of pNETs
From date of first blood draw until first documented pNETs diagnosis, assessed up to 3 years.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Positive predictive value and negative predictive value
Time Frame: From date of first blood draw until first documented pNETs diagnosis, assessed up to 3 years
Positive predictive value (PPV) and negative predictive value (NPV) of the integrated model using fragmentomic profiles of plasma cfDNA for early detection of pNETs
From date of first blood draw until first documented pNETs diagnosis, assessed up to 3 years
Accuracy of the model in predicting AJCC stage (where applicable) and tumor grade
Time Frame: From date of first blood draw until first documented histopathological diagnosis, assessed up to 3 years
Sensitivity and specificity of the integrated model using fragmentomic profiles of plasma cfDNA in predicting AJCC stage (where applicable) and tumor grade
From date of first blood draw until first documented histopathological diagnosis, assessed up to 3 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sensitivity and specificity in distinguishing NETs from different tissue origins
Time Frame: From date of first blood draw until first documented pNETs diagnosis, assessed up to 3 years
Sensitivity and specificity of the integrated model using fragmentomic profiles of plasma cfDNA in distinguishing NETs from different tissue origins
From date of first blood draw until first documented pNETs diagnosis, assessed up to 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fudan University

Collaborators

West China Hospital

Investigators

  • Principal Investigator: Xianjun Yu, MD, PhD, Fudan University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 27, 2023

Primary Completion (Estimated)

June 30, 2026

Study Completion (Estimated)

June 30, 2026

Study Registration Dates

First Submitted

April 27, 2023

First Submitted That Met QC Criteria

April 27, 2023

First Posted (Actual)

May 8, 2023

Study Record Updates

Last Update Posted (Actual)

March 25, 2026

Last Update Submitted That Met QC Criteria

March 23, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CSPAC-NEN-4

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Pancreatic Neuroendocrine Tumor

Clinical Trials on Blood collection

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Turkmenistan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe