Immune Repertoire Decoding for Chronic Pancreatitis-to-Pancreatic Cancer Risk Stratification

N/ANot Yet RecruitingNCT07612566

Changhai Hospital800 enrolled

Overview

This study will follow people with chronic pancreatitis, people with pancreatic cancer, and healthy volunteers. The goal is to better understand why some people with chronic pancreatitis may later develop pancreatic cancer. Participants will provide blood samples and health information. Some participants may also provide tissue samples if these are available during routine medical care. The study team will look for changes in the immune system, genes, medical images, and clinical information that may be linked to the development of pancreatic cancer. People with chronic pancreatitis will be followed over time. The information collected in this study may help researchers develop a model to identify patients with chronic pancreatitis who have a higher risk of pancreatic cancer.

Chronic pancreatitis is considered an important precancerous condition for pancreatic ductal adenocarcinoma, but the immune changes associated with malignant transformation remain incompletely understood. This prospective observational cohort study will enroll healthy controls, patients with chronic pancreatitis, and patients with newly diagnosed pancreatic ductal adenocarcinoma at Changhai Hospital. The study will collect standardized clinical information, laboratory data, abdominal CT or MRI imaging data, peripheral blood samples, and, when available, tissue samples. Peripheral blood samples will be used for immune repertoire profiling, including T-cell receptor and B-cell receptor sequencing. Additional analyses may include antibody repertoire profiling, germline genetic testing, single-cell sequencing, spatial transcriptomics, and multiplex immunofluorescence in selected representative cases. Patients with chronic pancreatitis will undergo longitudinal follow-up approximately every 6 to 12 months. The study will compare immune repertoire features across healthy controls, chronic pancreatitis, and pancreatic ductal adenocarcinoma, and will evaluate dynamic immune changes during disease progression. The collected immune, genetic, imaging, and clinical data will be integrated to develop and validate an artificial intelligence-based risk stratification model for identifying patients with chronic pancreatitis who may be at increased risk of pancreatic cancer. Participant enrollment and baseline sample collection are planned to be completed by June 2028. Follow-up, data processing, model development, and final data collection are planned to continue through December 2028.

Study Type

OBSERVATIONAL

Enrollment

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Adults aged 18 years or older. * Able to understand the study procedures and provide written informed consent. * Healthy controls: participants without a known history of chronic pancreatitis or pancreatic cancer. * Chronic pancreatitis cohort: participants diagnosed with chronic pancreatitis according to clinical guidelines, based on clinical, imaging, and/or genetic information. * Pancreatic ductal adenocarcinoma cohort: participants with newly diagnosed pancreatic ductal adenocarcinoma based on clinical, imaging, and/or pathological evaluation. * Willing to provide blood samples and relevant clinical information. * For participants with chronic pancreatitis, willing to undergo longitudinal follow-up approximately every 6 to 12 months. Exclusion Criteria: * Unable or unwilling to provide written informed consent. * Unable to provide required clinical information or biological samples. * Prior diagnosis of another active malignant tumor, except adequately treated non-melanoma skin cancer or carcinoma in situ, if considered not to affect study participation by the investigator. * Current severe acute infection or other serious medical condition that, in the investigator's judgment, may interfere with study participation or interpretation of immune-related analyses. * Use of systemic immunosuppressive therapy or immunotherapy within a period considered clinically relevant by the investigator. * Any condition that, in the investigator's judgment, makes the participant unsuitable for this study.

Outcomes

Primary Outcomes

Change in Peripheral Blood TCR/BCR Immune Repertoire Features Over 30 Months

Peripheral blood T-cell receptor and B-cell receptor immune repertoire features will be measured from blood samples. Features will include clonotype diversity, clonal expansion, V/J gene usage, CDR3 sequence characteristics, B-cell receptor somatic hypermutation, and shared immune clonotype clusters. These features will be compared across healthy controls, participants with chronic pancreatitis, and participants with pancreatic ductal adenocarcinoma, and longitudinal changes will be evaluated in participants with chronic pancreatitis.

Time frame: Baseline and every 6 to 12 months for up to 30 months after enrollment

Secondary Outcomes

Performance of a Multimodal Risk Stratification Model for Pancreatic Cancer in Chronic Pancreatitis

A risk stratification model will be developed using immune repertoire, germline genetic, imaging, and clinical features to identify participants with chronic pancreatitis who may be at increased risk of pancreatic cancer. Model performance will be assessed using discrimination, calibration, sensitivity, specificity, and other predictive performance measures.

Time frame: Baseline and follow-up data collected up to 30 months after enrollment

Number of Participants With Chronic Pancreatitis Who Develop Pancreatic Ductal Adenocarcinoma

The number of participants with chronic pancreatitis who develop pancreatic ductal adenocarcinoma during follow-up will be recorded. The diagnosis will be based on clinical evaluation, imaging findings, pathology when available, and follow-up information.

Time frame: From enrollment to the last scheduled follow-up, up to 30 months