TY - JOUR
T1 - A Combined DNA/RNA-based Next-Generation Sequencing Platform to Improve the Classification of Pancreatic Cysts and Early Detection of Pancreatic Cancer Arising From Pancreatic Cysts
AU - Nikiforova, Marina N.
AU - Wald, Abigail I.
AU - Spagnolo, Daniel M.
AU - Melan, Melissa A.
AU - Grupillo, Maria
AU - Lai, Yi Tak
AU - Brand, Randall E.
AU - O'Broin-Lennon, Anne Marie
AU - McGrath, Kevin
AU - Park, Walter G.
AU - Pfau, Patrick R.
AU - Polanco, Patricio M.
AU - Kubiliun, Nisa
AU - Dewitt, John
AU - Easler, Jeffrey J.
AU - Dam, Aamir
AU - Mok, Shaffer R.
AU - Wallace, Michael B.
AU - Kumbhari, Vivek
AU - Boone, Brian A.
AU - Marsh, Wallis
AU - Thakkar, Shyam
AU - Fairley, Kimberly J.
AU - Afghani, Elham
AU - Bhat, Yasser
AU - Ramrakhiani, Sanjay
AU - Nasr, John
AU - Skef, Wasseem
AU - Thiruvengadam, Nikhil R.
AU - Khalid, Asif
AU - Fasanella, Kenneth
AU - Chennat, Jennifer
AU - Das, Rohit
AU - Singh, Harkirat
AU - Sarkaria, Savreet
AU - Slivka, Adam
AU - Gabbert, Charles
AU - Sawas, Tarek
AU - Tielleman, Thomas
AU - Vanderveldt, Hendrikus Dutch
AU - Tavakkoli, Anna
AU - Smith, Lynette M.
AU - Smith, Katelyn
AU - Bell, Phoenix D.
AU - Hruban, Ralph H.
AU - Paniccia, Alessandro
AU - Zureikat, Amer
AU - Lee, Kenneth K.
AU - Ongchin, Melanie
AU - Zeh, Herbert
AU - Minter, Rebecca
AU - He, Jin
AU - Nikiforov, Yuri E.
AU - Singhi, Aatur D.
N1 - Publisher Copyright:
Copyright © 2023 The Author(s).
PY - 2023/10/1
Y1 - 2023/10/1
N2 - Objective: We report the development and validation of a combined DNA/RNA next-generation sequencing (NGS) platform to improve the evaluation of pancreatic cysts. Background and Aims: Despite a multidisciplinary approach, pancreatic cyst classification, such as a cystic precursor neoplasm, and the detection of high-grade dysplasia and early adenocarcinoma (advanced neoplasia) can be challenging. NGS of preoperative pancreatic cyst fluid improves the clinical evaluation of pancreatic cysts, but the recent identification of novel genomic alterations necessitates the creation of a comprehensive panel and the development of a genomic classifier to integrate the complex molecular results. Methods: An updated and unique 74-gene DNA/RNA-targeted NGS panel (PancreaSeq Genomic Classifier) was created to evaluate 5 classes of genomic alterations to include gene mutations (e.g., KRAS, GNAS, etc.), gene fusions and gene expression. Further, CEA mRNA (CEACAM5) was integrated into the assay using RT-qPCR. Separate multi-institutional cohorts for training (n=108) and validation (n=77) were tested, and diagnostic performance was compared to clinical, imaging, cytopathologic, and guideline data. Results: Upon creation of a genomic classifier system, PancreaSeq GC yielded a 95% sensitivity and 100% specificity for a cystic precursor neoplasm, and the sensitivity and specificity for advanced neoplasia were 82% and 100%, respectively. Associated symptoms, cyst size, duct dilatation, a mural nodule, increasing cyst size, and malignant cytopathology had lower sensitivities (41-59%) and lower specificities (56-96%) for advanced neoplasia. This test also increased the sensitivity of current pancreatic cyst guidelines (IAP/Fukuoka and AGA) by >10% and maintained their inherent specificity. Conclusions: PancreaSeq GC was not only accurate in predicting pancreatic cyst type and advanced neoplasia but also improved the sensitivity of current pancreatic cyst guidelines.
AB - Objective: We report the development and validation of a combined DNA/RNA next-generation sequencing (NGS) platform to improve the evaluation of pancreatic cysts. Background and Aims: Despite a multidisciplinary approach, pancreatic cyst classification, such as a cystic precursor neoplasm, and the detection of high-grade dysplasia and early adenocarcinoma (advanced neoplasia) can be challenging. NGS of preoperative pancreatic cyst fluid improves the clinical evaluation of pancreatic cysts, but the recent identification of novel genomic alterations necessitates the creation of a comprehensive panel and the development of a genomic classifier to integrate the complex molecular results. Methods: An updated and unique 74-gene DNA/RNA-targeted NGS panel (PancreaSeq Genomic Classifier) was created to evaluate 5 classes of genomic alterations to include gene mutations (e.g., KRAS, GNAS, etc.), gene fusions and gene expression. Further, CEA mRNA (CEACAM5) was integrated into the assay using RT-qPCR. Separate multi-institutional cohorts for training (n=108) and validation (n=77) were tested, and diagnostic performance was compared to clinical, imaging, cytopathologic, and guideline data. Results: Upon creation of a genomic classifier system, PancreaSeq GC yielded a 95% sensitivity and 100% specificity for a cystic precursor neoplasm, and the sensitivity and specificity for advanced neoplasia were 82% and 100%, respectively. Associated symptoms, cyst size, duct dilatation, a mural nodule, increasing cyst size, and malignant cytopathology had lower sensitivities (41-59%) and lower specificities (56-96%) for advanced neoplasia. This test also increased the sensitivity of current pancreatic cyst guidelines (IAP/Fukuoka and AGA) by >10% and maintained their inherent specificity. Conclusions: PancreaSeq GC was not only accurate in predicting pancreatic cyst type and advanced neoplasia but also improved the sensitivity of current pancreatic cyst guidelines.
KW - intraductal oncocytic papillary neoplasm
KW - intraductal papillary mucinous neoplasm
KW - mucinous cystic neoplasm
KW - pancreatic ductal adenocarcinoma
KW - pancreatic neuroendocrine tumor
KW - pseudocyst
KW - serous cystadenoma
UR - http://www.scopus.com/inward/record.url?scp=85170294602&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85170294602&partnerID=8YFLogxK
U2 - 10.1097/SLA.0000000000005904
DO - 10.1097/SLA.0000000000005904
M3 - Article
C2 - 37212422
AN - SCOPUS:85170294602
SN - 0003-4932
VL - 278
SP - E789-E797
JO - Annals of surgery
JF - Annals of surgery
IS - 4
ER -