Role of Molecular Profiling of Pancreatic Cancer After Neoadjuvant Therapy: Does it Change Practice?

• Published in: Journal of gastrointestinal surgery 2020-02, Vol.24 (2), p.235-242
• Main Authors: Krepline, Ashley N., Bliss, Lindsay, Geurts, Jennifer, Akinola, Idayat, Christians, Kathleen K., George, Ben, Ritch, Paul S., Hall, William A., Erickson, Beth A., Evans, Douglas B., Tsai, Susan
• Format: Article
• Language: English
• Subjects: 2019 SSAT Plenary Presentation; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Biopsy; BRCA1 Protein - genetics; BRCA1 Protein - metabolism; BRCA2 Protein - genetics; BRCA2 Protein - metabolism; Cancer therapies; Deoxyribonucleic acid; DNA; DNA, Neoplasm - genetics; Gastroenterology; Genes; Genetic counseling; High-Throughput Nucleotide Sequencing - methods; Humans; Laboratories; Medical schools; Medicine; Medicine & Public Health; Metastasis; Mutation; Neoadjuvant Therapy; Pancreatic cancer; Pancreatic Neoplasms; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - therapy; Patients; Reproducibility of Results; Surgery
• ISSN: 1091-255X; 1873-4626
• DOI: 10.1007/s11605-019-04423-6

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.