Role of Molecular Profiling of Pancreatic Cancer After Neoadjuvant Therapy: Does it Change Practice?
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.
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.
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.
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.
KeywordsNext generation sequencing Molecular profiling Targeted therapy Pancreatic cancer
Ashley N. Krepline: data collection and analysis, manuscript preparation
Lindsay Bliss: data collection and analysis
Jennifer Geurts: manuscript preparation
Idayat Akinola: data collection and analysis
Kathleen K. Christians: manuscript preparation
Ben George: manuscript preparation
Paul S. Ritch: manuscript preparation
William A. Hall: manuscript preparation
Beth A. Erickson: manuscript preparation
Douglas B. Evans: data analysis, manuscript preparation
Susan Tsai: concept, data analysis, manuscript preparation
This study received financial support from the Ronald Burkland Eich Fund and Medical College of Wisconsin Department of Surgery.
Compliance with Ethical Standards
This study was approved by the Institutional Review Board at the Medical College of Wisconsin.
Conflicts of Interest
The authors declare that they have no conflict of interest.
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