Routine Molecular Profiling in Both Resectable and Unresectable Pancreatic Adenocarcinoma: Relevance of Cytologic...

Area of Science:

• Oncology
• Genomics
• Molecular Diagnostics

Background:

• Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer requiring prompt molecular profiling for targeted therapy.
• Endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) is crucial for PDAC diagnosis and molecular characterization.

Purpose of the Study:

• To evaluate the feasibility of using next-generation sequencing (NGS) for comprehensive molecular profiling of PDAC.
• To assess the concordance of mutational profiles between cytologic and histologic samples.
• To determine the prevalence of actionable mutations in PDAC patients, irrespective of tumor resectability.

Main Methods:

• Targeted NGS was performed on 2 independent PDAC patient cohorts (n=77 resectable, n=20 unresectable).
• Cohort 1 included histologic and EUS-FNA cytologic samples; Cohort 2 included only EUS-FNA cytologic samples.
• Analysis focused on identifying clinically relevant and actionable mutations.

Main Results:

• High concordance (88%) was observed between cytologic and histologic samples for mutational profiles in resectable PDAC.
• Actionable mutations were identified in 20% of resectable and 15% of unresectable PDAC patients.
• Commonly altered genes included KRAS, TP53, CDKN2A, and SMAD4.

Conclusions:

• NGS is feasible for molecular profiling of PDAC using both surgical and cytologic samples.
• The proposed model enables comprehensive molecular profiling for all PDAC patients, including those with unresectable disease.
• This approach facilitates personalized therapeutic decisions for PDAC management.