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Diagnostic value of targeted next-generation sequencing in patients with suspected pancreatic or periampullary cancer
  1. Babs G Sibinga Mulder1,
  2. J Sven D Mieog1,
  3. Arantza Farina Sarasqueta2,
  4. Henricus JM Handgraaf1,
  5. Hans F A Vasen3,
  6. Rutger-Jan Swijnenburg1,
  7. Saskia A C Luelmo4,
  8. Shirin Feshtali5,
  9. Akin Inderson3,
  10. Alexander L Vahrmeijer1,
  11. Bert A Bonsing1,
  12. Tom van Wezel2,
  13. Hans Morreau2
  1. 1 Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
  2. 2 Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
  3. 3 Department of Gastroenterology, Leiden University Medical Center, Leiden, The Netherlands
  4. 4 Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands
  5. 5 Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
  1. Correspondence to Professor Hans Morreau, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands; j.morreau{at}


Aims Radiological imaging and morphological assessment of cytology material have limitations for preoperative classification of pancreatic or periampullary lesions, often resulting in surgical resection without definitive diagnosis. Our prospective study aims to define the diagnostic value of targeted next-generation sequencing (NGS) of DNA from cytology material.

Methods Patients with a suspect pancreatic or periampullary lesion underwent standard diagnostic evaluation including preoperative morphological cytology assessment. Treatment options for suspect lesions were surgical exploration with possible resection, follow-up or palliation. The cytology samples were analysed with NGS, in which 50 genes were sequenced for the presence of pathogenic variants. The NGS results were integrated with the clinical information during multidisciplinary team meetings, and changes in the treatment plan were scored. Diagnostic accuracy of NGS analysis (malignancy vs benign disease) was calculated.

Results NGS results of the cytology samples were confirmed in the resection specimens of the first 10 included patients. The integration of the NGS results led to a change in treatment plan in 7 out of 70 patients (from exploration to follow-up, n=4; from follow-up to exploration and resection, n=2; from palliation to resection, n=1). In four patients, the NGS results were contradictory, but did not affect the treatment plan. In the remaining 59 patients, NGS analysis supported the initial treatment plan. The diagnostic accuracy of NGS analysis was 94% (sensitivity=93%; specificity=100%).

Conclusions NGS can change the treatment plan in a significant portion of patients with suspect pancreatic or periampullary lesions. Application of NGS can optimise treatment selection and diminish unnecessary surgeries.

  • pancreatic cancer
  • molecular pathology
  • diagnostics

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  • Handling editor Runjan Chetty.

  • Contributors HJMM has initiated and coordinated the study and edited the manuscript. BGSM wrote the initial draft. JSDM, HJMH and TW contributed to the study concept and design and critically revised the manuscript. R-JS, SACL, SF, AI, ALV and BAB are the clinicians who are part of the multidisciplinary team. AFS and HFAV critically revised the manuscript. All authors have read and approved the final version of the manuscript.

  • Funding This work was supported by the Bas Mulder Award (grant UL2015-7665) from the Dutch Cancer Society. The NGS analysis was financially supported by an institutional grant in the LUMC in order to install up-to-date molecular testing in the Department of Pathology with the purpose to refine primary diagnoses and for companion diagnostic stratification.

  • Competing interests None declared.

  • Ethics approval All patient samples and clinical data were handled in accordance with the medical ethics guidelines described in the Code of Conduct for the Proper Secondary Use of Human Tissue of the Dutch Federation of Biomedical Scientific Societies.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Correction notice This article has been corrected since it was published Online First. Babs G Sibinga Mulder and Arantza Farina Sarasqueta surnames were corrected.