Role of Molecular Profiling of Pancreatic Cancer After Neoadjuvant Therapy: Does it Change Practice? J Gastrointest Surg 2020 Feb;24(2):235-242
Date
11/21/2019Pubmed ID
31745905DOI
10.1007/s11605-019-04423-6Scopus ID
2-s2.0-85076028351 (requires institutional sign-in at Scopus site) 10 CitationsAbstract
INTRODUCTION: Tumor profiling can improve the selection of oncologic therapies in patients with pancreatic cancer (PC). The impact of neoadjuvant therapy on tumor testing is unknown.
METHODS: Molecular profiling using commercially available 53-, 315-, or 472-gene next generation sequencing (NGS) panels was performed on surgical specimens following neoadjuvant therapy. All specimens with 472-gene sequencing also had immunohistochemical (IHC) testing. Treatment recommendations were based on somatic variants and IHC staining.
RESULTS: NGS was performed on 74 patient specimens: 42 (57%) with a 472-gene panel, 28 (38%) with a 315-gene panel, 3 (4%) had 472- and 315-gene panels, and 1 (1%) patient had 53- and 472-gene panels (78 total tests). Likely pathogenic/pathogenic variants were identified in 73 (94%) of the 78 tests. Of the 73 samples with variants identified, 13 (18%) variants were associated with an actionable treatment: ATM (n = 10), BRCA1 (n = 1), PIK3CA (n = 1), and BRCA2 (n = 1). No patient had more than one actionable variant. Based on NGS results, the most commonly recommended therapy was a platinum agent (n = 12/78, 15%). Of the 46 specimens that underwent IHC analysis, overlapping chemotherapeutic treatment recommendations were identified in 40 (87%) specimens.
CONCLUSION: Using current multigene NGS panels, actionable variants were identified in 13 (18%) of 74 surgical specimens and primarily involved genes of the DNA repair pathway. Anecdotal reproducibility of test concordance was low.
Author List
Krepline AN, Bliss L, Geurts J, Akinola I, Christians KK, George B, Ritch PS, Hall WA, Erickson BA, Evans DB, Tsai SAuthors
Kathleen K. Christians MD Professor in the Surgery department at Medical College of WisconsinBeth A. Erickson MD Professor in the Radiation Oncology department at Medical College of Wisconsin
Douglas B. Evans MD Chair, Professor in the Surgery department at Medical College of Wisconsin
Ben George MD Professor in the Medicine department at Medical College of Wisconsin
Jennifer L. Geurts MS, CGC Director, Assistant Professor in the Institute for Health and Humanity department at Medical College of Wisconsin
William Adrian Hall MD Chair, Professor in the Radiation Oncology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
BRCA1 ProteinBRCA2 Protein
Biomarkers, Tumor
DNA, Neoplasm
High-Throughput Nucleotide Sequencing
Humans
Neoadjuvant Therapy
Pancreatic Neoplasms
Reproducibility of Results
