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

Krepline AN1, Bliss L1, Geurts J1, Akinola I1, Christians KK1, George B2, Ritch PS2, Hall WA3, Erickson BA3, Evans DB1, Tsai S4.

Author information

1: Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA.
2: Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
3: Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, USA.
4: Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA. stsai@mcw.edu.

Abstract

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.