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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. Annals of surgery Nikiforova, M. N., Wald, A. I., Spagnolo, D. M., Melan, M. A., Grupillo, M., Lai, Y., Brand, R. E., O'Broin-Lennon, A. M., McGrath, K., Park, W. G., Pfau, P. R., Polanco, P. M., Kubiliun, N., DeWitt, J., Easler, J. J., Dam, A., Mok, S. R., Wallace, M. B., Kumbhari, V., Boone, B. A., Marsh, W., Thakkar, S., Fairley, K. J., Afghani, E., Bhat, Y., Ramrakhiani, S., Nasr, J., Skef, W., Thiruvengadam, N. R., Khalid, A., Fasanella, K., Chennat, J., Das, R., Singh, H., Sarkaria, S., Slivka, A., Gabbert, C., Sawas, T., Tielleman, T., Vanderveldt, H. D., Tavakkoli, A., Smith, L. M., Smith, K., Bell, P. D., Hruban, R. H., Paniccia, A., Zureikat, A., Lee, K. K., Ongchin, M., Zeh, H., Minter, R., He, J., Nikiforov, Y. E., Singhi, A. D. 2023

Abstract

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. Next-generation sequencing 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 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 was 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: Combined DNA/RNA NGS was not only accurate in predicting pancreatic cyst type and advanced neoplasia, but also improved the sensitivity of current pancreatic cyst guidelines.

View details for DOI 10.1097/SLA.0000000000005904

View details for PubMedID 37212422