Diagnostic value of ultra-deep targeted next-generation sequencing in patients with suspect pancreatic and periampullary lesions

Abstract

Background: Radiologic imaging and morphological cytology assessment have limitations for preoperative classification of pancreatic and periampullary lesions, often resulting in surgical resection without definitive diagnosis. Our study aims to define the diagnostic value of targeted Next-Generation Sequencing (NGS) of DNA in cytology material. Methods: Cytology material (brush/fine-needle aspirate) of patients with a suspect pancreatic or periampullary lesion was analyzed with NGS, in which 50 genes were deep sequenced for the presence of pathogenic variants. Results were discussed by the multidisciplinary team and changes to treatment plan noted. Diagnostic accuracy of NGS analysis was calculated. Results: In total, 70 consecutive patients were included. The integration of NGS results led to a change in treatment plan in 7 patients (exploration to follow-up n=4; follow-up to resection n=2; palliation to resection, n=1), and supported the treatment plan in 59 patients. In 4 patients, the NGS results were negative but did not influence the treatment plan as sampling error of cytology was suspected; NGS analysis on resection material revealed pathogenic variants in all 4 patients. Diagnostic accuracy of NGS analysis was 94% (sensitivity=93%; specificity=100%). Conclusion: In our study, NGS analysis changed the treatment plan in 10% of the patients. Application of in-depth preoperative molecular analysis can optimize treatment selection and can conversely diminish unnecessary resections in patients with a benign disease.