Prediction of Neoadjuvant Chemotherapy Response in Pancreatic Cancer

An Exosomal miRNA Based Predictive Model for Personalized Neoadjuvant Chemotherapy Selection in Pancreatic Ductal Adenocarcinoma

This study aims to develop and validate a predictive microRNA (miRNA) panel to assess the response to neoadjuvant chemotherapy (NACT) in patients with resectable and borderline resectable pancreatic ductal adenocarcinoma (PDAC).

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with a five-year overall survival rate below 12%. Surgical resection combined with systemic chemotherapy offers the best chance for cure; however, only a subset of patients truly benefits from neoadjuvant chemotherapy (NACT). Currently, there are no validated biomarkers to predict response to NACT, making treatment selection largely empirical.

The PRECEPT study (PREdiction of Chemotherapy Effect in Pancreatic Cancer Treatment) aims to identify and validate microRNA (miRNA)-based biomarkers from pre-treatment plasma that can predict therapeutic response to neoadjuvant chemotherapy in patients with resectable or borderline resectable PDAC. Specifically, the study focuses on two standard regimens: FOLFIRINOX and gemcitabine plus nab-paclitaxel (GEM-NABP).

This is a retrospective, non-interventional, observational study using archived plasma samples collected before the initiation of NACT. Exosomal miRNA sequencing (small RNA-seq) has been performed to identify candidate predictive miRNAs. These candidates will be validated using quantitative reverse transcription PCR (qRT-PCR) in an independent patient cohort. The association between miRNA expression levels and pathologic response (CAP grade or tumor regression score) will be analyzed. Additionally, correlations with overall survival (OS) and recurrence-free survival (RFS) will be explored.

Inclusion Criteria:

• Histologically confirmed pancreatic ductal adenocarcinoma (PDAC).
• Underwent neoadjuvant chemotherapy (FOLFIRINOX or Gemcitabine/nab-paclitaxel).
• Availability of pre-treatment plasma samples.
• Underwent curative-intent resection (R0 or R1).

Exclusion Criteria:

• Inadequate plasma samples or poor RNA quality for exosomal miRNA analysis.
• Non-adenocarcinoma histology.
• Presence of synchronous or multiple primary malignancies.
• Receipt of chemotherapy regimens other than standard FOLFIRINOX or gemcitabine plus nab-paclitaxel (GEM-NABP).
• Presence of active inflammatory or autoimmune diseases.