The purpose of this study is to evaluate the value of ctDNA detection in the assessment of response rate to neoadjuvant chemotherapy in pancreatic cancer and to explore the correlation between ctDNA clearance and prognosis at different time points. Meanwhile, whole exome sequencing (WES) and RNA Sequencing (RNA-seq) of samples of responders and non-responders to neoadjuvant chemotherapy before and after treatment are performed to explore the mechanisms of drug resistance and provide guidance for clinical decision making.

Pancreatic cancer is highly malignant with poor prognosis, and the overall 5-year survival rate is only about 9%. The value of neoadjuvant therapy in pancreatic cancer has been demonstrated by many studies, and a scientific and accurate evaluation of the efficacy of neoadjuvant therapy is crucial to its implementation and achieving the best outcomes. Circulating tumor DNA (ctDNA) analysis provides a non-invasive way to repeatedly assess the genomic profile of tumor. With improvements in detection techniques providing higher levels of sensitivity, ctDNA analysis is rapidly being accepted as a reliable tool in oncology. The purpose of this study is to evaluate the value of ctDNA detection in the assessment of response rate to neoadjuvant chemotherapy in pancreatic cancer and to explore the correlation between ctDNA clearance and prognosis at different time points. Meanwhile, whole exome sequencing (WES) and RNA Sequencing (RNA-seq) of samples of responders and non-responders to neoadjuvant chemotherapy before and after treatment are performed to explore the mechanisms of drug resistance and provide guidance for clinical decision making.

Inclusion Criteria:

• Newly diagnosed patients with non-metastatic pancreatic cancer;
• The pathological features were identified as pancreatic ductal carcinoma;
• Patients with clinical risk factors including significantly elevated CA19-9 levels at diagnosis, large primary tumor volume, large regional lymph node diameter, significant weight loss, and extreme pain;
• Patients accept neoadjuvant chemotherapy voluntarily with the regimen of modified FOLFIRINOX, and disease evaluation should be conducted every two courses, surgery should be performed without delay if resection criteria have been met, and at least two courses of chemotherapy should be completed;
• Age ≥18 years old;
• No other tumor treatment within 4 weeks prior to enrollment;
• Complete clinical data, including basic information, pathological information, treatment information;
• The subjects voluntarily join the study and sign the informed consent with good compliance, and cooperate with the acquisition of tissue samples and regular blood samples.

Exclusion Criteria:

• Any other systemic antitumor therapy priorly;
• Concomitant malignancies under treatment;
• Patients with a history of allergy to relevant chemotherapy agents;
• Failure to comply with the requirements of the visit plan;
• Patients who may be absent from the visit period for 2 weeks or more during the treatment period;
• The researchers determine that the subjects have other factors that could have caused the study to be discontinued.

Patients with non-metastatic pancreatic cancer. Evaluation of tumor resectability should be made in consensus at multidisciplinary meetings/discussions, according to NCCN guideline of pancreatic adenocarcinoma, Version 1.2022.

The IPD will not be shared with other researchers in order to protect patients' privacy.