Advertisement

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

  • Ashley N. Krepline
  • Lindsay Bliss
  • Jennifer Geurts
  • Idayat Akinola
  • Kathleen K. Christians
  • Ben George
  • Paul S. Ritch
  • William A. Hall
  • Beth A. Erickson
  • Douglas B. Evans
  • Susan TsaiEmail author
2019 SSAT Plenary Presentation

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.

Keywords

Next generation sequencing Molecular profiling Targeted therapy Pancreatic cancer 

Notes

Author Contribution

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

Funding Information

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.

References

  1. 1.
    Lander ES, Linton LM, Birren B, et al. Initial sequencing and analysis of the human genome. Nature. 2001;409(6822):860-921.CrossRefPubMedGoogle Scholar
  2. 2.
    Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. The New England journal of medicine. 2013;369(18):1691-1703.CrossRefGoogle Scholar
  3. 3.
    Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. The New England journal of medicine. 2011;364(19):1817-1825.CrossRefPubMedGoogle Scholar
  4. 4.
    Pishvaian MJ, Bender RJ, Halverson D, et al. Molecular Profiling of Patients with Pancreatic Cancer: Initial Results from the Know Your Tumor Initiative. Clinical cancer research : an official journal of the American Association for Cancer Research. 2018;24(20):5018-5027.Google Scholar
  5. 5.
    Sicklick JK, Kato S, Okamura R, et al. Molecular profiling of cancer patients enables personalized combination therapy: the I-PREDICT study. Nature medicine. 2019;25(5):744-750.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Dimou F, Sineshaw H, Parmar AD, Tamirisa NP, Jemal A, Riall TS. Trends in Receipt and Timing of Multimodality Therapy in Early-Stage Pancreatic Cancer. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract. 2016;20(1):93-103; discussion 103.CrossRefGoogle Scholar
  7. 7.
    Geertjan Van Tienhoven EV, Mustafa Suker, Karin B.X. Groothuis, Olivier R. Busch, Bert A. Bonsing. Preoperative chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer (PREOPANC-1): A randomized, controlled, multicenter phase III trial. Jour Clin Oncol. 2018 36(18_suppl).Google Scholar
  8. 8.
    Sohal D, McDonough S, Ahmad SA, et al. SWOG S1505: Initial findings on eligibility and neoadjuvant chemotherapy experience with mfolfirinox versus gemcitabine/nab-paclitaxel for resectable pancreatic adenocarcinoma. Journal of Clinical Oncology. 2019;37(4_suppl):414-414.CrossRefGoogle Scholar
  9. 9.
    Tsai S, Christians KK, George B, et al. A Phase II Clinical Trial of Molecular Profiled Neoadjuvant Therapy for Localized Pancreatic Ductal Adenocarcinoma. Annals of surgery. 2018;268(4):610-619.CrossRefPubMedGoogle Scholar
  10. 10.
    Aguirre AJ, Nowak JA, Camarda ND, et al. Real-time Genomic Characterization of Advanced Pancreatic Cancer to Enable Precision Medicine. Cancer discovery. 2018;8(9):1096-1111.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Collisson EA, Sadanandam A, Olson P, et al. Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy. Nature medicine. 2011;17(4):500-503.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Bailey P, Chang DK, Nones K, et al. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature. 2016;531(7592):47-52.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Moffitt RA, Marayati R, Flate EL, et al. Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma. Nature genetics. 2015;47(10):1168-1178.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Chantrill LA, Nagrial AM, Watson C, et al. Precision Medicine for Advanced Pancreas Cancer: The Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) Trial. Clinical cancer research : an official journal of the American Association for Cancer Research. 2015;21(9):2029-2037.CrossRefGoogle Scholar
  15. 15.
    Aung KL, Fischer SE, Denroche RE, et al. Genomics-Driven Precision Medicine for Advanced Pancreatic Cancer: Early Results from the COMPASS Trial. Clinical cancer research : an official journal of the American Association for Cancer Research. 2018;24(6):1344-1354.CrossRefGoogle Scholar
  16. 16.
    McNair AG, Choh CT, Metcalfe C, et al. Maximising recruitment into randomised controlled trials: the role of multidisciplinary cancer teams. European journal of cancer. 2008;44(17):2623-2626.CrossRefPubMedGoogle Scholar
  17. 17.
    Onukwugha E, Petrelli NJ, Castro KM, et al. ReCAP: Impact of Multidisciplinary Care on Processes of Cancer Care: A Multi-Institutional Study. J Oncol Pract. 2016;12(2):155-156; e157-168.CrossRefPubMedGoogle Scholar
  18. 18.
    Jennings LJ, Arcila ME, Corless C, et al. Guidelines for Validation of Next-Generation Sequencing-Based Oncology Panels: A Joint Consensus Recommendation of the Association for Molecular Pathology and College of American Pathologists. The Journal of molecular diagnostics : JMD. 2017;19(3):341-365.CrossRefPubMedGoogle Scholar
  19. 19.
    Li MM, Datto M, Duncavage EJ, et al. Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists. The Journal of molecular diagnostics : JMD. 2017;19(1):4-23.CrossRefPubMedGoogle Scholar

Copyright information

© The Society for Surgery of the Alimentary Tract 2019

Authors and Affiliations

  • Ashley N. Krepline
    • 1
  • Lindsay Bliss
    • 1
  • Jennifer Geurts
    • 1
  • Idayat Akinola
    • 1
  • Kathleen K. Christians
    • 1
  • Ben George
    • 2
  • Paul S. Ritch
    • 2
  • William A. Hall
    • 3
  • Beth A. Erickson
    • 3
  • Douglas B. Evans
    • 1
  • Susan Tsai
    • 1
    Email author
  1. 1.Department of SurgeryMedical College of WisconsinMilwaukeeUSA
  2. 2.Department of MedicineMedical College of WisconsinMilwaukeeUSA
  3. 3.Department of Radiation OncologyMedical College of WisconsinMilwaukeeUSA

Personalised recommendations