Log in

Emergence of Imatinib Resistance Associated with Downregulation of C-Kit Expression in Recurrent Gastrointestinal Stromal Tumor (GIST): Optimal Timing of Resection

  • Case Report
  • Published:
Journal of Gastrointestinal Surgery

Abstract

Introduction

Gastrointestinal stromal tumors (GISTs) are the most common gastrointestinal mesenchymal tumors. The activating mutation in the KIT (c-kit; CD117) proto-oncogene with subsequent tyrosine kinase activation plays a central role in the pathogenesis of GIST. Tyrosine kinase inhibitors are an integral part of GIST therapy. Initial response to neoadjuvant imatinib can be expected in up to 70% of the patients, thus offering an opportunity to surgically treat those with locally advanced primary or recurrent GIST. This favorable response to imatinib, however, is plagued with development of secondary resistance during the course of therapy.

Case description

We herein report a case of recurrent locally advanced GIST in an elderly man, with excellent performance status, successfully managed with the integration of neoadjuvant targeted therapy and surgery.

Discussion

Continued monitoring by a multidisciplinary team, including a surgeon, is vital for the success of neoadjuvant imatinib therapy for unresectable primary or recurrent GIST in the context of emergence of secondary resistance. As such, surgeons should participate in managing imatinib-treated GIST, as resection may become a viable curative option. This case also highlights that major oncologic resections can be safely performed in older persons when their performance status and comorbidities are carefully considered.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1
Figure 2
Figure 3

References

  1. Fletcher CD, Berman JJ, Corless C, Gorstein F, Lasota J, Longley BJ, Miettinen M, O'Leary TJ, Remotti H, Rubin BP, Shmookler B, Sobin LH, Weiss SW. Diagnosis of gastrointestinal stromal tumors: A consensus approach. Hum Pathol 2002;33(5):459–465.

    Article  PubMed  Google Scholar 

  2. Andtbacka RH, Ng CS, Scaife CL, Cormier JN, Hunt KK, Pisters PW, Pollock RE, Benjamin RS, Burgess MA, Chen LL, Trent J, Patel SR, Raymond K, Feig BW. Surgical resection of gastrointestinal stromal tumors after treatment with imatinib. Ann Surg Oncol 2007;14(1):14–24.

    Article  PubMed  Google Scholar 

  3. Scaife CL, Hunt KK, Patel SR, Benjamin RS, Burgess MA, Chen LL, Trent J, Raymond AK, Cormier JN, Pisters PW, Pollock RE, Feig BW. Is there a role for surgery in patients with "unresectable" cKIT+ gastrointestinal stromal tumors treated with imatinib mesylate? Am J Surg 2003;186(6):665–669.

    Article  PubMed  Google Scholar 

  4. Heinrich MC, Corless CL, Demetri GD, Blanke CD, von Mehren M, Joensuu H, McGreevey LS, Chen CJ, Van den Abbeele AD, Druker BJ, Kiese B, Eisenberg B, Roberts PJ, Singer S, Fletcher CD, Silberman S, Dimitrijevic S, Fletcher JA. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol 2003;21(23):4342–4349.

    Article  CAS  PubMed  Google Scholar 

  5. George S, Blay JY, Casali PG, Le Cesne A, Stephenson P, Deprimo SE, Harmon CS, Law CN, Morgan JA, Ray-Coquard I, Tassell V, Cohen DP, Demetri GD. Clinical evaluation of continuous daily dosing of sunitinib malate in patients with advanced gastrointestinal stromal tumour after imatinib failure. Eur J Cancer 2009;45:1959–1968.

    Article  CAS  PubMed  Google Scholar 

  6. Demetri GD, Benjamin RS, Blanke CD, Blay JY, Casali P, Choi H, Corless CL, Debiec-Rychter M, DeMatteo RP, Ettinger DS, Fisher GA, Fletcher CD, Gronchi A, Hohenberger P, Hughes M, Joensuu H, Judson I, Le Cesne A, Maki RG, Morse M, Pappo AS, Pisters PW, Raut CP, Reichardt P, Tyler DS, Van den Abbeele AD, von Mehren M, Wayne JD, Zalcberg J. NCCN Task Force report: management of patients with gastrointestinal stromal tumor (GIST)--update of the NCCN clinical practice guidelines. J Natl Compr Canc Netw 2007;5(Suppl 2):S1-S29; quiz S30.

    PubMed  Google Scholar 

  7. Verweij J, Casali PG, Zalcberg J, LeCesne A, Reichardt P, Blay JY, Issels R, van Oosterom A, Hogendoorn PC, Van Glabbeke M, Bertulli R, Judson I. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet 2004;364(9440):1127–1134.

    Article  CAS  PubMed  Google Scholar 

  8. Heinrich MC, Corless CL, Blanke CD, Demetri GD, Joensuu H, Roberts PJ, Eisenberg BL, von Mehren M, Fletcher CD, Sandau K, McDougall K, Ou WB, Chen CJ, Fletcher JA. Molecular correlates of imatinib resistance in gastrointestinal stromal tumors. J Clin Oncol 2006;24(29):4764–4774.

    Article  CAS  PubMed  Google Scholar 

  9. Aloia TA, Lee JE, Vauthey JN, Abdalla EK, Wolff RA, Varadhachary GR, Abbruzzese JL, Crane CH, Evans DB, Pisters PW. Delayed recovery after pancreaticoduodenectomy: a major factor impairing the delivery of adjuvant therapy? J Am Coll Surg 2007;204(3):347–355.

    Article  PubMed  Google Scholar 

  10. Asmis TR, Ding K, Seymour L, Shepherd FA, Leighl NB, Winton TL, Whitehead M, Spaans JN, Graham BC, Goss GD. Age and comorbidity as independent prognostic factors in the treatment of non small-cell lung cancer: a review of National Cancer Institute of Canada Clinical Trials Group trials. J Clin Oncol 2008;26(1):54–59.

    Article  CAS  PubMed  Google Scholar 

  11. Carreca I, Balducci L, Extermann M. Cancer in the older person. Cancer Treat Rev 2005;31(5):380–402.

    Article  PubMed  Google Scholar 

  12. Schneider T, Pfannschmidt J, Muley T, Reimer P, Eberhardt R, Herth FJ, Dienemann H, Hoffmann H. A retrospective analysis of short and long-term survival after curative pulmonary resection for lung cancer in elderly patients. Lung Cancer 2008;62(2):221–227.

    Article  PubMed  Google Scholar 

  13. Al-Refaie WB, Parsons HM, Henderson WG, Jensen EH, Tuttle TM, Vickers SM, Rothenberger DA, Virnig BA. Major cancer surgery in the elderly: results from the American College of Surgeons National Surgical Quality Improvement Program. Ann Surg 2009 (in press).

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Waddah B. Al-Refaie.

Additional information

Supported by “The 2008 Veterans of Foreign Wars (VFW) and Ladies Cancer Research Center Endowment Fund”

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dudeja, V., Armstrong, L.H., Gupta, P. et al. Emergence of Imatinib Resistance Associated with Downregulation of C-Kit Expression in Recurrent Gastrointestinal Stromal Tumor (GIST): Optimal Timing of Resection. J Gastrointest Surg 14, 557–561 (2010). https://doi.org/10.1007/s11605-009-1121-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11605-009-1121-2

Keywords

Navigation