Application of ctDNA in Evaluation of Neoadjuvant Chemotherapy Efficacy and Exploration of Chemoresistance Mechanisms in Pancreatic Cancer

Shanghai Zhongshan Hospital92 enrolled

Overview

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.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Patients With Non-metastatic Pancreatic Cancer Evaluation of Tumor Resectability Shall be Made in Consensus at Multidisciplinary Meetings, According to NCCN Guideline Version 1.2022 Pancreatic Adenocarcinoma

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Objective response rate (ORR) of neoadjuvant therapy in patients with non-metastatic pancreatic cancer

Pre-treatment ctDNA detection and mutation characterization in blood are used to evaluate objective response rate (ORR) of neoadjuvant therapy in patients with non-metastatic pancreatic cancer.

Time frame: Up to 24 months

Secondary Outcomes

Rate of adverse reactions

ctDNA detection is performed to evaluate the rate of adverse reactions to neoadjuvant therapy in patients with non-metastatic pancreatic cancer.

Time frame: One week during therapy and 3 months thereafter up to 24 months.

The correlation between detection of blood ctDNA and mutation characteristics before treatment and the rate of adverse reactions

ctDNA detection is performed to analyze the correlation between detection of blood ctDNA and mutation characteristics before treatment and the rate of adverse reactions.

Time frame: One week during therapy and 3 months thereafter up to 24 months.

The correlation between postoperative ctDNA in blood and clearance of ctDNA after adjuvant therapy and overall survival (OS) in patients with operable pancreatic cancer

Correlation between postoperative ctDNA in blood and clearance of ctDNA after adjuvant therapy and overall survival (OS) in patients with operable pancreatic cancer.

Time frame: One week during therapy and 3 months thereafter up to 48 months.

The recurrence of pancreatic cancer

Blood ctDNA after treatment is used to monitor the recurrence of pancreatic cancer.

Time frame: One week during therapy and 3 months thereafter up to 24 months.

The timeliness and accuracy of ctDNA with CA19-9 and medical imaging in the detection of disease recurrence

Blood ctDNA after treatment is used to compare the timeliness and accuracy of ctDNA with CA19-9 and medical imaging in the detection of disease recurrence.

Time frame: Up to 24 months.

The mechanisms of drug resistance to neoadjuvant chemotherapy

WES and RNA-seq of tissue samples of pancreatic cancer patients before and after treatment are performed to explore the mechanisms of drug resistance to neoadjuvant chemotherapy.

Time frame: One week during therapy and 3 months thereafter up to 24 months.

Application of ctDNA in Evaluation of Neoadjuvant Chemotherapy Efficacy and Exploration of Chemoresistance Mechanisms in Pancreatic Cancer

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts